Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

Volume-reserving Surgery after Photodynamic Therapy for Biliary Papillomatosis: A Case Report / 대한소화기학회지

Biliary papillomatosis is rare, and its pathogenic mechanisms are not yet clear. Because of its high risk for malignancy transformation, surgical resection is regarded as a standard treatment. Photodynamic therapy (PDT) has been used by the intravenous administration of hematoporphyrin derivative followed by laser exposure. A photochemical process causes disturbance of the microvascular structure and degradation of membrane. Cholangitis is a major complication after PDT. A healthy 56-year-old man was diagnosed with biliary papillomatosis involving the common hepatic duct, both proximal intrahepatic bile ducts (IHD), and the right posterior IHD. After biliary decompression by endoscopic nasobiliary drainage, PDT was performed to avoid extensive liver resection and recurrence using endoscopic retrograde cholangiographic guidance. After portal vein embolization, the patient underwent extended right hemihepatectomy. Following administration of chemoradiation therapy with tegafur-uracil and 45 Gy due to local recurrence at postoperative 13 months, there was no local recurrence or distant metastases. This is the first case report on PDT for biliary papillomatosis in Korea. Preoperative PDT is beneficial for reducing the lesion in diffuse or multifocal biliary papillomatosis and may lead to curative and volume reserving surgery. Thus, PDT could improve the quality of life and prolong life expectation for biliary papillomatosis patients.

High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer / 부인종양

OBJECTIVE: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. METHODS: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. RESULTS: In the UFT group, 103 patients (63.6%) received UFT for > or =90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). CONCLUSION: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.

Efeito da revascularização renal sobre a evolução da disfunção renal na nefropatia isquêmica aterosclerótica / Effect of renal revascularization on the development of renal dysfunction in atherosclerotic ischemic nephropathy

A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial (HA) e diabete melito. Entre as causas de HA, podemos destacar a doença renal aterosclerótica (DRA). O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento, não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho analisa os estudos mais significantes sobre os desfechos renais em pacientes portadores de DRA submetidos à revascularização ou ao tratamento clínico exclusivo.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. The present paper analyzes the most significant studies on renal outcomes in patients with ARD undergoing revascularization or medical treatment alone.

Discomfort and unease of the subject in the interpretation movement of a Tuberculosis questionnaire / O desconforto e inquietação do sujeito em seu movimento de interpretação de um questionário sobre a tuberculose / Malestar e inquietud del sujeto en su movimiento de interpretación de un cuestionario sobre la Tuberculosis

OBJECTIVE: to propose a discussion about traces of the derivation of meanings, the subjects' discomfort and resistance when they are called upon to signify a questionnaire on the transfer of the Directly Observed Treatment of Tuberculosis policy, in order to reveal the limitations of closed questionnaires in the subject's interpretation process. METHOD: health professionals from a Primary Health Care Unit in Porto Alegre/RS were interviewed and some excerpts from the interviews were investigated in the light of French Discourse Analysis. RESULTS: resistance, discomfort, slips, silencing and the derivation of meanings were observed in the subjects' interpretation. CONCLUSION: the interpretation process has multiple meanings and varies from subject to subject. The questionnaire, as a prototype of the logically stabilized universe, fails when the purpose is to control the interpretation. Its isolated use in health research can entail inexactness or incompleteness of the collected data. Therefore, its use associated with qualitative research techniques is ideal. .

OBJETIVO: propor uma discussão a respeito de vestígios da derivação de sentidos, do desconforto e resistência dos sujeitos, quando convocados a significar um questionário referente à transferência da política do tratamento diretamente observado da tuberculose, de modo a revelar as limitações de questionários fechados, quando se trata do processo interpretativo do sujeito. MÉTODO: profissionais de saúde de uma Unidade de Atenção Primária de Saúde de Porto Alegre, RS, foram entrevistados e alguns recortes das entrevistas examinados à luz da Análise de Discurso de linha francesa. RESULTADOS: observou-se a resistência, o incômodo, o deslizamento, o silenciamento e a derivação dos sentidos no ato de interpretação dos sujeitos. CONCLUSÃO: o processo de interpretação é polissêmico e varia de sujeito para sujeito. O questionário, enquanto um protótipo do universo logicamente estabilizado, falha quando o propósito é o de controlar a interpretação. O seu uso de forma isolada, em pesquisas em saúde, pode incorrer em inexatidão ou incompletude dos dados obtidos, sendo ideal a sua utilização associada a técnicas qualitativas de pesquisa. .

