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1.
urol. colomb. (Bogotá. En línea) ; 30(4): 277-285, 15/12/2021. tab, ilus
Article in Spanish | LILACS, COLNAL | ID: biblio-1369044

ABSTRACT

Objetivo Evaluar la costoefectividad incremental del régimen combinado de mirabegron/solifenacina en comparación con el uso temprano de toxina botulínica, desde la perspectiva del sistema de salud colombiano, para el tratamiento de adultos con vejiga hiperactiva. Métodos Se empleó un modelo de Markov en que se comparan dos secuencias de tratamiento, una con y otra sin mirabegron/solifenacina, para evaluar la costoefectividad en un horizonte temporal de cinco años. Debido a la perspectiva de análisis, sólo se tuvieron en cuenta los costos médicos directos. La eficacia del tratamiento evaluado y su comparador fue medida en términos de la reducción de episodios diarios de incontinencia y de la frecuencia de micciones. Los costos fueron expresados en pesos colombianos de 2019, y se aplicó una tasa de descuento de 5% tanto para desenlaces como para costos. Resultados Para el caso base, el costo del tratamiento en la secuencia que incluye mirabegron/solifenacina fue mayor, pero generó un mayor número de años de vida ajustados por calidad, y así e obtuvo una razón de costoefectividad incremental de $13.637,184 si se considera el desenlace de reducción de episodios diarios de incontinencia de 50%, y de $29.313,848 si se considera el del 100%. Conclusiones De acuerdo con los resultados de esta evaluación, para un horizonte de análisis de cinco años, la secuencia de tratamiento con mirabegron/solifenacina es una alternativa costoefectiva, si se considera un umbral de disposición a pagar de tres veces el producto interno bruto (PIB) per cápita.


Aim To evaluate the incremental cost-effectiveness of the combined regimen of mirabegron/solifenacin compared with the early use of botulinum toxin, from the perspective of the Colombian health system, for the treatment of adults with overactive bladder. Methods A Markov model comparing two treatment sequences, one with and one without mirabegron/solifenacin, was used to assess cost-effectiveness over a five-year period. Due to the perspective of the analysis, only direct medical costs were considered. The efficacy of the evaluated treatment and its comparator was measured in terms of the reduction in the daily incontinence episodes and the frequency of micturition. The costs were expressed in Colombian pesos of 2019, and a discount rate of 5% was applied for both outcomes and costs. Results For the base case, the cost of the treatment in the sequence that includes mirabegron/solifenacin was higher, but it generated a greater number of quality-adjusted years of life, thus obtaining an incremental cost-effectiveness ratio of $13,637,184 when considering the outcome of 50% of reduction in the daily incontinence episodes, and $29,313,848 when considering 100%. Conclusions According to the results of the present assessment, for a five-year period of analysi, the mirabegron/solifenacin treatment sequence is a cost-effective alternative when considering a threshold of willingness to pay three times the per capita gross domestic product (GDP).


Subject(s)
Humans , Syndrome , Urinary Bladder, Overactive , Guanosine Diphosphate , Effectiveness , Botulinum Toxins , Treatment Outcome , Solifenacin Succinate , Gender Identity
2.
Arq. Asma, Alerg. Imunol ; 3(1): 37-50, jan.mar.2019. ilus
Article in Portuguese | LILACS | ID: biblio-1381139

ABSTRACT

Objetivo: Avaliar a custo-efetividade e o impacto orçamentário da adição do omalizumabe (Oma) ao tratamento padrão [corticosteroide inalatório [CI] em dose média/alta e agente beta 2-agonista de longa ação (LABA)] no tratamento da asma alérgica grave não controlada, sob a perspectiva do sistema privado de saúde no Brasil. Método: Na análise econômica, utilizou-se o modelo de Markov baseado na evolução da asma, considerando os seguintes desfechos clínicos: exacerbações graves clinicamente significantes (EGCS) e exacerbações não graves clinicamente significantes (ECS), além de taxa de mortalidade por asma e uso de recursos e custos com o tratamento. Calculou-se razões de custo-efetividade incremental (RCEI) e o impacto orçamentário, com base em dados da saúde suplementar sobre população elegível e horizonte de 5 anos. Resultados: A análise de custoefetividade realizada mostrou que o tratamento com Oma teve maior benefício, se comparado ao tratamento padrão, e gerou uma RCEI de R$ 60.293,00 por ano de vida salvo, que é três vezes inferior ao produto interno bruto (PIB) per capita no Brasil. A análise de sensibilidade, para avaliar o impacto da incerteza dos parâmetros sobre o resultado encontrado, demonstrou que os resultados permanecem estáveis a favor do Oma. A análise do impacto orçamentário apontou um custo por beneficiário de R$ 0,40 no primeiro ano, chegando a R$ 1,80 no quinto ano. Conclusão: A análise econômica demonstrou que a combinação do tratamento com Oma com o padrão para asma alérgica grave não controlada é custo-efetivo no cenário nacional, e a sua incorporação na saúde suplementar é viável.


