Application of six sigma quality improvement model in the laboratory research of generic drugs / 药学实践杂志

Objective To improve laboratory research of generic drugs in Chinese pharmaceutical enterprises, avoid the defects in the research process, and explore the feasibility of six sigma management (DMAIC) as improvement model in the process of generic drugs laboratory research. Methods The effectiveness of DMAIC implementation was evaluated through the literature search and case study of a generic API’s process with the DMAIC model. Results The DMAIC model was successfully applied in this case. The model made laboratory research more reasonable, helped R&D personnel to pinpoint key quality attributes and process parameters, etc., ensured the authenticity and completeness of experimental data, and provided valuable data for subsequent industrial production as well as meeting registration requirements. Conclusion DMAIC model can solve the problems, such as poor overall arrangement, poor connection with production, and irregular management. It embodied the idea of Quality by Design (QbD) and can be used as good reference for domestic laboratory research of generic drugs.

Avaliação dos efeitos biológicos da exposição a toxicantes em trabalhadores de uma metalúrgica de Caxias do Sul, RS / Assessment of the biological effects of exposure to toxicants among workers at a metallurgical company in Caxias do Sul, RS, Brazil

Introdução: Metalúrgicos compõem uma população de risco pela sua exposição ocupacional a toxicantes, como metais pesados, gases, hidrocarbonetos aromáticos e silicato. Objetivo: Avaliar a existência de efeitos biológicos em trabalhadores expostos a toxicantes de vários setores de uma metalúrgica de Caxias do Sul, Rio Grande do Sul. Método: Foi realizado um estudo transversal com 31 trabalhadores de 10 setores em que foi aplicado um questionário sobre hábitos ocupacionais e de vida. Exames hematológicos e toxicológicos foram comparados com os resultados do questionário. Resultados: 19,4% (n=6) dos trabalhadores não usaram todos os equipamentos de proteção individual (EPIs). Foi possível observar diminuição dos parâmetros do eritrograma e alterações na série branca, como leucocitose, neutrofilia e eosinofilia, e no chumbo sérico. Evidenciaram-se valores diminuídos na série vermelha e leucocitose dos trabalhadores que não faziam uso adequado dos EPIs. Quando avaliado o setor de trabalho, pôde-se evidenciar as seguintes associações significativas: fumantes e neutrofilia (p=0,000); setor da moldagem e leucocitose (p=0,023) e eosinofilia (p=0,007); mais de 10 anos de trabalho e leucocitose (p=0,008). Conclusões: Os dados sugerem que o tempo de trabalho, o tipo de exposição e o uso de EPIs podem alterar exames laboratoriais

Background: Metallurgical workers are a high-risk population as a function of their occupational exposure to toxicants, such as heavy metals, aromatic hydrocarbons and silicate. Objective: To investigate the occurrence of biological effects among workers exposed to toxicants in various areas of a metallurgical company in Caxias do Sul, Rio Grande do Sul, Brazil. Methods: Cross-sectional study with 31 workers from 10 areas who responded a questionnaire on occupational and lifestyle habits. Blood and toxicology tests were compared to the questionnaire results. Results: About 19.4% (n=6) of the sample did not use all the required personal protective equipment (PPE). Reduction of red blood cell parameters and leukocyte abnormalities were found, including leukocytosis, neutrophilia and eosinophilia, as well as in the blood lead levels. The following significant associations were found on analysis per work area: smoking and neutrophilia (p=0.000); work in the mold section and leukocytosis (p=0.023) and eosinophilia (p=0.007); and more than 10 years of work and leukocytosis (p=0.008). Conclusions: The data suggest that length of work, type of exposure and use of PPE might cause changes in the results of laboratory tests

Effect of restoration technique on stress distribution in extensively destroyed premolars: a finite element analysis study / Efeito da técnica restauradora na distribuição de tensões em pré-molares extensamente destruídos: uma análise por elementos finitos

ABSTRACT Objective: The objective of this study by the finite element method was to analyze the stress distribution on a single-rooted mandibular premolar tooth restored in two different ways. Methods: Laboratory simulation considered the following situations: 1) premolar restored with gold cast post and ceramic crown; 2) premolar restored with glass fiber post, composite resin core and ceramic crown. For this we used a two-dimensional model of a premolar with load application of 300N in the axial and oblique directions within the ANSYS program for Windows. Results: Under the axial load, a higher concentration of stresses was observed around the cast post (166 MPa). In the oblique load simulation, there was a concentration of stresses on the buccal root wall, internally and externally, in the tooth restored with cast post (222 MPa). In both load directions, the glass fiber post dissipated the stress received with greater uniformity (55 to 111 MPa). Conclusion: These data suggested that from the biomechanical point of view, the use of a glass fiber post and composite resin core could be more advantageous than the cast post technique for a mandibular single-rooted premolar tooth.

