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Estudo da distribuição de doses limiares em TFD para um modelo de cultura tridimensional de células obtido pelo método de levitação magnética; Study of the threshold doses distribution in PDT using the three-dimensional cell cultures obtained by the method of magnetic levitation

Sabino, Luis Gustavo
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 21/10/2014 PT
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25.94%
Um conceito central na dosimetria da terapia fotodinâmica (TFD) é o limiar de dose (Dth do inglês threshold dose). O Dth é definido como a quantidade mínima de luz que deve ser absorvida pelas moléculas de fotossensibilizador (FS) dentro das células malignas a serem tratadas para que ocorra a morte celular por necrose ou apoptose. Os resultados do estudo da captação de FS por células Hep G2 demonstraram que uma população celular de linhagem, cultivada em monocamada, apresenta captação de Photogem (PG) heterogênea, ou seja, algumas células têm maior capacidade de captar moléculas de PG, outras células captam o PG em menor quantidade. A captação heterogênea de PG pode ser a causa para fenômenos de seleção de células mais resistentes à TFD. É razoável supor que as subpopulações celulares de uma mesma massa de células malignas possam apresentar diferentes valores de Dth. Definiu-se uma função de distribuição das doses limiares (g()) como uma função de distribuição gaussiana, e para a sua parametrização desenvolveu-se um método para o cultivo in vitro de culturas tridimensionais (culturas 3D), mais fidedignas ao tecido neoplásico maligno que as culturas tradicionais. Utilizando-se o método de levitação magnética (MLM) e o método de impressão magnética (MIM) para a dosimetria da TFD...

Effects of low-level laser therapy (685 nm) at different doses in osteogenic cell cultures

Schwartz-Filho, Humberto Osvaldo; Reimer, Aline C.; Marcantonio, Claudio; Marcantonio, Elcio; Marcantonio, Rosemary Adriana Chierici
Fonte: Springer London Ltd Publicador: Springer London Ltd
Tipo: Artigo de Revista Científica Formato: 539-543
ENG
Relevância na Pesquisa
35.91%
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); The present in vitro study evaluated parameters of osteogenesis under the influence of low-level laser therapy (LLLT) at different doses. Osteogenic cells originated from rat calvaria were cultivated in polystyrene plates and exposed to a laser irradiation using an indium-gallium-aluminum phosphide therapeutic laser (InGaAIP), at wavelength of 685 nm, power of 35 mW, 600-mu m-diameter optical fiber, and continuous wave. In the attempt of observing the existence of a dose response and its effects, laser irradiation was performed at 25, 77, and 130 J/cm(2) (7, 22, and 37 s, respectively). The following parameters were assessed: growth curve (4, 7, and 11 days), cell viability (24 h), and nodular formation of mineralized matrix (14 days). The results did not show significant differences related to the growth curve (4, 7, and 11 days) and cell viability (24 h). Within 14 days, osteogenic cultures showed nodular areas with well-defined calcified matrix. The total area stained with Alizarin Red did not show any differences between doses of 25 and 130 J/cm(2). However, the percentage of stained area was significantly higher in the 25 J/cm(2) group when compared to the group of 77 J/cm(2) (Kruskal-Wallis test...

Expression and characterization of a therapeutic monoclonal antibody in mammalian cells

Costa, A. R.
Fonte: Universidade do Minho Publicador: Universidade do Minho
Tipo: Tese de Doutorado
Publicado em 30/01/2013 ENG
Relevância na Pesquisa
26.11%
Doctoral dissertation for PhD degree in Biomedical Engineering; The advent of therapeutic recombinant proteins has revolutionized modern medicine. Since the approval of recombinant insulin in 1982 to treat diabetes, many other recombinant proteins have emerged for a diversity of previously incurable conditions. In these years, the manufacturing processes have greatly evolved, but have also often disregarded product quality, an issue only recently addressed and currently a major challenge in biopharmaceutical industry. Regulatory agencies require now a tight control of product quality during production, which typically involves characterization of the protein’s glycosylation, known to affect properties like serum half-life, biological activity and immunogenicity. However, control of this property is not simple due to its intrinsic high variability and its high sensitivity to small changes in the manufacturing process, in ways that are far from being understood. Therefore, the development of products of consistent high-quality requires a deeper understanding on the effect of the production parameters/ processes on glycosylation. In this context, the work described in this thesis intended to contribute to this field of knowledge by evaluating changes on glycosylation of a monoclonal antibody (mAb) produced by Chinese hamster ovary (CHO) cells during different stages of process development...

