Manifestações orais associadas ao consumo da droga de abuso MDMA

O uso para fins ou meios festivos de lazer da droga ilícita MDMA, também chamado de Ecstasy ou Moly, tem vindo a aumentar drasticamente em Portugal e no Mundo. Esta situação desafia os profissionais de saúde para vários parâmetros na saúde oral e geral. O objetivo desta dissertação visa avaliar e descrever as lesões e patologias na cavidade oral que estão relacionadas com o consumo da substância ilícita MDMA. As consequências para a cavidade oral podem ser a xerostomia, o bruxismo, as cáries rampantes, a doença periodontal, o desgaste e a erosão dentária, e as lesões dos tecidos moles. Os indivíduos consumidores podem apresentar carências nutricionais e um estímulo aumentado à dor. A gestão do prognóstico e o tratamento realizado aos consumidores de MDMA, pois afeta vários órgãos e sistemas no corpo humano, requer uma abordagem multidisciplinar que inclui educação, prevenção e tratamento integrados. Esta revisão bibliográfica teve com base artigos publicados em revistas científicos e monografias disponíveis em vários motores de busca. As palavras-chave usadas foram: “ecstasy”, “MDMA”, “oral manifestations”, “oral health”, “substance abuse”, ”overdose treatment”, “xerostomia” e “methamenfetamine” e a sua conjugação. As situações orais, perante as mais prevalentes comorbidades patogénicas relacionadas com o MDMA e outras dependências ilícitas, necessitam de mais atenção e reforço em relação à prática clínica e aos serviços de saúde. Uma das dificuldades para o tratamento correto destes indivíduos é a falta de informação sobre o assunto referente à prática na clínica dentária. A omissão sobre o consumo por parte do paciente bem como de uma recaída no uso, apresentam dúvidas sobre o fator em causa ou até mesmo no diagnóstico. São, muitas vezes, os Médicos Dentistas os primeiros a terem a oportunidade de diagnosticar o aparecimento de possíveis alterações surgidas em virtude do consumo de MDMA.

What do infectious diseases physicians do? a 2-week snapshot of inpatient consultative activities across Australia, New Zealand and Singapore

The practice of an infectious diseases (ID) physician is evolving. A contemporary understanding of the frequency and variety of patients and syndromes seen by ID services has implications for training, service development and setting research priorities. We performed a 2-week prospective survey of formal ID physician activities related to direct inpatient care, encompassing 53 hospitals throughout Australia, New Zealand and Singapore, and documented 1722 inpatient interactions. Infections involving the skin and soft tissue, respiratory tract and bone/joints together accounted for 49% of all consultations. Suspected/confirmed pathogens were primarily bacterial (60%), rather than viral (6%), fungal (4%), mycobacterial (2%) or parasitic (1%). Staphylococcus aureus was implicated in 409 (24%) episodes, approximately four times more frequently than the next most common pathogen. The frequency of healthcare-related infections (35%), immunosuppression (21%), diabetes mellitus (19%), prosthesis-related infections (13%), multiresistant pathogens (13%) and non-infectious diagnoses (9%) was high, although consultation characteristics varied between geographical settings and hospital types. Our study highlights the diversity of inpatient-related ID activities and should direct future teaching and research. ID physicians' ability to offer beneficial consultative advice requires broad understanding of, and ability to interact with, a wide range of referring specialities.

Methicillin-susceptible Staphylococcus aureus endocarditis isolates are associated with clonal complex 30 genotype and a distinct repertoire of enterotoxins and adhesins.

BACKGROUND: Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. METHODS: IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. RESULTS: 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P < .05 for all). CONCLUSIONS: MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.

Caracterización de trastornos musculo esqueléticos en trabajadores de dos empresas de servicios en Bogotá D.C 2015

