• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1807-1810
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• 2014

Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 ${\mu}M$ for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6351-6356
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• 2013

Background: Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. Materials and Methods: Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 ${\mu}g/day$ B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. Results: The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was $2.7{\pm}2.2$. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was $4.9{\pm}2.4$. Conclusions: Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.

• Bulletin of the Korean Chemical Society
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• v.32 no.2
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• pp.651-655
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• 2011

We synthesized a novel cationic dendrimer consisting of a poly(amidoamine) dendrimer (PAMAM, generation 4) backbone with both L-arginine (Arg) at the termini and 6-aminohexanoic acid (Ahx) between the original core polymer and the peripheral Arg units. The sequential chemical modification of PAMAM G4 with Ahx and Arg resulted in higher transfection efficiency with much less cytotoxicity. PAMAM G4-Ahx-Arg formed stable polyplexes at weight ratios of 8:1 or higher (polymer: plasmid DNA), and the mean polyplex diameter was $180{\pm}20nm$. PAMAM G4-Ahx-Arg showed much higher transfection ability than PAMAM G4 or PAMAM G4-Ahx. Furthermore, PAMAM G4-Ahx-Arg was much less cytotoxic than PEI25KD and PAMAM G4-Arg. In addition to Arg grafting of the PAMAM dendrimer, which endows a higher transfection capability, the addition of Ahx spacer increased dendrimer hydrophobicity, introduced flexibility into the conjugated amino acids, and reduced cytotoxicity. Overall, it appears that the concomitant modification of PAMAM with Ahx and Arg could lead to new PAMAM conjugates with better performances.

• Journal of Sasang Constitutional Medicine
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• v.23 no.1
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• pp.53-62
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• 2011

1. Background: This is the first documented study on the four medications for the Mangeum symptomatology (亡陰證) in the Soyangin disease category. The four medications, Hyeongbangsabaek-san (荊防瀉白散), Jeoryeongchajeonja-tang (猪苓車前子湯), Hyeongbangjihwang-tang (荊防地黃湯), and Hwalseokgosam-tang (滑石苦蔘湯), were comparatively analyzed on their compositive principles and respective symptomatologies. 2. Methods: Previous literature, including classical works on earlier Sasang Constitutional Medicine (different editions of Donguisusebowon and Dongmuyugo), were reviewed for relevant material on the Mangeum medications. 3. Results and Conclusions: 1) Hyeongbangsabaek-san (荊防瀉白散) is used in pathologies of early stages of invasion of the internal heat in the lower-most burn-center (locus related to the Kidney system). 2) Jeoryeongchajeonja-tang (猪苓車前子湯) is used when pathogenic dampness-heat invades the lower-most burn-center (locus related to the Kidney system). 3) Hyeongbangjihwang-tang (荊防地黃湯) is used to treat deficient heat involving injury of the lower-most burn-center (locus related to the Kidney system). 4) Hwalseokgosam-tang (滑石苦蔘湯) is used when the lower-most burn-center (locus related to the Kidney system) is in the early stages of exhaustion, expecially accompanied by concomitant dampness-heat. 5) The Mangeum symptomatology (亡陰證) was fully understood only after the completion of the 1901 Sinchuk edition (辛丑本) of Donguisusebowon (東醫壽世保元).

• YAKHAK HOEJI
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• v.37 no.5
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• pp.544-548
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• 1993

