RESUMO
OBJECTIVE: This work aims to evaluate the ability of biorelevant dissolution media to simulate the bioavailability of efavirenz tablets, establish an in vitro-in vivo relationship (IVIVR) based on in vivo data using GastroPlus® and simulate formulation changes using DDDPlus™. METHODS: Solubility and drug release profiles were conducted in SLS 0.5% and biorelevant media, such as FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2. The efavirenz physicochemical properties were used to simulate the plasma concentration profile and compare the simulated pharmacokinetic parameters in fasted and fed states. An IVIVR was developed using Loo-Riegelman as the deconvolution method to estimate drug bioavailability. DDDPlus™ was used to perform virtual trials of formulations to evaluate whether formulations changes and the efavirenz particle size could influence the bioavailability. RESULTS: The drug dissolution displayed higher levels in the biorelevant media that simulated gut-fed state (FeSSIF and FeSSIF-V2). The absorption model successfully predicted the efavirenz pharmacokinetics, and FeSSIF-V2 was chosen as the predictive dissolution media, while an IVIVR was established using the Loo-Riegelman deconvolution method. CONCLUSIONS: The present work provides valuable information about efavirenz solubility and kinetics in the gastrointestinal tract, allowing an IVIVR to support future formulation changes. This understanding is essential for rational science-driven formulation development. At least, this study also showed the validity and applicability of in vitro and in silico tools in the regulatory scenario helping on drug development.
Assuntos
Modelos Biológicos , Alcinos , Benzoxazinas , Disponibilidade Biológica , Simulação por Computador , Ciclopropanos , Solubilidade , ComprimidosRESUMO
Leishmaniasis is a spectrum of neglected tropical diseases and its cutaneous form (CL) is characterized by papillary or ulcerated skin lesions that negatively impact patients' quality of life. Current CL treatments suffer limitations, such as severe side effects and high cost, making the search for new therapeutic alternatives an imperative. In this context, heat shock protein 90 (Hsp90) could present a novel therapeutic target, as evidence suggests that Hsp90 inhibitors, such as 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG), may represent promising chemotherapeutic agents against CL. As innovative input for formulation development of 17-DMAG, nano-based drug delivery systems could provide controlled release, targeting properties, and reduced drug toxicity. In this work, a double emulsion method was used to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing 17-DMAG. The nanoparticle was developed using two distinct protocols: Protocol 1 (P1) and Protocol 2 (P2), which differed concerning the organic solvent (acetone or dichloromethane, respectively) and procedure used to form double-emulsions (Ultra-Turrax® homogenization or sonication, respectively). The nanoparticles produced by P2 were comparatively smaller (305.5 vs. 489.0 nm) and more homogeneous polydispersion index (PdI) (0.129 vs. 0.33) than the ones made by P1. Afterward, the P2 was optimized and the best composition consisted of 2 mg of 17-DMAG, 100 mg of PLGA, 5% of polyethylene glycol (PEG 8000), 1.5 mL of the internal aqueous phase, 1% of polyvinyl alcohol (PVA), and 4 mL of the organic phase. Optimized P2 nanoparticles had a particle size of 297.2 nm (288.6-304.1) and encapsulation efficacy of 19.35% (15.42-42.18) by the supernatant method and 31.60% (19.9-48.79) by the filter/column method. Release kinetics performed at 37°C indicated that ~16% of the encapsulated 17-DMAG was released about to 72 h. In a separate set of experiments, a cell uptake assay employing confocal fluorescence microscopy revealed the internalization by macrophages of P2-optimized rhodamine B labeled nanoparticles at 30 min, 1, 2, 4, 6, 24, 48, and 72 h. Collectively, our results indicate the superior performance of P2 concerning the parameters used to assess nanoparticle development. Therefore, these findings warrant further research to evaluate optimized 17-DMAG-loaded nanoparticles (NP2-17-DMAG) for toxicity and antileishmanial effects in vitro and in vivo.
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Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.