RESUMO Objetivo: Analisar, por meio do método dos elementos finitos, a distribuição de tensões em elemento dental pré-molar inferior unirradicular restaurado de duas maneiras distintas. Métodos: A simulação laboratorial considerou as seguintes situações: 1) pré-molar restaurado com núcleo metálico fundido em liga áurea e coroa em cerâmica; 2) pré-molar restaurado com pino de fibra de vidro, núcleo de preenchimento em resina composta e coroa em cerâmica. Para isso foi utilizado um modelo bidimensional de um pré-molar com aplicação de carga de 300N nas direções axial e oblíqua com uso de programa ANSYS para Windows. Resultados: Diante da carga axial, foi observada uma maior concentração de tensões na região do núcleo fundido (166 Mpa). Na simulação de carga oblíqua, observou-se uma concentração de tensões na parede radicular vestibular, interna e externamente, no dente restaurado com núcleo fundido (222 Mpa). Nas duas situações em estudo, o pino de fibra de vidro e núcleo de preenchimento dissipou, com maior uniformidade, a tensão recebida (55 a 111 Mpa). Conclusão: Esses dados sugerem que o uso de pino de fibra pré-fabricado e núcleo de preenchimento em resina composta pode ser mais vantajoso que a indicação de núcleo fundido, sob o ponto-de-vista biomecânico, em dente pré-molar inferior unirradicular.

Antimicrobial potential of Casearia sylvestris against oral bacteria / Potencial antimicrobiano da Casearia sylvestris frente a bactérias orais

Aim: The aim of this study was to obtain Casearia sylvestris leave extracts by different extractive methods, including the obtention of essential oil, in order to compare their antimicrobial activities to conventional mouthwash chlorhexidine against oral bacteria. Material and method: For this evaluation, extracts from the leaves were obtained by different methods of extraction (infusion, decoction, maceration and percolation) using different solvent systems: water 100%, ethanol 100%, methanol 100%, water: ethanol 3:7; water: ethanol 7:3; water: methanol 7:3 and water: methanol 3:7. The essential oil, which corresponds to a volatile fraction, was obtained by hydrodistillation using Clevenger modified apparatus. The microdilution broth method was used to determine the values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the following microorganisms: Streptococcus mutans ATCC 25175, S. mitis ATCC 49456, S. sanguinis ATCC 10556, S. salivarius ATCC 25975, Lactobacillus casei ATCC 11578 and Enterococcus faecalis ATCC4082. Chlorhexidine gluconate was used as a positive control. Result: All extracts evaluated in the used protocol displayed MIC values higher than 400 µg/mL and few showed bactericidal activity. The antimicrobial activity of essential oil was higher than the activity of the extracts, and the best minimum inhibitory concentration and minimum bactericidal concentration values were obtained against L. casei (MIC of 0.023 µg/mL and MBC of 0.046 µg/mL) and S. mutans (MIC of 25 µg/mL and MBC of 50 µg/mL), respectively. Conclusion: The essential oil of Casearia sylvestris has significant antimicrobial activity against oral microorganisms.

Objetivo: O objetivo deste estudo foi obter extratos por diferentes métodos de extração de Casearia sylvestris, incluindo a obtenção de óleo essencial, a fim de comparar suas atividades antimicrobianas em relação aos enxaguatórios bucais convencionais com clorexidina contra bactérias orais. Material e método: Para esta avaliação, extratos das folhas foram obtidos por diferentes métodos de extração (infusão, decocção, maceração e percolação) utilizando diferentes sistemas de solventes: 100% de água, 100%, de etanol, metanol 100%, água: etanol 3: 7; água: etanol 7: 3; água: metanol 7: 3 e água: metanol 3: 7. O óleo essencial, que corresponde a uma fração volátil, foi obtido por hidrodestilação usando o aparelho de Clevenger modificado. O método de microdiluição em caldo foi usado para determinar os valores de concentração inibitória mínima (MIC) e a concentração bactericida mínima (MBC) para os seguintes microrganismos: Streptococcus mutans ATCC 25175, ATCC 49456 S. mitis, S. sanguinis ATCC 10556, S. salivarius ATCC 25975, Lactobacillus casei ATCC 11578 e Enterococcus faecalis ATCC4082. Gluconato de clorexidina foi usada como um controle positivo. Resultado: Todos os extratos avaliados no protocolo utilizado apresentaram valores de MIC superior a 400 ug/mL e alguns mostraram atividade bactericida. A atividade antimicrobiana do óleo essencial foi maior do que a atividade dos extratos, e a melhor concentração inibitória mínima e valores de concentração bactericida mínima foram obtidos contra L. casei (MIC de 0,023 ug/mL e MBC de 0,046 ug/mL) e S. mutans (MIC de 25 ug/mL e MBC de 50 ug /mL), respectivamente. Conclusão: O óleo essencial de Casearia sylvestris tem atividade antimicrobiana significativa contra microrganismos orais.

