• Title/Summary/Keyword: e-Clinical Trials

검색결과 154건 처리시간 0.032초

렙틴 저항성의 개선 (Improvement of Leptin Resistance)

  • 김용운
    • Journal of Yeungnam Medical Science
    • /
    • 제30권1호
    • /
    • pp.4-9
    • /
    • 2013
  • Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

유전자 수송계의 현재까지의 연구동향 및 앞으로의 개발전략 (Recent Advances and Future Strategy in Gene Delivery System)

  • 최우정;김종국
    • Journal of Pharmaceutical Investigation
    • /
    • 제30권1호
    • /
    • pp.1-12
    • /
    • 2000
  • Gene therapy is a method for the treatment of diseases with introducing the gene-engineered materials into a patient with gene-deficiency disease (e.g. cystic fibrosis) or cancer to produce a therapeutic protein in a patient's cells. Successful gene therapy requires establishing both gene expression systems and delivery systems. Viral and non-viral vectors have been used for gene delivery. Viral vectors have a high transfection efficiency, but are limited in relations to issues of safety, toxicity and immunogenecity. Non-viral vectors are easy to prepare and relatively safe. However, non-viral vectors have a low transfection efficiency. Cationic liposomes are the most available among non-viral vectors. Cationic liposomes have been used to transfect cells both in vitro and in vivo experiments. Besides, several formulations containing cationic lipid are being used in clinical trials in cases of cystic fibrosis or cancer. A crucial subject to the further development of gene delivery vectors will be a long-term gene expression with following characteristics; protecting and deliverying DNA efficiently, non-toxic and non-immunogenic, and easy to produce in large scale.

  • PDF

진세노사이드의 혈관확장작용과 분자기전 (Ginsenosides-mediated Vascular Relaxation and Its Molecular Mechanisms)

  • 김낙두
    • Journal of Ginseng Research
    • /
    • 제32권2호
    • /
    • pp.89-98
    • /
    • 2008
  • There are increasing evidences in the literatures on the potential role of ginsenosides in treating cardiovascular diseases. In this article, current information about ginsenosides-mediated vascular relaxation are reviewed. From the published studies using isolated organs, cell culture systems and animal models, ginsenosides are shown to relax blood vessels and improve blood flow through diverse mechanisms, including nitric oxide release by activating eNOS phosphorylation via PI3K/Akt and/or ERK1/2 pathways in endothelial cells, induction of inducible nitric oxide synthase through activation of NF-${\kappa}$B, reducing the intracelluar Ca$^{2+}$ levels by activating Ca$^{2+}$-activated K$^{+}$ channels in vascular smooth muscle cells and reducing platelet aggregation by decreasing thromboxane A$_2$ formation and intracelluar Ca$^{2+}$in platelets. In addition, the relevant clinical trials regarding the effects of ginsenosides on the cardiovascular disease are summarized, particulary focusing on managing hypertension and improving thrombotic disorders. Finally, antagonistic effects of ginsenosides on the prostaglandin H$_2$ receptor and scavenging effects on the generation of oxygen-derived free radicals in spontaneously hypertensive rats (SHR) are discussed.

Development of Refolding Process to Obtain Active Recombinant Human Bone Morphogenetic Protein-2 and its Osteogenic Efficacy on Oral Stem Cells

  • Lee, Ji-Hye;Jang, Young-Joo
    • International Journal of Oral Biology
    • /
    • 제42권2호
    • /
    • pp.71-78
    • /
    • 2017
  • BMP-2 is a well-known TGF-beta related growth factor, having a significant role in bone and cartilage formation. It has been employed to promote bone formation in some clinical trials, and to differentiate mesenchymal stem cells into osteoblasts. However, it is difficult to obtain this protein in its soluble and active form. hBMP-2 is expressed as an inclusion body in the bacterial system. To continuously supply hBMP-2 for research, we optimized the refolding of recombinant hBMP-2 expressed in E. coli, and established an efficient method by using detergent and alkali. Using a heparin column, the recombinant hBMP-2 was purified with the correct refolding. Although combinatorial refolding remarkably enhanced the solubility of the inclusion body, a higher yield of active dimer form of hBMP-2 was obtained from one-step refolding with detergent. The refolded recombinant hBMP-2 induced alkaline phosphatase activity in mouse myoblasts, at $ED_{50}$ of 300-480ng/ml. Furthermore, the expressions of osteogenic markers were upregulated in hPDLSCs and hDPSCs. Therefore, using the process described in this study, the refolded hBMP-2 might be cost-effectively useful for various differentiation experiments in a laboratory.