Assuntos
Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/terapia , Idade de Início , Argentina , Prova Pericial , Doença de Depósito de Glicogênio Tipo II/complicações , HumanosRESUMO
La enfermedad de Pompe (EP) es un desorden metabólico autosómico recesivo infrecuente, producido por la ausencia o deficiencia de la enzima lisosomal alfa-glucosidasa ácida en los tejidos de los individuos afectados. Se considera enfermedad de Pompe de inicio tardío (EPIT) en aquellos individuos de más de un año de edad al comienzo de los síntomas. El objetivo del presente consenso es el de actualizar las pautas y recomendaciones para un correcto tratamiento de los pacientes con EPIT, tomando como referencia los lineamientos del Consenso Argentino para el diagnóstico, seguimiento y tratamiento de la enfermedad de Pompe publicado en el año 2013. Se organizó un consenso que reunió profesionales con experiencia en la EP en las áreas de clínica médica, diagnóstico de laboratorio, neuropatología, neumonología, nutrición, neurología, enfermedades metabólicas, enfermedades neuromusculares y rehabilitación. Se realizó una actualización de la bibliografía sobre EPIT, con especial atención en las publicaciones relevantes de los últimos cuatro años. Los términos finales del documento fueron consensuados por todo el grupo de trabajo. Cada participante proporcionó su declaración de conflicto de intereses. El resultado es una actualización del último Consenso Argentino para la EP, con particular enfoque en su forma de comienzo tardío. Tratándose de una afección infrecuente, en la que los datos disponibles son limitados, las presentes recomendaciones deben ser consideradas como opinión de expertos.
Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.
Assuntos
Humanos , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/terapia , Argentina , Doença de Depósito de Glicogênio Tipo II/complicações , Idade de Início , Prova PericialRESUMO
Este artigo apresenta a atuação do tribunal de Contas da União (TCU) na avaliação da governança na saúde pública sob diferentes perspectivas. Primeiramente, discute as implicações da execução da politica de saúde frente aos desafios da descentralização, situando o papel da governança e sus importância para as relações interfederativas, diante da necessária cooperação entre entes para assegurar a integralidade na oferta de serviços de saúde aos cidadãos . Destaca, também, a necessária harmonização dos recursos e esforços dentro de cada secretaria de saúde e de cada conselho de saúde, sob o ponto de vista da governança organizacional. O Conselho de Saúde representa o principal ator da governança, enquanto a Secretaria de Saúde o principal ator da gestão. Enquanto o primeiro dita os rumos e acompanha os resultados, o segundo mobiliza os recursos para o cumprimento dos objetivos. A governança organizacional orienta a organização para que organize os componentes de liderança, estratégia, processos de trabalho e controles, de modo a reduzir os riscos e aumentar o potencial de sucesso rumo aos objetivos. Cada organização operando de forma mais organizada significa também que estão potencialmente mais aptas às discussões e pactuações necessárias ao estabelecimento de acordos interfederativos, capazes de assegurar a prestação de serviços de saúde de forma otimizadas nas regiões de saúde. Por fim, são apresentados os resultados das avaliações realizadas pelo TCU e as principais recomendações
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Saúde Pública , Gestão em Saúde , Política de Saúde , Direção e Governança do Setor de SaúdeRESUMO
METHODS: This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. RESULTS: Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). DISCUSSION: In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.
Assuntos
Esclerose Lateral Amiotrófica/complicações , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/patologia , Biomarcadores , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Substância Branca/patologia , Adulto JovemRESUMO
BACKGROUND: Different epidemiological studies, especially in Europe, have estimated the incidence density of myasthenia gravis (MG) to range between 1.7 and 21.3/1,000,000/person-year; however, data from regions such as Latin America are scarce. This study is aimed at estimating the incidence and prevalence of acquired MG in Buenos Aires, Argentina. METHODS: The study population comprised of affiliates of the Italian Hospital Medical Care Program, a prepaid health maintenance organization located in Buenos Aires. The evaluation method for case detection included a retrospective search from January 1, 2006, through December 31, 2012. RESULTS: Of the 60 cases identified, 36 (60%) were females. The median age at diagnosis was 69 years (IQR 51.5-79). The mean age at diagnosis was 63.3 years (SD ±20). A total of 28 patients (46.7%) had generalized MG and 32 had ocular MG (53.3%). Thirty five patients (58.3%) had acetylcholine receptor antibodies and 2 (3.3%) had muscle-specific receptor tyrosine kinase antibodies. The crude incidence density (ID) of MG was 61.33 per 1,000,000 person-years (95% CI 47.62-79.99). The adjusted ID for the Argentinean population was 38.8 per 1,000,000 person-years (95% CI 27.09-50.51) and for the Buenos Aires population was 47.49 (95% CI 34.73-60.25). CONCLUSIONS: The results obtained are similar to those published for other geographical areas.
