Objective : Although management of asthma has become increasingly effective, its cure remains elusive, necessitating a new modality to prevent or eliminate causes triggering clinical progress. Based in the clinical experiences, a novel decoration Cheongsangbiyeum (CSB), has been developed to treat asthma, which consists of Polyporus, Semen Myristicae, Pericarpium citri Reticulatae, Rhizoma Cimicifugae, Cortex Albizziae, Fructus Rubi, Rhizoma Zedoariae, and Rhizoma Rhei. In the current study, its anti-asthmatic efficacy was evaluated using a mouse model of asthma. Methods : Experimental allergic asthma was induced by repeated intraperitioneal sensitization and intranasal challenge of ovalbumin (OVA). Water extract of CSB (1 mg/mouse/day) was administrated orally whereas control mice on given with identical volume of phosphate-buffered saline (PBS) for 5 days during the course of antigen challenge. When airway hyperreactivity(AHR) measured by ${\bata}-methacoline-induced$ airflow obstruction was compared, AHR of CSB-treated mice was significantly lower than those of control mice, indicating that CM extract can attenuate an asthmatic symptom. Airway recruitment of leukocytes and eosinophils was also markedly reduced by CSB treatment suggesting that oral treatment of CSB can alleviate the airway inflammation. For a better understanding of possible mechanisms underlying anti-asthmatic effet of CSB, cytokine (IL-4, IL-5, IL-13 and $IFN{\gamma}$ levels in bronchoalveola lavage fluid (BALF) and lung tissues were determined. Results : The results showed that cytokine levels were significantly lowered by CSB treatment. Additionally, number of draining lymph node cells was significantly lower than those of control mice. These data indicate that CSB suppress in vivo allergen-specific response. However, notably, levels of type 2 cytokines such as IL-5 and IL-13 were more profoundly influenced. Moreover, in vitro OVA-specific proliferative response and type 2 cytokine (IL-4, IL-5 and IL-13) production lymph node cells was markedly decreased in CSB-treated mice, whereas their $IFN{\gamma}$ production was not significantly altered Thrse data clearly showed a preferential inhibition of type 2 T cell (Th2) response by CSB treatment. This finding was also supported by serum antibody data showing that levels of OVA-specific type 2 antibodies, IgE and IgG1, in CSB-treated mice were significantly lower than in control mice, while type 1 antibody, IgG2a level m rather higher than controls, although the difference was in significant. Conclusions : In conclusion, oral administration of CSB attenuates asthmatic manifestations including AHR ad airway recruitment of eosinophils in a mouse model which possibly results from selective inhibition of Th2 cell response to allergen. Our data suggest a potential clinical application of CSB for control of allergic asthma.
The short and variabke transit of drug throught GI tracj and the inter-and intra-subject variations of the transit restrict the sustained drug absorption after oral adminstration. These restrictions may be solved by retaining the dosage forms in the stomach. Then the dosage form will act as a platform which releases the drug slowly and makes the GI absorption occur for a long time. In this study, as the platforms, PVP hydrogels were synthesized by chemical and y-irradiation method in the cylindrical test tube. The chemical method means the synthesis of the hydrogel by heating the mixed solution of N-vinyl-2-pyrrolidone [monomer], acrylated albumin [crosslinking agent], 2, 2'-agobis(2-methylpropionitrile) [initiator] and proxyphylline [drug] at $65^{\circ}C$ for 5 hr. The $\gamma$-irradiation method means the synthesis of the hydrogel by irradiation with $^{60}$ Co $\gamma$-ray of the mixed solution of the monomer, acrylated albumin, and flurbiprofen [drug] at room temperature with total 0.2 Mrad for 3 hr. Our intention is to design the hydrogel tablet (diameter : 1.20 cm, thickness : 0.60 cm) which swells in the gastric fluid after oral administration to such a size that passing through the pylorus could be inhibited during the period of drug release. After releasing drug, the hydrogel should be degraded by the enzymeatic digestion in the stomach, or by hydrolysis and eventually solubilized. Thus, in votro tests were performed to examine the factors that affect swelling and drug release from the PVP hydrogels. Experimental results show that the hydrogels swell to a size larger than the diameter of the pylorus(l.3$\pm$0.7 cm) and the hydrogel prepared by the chemical method is digested by pepsin. But the hydrogel prepared by the $\gamma$-irradiation method was not digested by the pepsin and just collapsed with time. Thus, the swelling of the hydrogel synthesized by $\gamma$-irradiation was independent albumin acrylation time and pepsin concentration. But drug content and radiation dose affected the swelling and drug release kinetics of the hydrogel. Drug release from the hydrigels was prolonged up to about 24 hr. Therefore, it was concluded that by adjusting these factors, the albumin-crosslinked PVP hydrogel synthesized by $\gamma$-irradiation method is expected to be retained in the stomach for up to 60hr and be a potential platform of drugs for long-term GI absorption.