Evaluación externa de la calidad mediante la veracidad en las investigaciones de laboratorio clínico / External assessment of quality through accuracy in investigations in clinical laboratories

FUNDAMENTO: la utilización del Programa de Evaluación Externa de la Calidad (PEEC) para laboratorios clínicos, son actualmente un requisito indispensable en su proceso de acreditación. La participación y el desempeño aceptable en estos programas, cumplen una función de mejora en la práctica de los laboratorios clínicos y educan sobre los beneficios y limitaciones de los procedimientos analíticos. OBJETIVO: demostrar la utilidad de la evaluación de la veracidad para detectar los laboratorios que desvían la media consenso, aumentan la dispersión y causan falsos resultados en la evaluación. MÉTODOS: se realizó un estudio observacional descriptivo, longitudinal y retrospectivo para evaluar la veracidad desde el año 1999 al 2013, para ello se procesaron las muestras de los 64 laboratorios asistenciales de la provincia y de forma paralela en el laboratorio de referencia del Centro Coordinador del PEEC, se consideraron aceptados los valores comprendidos en el rango ± 3 desviaciones estándar y rechazados, los que están fuera de rango. RESULTADOS: la veracidad mejoró en el tiempo en los laboratorios de ambos niveles de atención con excepción de los componentes de uratos y conteo global de leucocitos que disminuyó debido a dificultades de equipos, reactivos o procedimientos. CONCLUSIONES: en catorce años de aplicado el programa en la provincia se ha obtenido un promedio de 74 % de resultados aceptados demostrando que el sistema propuesto es eficaz y beneficioso.

BACKGROUND: the use of the Program of External Quality Assessment (PEQA) for clinical laboratories is nowadays an indispensable requirement in its accreditation process. The acceptable participation and performance in these programs act as an improvement in the practice of clinical laboratories and instruct about the benefits and limitations of the analytic procedures. OBJECTIVE: to demonstrate the usefulness of the assessment of accuracy to detect those laboratories that deviate average consensus, increases straying and cause false results in the evaluation. METHOD: a retrospective, longitudinal, descriptive, observational study was conducted to assess accuracy from 1999 to 2013. Samples from the 64 clinical laboratories in the province were processed; in parallel, values included in the level ± 3 standard deviations and rejected (which are out of the level) were considered "accepted" in the reference laboratory of the Coordinating Center of the PEQA. RESULTS: accuracy improved in time in the laboratories in both levels of attention with the exception of the urate components and leukocyte overall count, that decreased due to difficulties with equipments, reagents or procedures. CONCLUSIONS: during the 14 years of the application of the program in the province, an average of a 74 % of accepted results has been obtained demonstrating that the system proposed is efficient and beneficial.

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.

Dimensional stability of a novel polyvinyl siloxane impression technique

AIM: To introduce a modification of the reline impression technique (MRIT), and compare the dimensional changes of impressions obtained by MRIT and by conventional reline impression technique (CRIT). METHODS: An acrylic resin tablet was milled by a CAD-CAM system to simulate three abutments (A, B and C) with different distances among them. The abutments were molded using both impression techniques. For MRIT, before completing the putty silicone polymerization, the relieve procedure was made by compression and it was immediately repositioned to complete the polymerization. Impressions were stored dry at room temperature for different periods (immediately, 1 h, 2 days and 7 days). The distances were obtained by scanning. The differences between the impressions and their respective matrix reference measurements were calculated to determine the dimensional changes. Data were subjected to ANOVA and Tukey's test (p<0.05). RESULTS: For AB and BC distances, there was no statistically significant difference between CRIT and MRIT (p=0.0597 and p=0.2167, respectively). For AC, there was statistically significant difference between the techniques for the immediate storage time (p=0.006). In general, for CRIT the material showed expansion, while for MRIT it showed contraction. CONCLUSIONS: It was verified that the addition silicon impressions obtained by both impression techniques showed dimensional stability, except for the immediate time-point...