Assuntos
Miastenia Gravis/epidemiologia , Idoso , Argentina , Feminino , Sistemas Pré-Pagos de Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
ABSTRACT The objective of this preliminary study was to correlate diffusion tensor imaging (DTI) alterations with the cognitive profile of patients with amyotrophic lateral sclerosis (ALS). Methods This was a case-control study conducted from December 1, 2012 to December 1, 2014. Clinical and demographic data were recorded. A neuropsychological test battery adapted to ALS patients was used. An MRI with DTI was performed in all patients and fractional anisotropy (FA) was analyzed in the white matter using the tract based spatial statistics program. Results Twenty-four patients with ALS (15 females, mean age 66.9 + -2.3) and 13 healthy controls (four females, average age 66.9 + - 2) were included. The DTI showed white matter damage in ALS patients vs. healthy controls (p < 0.001). Discussion In our preliminary study the alterations of white matter in DTI were significantly associated with cognitive impairment in patients with ALS.
RESUMEN El objetivo del presente estudio preliminar fue correlacionar alteraciones del Tensor de Difusión (TD) con el perfil cognitivo de pacientes con Esclerosis Lateral Amiotrofica (ELA). Metodos Se realizó estudio casos-controles entre el 1 de Diciembre del 2012 hasta el 1 de Diciembre del 2014. Se registraron datos clínicos y demográficos. Se utilizó batería de tests neuropsicológicos adaptada a ELA. Se realizó RMN de cerebro con TD en todos los pacientes, la Fracción de Anisotropía (FA) se analizó en sustancia blanca, utilizando el programa Tract Based Spatial Statistics. Resultados Se incluyeron 24 pacientes con ELA (15 mujeres, edad media 66.9 + -2.3) y 13 controles sanos (4 mujeres, edad media 66.9 +-2). El TD mostró daño en sustancia blanca en los pacientes con ELA vs controles (p < 0.001). Discusión En nuestro estudio preliminar las alteraciones de sustancia blanca en TD se asociaron significativamente con alteraciones cognitivas en pacientes con ELA.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Imagem de Tensor de Difusão , Disfunção Cognitiva/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Esclerose Lateral Amiotrófica/complicações , Biomarcadores , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Substância Branca/patologia , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Testes NeuropsicológicosRESUMO
Esta obra faz parte do projeto de recuperação da memória histórica do Centro de Epidemiologia, Pesquisa e Informação (CEPI 1989), do Programa de Aprimoramento das Informações de Mortalidade no Município São Paulo (PRO-AIM 1989) e da Coordenação de Epidemiologia e Informação (CEInfo - 2001), estruturas da Secretaria Municipal da Saúde de São Paulo (SMS-SP). Trata-se de versão de uma história composta a partir, principalmente, de depoimentos e de informações extraídas de documentos recuperados de um acervo existente e disperso que se encontrava guardado pelos personagens dessa história.
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Humanos , Masculino , Feminino , Epidemiologia , Sistema Único de Saúde , Mortalidade , Saúde PúblicaRESUMO
An outbreak of postoperative bone mucormycosis following arthroscopic anterior cruciate ligament reconstruction in a tertiary referral center in Paraná, Argentina, could have been transmitted through an arthroscopic anterior cruciate ligament reconstruction-exclusive contaminated item. The outbreak was controlled after changing from a system of direct delivery of implants and instruments to the operating room without proper verification, to a controlled and centralized process; specifically, the institution's pharmacy verified the quality and traceability of implants, and instruments were processed only by the institution's central sterile services department.
