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1.
Alzheimers Dement ; 14(4): 444-453, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29244999

RESUMEN

INTRODUCTION: Exposure to traumatic brain injury is a core risk factor that predisposes an individual to sporadic neurodegenerative diseases. We provide evidence that mechanical stress increases brain levels of hallmark proteins associated with neurodegeneration. METHODS: Wild-type mice were exposed to multiple regimens of repetitive mild traumatic brain injury, generating a range of combinations of impact energies, frequencies, and durations of exposure. Brain concentrations of amyloid ß 1-42 (Aß1-42), total tau, and α-synuclein were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: There was a highly significant main effect of impact energy, frequency, and duration of exposure on Aß1-42, tau, and α-synuclein levels (P < .001), and a significant interaction between impact energy and duration of exposure for Aß1-42 and tau (P < .001), but not for α-synuclein. DISCUSSION: Dose-dependent and cumulative influence of repetitive mild traumatic brain injury-induced mechanical stress may trigger and/or accelerate neurodegeneration by pushing protein concentration over the disease threshold.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Conmoción Encefálica/metabolismo , Encéfalo/metabolismo , Fragmentos de Péptidos/metabolismo , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismo , Animales , Fenómenos Biomecánicos , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos BALB C , Distribución Aleatoria , Estrés Mecánico
2.
Int J Health Care Qual Assur ; 30(3): 208-215, 2017 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-28350224

RESUMEN

Purpose Failure modes and effects analysis (FMEA) is a practical tool to evaluate risks, discover failures in a proactive manner and propose corrective actions to reduce or eliminate potential risks. The purpose of this paper is to apply FMEA technique to examine the hazards associated with the process of service delivery in intensive care unit (ICU) of a tertiary hospital in Yazd, Iran. Design/methodology/approach This was a before-after study conducted between March 2013 and December 2014. By forming a FMEA team, all potential hazards associated with ICU services - their frequency and severity - were identified. Then risk priority number was calculated for each activity as an indicator representing high priority areas that need special attention and resource allocation. Findings Eight failure modes with highest priority scores including endotracheal tube defect, wrong placement of endotracheal tube, EVD interface, aspiration failure during suctioning, chest tube failure, tissue injury and deep vein thrombosis were selected for improvement. Findings affirmed that improvement strategies were generally satisfying and significantly decreased total failures. Practical implications Application of FMEA in ICUs proved to be effective in proactively decreasing the risk of failures and corrected the control measures up to acceptable levels in all eight areas of function. Originality/value Using a prospective risk assessment approach, such as FMEA, could be beneficial in dealing with potential failures through proposing preventive actions in a proactive manner. The method could be used as a tool for healthcare continuous quality improvement so that the method identifies both systemic and human errors, and offers practical advice to deal effectively with them.


Asunto(s)
Análisis de Modo y Efecto de Fallas en la Atención de la Salud/organización & administración , Unidades de Cuidados Intensivos/organización & administración , Mejoramiento de la Calidad/organización & administración , Gestión de Riesgos/organización & administración , Humanos , Unidades de Cuidados Intensivos/normas , Irán , Errores Médicos/prevención & control , Estudios Prospectivos , Indicadores de Calidad de la Atención de Salud , Medición de Riesgo
3.
Asian J Transfus Sci ; 18(1): 115-123, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39036697

RESUMEN

INTRODUCTION: Patient blood management (PBM) is outlined as evidence-based medical and surgical concepts with a multidisciplinary method. AIMS AND OBJECTIVES: The aim of this article is to review the PBM implementation and analyses the issues, challenges, and opportunities. METHODOLOGY: In this article, we have an overview of PBM implementation in literature and our experience in one hospital in Iran. We used databases including Embase, CINAHL, Scopus, Google Scholar, Google, Science Direct, ProQuest, ISI Web of Knowledge, and PubMed to attain the related literature published in the English language. RESULTS: There are different barriers and challenges of implementation of PBM, such as hospital culture confrontation, reduced staff with restricted time, lack of interdisciplinary conversation, change of practice, the lack of experience with PBM, the feasibility to integrate PBM, electronic documentation and schedule budget for required instruments, resources, and personnel. Hospitals differ globally in the aspect of infrastructure, personnel and properties, and it is necessary to individualize according to the local situation. CONCLUSION: The review highlights the importance of PBM and its implementation for obtaining patient safety. PBM establishing in hospitals as a complex process have different challenges and barriers. Sharing experiences is essential to success in the PBM programs. Cooperation between countries will be useful in PBM spreading.

