Infecções odontogénicas

Introdução: As infecções odontogénicas constituem uma das patologias mais prevalentes e o principal motivo para a procura de cuidados médico-dentários a nível mundial. Todos os Médicos Dentistas deverão mostrar-se aptos a realizar um rápido diagnóstico bem como decidir de forma eficaz, ponderada e devidamente fundamentada qual o tratamento a aplicar a cada caso tendo consciência que a progressão de uma infecção odontogénica é, muitas vezes, imprevisível e um tratamento tardio ou incorrecto poderá acarretar complicações que implicam risco de vida para o paciente ao comprometer os espaços faciais profundos da cabeça e pescoço. Objectivo: Esta dissertação pretende, recorrendo à literatura existente, auxiliar o Médico Dentista no diagnóstico de uma infecção odontogénica e, essencialmente, evidenciar qual o tratamento preconizado ou considerado mais eficaz para este tipo de infecções orais. Materiais e métodos: Para a execução desta revisão da literatura, foi desenvolvida uma pesquisa, entre Janeiro e Junho de 2016, recorrendo à Biblioteca Ricardo Reis da Universidade Fernando Pessoa e à Biblioteca da Faculdade de Medicina Dentária da Universidade do Porto, ao portal “DGS” e às bases de dados electrónicas: PUBMED, SCIENCEDIRECT e Repositório Institucional da Universidade de Barcelona utilizando, para esse fim, as “palavras-chave” estabelecidas. Em suma, na realização da presente dissertação, foram consultadas três obras literárias e 23 artigos científicos. Conclusão: Segundo a literatura analisada, não existe consenso absoluto sobre qual o antibiótico que deverá ser prescrito no tratamento de infecções odontogénicas. A amoxicilina continua a ser referenciada como primeira linha de tratamento e, a necessidade e as vantagens da associação desta ao ácido clavulânico, são evidenciadas por diversos autores. A clindamicina é o antibiótico que se apresenta como segunda linha de tratamento, em casos de alergia aos beta-lactâmicos.

Estágio realizado no Programa Comunitário PLE²NO

A OA é a doença reumática mais comum no ser humano e uma doença crónica com impacto elevado na sociedade. Tem repercussões na saúde, ao nível da funcionalidade, comprometendo a realização das atividades da vida diária e a qualidade de vida dos indivíduos. Uma das articulações mais afetada pela OA é a articulação do joelho. O tratamento eficaz requer a combinação de tratamentos farmacológicos e não farmacológicos. Os tratamentos não farmacológicos, principalmente o exercício e a educação do doente têm vindo a ganhar importância, no que se refere ao controlo dos sintomas. A realização do estágio curricular surge no programa comunitário PLE²NO. O programa é considerado uma opção não farmacológica no tratamento e controlo dos sintomas da Osteoartrose (OA) no joelho. Os principais objetivos do estágio no PLE²NO consistiram: aquisição de conhecimentos teóricos relacionados com OA e práticos com vista ao aperfeiçoamento da prescrição do exercício; aquisição de competências essenciais à ótima liderança e comunicação com as pessoas e instituições envolvidas; prescrição de exercício a indivíduos com OA no joelho; cativar e motivar as pessoas para a prática de exercício; e determinar a eficácia de um programa de 3 meses de educação e exercício nos sintomas, aptidão física e qualidade de vida dos idosos com OA no joelho. Na aptidão física verificaram-se diferenças significativas na capacidade aeróbia, flexibilidade e velocidade da marcha. Nos indicadores de saúde houve melhoria em praticamente todos os parâmetros avaliados: mobilidade, cuidados pessoais, dor/mal-estar e sintomas de ansiedade/depressão. Assim, esta intervenção revelou-se ser uma mais-valia para o tratamento não farmacológico da osteoartrose do joelho a médio prazo.