Assuntos
Artroscopia/efeitos adversos , Surtos de Doenças , Controle de Infecções/métodos , Mucormicose/epidemiologia , Osteomielite/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Argentina/epidemiologia , Estudos de Coortes , Feminino , Humanos , Ligamentos Articulares/cirurgia , Masculino , Mucormicose/prevenção & controle , Osteomielite/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controleRESUMO
Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a hereditary disease with variable geographical distribution. The aim of this study was to present our experience with TTR-FAP patients. We retrospectively analyzed nine cases belonging to different families. Diagnostic criteria were based on the combination of compatible clinical picture, histopathological findings and genetic confirmation. Five cases showed the classic presentation and other 4 the late onset variant. The p.Val30Met mutation in the TTR gene was found in 6 cases and p.Ala36Pro, p.Thr60Ala and p.Tyr114Cys in the remaining 3, respectively. The median age of symptom onset was 35 years (26-60 range). Mean time to diagnosis was 4.2 ± 1.5 years. Our patient series showed the heterogeneity in clinical presentation of TTR-FAP in a non-endemic region of South America.
Assuntos
Neuropatias Amiloides Familiares/genética , Pré-Albumina/genética , Adulto , Neuropatias Amiloides Familiares/terapia , Argentina , Benzoxazóis/uso terapêutico , Evolução Fatal , Feminino , Humanos , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Mutação , Estudos RetrospectivosRESUMO
La polineuropatía amiloidótica familiar asociada a transtiretina (PAF-TTR) es una enfermedad hereditaria con distribución geográfica variable. El objetivo de este trabajo fue presentar nuestra experiencia con pacientes con PAF-TTR. Se evaluaron retrospectivamente 9 casos pertenecientes a diferentes familias. Los criterios diagnósticos utilizados se basaron en la combinación de un cuadro clínico compatible, hallazgos histopatológicos y confirmación genética. Cinco casos mostraron la presentación clásica y 4 la variante de inicio tardío. La mutación p.Val30Met en el gen TTR fue hallada en 6 casos y p.Ala36Pro, p.Thr60Ala y p.Tyr114Cys en los 3 los restantes, respectivamente. La edad media de inicio fue 35 años (rango 26-60). El tiempo medio al diagnóstico fue de 4.2 ± 1.5 años. Siete pacientes recibieron diagnóstico erróneo inicial, 3 de la variante clásica y 4 de la tardía. Nuestra serie de pacientes mostró marcada heterogeneidad en la presentación clínica del grupo de PAF-TTR de inicio tardío, en una región no endémica de Sudamérica.
Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) is a hereditary disease with variable geographical distribution. The aim of this study was to present our experience with TTR-FAP patients. We retrospectively analyzed nine cases belonging to different families. Diagnostic criteria were based on the combination of compatible clinical picture, histopathological findings and genetic confirmation. Five cases showed the classic presentation and other 4 the late onset variant. The p.Val30Met mutation in the TTR gene was found in 6 cases and p.Ala36Pro, p.Thr60Ala and p.Tyr114Cys in the remaining 3, respectively. The median age of symptom onset was 35 years (26-60 range). Mean time to diagnosis was 4.2 ± 1.5 years. Our patient series showed the heterogeneity in clinical presentation of TTR-FAP in a non-endemic region of South America.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Pré-Albumina/genética , Neuropatias Amiloides Familiares/genética , Argentina , Benzoxazóis/uso terapêutico , Estudos Retrospectivos , Transplante de Fígado/estatística & dados numéricos , Evolução Fatal , Neuropatias Amiloides Familiares/terapia , MutaçãoRESUMO
The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimer's disease. We performed a retrospective study including patients with mild stage of Alzheimer's disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimer's disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11% of the patients (n = 23) remained in the mild stage of the disease, 54% (n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35% (n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimer's disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimer's disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate genotoxicity and mutagenicity in peripheral blood and buccal mucosal cells in mucopolysaccharidosis (MPS) I, II or VI patients. METHODS: A total of 12 patients with MPS type I, II and VI attended at the Institute of Genetics and Inborn Errors of Metabolism treated with enzyme replacement therapy (ERT) and 10 healthy control volunteers were included in this study. Mechanically exfoliated cells from cheek mucosa (left and right side) were used to micronucleus test and single cell gel (comet) assay in peripheral blood cells. RESULTS: The results of this study detected the presence of genetic damage in peripheral blood for all individuals with MPS treated with ERT, regardless of type of MPS as depicted by tail moment results. In addition, an increased number of micronucleated cells were found in buccal cells of MPS type II patients. It was also observed an increase of other nuclear alterations closely related to cytotoxicity as depicted by the frequency of pyknosis, karyolysis and karyorrhexis in buccal mucosa cells of MPS VI patients (p < 0.05). CONCLUSION: Taken together, such results demonstrate that metabolic alterations induced by the enzymatic deficiency characteristic of MPS associated with ERT therapy can induce genotoxicity and mutagenicity in peripheral blood and buccal mucosa cells, respectively. This effect appears to be more pronounced to MPS II.
