• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.1
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• pp.39-44
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• 2020

Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder that presents as abnormally elevated levels of low-density lipoprotein cholesterol and premature heart disease, requiring frequent intervention through lipid apheresis for management. The risk of perioperative cardiac events is higher in patients with HoFH because of its pathophysiological manifestations in the vascular system. Careful cardiac precautions and anesthetic assessments are necessary to ensure patient safety. In the following case report, we discuss the clinical course and anesthetic considerations for a 14-year-old girl with HoFH undergoing sedation for dental extractions and mandibular molar uprighting in an outpatient oral surgery clinic. Considerations included the use of heparin in the patient's weekly plasma lipid apheresis treatment. In order to reduce the risks of peri- and postoperative bleeding and perioperative cardiac events, the operation was scheduled for 4 days after apheresis. This allowed for adequate heparin clearance, while also reducing the likelihood of possible cardiac events. A literature review revealed no results for the outpatient management of patients with HoFH undergoing sedation for noncardiac procedures. Our reported case serves as a clinical example for physicians to be utilized in the future.

• Korean Circulation Journal
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• v.48 no.12
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• pp.1097-1119
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• 2018

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.8
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• pp.1139-1147
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• 2014

We investigated whether or not Schisandra chinensis (SC), a traditional herbal medicine, has protective effects against alcohol-induced fatty liver and blood alcohol clearance. Two tests focused on acute intoxication and chronic ethanol treatment were carried out. For the chronic ethanol treatment test, rats were fed ethanol by intragastric administration everyday for 8 weeks to induce alcoholic fatty liver. Ethanol treatment significantly increased blood alcohol concentration at 90 min after acute ethanol intoxication. Compared with the two ethanol-treated groups, rats administered ethanol along with SC extracts showed an approximately 13% increased blood alcohol clearance rate at 360 min. Chronic ethanol treatment significantly increased serum and hepatic triglyceride (TG) levels, and caused fatty degeneration of liver. Ethanol treatment also elevated the serum total-cholesterol (TC) level. However, after feeding of ethanol plus SC extracts, ethanol-induced elevation of hepatic TG levels reversed, whereas elevation of serum TG and TC levels was not observed after treatment with SC extracts. Ethanol treatment significantly increased ${\gamma}$-GT, aspartate aminotransferase, and alanine aminotransferase activities after 8 weeks. Compared with the ethanol-fed group, rats administered ethanol plus SC extracts for 4 weeks showed attenuated fatty degeneration as well as decreased hepatic function test values. SC administration also significantly increased intracellular lipid accumulation in hepatocytes and reduced steatosis score and hepatic TG levels, as measured by biochemical and histolopathological analyses. Our results indicate that the protective effects of SC are accompanied by a significant decrease in hepatic TG levels, thereby suggesting SC has the ability to prevent ethanol-induced fatty liver, by reducing hepatic TG and enzyme levels in alcoholic rats.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.42-47
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• 1999

Angiotensin-converting enzyme inhibitors lower urinary protein excretion in hypertensive and normotensive patients with renal disease. Most children with nephrotic syndrome have minimal change histology and the great majority of these patients respond to the treatment with oral prednisone. Here we have studied the effects of combination of Inhibace and oral prednisone in pediatric patients with nephrotic syndrome. 45 patients with nephrotic syndrome were selected. Of these, 29 patients were treated with prednisone(2mg/kg/day) and 16 children were treated with prednisone and Inhibace(2.5mg/day). Urinary protein, blood pressure, creatinine clearance, serum creatinine, serum albumin and serum cholesterol were measured in both control and Inhibace group. Also the duration to remission after treatment was compared in both groups. The amounts of proteinuria before and after treatment were not significantly different in both group. The duration to remission of proteinuria was significantly shorter in Inhibace group compared to that in control group. The changes of blood pressure and creatinine clearance were not significant in Inhibace group. In conclusion, the combination therapy of oral prednisone and ACE inhibitor have shortened the duration to remission of proteinuria in nephrotic syndrome of children.