Objective: To evaluate the cost-effectiveness and budgetary impact of adding omalizumab (Oma) to standard treatment (medium/highdose inhaled corticosteroid [ICS] and long-acting beta 2-agonist [LABA]) in the treatment of severe uncontrolled allergic asthma, from the perspective of the Brazilian private health system (PHS). Method: In economic analysis, the Markov model was used based on the progression of asthma considering the following clinical outcomes: clinically significant severe exacerbations (CSSE) and clinically significant non-severe exacerbations (CSNSE), as well as asthma mortality rate and use of resources and costs of treatment. Incremental cost-effectiveness ratios (ICER) and budgetary impact were calculated based on PHS data regarding eligible population and 5-year horizon scanning. Results: The cost-effectiveness analysis showed that treatment with Oma provided greater benefit compared to the standard treatment and generated an ICER of BRL 60,293 per life-years saved, corresponding to less than three times the gross domestic product (GDP) per capita in Brazil. A sensitivity analysis to evaluate the impact of parameter uncertainty showed that results still favor Oma. The budget impact analysis showed a cost of BRL 0.40 per recipient in the first year, reaching BRL 1.80 in the fifth year. Conclusion: The economic analysis demonstrated that combined Oma treatment and standard treatment of uncontrolled severe allergic asthma is cost-effective in the national setting and its incorporation into PHS is feasible.


Subject(s)
Humans , Asthma , Adrenal Cortex Hormones , Supplemental Health , Cost-Effectiveness Analysis , Omalizumab , Analysis of the Budgetary Impact of Therapeutic Advances , Patients , Therapeutics , Effectiveness , Health Systems , Cost-Benefit Analysis , Dosage , Gross Domestic Product , Guanosine Diphosphate , Health Resources
3.
Arq. Asma, Alerg. Imunol ; 3(1): 51-63, jan.mar.2019. ilus
Article in Portuguese | LILACS | ID: biblio-1381140

ABSTRACT

Objetivos: Determinar a relação custo-efetividade da adição do omalizumabe (Oma) no tratamento da urticária crônica espontânea (UCE) refratária aos tratamentos convencionais, bem como o impacto orçamentário no contexto da saúde suplementar (SS) no Brasil. Métodos: Na análise econômica, utilizou-se o modelo de Markov baseado no Urticaria Activity Score for 7 days (UAS7), considerando- se os desfechos clínicos: anos de vida salvos com doença controlada (UAS7 = 0 ou UAS7 ≤ 6), e anos de vida ajustados à qualidade (QALY). Três razões de custo-efetividade incremental (RCEI) foram calculadas. O impacto orçamentário foi calculado com base em dados da SS, população elegível e o horizonte de 5 anos. Resultados: As RCEI calculadas para o desfecho anos de vida salvos com doença controlada nos horizontes de 3 e 5 anos foram R$ 108.935,42 e R$ 166.977,29, respectivamente. O impacto orçamentário, do primeiro ao quinto ano, da incorporação do Oma à SS para o tratamento de pacientes com UCE refratária variou entre R$ 65 milhões e R$ 157 milhões, que equivaleria a R$ 1,38/assistido no primeiro ano incorporação. Sendo assim, ao analisar os custos adicionais por desfecho adicional salvo, nota-se que a RCEI também se mostrou menor que três vezes o PIB per capita no Brasil, podendo-se dizer que o tratamento com Oma é custo-efetivo em comparação ao tratamento atual também neste desfecho. Conclusão: A análise econômica demonstrou que o tratamento com Oma da UCE refratária ao tratamento com antihistamínicos H1 em doses elevadas é custo-efetivo no cenário nacional, e a sua incorporação na SS é viável.