4.
Invest New Drugs ; 31(2): 256-64, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22797854

RESUMEN

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.


Asunto(s)
Capsaicina/uso terapéutico , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Citratos/uso terapéutico , Melanoma Experimental/tratamiento farmacológico , Ácido Tióctico/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Antioxidantes/uso terapéutico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Humanos , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Fármacos del Sistema Sensorial/uso terapéutico , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología
5.
Daru ; 21(1): 25, 2013 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-23514587

RESUMEN

BACKGROUND AND THE PURPOSE OF THE STUDY: Affinity-based target deconvolution is an emerging method for the identification of interactions between drugs/drug candidates and cellular proteins, and helps to predict potential activities and side effects of a given compound. In the present study, we hypothesized that a part of safranal pharmacological effects, one of the major constituent of Crocus sativus L., relies on its physical interaction with target proteins. METHODS: Affinity chromatography solid support was prepared by covalent attachment of safranal to agarose beads. After passing tissue lysate through the column, safranal-bound proteins were isolated and separated on SDS-PAGE or two-dimensional gel electrophoresis. Proteins were identified using MALDI-TOF/TOF mass spectrometry and Mascot software. RESULTS AND MAJOR CONCLUSION: Data showed that safranal physically binds to beta actin, cytochrome b-c1 complex sub-unit 1, trifunctional enzyme sub-unit beta and ATP synthase sub-unit alpha and beta. These interactions may explain part of safranal's pharmacological effects. However, phenotypic and/or biological relevance of these interactions remains to be elucidated by future pharmacological studies.

6.
Gastroenterology ; 141(2): 642-52, 652.e1-4, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21683076

RESUMEN

BACKGROUND & AIMS: Mycobacterium bovis Bacillus Calmette-Guérin (BCG), killed by extended freeze-drying (EFD), induces secretion of interleukin-10 and reduces lung inflammation in a mouse model of asthma. We investigated the effects of EFD BCG in mouse models of inflammatory bowel disease. METHODS: EFD BCG was administered subcutaneously to mice with colitis induced by dextran sodium sulfate (DSS), oxazolone, or adoptive transfer of CD4(+)CD45RB(high)Foxp3(-) T cells from C57Bl/6 Foxp3GFP mice to RAG2(-/-) mice. RESULTS: EFD BCG, administered either before induction of DSS and oxazolone colitis or after development of acute or chronic DSS-induced colitis, reduced symptom scores, loss of body weight, and inflammation. Although transfer of CD4(+)CD45RB(high)Foxp3(-) cells induced colitis in RAG2(-/-) mice, administration of EFD BCG at the time of the transfer converted Foxp3(-) T cells to Foxp3(+) T cells and the mice did not develop colitis. EFD BCG protected mice from colitis via a mechanism that required expansion of T regulatory cells and production of interleukin-10 and transforming growth factor ß. EFD BCG activated the retinoid X receptor (RXR)-α-peroxisome proliferator-activated receptor (PPAR)-γ heterodimer, blocked translocation of nuclear factor κB to the nucleus, and reduced colonic inflammation; it did not increase the number of colon tumors that formed in mice with chronic DSS-induced colitis. CONCLUSIONS: EFD BCG controls severe colitis in mice by expanding T regulatory cell populations and PPAR-γ and might be developed to treat patients with inflammatory bowel disease.