Trifocal versus Bifocal Diffractive Intraocular Lens Implantation after Cataract Surgery or Refractive Lens Exchange: a Meta-analysis

  • Yoon, Chang Ho;Shin, In-Soo;Kim, Mee Kum
    • Journal of Korean Medical Science
    • /
    • 제33권44호
    • /
    • pp.275.1-275.15
    • /
    • 2018
  • Background: We compared the efficacy between trifocal and bifocal diffractive intraocular lens (IOL) implantation. Methods: Through PubMed, MEDLINE, EMBASE, and CENTRAL, we searched potentially relevant articles published from 1990 to 2018. Defocus curves, visual acuities (VAs) were measured as primary outcomes. Spectacle dependence, postoperative refraction, contrast sensitivity (CS), glare, and higher-order aberrations (HOAs) were measured as secondary outcomes. Effects were pooled using random-effects method. Results: We included 11 clinical trials, with a total of 787 eyes (395 subjects). The trifocal IOL group showed better binocular distance VA corrected with defocus levels of -0.5, -1.0, -1.5, and -2.5 diopter than the bifocal IOL group (All $P{\leq}0.004$). The trifocal IOL group showed better monocular uncorrected distance and intermediate VAs (mean difference [MD], -0.04 logarithm of the minimum angle of resolution [logMAR]; 95% confidence interval [CI], -0.07, -0.01; P = 0.006 and MD, -0.07 logMAR; 95% CI, -0.13, -0.01; P = 0.03, respectively). Postoperative refraction, glare, CS, and HOAs were not significantly different from each other. Conclusion: The overall findings indicate that trifocal diffractive IOL implantation is better than the bifocal diffractive IOL in intermediate VA, and provides similar or better in distance and near VAs without any major deterioration in the visual quality.

바이러스성 간질환 치료약 (Drugs for the Treatment of Viral Hepatitis)

  • 김충섭
    • 약학회지
    • /
    • 제57권1호
    • /
    • pp.43-54
    • /
    • 2013
  • Viral hepatitis is the inflammation of liver cells caused by viruses, and still one of the major health-care problems worldwide. A number of viruses to cause hepatitis are type A, B, C, D, E or G. Among these viruses leading to hepatitis, B and C are more troublesome being more prone to chronic illness which can cause the potentially fatal conditions of hepatocellular carcinoma (HCC) and/or liver failure. If immediate treatment is not initiated, liver transplant is the only option left. Over the past few decades there has been remarkable progress in diagnose and monitor all hepatitis virus infections for treatment and prevention. Nonetheless, important challenges remain to develop more effective and safe vaccines for prevention as well as antiviral agents to reduce viremia/viral load by inhibiting viral replication. The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years has heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus. The introduction of Direct Acting Antivirals (DDAs) for the treatment of HBV carriers has permitted the long term use of these compounds for the continuous suppression of viral replication. This review aims to summarize the current status and development approaches of antiviral drugs for the treatment of viral hepatitis and future perspectives.

An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug

  • Hong, Yunjung;Jeon, Sangil;Choi, Suein;Han, Sungpil;Park, Maria;Han, Seunghoon
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제25권6호
    • /
    • pp.545-553
    • /
    • 2021
  • Fixed-dose combinations development requires pharmacokinetic drugdrug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and model-based analyses were compared for their performance to evaluate DDI using amlodipine as an example. Raw data without DDI or simulated data using pharmacokinetic models were compared to the data obtained after concomitant administration. Regardless of the methodology, all the results fell within the classical BE limit. It was shown that the model-based approach may be valid as the conventional approach and reduce the possibility of DDI overestimation. Several advantages (i.e., quantitative changes in parameters and precision of confidence interval) of the model-based approach were demonstrated, and possible application methods were proposed. Therefore, it is expected that the model-based analysis is appropriately utilized according to the situation and purpose.