Objetivo: El objetivo de este estudio fue determinar la prevalencia de los trastornos músculoesqueléticos y la asociación con factores sociodemográficos y hábitos de vida en trabajadores de las áreas administrativa y operativa de dos empresas de servicio de la ciudad de Bogotá 2015. Materiales y Métodos: Se realizó un estudio de corte transversal, con información secundaria, procedente de bases de datos suministrada por las dos empresas con 696 registros de trabajadores de servicios generales, y 943 registros de trabajadores del área administrativa, para un total de 1639 registros, en los cuales se evaluó la presencia de síntomas osteomusculares clasificados por segmento. Adicionalmente se contaba con información de características sociodemográficas y estilos de vida de estos trabajadores. Se obtuvieron las distribuciones de frecuencias absolutas y relativas para las variables cualitativas, y las medidas de tendencia central y de dispersión para las variables cuantitativas. Para establecer la asociación entre factores sociodemográficos con las variables dependientes se utilizó la prueba chi2 de asociación. Resultados: La prevalencia de molestia o dolor en los diferentes segmentos corporales fue de 21.5 % (n = 203) en cuello para la población administrativa y de 17.5% (n = 148) en mano y muñeca derecha para la población de servicios generales. Vale la pena aclarar que el diagnóstico médico más frecuente referido por la población en estudio fue traumas en musculo, bursa tendón y/o ligamento con 10.5% en la población administrativa y con el 12.4% en la población de servicios generales. De las asociaciones significativas entre diagnósticos presentes y hábitos de vida y sueño se encontró que sueño no reparador se asoció significativamente con enfermedad general de músculos y huesos (p = 0.001), enfermedad o trauma activo de tejidos blandos (p = 0,000) y antecedente o enfermedad actual de columna vertebral (p = 0,000). De manera similar, el consumo de medicamentos para conciliar el sueño se asoció con enfermedad de tejidos blandos (p = 0,000) y enfermedad actual de columna vertebral (p = 0,000). El consumo de café (p = 0.001) y el sedentarismo (p = 0.031) están asociados con la enfermedad general de músculos y huesos. Conclusiones: Los TME son un factor de alta prevalencia en la población trabajadora de Colombia, y como se demostró en este estudio, afectan a la población de las empresas de servicio. Se evidencia cada vez más que los segmentos corporales más afectados en la población administrativa, son cabeza y cuello, debido a las posturas mantenidas por largos periodos de tiempo, y en la población de servicios se encontró molestia y dolor en muñecas y manos debido a los movimientos repetitivos que deben de realizar durante la jornada laboral. Se hace necesario profundizar más en la asociación significativa de los trastornos del sueño y la presencia de los TME, ya que se encontró una relación importante entre estos dos.

Can tissue engineering concepts advance tumor biology research?

Advances in tissue engineering have traditionally led to the design of scaffold- or matrix-based culture systems that better reflect the biological, physical and biochemical environment of the natural extracellular matrix. Although their clinical applications in regenerative medicine tend to receive most of the attention, it is obvious that other areas of biomedical research could be well served by the powerful tools that have already been developed in tissue engineering. In this article, we review the recent literature to demonstrate how tissue engineering platforms can enhance in vitro and in vivo models of tumorigenesis and thus hold great promise to contribute to future cancer research.

An adipoinductive role of inflammation in adipose tissue engineering : key factors in the early development of engineered soft tissues

Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

Association of CYP1B1 codon 432 mutant allele in head and neck squamous cell cancer is reflected by somatic mutations of p53 in tumor tissue

Tobacco use is causally associated with head and neck squamous cell cancer (HNSCC). Here, we present the results of a case-control study that investigated the effects that the genetic variants of the cytochrome (CYP)1A1, CYP1B1, glutathione-S-transferase (GST)M1, GSTT1, and GSTP1 genes have on modifying the risk of smoking-related HNSCC. Allelisms of the CYP1A1, GSTT1, GSTM1, and GSTT1 genes alone were not associated with an increased risk. CYP1B1 codon 432 polymorphism was found to be a putative susceptibility factor in smoking-related HNSCC. The frequency of CYP1B1 polymorphism was significantly higher (P < 0.001) in the group of smoking cases when compared with smoking controls. Additionally, an odds ratio (OR) of 4.53 (2.62-7.98) was discovered when investigating smoking and nonsmoking cases for the susceptible genotype CYP1B1*2/*2, when compared with the presence of the genotype wild type. In combination with polymorphic variants of the GST genes, a synergistic-effect OR was observed. The calculated OR for the combined genotype CYP1B1*2/*2 and GSTM1*2/*2 was 12.8 (4.09-49.7). The calculated OR for the combined genotype was 13.4 (2.92-97.7) for CYP1B1*2/*2 and GSTT1*2/*2, and 24.1 (9.36-70.5) for the combination of CYP1B1*2/*2 and GSTT1-expressors. The impact of the polymorphic variants of the CYP1B1 gene on HNSCC risk is reflected by the strong association with the frequency of somatic mutations of the p53 gene. Smokers with susceptible genotype CYP1B1*2/*2 were 20 times more likely to show evidence of p53 mutations than were those with CYP1B1 wild type. Combined genotype analysis of CYP1B1 and GSTM1 or GSTT1 revealed interactive effects on the occurrence of p53 gene mutations. The results of the present study indicate that polymorphic variants of CYP1B1 relate significantly to the individual susceptibility of smokers to HNSCC.

