• Title/Summary/Keyword: new drugs

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Structure and Function of RGD Peptides Derived from Disintegrin Proteins

  • Kim, Jiun;Hong, Sung-Yu;Park, Hye-seo;Kim, Doo-Sik;Lee, Weontae
    • Molecules and Cells
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    • v.19 no.2
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    • pp.205-211
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    • 2005
  • The Arg-Gly-Asp (RGD) sequence serves as the primary recognition site in extracellular matrix proteins, and peptides containing this sequence can mimic the biological activities of matrix proteins. We have initiated structure-function studies of two RGD containing peptides, RGD-5(AGGDD) and cyclic RGD-6(CARGDDC). Assays have shown that cyclic RGD-peptides inhibit platelet aggregation more efficiently than linear ones. NMR data revealed that RGD-5 and RGD-6 have entirely different conformation. RGD-5 has a linear extended structure and RGD-6 has a stable loop conformation. In RGD-5 the guanidinium group of Arg2 and the carboxyl group of Asp4 lie in parallel, whereas the side-chains of Arg3 and Asp5 of RGD-6 are located in different planes, supporting the idea that the stability of the cyclic form derives from the packing of the side chain of the Arg and Asp residues. The structural features of these peptides could provide a basis for designing new drugs against diseases related to platelet aggregation and as cancer antagonists.

Rheumatiod Arthritis: An Updated Overview of Latest Therapy and Drug Delivery

  • Kesharwani, Disha;Paliwal, Rishi;Satapathy, Trilochan;Paul, Swarnali Das
    • Journal of Pharmacopuncture
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    • v.22 no.4
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    • pp.210-224
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    • 2019
  • Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.

An Information-Intensive Approach to the Molecular Pharmacology of Cancer

  • John N. Weinstein;Timothy G. Myers;Patrick M. O′Connor;Stephen H. Friend;Albert J. Fornace Jr;Kurt W. Kohn;Tito Fojo;Susan E. Bates;Lawrence V. Rubinstein;N. Leigh Anderson;John K. Buolamwini;Wiliam W. van Osdol;Anne P. Monks;Dominic A. Scudiero;Edward A. Sausville;Daniel W. Zaharevitz;Barry Bunow;Vellarkda N. Viswanadhan;Georage S. Johnson;Robert E. Wittes;Kennety D. Paull
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2001.08a
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    • pp.139-149
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    • 2001
  • Since 1990, the National Cancer Institute(NCI) has screened more than 60.000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI$_{50}$) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460, 000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.s.

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Difficult Clinical Problems of Treatment in Depression (우울증 치료에서의 어려운 문제들)

  • Min, Kyung-Joon
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.37-46
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    • 2001
  • Whenever a clinician manages the patients with depression, he may meet various problems that make it difficult to treat them. Even though he has good skills and knowledge about depression, some barriers will be appear during his practice. In general, the difficulties in treating depression are treatment-resistance, adverse effects of antidepressants, pregnancy in female patients, comorbid medical conditions, poor compliance, drug-drug interactions, and so on, which are related with pharmacological treatments. Here, only the two of them, the treatment-resistant depression and difficult problems concerned with pregnancy, were discussed. Some level of treatment resistance is the norm rather than the exception. As the treatment failure stems from inadequate treatment, it is important that the clinician should prescribe medications with sufficient doseage and adequate duration. And to overcome the treatment resistant depression the polypharmacy is necessary, in that case, the side effects and toxicities should be explored and managed immediately. So the clinician have to learn more about the pharmacokinetic and pharmacodynamic mechanisms of each drugs used in treatment of depression. When the risk of the fetus by the exposure is higher than the risk of untreated maternal psychiatric disorder, psychotropic medications should be used during pregnancy. Women who are maintained on psychotropics and become pregnant, as well as women with the new onset of psychiatric symptoms during pregnancy, should be carefully reassessed. However, data concerning the potential risk of long-term behavioral changes following prenatal exposure to psychotropics is rare, so further longitudinal follow-up studies are needed.