Objectives: To determine the cost-effectiveness of adding omalizumab (Oma) to the treatment of chronic spontaneous urticaria (CSU) refractory to conventional treatments, as well as its budgetary impact in the context of private health insurance (PHI) in Brazil. Methods: In the economic analysis, the Markov model based on the Urticaria Activity Score over 7 days (UAS7) was used considering the following clinical outcomes: life years saved with controlled disease (UAS7 = 0 or UAS7 ≤ 6) and quality-adjusted life years (QALYs). Three incremental cost-effectiveness ratios (ICERs) were calculated. The budgetary impact was calculated using PHI data, eligible population, and 5-year horizon. Results: The estimated ICERs for life years saved with controlled disease in 3- and 5-year horizons were R$ 108,935.42 and R$ 166,977.29, respectively. The budgetary impact from the first to the fifth year of the incorporation of Oma into PHI for the treatment of patients with refractory CSU ranged from R$ 65 million to R$ 157 million, equivalent to R$ 1.38/assisted patient in the first year of incorporation. When additional costs were analyzed per additional outcome saved, ICER was shown to be less than three times the GDP per capita in Brazil. Thus, Oma is cost-effective compared to the current treatment in this outcome as well. Conclusion: The economic analysis demonstrated that treatment with Oma of CSU refractory to the treatment with H1 antihistamines in high doses is cost-effective in the Brazilian setting and its incorporation into the PHI system is feasible.


Subject(s)
Humans , Supplemental Health , Cost-Effectiveness Analysis , Omalizumab , Analysis of the Budgetary Impact of Therapeutic Advances , Chronic Urticaria , Histamine Antagonists , Patients , Therapeutics , Effectiveness , Cost-Benefit Analysis , Quality-Adjusted Life Years , Gross Domestic Product , Guanosine Diphosphate , Methods
4.
Health Policy and Management ; : 206-219, 2019.
Article in Korean | WPRIM | ID: wpr-763910

ABSTRACT

This paper aims to demonstrate current health expenditure (CHE) and National Health Accounts of the years 2018 constructed according to the SHA2011, which is a manual for 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 analyzing health accounts of OECD member countries. Particularly, scale and trends of the total CHE financing as well as public-private mix are parsed in depth. In the case of private financing, estimation of total expenditures for (revenues by) provider groups (HP) is made from both survey on the benefit coverage rate of National Health Insurance (by National Health Insurance Service) and Economic Census and Service Industry Census (by National Statistical Office); and other pieces of information from Korean Health Panel Study, etc. are supplementarily used to allocate those totals into functional classifications. CHE was 144.4 trillion won in 2018, which accounts for 8.1% of Korea's gross domestic product (GDP). It was a big increase of 12.8 trillion won, or 9.7%, from the previous year. GDP share of Korean CHE has already been close to the average of OECD member countries. Government and compulsory schemes' share (or public share), 59.8% of the CHE in 2018, is much lower than the OECD average of 73.6%. ‘Transfers from government domestic revenue’ share of total revenue of health financing was 16.9% in Korea, lower than the other social insurance countries. When it comes to ‘compulsory contributory health financing schemes,’ ‘transfers from government domestic revenue’ share of 13.5% was again much lower compared to Japan (43.0%) and Belgium (30.1%) with social insurance scheme.


Subject(s)
Belgium , Censuses , Classification , Gross Domestic Product , Guanosine Diphosphate , Health Expenditures , Healthcare Financing , Japan , Korea , National Health Programs , Organisation for Economic Co-Operation and Development , Social Security , World Health Organization
5.
Korean Journal of Family Medicine ; : 162-167, 2015.
Article in English | WPRIM | ID: wpr-46110

ABSTRACT

BACKGROUND: The relationship between economics and health has been of great interest throughout the years. The accumulated data is not sufficient enough to carry out long-term studies from the viewpoint of morbidity, although Korea National Health and Nutrition Examination Survey (KNHANES) was carried out yearly since 1998 in Korea. Thus, we investigated the effect of the 2008 global economic crisis on health indicators of Korea. METHODS: Health indicators were selected by paired t-test based on 2007 and 2009 KNHANES data. Age, gender, body mass index (BMI), smoking, drinking, exercise, education, income, working status, and stress were used as confounding factors, which were analyzed with logistic and probit analyses. Validation was done by comparing gross domestic product (GDP) growth rates and probit analyses results of 2007-2012 KNHANES data. RESULTS: Among several health indicators, the prevalence of hypertension and stress perception was higher after the economic crisis. Factors related with higher hypertension prevalence include older age, male gender, higher BMI, no current tobacco use, recent drinking, lower education levels, and stress perception. Factors related with more stress perception were younger age, female gender, current smoking, lower education levels, and lower income. GDP growth rates, a macroeconomic indicator, are inversely associated with hypertension prevalence with a one-year lag, and also inversely associated with stress perception without time lag. CONCLUSION: The economic crisis increased the prevalence of hypertension and stress perception. In the case of GDP growth rate change, hypertension was an inversely lagging indicator and stress perception was an inversely-related coincident indicator.