Antioxidant properties of A. ponderosa cultures and antiproliferative effect against MDA-MB-231 human breast cancer cells

Salvador, Cátia; Martins, M. Rosário; Duarte, M. Fátima; Caldeira, A. Teresa
Fonte: Universidade de Aveiro Publicador: Universidade de Aveiro
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
25.94%
Mushrooms are appreciated, not only for texture and flavor but also for their chemical and nutritional properties. They have been reported as therapeutic foods that are useful in preventing diseases such as hypertension, hypercholesterolemia and cancer. In fact, mushrooms have become attractive as functional foods and as a source of bioactive compounds because they are rich sources of antioxidant compounds such as phenolic compounds, carotenoids and polysaccharides [1, 2]. The medicinal property for which mushrooms of several species have been most extensively investigated and reported is their antitumor activity. A. ponderosa are a wild edible mushrooms, that grows in Mediterranean forests in mounted areas of holm oaks and cork trees, namely in Alentejo region (Southern Portugal) and Andalusia (Southern Spain). There are few studies with respect to this species, however in this work was possible to obtain A. ponderosa pure cultures from strains collected in different areas of Alentejo [3]. Thus, the present work aims to evaluate antioxidant activity of A. ponderosa mushrooms and cultures from isolated mycelia and characterize the anti-tumoral activity of cultures, in a human breast cancer cell in vitro model (MDA-MB231). For the screening of mushroom antioxidant properties...

Medicamentos, consumos de performance e culturas terapêuticas em mudança

Lopes, Noémia Mendes; Rodrigues, Carla F.
Fonte: Editora Mundos Sociais Publicador: Editora Mundos Sociais
Tipo: Artigo de Revista Científica
Publicado em 01/05/2015 POR
Relevância na Pesquisa
46.02%
O uso de fármacos e produtos naturais para a gestão do desempenho pessoal, aqui designado consumos de performance, constitui o foco deste artigo e dá suporte a uma reflexão analítica sobre a mudança nas culturas terapêuticas. Tendo por referência a atual problemática da farmacologização, bem como o lugar do natural na expansão do uso do medicamento, demonstra-se que a farmacologização do quotidiano está a emergir noutros campos, que não exclusivamente o da saúde, dando lugar a novas lógicas de relação com estes recursos. A sustentação empírica desta abordagem tem por base os resultados de um estudo nacional sobre os consumos de performance na população jovem em Portugal.; This article focuses on the use of pharmaceutical drugs and natural products to manage personal performance — i.e. the consumption of performance-enhancing substances, or what the authors refer to as performance-enhancing consumption. This in turn serves as the basis for an analytical reflection on the change in therapeutic cultures. Taking the current issue of pharmacologisation and the role of the natural in the expanding use of medicines as their points of reference, the authors show that the pharmacologisation of daily life is also emerging in fields other than just health...