Adesão à terapêutica em doentes diabéticos tipo 2: estudo de caso numa farmácia em Almada

Dissertação de Mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2016

Nurses knowledge of health effects of dietary fibre

Introduction: Nurses accompany patients throughout their health care to prevent and treat disease, so their knowledge about diet and dietary fibre is key to successful diet therapy, which is an essential part of a patient's non-pharmacological treatment. It is known from the literature that a high proportion of nurses have limited knowledge about diet therapy and about sources of soluble fibre and other foods that can prevent or treat certain diseases. Given the position of nurses as key providers of dietary guidance, and given the health benefits of dietary fibre, we wanted to assess the level of fibre-related knowledge among nurses in Croatia. Material and Methods: Cross-sectional study based on data collected between October 2014 and March 2015 using a survey developed by the CI&DETS Polytechnic Institute in Viseu, Portugal. The survey contains questions about demographic characteristics as well as about knowledge of sources of dietary fibre, recommended daily intake and effects of fibre intake on particular diseases. The study included a total of 369 nurses from two health institutions and one nursing school from Croatia older than 18 years. Differences in knowledge were assessed for significance using the non-parametric Mann-Whitney U test. Possible associations among variables were explored using Spearman's rank correlation. For all statistical analyses, the threshold of significance was defined as P<0.05. Results: The level of knowledge among nurses in Croatia about dietary fibre varied from «undecided» to «partial knowledge». The median for level of knowledge ranged from 3 to 4 with low variability ranging from 0.11 to 0.33. Average levels of knowledge in percentages varied from 57.6% to 82.1%. Nurses with higher education levels showed significantly higher knowledge levels about the influence of dietary fiber intake on the risk of certain diseases (p = 0.007), constipation (p = 0.016), bowel cancer (p = 0.005) and breast cancer (p = 0.039). Conclusion: The level of nurses’ knowledge about dietary fiber is suboptimal. This indicates the need to strengthen nurse education in the areas of diet and diet therapy. Increase the level of knowledge of nurses about nutrition can positively influence the quality of care.

Diclofenaco comparado con ibuprofeno para el cierre de Ductus arterioso persistente, en recién nacidos prematuros

Introducción: El Ductus arterioso persistente (DAP), es uno de los defectos congénitos cardiacos más comunes, requiere manejo farmacológico y/o quirúrgico; presenta complicaciones hemodinámicas, respiratorias y muerte. Los medicamentos de elección para su manejo son indometacina e ibuprofeno, pero su costo y accesibilidad llevo al uso de diclofenaco como alternativa de manejo en algunos hospitales. Objetivo: Comparar respuesta al tratamiento con diclofenaco vs ibuprofeno en cierre de DAP. Materiales y Métodos: Estudio observacional analítico retrospectivo, que compara los resultados obtenidos al usar Diclofenaco e Ibuprofeno para el cierre del DAP en recién nacidos pretérmino. Se recolecto información de pacientes hospitalizados en la Unidad Neonatal de un Hospital II nivel de Bogotá. Se revisaron las historias clínicas de pacientes de edad gestacional entre 24 y 36 semanas por Ballard con los criterios para diagnóstico de DAP y recibieron tratamiento farmacológico con una de las siguientes opciones: Ibuprofeno 10 mg/Kg dosis inicial después 5mg/Kg a las 24 48 horas, o Diclofenaco 0.2 mg/Kg dosis cada 12 horas tres dosis. Se comparó el Diclofenaco y el Ibuprofeno para el tratamiento farmacológico de DAP en recién nacidos prematuros. Resultados: Fueron evaluados 103 pacientes, el diagnóstico de DAP se realizó con ecocardiograma transtorácico, el 66.6 % de los pacientes presentó cierre farmacológico con Diclofenaco y 69 % con Ibuprofeno, La mortalidad fue de 17.65 % con Diclofenaco y 11.54 % con ibuprofeno; en ambos casos asociadas a la prematurez. Conclusiones: El éxito farmacológico fue similar en ambos grupos, el diclofenaco es una alternativa interesante cuando la terapia convencional no esté disponible.

