• Archives of Pharmacal Research
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• v.28 no.4
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• pp.483-487
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• 2005

The aim of this study was to investigate the pharmacokinetic changes of verapamil and its major metabolite, norverapamil, after oral administration of verapamil (10 mg/kg) in rabbits with slight, moderate and severe hepatic failure induced by carbon tetrachloride. The plasma verapamil concentrations in all groups of hepatic failure were significantly higher (p<0.01) than the control. However, the plasma norverapamil concentrations in severe hepatic failure were significantly higher (p<0.05) than the control. The peak concentrations ($C_{max}$) and the areas under the plasma concentration-time curve (AUC) of verapamil in the rabbits were significantly (p<0.01) higher than the control. The absolute bioavailability ($F_{A.B}$) and the relative bioavailability ($F_{R.B}$) of verapamil in the rabbits with hepatic failure were significantly higher ($13.6-22.2\% and 150-244\%$, respectively) than the control ($9.1\% and 100\%$, respectively). Although the AUC and $C_{max}$ of its major metabolite, norverapamil, in slight, moderate hepatic failure were not significantly lower than the control, the metabolite-parent AUC ratio in all groups of hepatic failure was decreased significantly (p<0.05, in slight group; p<0.01, in moderate and severe group) than the control. This could be due to decrease in metabolism of verapamil in the liver because of suppressed hepatic function in the hepatic failure groups because verapamil is mainly metabolized in the liver. From our data, it would seem appropriate that in patients with liver disease, doses of verapamil should be decreased by degree of hepatic failure.

• Journal of Microbiology and Biotechnology
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• v.26 no.8
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• pp.1392-1397
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• 2016

Curcumin is a polyphenol derived from the plant Curcuma longa, which is used for the treatment of diseases associated with oxidative stress and inflammation. The present study was undertaken to determine the protective effect of curcumin against naproxen-induced gastric antral ulcerations in rats. Different doses (10, 50, and 100 mg/kg) of curcumin or vehicle (curcumin, 0 mg/kg) were pretreated for 3 days by oral gavage, and then gastric mucosal lesions were caused by 80 mg/kg naproxen applied for 3 days. Curcumin significantly inhibited the naproxen-induced gastric antral ulcer area and lipid peroxidation in a dose-dependent manner. In addition, curcumin markedly increased activities of radical scavenging enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase in a dose-dependent manner. Specifically, 100 mg/kg curcumin completely protected the gastric mucosa against the loss in the enzyme, resulting in a drastic increase of activities of radical scavenging enzymes up to more than the level of untreated normal rats. Histological examination obviously showed that curcumin prevents naproxen-induced gastric antral ulceration as a result of direct protection of the gastric mucosa. These results suggest that curcumin blocks naproxen-induced gastric antral ulcerations through prevention of lipid peroxidation and activation of radical scavenging enzymes, and it may offer a potential remedy of gastric antral ulcerations.

• Journal of Oriental Neuropsychiatry
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• v.28 no.2
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• pp.123-136
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• 2017

Objectives: The objective of this study is to investigate the anti-amnesic effects of AR, Aucklandiae Radix, ground powder on scopolamine (Sco)-induced memory impairment in mice (C57BL/6) through its favorable acetylcholine (ACh) and acetylcholinesterase (AChE) activity, Choline acetyltransferase (ChAT) mRNA expression, and antioxidant effect. Methods: Six groups, a total of 20 intact or 100 Sco treated mice, were selected based on their body weights and were used in this study. Half of the mice in each group were used for the passive avoidance task test and the measurements of hippocampus ACh content, AChE activity and ChAT mRNA expression. The remaining half of the mice in each group were used for the Morris water maze test and cerebral antioxidant defense system measurement. Results: Marked decreases in step-through latency times in the passive avoidance task test and increases in escape latency times in the Morris water maze test were observed with decreases in the hippocampus ACh content and ChAT mRNA expression, and increases in the hippocampal AChE activities, as a result of Sco intraperitoneal treatment, in the present study. In addition, destruction of the cerebral cortex antioxidant defense systems was observed in Sco control mice as compared with intact vehicle control mice. However, 28 days of continuous oral pre-treatment with AR ground powder at doses of 400, 200 and 100 mg/kg markedly and dose-dependently inhibited the Sco treatment-related amnesia. Conclusions: The results prove that oral administration of AR ground powder reduces Sco-induced memory impairment. This is because it can preserve ACh, related to ChAT mRNA expression, cause AChE inhibition, and activate the cerebral antioxidant defense system.