OBJETIVO: proponer una discusión respecto a vestigios de la derivación de sentidos, del malestar y resistencia de los sujetos cuando convocados a significar un cuestionario respecto a la trasferencia de la política del Tratamiento Directamente Observado de la Tuberculosis, de manera a revelar las limitaciones de cuestionarios cerrados cuando se trata del proceso interpretativo del sujeto. MÉTODO: profesionales de salud de una Unidad de Atención Primaria de Salud de Porto Alegre/RS fueron entrevistados y algunos recortes de las entrevistas examinados a la luz del Análisis de Discurso de línea Francesa. RESULTADOS: fueron observados la resistencia, la molestia, el deslizamiento, el silenciamiento y la derivación de los sentidos en el acto de interpretación de los sujetos. CONCLUSIÓN: el proceso de interpretación es polisémico y varia de sujeto a sujeto. El cuestionario como un prototipo del universo lógicamente estabilizado falla cuando el objetivo es el de controlar la interpretación. Su uso de forma aislada en investigaciones en salud puede llevar a datos inexactos o incompletos, siendo ideal su utilización asociada a técnicas cualitativas de investigación. .

Consejería en la detección de VPH como prueba de tamizaje de cáncer cervical: un estudio cualitativo sobre necesidades de mujeres de Michoacán, México / Counseling for HPV detection when used to screen for cervical cancer: a qualitative study on the needs of women from Michoacan, Mexico

Objetivo. Explorar las necesidades de información y consejería de un grupo de mujeres mexicanas al utilizar la prueba de virus de papiloma humano (VPH). Material y métodos. En 2011, se realizaron 24 entrevistas semiestructuradas a mujeres que recibieron el resultado de una prueba de VPH, en dos municipios del estado de Michoacán. El análisis cualitativo de las entrevistas se realizó con las técnicas de la comparación constante. Resultados. Durante el tamizaje, las mujeres recibieron escasa consejería; experimentaron angustia y confusión. Las usuarias de la prueba se mostraron interesadas en recibir información sobre el VPH y el cáncer cervical, el significado de sus resultados, los pasos que habrían de realizar en la atención, apoyo emocional e información vinculada con la transmisión sexual de VPH. Conclusiones. Se requiere diseñar e implementar políticas para impartir educación para la salud y consejería, a la par de la realización de pruebas de VPH.

Objective. To explore the information and counseling needs of a group of Mexican women during use of the HPV test. Materials and methods. In 2011, 24 semistructured interviews were done with women upon receiving HPV test results in two municipalities in the state of Michoacan. Qualitative analysis of the interviews was done using constant comparison techniques. Results. During their use of screening services women received limited counseling; they felt anguish and confusion. Women were interested in receiving information and advice on HPV and cervical cancer, the meaning of test result, next steps to be taken in their healthcare use as well as information and emotional support related to the sexual transmission of HPV. Conclusions. The design and implementation of policies are needed which instigate health education and counseling in conjunction with HPV testing.

Effect of Tibetan medicine zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2 / 药学学报

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.

A novel dipeptidyl peptidase IV inhibitors developed through scaffold hopping and drug splicing strategy / 药学学报

Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.