• The Journal of the Korean Society for Microbiology
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• v.35 no.3
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• pp.251-261
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• 2000

V. vulnificus is an estuarine bacterium which causes septicemia and shock in susceptible patients. The organism produces a hemolytic cytolysin (VvH), which has a membrane damaging effect on erythrocytes. To clarify the mechanisms by which VvH might contribute to virulence, we examined its effect on macrophages. When mouse peritoneal macrophages were harvested and co-cultured with hemolysin-positive V. vulnificus strains (100 bacteria/cell), about 60% of the macrophages were killed; macrophages were not killed when co-cultured V. vulnificus strain CVD 707, a VvH-negative deletion mutant. Exposure of macrophages to filtered culture supernatants (2.5 HU/ml) and purified VvH (3 HU/ml) resulted in an increase in dead cells (80 and 90%, respectively), as determined by the trypan blue dye exclusion method and LDH release from macrophages was also increased (70 and 65.5%, respectively). The cytotoxic effect of VvH on macrophages was both the dose- and time-dependent. The VvH caused damage to the macrophage membrane and was blocked significantly by preincubation with cholesterol (p<0.01). Fetal bovine serum showed remarkable inhibition of VvH synthesis by V. vulnificus and inhibited VvH activity in culture supernatant. Cell viability was increased by 35% (p<0.01) and LDH release decreased by 28% (p<0.01) when macrophages were incubated with V. vulnificus (100 bacterial cell) in DMEM-10% FBS for 2 hr. Bacterial clearance activity of mice against V. vulnificus CVD 707 was decreased by pretreatment with 10 HU of VvH. This result suggests that the VvH can impair the membrane of macrophages and may playa role in the pathogenesis of V. vulnificus septicemia.

• Journal of Ginseng Research
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• v.47 no.1
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• pp.97-105
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• 2023

Background: Hyperactivated airway mucosa cells overproduce mucin and cause severe breathing complications. Here, we aimed to identify the effects of saponins derived from Panax ginseng on inflammation and mucin overproduction. Methods: NCI-H292 cells were pre-incubated with 16 saponins derived from P. ginseng, and mucin overproduction was induced by treatment with phorbol 12-myristate 13-acetate (PMA). Mucin protein MUC5AC was quantified by enzyme-linked immunosorbent assay, and mRNA levels were analyzed using quantitative polymerase chain reaction (qPCR). Moreover, we performed a transcriptome analysis of PMA-treated NCI-H292 cells in the absence or presence of Rg5, and differential gene expression was confirmed using qPCR. Phosphorylation levels of signaling molecules, and the abundance of lipid droplets, were measured by western blotting, flow cytometry, and confocal microscopy. Results: Ginsenoside Rg5 effectively reduced MUC5AC secretion and decreased MUC5AC mRNA levels. A systematic functional network analysis revealed that Rg5 upregulated cholesterol and glycerolipid metabolism, resulting in the production of lipid droplets to clear reactive oxygen species (ROS), and modulated the mitogen-activated protein kinase and nuclear factor (NF)-kB signaling pathways to regulate inflammatory responses. Rg5 induced the accumulation of lipid droplets and decreased cellular ROS levels, and N-acetyl-ⳑ-cysteine, a ROS inhibitor, reduced MUC5AC secretion via Rg5. Furthermore, Rg5 hampered the phosphorylation of extracellular signal-regulated kinase and p38 proteins, affecting the NF-kB signaling pathway and pro-inflammatory responses. Conclusion: Rg5 alleviated inflammatory responses by reducing mucin secretion and promoting lipid droplet-mediated ROS clearance. Therefore, Rg5 may have potential as a therapeutic agent to alleviate respiratory disorders caused by hyperactivation of mucosa cells.

• Clinical and Experimental Pediatrics
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• v.46 no.9
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• pp.889-892
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• 2003

Purpose : This study aimed to evaluate risk factors of the first year relapse in children with nephrotic syndrome(NS) without the need for biopsy. Methods : We reviewed, retrospectively, 78 children diagnosed with steroid responsive nephrotic syndrome between July 1997 and June 2002. Median years to follow up were 4.4 years(range : 1-5 years). We divided the patients into two groups(group I : primary responders with no relapse or with only two relapses in the first year after initial response; group II : initial steroid responders with three or more relapses within the first year). We retrospectively reviewed and compared variables - sex, onset age, serum albumin, serum cholesterol, 24 hours urinary protein, creatinine clearance(Ccr), presence of hematuria and hypertension(HTN), and days from initial attack to remission. Results : Of 78 patients(male : 61(78.2%), female : 17(21.8%), age range 1.1 years to 14 years, median $5.1{\pm}3.0years$), 47(60.3%) were in group I and 31(39.7%) were in group II. There were no statistically significant differences in sex, serum albumin, serum cholesterol, 24 hours urinary protein, Ccr, presence of hematuria or HTN. The median age of onset showed no statistical difference between the two groups. However, if the patients are dividing into two groups according to the age of onset of three-years, patients theree yrs old or less fit into group II, as opposed to patients older than three yrs in age(63.2% vs. 32.2%, P<0.05). The days from initial attack to remission was longer in group II($12.9{\pm}0.5$ vs. $16.2{\pm}1.1$, P<0.05). Conclusion : We may conclude that the age of onset of three yrs old or less, and the longer time remission to initial steroid therapy, are risk factors of the first year relapse.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.159-166
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• 2005