Development of a factorial design for a therapeutic plasmid DNA biosynthesis

Martins, Luís Miguel Candeias
Fonte: Universidade da Beira Interior Publicador: Universidade da Beira Interior
Tipo: Dissertação de Mestrado
Publicado em //2013 ENG
Relevância na Pesquisa
25.97%
Therapeutic applications of plasmid DNA (pDNA) have significantly advanced during the last years. Currently, several pDNA-based drugs are already in the market, whereas several others have entered to phases 2 and 3 of clinical trials. The present and future demand for pDNA requires the development of efficient bioprocesses to produce it. Commonly, pDNA is produced by cultures of Escherichia coli. It has been previously demonstrated that specific strains of E. coli with a modified substrate transport system can be able to attain high cell densities in batch mode, due to the very low overflow metabolism displayed. However, the large amounts of oxygen demanded can lead to microaerobic conditions after some hours of cultivation, even at small-scale. Typically, the inherent problems for these cultures are the high oxygen demand and the accumulation of acetate, a metabolic by-product that is synthesized aerobically when the glucose rate exceeds limits. In recent years, various researches have been focused on the study of induction of plasmid DNA as well as strategies for fermentation using semi-defined mediums. These studies conceived relevant results that allow us to design a production platform for enhanced plasmid DNA. The main goal of this study is to optimize the yield of therapeutic plasmid DNA by culture of recent developed strain of Escherichia coli. The strategy is based on the variation of composition of the fermentation media in terms of nutrients and by a development of an experimental design directed to aromatic amino acids pathway. Monitoring through analytical methods is an advantage both in control and optimization of the intervenients in fermentation process. The change of composition and concentration of the substrates affect the growth of Escherichia coli VH33 and simultaneously...

beta-Amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger.

Bruce, A J; Malfroy, B; Baudry, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 19/03/1996 EN
Relevância na Pesquisa
25.94%
Oxygen free radicals have been proposed to mediate amyloid peptide (beta-AP)-induced neurotoxicity. To test this hypothesis, we evaluated the effects of EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, on neuronal injury produced by beta-AP in organotypic hippocampal slice cultures. Cultures of equivalent postnatal day 35 (defined as mature) and 14 (defined as immature) were exposed to various concentrations of beta-AP (1-42 or 1-40) in the absence or presence of 25 microM EUK-8 for up to 72 hours. Neuronal injury was assessed by lactate dehydrogenase release and semiquantitative analysis of propidium iodide uptake at various times after the initiation of beta-AP exposure. Free radical production was inferred from the relative increase in dichlorofluorescein fluorescence, and the degree of lipid peroxidation was determined by assaying thiobarbituric acid-reactive substances. Treatment of mature cultures with beta-AP (50-250 microg/ml) in serum-free conditions resulted in a reproducible pattern of damage, causing a time-dependent increase in neuronal injury accompanied with formation of reactive oxygen species. However, immature cultures were entirely resistant to beta-AP-induced neurotoxicity and also demonstrated no dichlorofluorescein fluorescence or increased lipid peroxidation after beta-AP treatment. Moreover...

Clinical implications of positive blood cultures.

Bryan, C S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1989 EN
Relevância na Pesquisa
25.96%
Positive blood cultures can be classified according to their veracity (true-positive or false-positive culture), clinical severity (inconsequential or life threatening), place of origin (community acquired or nosocomial), source (primary or secondary), duration (transient, intermittent, or continuous), pattern of occurrence (single episode, persistent, or recurrent), or intensity (high or low grade). In general, however, positive blood cultures identify a patient population at high risk of death. In my studies, patients with positive blood cultures were 12 times more likely to die during hospitalization than patients without positive blood cultures. Many bacteremias and fungemias occur in complicated clinical settings, and it appears that only about one-half of the deaths among affected patients are due directly to infection. Hence, it is appropriate to speak of "crude mortality" and "attributable mortality." Among hospitalized patients, recent trends include rising incidences of Staphylococcus aureus and coagulase-negative staphylococcal and enterococcal bacteremias and a dramatic increase in the incidence of fungemias. The diagnostic and therapeutic implications of blood cultures positive for specific microorganisms continue to evolve and are the subject of a large and growing medical literature.

Effects of therapeutic drugs on lymphocyte transformation.