Estrategia de genotipado del gen FMR1: Método de diagnóstico alternativo para el Síndrome X Frágil y otras enfermedades por expansión de trinucleotidos / Genotyping strategy for the FMR1 gene: An alternative diagnostic method for the Fragile X syndrome and other trinucleotide expansion diseases

Objetivos: Diseñar una estrategia alternativa por PCR para el genotipado de secuencias ricas en citosinas, basada en modificación nucleotídica. Material y métodos: Se modificó el gen FMR1 nativo de ocho individuos clínicamente no afectados por el Síndrome X frágil, cambiando las citosinas por uracilos, empleando bisulfito de sodio. El ADN modificado fue purificado y cuantificado por espectrofotometría. Las estructuras alternativas y potenciales islas CpG que adopta el microsatélite inestable fueron simuladas con los programas MFOLD y CpGplot. Se generaron cebadores específicos que hibriden tanto con el microsatélite modificado (Primer T) y con una secuencia modificada de las islas CpG (Primer M), utilizando el programa MethPrimer. Finalmente, ambas secuencias fueron amplificadas por PCR y los amplicones fueron separados por electroforesis en gel de poliacrilamida (PAGE por sus siglas en inglés) al 6% y visualizados con tinción de nitrato de plata. Resultados: La modificación del ADN fue evidenciada por espectrofotometría al uracilo. Las estructuras observadas en la simulación fueron las horquillas encontrándose dos potenciales islas CpG. La amplificación con los cebadores T, confirmó el diseño in silico desarrollado para abordar la estructura en horquillas. La amplificación con los cebadores M permitió detectar metilación de la primera isla CpG del gen FMR1.Conclusión: Se propone un diseño alternativo para amplificación de secuencias de microsatélite que contengan citosinas metiladas y no metiladas. Se requieren estudios posteriores con muestras de ADN que contengan microsatélites muy expandidos para validar su aplicación para diagnóstico molecular. (AU)

Objectives: To design an alternative strategy for genotyping cytosine-rich sequences using PCR and nucleotide modification. Methods: The FMR1 gene wild type was modified in the DNA obtained from eight individuals clinically unaffected for Fragile X Syndrome; cytosines were replaced by uracils using sodium bisulfite. Modified DNA was purified and quantified by spectrophotometry. Alternative structures and potential CpG islands of the unstable microsatellite were simulated using MFOLD and CpGplot tools. Specific primers were generated to hybridize with both the modified microsatellite (Primer G) and a modified sequence of CpG islands (Primer M) using the MethPrimer software. Finally, both sequences were amplified by PCR and the amplicons were separated by electrophoresis in silver-stained PAGE 6% gels. Results: The DNA modification was evidenced by spectrophotometry to uracil. We found two potential CpG islands. The amplification with T primers confirmed the "in silico" design developed to engage hairpin structures. The amplification with M primers detected methylation of the first CpG island in the FMR1 gene. Conclusion: We propose an alternative design for amplifying microsatellite sequences that contain methylated and unmethylated cytosine bases. Further studies are required with DNA samples containing expanded microsatellites to validate its molecular diagnostic application. (AU)

Clonagem, expressão heterológica e caracterização molecular das enzimas gliconato cinase e uracil fosforribosiltransferase de trypanosoma cruzi / Cloning, expression and molecular characterization heterological enzymes gluconate kinase and uracil phosphoribosyltransferase of Trypanosoma cruzi