Colorimetric photoelastic analysis of tension distribution around dental implants

Objective: To demonstrate a colorimetric photoelastic analysis of tension distribution around dental implants under axial loads. Material and methods: Eight different designs of implant from two manufacturers were connected to their abutments, placed into epoxy resin blocks and observed under a polariscope coupled to a universal testing machine while subjected to axial loads of 5 N. The obtained images were quantitatively analyzed by image analysis software. Results: A strong correlation was found between the surface area and the implant fringe transition area (magenta color) of most samples (r = 0.908), and a moderate correlation was found between the fringe transition area and the mean thread height of the implants (r = 0.706, or r = 0.768 using a quadratic function). Conclusion: By this biomechanical study, it was possible to demonstrate a correlation of some implant characteristics to the colored fringe areas of tension distribution, a colorimetric method that can be used in comparative studies of photoelastic analysis. Clinical significance: An accurate planning and knowledge of oral implant biomechanics is important so that a safe and long-lasting treatment can be achieved. This biomechanical study presented some correlations of the implant features and its photoelastic behavior, information that could be used by the practitioner while choosing the implant design for each clinical situation.

Estudo exploratório acerca da utilização de métodos alternativos em substituição aos animais não humanos / Estudio exploratorio sobre el uso de métodos alternativos para la substitución de animales no humanos / Exploratory study concerning the use of alternative methods in substitution tothe non human animals

Este artigo decorre de pesquisa realizada para levantar a aceitação do uso de animais na pesquisa e docência. Esta prática tem gerado conflitos morais na sociedade atual, os quais vêm sendo discutidos na esfera da ética animal. Nesta área a substituição de animais por métodos alternativos ganha espaço, sendo frequentemente utilizada. A aprovação da Lei 11.794/08, oficializada pelo Decreto 6.899/09, incentivou o debate sobre a temática em nosso país. A busca do interesse dos profissionais da área da saúde (incluindo biologia) pelo tema, considerando que este segmento será diretamente afetado pela legislação, levou à proposta desta pesquisa de campo em nossa universidade. A análise das respostas permitiu concluir que o percentual de professores preocupados com o tema é pequeno. Da amostra, significativo número se posiciona como atento ao bem-estar, dor e diminuição do número de animais, aceitando as alternativas e não se opondo a testá-las. Muitos respondentes, entretanto, afirmam desconhecer métodos alternativos.

El uso de animales en la investigación y la docencia no es nuevo en la Ciencia. Esta práctica ha generado conflictos morales en la sociedad actual, discutido en el ámbito de la Animal Ethics. Enesta área la substitución de animales por alternativas tiene espacio siendo frecuentemente abordada. La aprobación de la Ley 11.794/08 oficializada por el Decreto 6.899/09 en Brasil ha fomentado el debate sobre el tema en nuestro país. La búsqueda en el interés de los profesionales de la salud (incluyendo la biología) en el tema, teniendo en cuenta que este segmento se verá directamente afectado por la legislación, llevó a la proposición de esta investigación en nuestra universidad. El análisis de las respuestas nos permitió concluir que el percentaje de maestros preocupados con el tema es pequeño. De la muestra, un número significativo se coloca atento al bienestar, dolor y reducción de números de animales aceptando las alternativas e no recusándose a experimentar. Pero muchos de los encuestados afirman no conocer los métodos alternativos.

The use of animals in the research and teaching is not new in Science. This practical comes exciting moral conflicts in the current society, argued in the scope of Animal Ethics. It is in this area that the substitution of animals for alternatives methods gains space, being frequently boarded. In Brazil, the approval of the Law 11.794/08, regulated by the pelo Decree 6.899/09 stimulated the debate about this thematic. The search of the subject for the professionals of health (included biology) ? considering that this segment will be directly affected by the legislation ? led to the proposal of this research in our university. The analysis of the answers allowed us conclude that the percentage of professors worried about the subject is small. Of the sample, a significant number positioned itself as intent to welfare, pain and reduction of the number of animals, accepting the alternatives and not opposing to test them. Many respondents, however, affirm to be unaware of the alternative methods.