Asunto(s)
Vacuna BCG/farmacología , Colitis/prevención & control , Colon/metabolismo , Factores de Transcripción Forkhead/metabolismo , Mycobacterium bovis , Linfocitos T Reguladores/metabolismo , Animales , Vacuna BCG/administración & dosificación , Colitis/inducido químicamente , Colitis/inmunología , Colon/patología , Sulfato de Dextran , Liofilización , Interleucina-1/sangre , Interleucina-10/metabolismo , Interleucina-6/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Oxazolona , PPAR gamma/metabolismo , Peroxidasa/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Pérdida de Peso
7.
Invest New Drugs ; 30(1): 200-11, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20931262

RESUMEN

Altered metabolism of cancer first highlighted by Otto Warburg has a long history. Although ignored for a considerable amount of time, it is now receiving substantial attention. We recently published results obtained with a combination of two drugs, lipoic acid and hydroxycitrate, targeting metabolic enzymes particularly affected in cancer: ATP citrate lyase and pyruvate dehydrogenase kinase. This treatment was as efficient as chemotherapy in the three mouse cancer models that were tested. In this work, we asked if our drug combination could be used in conjunction with standard cytotoxic chemotherapy, in particular cisplatin, to improve basic protocol efficacy. A combination of lipoic acid and hydroxycitrate was administered to mice implanted with syngeneic cancer cells, LL/2 lung carcinoma and MBT-2 bladder carcinoma, concommitantly with classical chemotherapy (cisplatin or methotrexate). We demonstrate that the triple combination lipoic acid + hydroxycitrate + cisplatin or methotrexate is more efficient than cisplatin or methotrexate used individually or the combination of lipoic acid and hydroxycitrate administered alone. Of particular note are the results obtained in the treatment of an 80 year-old female who presented with ductal adenocarcinoma of the pancreas accompanied by liver metastases. A treatment course using gemcitabine plus α-lipoic acid and hydroxycitrate gave highly promising results. The in vivo data, coupled with the case study results, suggest a possible advantage in using a treatment targeted at cancer metabolism in association with classical chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Metabolismo Energético/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anciano de 80 o más Años , Animales , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/secundario , Línea Celular Tumoral , Cisplatino/administración & dosificación , Citratos/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Metotrexato/administración & dosificación , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Ácido Tióctico/administración & dosificación , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Gemcitabina
8.
Invest New Drugs ; 30(4): 1331-42, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21655919

RESUMEN

Alterations in metabolic pathways are known to characterize cancer. In order to suppress cancer growth, however, multiple proteins involved in these pathways have to be targeted simultaneously. We have developed a screening method to assess the best drug combination for cancer treatment based on targeting several factors implicated in tumor specific metabolism. Following a review of the literature, we identified those enzymes known to be deregulated in cancer and established a list of sixty-two drugs targeting them. These molecules are used routinely in clinical settings for diseases other than cancer. We screened a first library in vitro against four cell lines and then evaluated the most promising binary combinations in vivo against three murine syngeneic cancer models, (LL/2, Lewis lung carcinoma; B16-F10, melanoma; and MBT-2, bladder cancer). The optimum result was obtained using a combination of α-lipoic acid and hydroxycitrate (METABLOC(TM)). In this study, a third agent was added by in vivo evaluation of a large number of combinations. The addition of octreotide strongly reduced tumor development (T/C% value of 30.2 to 34.5%; P < 0.001) in the same models and prolonged animal survival (P < 0.001) as compared to cisplatin. These results were confirmed in a different laboratory setting using a human xenograft model (NCI-H69, small cell lung cancer). None of these three molecules are known to target DNA. The effectiveness of this combination in several animal models, as well as the low toxicity of these inexpensive drugs, emphasizes the necessity of rapidly setting up a clinical trial.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Animales , Antineoplásicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Citratos/farmacología , Citratos/uso terapéutico , Modelos Animales de Enfermedad , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Ratones Endogámicos C57BL , Neoplasias/patología , Octreótido/farmacología , Octreótido/uso terapéutico , Reproducibilidad de los Resultados , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Resultado del Tratamiento
9.
J Immunol ; 184(2): 1062-70, 2010 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-20007537

