• Molecules and Cells
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• v.38 no.4
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• pp.285-296
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• 2015

Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-${\beta}$. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.3
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• pp.149-154
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• 2002

The blood pressure (BP) is regulated by the nervous system and humoral factors, such as renin- angiotensin system, vasopressin and others. In the present study, we examined the central effects of glutamate and GABA on the cardiovascular regulation by injection of these substances into the lateral ventricle and also investigated the relationship between these central effects and the action of angiotensin II (Ang). Male Sprague Dawley rats, $350{\sim}400$ g, were anesthetized with urethane and instrumented with an arterial catheter for direct measurement of BP and heart rate (HR), and an guide cannula in the lateral ventricle for drug injection. A glass microelectode was inserted into the rostral ventrolateral medulla (RVLM) for recording single unit spikes. Barosensitive neurons were identified by changes of single unit spikes in RVLM following intravenous injection of nitroprusside and phenylephrine. The effects of GABA and glutamate injected into the lateral ventricle were studied in single neuronal activity of the RVLM in addition to changes in BP and heart rate, and compared the results before and after treatment with intravenous losartan, nonpeptide Ang II-type 1 receptor antagonist (1 mg/100 g BW). Intracerebroventricular administration of GABA decreased systolic blood pressure (SBP) and HR, but increased the firing rates in the RVLM. However, intracerebroventricular glutamate injection produced effects opposite to GABA. After pretreatment of intravenous losartan, the central effects of GABA on BP and firing rate in the RVLM were significantly attenuated and that of glutamate showed a tendency of attenuation. These results suggested that central GABA and glutamate regulated BP and firing rates in RVLM were inversely related to BP change. The central effects of GABA or glutamate on the autonomic nervous function were modulated by humoral factor, Ang II, by maintaining BP.

• Proceedings of the Korean Nutrition Society Conference
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• 2002.05a
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• pp.29-41
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• 2002

While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the nutritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. For this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research, All the available analytical techniques can and should be used in modern nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

• Proceedings of the Korean Nutrition Society Conference
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• 2002.06a
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• pp.598-603
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• 2002

While the sequencing of several genomes was underway, several advanced techniques in genetics, molecular biology and protein chemistry emerged. Within the notritional sciences, while the focus on nutrition education, epidemiology and public health aspects remains essential; it is crucial to incorporate the new advances in gene and protein discovery in nutritional studies. Nutrition is a discipline that has always integrated social, biochemical and physiological sciences from the studies at the molecule level to studies at the population level. for this reason, nutritionists are in a prime position to readily incorporate the current genomics approaches in nutrition research. All the available analytical techniques can and should be used in modem nutritional sciences. These include genetics, genomics, proteomics and metabolomics which also require integration and use of bioinformatics and computational methods for data analysis and management. These applications will be briefly reviewed with a primary focus on what the genomics and genetics approaches offer to nutritionists. We will use one of our research focus areas to illustrate uses of some of these applications in obesity-hypertension research. Our central hypothesis is that adipose tissue is an endocrine organ that plays a major role in obesity and related hypertension. We are primarily studying the renin angiotensin system (RAS). We provide evidence from our own studies and others for the paracrine as well as endocrine role of adipocyte-derived angiotensin II in adipocyte gene expression, adiposity and blood pressure regulation. Both cell culture studies as well as knockout and transgenic mice models are used to test our hypothesis. Genomics and proteomics technologies are currently developed to complement our physiological and molecular studies on the RAS and for a fine analysis of this system and its function in health and disease.