Objectives: Oriental pear was used as traditional remedies for respiratory diseases like cough and asthma etc. The purpose of this study was to observe the effects of preventing asthma by the combination of phenolic compound extracted from pear and herbal drugs. Methods: In order to study the effects of preventing asthma by the combination of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) on allergic asthma, mice were pre-treated by oral administration of the solution before antigen sensitization for 10 days and 20days. And 2 days later, mice were actively sensitized with a subcutaneous injection of ovalbumin and 13 days later, they were provoked with ovalbumin aerosols. The experimental groups were divided 6groups(10d1P, 10d2P, 10d4P, 20d1P, 20d2P and 20d4P) by meditation quantity and period. We measured isometric contractile responses to acetylcholine(ACh) and KCl in the isolated tracheal smooth muscle(TSM), IL-4, eosinophil and lymphocyte in bronchoalveolar lavage fluid(BALF), IgE in serum, WBC, RBC and hemoglobin in blood. Results: Contractile responses of TSM to ACh, the sensitivity of TSM to Ach and the maximal contractile response of TSM to KCl were decreased by direct proportion of meditation quantity. Eosinophil and IL-4 level in BALF were more significantly decreased, and IgE level in serum was more significantly increased in 10d4P and 20d4P group than the control group. Conclusions: Based on the above results, it is assumed that oral administration of the combination of phenolic compound extracted from pear and herbal drugs(Platycodon grandiflorum, Prunus armeniaca) can help the preventing effects of allergic asthma.
Many dental composites are Bis-GMA based resin which diluted with the more fluid monomer triethylenglycol dimethacrylate(TEGDMA). TEGDMA is often present in exess so that some quantity remains unreacted following photo-initiated polymerization. TEGDMA is a component of some resin composites which contributes to their cytotoxicity. The presence of dentin between resin composite and pulp space reduce the cytotoxicity in vitro. The root system from extrcted human third molar was removed and then a circular occlusal cavity 4mm in diameter was prepared, leaving a remaining dentinal thickness to the roof of the pulpal chamber within the range 1.0-1.5mm. Dentine was treated with 37% phosphoric acid prior to Z 100 placement without using bonding resin(group 1). In group 2, SMP(Scotchbond Multi Purpose) primer, bonding resin prior to Z 100 placement were applied sequently. In group 3, moulds with internal dimensions 4mm diameter by 2mm depth were used to contain the composite alone with an equvalent mass on tooth model, and then they were immersed directly into water. The purpose of this study is to evaluate the release rate and quantity of TEGDMA with or without the application of bonding resin. Both release rate and total cumulative amount of TEGDMA for the three groups were determined using reversed-phase HPLC at times up to 10 days. The results were as follows: 1. All experimental groups showed the highest rate of release was in the first sample period(0-4.32 min) and the rate of release declined exponentially thereafter. 2. The maximum release rate and total cumulative account of TEGDMA in the tooth model of group 1 and group 2 with the use of SMP bonding resin were reduced however ther were no significant differences between these groups(P>0.05). 3. In the first sample period(0-4.32 min), the rate of release of TEGDMA from composite resin in group 3 immersed directly into water was significantly higher than that in group 1 and group 2 of tooth model(P<0.05). Conclusively, TEGDMA diffusion from Z 100 resin was not effectively prevented by the presence of dentin in spite of using the SMP bonding resin.
The periodontal health has been evaluated clinically by various epidemiological indices, and in researches by measurement of gingival crevicular fluid. Laser Doppler flowmetry is a reliable and objective method that allows immediate measurement of erythrocyte flux in approximately one cubic mm of the capillary bed without disturbing the tissues. The purpose of the present study was to determine whether human gingival blood flow was different according to measuring area, measuring time, and sex or not. Forty volunteers with good general and periodontal health, aged early twenties and unmarried, were selected. Laser Doppler flowmetry($floLAB^{(R)}$, Moor Instruments Ltd., England) was applied to measure the gingival blood flow of marginal gingiva, interdental papilla, attached gingiva and alveolar mucosa. The blood flow of interdental papilla was measured at 9-10 AM, 1-2 PM, and 5-6 PM. The difference of blood flow according to measuring area and measuring time was statistically analyzed by one way AOVA and Dunkan test, and the difference of blood flow between men and women was statistically analyzed by t-test. (1) Mean blood flow was significantly higher in alveolar mucosa than in the gingiva(p<0.05), and there was no significant difference in blood flow between marginal gingiva and interdental papilla(p>0.1). (2) Mean blood flow was significantly higher at 5-6 PM than at 9-10 AM and 1-2 PM(p<0.05). But there was no significant difference in gingival blood flow between 9-10 AM and 1-2 PM(p>0.1). (3) There was no significant difference in gingival blood flow between men and women(p>0.1). The above results suggest that the measurment of gingival blood flow using laser Doppler flowmetry may be clinically applicable to early determination of gingival inflammation and evaluation of healing status, but further studies are necessary to standardize and simplify the measuring procedure.