Subject(s)
Female , Humans , Male , Body Mass Index , Drinking , Economic Recession , Education , Gross Domestic Product , Guanosine Diphosphate , Hypertension , Korea , Nutrition Surveys , Prevalence , Smoke , Smoking , Tobacco Use
6.
Protein & Cell ; (12): 139-146, 2015.
Article in English | WPRIM | ID: wpr-757621

ABSTRACT

Formation of the endoplasmic reticulum (ER) network requires homotypic membrane fusion, which involves a class of atlastin (ATL) GTPases. Purified Drosophila ATL is capable of mediating vesicle fusion in vitro, but such activity has not been reported for any other ATLs. Here, we determined the preliminary crystal structure of the cytosolic segment of Drosophila ATL in a GDP-bound state. The structure reveals a GTPase domain dimer with the subsequent three-helix bundles associating with their own GTPase domains and pointing in opposite directions. This conformation is similar to that of human ATL1, to which GDP and high concentrations of inorganic phosphate, but not GDP only, were included. Drosophila ATL restored ER morphology defects in mammalian cells lacking ATLs, and measurements of nucleotide-dependent dimerization and GTPase activity were comparable for Drosophila ATL and human ATL1. However, purified and reconstituted human ATL1 exhibited no in vitro fusion activity. When the cytosolic segment of human ATL1 was connected to the transmembrane (TM) region and C-terminal tail (CT) of Drosophila ATL, the chimera still exhibited no fusion activity, though its GTPase activity was normal. These results suggest that GDP-bound ATLs may adopt multiple conformations and the in vitro fusion activity of ATL cannot be achieved by a simple collection of functional domains.


Subject(s)
Animals , Humans , Dimerization , Drosophila , Drosophila Proteins , Chemistry , Genetics , Endoplasmic Reticulum , Chemistry , GTP Phosphohydrolases , Chemistry , Genetics , GTP-Binding Proteins , Chemistry , Genetics , Guanosine Diphosphate , Chemistry , Metabolism , Membrane Proteins , Chemistry , Genetics , Mutation , Protein Conformation , Protein Structure, Secondary
7.
Acta Physiologica Sinica ; (6): 647-657, 2014.
Article in English | WPRIM | ID: wpr-255990

ABSTRACT

A growing number of studies have shown that arginine vasopressin (AVP) plays an analgesia role in the modulation of nociception. Previous studies have focused on the central mechanisms of AVP analgesia. The aim of the present study was to find out whether peripheral mechanisms are also involved. The effect of AVP on GABA-activated currents (IGABA) and GABAA receptor function in freshly isolated dorsal root ganglion (DRG) neurons of rats were studied using whole cell patch clamp technique. The result showed that, IGABA were potentiated by pre-treatment with AVP (1 × 10⁻¹⁰-1 × 10⁻⁵ mol/L) in a concentration-dependent manner. Meanwhile, the GABA concentration-response curve was shifted upwards, with an increase of (49.1 ± 4.0)% in the maximal current response but with no significant change in the EC50 values. These results indicate that the enhancing effect is non-competitive. In addition, the effects of AVP on IGABA might be voltage-independent. This potentiation of IGABA induced by AVP was almost completely blocked by the V1a receptor antagonist SR49059 (3 × 10⁻⁶ mol/L). Also it could be removed by intracellular dialysis of either GDP-β-S (5 × 10⁻⁴mol/L), a non-hydrolyzable GDP analog, or GF109203X (2 × 10⁻⁶ mol/L), a selective protein kinase C (PKC) inhibitor, with the re-patch clamp. These results suggest that AVP up-regulates the function of the GABAA receptor via G protein-coupled receptors and PKC-dependent signal pathways in rat DRG neurons, and this potentiation may underlie the analgesia induced by AVP.


Subject(s)
Animals , Rats , Arginine Vasopressin , Pharmacology , Ganglia, Spinal , Cell Biology , Guanosine Diphosphate , Pharmacology , Indoles , Maleimides , Membrane Potentials , Neurons , Patch-Clamp Techniques , Rats, Sprague-Dawley , Receptors, GABA-A , Metabolism , Signal Transduction , Thionucleotides , Pharmacology , gamma-Aminobutyric Acid , Pharmacology
8.
Toxicological Research ; : 149-155, 2013.
Article in English | WPRIM | ID: wpr-193680

ABSTRACT

G protein-coupled receptors (GPCRs) are membrane receptors; approximately 40% of drugs on the market target GPCRs. A precise understanding of the activation mechanism of GPCRs would facilitate the development of more effective and less toxic drugs. Heterotrimeric G proteins are important molecular switches in GPCR-mediated signal transduction. An agonist-activated receptor interacts with specific sites on G proteins and promotes the release of GDP from the Galpha subunit. Because of the important biological role of the GPCR-G protein coupling, conformational changes in the G protein upon receptor coupling have been of great interest. One of the most important questions was the interface between the GPCR and G proteins and the structural mechanism of GPCR-induced G protein activation. A number of biochemical and biophysical studies have been performed since the late 80s to address these questions; there was a significant breakthrough in 2011 when the crystal structure of a GPCR-G protein complex was solved. This review discusses the structural aspects of GPCR-G protein coupling by comparing the results of previous biochemical and biophysical studies to the GPCR-G protein crystal structure.