• Childhood Kidney Diseases
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• v.22 no.2
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• pp.91-96
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• 2018

Nephrotic syndrome in the first year of life, characterized by renal dysfunction and proteinuria, is associated with a heterogeneous group of disorders. These disorders are often related to genetic mutations, but the syndrome can also be caused by a variety of other diseases. We report an infant with nephrotic syndrome associated with a neuroblastoma. A 6-month-old girl was admitted with a 10% weight loss over 10 days and nephrotic-range proteinuria. She was ill-looking, and her blood pressure was higher than normal for her age. Her cystatin-C glomerular filtration rate was decreased, and levels of plasma renin, aldosterone, and catecholamines were elevated. Renal ultrasonography and abdominal computed tomography showed a retroperitoneal prevertebral mass encasing both renal arteries and the left renal vein. The mass was partially resected laparoscopically, and the pathologic diagnosis was neuroblastoma. Findings on a simultaneous renal biopsy were unremarkable. The patient was treated with chemotherapy and several anti-hypertensive drugs, including an alpha blocker. Two months later, the mass had decreased in size and the proteinuria and hypertension were gradually improving. In an infant with abnormal renin-angiotensin system activation, severe hypertension, and nephrotic-range proteinuria, neuroblastoma can be considered in the differential diagnosis.

• The Journal of Korean Medicine
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• v.32 no.5
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• pp.134-138
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• 2011

Glycyrrhetinic acid, which is a component of licorice, can cause hypermineralocorticoidism through the inhibition of $11{\beta}$-hydroxysteroid dehydrogenase. So, a high dose intake of licorice can lead to hypermineralocorticoidism with potassium loss and depression of the renin-angiotensin-aldosterone system. We report a 73-year-old man with muscle weakness of proximal lower limbs with hypokalemia (Serum $K^+$: 1.4 mEq/L) due to taking self-prescribed licorice without OMD's diagnosis. He boiled 60~100g licorice / day in water and drank it intermittently for 1 month due to arthralgia and swelling of both his knees. Patient's serum renin activity and aldosterone level were far beyond the normal range. He also had metabolic alkalosis with pH 7.552. After quitting the licorice, hypokalemia and muscle weakness of proximal lower limbs gradually improved within 1week.

• The Journal of Korean Medicine
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• v.17 no.1 s.31
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• pp.212-221
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• 1996

The aim of this experiment was to elucidate the effects of Saseuptang water extract on the renal function plasma renin activity and plasma levels of atrial natriuretic peptide and aldosterone in rat The results were as follows; 1. Water balance decreased significantly after the administration of Saseuptang water extract, 0.4 and 0.8ml/kg. 2. Urine volume increased significantly after the administration of Saseuptang water extract, $0.4\;m{\ell}/kg$. 3. Urinary excretion of chloride increased significantly after the administration of Saseupthang water extract, $0.8\;m{\ell}/kg$. 4. Free water clearance increased significantly after the administration of Saseuptang water extract, $0.8\;m{\ell}/kg$. 5. Urinary excretion of creatinine increased significantly after the administration of Saseuptang water extract, $0.8\;m{\ell}/kg$. 6. Plasma levels of atrial natriuretic peptide (ANP) decreased significantly after administration of Saseupthang water extract, $0.8\;m{\ell}/kg$. These results suggest that the changes of urine volume after the administration of Saseuptang water extracts are related to the increments of glomerular filtration rate and free water clearance, and it is suggested that the changes of renal function by which Saseuotang may related to the renin-angiotensin and atrial natriuretic peptide system.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.21-31
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• 1991