Estado de las enfermedades raras que cursan con discapacidad intelectual en Colombia

Las enfermedades raras o huérfano son una problemática que ha tomado mucha importancia en el contexto mundial del presente siglo, estas se han definido como crónicas, de difícil tratamiento de sus síntomas y con baja prevalencia en la población; muchas de estas enfermedades cursan con varios tipos de discapacidad, siendo el objetivo del presente trabajo el enfocarse en aquellas enfermedades raras que cursan con discapacidad intelectual. Para poder profundizar en estas enfermedades se realizó una revisión teórica sobre las enfermedades raras, así como de la discapacidad psíquica y su importancia a nivel mundial y nacional. A partir de estas definiciones, se revisaron en profundidad 3 enfermedades raras que cursan con discapacidad intelectual en el contexto colombiano, como son: el síndrome de Rett, el síndrome de Prader-Willi y el síndrome de X frágil. En cada una de estas enfermedades además se explicaron los tipos de diagnóstico, intervención, prevención, grupos de apoyo y tipos de evaluación que más se usan en el contexto nacional

Evidencia sobre la eficacia de cannabinoides en el dolor neuropático oncológico

Contexto: La eficacia de los cannabinoides en el dolor neuropático es desconocida. El control del dolor es determinante en los pacientes ya que genera un impacto negativo en la calidad de vida de los pacientes. Objetivo: El presente trabajo pretende demostrar la evidencia sobre la eficacia de los medicamentos cannabinoides en el control del dolor neuropático oncológico, mediante la evaluación de la literatura disponible. Metodología: Se realizó una revisión sistemática de literatura incluyendo estudios experimentales, observacionales y revisiones sistemáticas en un periodo de 15 años. Se incluyeron todos los estudios desde el años 2000 con evidencia IB según la escala de evidencia de Oxford. Resultados: Cuatro estudios cumplieron criterios para su inclusión, sin embargo la evidencia es baja y no permite recomendar o descartar los cannabinoides como terapia coadyuvante en control del dolor neuropático oncológico. La combinación de THC/CDB (Sativex®) parece ser un medicamento seguro pues no se reportaron muertes asociadas a su uso, sin embargo la presentación de eventos adversos a nivel gastrointestinal y neurológico podría aumentar el riesgo de interacciones medicamentosas y tener un impacto negativo en la calidad de vida de los pacientes oncológicos. Conclusiones: No hay suficiente literatura y la evidencia no es suficiente para recomendar o descartar el uso de los cannabinoides en dolor neuropático oncológico. Futuros estudios deben realizarse para analizar el beneficio de estos medicamentos. Aunque ética y socialmente hay resistencia para el uso de los cannabinoides, actualmente hay una gran discusión política en el mundo y en Colombia para su aceptación como terapia en el control del dolor.

TAZ role in lung cancer: resistance to BET inhibitors and functional interaction with lncRNA

Despite extensive research and introduction of innovative therapy, lung cancer prognosis remains poor, with a five years survival of only 17%. The success of pharmacological treatment is often impaired by drug resistance. Thus, the characterization of response mechanisms to anti-cancer compounds and of the molecular mechanisms supporting lung cancer aggressiveness are crucial for patient’s management. In the first part of this thesis, we characterized the molecular mechanism behind resistance of lung cancer cells to the Inhibitors of the Bromodomain and Extraterminal domain containing Proteins (BETi). Through a CRISPR/Cas9 screening we identified three Hippo Pathway members, LATS2, TAOK1 and NF2 as genes implicated in susceptibility to BETi. These genes confer sensitivity to BETi inhibiting TAZ activity. Conversely, TAZ overexpression increases resistance to BETi. We also displayed that BETi downregulate both YAP, TAZ and TEADs expression in several cancer cell lines, implying a novel BETi-dependent cytotoxic mechanism. In the second part of this work, we attempted to characterize the crosstalk between the TAZ gene and its cognate antisense long-non coding RNA (lncRNA) TAZ-AS202 in lung tumorigenesis. As for TAZ downregulation, TAZ-AS202 silencing impairs NSCLC cells proliferation, migration and invasion, suggesting a pro-tumorigenic function for this lncRNA during lung tumorigenesis. TAZ-AS202 regulates TAZ target genes without altering TAZ expression or localization. This finding implies an uncovered functional cooperation between TAZ and TAZ-AS202. Moreover, we found that the EPH-ephrin signaling receptor EPHB2 is a downstream effector affected by both TAZ and TAZ-AS202 silencing. EPHB2 downregulation significantly attenuates cells proliferation, migration and invasion, suggesting that, at least in part, TAZ-AS202 and TAZ pro-oncogenic activity depends on EPH-ephrin signaling final deregulation. Finally, we started to dissect the mechanism underlying the TAZ-AS202 regulatory activity on EPHB2 in lung cancer, which may involve the existence of an intermediate transcription factor and is the object of our ongoing research.