Subject(s)
GTP-Binding Proteins , Guanosine Diphosphate , Heterotrimeric GTP-Binding Proteins , Membranes , Signal Transduction
9.
Protein & Cell ; (12): 44-50, 2012.
Article in English | WPRIM | ID: wpr-757310

ABSTRACT

As a large family of hydrolases, GTPases are widespread in cells and play the very important biological function of hydrolyzing GTP into GDP and inorganic phosphate through binding with it. GTPases are involved in cell cycle regulation, protein synthesis, and protein transportation. Chaperones can facilitate the folding or refolding of nascent peptides and denatured proteins to their native states. However, chaperones do not occur in the native structures in which they can perform their normal biological functions. In the current study, the chaperone activity of the conserved GTPases of Escherichia coli is tested by the chemical denaturation and chaperone-assisted renaturation of citrate synthase and α-glucosidase. The effects of ribosomes and nucleotides on the chaperone activity are also examined. Our data indicate that these conserved GTPases have chaperone properties, and may be ancestral protein folding factors that have appeared before dedicated chaperones.


Subject(s)
Citrate (si)-Synthase , Chemistry , Cloning, Molecular , Conserved Sequence , Escherichia coli , Cell Biology , GTP Phosphohydrolases , Chemistry , Genetics , Metabolism , Guanosine Diphosphate , Pharmacology , Guanosine Triphosphate , Pharmacology , Molecular Chaperones , Chemistry , Genetics , Metabolism , Protein Denaturation , Protein Renaturation , Ribosomes , Metabolism , alpha-Glucosidases , Chemistry
10.
Safety and Health at Work ; : 294-297, 2012.
Article in English | WPRIM | ID: wpr-140211

ABSTRACT

Previous studies on the vast increase in suicide mortality in Southeast Asia have indicated that suicide rates increase in parallel with a rise in unemployment or during periods of economic recession. This paper examines the effects of economic recession on suicidal rates amongst agriculture, fisheries, and forestry workers in Korea. Monthly time-series gross domestic product (GDP) data were linked with suicidal rates gathered from the cause of death records between1993-2008. Data were analyzed using generalized additive models to analyze trends, while a polynomial lag model was used to assess the unconstrained time lag effects of changes in GDP on suicidal rate. We found that there were significant inverse correlations between changes in GDP and suicide for a time lag of one to four months after the occurrence of economic event. Furthermore, it was evident that the overall relative risks of suicide were high enough to bring about social concern.


Subject(s)
Agriculture , Asia, Southeastern , Cause of Death , Economic Recession , Fisheries , Forestry , Gross Domestic Product , Guanosine Diphosphate , Korea , Suicide , Unemployment
11.
Safety and Health at Work ; : 294-297, 2012.
Article in English | WPRIM | ID: wpr-140210

ABSTRACT

Previous studies on the vast increase in suicide mortality in Southeast Asia have indicated that suicide rates increase in parallel with a rise in unemployment or during periods of economic recession. This paper examines the effects of economic recession on suicidal rates amongst agriculture, fisheries, and forestry workers in Korea. Monthly time-series gross domestic product (GDP) data were linked with suicidal rates gathered from the cause of death records between1993-2008. Data were analyzed using generalized additive models to analyze trends, while a polynomial lag model was used to assess the unconstrained time lag effects of changes in GDP on suicidal rate. We found that there were significant inverse correlations between changes in GDP and suicide for a time lag of one to four months after the occurrence of economic event. Furthermore, it was evident that the overall relative risks of suicide were high enough to bring about social concern.


