Background: The adverse effects of the phosphodiesterase-4 inhibitor roflumilast, appear to be more frequent in clinical practice than what was observed in chronic obstructive pulmonary disease (COPD) clinical trials. Thus, we designed this study to determine whether adverse effects could be reduced by starting roflumilast at half the dose, and then increasing a few weeks later to $500{\mu}g$ daily. Methods: We retrospectively investigated 85 patients with COPD who had taken either $500{\mu}g$ roflumilast, or a starting dose of $250{\mu}g$ and then increased to $500{\mu}g$. We analyzed all adverse events and assessed differences between patients who continued taking the drug after dose escalation and those who had stopped. Results: Adverse events were reported by 22 of the 85 patients (25.9%). The most common adverse event was diarrhea (10.6%). Of the 52 patients who had increased from a starting dose of $250{\mu}g$ roflumilast to $500{\mu}g$, 43 (82.7%) successfully maintained the $500{\mu}g$ roflumilast dose. No difference in factors likely to affect the risk of adverse effects, was detected between the dose-escalated and the discontinued groups. Of the 26 patients who started with the $500{\mu}g$ roflumilast regimen, seven (26.9%) discontinued because of adverse effects. There was no statistically significant difference in discontinuation rate between the dose-escalated and the control groups (p=0.22). Conclusion: Escalating the roflumilast dose may reduce treatment-related adverse effects and improve tolerance to the full dose. This study suggests that the dose-escalated regimen reduced the rate of discontinuation. However, longer-term and larger-scale studies are needed to support the full benefit of a dose escalation strategy.
Forty-two percent of the patients with renal failure that requires continuous renal replacement therapy (CRRT) have been reported to have severe malnutrition, and preexisting malnutrition is a statistically significant and independent predictor of negative hospital outcomes. We performed this study to evaluate the appropriateness of the calorie and protein provided for the critically ill patients who require CRRT. One hundred forty-nine patients who received CRRT were enrolled. The demographic data, the length of the ICU stay and the mortality were recorded. The calorie/protein intake and the blood urea nitrogen (BUN), albumin and creatinine levels were used as nutritional parameters. The mean daily calorie intake during CRRT was 16.1${\pm}$7.4 kcal/kg, which was 64% of the recommended intake. Only 10% of the patients received the recommended caloric intake and the ratio of the enteral and parenteral calories was 26%/74%. The mean protein intake was 0.58${\pm}$0.34 g/kg, which was 38% of the recommended intake. The calorie and protein intakes at the termination of CRRT were significantly increased compared to the initial day of treatment, but they stayed under the recommended intake. The BUN, creatinine and albumin levels were significantly increased in the survival group (odds ratio for albumin: 2.73; creatinine: 2.43). A strategy to increase the nutrition provision is needed to improve the nutritional statuses and clinical outcomes of the critically ill patients who require CRRT.
Epilepsy is characterized by the presence of spontaneous episodes of abnormal neuronal discharges and its pathogenic mechanisms remain poorly understood. Recently, we found that the expression of creatine kinase (CK) was markedly decreased in an epilepsy animal model using proteomic analysis. A human CK gene was fused with a HIV-1 Tat peptide to generate an in-frame Tat-CK fusion protein. The purified Tat-CK fusion protein was efficiently transduced into PC12 cells in a time- and dose-dependent manner when added exogenously to culture media. Once inside the cells, the transduced Tat-CK fusion protein was stable for 48 h. Moreover, the Tat-CK fusion protein markedly increased endogenous CK activity levels within the cells. These results suggest that Tat-CK provides a strategy for the therapeutic delivery of proteins in various human diseases including the delivery of CK for potential epilepsy treatment.