Tissue-engineered 3D tumor angiogenesis models : potential technologies for anti-cancer drug discovery

Angiogenesis is indispensable for solid tumor expansion, and thus it has become a major target of cancer research and anti-cancer therapies. Deciphering the arcane actions of various cell populations during tumor angiogenesis requires sophisticated research models, which could capture the dynamics and complexity of the process. There is a continuous need for improvement of existing research models, which engages interdisciplinary approaches of tissue engineering with life sciences. Tireless efforts to develop a new model to study tumor angiogenesis result in innovative solutions, which bring us one step closer to decipher the dubious nature of cancer. This review aims to overview the recent developments, current limitations and future challenges in three-dimensional tissue-engineered models for the study of tumor angiogenesis and for the purpose of elucidating novel targets aimed at anti-cancer drug discovery.

Concise review: Humanized models of tumor immunology in the 21st century: Convergence of cancer research and tissue engineering

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human.” To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.

Methylation of tumor associated genes in tissue and plasma samples from liver disease patients

To investigate whether aberrant hypermethylation in plasma DNA could be used as diagnosis makers for hepatocellular carcinoma (HCC), we performed methylation-specific PCR (MSP) to check the methylation status of five tumor associated genes in 36 cases of

Hand-held spectroscopic device for in vivo and intraoperative tumor detection: contrast enhancement, detection sensitivity, and tissue penetration.

Surgery is one of the most effective and widely used procedures in treating human cancers, but a major problem is that the surgeon often fails to remove the entire tumor, leaving behind tumor-positive margins, metastatic lymph nodes, and/or satellite tumor nodules. Here we report the use of a hand-held spectroscopic pen device (termed SpectroPen) and near-infrared contrast agents for intraoperative detection of malignant tumors, based on wavelength-resolved measurements of fluorescence and surface-enhanced Raman scattering (SERS) signals. The SpectroPen utilizes a near-infrared diode laser (emitting at 785 nm) coupled to a compact head unit for light excitation and collection. This pen-shaped device effectively removes silica Raman peaks from the fiber optics and attenuates the reflected excitation light, allowing sensitive analysis of both fluorescence and Raman signals. Its overall performance has been evaluated by using a fluorescent contrast agent (indocyanine green, or ICG) as well as a surface-enhanced Raman scattering (SERS) contrast agent (pegylated colloidal gold). Under in vitro conditions, the detection limits are approximately 2-5 × 10(-11) M for the indocyanine dye and 0.5-1 × 10(-13) M for the SERS contrast agent. Ex vivo tissue penetration data show attenuated but resolvable fluorescence and Raman signals when the contrast agents are buried 5-10 mm deep in fresh animal tissues. In vivo studies using mice bearing bioluminescent 4T1 breast tumors further demonstrate that the tumor borders can be precisely detected preoperatively and intraoperatively, and that the contrast signals are strongly correlated with tumor bioluminescence. After surgery, the SpectroPen device permits further evaluation of both positive and negative tumor margins around the surgical cavity, raising new possibilities for real-time tumor detection and image-guided surgery.

Soft-computing techniques applied to artificial tissue temperature estimation

Tese dout., Engenharia electrónica e computação - Processamento de sinal, Universidade do Algarve, 2008