Subject(s)
Agriculture , Asia, Southeastern , Cause of Death , Economic Recession , Fisheries , Forestry , Gross Domestic Product , Guanosine Diphosphate , Korea , Suicide , Unemployment
12.
Protein & Cell ; (12): 64-73, 2011.
Article in English | WPRIM | ID: wpr-757663

ABSTRACT

Human NUDT16 (hNUDT16) is a decapping enzyme initially identified as the human homolog to the Xenopus laevis X29. As a metalloenzyme, hNUDT16 relies on divalent cations for its cap-hydrolysis activity to remove m⁷GDP and m²²⁷GDP from RNAs. Metal also determines substrate specificity of the enzyme. So far, only U8 small nucleolar RNA (snoRNA) has been identified as the substrate of hNUDT16 in the presence of Mg²(+). Here we demonstrate that besides U8, hNUDT16 can also actively cleave the m⁷GDP cap from mRNAs in the presence of Mg²(+) or Mn²(+). We further show that hNUDT16 does not preferentially recognize U8 or mRNA substrates by our cross-inhibition and quantitative decapping assays. In addition, our mutagenesis analysis identifies several key residues involved in hydrolysis and confirms the key role of the REXXEE motif in catalysis. Finally an investigation into the subcellular localization of hNUDT16 revealed its abundance in both cytoplasm and nucleus. These findings extend the substrate spectrum of hNUDT16 beyond snoRNAs to also include mRNA, demonstrating the pleiotropic decapping activity of hNUDT16.


Subject(s)
Humans , Amino Acid Motifs , Biocatalysis , Cell Nucleus , Consensus Sequence , Cytoplasm , Metabolism , Guanosine Diphosphate , Metabolism , Histidine , Metabolism , Hydrolysis , Luciferases , Genetics , Magnesium , Metabolism , Manganese , Metabolism , Mutagenesis , Mutation , Pyrophosphatases , Chemistry , Genetics , Metabolism , RNA Caps , Chemistry , Metabolism , Pharmacology , RNA, Small Nucleolar , Chemistry , Metabolism , Pharmacology
13.
Protein & Cell ; (12): 308-319, 2011.
Article in English | WPRIM | ID: wpr-757101

ABSTRACT

The guanine-nucleotide exchange factor (GEF) RalGPS1a activates small GTPase Ral proteins such as RalA and RalB by stimulating the exchange of Ral bound GDP to GTP, thus regulating various downstream cellular processes. RalGPS1a is composed of an Nterminal Cdc25-like catalytic domain, followed by a PXXP motif and a C-terminal pleckstrin homology (PH) domain. The Cdc25 domain of RalGPS1a, which shares about 30% sequence identity with other Cdc25-domain proteins, is thought to be directly engaged in binding and activating the substrate Ral protein. Here we report the crystal structure of the Cdc25 domain of RalGPS1a. The bowl shaped structure is homologous to the Cdc25 domains of SOS and RasGRF1. The most remarkable difference between these three Cdc25 domains lies in their active sites, referred to as the helical hairpin region. Consistent with previous enzymological studies, the helical hairpin of RalGPS1a adopts a conformation favorable for substrate binding. A modeled RalGPS1a-RalA complex structure reveals an extensive binding surface similar to that of the SOS-Ras complex. However, analysis of the electrostatic surface potential suggests an interaction mode between the RalGPS1a active site helical hairpin and the switch 1 region of substrate RalA distinct from that of the SOS-Ras complex.


Subject(s)
Humans , Amino Acid Sequence , Binding Sites , Catalytic Domain , Cloning, Molecular , Crystallography, X-Ray , Escherichia coli , Guanosine Diphosphate , Metabolism , Guanosine Triphosphate , Metabolism , Models, Molecular , Molecular Conformation , Molecular Sequence Data , Plasmids , Metabolism , Protein Binding , Protein Structure, Tertiary , Genetics , Recombinant Proteins , Chemistry , Genetics , Metabolism , ral GTP-Binding Proteins , Chemistry , Genetics , Metabolism , ral Guanine Nucleotide Exchange Factor , Chemistry , Genetics , Metabolism
14.
The Korean Journal of Nutrition ; : 533-542, 2010.
Article in Korean | WPRIM | ID: wpr-653458