Longitudinal Micro CT-driven biomarkers as a tool to evaluate lung fibrosis progression and antifibrotic efficacy in a refined Bleomycin mouse model

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with no curative pharmacological treatment. Animal models play an essential role in revealing molecular mechanisms involved in the pathogenesis of the disease. Bleomycin (BLM)-induced lung fibrosis is the most widely used and characterized model for anti-fibrotic drugs screening. However, several issues have been reported, such as the identification of an optimal BLM dose and administration scheme as well as gender-specificity. Moreover, the balance between disease resolution, an appropriate time window for therapeutic intervention and animal welfare remains critical aspects yet to be fully elucidated. In this thesis, Micro CT imaging has been used as a tool to identify the ideal BLM dose regimen to induce sustained lung fibrosis in mice as well as to assess the anti-fibrotic effect of Nintedanib (NINT) treatment upon this BLM administration regimen. In order to select the optimal BLM dose scheme, C57bl/6 male mice were treated with BLM via oropharyngeal aspiration (OA), following either double or triple BLM administration. The triple BLM administration resulted in the most promising scheme, able to balance disease resolution, appropriate time-window for therapeutic intervention and animal welfare. The fibrosis progression was longitudinally assessed by micro-CT every 7 days for 5 weeks after BLM administration and 5 animals were sacrificed at each timepoint for the BALF and histological evaluation. The antifibrotic effect of NINT was assessed following different treatment regimens in this model. Herein, we have developed an optimized mouse model of pulmonary fibrosis, enabling three weeks of the therapeutic window to screen putative anti-fibrotic drugs. micro-CT scanning, allowed us to monitor the progression of lung fibrosis and the therapeutical response longitudinally in the same subject, drastically reducing the number of animals involved in the experiment.

Nuclear shape instability caused by lamin A deregulation promotes invasiveness in pediatric bone sarcomas: from nucleo-cytoskeleton dynamics to novel therapeutic opportunities

Osteosarcoma (OS) and Ewing sarcoma (EWS) are the two most frequent primary bone tumors, in which metastases remain the most relevant adverse prognostic factor. Lamin A is the main constituent of the nuclear lamina, with a fundamental role in maintaining the connection between nucleus and cytoskeleton (through LINC complex proteins interactions), and its alterations can be implicated in tumor progression. We investigated how nucleo-cytoskeleton dynamics is influenced by lamin A modulation in OS and EWS, demonstrating that both these cancer models had low levels of lamin A, which are linked to a significantly more marked nuclear misshaping. In our in vitro studies, reduced levels of lamin A promoted migratory abilities in these tumors. Moreover, these findings were corroborated by gene expression analyses on EWS patient samples, showing that LMNA levels were significantly lower in metastatic lesions compared to primary tumors and that patients with low LMNA had a significant worse overall survival. We also found that LMNA expression significantly impaired EWS metastases formation in vivo. We demonstrated that low lamin A expression was linked to a severe mislocalization of LINC complex proteins, thus disrupting nucleo-cytoskeleton interactions, with a corresponding gain in malignant properties, which resulted in increased invasiveness. Lamin A overexpression or its accumulation by a statin-based pharmacological treatment allowed us to reconstitute a functional nucleo-cytoskeleton interplay, which resulted in significant downmodulation of ROCK2 and YAP, two crucial drivers of EWS aggressiveness. Our study demonstrated that lamin A is a favorable mediator of nuclear shape stability in bone sarcomas, and its modulation rescues LINC complex protein localization and regulates mechano-signaling pathways, thus promoting a less aggressive cancer phenotype. We also identified statins, already employed in clinical practice, as a tool capable to increase lamin A levels, and to reconstitute functional nucleo-cytoskeletal dynamics, resulting in reduced cellular migration.