“Unmixing” Tissue Gene Expression Signatures from Tumor Biopsies

Emergent molecular measurement methods, such as DNA microarray, qRTPCR, and many others, offer tremendous promise for the personalized treatment of cancer. These technologies measure the amount of specific proteins, RNA, DNA or other molecular targets from tumor specimens with the goal of “fingerprinting” individual cancers. Tumor specimens are heterogeneous; an individual specimen typically contains unknown amounts of multiple tissues types. Thus, the measured molecular concentrations result from an unknown mixture of tissue types, and must be normalized to account for the composition of the mixture. For example, a breast tumor biopsy may contain normal, dysplastic and cancerous epithelial cells, as well as stromal components (fatty and connective tissue) and blood and lymphatic vessels. Our diagnostic interest focuses solely on the dysplastic and cancerous epithelial cells. The remaining tissue components serve to “contaminate” the signal of interest. The proportion of each of the tissue components changes as a function of patient characteristics (e.g., age), and varies spatially across the tumor region. Because each of the tissue components produces a different molecular signature, and the amount of each tissue type is specimen dependent, we must estimate the tissue composition of the specimen, and adjust the molecular signal for this composition. Using the idea of a chemical mass balance, we consider the total measured concentrations to be a weighted sum of the individual tissue signatures, where weights are determined by the relative amounts of the different tissue types. We develop a compositional source apportionment model to estimate the relative amounts of tissue components in a tumor specimen. We then use these estimates to infer the tissuespecific concentrations of key molecular targets for sub-typing individual tumors. We anticipate these specific measurements will greatly improve our ability to discriminate between different classes of tumors, and allow more precise matching of each patient to the appropriate treatment

Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model

Background: The expression levels of the clotting initiator protein Tissue Factor (TF) correlate with vessel density and the histological malignancy grade of glioma patients. Increased procoagulant tonus in high grade tumors (glioblastomas) also indicates a potential role for TF in progression of this disease, and suggests that anticoagulants could be used as adjuvants for its treatment. Objectives: We hypothesized that blocking of TF activity with the tick anticoagulant Ixolaris might interfere with glioblastoma progression. Methods and results: TF was identified in U87-MG cells by flow-cytometric and functional assays (extrinsic tenase). In addition, flow-cytometric analysis demonstrated the exposure of phosphatidylserine in the surface of U87-MG cells, which supported the assembly of intrinsic tenase (FIXa/FVIIIa/FX) and prothrombinase (FVa/FXa/prothrombin) complexes, accounting for the production of FXa and thrombin, respectively. Ixolaris effectively blocked the in vitro TF-dependent procoagulant activity of the U87-MG human glioblastoma cell line and attenuated multimolecular coagulation complexes assembly. Notably, Ixolaris inhibited the in vivo tumorigenic potential of U87-MG cells in nude mice, without observable bleeding. This inhibitory effect of Ixolaris on tumor growth was associated with downregulation of VEGF and reduced tumor vascularization. Conclusion: Our results suggest that Ixolaris might be a promising agent for anti-tumor therapy in humans.

Does alveolar soft-part sarcoma exhibit skeletal muscle differentiation? An immunocytochemical and biochemical study of myogenic regulatory protein expression

There has been persistent controversy regarding the nature of cell differentiation in alveolar soft-part sarcoma (ASPS) since its first description in 1952. Some studies suggest that ASPS might represent an unusual variant of skeletal muscle tumor, Given the availability of new monoclonal antibodies to probe for skeletal muscle differentiation and the rapid advance in immunocytochemical techniques for deparaffinized, formalin-fixed tissue sections, we wished to test the proposed hypothesis that ASPS might represent a new type of rhabdomyosarcoma Twelve archival samples of ASPS were retrieved, and we investigated the expression of two myogenic regulatory proteins, MyoD1 and myogenin, as rvell as other muscle-associated proteins, using sensitive immunocytochemical techniques. Despite the presence of desmin immunostaining in six ASPSs, no tumors were positive for either muscle actin or myoglobin Most importantly, no specimen showed nuclear expression of MyoD1 or myogenin, In 11 tumors, however, there was considerable granular immunostaining in the tumor cell cytoplasm with the anti-MyoD1 monoclonal antibody 5.8A, a phenomenon observed in various nonmuscle normal and neoplastic tissues with this antibody, To analyze the exact nature of immunostaining of MyoD1 and desmin in ASPS, biochemical analyses using available fresh frozen tumor tissue were performed, Although a 53-kDa band was noted with antidesmin antibody on Western blot analysis, no specific protein band that corresponds to the 45-kDa MyoD1 was detected with antibody 5.8A. These results confirm the presence of desmin in ASPS but argue against authentic expression of MyoD1, They also suggest that the cytoplasmic immunostaining observed with anti-MyoD1 antibody 5.8A most likely represents a nonspecific cross-reaction with an unknown cytoplasmic antigen, Considering the master role that MyoD1 and myogenin play in skeletal muscle commitment and differentiation and the lack of expression of these two proteins in ASPS as determined immunocytochemically and biochemically, we think that the histogenesis of ASPS remains unknown.