ABSTRACT

The objective of this study is to provide basic information and policy implications needed to balance the supply and demand for dietitian by projecting supply and demand for dietitian. The data from the Ministry of Health Welfare and Family on the number of licensed nutritionist, resident registration data of the Ministry of Public Administration and Security, and health insurance qualification data of the National Health Insurance Corporation were used to examine the current status of supply. To project the supply of nutritionist workforce, the in-out moves method and demographic method were used. The ratios of nutritionist to population and GDP, and that of other countries were applied as the demand projection method. According to the study results, the projection on the imbalance of supply and demand for dietitian by year 2021 differs depending on the method used. First, according to the results based on age-adjusted population ratio, there is an oversupply of 1,643 dietitians in year 2010, and 2,076 dietitians in year 2020. Second, although the projection on the imbalance of the supply and demand for dietitian differs depending on whether the GDD is calculated in won(won) or dollar($). it is expected that there will be an oversupply in general. Third, as to the scenario using the nutritionist ratio in foreign countries, the oversupply of dietitian is likely in Korea, under any scenario, when comparing the nutritionist supply projection with the demand projection based on the nutritionist ratio in the United States. However, the projection of the supply and demand varies in each scenario when the European nutritionist ratio is applied. Under European 'scenario 1', an oversupply is expected, whereas under 'scenario 2', a shortage of supply is expected. A careful approach is required in interpreting the supply and demand projection using criteria of other countries, because dietitian assumes different roles and functions in each country. Although a slight oversupply of nutritionist workforce is projected, it does not cause a major problem as the demand for diet therapy is expected to rise due to aging and the increase of chronic diseases, and as the demand for clinical dietitians in hospitals increases. Accordingly, the demand for dietitians will rise and, in this context, the oversupply of nutritionist will not incur much problem. However, the nutritionist qualification is much too open in Korea, and this has a negative effect on the quality of the nutritionist workforce. Therefore, it is important that the nutritionist qualifications and requirements are reinforced in the future, enhance the quality level of the nutritionist supply, and maintain the balance between the supply and demand.


Subject(s)
Humans , Aging , Chronic Disease , Guanosine Diphosphate , Insurance, Health , Korea , National Health Programs , United States
15.
Journal of Breast Cancer ; : 104-110, 2010.
Article in Korean | WPRIM | ID: wpr-136988

ABSTRACT

PURPOSE: The aim of this study was to determine the incremental effectiveness (the differences in progression-free survival between treatments), the incremental cost and the incremental cost-effectiveness of Genexol-PM compared to Paclitaxel when these drugs were used as treatment for patients with metastatic breast cancer. METHODS: In the absence of any comparative direct evidence of the relative efficacy of Paclitaxel and Genexol-PM in this setting, a meta-analysis was conducted to determine the effects of the Paclitaxel on the health outcome. The decision tree model was constructed to evaluate the two treatment regimens. All the costs are in 2008 Korean Won (KW) and they were evaluated according to the 3rd party payer perspective, and the direct nonmedical and indirect costs were excluded. RESULTS: When compared with Paclitaxel, Genexol-PM was shown to increase the response rate and the time to progression for patients with metastatic breast cancer. Although the overall treatment costs of Genexol-PM were slightly higher than those of Paclitaxel, Genexol-PM was associated with a delayed time to progression of 4.78 months per patient. The incremental cost effectiveness ratio for Genexol-PM versus Paclitaxel was KW 2,295,228 per year gained, which is far below the per capita GDP or the threshold of the willingness-to-pay in Korea. CONCLUSION: Compared with Paclitaxel, Genexol-PM for treating metastatic breast cancer is within the acceptable range of the cost-effectiveness ratio for medical intervention.


Subject(s)
Humans , Breast , Breast Neoplasms , Cost-Benefit Analysis , Decision Trees , Disease-Free Survival , Guanosine Diphosphate , Health Care Costs , Neoplasm Metastasis , Paclitaxel
16.
Journal of Breast Cancer ; : 104-110, 2010.
Article in Korean | WPRIM | ID: wpr-136982

ABSTRACT

PURPOSE: The aim of this study was to determine the incremental effectiveness (the differences in progression-free survival between treatments), the incremental cost and the incremental cost-effectiveness of Genexol-PM compared to Paclitaxel when these drugs were used as treatment for patients with metastatic breast cancer. METHODS: In the absence of any comparative direct evidence of the relative efficacy of Paclitaxel and Genexol-PM in this setting, a meta-analysis was conducted to determine the effects of the Paclitaxel on the health outcome. The decision tree model was constructed to evaluate the two treatment regimens. All the costs are in 2008 Korean Won (KW) and they were evaluated according to the 3rd party payer perspective, and the direct nonmedical and indirect costs were excluded. RESULTS: When compared with Paclitaxel, Genexol-PM was shown to increase the response rate and the time to progression for patients with metastatic breast cancer. Although the overall treatment costs of Genexol-PM were slightly higher than those of Paclitaxel, Genexol-PM was associated with a delayed time to progression of 4.78 months per patient. The incremental cost effectiveness ratio for Genexol-PM versus Paclitaxel was KW 2,295,228 per year gained, which is far below the per capita GDP or the threshold of the willingness-to-pay in Korea. CONCLUSION: Compared with Paclitaxel, Genexol-PM for treating metastatic breast cancer is within the acceptable range of the cost-effectiveness ratio for medical intervention.