Assuntos
Núcleo Celular/patologia , Cromatina/patologia , Dano ao DNA , Fragmentação do DNA , Mucopolissacaridose II/patologia , Mucopolissacaridose IV/patologia , Mucopolissacaridose I/patologia , Adolescente , Adulto , Células Sanguíneas/patologia , Brasil , Forma do Núcleo Celular , Criança , Pré-Escolar , Análise Citogenética , Terapia de Reposição de Enzimas , Feminino , Humanos , Masculino , Mucosa Bucal/patologia , Mucopolissacaridose I/sangue , Mucopolissacaridose I/genética , Mucopolissacaridose I/terapia , Mucopolissacaridose II/sangue , Mucopolissacaridose II/genética , Mucopolissacaridose II/terapia , Mucopolissacaridose IV/sangue , Mucopolissacaridose IV/genética , Mucopolissacaridose IV/terapia , Adulto JovemRESUMO
The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimers disease. We performed a retrospective study including patients with mild stage of Alzheimers disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimers disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11
of the patients (n = 23) remained in the mild stage of the disease, 54
(n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35
(n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimers disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimers disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The aim of the study was to analyze the impact of treatment with vitamin D in the progression of Alzheimers disease. We performed a retrospective study including patients with mild stage of Alzheimers disease with more than four years of follow-up. The presence of cardiovascular risk factors, osteoporosis, treatment with memantine, acetylcholinesterase inhibitors drugs and vitamin D were analyzed as independent variables. Time of progression to moderate and severe Alzheimers disease was analyzed as dependent variable. The analysis was done using multivariate linear regression model, Kaplan Meier analysis, Chi-square and T test. Two hundred and two patients met the inclusion criteria. 11
of the patients (n = 23) remained in the mild stage of the disease, 54
(n = 110) developed the moderate form in a mean time of 3 ± 1.4 years while 35
(n = 69) developed the severe form in a mean time of 4.6 ± 1.4 years. Time of progression to severe stage of Alzheimers disease was slower in patients under treatment with vitamin D compared with those without treatment (5.4 ± 0.4 years vs. 4.4 ± 0.16 years respectively, p=0.003). Treatment with vitamin D may be an independent protecting factor in the progression of Alzheimers disease.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Estudos Retrospectivos , Feminino , Humanos , Idoso , Masculino , Pessoa de Meia-Idade , Progressão da Doença , Índice de Gravidade de DoençaRESUMO
Objective: The aim of this study was to evaluate the characteristics of ethical procedures against dentists registered in the Regional Council of Dentistry of Ceará, analyzing the ethical procedures judged from 2004 to 2010. Methods: As methodological procedure, it was used a descriptive, observational, quantitative, retrospective research held from the categorization and analysis of secondary data obtained from the website of the Regional Council of Dentistry of Ceará. Results: The results showed that there is a certain regularity in the number of complains, in exception of 2009, in which there was a significant increase of those. Regarding the origin of the processes, it is observed that the majority of the lawsuits were held by patients disappointed with the service received from the professional or from the institution entered in the Council. Regarding to the subject of complaints or complaint, it was found an emphasis on possible technical errors of the professionals, which was the majority, with nearly half of the complaints. Regarding to dental specialties, Orthodontics had the highest percentage of cases, followed by Prosthesis and Implant. It was also observed that in most cases, there was archiving of the process by agreement between the parts. Resulting from the ethical processes initiated and prosecuted, the conviction of the accused dentists was the most applied decision. Conclusion: It is important that in the process of formation of a professional it should not only be technical and scientific improvements, but also a deep study of ethical values, bioethics and deontological. Therefore, it is expected to reduce the involvement of disciplinary infractions.