Human papillomavirus (HPV) detection in lip squamous cell carcinoma: correlation with clinical aspects and risk factors / Detecção do papilomavírus humano (HPV) em carcinoma espinocelular de lábio: correlação com aspectos clínicos e fatores de risco

O papilomavírus humano (HPV) está associado a um largo espectro de lesões em humanos e tem sido ligado à carcinogênese oral. O objetivo deste estudo foi investigar a presença do DNA do HPV em pacientes com carcinoma espinocelular de lábio e correlacioná-la com aspectos clínicos e fatores de risco. Foram estudados 33 pacientes com carcinoma espinocelular de lábio. Destes, 30 pacientes foram positivos para o gene da beta-globina humana e então foram testados para o DNA do HPV com uso da reação em cadeia de polimerase em duas etapas (PCR e nPCR) com os oligonucleotídeos iniciadores MY11/MY09 e GP5+/ GP6+. O DNA do HPV foi detectado em 43,33 por cento dos 30 pacientes analisados. Não houve associação com os fatores de risco analisados.

Human papillomavirus (HPV) is associated with a wide spectrum of lesions in humans, and it has been linked to oral carcinogenesis. The aim of this study was to investigate the presence of HPV DNA in patients with lip squamous cell carcinoma and to correlate it with clinical characteristics and risk factors. We studied 33 patients with lip squamous cell carcinomas. Of these, 30 were positive for human beta globin gene and tested for HPV DNA, using polymerase chain reaction in two steps (PCR and nPCR) with MY11/MY09 and GP5+/GP6+ primers. HPV DNA was detected in 43.33% of patients analyzed. There was no association with the risk factors analyzed.

Loss of residual monomer from resilient lining materials processed by different methods / Perda de monômero residual de reembasadores resilientes processados por diferentes métodos

Purpose: To evaluate residual monomer release from resilient denture lining materials polymerized by different methods. Methods: Two materials were assessed: Ever-Soft polymerized by hot water bath or microwave energy, and Light Liner polymerized by chemical reaction and visible light (dual polymerization). Residual monomer release was measured in 12 specimens (40x10x0.3mm) made of each material and polymerization method. The specimens were stored in distilled water for 168 hours at 37ºC, and analyzed daily by ultraviolet spectrometry (Light Liner: 204nm, Ever-Soft: 206nm). Data were analyzed by one-way ANOVA and Bonferroni test (α=0.05). The residual monomer released as a function of time was determined by polynomial regression analysis. Results: Residual monomer amount released at 168 hours from specimens polymerized by hot water bath (0.27±0.01μg/cm²) was significantly greater (P < 0.05) than from those processed by microwave energy (0.25±0.02μg/cm²). Ever-Soft showed decrease in monomer release over time, tending to stabilize at 96 hours. Light Liner continued to release monomer over time. Conclusion: Ever-Soft may be polymerized by microwave energy. Residual monomer release values were low, and the monomer levels decreased over time.

Objetivo: Avaliar o monômero residual liberado de materiais resilientes para reembasamento polimerizados por diferentes métodos. Metodologia: Dois materiais foram testados: Ever-Soft polymerizado por banho quente de água ou por energia de microondas, e Light Liner polimerizado quimicamente e por luz visível (polimerização dual). O monômero residual liberado foi mensurado em 12 espécimes (40x10x0,3mm) fabricados com cada material e método de polimerização. Os espécimes foram armazenados em água destilada por 168 horas a 37ºC, e analisados diariamente por espectrometria ultravioleta (Light Liner: 204nm, Ever-Soft: 206nm). Os dados foram analisados por ANOVA de fator único e teste de Bonferroni (α=0,05). O monômero residual liberado em relação ao tempo foi determinado por análise de regressão polinomial. Resultados: O monômero residual liberado em 168 horas do teste (μg/cm²) em espécimes polimerizados por banho de água quente (0,27±0,01μg/cm²) foi significativamente maior (P < 0,05) que em espécimes processados por energia de microondas (0,25±0,02μg/cm²). Ever-Soft mostrou uma redução na liberação de monomer residual com o tempo, tendendo a se estabilizar em 96 horas. Light Liner continuou a liberar monômero com o tempo. Conclusão: Ever-Soft pode ser polimerizado por energia de microondas. Os valores de monômero residual liberado foram baixos, e os níveis de monômero diminuíram com o tempo.