Problems appear when triptans are taken orally. For example, the bioavailability of triptan is reduced by the digestive system, and the drug level in the blood reduces rapidly over time; there is also a possibility of gastrointestinal disorder. To improve side effects, a transdermal patch has been prepared in hydrogel form. The polymer matrix that makes up the hydrogel uses PVA; PEG is used as an additive to induce inter/intra hydrogen bonding of the PVA and almotriptan drug is added. In addition, to accelerate micro-phase separation between PVA chains, liquid nitrogen is used. In FT-IR analysis, the absorption bands of PVA, PEG, and almotriptan were found. The degree of crystallinity, the water uptake ability and tensile strength were increased with increasing PEG content. In drug release tests, the amount of drug released increased depending on the PEG content. In this study, hydrogels with 10 wt% PEG showed better performance in drug release. Approximately 60% of the total drug amount was released in 2 hr, and the drug continued to release for 1 day. Thus, the prepared hydrogel patch is suitable as a transdermal formulation for the second dose administration of triptans to patients who require recurrent migraine treatment within 24 hr after the first administration.
Objectives : Magnoliae officinalis Cortex (MOC) has been used in traditional medicine for digestive diseases in Korea, China and Japan. However, Machili thunbergii Cortex (MTC) also has been used as a substitute of MOC in Korea sometimes. Thus, this study was carried out to investigate and compare the effects of MOC and MTC on intestinal motility of isolated small intestinal segments from ICR mouse. Methods : Changes in motility were recorded via isometric transducers connected to a data acquisition system and amplitude, frequency and area under the curve (AUC) of intestinal spontaneous phasic contraction were compared. Results : The MOC extracts ($1{\sim}{\mu}g/mL$) dose-dependently decreased both amplitudes and frequencies of the spontaneous phasic contraction, but not AUC. However, high concentration of MOC (100 ${\mu}g$/mL) evoked tonic contraction. And it was not inhibited by tetrodotoxin, a sodium channel blocker, and nifedipine, a L-type $Ca^{2+}$ channel antagonist. These results suggested that MOC (100 ${\mu}g$/mL)-induced tonic contraction is not mediated by nerve or L-type $Ca^{2+}$ channel. On the other hand, the MTC extracts dose-dependently inhibited amplitude and AUC, but not the frequency. Conclusions : Although both MOC and MTC affected intestinal motility, MOC is more effective on intestinal motility than MTC. And MOC has been used as a traditional medicine for a long time but not MTC. Thus, we suggested that MTC should not be used in Korea as a substitute of MOC and MOC might be useful traditional medicine for gastrointestinal disease. The mechanism of MOC is still remained to elucidate.
Journal of The Korean Society of Clinical Toxicology
/
v.7
no.2
/
pp.164-171
/
2009
Purpose: The number of patients who take warfarin is growing and so is the number of complications. Hemorrhage is the major complication, but the clinical characteristics and outcomes have not been determined for Korean patients. Therefore, we tried to evaluate the characteristics of the patients with hemorrhagic complications after taking warfarin as anticoagulation therapy. Methods: We retrospectively reviewed the medical records of the patients who visited the emergency room with bleeding complications after taking warfarin anticoagulation at the out-patient clinic for 1 year from 1 st January 2008. We compared between two groups (the major hemorrhage group vs. the minor hemorrhage group) according to the clinical criteria, the unstable vital signs that required blood transfusion, transfusion more than 2 units of blood, the need for further laboratory follow-up, the need for interventional treatment and the development of critical complications or death due to bleeding. Results: There were 150 patients who met the criteria and had acute hemorrhagic complications (the major group: 90 patients and the minor group: 60 patients). In the major hemorrhage group, the frequent sites of bleeding were the gastro-intestinal system (40 patients), lung (14 patients) and intracranium (7 patients). At the emergency room, the major group showed a higher initial INR of the activated prothrombin time than did the minor group (p=0.02). The bleeding sites of the fatal cases were the gastro-intestinal system (3 patients), lung (3 patients) and intracranium (3 patients), but the percentage of fatality was the highest for intracranium bleeding. Conclusion: In the major hemorrhage group, gastrointestinal bleeding was the most frequent complication and fatality was the highest for intracranium bleeding. An initially higher INR showed a greater risk of major bleeding, but not more fatalities.
Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.