• Mass Spectrometry Letters
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• v.12 no.4
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• pp.200-205
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• 2021

Polynemoraline C, a pyridocoumarin alkaloid, exhibits anticholinergic, anti-inflammatory, antitumor, and antimicrobial activities. A sensitive analytical method of polynemoraline C in mouse plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Polynemoraline C and ¹³C-caffeine (internal standard) in mouse plasma were extracted using a liquid-liquid extraction method coupled with ethyl acetate. This extraction method resulted in high and reproducible extraction recovery in the range of 73.49%-77.31% with no interfering peaks around the peak retention time of polynemoraline C and ¹³C-caffeine. The standard calibration curves for polynemoraline C were linear over the range of 0.5-200 ng/mL with r² > 0.985. The accuracy, precision, and the stability of the data were within acceptable limits on the FDA guideline. After intravenous and oral administration of polynemoraline C at doses of 5 and 30 mg/kg, respectively, the present method was successfully applied to the pharmacokinetic study of polynemoraline C. Polynemoraline C in mouse plasma showed a multi-exponential elimination pattern with a high volume of distribution values. This compound's absolute oral bioavailability was found to be 17.0%. Polynemoraline C's newly developed LC-MS/MS method can be used for further studies on the efficacy, toxicity, and biopharmaceutics of polynemoraline C, as well as its pharmacokinetic studies.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.55-62
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• 2019

HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the $T_{1/2}$ was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice ($19.32{\pm}1.16mg/g$) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.606-624
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• 2022

Objective: The aim of this study was to compare the effects of different doses of Geumnyeonyijin-tang (GNYJT) water extracts with those of metformin (250 mg/kg) in mild diabetic-obese mice. Methods and Results: The 48 mice were divided into 1 normal pellet diet (NFD) group and 5 high-fat diet (HFD) groups. At the end of 12 weeks of oral administration of metformin (250 mg/kg) or GNYJT water extracts (400, 200, or100 mg/kg), the effects were evaluated. The HFD control mice showed noticeable increases in body weight, adipose tissue density, fat pad weight of the periovarian and abdominal wall, and insulin, blood glucose, and HbA1c levels, with decreases in serum HDL levels. Increases in the periovarian and dorsal abdominal fat pad, regions of steatohepatitis, adipocyte hypertrophy, and hepatocyte hypertrophy were also discovered. The HFD group showed a decline in glucose levels and elevation of hepatic gluconeogenesis, suggesting an HFD-induced AMPK downregulation related to glucose dysregulation, as well as lipid metabolism related to obese insulin-resistant type II diabetes, dyslipidemia, and oxidative stress related diabetic hepatopathy (non-alcoholic fatty liver disease, NAFLD). Conclusion: Assessment of the key parameters for inhibition of diabetes and related complications in HFD-fed diabetic-obese mice demonstrated that GNYJT water extracts have favorable ameliorating effects. The effect of GNYJT was manifested through the stimulation of AMPK upregulation of related hepatic glucose enzyme activities and expression of lipid metabolism-related genes. Therefore, appropriate oral dosages of GNYJT could be promising as a new preventive candidate for controlling diabetes and related complications. Further screening of biologically active compounds, elucidation of detailed mechanisms, and more animal studies are warranted.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.619-628
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• 2023

In the modern era, chronic kidney failure due to diabetes has spread across the globe. Prunetin (PRU), a component of herbal medicines, has a broad variety of pharmacological activities; these may help to slow the onset of diabetic kidney disease. The anti-nephropathic effects of PRU have not yet been reported. The present study explored the potential nephroprotective actions of PRU in diabetic rats. For 28 days, nephropathic rats were given oral doses of PRU (20, 40, and 80 mg/kg). Body weight, blood urea, creatinine, total protein, lipid profile, liver marker enzymes, carbohydrate metabolic enzymes, C-reactive protein, antioxidants, lipid peroxidative indicators, and the expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 2 (GLUT-2) mRNA genes were all examined. Histological examinations of the kidneys, liver, and pancreas were also performed. The oral treatment of PRU drastically lowered the blood glucose, HbA1c, blood urea, creatinine, serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, lipid profile, and hexokinase. Meanwhile, the levels of fructose 1,6-bisphosphatase, glucose-6-phosphatase, and phosphoenol pyruvate carboxykinase were all elevated, but glucose-6-phosphate dehydrogenase dropped significantly. Inflammatory marker antioxidants and lipid peroxidative markers were also less persistent due to this administration. PRU upregulated the IRS-1 and GLUT-2 gene expression in the nephropathic group. The possible renoprotective properties of PRU were validated by histopathology of the liver, kidney, and pancreatic tissues. It is therefore proposed that PRU (80 mg/kg) has considerable renoprotective benefits in diabetic nephropathy in rats.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.26 no.3
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• pp.244-250
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• 2022

