Kang, Ju-Hee;Ryoo, Na-Young;Shin, Dong Wun;Trojanowski, John Q.;Shaw, Leslie M.
The Korean Journal of Physiology and Pharmacology
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v.18
no.6
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pp.447-456
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2014
Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) $A{\beta}_{1-42}$, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the clinical utility of CSF biomarkers and the integration of CSF biomarkers in current clinical trials.
Journal of the Korea Institute of Information and Communication Engineering
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v.20
no.12
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pp.2395-2400
/
2016
Conventional drug carriers such as liposomes, nanoparticles, polymer micelles, polymeric conjugate and lipid microemulsion for cancer chemotherapy shield normal tissues from toxic drugs to treat cancer cells in tumors. However, inaccurate tumor targeting uncontrolled drug release from the carriers and unwanted accumulation in healthy sites can limit treatment efficacy with current conventional drug carriers with insufficient concentrations of drugs in the tumors and unexpected side effects as a result. Sickle red blood cells show natural tumor preferential accumulation without any manipulation due to the adhesive interaction between molecular receptors on the membrane surface and counter-receptor on endothelial cells. In addition, structural changes of microvascular in tumor sites enhances polymerization of sickle red blood cells. In this research, we examined the use of sickle red blood cells as a new drug carrier with novel tumor targeting and controlled release properties to quantify its therapeutic effects.
Kim, Hye-Lin;Park, Jae-A;Sin, JiYoung;Park, Seung-Hoo;Lee, Eui-Kyung
Korean Journal of Clinical Pharmacy
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v.26
no.4
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pp.341-347
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2016
Background: Liver cirrhosis causes substantial socio-economic burden and is one of the major severe liver diseases in Korea. Nonetheless, there is only a few studies that analyzes disease burden of liver cirrhosis in Korea. Such study must be carried out due to its increasing need from the invention of new drugs for chronic hepatitis and demand for cost-effectiveness analyses. Methods: Patient sample data with ensured representativeness was analyzed retrospectively to compare the medical costs and uses for patients with compensated cirrhosis and decompensated cirrhosis. Patient claims data that include K74 and K703 from the year of 2014 were selected. Within the selected data, decompensated cirrhosis patient was identified if complications such as ascites (R18), encephalopathy (B190), hepatic failure (K72), peritonitis (K65), or esophageal varices (I85) were included, and they were compared to compensated cirrhosis patients. Results: 6,565 patients were included in the analysis. The average cost per patient was 6,471,020 (SD 8,848,899) KRW and 2,173,203 (4,220,942) KRW for decompensated cirrhosis and compensated cirrhosis, respectively. For inpatients, the average hospitalized days was 38.0 (56.4) days and 27.2 (57.2) days for decompensated cirrhosis and compensated cirrhosis, respectively. For outpatients, the average number of visits was 8.7 (9.1) days and 5.3 (7.5) days for compensated cirrhosis and decompensated cirrhosis, respectively. Conclusion: Compared to compensated cirrhosis patients, decompensated cirrhosis patients had higher costs, especially for hospitalization, injection, examination, and drugs administrated within medical institutions.
Jeechool-Whan (JW) is a prescription of Ponciri Fructus Immaturus and Atractylodis Rhizoma Alba and improves the functions of the stomach and the spleen. Although it is said in Korean Medicine that the spleen and the stomach are the roots of the body's resistance, the meaning of 'improving the spleen and the stomach' is very comprehensive. Moreover, there are lots of drugs that are said to improve the spleen and the stomach, and the number of prescriptions using these drugs is huge. In this study, we focused on the new effect and mechanism of the JW on the ovalbumin (OVA)-induced allergic rhinitis (AR) model. The increased number of rubs and the increased levels of IgE and histamine in the OVA-sensitized mice were inhibited by JW administration. The balance of Th1/Th2 cytokine level was regulated by JW administration. The levels inflammatory proteins were decreased by JW administration in the nasal mucosa of the OVA-sensitized mice. Eosinophils and mast cells infiltration increased by OVA-sensitization was also decreased in the JW-administered mice. In addition, JW inhibited caspase-1 activity in the same nasal mucosa tissue. In activated human mast cells, JW inhibited the receptor interacting protein-2, I${\kappa}$B kinase-${\beta}$, nuclear factor-${\kappa}$B/Rel A, and caspase-1 activation. In conclusion, this study will be support the clear understanding of the concept of the spleen and the stomach in traditional Korean medicine as well as for a possibility of finding a cure for this AR in traditional medical treatments.