Objective : Dear antler (Cervus korean TEMMINCK var. mantchuricus Swinhoe) used for traditional immunosuppressive and immuno-activating action. The effect of deer antler herbal-acupuncture(DAH) solution, prepared by water extract method, on cathepsin activities in bone tissues (cartilage and synovial) cells from mouse rheumatoid arthritis (RA) model was studied. The cysteine endoprotease cathepsin mediates degradation of the MHC class II invariant chain (Ii) in human and mouse antigen-presenting cells. The studies described here examine the functional significance of cathepsin inhibition on autoantigen presentation and organ-specific autoimmune diseases in a murine model for RA. Methods : An animal model for RA in BALB/c mice thymectomized 3 days after birth (3d-Tx) was constructed All 3d-Tx BALB/c mice developed autoimmune lesions in the bone tissue cells, starting at 3 weeks of age, and the disease mediated by CD4+ T cells was chronic and progressive. Significant inhibitory effects of DAH solution on cathepsin S and L were observed in each organ in a dose-dependent manner. Moreover, we confirmed that cathepsin S and L activity in each organ were clearly inhibited by DAB solution. When we examined the inhibitory effects of DAH solution against autoantigen-specific T cell responses in vitro, in regional lymph node cells, but not in spleens, from model mice, a significant inhibitory effect of DAB solution was observed in a dose-dependent manner. DAH solution do not block T cell proliferation to Con A, indicated that the dose of DAB solution 10 to $20\;{\mu}g/m{\ell}$ was sufficient to inactivate the autoantigen-specific T cell responses in vitro. In vivo therapeutic effects of DAB solution were examined in a murine model for RA, autoantigen-specific (C-II-specific) T cell response were significantly inhibited in LNCs from DAH solution-treated mice. Results : Iinhibition of cathepsin S and L in vivo alters autoantigen presentation and development of organ-specific autoimmunity in RA model. Conclusion : These data identify selective inhibition of cysteine protease cathepsin S and L as a potential therapeutic strategy for autoimmune disease process such RA. Thus, DAH solution will served as a potent anti-inflammatory and anti-arthritic agents for treatment of human RA.
Journal of agricultural medicine and community health
/
v.31
no.2
/
pp.157-164
/
2006
Objectives: Early diagnosis and treatment is the most important strategy to control malaria effectively. Microscopic examination of blood films is a traditional and standard method for diagnosing malaria, which takes a long time and needs expertise, Therefore, the alternative method, rapid diagnostic kit has been used for quick diagnosis in some counties, a highly infectious region by P. vivax. The purpose of this study was to evaluate the utility of malaria rapid diagnostic kit in Ganghwa county. Methods: The utility was evaluated by mean diagnosis time and sensitivity and specificity. For monitoring mean diagnosis time, 942 cases which were diagnosed for P. vivax were collected between 1998 and 2005, And for calculating sensitivity and specificity, 434 whole bloods in EDTA which were presented for P. vivax by microscopy and rapid diagnostic kit were collected between 2004 and 2005. Results: After malaria rapid diagnostic kit was used in 2003, mean diagnosis time has decreased to 3.36-3.14 day. The sensitivity and specificity of the rapid diagnostic kit was 98.2% and 98,5% and comparable to that of microscopic examination. Conclusions: The malaria rapid diagnostic kit is useful tool in a highly infectious region like Ganghwa county.
Journal of the Korean Academy of Esthetic Dentistry
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v.25
no.1
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pp.15-24
/
2016
It is considered an implant failure when there is esthetic problems in the anterior area although the prosthesis function normally. In 2003, Dr. Kan et al stated that implant bone level is determined by the adjacent teeth. After that many scholars have studied how can achieve the esthetics result on adjacent teeth bone loss cases. In 2012, Dr. Takino published an article in Quintessence. He summarized previous articles and reclassified the defects from class 1 through 4. Class 1 and 2 depicts a situation where there is no bone loss on adjacent teeth. In Class 3 and 4, interproximal bone loss extends to the adjacent tooth. If one side is involved, it is Class 3. If both sides are involved, it is Class 4. The clue for esthetic implant restoration is whether bone loss extends to adjacent tooth or not. If the bone level of adjacent tooth is sound, we can easily achieve the esthetic but the bone level is not sound, the surgery will be complicated and the esthetic result will be unpredictable. So regenerative surgery for adjacent tooth is necessary for long-term maintenance. But the options and process were so complicated, the purpose of this article is to report the method simplify the surgery and gain a similar outcome.
The regeneration of lost periodontal tissue is a major goal of therapy. Periodontal ligament cell(PDL) is a specialized connective tissue that connects cementum and alveolar bone to maintain and support teeth in situ and preserve tissue homoeostasis. Bone morphogenetic proteins(BMPs) have shown much potential in the reconstruction of the periodontum by stimulate new bone and new cementum formation. Limitiations of BMP administration to periodontal lesions is high dose delivery, BMP transient biological activity, and low bioavailability of factors at the wound site. Gene delivery method can be alternative treatment strategy to deliver BMPs to periodontal tissue. The purpose of this study is to investigate efficiency of BMP-2 gene delivery with cell-based therapy using PDL cells. PDL cell were transduced with adenoviruses encoding either BMP-2 or Lac-Z gene. To evaluate osteogenic activity of expressed BMP-2 on PDL cells, we investigated secreted BMP-2, cellular activity, ALPase, produced mineralized nodules. To evaluate collagen scaffold as carrier for transduced cell delivery, we examined morphology and secreted BMP-2 of transducd PDL cells on it. BMP-2 transducd PDL cells produced higher levels of BMP-2, ALPase, mineralized nodules than non transduced cells. Cellular activity of transduced cells was showed similar activity to non transduced cells. Transduce cells attached on collagen scaffold secreted BMP-2 at 7day and was showed similar morphology to non transduced cells. These results demonstrated that transduced PDL cells produced biologically active BMP-2 and collagen scaffold could be carrier of transducd cells.