Park, Hyeon-Woo;Chung, Suk-Jae;Lee, Myung-Gull;Shim, Chang-Koo
Archives of Pharmacal Research
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제24권6호
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pp.584-589
/
2001
Isopropryl 2-(1-3-dithiethane-2-ylidene)-2 [N-(4-methyl-thiazole-2-yl) carbamoyl] acetate (YH439) is currently under phase ll clinical trials by the Yuhan Research Center for use as a hepatoprotective agent. Unfortunately, the oral bioavailbility of YH439, which is sparingly soluble in water (i.e., $0.3{\;}\mu\textrm{g}/ml{\;}or{\;}0.91{$\mu}M$ at room temperature), reportedly, is negligibleregardless of the dose administered to rats in the 10-300 mg/kg range. The bioavailability of the compound increased up to 24%, when administered in the form of a micellar solution ($700{\;}\mu\textrm{g}/ml$or 2.1 mM for YH439) at a dose of 10 mg/kg, suggesting that its limited solubility is associated with its negligible bioavailability. In order to obtain additional informmation concerning the bioavailability of YH439, the mechanism(s) involved in gastrointestinal (Gl) absorption were investigated in the present study. For this purpose, the transport of YH430 across a Caco-2 cell monolayer was measured in a $Transwell^{\circledR}$. A permeability of $4.07{\times}10^{-5}{\;}cm/s$ was obtained for the absorptive (i.e., apical to basolateral direction) transport of $0.42{\mu}M$ YH439, implicating that the in vivo Cl absorption is nearly complete. The absorptive transport exhibited a slight concentration-dependency with an intrinsic clearance ($CL_{i}$) of $0.38{\mu}L/{\textrm{cm}^2}/sec$, which accounted for 28.1% of the total intrinsic clearance (i.e., $CL_i$ plus the intrinsic clearance for the linear component) of the transport. Thus, saturation of the absorption process appears to be a minor factor in limiting the bioavailability of the compound. The apparent permeability of YH439 from the basolateral to the apical direction (i.e., efflux, $6.67{\times}10^{-5}{\;}cm/s$) was comparable to that for absorptive transport, but, interestingly, a more distinct concentration-dependency was observed for this transport. However, the efflux does not appear to influence the bioavailability of the compound, as evidenced by the sufficiently high permeability in the absorption direction. Rather, a reportedly extensive first-pass hepatic metabolism appears to be a principal factor in limiting the bioavailability. In this respect, reducing the first-pass metabolism by some means would lead to a higher bioavailability of the compound. Thus, elevation of the absorption rate of YH439 becomes a necessity. From a practical point of view, increasing the concentration of YH439 in the Cl fluid appears to be a feasible way to increase the absorption rate, because the compound is primarily absorbed via a linear mechanism. In summary, the solubilization of YH439, as previously demonstrated for a micellar solution of the compound, appears to be a practical way to increase the oral bioavailability of YH439.
Background: Gintonin is a ginseng-derived exogenous G-protein-coupled lysophosphatidic acid (LPA) receptor ligand, which exhibits in vitro and in vivo functions against Alzheimer disease (AD) through lysophosphatidic acid 1/3 receptors. A recent study demonstrated that systemic treatment with gintonin enhances paracellular permeability of the blood-brain barrier (BBB) through the LPA1/3 receptor. However, little is known about whether gintonin can enhance brain delivery of donepezil (DPZ) (Aricept), which is a representative cognition-improving drug used in AD clinics. In the present study, we examined whether systemic administration of gintonin can stimulate brain delivery of DPZ. Methods: We administered gintonin and DPZ alone or coadministered gintonin with DPZ intravenously or orally to rats. Then we collected the cerebral spinal fluid (CSF) and serum and determined the DPZ concentration through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results: Intravenous, but not oral, coadministration of gintonin with DPZ increased the CSF concentration of DPZ in a concentration- and time-dependent manner. Gintonin-mediated enhancement of brain delivery of DPZ was blocked by Ki16425, a LPA1/3 receptor antagonist. Coadministration of vascular endothelial growth factor (VEGF) + gintonin with DPZ similarly increased CSF DPZ concentration. However, gintonin-mediated enhancement of brain delivery of DPZ was blocked by axitinip, a VEGF receptor antagonist. Mannitol, a BBB disrupting agent that increases the BBB permeability, enhanced gintonin-mediated enhancement of brain delivery of DPZ. Conclusions: We found that intravenous, but not oral, coadministration of gintonin facilitates brain delivery of DPZ from plasma via LPA1/3 and VEGF receptors. Gintonin is a potential candidate as a ginseng-derived novel agent for the brain delivery of DPZ for treatment of patients with AD.