A doença de Chagas é um problema de saúde pública na América Latina, com um forte impacto no Brasil. De acordo com estimativas da Organização Panamericana de Saúde (OPAS), em torno de 8 milhões de pessoas nas Américas estão infectados pelo Trypanosoma cruzi, com uma taxa de mortalidade de 12.000 indivíduos por ano. Apesar desta situação, os medicamentos utilizados no tratamento desta doença são ativos somente na fase aguda, apresentam uma baixa eficácia e uma série de efeitos colaterais. Portanto, a busca por novos alvos terapêuticos, através do estudo do metabolismo de T. cruzi, é uma alternativa no desenvolvimento de novos fármacos. Neste contexto, utilizou-se o AnEnPi, uma ferramenta computacional capaz de identificar e classificar proteínas com uma potencial atividade enzimática, utilizando dados genômicos previamente publicados, permitindo a reconstrução de diferentes vias metabólicas. Por meio dessa abordagem foram identificados em T. cruzi duas proteínas, as quais apresentam as seguintes atividades enzimáticas: uracil fosforibosiltransferase (UPRT) e gliconato cinase (GK). A UPRT é uma enzima da via de salvação de pirimidinas que converte uracil e D-5-fosforibosil-1-fosfato (PRPP) a monofosfato de uridina (UMP) e pirofosfato (PPi). E a GK é uma enzima da via das pentoses-fosfato que catalisa a fosforilação de gliconato a 6-fosfogliconato. Análises das sequências genômicas codificante para essas proteínas, utilizando diferentes ferramentas de bioinformática, permitiram a identificação de dois genes para cada uma dessas atividades enzimáticas em T. cruzi e confirmaram essas atividades pela identificação de seus motivos estruturais. Posteriormente, foi realizada a caracterização molecular das enzimas GK e UPRT de T. cruzi, através da clonagem dos respectivos genes, utilizando os vetores pBAD-TOPO TA e pET28a, e da expressão heteróloga em Escherichia coli, cepa BL21(DE3). As proteínas recombinantes GK e UPRT foram expressas na fração solúvel e insolúvel com pesos moleculares aproximados de 23 kDa e 28 kDa, respectivamente. Essas proteínas recombinantes foram purificadas sob condições desnaturantes através de cromatografia de afinidade. Os soros policlonais produzidos contra as proteínas purificadas foram eficazes no reconhecimento das proteínas recombinantes e de suas formas nativas presentes na forma epimastigota de T. cruzi. O ensaio de imunofluorescência revelou que as enzimas GK e UPRT estão localizadas possivelmente no citoplasma e no interior de vesículas citoplasmáticas ao longo do parasita. Além disto, a estrutura de ambas as enzimas foi deduzida através de modelagem por homologia. Este trabalho visa contribuir para o melhor entendimento do metabolismo deste parasita, de forma a auxiliar na busca de novos alvos terapêuticos contra a doença de Chagas.

Comparison of DPP-4 Inhibitors / 임상당뇨병

During past several years, a novel class of antihyperglycemic agents, dipeptidyl peptidase-4 (DPP-4) inhibitors, has become one of the most important options in the management of type 2 diabetes. These agents have unique insulinotropic actions as well as other advantages such as lower hypoglycemia and a weight-neutral effect compared to traditional insulin secretagogues. To date, 6 different DPP-4 inhibitors have been introduced: sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin and gemiglitin. This review provides a summary of the clinical data for each DPP-4 inhibitor, and discusses the similarities and differences between them.

Aprendizaje cooperativo para forjar vivienda saludable en Bogotá: estudio de caso / Cooperative learning for improving healthy housing conditions in Bogota: a case study

Objetivo Construir desde la comunidad una propuesta educativa orientada al auto empoderamiento para mejorar las condiciones sanitarias y de habitabilidad de la vivienda. Método Con un enfoque constructivista y con base en el programa "Gestores comunitarios del hábitat", se trabajó con quince familias residentes en el barrio Mochuelo Bajo de la Localidad de Ciudad Bolívar en Bogotá, Colombia, con el fin de que identificaran los aspectos sanitarios más relevantes para el mejoramiento de sus viviendas y propusieran la metodología y organización de la propuesta educativa. Resultados Se identificaron veinti ún indicadores epidemiológicos ligados a una vivienda insalubre, los cuales sirvieron como base para definir las problemáticas específicas y establecer la metodología para diseñar la propuesta educativa. Discusión El curso diseñado pretende fomentar la educación y las capacidades en salud de la comunidad con el fin de mejorar las condiciones de habitabilidad de las viviendas y lograr un entorno saludable del hábitat que les permita desarrollarse con bienestar y dignidad.