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Maximum tolerated dose estimation by Biased coin design and stopping rule in Phase I clinical trial (제 1상 임상시험에서 Biased Coin Design과 멈춤규칙을 이용한 MTD 추정법)

  • Jeon, Soyoung;Kim, Dongjae
    • The Korean Journal of Applied Statistics
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    • v.33 no.2
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    • pp.137-145
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    • 2020
  • Phase I clinical trials (Dose Finding Studies) are the first step in administering new drugs developed through animal experiments or in vitro experiments to humans. An important area of interest in designing Phase I clinical trials is determining the dose that provides the greatest efficacy and acceptable safe dose to the patient. In this paper, we propose a method to determine the maximum tolerated dose considering efficacy and safety using Biased coin design and stopping rule. The proposed method is compared with existing methods through simulation.

Novel Alternative Methods in Toxicity Testing

  • Satoh, Tetsuo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.129-130
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    • 1994
  • The science of toxicology is the understanding of the mechanisms by which exogenous agents produce deleterious effects in biological systems. The actions of chemicals such as drugs are ultimately exerted at the cellular and gene levels. Over the past decade. several in vitro alternative methods such as cultured cells for assessing the toxicity of various xenobiotics have been proposed to reduce the use of animals. In this workshop three advanced methods will be presented. These methods are novel important models for toxicologic studies. Dr. Tabuchis group has establishcd two immortalized gastric surface mucosa cell lines from the pminary cultore of gastric fundic mucosal cells of adult transgenic mice harboring a temperature sensitive simian virus 40 large T-anugen gene. As the immortalized cell lines of various tissues possess unique characteristics to maintain their normal functions for several months, these cell lines are extremely useful for not only toxicity testing but also pharmacological screening in new drug development. Professor Funatsu have studied the formation of spherical multicelluar aggregates of adult rat hepatocytes(spheroid) having tissue like structure. The sphcroid shown thre is a prototype module of an artificial liver support system. Thus, the urea synthesis activity of the artificial liver was maintained at least to days in 100% rat blood plasma. Dr. Takezawa and his coworkers have developed a novel culture system of multicellular spheroids considered 〃organoids〃 by utilizing a thermo-responsive polymer as a substratum of anchorage dependent cells. His final goal is to reconstitute the organoids of various normal organs, e.g., liver, skin etc. and also abnormal deseased organs such as tumor.

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CORRELATION BETWEEN RAT, DOG AND HAMAN SMALL INTESTINAL PERMEABILITIES OF RANITIDINE

  • Kim, Ok-Nam;Gordon L. Amidon
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.272-272
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    • 1996
  • While ranitidine is well known to be absorbed rapidly, the underlying cause of variable bioavailability in intra- and inter-subjects has not been clarified yet. Intestinal permeability is a key controlling factor for oral absorption of highly soluble drugs, In the present study, intestinal ferfusions have been conducted to determine the intestinal permeabilities(Peffs) of ranitidine in the rats, dogs and humans and compared to the estimated fractions of dose absorbed (FAs) in humans. A new in vivo methodology, using a regional segmental perfusion technique, has been used in the dogs and humans. In situ single-pass perfusion experiments have been performed in the rats. In the dog and human studies, perfusion experiments have been conducted on two periods to determine the intrasubject variability, There was low significant intrasubject variation as compared to intersubject variation. The Peffs of ranitidine were 33%, 51%, and 45% inthe rats, dogs and humans, respectively. The FAs were approximately the same for all three species models, suggesting rats and dogs are good animal models for estimating the oral absorption of ranitidine in humans. In addition, the estimated extent of absorption of this drug is consistent with the average bioavailability, indicating that ranitidine has permeability-limited absorption characteristics. Supported by FDA Grant FD01462.