RESUMEN

We have previously shown that bacillus Calmette-Guérin (BCG) inactivated by extended freeze-drying (EFD) reduces airway hyperresponsiveness, whereas live and heat-killed BCG fail to do so. However, the cells involved in the protective effect and the signaling and transcriptional networks that could reprogram T cell commitment after EFD BCG treatment remained to be elucidated. We investigated whether EFD BCG targets plasmacytoid dendritic cells (pDCs) potentially involved in the polarization of regulatory T cells (Tregs) and the transcriptional factors that regulate allergic inflammation. OVA-sensitized mice were s.c. injected with EFD, live, or heat-killed BCG. We analyzed after the injection of the various BCG preparations: 1) pDCs recruited in the draining lymph nodes (day 4); 2) transcription factors involved in inflammation and T cell commitment in spleen and lungs after OVA challenge (day 28). Airway hyperresponsiveness and transcription factors were determined after in vivo depletion of pDCs or Tregs in EFD BCG-treated and OVA-challenged mice. EFD BCG reduced inflammation via the recruitment of pDCs polarizing the differentiation of naive CD4+ T lymphocytes into Tregs. In vivo, pDC or Treg depletion at the time of EFD BCG treatment abrogated the protection against inflammation. EFD BCG treatment upregulated Forkhead-winged helix transcription factor (Treg signature) and downregulated GATA-3 and RORgammat (Th2 and Th17 signatures) more efficiently than live and heat-killed BCG. Moreover, only EFD BCG enhanced peroxisome proliferator-activated receptor gamma expression and blocked NF-kappaB activation, cyclooxygenase expression, and p38 MAPK phosphorylation. EFD BCG reduced allergic inflammation by recruiting pDCs that promoted Tregs; EFD BCG acted as a peroxisome proliferator-activated receptor gamma agonist and thus could be used in asthma and other inflammatory diseases.


Asunto(s)
Vacuna BCG/farmacología , Células Dendríticas/efectos de los fármacos , Liofilización , Mycobacterium bovis , Neumonía/prevención & control , Animales , Vacuna BCG/administración & dosificación , Pulmón/inmunología , Masculino , Ratones , Ratones Endogámicos , Ovalbúmina , PPAR gamma/agonistas , Neumonía/terapia , Bazo/inmunología , Linfocitos T Reguladores , Factores de Transcripción , Resultado del Tratamiento
10.
Respir Res ; 11: 49, 2010 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-20429932

RESUMEN

BACKGROUND: Lungs of cystic fibrosis (CF) patients are chronically infected with Pseudomonas aeruginosa. Increased airway constriction has been reported in CF patients but underplaying mechanisms have not been elucidated. AIM: To examine the effect of P. aeruginosa LPS on airway constriction in CF mice and the implication in this process of cytosolic phospholipase A2alpha (cPLA2alpha), an enzyme involved in arachidonic acid (AA) release. METHODS: Mice were instilled intra-nasally with LPS. Airway constriction was assessed using barometric plethysmograph. MIP-2, prostaglandin E2 (PGE2), leukotrienes and AA concentrations were measured in BALF using standard kits and gas chromatography. RESULTS: LPS induced enhanced airway constriction and AA release in BALF of CF compared to littermate mice. This was accompanied by increased levels of PGE2, but not those of leukotrienes. However, airway neutrophil influx and MIP-2 production remained similar in both mouse strains. The cPLA2alpha inhibitor arachidonyl trifluoro-methyl-ketone (ATK), but not aspirin which inhibit PGE2 synthesis, reduced LPS-induced airway constriction. LPS induced lower airway constriction and PGE2 production in cPLA2alpha -/- mice compared to corresponding littermates. Neither aspirin nor ATK interfered with LPS-induced airway neutrophil influx or MIP-2 production. CONCLUSIONS: CF mice develop enhanced airway constriction through a cPLA2alpha-dependent mechanism. Airway inflammation is dissociated from airway constriction in this model. cPLA2alpha may represent a suitable target for therapeutic intervention in CF. Attenuation of airway constriction by cPLA2alpha inhibitors may help to ameliorate the clinical status of CF patients.