A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer.

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250 mg/m(2)/DXR 40 mg/m(2) every 3 weeks for schedule 1 and VFL 120 mg/m(2)/DXR 25 mg/m(2) days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.

Sufentanil-2-hydroxypropyl-beta-cyclodextrin inclusion complex for pain treatment: Physicochemical, cytotoxicity, and pharmacological evaluation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature

Abstract Background Cannabis intoxication is related to a number of physical and mental health risks with ensuing social costs. However, little attention has been given to the investigation of possible pharmacological interactions in this condition. Objective To review the available scientific literature concerning pharmacological interventions for the treatment of the acute effects of cannabis. Methods A search was performed on the Pubmed, Lilacs, and Scielo online databases by combining the terms cannabis, intoxication, psychosis, anxiety, and treatment. The articles selected from this search had their reference lists checked for additional publications related to the topic of the review. Results The reviewed articles consisted of case reports and controlled clinical trials and are presented according to interventions targeting the physiological, psychiatric, and cognitive symptoms provoked by cannabis. The pharmacological interventions reported in these studies include: beta-blockers, antiarrhythmic agents, antagonists of CB-1 and GABA-benzodiazepine receptors, antipsychotics, and cannabidiol. Conclusion Although scarce, the evidence on pharmacological interventions for the management of cannabis intoxication suggests that propanolol and rimonabant are the most effective compounds currently available to treat the physiological and subjective effects of the drug. Further studies are necessary to establish the real effectiveness of these two medications, as well as the effectiveness of other candidate compounds to counteract the effects of cannabis intoxication, such as cannabidiol and flumazenil.

Pharmacological prevention and treatment in clinical at-risk states for psychosis

Over the last couple of decades, the treatment of psychoses has much advanced; yet, despite all progress, the individual and societal burden associated with psychosis and particularly schizophrenia has largely remained unchanged. Therefore, much hope is currently placed on indicated prevention as a mean to fight these burdens before they set in. Though the number of studies investigating pharmacological interventions is still limited, encouraging results have been reported from the pioneering trials, despite several methodological limitations. Furthermore, it has become clear that persons characterized by the at-risk criteria are already ill and do not only need preventive intervention, but also treatment. In consequence, outcome criteria have to be broadened to cover the current needs of the patients. As is indicated by a recent study successfully using Omega-3 fatty acids for both purposes, it may be promising to develop and investigate interventions especially for the at-risk state, independent of their effectiveness in manifest disease states. Treatment studies may become promoted by the proposed introduction of a new disorder category into DSM-V. Future prevention studies, however, need to solve the challenge of changing immediate transition rates, demanding for new risk enrichment strategies as a prerequisite for feasible trial designs.

Bryophyllum pinnatum inhibits detrusor contractility in porcine bladder strips--a pharmacological study towards a new treatment option of overactive bladder

A broad spectrum of synthetic agents is available for the treatment of overactive bladder. Anti-cholinergic drugs show a poor compliance due to side effects. There is an increasing use of plant extracts in medicine. We have therefore investigated the inhibitory effects of leaf press juice from Bryophyllum pinnatum (Lam.) Oken (Kalanchoe pinnata L.) on bladder strips and compared the effects to that of oxybutynin.