Arsenic trioxide($As_2O_3$) was introduced into the treatment of refractory or relapsed acute promyelocytic Ieukemia. Some investigators have reported that arsenic trioxide had induced apoptosis in a variety of solid human tumor cell lines, including non-small cell lung cancer. Non-steroidal anti-inflammatory drugs(NSAIDs) are powerful chemopreventive agents for gastrointestinal cancers and the growth of established tumors are reduced by inducing apoptosis. It's also reported that NSAIDs enhanced tumor response to chemotherapeutic drugs or radiation. In this study, we aimed to determine whether combination of arsenic trioxide with sulindac augmented its apoptotic potential in NCI-H157 human lung cancer cells. The human lung cancer cell line NCI-H157 was treated with arsenic trioxide and sulindac. Cell viability was measured by the MTT assay. Apoptosis was measured by nuclear staining and flow cytometric analysis. The catalytic activity of the caspase families were measured by the fluorogenic cleavage of biosubstrates. The western blotting were also performed to define the mechanical basis of apoptosis. Combination treatment of arsenic trioxide and sulindac decreased the viability of NCI-H157 human lung cancer cells in a dose-dependent manner. The catalytic activity of caspase-3, 8 and 9 proteases were increased after combination treatment. Consistently PARP was cleaved from 116kDa to 85kDa fragments, and the expression of ICAD was decreased by time-dependent manner. Also combination treatment increased the expression of Fas and Fas/L. Combination therapy of arsenic trioxide with sulindac augments cell death and induces apoptosis via the activation of caspase cascade in NCI-H157 human lung carcinoma cells.
Journal of Korean Academy of Oral and Maxillofacial Radiology
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v.26
no.2
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pp.133-145
/
1996
Aspirating or swallowing foreign bodies is a common occurrence. If they are wholly or partly radiopaque, their localization in and progress through the gastrointestinal tract can be more effective. Of the dental origin foreign materials swallowed, the most common things are fragments of anterior maxillary partial denture. But the radiopacity of denture base resins is not sufficient to determine the location of the objects. The purpose of this study was to develop a radiopaque dental acrylic resin, which has clinically detectible radiopacity with minimal change of mechanical properties and color. The radiopacity, color change(CIE 6..E) and microhardness of acrylic resins were determined after mixing barium sulfate or iodide compound. Thermocycling course was conducted to determine the change of characteristic of resins after using for a long time in the mouth. Five or ten percent of barium sulfate to total weight of cured material was mixed with heat curing dental acrylic resin or chemically curing orthodontic resin. In the case of iodide compound, the mixing ratio was two or three percent. After mixing the high radiopaque materials, resin was cured to 20×20×2 mm plate, polished with #600 sand paper and finally polished with Microcloth(Buehler). The specimens were thermocycled in 5 and 55 t distilled water for 2,000 times, and the measurement of radiopacity, color and Vickers hardness was repeated every 500 times thcrmocycling. The radiopacity of specimens on the X -ray films was measured with densitometer(X-rite). The color change was detennined with differential colorimeter(Model TC-6FX, Tokyo Denshoku), and the Vickers hardness number was measured with microhardness tester(Mitsuzawa). The following results were obtained : 1. All the three variables, the kinds of acrylic resins, the mixing or the kinds of high radiopaque materials and thermocycling, had combined effect on the radiopacity of the dental acrylic resins(p<0.0l). 2. The two variables, the mixing or the kinds of high radiopaque materials and thermocycling, influenced on the radiopacity of the dental acrylic resins(p<0.01). But the kinds of acrylic resins did not influence on the color change of mixed dental acrylic resins(p>0.05). 3. Each of the three variables, the kinds of acrylic resins, the mixing or the kinds of high radiopaque materials and thermocycling, influenced on the radiopacity of dental acrylic resins(p<0.0l). 4. The high radiopaque materials used in this study did not yield clinically usable radiopacity, and the color change was great after mixing those materials.
Panax ginseng C. A. Meyer, which has been known for more than EWO years. occupies a Particular prince in folk medicine as so called tonic remedy. The pharmacolgical investigations of ginseng, based on the scientific concepts and methodology, have been performed by many researchers through the past 50∼60 years at different parts of the world. The pharmacological action of Panax ginseng compiled from the numerous reports can be summarized as follows: 1. On central nervous system, the effect of Panax ginseng is timulatory in smaller doses and somewhat depressive in larger doses. From the psychopharmacological aspect, ginseng seems to increase the mental efficiency of man. 2. Ginseng has the effect tending to Protect organism from various physical and chemical stresses. 3. The growth and basal metabolic rates of experimental animals are stimulated by ginseng. Ginseng also prolongs the survival time of animals under adverse influences. 4. Increasing the physical and mental efficiency, ginseng postpones the onset of fatigue and increases the working capacities. 5. In the case of the intravenous administration of ginseng, a transitory and slight hypotensive effect is observed. These hypotensive effects seems to include that of a direct action and actions related to the release of histamine and/or serotonin by ginseng. 6. It is Presumed that ginseng lowers the elevated bleed ingar and cholesterol level. 7. Ginseng tends to increase the gastrointestinal motizity and tone 8. It is presumed that ginseng Promotes the iron metabolism and activates the hematopoietic factors. 9. Ginseng tends to stimulate the biosynthesis of nucleic acid and release of histamine and serotonin. 10. The toxicity end adverse reactions of ginseng appear to be nothing that warrants apprehension. 11. Anticancer erects of ginseng seem to be due to indirect action rather than direct action on cancer cell, by improving the host condition 12. Recent clinical trials of ginseng harts obtained sent good results, but Present trial is still limited in its range, so it is necessary to broaden the scope of trial covering many kinds of organs and diseases. From the above, although it appears that substantial advancements have been achieved in the studies on the Pharmacological actions of Panax ginseng there are many discrepancies noticed in the reported data. Furthermore the precise mechanisms of actions of ginseng are sometimes obscure, even unknown in other actions as the students stand now. The main reasons for this are considered to be that even though saponin has been identified at one of the active substances of ginseng, other components have not fully been identified and that the experimental approaches of the investigations varied with different researchers. Thus a thorough analysis of the chemical components and newer standardized concepts and metohds appear to be the pre-requisites for further study of the pharmacolgical effects and mechaisms of Panax ginseng.