The pharmacokinetics of DWP302, a new combined ranitidine preparation in rats and dogs was studied using HPLC. DWP302 was composed of ranitidine, sucralfate and tripotassium dicitrato bismuthate. Especially, this study was focused on the possibilities that the concomitant administration of either sucralfate or TDB may affect the absorption of orally administered ranitidine. Ranitidine and DWP302 were orally administered to rats at a dose of ranitidine 10mg/kg. Several rats showed the biphasic peak of plasma concentration. AUC$_{S_{0-8}}$ of ranitidine and DWP302 group were found to be 1040$\pm$109 and 945$\pm$124 ng.hr/ml, respectively, and there was no significant difference between both AUCs. In a cross-over study for dogs, $C_{max}$, t$_{1/2}$ beta and total AUC of ranitidine group were found to be 625.8$\pm$86.7 ng/ml, 2.80$\pm$0.28 hr and 1688$\pm$127 ng.hr/ml, and those of DWP302 group were 562.6$\pm$120.9 ng/ml, 3.05$\pm$0.30 hr and 1673$\pm$123 ng.hr/ml, respectively. There was no significant difference between those parameters, but Tmax of DWP302 group (1.69$\pm$0.31 hr) was significantly different from ranitidine group (1.13$\pm$0.26 hr). The results suggest that either sucralfate or TDB may affect the lag-time or rate of absorption of ranitidine but not the extent of absorption.

• Safety and Health at Work
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• v.8 no.2
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• pp.162-168
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• 2017

Background: Pelvic ring fractures (PRFs) may influence the daily activities and quality of life of the injured. The aim of this retrospective study was to explore the functional outcomes and factors related to return to work (RTW) after PRF. Methods: During the years 2003-2012, 282 injured individuals aged 20-55 years on the date of the accident, were hospitalized and treated for PRFs in a large tertiary hospital in Athens, Greece. One hundred and three patients were traced and contacted; 77 who were on paid employment prior to the accident gave their informed consent to participate in the survey, which was conducted in early 2015 through telephone interviews. The questionnaire included variables related to injury, treatment and activities, and the Majeed pelvic score. Univariate and multiple regression analyses were used for statistical assessment. Results: Almost half of the injured (46.7%) fully RTW, and earning losses were reported to be 35% after PRF. The univariate analysis confirmed that RTW was significantly related to accident site (labor or not), the magnitude of the accident's force, concomitant injuries, duration of hospitalization, time to RTW, engagement to the same sport, Majeed score, and complications such as limp and pain as well as urologic and sexual complaints (p < 0.05 for all). On multiple logistic regression analysis, the accident sustained out of work (odds ratio: 6.472, 95% confidence interval: 1.626-25.769) and Majeed score (odds ratio: 3.749, 95% confidence interval: 2.092-6.720) were identified as independent predictive factors of full RTW. Conclusion: PRFs have severe socioeconomic consequences. Possible predictors of RTW should be taken into account for health management and policies.

• Journal of The Korean Society of Clinical Toxicology
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• v.4 no.1
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• pp.69-72
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• 2006

Dicamba is a benzoic acid and classified as a chemically related chlorophenoxy herbicide which is widely used for the control of broad-leaved weeds. While the chlorophenoxy herbicide poisoning is known to be uncommon, its ingestion can result in serious or sometimes fatal outcome. A 65-year-old man ingested about 300 ml of dicamba in a suicidal attempt and three hours later he was admitted hospital, complaining abdominal pain, nausea and vomiting. On admission his vital signs were normal and laboratory findings were not remarkable except metabolic acidosis in arterial blood gas analysis. Shortly after the admission endotracheal tube was inserted due to altered mental state and activated charcoal was given after performing gastric lavage. However, his vital signs became unstable 6hrs after the ingestion and mechanical ventilation was started with administration of inotropic agents. In spite of urine alkalization for rapid elimination of the absorbed dicamba, the metabolic acidosis was aggravated with concomitant rhabdomyolysis and acute renal failure, and he died 24 hrs after the ingestion.

• Korean Journal of Head & Neck Oncology
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• v.20 no.2
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• pp.189-193
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• 2004