Williams, W R; Davidson, L A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1983 EN
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26.04%
1 Over 40 non-steroidal drugs, routinely given on a long term therapeutic basis, were tested in lymphocyte transformation cultures at high therapeutic concentrations, or in serum cultures after short term oral drug administration. Lymphocyte transformation was assessed by measuring thymidine and 2-deoxyuridine incorporation into DNA. 2 When added in vitro, salicylate significantly inhibited thymidine (48%, n = 35) and deoxyuridine incorporation (20%, n = 12). Thymidine incorporation was specifically inhibited by phenylbutazone (39%, n = 6) and chlorpropamide (48%, n = 5). Specific inhibition of deoxyuridine incorporation, indicative of impaired lymphocyte folate metabolism, was obtained following the addition of pyrimethamine (51%, n = 3) and to some extent by carbimazole (30%, n = 2). In serum cultures, pyrimethamine inhibited deoxyuridine incorporation (30%, n = 3) and chloroquine inhibited the incorporation of both thymidine (37%, n = 3) and deoxyuridine (46%, n = 3). 3 Most classes of drugs used long term are unlikely to cause any significant clinical effect, by impairing lymphocyte function. Caution may be warranted when high doses of salicylate, phenylbutazone, chloroquine, pyrimethamine, chloropropamide or combinations of these drugs are prescribed.

Nuclear localization signal of HIV-1 as a novel target for therapeutic intervention.

Dubrovsky, L.; Ulrich, P.; Nuovo, G. J.; Manogue, K. R.; Cerami, A.; Bukrinsky, M.
Fonte: The Feinstein Institute for Medical Research Publicador: The Feinstein Institute for Medical Research
Tipo: Artigo de Revista Científica
Publicado em /01/1995 EN
Relevância na Pesquisa
25.98%
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) is a lentivirus and shares with other members of this retroviral subfamily the ability to replicate in nondividing cells, in particular, cells of the monocyte/macrophage lineage. This feature relies on the presence of a specific nuclear localization signal (NLS) within the viral matrix protein (MA p17), which to some degree can be complemented by the activity of the viral vpr gene product. The MA p17 NLS ensures efficient transportation of the viral preintegration complex into the nucleus of an infected macrophage and confers persistence of HIV-1 in quiescent T cells, and therefore presents an attractive target for therapeutic intervention. MATERIALS AND METHODS: Nuclear localization signals (NLS) in general and the HIV-1 MA p17 NLS in particular are characterized by a stretch of positively charged amino acids including one or more lysine residues. A series of compounds potentially capable of binding and reacting with lysine by forming Schiff base adducts was synthesized. Our special consideration was to make compounds that would preferentially bind to two closely contiguous amino functions, as opposed to isolated single lysine residues. We assumed that this approach might specifically target the compound to NLS while affecting other regions less...

Cerebrospinal Fluid and Plasma (1→3)-β-d-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous Candida Meningoencephalitis▿

Petraitiene, Ruta; Petraitis, Vidmantas; Hope, William W.; Mickiene, Diana; Kelaher, Amy M.; Murray, Heidi A.; Mya-San, Christine; Hughes, Johanna E.; Cotton, Margaret P.; Bacher, John; Walsh, Thomas J.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.05%
The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1→3)-β-d-glucan (β-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (102 to 103 CFU/ml), spinal cord, and meninges (10 to 102 CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for β-glucan were positive (755 to 7,750 pg/ml) (P < 0.001). The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg. A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, β-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of β-glucan concentrations in CSF...

Protective effects of tetramethylpyrazine on rat retinal cell cultures

Yang, Zhikuan; Zhang, Qingjiong; Ge, Jian; Tan, Zhiqun
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
26.07%
The retinal degeneration characterized with death of retinal ganglion cells is a pathological hallmark and the final common pathway of various optic neuropathies. Thus, there is an urgent need for identifying potential therapeutic compounds for retinal protection. Tetramethylpyrazine has been suggested to be neuroprotective for central neurons by acting as an antioxidant and a calcium antagonist. In this study, we tested the effects of tetramethylpyrazine on the viability of both neuronal and non-neuronal cells in mixed rat retinal cell cultures during a long-term cultivation or following hydrogen peroxide treatments. Cellular and biochemical analyses demonstrated that 50 μM tetramethylpyrazine significantly preserved neuronal morphology and survival in retinal cell cultures following 4-week in vitro cultivation as well as lethal exposures to hydrogen peroxide (10μM or 50 μM for 24 hr). Hydrogen peroxide treatments induced remarkable increases in lipid peroxidation and mitochondrial ROS generation paralleled by the loss of mitochondrial membrane potential, microtubule-associated protein-2 (MAP-2) in neuronal soma and rattin peptide in cultured cells. Addition of tetramethylpyrazine in the cultures efficiently attenuated the signs of oxidative stress and retained abundance of MAP-2 and rattin in association with cell survival. In addition...

Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targets

Rappa, Germana; Mercapide, Javier; Anzanello, Fabio; Prasmickaite, Lina; Xi, Yaguang; Ju, Jingfang; Fodstad, Oystein; Lorico, Aurelio
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
25.97%
Malignant tumors comprise a small proportion of cancer-initiating cells (CIC), capable of sustaining tumor formation and growth. CIC are the main potential target for anticancer therapy. However, the identification of molecular therapeutic targets in CIC isolated from primary tumors is an extremely difficult task. Here, we show that after years of passaging under differentiating conditions, glioblastoma, mammary carcinoma, and melanoma cell lines contained a fraction of cells capable of forming spheroids upon in vitro growth under stem cell-like conditions. We found an increased expression of surface markers associated with the stem cell phenotype and of oncogenes in cell lines and clones cultured as spheroids vs. adherent cultures. Also, spheroid-forming cells displayed increased tumorigenicity and an altered pattern of chemosensitivity. Interestingly, also from single retrovirally marked clones, it was possible to isolate cells able to grow as spheroids and associated with increased tumorigenicity. Our findings indicate that short-term selection and propagation of CIC as spheroid cultures from established cancer cell lines, coupled with gene expression profiling, represents a suitable tool to study and therapeutically target CIC: the notion of which genes have been down-regulated during growth under differentiating conditions will help find CIC-associated therapeutic targets.

Memantine Lowers Amyloid-beta Peptide Levels in Neuronal Cultures and in APP/PS1 Transgenic Mice

Alley, George M.; Bailey, Jason A; Chen, DeMao; Ray, Balmiki; Puli, Lakshman K.; Tanila, Heikki; Banerjee, Pradeep K; Lahiri, Debomoy K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/2010 EN
Relevância na Pesquisa
25.98%
Memantine is a moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that stabilizes cognitive, functional, and behavioral decline in patients with moderate to severe Alzheimer’s disease (AD). In AD, the extracellular deposition of fibrillogenic amyloid-beta peptides (Aβ) occurs due to aberrant processing of the full-length Aβ precursor protein (APP). Memantine protects neurons from the neurotoxic effects of Aβ and improves cognition in transgenic mice with high brain levels of Aβ. However, it is unknown how memantine protects cells against neurodegeneration and affects APP processing and Aβ production. We report the effects of memantine in three different systems. In human neuroblastoma cells, memantine, at therapeutically relevant concentrations (1-4 μM), decreased levels of secreted APP and Aβ1-40. Levels of the potentially amylodogenic Aβ1-42 were undetectable in these cells. In primary rat cortical neuronal cultures, memantine treatment lowered Aβ1-42 secretion. At the concentrations used, memantine treatment was not toxic to neuroblastoma or primary cultures and increased cell viability and/or metabolic activity under certain conditions. In APP/presenilin-1 (PS1) transgenic mice exhibiting high brain levels of Aβ1-42...

Three-Dimensional Lung Tumor Microenvironment Modulates Therapeutic Compound Responsiveness In Vitro – Implication for Drug Development