Objective This was a community-based effort at constructing an educational proposal orientated towards self-empowerment aimed at improving the target population's sanitary, housing and living conditions through cooperative learning. Methods A constructivist approach was adopted based on a programme called "Habitat community manger". The project involved working with fifteen families living in the Mochuelo Bajo barrio in Ciudad Bolívar in Bogotá, Colombia, for identifying the most relevant sanitary aspects for improving their homes and proposing a methodology and organisation for an educational proposal. Results Twenty-one poor housing-related epidemiological indicators were identified which formed the basis for defining specific problems and establishing a methodology for designing an educational proposal. Discussion The course which emerged from the cooperative learning experience was designed to promote the community's skills and education regarding health aimed at improving households' living conditions and ensuring a healthy environment which would allow them to develop an immediate habitat ensuring their own welfare and dignity.

Chemical constituents contained in seeds of Notopterygium franchetii / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents from the seeds of Notopterygium franchetii.</p><p><b>METHOD</b>Ethanol extracts of seeds N. franchetii were separated and purified by such methods as normal and reversed phase column chromatographies and thin-layer chromatography and structurally elucidated by MS and NMR evidences.</p><p><b>RESULT</b>Twenty nine compounds were separated, they were isoimperatorin (1), [3-sitosterol (2), phellopterin (3), bergapten (4), N-tetra, hexa, octacosanoylanthranilic acid (5-7), daucosterol (8), oxypeucedanin hydrate (9), umbelliferone (10), demethylfuropinnarin (11), (2S, 3S, 4R, 8E)-2-[(2'R)- 2'-hydroxydoco, trico, tetraco, entaco, hexaco sanosylamino] -octadecene-1, 3, 4-triol (12-16), (-)-oxypeucedanin (17), diosmetin (18), bergaptol-O-beta-D-glucopyranoside (19), nodakenin (20), 1'-O-beta-D-glucopyranosyl-(2R, 3S)-3-hydroxynodakenetin (21), uracil (22), decuroside V (23), 8-O-beta-D-glucopyranosyl-5-hydroxypsoralen (24), 8-O-beta-D-glucopyranosyl-5-methoxylpsoralen (25), diosmin (26), alaschanioside C (27), kynurenic acid (28) and mannitol (29).</p><p><b>CONCLUSION</b>All of these compounds were separated from the seeds of N. franchetii for the first time. Of them, 18, 22, 26 and 29 were firstly obtained from genus Notopterygium.</p>

Pharmacokinetics of S-1 capsule in patients with advanced gastric cancer / 药学学报

The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.

Research on HPCE fingerprint of eupolyphaga steleophaga / 中国中药杂志

<p><b>OBJECTIVE</b>To set up the fingerprint of HPCE for medicinal material Eupolyphaga Steleophaga.</p><p><b>METHOD</b>Separation was performed at 25 degrees C on an Agilent uncoated silica capillary column (40 cm x 75 microm) with 20 mmol x L(-1) borax buffer solution (pH 9.44) as CE buffer. The isolating voltage was 13 KV, and the DAD detection was set at 265 nm.</p><p><b>RESULT</b>The characteristic peak of fingerprint of Eupolyphaga Steleophaga was consisted of 6 common peaks.</p><p><b>CONCLUSION</b>The method can be used for the quality control of Eupolyphaga Steleophaga.</p>

Meta-analysis of late course accelerated hyperfractionated radiotherapy combined with FP chemotherapy for esophageal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Although there are many randomized clinical trials of late course accelerated hyperfractionated radiotherapy (LCAHFR) combined with FP chemotherapy for esophageal cancer, the efficacy and toxicity are controversial. This study was to evaluate the efficacy and toxicity of LCAHFR combined with FP chemotherapy in treating esophageal cancer.</p><p><b>METHODS</b>Reports of randomized clinical trials on LCAHFR combined with FP chemotherapy for esophageal cancer published between January 1999 and January 2009 were researched through Wanfang, CNKI, and PubMed databases. RevMan4.2 software was used for Meta-analysis.</p><p><b>RESULTS</b>Twenty-one reports, including 2030 patients, were included in the meta-analysis. Of the 2030 patients, 1006 underwent LCAHFR (LCAHFR group), and 1024 underwent LCAHFR combined with FP chemotherapy (combination group). Compared with those of the LCAHFR group, the 1-, 2-, 3-, 5-years survival rates and 1-, 2-, 3-year local control rates of the combination group were significant increased, and the acute toxicity was also increased, but chronic toxicity showed no significant difference.</p><p><b>CONCLUSIONS</b>LCAHFR combined with FP chemotherapy can improve the survival rate and the local control rate of the patients with esophageal cancer. The increased acute toxicity need to be concerned, whereas the chronic toxicity needs a long-term observation.</p>