Asunto(s)
Broncoconstricción/efectos de los fármacos , Fibrosis Quística/enzimología , Fosfolipasas A2 Grupo IV/metabolismo , Lipopolisacáridos/farmacología , Pulmón/efectos de los fármacos , Pseudomonas aeruginosa , Administración Intranasal , Animales , Ácido Araquidónico/metabolismo , Ácidos Araquidónicos/farmacología , Aspirina/farmacología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CXCL2/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Fibrosis Quística/inmunología , Fibrosis Quística/fisiopatología , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Fosfolipasas A2 Grupo IV/antagonistas & inhibidores , Fosfolipasas A2 Grupo IV/deficiencia , Fosfolipasas A2 Grupo IV/genética , Leucotrienos/metabolismo , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/aislamiento & purificación , Pulmón/enzimología , Pulmón/inmunología , Pulmón/fisiopatología , Ratones , Ratones Endogámicos CFTR , Ratones Noqueados , Infiltración Neutrófila/efectos de los fármacos , Neumonía/enzimología , Neumonía/inmunología , Neumonía/fisiopatología , Pseudomonas aeruginosa/química , Factores de Tiempo
11.
J Ultrasound Med ; 28(11): 1535-47, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19854969

RESUMEN

OBJECTIVE: Noninvasive real-time thermal change monitoring of human internal organs can play a critical role in diagnosis and treatment of many disorders, including reperfusion of renal arteries during anticoagulation therapy. METHODS: This article focuses on tissue temperature detection using ultrasound velocity changes in different structures and their related speckle shift from their primary locations on high-quality B-mode digital sonography. We evaluated different speckle-tracking techniques and optimized them using appropriate motion estimation methods to determine the best algorithm and parameters. RESULTS: Performing thermal detection methods on simulated phantoms showed a good correlation between speckle shifts and the ground truth temperature. For the simulated images, average thermal error was 0.5 degrees C with an SD of 0.5 degrees C, where lower errors can be obtained in noiseless (motionless) data. The proposed technique was evaluated on real in vivo cases during surgical occlusion and reopening of the renal segmental artery and showed the potential of the algorithm for observation of internal organ changes using only digital ultrasound systems for diagnosis and therapy. CONCLUSIONS: The adaptive Rood pattern search proved to be the best block-matching technique, whereas the multiresolution Horn-Schunck technique was the best gradient optical flow method. The extracted thermal change during in vivo revascularization therapy is promising. In addition, we present an evaluation of several block-matching and optical flow motion estimation techniques.


Asunto(s)
Imagenología Tridimensional/métodos , Reconocimiento de Normas Patrones Automatizadas/métodos , Arteria Renal/diagnóstico por imagen , Arteria Renal/cirugía , Termografía/métodos , Ultrasonografía/métodos , Procedimientos Quirúrgicos Vasculares/métodos , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Fantasmas de Imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador , Cirugía Asistida por Computador/métodos
12.
J Allergy Clin Immunol ; 121(2): 471-8, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18037160

RESUMEN

BACKGROUND: Live BCG administered intranasally to mice inhibits the development of ovalbumin (OVA)-induced eosinophilia and airway hyperresponsiveness (AHR). It is unacceptable to treat human subjects intranasally with live BCG. OBJECTIVE: We investigated whether BCG killed by extended freeze-drying (EFD) and subcutaneously injected has a protective effect in murine and guinea pig models of allergic airway inflammation. METHODS: Mice were OVA sensitized (days 0 and 7), treated subcutaneously (day 14) with EFD and live or heat-killed BCG, and then OVA challenged (day 42). OVA-sensitized mice (days 0 and 7) were challenged (day 14) and EFD treated (day 18) before OVA rechallenge (day 46) to demonstrate the capacity of EFD to reverse the established lung inflammation. Guinea pigs were OVA sensitized (days 0 and 14), treated intradermally (day 35) with EFD, and OVA challenged (days 90-105). RESULTS: In mice and guinea pigs EFD treatment reduced AHR. Among 3 BCG preparations, only EFD efficiently reduced AHR, eosinophilia, and the recruitment of dendritic cells to the lungs after OVA challenge. The protective effect of EFD is associated with production of the immunoregulatory cytokine IL-10. Moreover, EFD treatment did not induce toxic effects or delayed-type hypersensitivity to mycobacterial antigens; that is, it did not interfere with the diagnosis of tuberculosis. CONCLUSION: EFD administered subcutaneously inhibits the development of allergic airway inflammation and prevents AHR without inducing delayed-type hypersensitivity and side effects associated with live or heat-killed BCG.