Ekert, Jason E.; Johnson, Kjell; Strake, Brandy; Pardinas, Jose; Jarantow, Stephen; Perkinson, Robert; Colter, David C.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 17/03/2014 EN
Relevância na Pesquisa
25.96%
Three-dimensional (3D) cell culture is gaining acceptance in response to the need for cellular models that better mimic physiologic tissues. Spheroids are one such 3D model where clusters of cells will undergo self-assembly to form viable, 3D tumor-like structures. However, to date little is known about how spheroid biology compares to that of the more traditional and widely utilized 2D monolayer cultures. Therefore, the goal of this study was to characterize the phenotypic and functional differences between lung tumor cells grown as 2D monolayer cultures, versus cells grown as 3D spheroids. Eight lung tumor cell lines, displaying varying levels of epidermal growth factor receptor (EGFR) and cMET protein expression, were used to develop a 3D spheroid cell culture model using low attachment U-bottom plates. The 3D spheroids were compared with cells grown in monolayer for 1) EGFR and cMET receptor expression, as determined by flow cytometry, 2) EGFR and cMET phosphorylation by MSD assay, and 3) cell proliferation in response to epidermal growth factor (EGF) and hepatocyte growth factor (HGF). In addition, drug responsiveness to EGFR and cMET inhibitors (Erlotinib, Crizotinib, Cetuximab [Erbitux] and Onartuzumab [MetMab]) was evaluated by measuring the extent of cell proliferation and migration. Data showed that EGFR and cMET expression is reduced at day four of untreated spheroid culture compared to monolayer. Basal phosphorylation of EGFR and cMET was higher in spheroids compared to monolayer cultures. Spheroids showed reduced EGFR and cMET phosphorylation when stimulated with ligand compared to 2D cultures. Spheroids showed an altered cell proliferation response to HGF...

Differential marker expression by cultures rich in mesenchymal stem cells

Wetzig, Andrew; Alaiya, Ayodele; Al-Alwan, Monther; Pradez, Christian Benedict; Pulicat, Manogaran S; Al-Mazrou, Amer; Shinwari, Zakia; Sleiman, Ghida Majed; Ghebeh, Hazem; Al-Humaidan, Hind; Gaafar, Ameera; Kanaan, Imaduddin; Adra, Chaker
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
26%
Background: Mesenchymal stem cells have properties that make them amenable to therapeutic use. However, the acceptance of mesenchymal stem cells in clinical practice requires standardized techniques for their specific isolation. To date, there are no conclusive marker (s) for the exclusive isolation of mesenchymal stem cells. Our aim was to identify markers differentially expressed between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. We compared and contrasted the phenotype of tissue cultures in which mesenchymal stem cells are rich and rare. By initially assessing mesenchymal stem cell differentiation, we established that bone marrow and breast adipose cultures are rich in mesenchymal stem cells while, in our hands, foreskin fibroblast and olfactory tissue cultures contain rare mesenchymal stem cells. In particular, olfactory tissue cells represent non-stem cell mesenchymal cells. Subsequently, the phenotype of the tissue cultures were thoroughly assessed using immuno-fluorescence, flow-cytometry, proteomics, antibody arrays and qPCR. Results: Our analysis revealed that all tissue cultures, regardless of differentiation potential, demonstrated remarkably similar phenotypes. Importantly, it was also observed that common mesenchymal stem cell markers...

Health : Indigenous Knowledge, Equitable Benefits

Moran, Katy
Fonte: World Bank, Washington, DC Publicador: World Bank, Washington, DC
Relevância na Pesquisa
25.98%
The note looks at the intellectual property rights connected with the use, and value of medicinal plants, which has become a metaphor to describe indigenous ownership of traditional knowledge, generating options for contractual mechanisms to ensure benefits return to source cultures, and countries. However, through time, the extinction rate of species, and cultures continues to accelerate, while human health further deteriorates from diseases for which no cure exists. The note seeks answers on how to apply lessons from the Convention on Biological Diversity, and how to move on to implementing such lessons. Through the case study in Nigeria, practical information shows how countries, companies, and cultures can cooperate. It explains the work of the Bio-Resources Development and Conservation Program, organized as a focal point for collaborative research, that builds technical skills in Nigeria, thus generating pharmaceutical leads that target therapeutic categories for tropical diseases. Within this setting...