Determination of thymine, hypoxanthine and uracil contents in medical pipefish by HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a RP-HPLC method for simultaneous determination of thymine, hypoxanthine and uracil contents in medical pipefish.</p><p><b>METHOD</b>Samples were extracted with distilled water by ultrasonic wave and separated on Waters C18 column eluted with a mobile phase of 0.05 mol x L(-1) KFI2PO4-acetonitrile (97:3). The flow rate was 0.6 mL x min(-1). The determination wavelength was 260 nm and the column temperature was set at 40 degrees C.</p><p><b>RESULT</b>The method had good linearity in the range of 0.033-0.660 (r = 0.9996), 0.620-12.400 (r = 0.9999), 0.048-0.960 microg (r = 0.9995), with average recoveries of 98.67% (RSD 1.6%), 99.03% (RSD 0.74%), 98.65% (RSD 1.8%), for thymine, hypoxanthine and uracil respectively.</p><p><b>CONCLUSION</b>The simultaneous determination method of thymine, hypoxanthine and uracil in medical pipefish is established by RP-HPLC for the first time. The contents of the three constituents in different kinds of medical pipefish are significantly different. The method is simple, rapid and sensitive, and can be used for control the quality of medical pipefish.</p>

A Case of Fixed Drug Eruption Induced by Tegafur-Uracil(TEGASIL) / 대한피부과학회지

A mixture of tegafur and uracil (TEGASIL) is a common antineoplastic agent. Tegafur is a fluoropyrimidine structurally similar to 5-fluorouracil (5-FU); uracil slows the degradation of 5-FU by dihydropyrimidine dehydrogenase, which results in higher 5-FU concentrations in tumors. Mucocutaneous side effects induced by this agent are rare and include photosensitivity of lichenoid and eczematous types, acral erythema, hyperpigmentation and palmoplantar keratoderma. However, there have been no reports of fixed drug eruption associated with TEGASIL. We report here on a case of fixed drug eruption due to oral TEGASIL.

Discoid Lupus Erythematosus-like Eruption Induced by Tegafur - Uracil (UFT) / 대한피부과학회지

The second-generation oral anticancer agent UFT is a combination of uracil, which has fluorouracil's (5-FU) degradation-inhibitory effect, and tegafur, which is slowly converted to 5-FU in vivo, and UFT shows a higher 5-FU concentration in the tumor tissues than is achieved by tegafur alone or with comparable doses of intravenous 5-FU. Mucocutaneous side reactions induced by UFT are rare and these include photosensitivity of the lichenoid and eczematous types, acral erythema, hyperpigmentation, palmoplantar keratoderma and scleroderma-like reactions, and discoid lupus erythematosus (DLE)-like eruption. However, there has been no report in the Korean medical literature on patients presenting with a DLE-like eruption associated with UFT. So, we report here a case of DLE-like eruption induced by oral UFT.

Hidroperóxido de timina como fonte biológica de oxigênio molecular singlete [O2 (1 Delta g)] / Thymine hydroperoxide as biological source of singlet molecular oxygen [O2 (1 Delta g)]