Journal of The Korean Association For Science Education
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v.32
no.10
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pp.1551-1566
/
2012
In this study, the effects of grouping by students' collectivism in cooperative learning strategy applied to middle school science classes on their academic achievement, science learning motivation, and perceptions of science learning environment were investigated. Students' perceptions of cooperative learning were also studied through survey and interview. The students were assigned to the control, heterogeneous, and homogeneous groups, and taught for 12 class hours. The analyses of results revealed that interactive effects between the instruction and the level of collectivism were found in the test scores of achievement, science learning motivation, and relevance, and that there were main effects in the test scores of confidence, perceptions of science learning environment, affiliation, and rule clarity. The achievement test scores of the students with low collectivism in the homogeneous group were significantly higher than those in the heterogeneous group. The test scores on science learning motivation and relevance of the students with high collectivism in the homogeneous and heterogeneous groups were significantly higher than those in the control group. In addition, the test scores of confidence and affiliation in the treatment groups were significantly higher than those in the control group. The test scores on perceptions of science learning environment and rule clarity in the homogeneous groups were significantly higher than those in the control group. There were also differences in the perceptions of science cooperative learning by students' collectivism.
Kang, Se Hyun;Moon, Young-Kyun;Jeong, Woo-Yeol;Nam, Hae-Jung;Kim, Yoon-Bum;Lee, Jun-Hee;Kim, Kyuseok
The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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v.29
no.2
/
pp.12-32
/
2016
Objectives : The objective of this study is to develop the strategies of the psoriasis clinical trials guideline on Korean medicine by comparison between Clinical guidelines and domestic and foreign clinical trials papers of psoriasis on Korean medicine. Methods : This study is based on analysis of papers on Clinical trials guidelines, Clinical practice guideline and clinical trials about Korean medicine. The papers were searched from Pubmed, Medline, Oasis(Oriental Medicine Advanced Searching Integrated System), Korean Traditional Knowledge Portal and Google portal database. Results : A total 8 Clinical practice guidelines and 2 Clinical trials guidelines were found. Moreover, there were 15 foreign papers about clinical trials and 29 internal articles about case studies. They suggested the diagnostic strategy, classification, effective outcome measure, severity measure, precaution of combination therapy, precaution and treatment period of clinical trials, safety evaluation, patterns of Korean Medicine, clinical specific features on psoriasis.Conclusions : The criteria of every item to provide the clinical trials guideline using Korean medicine on psoriasis were developed by apply the results. If we accumulate the more clinical articles on Korean medicine, it will be great help to develop the reliable standard of that guideline.
Background: KG-135, a standardized formulation enriched with Rk1, Rg3, and Rg5 ginsenosides, has been shown to inhibit various types of cancer cells; however, the underlying mechanisms are not fully understood. In this study, we explored its effects in A549 human lung cancer cells to investigate the induction of Forkhead Class box O3a (FOXO3a) and autophagy. Methods: Cell viability was determined by sulforhodamine B staining. Apoptosis and cell cycle distribution were analyzed using flow cytometry. The changes of protein levels were determined using Western blot analysis. Autophagy induction was monitored by the formation of acidic vesicular organelles stained with acridine orange. Results: KG-135 effectively arrested the cells in G1 phase with limited apoptosis. Accordingly, a decrease of cyclin-dependent kinase-4, cyclin-dependent kinase-6, cyclin D1, and phospho-retinoblastoma protein, and an increase of p27 and p18 proteins were observed. Intriguingly, KG-135 increased the tumor suppressor FOXO3a and induced the accumulation of autophagy hallmark LC3-II and acidic vesicular organelles without an increase of the upstream marker Beclin-1. Unconventionally, the autophagy adaptor protein p62 (sequestosome 1) was increased rather than decreased. Blockade of autophagy by hydroxychloroquine dramatically potentiated KG-135-induced FOXO3a and its downstream (FasL) ligand accompanied by the cleavage of caspase-8. Meanwhile, the decrease of Bcl-2 and survivin, as well as the cleavage of caspase-9, were also drastically enhanced, resulting in massive apoptosis. Conclusion: Besides arresting the cells in G1 phase, KG-135 increased FOXO3a and induced an unconventional autophagy in A549 cells. Both the KG-135-activated extrinsic FOXO3a/FasL/caspase-8 and intrinsic caspase-9 apoptotic pathways were potentiated by blockade of autophagy. Combination of KG-135 and autophagy inhibitor may be a novel strategy as an integrative treatment for cancers.
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