Purpose : Recently the merits of 6 weeks of initial prednisolone treatment for pediatric primary nephrotic syndrome have been reported, and the use of the 6 week regimen is increasing. We compared our experiences with the 6 week treatment versus the 4 week treatment for Korean patients. Methods : We conducted a retrospective analysis of 69 children who had primary nephrotic syndrome and who were followed up for at least 12 months in the 4 major medical centers in Daegu. The remission rate, the relapse rate, the frequency of relapse and complication of steroid treatment were compared between the 4 weeks and 6 weeks treatment group. Results : Of the 69 children, 42 were in the 4 week treatment group and 27 were in the 6 week group. The median age, blood pressure, serum total protein, serum albumin, cholesterol, creatinine, estimated creatinine clearance, 24 hour urine protein and 12 month cumulative dose did not differ between the two groups. Among the children who relapsed after steroid treatment, the relapse time was significantly later for the 6 week treatment group. The relapse rate after 1 year of treatment was 62$\%$ in the 4 week treatment group and 52$\%$ in the 6 week treatment group; however, there was no statistically significant difference between the two groups. The frequency of relapse at 12 months was $1.5{\pm}1.2$ times in the 4 week treatment group and $1.1{\pm}1.2$ times in the 6 week treatment group, and there was not different between the two groups. The most common side effects of steroid treatment were an increase of appetite and a cushingoid appearance, and there was no statistical difference between the two groups. Among the 27 children who had kidney biopsies performed, 21 suffered from minimal change nephrotic syndrome. Conclusion : The first relapse time after steroid treatment was significantly later in the 6 week steroid treatment group. The frequency of relapse and the 12 month cumulative dose of steroid were lower in the 6 week treatment group, but there was no statistical significance between the two groups. The side effects of steroid treatment did not differ between the two groups. We need to study the long term side effects and the advanced regimens of steroid treatment in the future.(J Korea Soc Pediatr Nephrol 2005;9:159-166)

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.48-56
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• 1999

Purpose : This multicenter collaboratory study was conducted to see the therapeutic efficacy and side effect of cyclosporine A (Cipol-$N^{(R)}$, Chong Kun Dang) on children with idiopathic nephrotic syndrome who experienced frequently relapsing (FR), steroid dependent (SD), or steroid resistant (SR) pattern. Patients and methods : Thirty-nine children with SD/FR NS and 3 children with SR NS were enrolled in the study. After induction of remission (SD/FR NS) with steroid or after 4 weeks of steroid therapy (SR NS), cyclosporine A was started in a dose of 4-5 mg/Kg/day in two divided dose and steroid (prednisolone or equivalent dose of deflazacort) was tapered slowly. During 16 weeks of study period, monthly check up of physical examination and various laboratory tests including BUN, creatinine, Ccr and cyclosporine blood level were done. Results : Out of 39 children with SD/FR NS, 35($89.7\%$) maintained sustained remission and at 4 weeks after therapy, values of serum protein, albumin, cholesterol, and 24 hours urinary protein excretion showed normal values. Two out of 3 children with SR NS showed and sustained remission with cyclosporine A therapy. Side reaction to cyclosporine A therapy showed hypertrichosis in 8 cases and hyperuricemia in 5 cases. However, other laboratory tests including CBC, liver profile, BUN, creatinine and GFR (creatinine clearance utilizing 24 hour urine) did not show any abnormalities during the 16 weeks of study period. Conclusion : Cyclosporine A (Cipoi-$N^{(R)}$ Chong Kun Dang) can be utilized quite effectively on children with SD/FR or SR NS and further trial of cyclosporine A on long-term basis (1-2 year period) is needed to determine it's efficacy and side effect (especially nephrotoxicity) of long-term administration of cyclosporine A.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.249-268
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• 2005

Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.