• Journal of Biomedical Engineering Research
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• v.16 no.2
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• pp.231-238
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• 1995

Tc-99m-MIBI (Sestamibi) myocardial SPECT along with TI-201 tomographic Imaging has demonstrated wide application and high image quality sufficient for the diagnosis of myocardial perfusion defect, which consequently reflects regional myocardial blood flow. The qualitative values of myocardial SPECT with Tc-99m-MIBI as well ds the quantitative cases depend in some degree on the reconstruction techniques of multiple projections. Filtered backprojection (FBP) Is the common standard method for reconstruction rather than the complicated and time-consuming arithmetic methods. In FBP it is known that the distribution of radioactivity in reconstructed transverse slices varies with the selected litter parameters such as cutoff frequencies and order (Butterworth case) The cutoff frequencies used in clinicAl practice partially remove and decrease the true radioactive distribution and alter the pixel counts, which lead to underestimation of true counts in specific myocardial regions. In this study, we have investigated the effect of cutoff frequencies of reconstruction filter on the artifactually induced perfusion defects, which are often demonstrated near inferior and/or inferoseptal cardiac walls due to the intense hepatic uptake of Tc-99m-MIBI. A computerized method for Identifying the relative degree of artifactual perfusion defect and for comparing those degrees along with the relative amount of hepatic uptake to myocardium was developed and patient images were studied to observe the quantitative degree of underestimation of myocardial perfusion, and to propose some reasonable threshold of cutoff frequency in the diagnosis of perfusion defect quantitatively. We concluded that from the quantitative viewpoint cutoff frequencies may be used as high as possible with the sacrifice of homogeneity of image quality, and those frequencies lower than the common 0.3 Wyquist frequency would reveal severe degradation of radioactive distribution near inferior and/or inferoseptal myocardium when applying Butterworth or low pass filter.

• Journal of Digestive Cancer Research
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• v.5 no.2
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• pp.91-96
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• 2017

Background: To evaluate whether DM affects the SUVmax of metastatic lesions on ¹⁸F-FDG PET/CT and whether the SUVmax can influence the prognosis of metastatic PDAC patients. Methods: We conducted a retrospective study of 86 patients with metastatic PDAC who underwent PET/CT before treatment. The SUVmax of primary and metastatic lesions and the ratios of the SUVmax were measured. Long-term survival was evaluated using clinical parameters. Results: The mean SUVmax of primary lesion was lower in the DM group than in the non-DM group (4.74 vs. 5.96, p=0.009). The SUVmax for all metastatic lesions, except those in the lung, were lower in the DM group than in the non-DM group, and these differences were statistically significant in the lymph nodes and peritoneum. In the 35 patients with hepatic metastasis, higher ratios of the liver SUVmax significantly correlated with shorter OS (HR, 2.625; p=0.013). Conclusion: DM can influence the lower SUVmax of metastatic lesions as well as primary lesions. The SUVmax ratio of hepatic metastasis could influence on prognosis in metastatic PDAC patients.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.565-574
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• 2021

Background: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, Panax ginseng, Schisandra chinensis, and Liriope platyphylla. SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown. Methods: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on in vitro XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC). Results: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1b levels in both the serum and kidneys. SMS-E inhibited both in vitro XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W. Conclusion: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

• Herbal Formula Science
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• v.27 no.3
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• pp.223-236
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• 2019

Dengropanax morfiferus (D), Broussonitia kazinoki (B), and Cudriania tricuspidata (E), a widely cultivated species in South Korea, has been used as traditional medicine to treat numerous diseases. In this study, we evaluated the antidiabetic effects in a various signaling mechanisms using mixed extract and major component contents were analyzed by HPLC in the combined extracts from Dengropanax morfiferus, Broussonitia kazinoki, and Cudriania tricuspidata (DBCE). DBCE inhibited ${\alpha}$-glucosidase and ${\alpha}$-amylase activation and showed potent antioxidant effects, which are evaluated using DPPH, ABTS, and SOD assay. Cytokines, which are released by inflammatory cells in pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. DBCE showed the protective effects in RINm5F cells against cytokines-induced damage by suppressing inducible nitric oxide (NO) synthase and COX-2 expression and NO production. Insulin resistance is the primary characteristic of type 2 diabetes. Therefore, the regulatory effect of DBCE on glucose uptake and production are investigated in insulin-responsive human HepG2 cells. DBCE stimulated glucose uptake, prevented Glut2 and phosphor-IRS1 downregulation induced by high glucose (HG, 30 mM). Moreover, DBCE pretreatment diminished glucose levels, PEPCK and G6Pase overexpression provoked by HG. These findings suggest that DBCE might be used for diabetes treatment through alpha-glucosidase or alpha-amylase activity regulation, pancreatic beta cell protection, hepatic glucose sensitivity improvement. Cytokines, which are released by inflammatory cells' infiltrations around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus.