When administered intracerebroventricularly (icv), cholinergic nicotinic agents, nicotine and DMPP, as well as cholinergic muscarinic agents, muscarine and bethanechol, produced pressor responses in urethane-anesthetized vagotomized rabbits. The response patterns to nicotine and to DMPP were similar, while the bethanechol response resembled the muscarine pattern. The pressor response to nicotine and DMPP was markedly inhibited by icv mecamylamine but not by icv pirenzepine, whereas the response to muscarine and bethanechol was inhibited by icv pirenzepine but not by icv mecamylamine, suggesting that both nicotinic and muscarinic receptors in the brain are involved in the action. Intravenous pretreatments of animals with regitine, reserpine, enalapril, saralasin, both regitine and enalapril, both regitine and saralasin, SK&F-100273 did not prevent the pressor response to nicotine and muscarine. Iv pretreatments with both regitine and SK&F-100273 inhibited the nicotine response without affecting the muscarine response, whereas pretreatments with three agents, regitine, enalapril and SK&F-100273, inhibited the muscarine response. The nicotine-induced elevated blood pressure as well as the muscarine-induced were lowered by regitine but not by enalapril or by SK&F-100273. Enalapril was without effect on the nicotine hypertension in rabbits treated with regitine or both regitine and SK&F-100273, whereas SK&F-100273 lowered the nicotine hypertension in regitine-treated animals. Enalapril did not enhance the lowering effect of SK&F-100273 in regitine-treated ones, nor did it cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and SK&F-100273. Likewise, SK&F-100273 did not cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and enalapril. These data suggest that the nicotine-induced hypertensive state is related to at least two systems in the periphery-sympathetic and vasopressin, whereas in the muscarine-induced hypertensive state three systems in the periphery are involved, i.e., the sympathetic, vasopressin and angiotensin system. The hypotensive effect of regitine on basal arterial blood pressure levels of rabbits was not influenced by pretreatment with either of enalapril or SK&F-100273, but significantly potentiated by treating with both enalapril and SK&F-100273, suggesting participation of the sympathetic and the renin-angiotensin system as well as the vasopressin system in maintenance of arterial blood pressure.

• Childhood Kidney Diseases
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• v.19 no.2
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• pp.71-78
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• 2015

The incidence of acute kidney injury (AKI) in critically ill pediatric patients has been reported as increasing to 25 %, depending on population characteristics. The etiology of AKI has changed over the last 10-20 years from primary renal disease to the renal conditions associated with systemic illness. The AKI in pediatric population is associated with increased mortality and morbidity, and prevention is needed to reduce the consequence of AKI. It is known that the most important risk factors for AKI in critically ill pediatric patients are clinical conditions to be associated with decreased renal blood flow, direct renal injury, and illness severity. Renal hypoperfusion leads to neurohormonal activation including renin-angiotensin-aldosterone system, sympathetic nervous system, antidiuretic hormone, and prostaglandins. Prolonged renal hypoperfusion can result in acute tubular necrosis. The direct renal injury can be predisposed under the condition of renal hypoperfusion, and appropriate treatment of volume depletion is important to prevent AKI. The preventable causes of AKI include contrast-induced nephropathy, hemodynamic instability, inappropriate mediation use, and multiple nephrotoxic insults. Given the evidence of preventable factors for AKI, several actions such as the use of protocol for prevention of contrast-induced nephropathy, appropriate treatment of volume depletion, vigorous treatment of sepsis, avoidance of combinations of nephrotoxic medications, and monitoring of levels of drugs should be recommended.

• Toxicological Research
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• v.17
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• pp.117-125
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• 2001

Envenoming by Russells viper causes a broad spectrum of renal impairment. Renal failure is an important complication in patients bitten by Russells viper. Experimental work in animals and in vitro has elucidated pathophysiological mechanisms that contribute to life threatening complications and have suggested possibilities for therapeutic intervention. The evidence in experimental animals regarding mechanisms of venom action in relation to changes in either extrarenal or intrarenal factors is presented. The cardiovascular system and renal hemodynamics are affected by venom. Reductions of renal function including renal hemodynamics are associated directly with changes in general circulation during envenomation. Possible endogenous mechanisms for releasing the hormone inducing renal vasoconstriction after envenomation are evident. Hormonal factor such as the catecholamine, prostaglandin and renin angiotensin systems induce these changes. Direct nephrotoxicity of venom action is studied in the isolated per-fused kidney. Characteristic polarization of the cell membrane, changes of mitochondrial activity and Na-K ATPase in renal tubular cells are observed. Changes in renal function and the cardiovascular system are observed of ter envenomation and are reversed by the administration of Russells viper antivenom (purified equine immunoglobulin, $Fab_2$ fragment). The neutralizing effects are more efficient when the intravenous injection of antivenom is given within 30 min after the envenomation.