Ginsenosides have been regarded as the principal components, responsible for the pharmacological and biological activities of ginseng. Absorption of major ginsenosides at the gastrointestinal tract was extremely low, when ginseng taken orally. In order to improve the absorption and bioavailability, transformation of major ginsenosides into more active and valuable minor ginsenoside is much required. In this present study, We isolated a lactic acid bacteria Leuconostoc fallax LH3 from the Korean fermented food Kimchi, which have higher ${\beta}$-glucosidase activity. Using the ethanol precipitated curd enzyme of Leuconostoc fallax LH3, we investigated the biotransformation of ginsenoside Rd at different experimental condition to increase transformation. The maximum convertion was supported at 30 $^{\circ}C$ and decreased when temperatures increased. In order to optimize the effect of pH, the curd enzyme was mixed 20 mM sodium phosphate buffer (pH 3.5 to pH 8.0). Ginsenoside Rd was almost hydrolyzed between pH 7.0 and pH 9.0, but not hydrolyzed above pH 10.0. Ginsenoside Rd was hydrolyzed after 24 hrs incubation, but whereas the ginsenoside F2 was appeared from 36 hrs, and all ginsenoside Rd was transformed to F2 after the 60 hrs incubation. Based on this study, the curd enzyme of Leuconostoc fallax LH3 transformed the ginsenoside Rd at the 30$^{\circ}C$ and the pH optimum of 7.0 to 9.0 after the 60 hrs incubation time.
Kang, Hye Jin;Kay, Chul-Seung;Son, Seok Hyun;Kim, Myungsoo;Jo, In Young;Lee, So Jung;Lee, Dong Hwan;Suh, Hong Jin;Choi, Yong Sun
Radiation Oncology Journal
/
v.34
no.1
/
pp.45-51
/
2016
Purpose: The aim of this work was to assess the efficacy and tolerability of hypofractionated intensity-modulated radiotherapy (IMRT) in patients with localized prostate cancer. Materials and Methods: Thirty-nine patients who received radical hypofractionated IMRT were retrospectively reviewed. Based on a pelvic lymph node involvement risk of 15% as the cutoff value, we decided whether to deliver treatment prostate and seminal vesicle only radiotherapy (PORT) or whole pelvis radiotherapy (WPRT). Sixteen patients (41%) received PORT with prostate receiving 45 Gy in 4.5 Gy per fraction in 2 weeks and the other 23 patients (59%) received WPRT with the prostate receiving 72 Gy in 2.4 Gy per fraction in 6 weeks. The median equivalent dose in 2 Gy fractions to the prostate was 79.9 Gy based on the assumption that the ${\alpha}/{\beta}$ ratio is 1.5 Gy. Results: The median follow-up time was 38 months (range, 4 to 101 months). The 3-year biochemical failure-free survival rate was 88.2%. The 3-year clinical failure-free and overall survival rates were 94.5% and 96.3%, respectively. The rates of grade 2 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 20.5% and 12.8%, respectively. None of the patients experienced grade ${\geq}3$ acute GU and GI toxicities. The grade 2-3 late GU and GI toxicities were found in 8.1% and 5.4% of patients, respectively. No fatal late toxicity was observed. Conclusion: Favorable biochemical control with low rates of toxicity was observed after hypofractionated IMRT, suggesting that our radiotherapy schedule can be an effective treatment option in the treatment of localized prostate cancer.
A study on the oral bioavailability and pharmacokinetics of an anticoccidal agent, toltrazuril, was conducted in broilers following a single oral doses of 10 mg/kg body weight (BW) or 40 mg/kg BW. The concentrations of toltrazuril in plasma were determined by a high-performance liquid chromatography/mass spectrometry. Plasma concentration-time data after single oral administration were analyzed by a non-compartmental analysis. Toltrazuril was very well-absorbed through the gastrointestinal tract with $C_{max}$ of $18.04{\pm}5.80{\mu}g/mL$ and $47.15{\pm}9.40{\mu]g/mL$ at $4.33{\pm}1.51h$ and $3.67{\pm}1.15h$ after oral dose of 10 mg/kg and 40 mg/kg in broilers, respectively. A comparison between 10 mg/kg and 40 mg/kg dose groups showed that $t_{max}$ were similar while $C_{max}$ and area under curve (AUC) increased with increasing dose.
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