Asunto(s)
Vacuna BCG/farmacología , Hiperreactividad Bronquial/fisiopatología , Liofilización , Vacunas de Productos Inactivados/farmacología , Animales , Vacuna BCG/administración & dosificación , Vacuna BCG/efectos adversos , Bronquitis/etiología , Bronquitis/patología , Células Dendríticas/patología , Eosinofilia/etiología , Eosinofilia/patología , Cobayas , Hipersensibilidad/complicaciones , Inyecciones Subcutáneas , Interleucina-10/biosíntesis , Pulmón/patología , Masculino , Ratones , Ovalbúmina/inmunología , Neumonía/etiología , Neumonía/patología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/efectos adversos
13.
J Mol Graph Model ; 87: 41-47, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30481698

RESUMEN

In our recent article, we had a successful experience in applying binuclear chromium (III) model ([Cr2F(tBuCO2)2(H2O)2(OH)4]-1) instead of real chromium-wheel host complex ([Cr8F8(tBuCO2)16]) to calculate the effect of bridged-ligands substitution on the exchange coupling constants (J) values of the complexes. In this work our experienced procedure was used to evaluate the effect of pivalate (tBuCO2) ligands substitution on the J values of the complexes. For this, at first two new groups of complexes were designed based on the replacement of pivalate by X-tBuCO2 and X-iPrCO2 anionic ligands (where X represents F, Cl, Br and I halogens) and then their J values were calculated. Since the existence of two halogen atoms in the structures of complexes leads to form different conformers, at first step a conformational analysis was carried out to identify the stable conformers of each complex. In X-tBuCO2-containing complexes four stable conformers were recognized, while X-iPrCO2-containing complexes had three stable conformers. At next step the J values of each of these conformers were calculated for all complexes. It was found that depending on which conformer was formed, the effect of these substitutions in each complex could be different, leading to a decrease or increase in the antiferromagnetic property of the complex. In both types of complexes, the formation of the least stable conformer, Conf1, led to the strengthening of the antiferromagnetic property of the complex but the impacts of the substitutions in other conformers were diverse. These new designed complexes could be considered as novel synthetic targets with different magnetic properties.


Asunto(s)
Cromo/química , Fenómenos Magnéticos , Modelos Moleculares , Algoritmos , Enlace de Hidrógeno , Ligandos , Conformación Molecular , Estructura Molecular
14.
Sci Rep ; 9(1): 3153, 2019 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-30816152

RESUMEN

In the recent years, cancer research succeeded with sensitive detection methods, targeted drug delivery systems, and the identification of a large set of genes differently expressed. However, although most therapies are still based on antimitotic agents, which are causing wide secondary effects, there is an increasing interest for metabolic therapies that can minimize side effects. In the early 20th century, Otto Warburg revealed that cancer cells rely on the cytoplasmic fermentation of glucose to lactic acid for energy synthesis (called "Warburg effect"). Our investigations aim to reverse this effect in reprogramming cancer cells' metabolism. In this work, we present a metabolic therapy specifically targeting the activity of specific enzymes of central carbon metabolism, combining the METABLOC bi-therapeutic drugs combination (Alpha Lipoic Acid and Hydroxycitrate) to Metformin and Diclofenac, for treating tumors implanted in mice. Furthermore, a dynamic metabolic model describing central carbon metabolism as well as fluxes targeted by the drugs allowed to simulate tumors progression in both treated and non-treated mice, in addition to draw hypotheses on the effects of the drugs on tumor cells metabolism. Our model predicts metabolic therapies-induced reversed Warburg effect on tumor cells.