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Unexpected Severe Cerebral Edema after Cranioplasty : Case Report and Literature Review

  • Lee, Gwang Soo;Park, Sukh Que;Kim, Rasun;Cho, Sung Jin
    • Journal of Korean Neurosurgical Society
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    • v.58 no.1
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    • pp.76-78
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    • 2015
  • This report details a case of unexpected, severe post-operative cerebral edema following cranioplasty. We discuss the possible pathological mechanisms of this complication. A 50-year-old female was admitted to our department with sudden onset of stuporous consciousness. A brain computed tomography (CT) revealed a subarachnoid hemorrhage with intracranial hemorrhage and subdural hematoma. Emergency decompressive craniectomy and aneurysmal neck clipping were performed. Following recovery, the decision was made to proceed with an autologous cranioplasty. The cranioplasty procedure was free of complications. An epidural drain was placed and connected to a suction system during skin closure to avoid epidural blood accumulation. However, following the procedure, the patient had a seizure in the recovery room. An emergency brain CT scan revealed widespread cerebral edema, and the catheter drain was clamped. The increased intracranial pressure and cerebral edema were controlled with osmotic diuretics, corticosteroids, and antiepileptic drugs. The edema slowly subsided, but new low-density areas were noted in the brain on follow-up CT 1 week later. We speculated that placing the epidural drain on active suction may have caused an acute decrease in intracranial pressure and subsequent rapid expansion of the brain, which impaired autoregulation and led to reperfusion injury.

Semantic Change of Crude Drug Preparations in Korea and Policy Evaluation (생약제제의 의미 변천과 정책적 문제 검토)

  • Kim, Yun-Kyung;Cho, Sunyoung;Kim, Jiyeon;Kang, Yeonseok
    • Herbal Formula Science
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    • v.21 no.2
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    • pp.29-43
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    • 2013
  • Objectives : The aim of this study is reviewing the past legal definition and regulations, to provide basis for the future desirable direction of Korean herbal pharmaceutical industry and national herbal drug policies. Methods : We reviewed how concept of herbal medicinal preparation has been utilized and changed along with various national laws and regulations. And this study also reviewed problems related herbal medicinal preparation policies. Results : Since 1990s, especially inauguration of Korea Food & Drug Administration (KFDA) at 1998, the concept of crude drug preparation has constantly expanded and distorted the scope of herbal medicinal preparations. This resulted in decline of herbal medicinal preparation industry. Conclusions : It means policies related herbal medicinal preparation which was driven steadily during this decade have lost their consistency. Also, it restricted the various medical options which can guarantee people's health rights.

Current state and prospective of the Korean medical research on the cancer metabolism (암특이적 대사에 대한 한의학적 연구의 현황 및 전망)

  • Chung, Tae-Wook;Kim, Eun-Yeong;Choi, Hee-Jin;Choi, Hee-Jung;Ha, Ki-Tae
    • Journal of Korean Traditional Oncology
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    • v.20 no.1
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    • pp.81-88
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    • 2015
  • Generally, normal cells synthesize adenosine triphosphate (ATP) through oxidative phosphorylation in the mitochondria. However, they produce ATP through lactic acid fermentation on hypoxic condition. Interestingly, many cancer cells rely on aerobic glycolysis for ATP generation instead of mitochondrial oxidative phosphorylation, which is termed as "Warburg effect". According to results from recent researches on differences of cancer cell metabolism from normal cell metabolism and because chemotherapy to suppress rapidly growing cells, as a side effect of cancer treatment, can still target healthy cells, there is merit in the development of small-molecule inhibitors targeting metabolic enzymes such as pyruvate dehydrogenase kinase (PDHK), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT). For new anticancer therapy, in this review, we show recent advances in study on cancer cell metabolism and molecules targeting metabolic enzymes which are importantly associated with cancer metabolism for cancer therapy. Furthermore, we would also like to emphasize the necessity of development of molecules targeting metabolic enzymes using herbal medicines and their constituents for anticancer drugs.