Pouresmaeili, Farkhondeh;Hosseini, S. Jalil;Farzaneh, Farah;Karimpour, Arezoo;Azargashb, Eznollah;Yaghoobi, Mohammad;Kamarehei, Maryam
Asian Pacific Journal of Cancer Prevention
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v.15
no.24
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pp.10603-10605
/
2015
Background: The Prostate cancer is the 2nd most common cancer worldwide for males, and the 5th most common cancer overall, with an estimated 900,000 new cases diagnosed in 2008 (14% of the total in males and 7% of the total overall) aim of this study was to assess some of the most proposed environmental factors influencing the incidence of prostate cancer among Iranian men. Smoking, opioids, occupation and living location were considered as studied risk factors of the prostate cancer in this research. Material and methods: Two groups of affected men with prostate cancer and controls aged 50-75 years referred to medical clinics were subjects in this case-control study. Living and working place, smoking and drug consuming habits were assessed for any associations with prostate cancer. Results: The largest number, of patients, in order, belonged to Tehran, provincial capitals, major industrial cities, small towns and villages, respectively. The disease showed links with smoking and drugs with a significant difference between controls and patients (P value <0.0001). Conclusions: Our recent evidence duplicates previously done researches confirming the serious adverse effects of smoking and drugs on the prostate cancer occurrence in Iranian men. Living place bearings some hazardous behaviors which increases the rate of diseases as well as advanced chance for associated cancers like prostate.
Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.
The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.
Background: This paper aims to demonstrate current health expenditure (CHE) and National Health Accounts of the years 2015 constructed according to the SHA2011, which is a new manual of System of Health Accounts (SHA) that was published jointly by the Organization for Economic Cooperation and Development (OECD), Eurostat, and World Health Organization in 2011. Comparison is made with international trends by collecting and analysing health accounts of OECD member countries. Particularly, financing public-private mix is parsed in depth using SHA data of both HF as financing schemes as well as FS (financing source) as their revenue types. Methods: Data sources such as Health Insurance Review and Assessment Service's publications of both motor insurance and drugs are newly used to construct the 2015 National Health Accounts. In the case of private financing, an estimation of total expenditures for revenues by provider groups is made from the Economic Census data; and the household income and expenditure survey, Korean healthcare panel study, etc. are used to allocate those totals into functional classifications. Results: CHE was 115.2 trillion won in 2015, which accounts for 7.4 percent of Korea's gross domestic product. It was a big increase of 9.3 trillion won, 8.8 percent, from the previous year. Government and compulsory schemes's share (or public share) of 56.4% of the CHE in 2015 was much lower than the OECD average of 72.6%. 'Transfers from government domestic revenue' share of total revenue of HF was 17.8% in Korea, lower than the other contribution-based countries. When it comes to 'compulsory contributory health financing schemes,' 'Transfers from government domestic revenue' share of 14.9% was again much lower compared to Japan (44.7%) and Belgium (34.8%) as contribution-based countries. Conclusion: Considering relatively lower public financing share in the inpatient care as well as overall low public financing share of total CHE, priorities in health insurance coverage need to be repositioned among inpatient care, outpatient care and drugs.
Park, So Jeong;Park, Doo Ri;Bhattarai, Deepak;Lee, Kyeong;Kim, Jaesang;Bae, Yun Soo;Lee, Soo Young
Molecules and Cells
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v.37
no.8
/
pp.628-635
/
2014
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.
Background: The new drug HP228 is a cytokine restraining agent with a broad spectrum of anti-inflammatory, analgesic, and antipyretic activity. Six healthy, adult, male volunteers were studied to determine the independent and interactive effects of HP228 and morphine on pain perception. Methods: Two groups of stimuli were applied to each volunteers before drug administration as control, 20 min after morphine and HP228 administration, and 20 min after combined administration of these two drugs. Two adhesive electrically-conducting pads were applied on opposite sides of the arm approximately 8 cm apart. The electrode were connected to an electrical impulse generator and 50 Hz 1 msec pulses of incrementally increasing intensity were delivered at 1 sec intervals. The analgesic endpoints were the current intensity (mA) at which the subject first detected the stimulus (THRESH), the intensity at which the stimulus was first idenfied as being painful (PAIN), and the intensity at which the subject requested that the stimulus be terminated due to discomfort (LIMIT). A second series of stimuli were applied immediately thereafter using 1-sec duration 50 Hz tetanus pulses with increasing intensities at 2~5 sec intervals. Results: There were significant differences between drug treatments (Morphine, HP228, HP228/Morphine) and control (No drugs) in any of the measurements (PAIN, LIMIT) except THRESH with the twitch and tetanus test. Conclusions: The data suggests that HP228 is an analgesic, but it does not appear to interact with morphine in an additive manner.
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