A oxidação do DNA por espécies reativas de oxigênio, como o oxigênio molecular singlete [O2 (1Δg)] , pode estar relacionada ao aparecimento de mutações e ao desenvolvimento de doenças. O O2 (1Δg) pode ser gerado biologicamente por reação de fotossensibilização, pela reação de H2O2 e HOCl e pela decomposição de peróxidos orgânicos contendo hidrogênio alfa (α-ROOH), na presença de metais de transição (Fe2+, Cu2+) ou HOCl. A decomposição de α-ROOH, como hidroperóxidos de lipídeos ou proteínas na presença de metais de transição, pode gerar O2 (1Δg) via mecanismo de Russell. Neste mecanismo, a oxidação de α -ROOH gera radicais peroxila, que podem reagir entre si, formando um intermediário tetraóxido linear. Este intermediário tetraóxido linear pode decompor através de um mecanismo cíclico e produzir O2 (1Δg), um álcool e um composto carbonílico. Como a decomposição de α-ROOH pelo mecanismo de Russell pode ser uma importante fonte biológica de O2 (1Δg) decidimos investigar se o α-hidroperóxido de timina, 5-(hidroperoximetil)uracil (5-HMPU), poderia gerar esta espécie reativa na presença de metais (Ce4+, Fe2+, Cu2+) e HOCl. Outro objetivo foi avaliar os efeitos oxidativos, em DNA plasmidial (pBR322), da decomposição de 5-HPMU na presença de Cu2+. A geração de O2 (1Δg) na reação de 5-HPMU e Ce4+ ou HOCl foi demonstrada por meio do monitoramento da emissão de luz monomolecular de O2 (1Δg) na região do infravermelho próximo (IR-próximo, λ = 1270 nm) e bimolecular na região do visível (λ = 634 e 703 nm). A aquisição do espectro de emissão de O2 (1Δg) forneceu evidências inequívocas da geração desta espécie reativa na reação de 5-HPMU e Ce4+ ou HOCl. Além disto, a formação de O2 (1Δg) na reação de 5-HPMU e Fe2+, Cu2+ ou HOCl foi demonstrada através da captação química de O2 (1Δg) utilizando 9,10- divinilsulfonatoantraceno (AVS) e detecção por HPLC/MS/MS do endoperóxido (AVSO2) formado. A detecção por HPLC/MS/MS dos produtos de decomposição de 5-HPMU...

Oxidation of DNA by singlet molecular oxygen O2 (1Δg) can be involved in the development of mutations and diseases. In vivo, O2 (1Δg) can be generated by photosensitization reaction, H2O2 and HOCl reaction and decomposition of organic hydroperoxides with α-hydrogen (α-ROOH) in the presence of metal ions (Fe2+, Cu2+) or HOCl. The α-ROOH decomposition, such as lipid or protein hydroperoxides in the presence of metal ions or HOCl can generate O2 (1Δg) by Russell mechanism. In this mechanism, the self-reaction of peroxyl radicals generates a linear tetraoxide intermediate that decomposes to O2 (1Δg) , an alcohol and an aldehyde. Therefore, the purpose of this work is to investigate if O2 (1Δg) can be generated by α-thymine hydroperoxide, 5- (hydroperoxymethyl)uracil (5-HPMU) in the presence of Ce4+, Fe2+, Cu2+ or HOCl. Another purpose is to study base modification and strand breaks formation in plasmid DNA (pBR322) by 5-HPMU decomposition in the presence of Cu2+. The generation of O2 (1Δg) in the reaction of 5- HPMU and Ce4+ or HOCl was monitored by monomol light emission in the near-infrared region (NIR, λ = 1270 nm) and dimol light emission in the visible region (λ = 634 e 703 nm). The generation of O2 (1Δg) during the reaction of 5-HPMU and Ce4+ or HOCl was confirmed by acquisition of the light emission spectrum in the NIR. Furthermore, the generation of O2 (1Δg) produced by 5-HPMU and Fe2+, Cu2+ or HOCl was also confirmed by chemical trapping using anthracene-9,10-divinylsulfonate (AVS) and HPLC/MS/MS detection of the corresponding endoperoxide (AVSO2). The detection by HPLC/MS/MS of 5-(hydroxymethyl)uracil (5-HMU) and 5-formyluracil (5-FoU), two 5-HPMU decomposition products, support the Russell mechanism. Plasmid results from pBR322, 5-HPMU and Cu2+ reaction showed formation of DNA open circular form (OC), probably produced by 5-HPMU peroxyl and alkoxyl radicals. Additionally, the reaction of pBR322, 5-HPMU and Cu2+ following by Fpg and NTH enzyme treatment...