Subject(s)
Humans , Breast , Breast Neoplasms , Cost-Benefit Analysis , Decision Trees , Disease-Free Survival , Guanosine Diphosphate , Health Care Costs , Neoplasm Metastasis , Paclitaxel
18.
Korean Journal of Blood Transfusion ; : 75-83, 2009.
Article in Korean | WPRIM | ID: wpr-160024

ABSTRACT

BACKGROUND: Due to the slowing of population growth, population ageing, and more aggressive medical treatment, Korea will be faced with the challenge of blood shortage. One solution to the blood shortage problem is to take advantage of the multicomponent collection technique. However, clinical application is limited due to the low prices of blood products. In this study, we compared the prices of blood products in 6 major countries. METHODS: Prices of leukoreduced red blood cells (RBC), platelet concentrate (PC), fresh frozen plasma (FFP), cryoprecipitate (CRYO), and apheresis platelets (AP) were compiled from US, United Kingdom, Japan, Australia, Spain, and Korea. Adjusted prices using per capita gross domestic product (GDP) and purchasing power parity (PPP) were estimated and analyzed. RESULTS: The RBC price in Korea was only 30% of the mean RBC price of the other 5 countries. Considering per capita GDP and PPP, the RBC prices in Korea were estimated up to 41% and 46%, respectively. The PPP adjusted price of PC, FFP, and AP of Korea was 70%, 72%, and 70% of mean price of the other 5 countries. Price ratios of PC, FFP, and CRYO to RBC were 0.59, 0.63, and 0.57, which were higher than the means of the other 5 countries (0.38, 0.47, and 0.32). CONCLUSION: Considering per capita GDP and PPP, blood product prices in Korea were cheaper than the mean prices of the other 5 countries. For adoption of multicomponent collection, the prices of blood products should be raised, especially the price of RBCs.


Subject(s)
Female , Adoption , Australia , Blood Component Removal , Blood Platelets , Erythrocytes , United Kingdom , Gross Domestic Product , Guanosine Diphosphate , Imidazoles , Japan , Korea , Nitro Compounds , Parity , Plasma , Population Growth , Spain
19.
Acta méd. costarric ; 50(supl.3): 53-54, nov. 2008.
Article in Spanish | LILACS | ID: lil-700668

ABSTRACT

Es un análogo nucleósido de guanosina con actividad selectiva contra hepatitis B, que ha surgido como una opción terapéutica en pacientes que desarrollan resistencia a la lamivudina con un perfil de seguridad similar a esta, encontrándose prácticamente ausencia de resistencia en casos de tratamiento por 1 año con una dosis de 1mg/día.


It is a nucleoside analogue of guanosine with selective activity against hepatitis B. It has come out as a therapeutic option for patients who develop resistance to Lamivudine with a security profile similar to this medicine. There is absence of resistance in case of 1 year treatments with a dosage of 1mg/day.


Subject(s)
Humans , Guanosine Diphosphate/administration & dosage , Hepatitis B virus
20.
Acta Physiologica Sinica ; (6): 492-496, 2008.
Article in Chinese | WPRIM | ID: wpr-316700

ABSTRACT

To investigate the regulatory role of purine nucleotide on uncoupling proteins (UCPs), the activity of UCPs and the expressions of UCP4 and UCP5 in mitochondria of rat brain tissues incubated with GDP were observed in vitro. The cerebral hemispheres of adult male Sprague-Dawley rats were removed and clipped into 8-10 mm3 tissue mass which incubated with 1 mmol/L GDP (GDP group), or only incubation medium (control group), for 30 min in vitro. The mitochondria from incubated tissue mass of rat brain were isolated by centrifugation. The activity of UCPs was detected by the method of [3H]-GTP binding with UCPs specifically. The maximal binding content (Bmax) and the dissociation constant (Kd) were determined from Scatchard plot. The mRNA and protein expressions of UCP4 and UCP5 were measured by RT-PCR and Western blot, respectively. The results showed that Bmax was increased and Kd was decreased in rat brain mitochondria in GDP group compared with that in control group. But the mRNA and protein expressions of UCP4 and UCP5 exhibited no statistically significant changes. It is thus suggested that GDP inhibits the activity of mitochondrial UCPs in rat brain in vitro, but exhibits no effect on the expressions of UCP4 and UCP5.


Subject(s)
Animals , Male , Rats , Brain , Metabolism , Guanosine Diphosphate , Pharmacology , In Vitro Techniques , Ion Channels , Metabolism , Mitochondria , Metabolism , Mitochondrial Membrane Transport Proteins , Metabolism , Mitochondrial Proteins , Metabolism , Mitochondrial Uncoupling Proteins , Nerve Tissue Proteins , Metabolism , RNA, Messenger , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
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