It has been known that ethanol stimulates the secretion of gastric acid regardless of its route of administration. Recently, however, some studies have challenged this view and claimed that ethanol inhibits the gastric acid secretion. This study was undertaken to investigate the effects of ethanol on the gastric acid secretion in anesthetized rat in respect to the route of administration and the concentration of alcohol. Normal saline (pH adjusted to 6.0) was used as standard perfusion solution and ethanol was mixed as 0.8, 1.7, 5, 10 and 20%. Four ml of perfusion fluid was given into stomach via gastric tube and drained from duodenal tube every 5 min. Acid secretion was measured by back titration to pH 6.0 with N/20 NaOH and expressed as ${\mu}Eq/5$ min. Low concentration of ethanol up to 1.7% in perfusion solution caused little changes in acid secretion, but moderate concentration such as perfusion of 5% or 10% ethanol solution inhibited both the basal and histamine-induced gastric secretion. Moreover, loss of perfused acid was seen by 20% ethanol, which means back diffusion of hydrogen ions into the gastric mucosa. However, intravenous administration of ethanol, maintained at the level of 0.1% alcohol in blood, caused significant stimulation of gastric acid. We, therefore, conclude that in anesthetized rat ethanol has dual effects on acid secretion, i.e., inhibiting and enhancing by oral and intravenous administration, respectively, but further investigation is necessary to clarify these effects.
Han, Ji-Hye;Kim, Hye-Mi;Seo, Deog-Gyu;Lee, Gene;Jeung, Eui-Bae;Yu, Frank H.
Journal of Periodontal and Implant Science
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제45권2호
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pp.69-75
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2015
Purpose: Salivary fluid formation is primarily driven by Ca2+-activated, apical efflux of chloride into the lumen of the salivary acinus. The anoctamin1 protein is an anion channel with properties resembling the endogenous calcium-activated chloride channels. In order to better understand the role of anoctamin proteins in salivary exocrine secretion, the expression of the ten members of the anoctamin gene family in the mouse submandibular gland was studied. Methods: Total RNA extracted from mouse submandibular salivary glands was reverse transcribed using primer pairs to amplify the full-length coding regions of each anoctamin gene and was subcloned into plasmid vectors for DNA sequencing. Alternative splice variants were also screened by polymerase chain reaction using primer pairs that amplified six overlapping regions of the complementary DNA of each anoctamin gene, spanning multiple exons. Results: Multiple anoctamin transcripts were found in the mouse submandibular salivary gland, including full-length transcripts of anoctamin1, anoctamin3, anoctamin4, anoctamin5, anoctamin6, anoctamin9, and anoctamin10. Exon-skipping splicing in the N-terminal exons of the anoctamins1, anoctamin5, and anoctamin6 genes resulted in multiple alternative splice variants. No expression of anoctamin2, anoctamin7, or anoctamin8 was found. Conclusions: The predominant anoctamin transcript expressed in the mouse submandibular gland is anoctamin1ac. The chloride channel protein produced by anoctamin1ac is likely responsible for the $Ca^{2+}$-activated chloride efflux, which is the rate-limiting step in salivary exocrine secretion.
진료실에서 지르코니아의 수요가 증가하고 있음에 따라 지르코니아의 생체적합성에 대한 평가가 필수적이다. 이번 논문에서는 지르코니아의 생체적 합성에 대한 문헌 중 in vitro 실험에서의 결과를 고찰하였다. Fibroblast, osteoblast, lymphocyte 등 다양한 세포를 이용한 in vitro 실험에서 지르코니아 블록은 뛰어난 생체적합성을 보였다. 여러 연구에서 지르코니아에 대한 세포독성 및 돌연변이 유발이 관찰되지 않았으며, 세균부착도 적은 것으로 나타났다. 장기간 체액노출조건을 모방한 in vitro 실험에서는 약간의 기계적 강도의 감소 외에는 악영향이 관찰되지 않았다. Osteoblast-like cell을 이용한 연구에서, 지르코니아 블록이 면역반응, 물질이동, 세포주기조절에 관여하는 유전자를 조절하여 생체적합을 높이는 것으로 관찰되었다. 여러 in vitro 연구에서 지르코니아 분말의 생체적합성에 대해서는 상이한 보고가 나타나고 있다. 종합적으로 지르코니아 분말은 어느 정도 세포독성을 가지고 있는 것으로 생각된다.
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