Basaloid squamous carcinoma (BSC) is an uncommon aggressive variant of squamous cell carcinoma with a predilection for hypopharynx, tongue base, and larynx. We present 5 cases of BSC of unusual sites, each from maxillary sinus, external auditory canal, submandibular gland, tonsil, and nasopharynx. Only a few cases arising in these sites have been reported to date. Patients included 3 men and 2 women with the age range of 45-69 years (mean, 56.4 years). Microscopically, the tumors were characterized by solid lobules and nests of ovoid basaloid cells with abundant desmoplastic stroma. Comedonecrosis, peripheral palisading of tumor cells, trabecular pattern, and rosette-like arrangement were commonly observed. Tumor cells had scanty cytoplasm and their nuclei were ovoid, relatively uniform, and hyperchromatic. In two cases, concomitant squamous cell carcinoma in situ was identified. Immunohistochemical stains revealed that tumor cells were strongly positive for pancytokeratin and negative or weakly positive for p63. Being aware of BSC that can arise from unusual sites would help diagnose correctly and treat properly this rare and distinct clinicopathologic entity.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.351-357
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• 1998

In order to understand the mechanism of the regulation of CYPIAI gene expression and ethoxy-resorufin deethylase (EROD) activity in ex vivo system, we have studied the action of TCDD and 3MC in theisolated perfused male rat liver. CYPIAI myNA level and EROD activity were measured in rat liver that wasisolated and perfused with va.ious chemicals such as 2,3,7,8-tet.achlorodibenzo-p-dioxin (TCDD), 3-methyl-cholanthrene (3MC), $17{\beta}$-est.adios ($E_2$), morin. TCDD or 3MC alone perfusion into male rat liver resulted in increase of CYPIAI mRNA level and the magnitude of stimulation was one and half times higher with TCDD treatment than 3MC treatment. However $E_2$ perfusion into male rat liver showed slight stimulation of CYPIAI mRNA level. When $10_{-8}$ M $E_2$ was perfused concomitantly with either $10_{-9}$ M TCDD or $10_{-9}$ M 3MC, stimulated CYPIAI mRNA by either TCDD or 3MC was inhibited. Morin was examined for its effects on CYPIAI mRNA level and result was similar to that was observed with estrogen except that morin alone did not change the level of CYPIAI mRNA. EROD activity was also stimulated with either TCDD or 3MC perfusion, and the magnitude of EROD stiumlation was similar to that of CYPIAI mRNA stimulation in response to TCDD or 3MC perfusion. This data is different from the data that we have obtained with female rat liver. Concomitant perfusion either $E_2$ or morin with TCDD or 3MC inhibited 3MC perFusion or TCDD perfusion stimulated EROD activity. These data confirm the hypothesis that TCDD and 3MC might act through the same mechanism of action on the regulation of CYPIAI gene expression in male rat liver.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.255-260
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• 2011

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after oral administration of diltiazem (15 $mg{\cdot}kg^{-1}$) with ticlopidine (3 or 9 $mg{\cdot}kg^{-1}$). The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activities were also evaluated. Ticlopidine inhibited CYP3A4 enzyme activity in a concentrationdependent manner with a 50% inhibition concentration ($IC_{50}$) of 35 ${\mu}M$. In addition, ticlopidine did not significantly enhance the cellular accumulation of rhodamine-123 in NCI/ADR-RES cells overexpressing P-gp. Compared with the control (given diltiazem alone), ticlopidine significantly altered the pharmacokinetic parameters of diltiazem. The peak concentration ($C_{max}$) and the area under the plasma concentration-time curve (AUC) of diltiazem were significantly (9 $mg{\cdot}kg^{-1}$, p<0.05) increased in the presence of ticlopidine. The AUC of diltiazem was increased by 1.44-fold in rats in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$). Consequently, the absolute bioavailability (A.B.) of diltiazem in the presence of ticlopidine (9.3-11.5%) was signifi cantly higher (9 $mg{\cdot}kg^{-1}$, p<0.05) than that in the control group (8.0%). Although ticlopidine significantly (p<0.05) increased the AUC of desacetyldiltiazem, the metabolite-parent AUC ratio (M.R.) in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$) was significantly decreased compared to that in the control group, implying that ticlopidine could effectively inhibit the metabolism of diltiazem. In conclusion, the concomitant use of ticlopidine significantly enhanced the oral bioavailability of diltiazem in rats by inhibiting CYP3A4-mediated metabolism in the intestine and/or liver rather than by inhibiting intestinal P-gp activity or renal elimination of diltiazem.