Development of a factorial design for a therapeutic plasmid DNA biosynthesis

Martins, Luís Miguel Candeias
Fonte: Universidade da Beira Interior Publicador: Universidade da Beira Interior
Tipo: Dissertação de Mestrado
Publicado em //2013 ENG
Relevância na Pesquisa
25.97%
Therapeutic applications of plasmid DNA (pDNA) have significantly advanced during the last years. Currently, several pDNA-based drugs are already in the market, whereas several others have entered to phases 2 and 3 of clinical trials. The present and future demand for pDNA requires the development of efficient bioprocesses to produce it. Commonly, pDNA is produced by cultures of Escherichia coli. It has been previously demonstrated that specific strains of E. coli with a modified substrate transport system can be able to attain high cell densities in batch mode, due to the very low overflow metabolism displayed. However, the large amounts of oxygen demanded can lead to microaerobic conditions after some hours of cultivation, even at small-scale. Typically, the inherent problems for these cultures are the high oxygen demand and the accumulation of acetate, a metabolic by-product that is synthesized aerobically when the glucose rate exceeds limits. In recent years, various researches have been focused on the study of induction of plasmid DNA as well as strategies for fermentation using semi-defined mediums. These studies conceived relevant results that allow us to design a production platform for enhanced plasmid DNA. The main goal of this study is to optimize the yield of therapeutic plasmid DNA by culture of recent developed strain of Escherichia coli. The strategy is based on the variation of composition of the fermentation media in terms of nutrients and by a development of an experimental design directed to aromatic amino acids pathway. Monitoring through analytical methods is an advantage both in control and optimization of the intervenients in fermentation process. The change of composition and concentration of the substrates affect the growth of Escherichia coli VH33 and simultaneously...

Magnetic Field-Assisted Gene Delivery: Achievements and Therapeutic Potential

Schwerdt, José I.; Goya, Gerardo F.; Calatayud, Pilar; Hereñú, Claudia B.; Reggiani, Paula C.; Goya, Rodolfo G.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 05/11/2011
Relevância na Pesquisa
26.01%
The discovery in the early 2000's that magnetic nanoparticles (MNPs) complexed to nonviral or viral vectors can, in the presence of an external magnetic field, greatly enhance gene transfer into cells has raised much interest. This technique, called magnetofection, was initially developed mainly to improve gene transfer in cell cultures, a simpler and more easily controllable scenario than in vivo models. These studies provided evidence for some unique capabilities of magnetofection. Progressively, the interest in magnetofection expanded to its application in animal models and led to the association of this technique with another technology, magnetic drug targeting (MDT). This combination offers the possibility to develop more efficient and less invasive gene therapy strategies for a number of major pathologies like cancer, neurodegeneration and myocardial infarction. The goal of MDT is to concentrate MNPs functionalized with therapeutic drugs, in target areas of the body by means of properly focused external magnetic fields. The availability of stable, nontoxic MNP-gene vector complexes now offers the opportunity to develop magnetic gene targeting (MGT), a variant of MDT in which the gene coding for a therapeutic molecule, rather than the molecule itself...

Avaliação mutagênica do canabidiol, um composto da maconha, por meio dos testes citogenéticos do micronúcleo e do cometa; Mutagenic evaluation of cannabidiol, a marihuana compound, by micronucleus and comet assay cytogenetic tests

SILVA, Leni Gomes da
Fonte: Universidade de São Paulo. Faculdade de Medicina Publicador: Universidade de São Paulo. Faculdade de Medicina
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; DTR2; Formato: application/pdf
Publicado em 07/11/2002 POR
Relevância na Pesquisa
26.08%
The plantCannabis sativa L., algo known as marihuana or maconha has been cultivated by man for many years. Despite its reputation as an abuse drug the plant has therapeutic qualities and has been indicated especially as an analgesic or antiemetic substance. This plant contains a considerable amount of the nonpsychoactive compound, the cannabidíol (CBD). It has been indicated as an anticonvulsant in view of the depressive effect it produces on neuromuscular transmission and response, both, in laboratory animaIs and in mano The efficacy of this substance, has been assessed in the control and treatment of epileptic convulsions and dystonic movement disorders. To evaluate the mutagenic potential of a drug or substance some cytogenetic tests such as the micronucleus (MN) and the comet (SCGE) assays can be performed. Micronuclei are represented by chromosomal material in the cell cytoplasm, originated from acentric fragments of DNA or complete chromosomes which failed to attach to the mitotic spindle. On the other hand, the comet assay permits the identification of DNA fragments in isolated cells that run away from the main nucleus when subjected to electrophoresis, resulting in a figure that resembles a cometo Preliminary studies have shown that the use of CBD may increase the frequency of chromosomal aberrations in human Iymphocytes treated in vitro...