• Journal of Yeungnam Medical Science
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• v.36 no.1
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• pp.26-35
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• 2019

Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

• Nutrition Research and Practice
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• v.17 no.6
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• pp.1099-1112
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• 2023

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.6
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• pp.525-530
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• 2013

Multidrug resistance 3 (MDR3) is expressed on the canalicular membrane of the hepatocytes and plays an important role in protecting the liver from bile acids. Altered ABCB4 gene expression can lead to a rare hepatic disease, low phospholipid-associated cholelithiasis (LPAC). In this study, we characterized 3 ABCB4 mutations in LPAC patients using various in vitro assay systems. We first measured the ability of each mutant to transport paclitaxel and then the mechanisms by which these mutations might change MDR3 transport activity were determined using immunoblotting, cell surface protein biotinylation, and immunofluorescence. Through a membrane vesicular transport assay, we observed that the uptake of paclitaxel was significantly reduced in membrane vesicles expressing 2 ABCB4 mutations, F165I and S320F. Both mutants showed significantly decreased total and cell surface MDR3 expression. These data suggest two missense mutations of ABCB4 may alter function of MDR3 and ultimately can be determined as LPAC-causing mutations.

• Korean Journal of Clinical Pharmacy
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• v.23 no.4
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• pp.316-321
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• 2013

Purpose: Atorvastatin, a HMG-CoA reductase inhibitor is widely prescribed in hyperlipidemic patients and telmisartan, an angiotensin receptor blocker is frequently used in the treatment of hypertension. Both drugs are substrates of organic anion transporting polypeptide (OATP) expressed in basolateral membrane in the liver, and undergo high first pass metabolism. Therefore, OATP-mediated hepatic uptake is important for disposition and metabolism of these drugs. The present study was designed to investigate the pharmacokinetic interactions between atorvastatin and telmisartan in rats. Method: Young adult SD rats were divided into three groups (n=6, each) and atorvastatin (10 mg/kg) and telmisartan (4 mg/kg) were orally given alone and together. Heparinized blood was serially taken and plasma concentrations of both drugs were measured using HPLC-MS/MS. Pharmacokinetic parameters of two drugs were calculated. Results: No significant pharmacokinetic change was found except a delay of time to peak of telmisartan when administered with atorvastatin. Each drug at the present dosage seemed to be insufficient to alter the pharmacokinetic parameters of its counterpart drug. Conclusion: Conclusively, co-administration of atorvastatin and telmisartan may lead to negligible clinical consequences.

• Fisheries and Aquatic Sciences
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• v.19 no.4
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• pp.19.1-19.7
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• 2016

A laboratory experiment was conducted to determine hexavalent chromium ($Cr^{6+}$) accumulation in the mullet and investigate $Cr^{6+}$ toxicity using a panel of biomarkers including metallothioneins (MTs), glutathione (GSH), glutathione S-transferase (GST), and superoxide dismutases (SODs) for 4 weeks. $Cr^{6+}$ bioaccumulation in all tissues, except muscle, was consistently time- and dose-dependent. The accumulation of $Cr^{6+}$ for 4-week exposures was in the following order: $kidney{\approx}liver$ > $intestine{\approx}gill$ > spleen > muscle. Compared with the control, $Cr^{6+}$ bioaccumulation was increased in ${\geq}200{\mu}g\;L^{-1}$ groups (P < 0.05). An independent relation was observed between accumulation factors (AFs) and exposure concentration. But AFs increased with exposure time. In the liver and gill, GST and SOD differed from the control at a high $Cr^{6+}$ concentration at 2 and 4 weeks (P < 0.05). This study indicated that the gills were as sensitive as the liver to $Cr^{6+}$ toxicity. However, the latter appeared to influence largely on the organism's adaptive response to $Cr^{6+}$, since $Cr^{6+}$ may elevate GSH and MT levels by enhancing the hepatic uptake of metal in the mullet.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2305-2309
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• 2012

Crocin, the main pigment of Crocus sativus L., has been shown to have antiproliferative effects on cancer cells, but the involved mechanisms are only poor understood. This study focused on probable effect of crocin on the immortality of hepatic cancer cells. Cytotoxicity of crocin ($IC_{50}$ 3 mg/ml) in hepatocarcinoma HepG2 cells was determined after 48 h by neutral red uptake assay and MTT test. Immortality was investigated through quantification of relative telomerase activity with a quantitative real-time PCR-based telomerase repeat amplification protocol (qTRAP). Telomerase activity in 0.5 ${\mu}g$ protein extract of HepG2 cells treated with 3 mg/ml crocin was reduced to about 51% as compared to untreated control cells. Two mechanisms of inhibition, i.e. interaction of crocin with telomeric quadruplex sequences and down regulation of hTERT expression, were examined using FRET analysis to measure melting temperature of a synthetic telomeric oligonucleotide in the presence of crocin and quantitative real-time RT-PCR, respectively. No significant changes were observed in the $T_m$ telomeric oligonucleotides, while the relative expression level of the catalytic subunit of telomerase (hTERT) gene showed a 60% decrease as compared to untreated control cells. In conclusion, telomerase activity of HepG2 cells decreases after treatment with crocin, which is probably caused by down-regulation of the expression of the catalytic subunit of the enzyme.