Photodynamic Diagnosis and Therapy for Peritoneal Carcinomatosis from Gastrointestinal Cancers: Status, Opportunities, and Challenges

  • Kim, Hyoung-Il;Wilson, Brian C.
    • Journal of Gastric Cancer
    • /
    • 제20권4호
    • /
    • pp.355-375
    • /
    • 2020
  • Selective accumulation of a photosensitizer and the subsequent response in only the light-irradiated target are advantages of photodynamic diagnosis and therapy. The limited depth of the therapeutic effect is a positive characteristic when treating surface malignancies, such as peritoneal carcinomatosis. For photodynamic diagnosis (PDD), adjunctive use of aminolevulinic acid- protoporphyrin IX-guided fluorescence imaging detects cancer nodules, which would have been missed during assessment using white light visualization only. Furthermore, since few side effects have been reported, this has the potential to become a vital component of diagnostic laparoscopy. A variety of photosensitizers have been examined for photodynamic therapy (PDT), and treatment protocols are heterogeneous in terms of photosensitizer type and dose, photosensitizer-light time interval, and light source wavelength, dose, and dose rate. Although several studies have suggested that PDT has favorable effects in peritoneal carcinomatosis, clinical trials in more homogenous patient groups are required to identify the true benefits. In addition, major complications, such as bowel perforation and capillary leak syndrome, need to be reduced. In the long term, PDD and PDT are likely to be successful therapeutic options for patients with peritoneal carcinomatosis, with several options to optimize the photosensitizer and light delivery parameters to improve safety and efficacy.

Silver nanoparticles in endodontics: recent developments and applications

  • Aysenur Oncu;Yan Huang ;Gulin Amasya ;Fatma Semra Sevimay;Kaan Orhan;Berkan Celikten
    • Restorative Dentistry and Endodontics
    • /
    • 제46권3호
    • /
    • pp.38.1-38.13
    • /
    • 2021
  • The elimination of endodontic biofilms and the maintenance of a leak-proof canal filling are key aspects of successful root canal treatment. Several materials have been introduced to treat endodontic disease, although treatment success is limited by the features of the biomaterials used. Silver nanoparticles (AgNPs) have been increasingly considered in dental applications, especially endodontics, due to their high antimicrobial activity. For the present study, an electronic search was conducted using MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and EMBASE. This review provides insights into the unique characteristics of AgNPs, including their chemical, physical, and antimicrobial properties; limitations; and potential uses. Various studies involving different application methods of AgNPs were carefully examined. Based on previous clinical studies, the synthesis, means of obtaining, usage conditions, and potential cytotoxicity of AgNPs were evaluated. The findings indicate that AgNPs are effective antimicrobial agents for the elimination of endodontic biofilms.

Outcomes of Gastrectomy for Gastric Cancer in Patients Aged >80 Years: A Systematic Literature Review and Meta-Analysis

  • Zelalem Chimdesa Merga ;Ji Sung Lee ;Chung-Sik Gong
    • Journal of Gastric Cancer
    • /
    • 제23권3호
    • /
    • pp.428-450
    • /
    • 2023
  • This meta-analysis examined the surgical management of older patients (>80 years) with gastric cancer, who were often excluded from randomized controlled trials. We analyzed 23 retrospective cohort studies involving 18,372 patients and found that older patients had a higher in-hospital mortality rate (relative risk [RR], 3.23; 95% confidence interval [CI], 1.46-7.17; P<0.01) and more post-operative complications (RR, 1.36; 95% CI, 1.19-1.56; P<0.01) than did younger patients. However, the surgical complications were similar between the two groups. Older patients were more likely to undergo less extensive lymph node dissection and longer hospital stays. Although older patients had statistically significant post-operative medical complications, they were not deprived of surgery for gastric cancer. The comorbidities and potential risks of post-operative complications should be carefully evaluated in older patients, highlighting the importance of careful patient selection. Overall, this meta-analysis provides recommendations for the surgical management of older patients with gastric cancer. Careful patient selection and evaluation of comorbidities should be performed to minimize the risk of post-operative complications in older patients, while recognizing that they should not be deprived of surgery for gastric cancer.