Objetivo: Avaliar as características dos processos éticos contra inscritos no Conselho Regional de Odontologia do Ceará, a partir da análise dos processos instaurados e julgados no período de 2004 a 2010. Métodos: Como procedimento metodológico, utilizou-se a pesquisa descritiva, observacional, quantitativa, retrospectiva, realizada a partir dacategorização e análise de dados secundários obtidos no site do Conselho Regional de Odontologia do Ceará. Resultados: Os resultados demonstram que existe certa regularidade no número de denúncias, excetuando-se o ano de 2009, no qual houve um aumento expressivo. Quanto à origem dos processos, observa-se que a maioria originou-se de pacientes insatisfeitos com o atendimento recebido por parte do profissional ou da instituição inscrita no Conselho. Com relação ao motivo ou queixa das denúncias, percebe-se destaque para o possível erro técnico do profissional, o qual se sobressaiu com quase metade das denúncias. No que se refere à especialidade, a ortodontia apresentou o maior percentual de processos, seguida pela prótese e pela implantodontia. Observou-se, ainda, que na maioria dos processoshouve arquivamento por acordo entre as partes. Resultantes dos processos éticos instaurados e julgados, a condenação dos denunciados foi a decisão mais aplicada. Conclusão: É relevante que no processo de formação de um profissional não deva existir somente aprimoramento técnico-científico, mas também um aprofundamento dos valores éticos, bioéticos e deontológicos. Dessa forma, espera-se conseguir uma redução no acometimento de infrações disciplinares.
Assuntos
Odontologia , Ética Odontológica , Ética ProfissionalRESUMO
The objective of this article was to evaluate the impact potential of nandrolone decanoate on DNA damage, cellular regulatory proteins and cyclooxygenase (COX)-2 in oral mucosa cells of Wistar rats. A total of 40 rats were distributed into four groups. Two experimental groups were treated with nandrolone decanoate, at 5 mg/kg doses, subcutaneously, three times a week in two periods: 15 and 30 days. The remaining groups received only 0.9% saline subcutaneously, three times a week. To evaluate genetic damage, nandrolone decanoate at 15 mg/kg dose was exposed to 24 h. In the histopathological analysis, no remarkable morphological changes were observed in tongue tissue in all groups. Significant increase in immunoexpression of Ki-67, p53, COX-2 proteins was detected in the groups treated with nandrolone decanoate during 15 and 30 days, when compared to their respective controls. A positive correlation between immunoexpression of p53 and COX-2 protein was detected following nandrolone decanoate exposure. DNA damage was induced by nandrolone decanoate in oral mucosa cells at 15 mg/kg dose. Our results suggest that nandrolone decanoate was able to alter the expression of cell cycle-related proteins, as well as to induce genetic damage and COX-2 immunoexpression in tongue cells of Wistar rats.
Assuntos
Anabolizantes/toxicidade , Ciclo-Oxigenase 2/biossíntese , Dano ao DNA , Antígeno Ki-67/biossíntese , Nandrolona/análogos & derivados , Língua/efeitos dos fármacos , Proteína Supressora de Tumor p53/biossíntese , Animais , Ensaio Cometa , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Imuno-Histoquímica , Masculino , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Nandrolona/toxicidade , Decanoato de Nandrolona , Ratos , Ratos Wistar , Língua/enzimologia , Língua/metabolismo , Língua/patologiaRESUMO
PURPOSE: The aim of this study was to analyze and compare the expression of osteocalcin, RANK-L, osteoprotegerin, in sinus lift procedures using bovine hydroxyapatite (HA). MATERIAL AND METHODS: Twenty four male rabbits underwent bilateral sinus lift procedures were distributed into two groups, according to the sinus filling material: Group 1) autogenous bone graft; and Group 2) bovine HA. All groups were sacrificed after 14 and 30 days, for microscopic and immunohistochemistry analysis. RESULTS: At 14 days after surgery, discrete osteogenesis was observed in the highly vascularized granulation tissue surrounding HA particles, as well as woven bone deposition on the biomaterial surface. Following 30 days, well organized bone trabeculas were seen surrounding the HA granules presenting areas of osteogenic activity. Morphometric findings did not show remarkable differences between groups. Bovine HA induced similar osteocalcin, RANK-L, osteoprotegerin immunoexpressivity when compared to autogenous bone graft group for both periods evaluated in this setting. CONCLUSION: Taken together, these data are consistent with the notion that HA has a similar biological behavior to autogenous bone graft in sinus lift of rabbits.