Backgrounds/Aims: Early recovery after surgery has become a popular trend. The aim of this study was to evaluate effect of nutritional intervention using Encover, an oral nutritional supplement, in patients undergoing hepato-biliary-pancreatic surgery. Methods: This single center, prospective case-control study was conducted in Gangnam Severance Hospital from September 2018 to April 2019. Through randomization, patients were divided into an experimental group (30 patients) and a control group (30 patients). At postoperative seven days, the experimental group was instructed to take two packs of Encover (JW Pharmaceutical, Seoul, Korea) daily for seven days. Body cell mass index was measured at seven days after surgery and 14 days after discharge and Patient-Generated Subjective Global Assessment (PG-SGA) was performed at 14 days after discharge. Results: Body cell mass index during outpatient follow-up was significantly decreased compared to that at discharge in both groups. However, the amount of body cell mass index showed no significant difference between postoperative seven days and outpatient follow-up in either group. During outpatient follow-up, the experimental group had a higher mean value of PG-SGA score than the control group (11.32 ± 3.46 vs. 9.48 ± 3.97; p = 0.037). Conclusions: Short-term Encover doses after surgery may not produce significant results in weight gain or other body cell mass index. Encover did not significantly affect other dietary conditions based on PG-SGA.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.17 no.4
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• pp.447-455
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• 1995

Cavernous sinus thrombosis is one of the major complications of abscesses of the maxillofacial region. The initial symptoms of CST are usually pain in the eye and tenderness to pressure. this is associated with high fluctuating fever, chills, rapid pulse, and sweating. Venous obstruction subsequently causes edema of the eyelids, lacrimation, proptosis, chemosis and retinal hemorrhages. Blindness is sometimes an accompaniment of cavernous sinus thrombosis when the infection also involves the orbit. There is also cranial nerve involvement (oculomotor, troclear, abducence) and ophthalmoplegia, diminished or absent corneal reflex, ptosis, and dilation of the pupil occur. The terminal stages bring signs of advanced toxemia and meningitis. Infections of the face can cause a septic thrombosis of the cavernous sinus. Furunculosis and infected hair follicles in the nose are frequent causes. Extractions of maxillary anterior teeth in the presence of acute infection and especially curettage of the sockets under such circumstances can cause this condition. The infection is usually staphylococcal. The inflection may spread directly through the pterygoid plexus of veins and the pterygomaxillary space and then ascend into the sinus or it may spread directly from the pterygopalatine space to the orbit. This is possible because of the absence of valves in the angular, facial, and ophthalmic veins. The treatment is empirical antibiotic therapy followed by specific anbibiotic therapy based on blood or pus culture. The inflection usually involves one side, however, it may easily spread to the opposite side through the circulus sinus. Unless it is treated early, the prognosis is poor even in this doses. Occasionally the antibiotics will not adequately resolve the septic thrombus, and death ensues. the use of anticoagulants to prevent venous thrombosis has been recommended, but the efficacy of such therapy has not been substantiated. Surgical access through eye enucleation has been suggested. We report a case which demonstrates cavernous sinus thrombosis by the infection after the functional neck dissection and the intraoral reconstruction with auriculomastoid fascio-cutaneous island flap.

• Journal of the korean academy of Pediatric Dentistry
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• v.46 no.2
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• pp.135-138
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• 2019

The aim of this study was to investigate the susceptibility of Mutans streptococci in both planktonic and biofilm states to erythrosine. S. mutans was cultured in brain-heart infusion (BHI) broth. Erythrosine was diluted in BHI broth and prepared at a concentration range of $0.02-10000{\mu}g/L$. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were measured using the microdilution method. After forming biofilms on 96-well plates, the minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were measured. S. mutans was susceptible to erythrosine in both planktonic and biofilm states. MIC and MBC values were both $19.5{\mu}g/L$ for the planktonic state, while MBIC and MBEC values were $313{\mu}g/L$ and $2500{\mu}g/L$, respectively, for the biofilm state. Erythrosine ($19.5{\mu}g/L$) exhibited a bactericidal effect on S. mutans (killing 99.9%) in the planktonic state. For biofilms, erythrosine inhibited biofilm growth and eradicated 99.9% of biofilm bacteria at higher concentrations than MIC and MBC. These MBIC and MBEC concentrations are much lower than known noxious doses, and the MIC, MBC, and MBIC values were even lower than clinical concentrations.