Asunto(s)
Carcinogénesis/efectos de los fármacos , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carbono/metabolismo , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patología , Línea Celular Tumoral , Citratos/farmacología , Diclofenaco/farmacología , Glucosa/metabolismo , Xenoinjertos , Humanos , Ácido Láctico/metabolismo , Metformina/farmacología , Ratones , Ácido Tióctico/farmacología
15.
Artículo en Inglés | MEDLINE | ID: mdl-28319795

RESUMEN

This paper studies donor-acceptor systems which incorporate benzodithiophene (BDT), benzodifuran (BDF) and benzodipyrrole (BDP) units as the electron-rich monomer with TT unit representing the electron-deficient monomer. This research is based on employing density functional theory (DFT) and time-dependent DFT (TD-DFT). The highest occupied molecular orbitals (HOMO) and the lowest unoccupied molecular orbitals (LUMO), HOMO-LUMO gaps and dihedral-angles of these copolymers were calculated using oligomer extrapolation technique and periodic boundary condition (PBC) method. The optical band gaps and UV-vis absorption spectra of aforementioned copolymers were obtained by TD-DFT at the same level of theory. Based on the fair agreement between PBC-DFT calculated results and experimental data, the substituent effects of Cl, Br, CCH, COH, NO2, OH, SH and NH2 groups were investigated by PBC-DFT method. The difference between the ground and excited-states dipole moment (Δµge) of all derivatives were also calculated. Taking these results into account, a better understanding of the substituent effects on the photo-physical properties of the copolymers under study was achieved. Due to the shift of HOMO and LUMO energy levels, smaller band gaps and higher Δµge are observed in some derivatives. The calculation results demonstrate that the substitution of COH and NO2 by fluorine in BDF-TT and BDP-TT leads to higher maximum theoretical efficiencies (η).

16.
Microbes Infect ; 8(9-10): 2341-51, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16872860

RESUMEN

BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.


Asunto(s)
Vacuna BCG/inmunología , Células Dendríticas/inmunología , Ganglios Linfáticos/inmunología , Tuberculosis/prevención & control , Administración Rectal , Animales , Animales Recién Nacidos , Vacuna BCG/administración & dosificación , Vacuna BCG/farmacocinética , Antígenos CD11/inmunología , Linfocitos T CD4-Positivos/inmunología , Células CACO-2 , Quimiocina CCL20 , Quimiocinas CC/inmunología , Humanos , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Proteínas Inflamatorias de Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Recto/inmunología , Tuberculosis/inmunología
17.
Metabolites ; 6(4)2016 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-27706102

RESUMEN

To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi) and concentrations of key metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells, extracted from fresh human colon tissues. Cells were sorted by elutriation and segregated in different phases of the cell cycle (G0/G1/S/G2/M) in order to study their redox (NAD, NADP) and bioenergetic (ATP, pHi) status. Our results show that the average ATP concentration over the cell cycle is higher and the pHi is globally more acidic in normal proliferating cells. The NAD+/NADH and NADP+/NADPH redox ratios are, respectively, five times and ten times higher in cancer cells compared to the normal cell population. These energetic differences in normal and cancer cells may explain the well-described mechanisms behind the Warburg effect. Oscillations in ATP concentration, pHi, NAD+/NADH, and NADP+/NADPH ratios over one cell cycle are reported and the hypothesis addressed. We also investigated the mitochondrial membrane potential (MMP) of human and mice normal and cancer cell lines. A drastic decrease of the MMP is reported in cancer cell lines compared to their normal counterparts. Altogether, these results strongly support the high throughput aerobic glycolysis, or Warburg effect, observed in cancer cells.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 136 Pt B: 373-80, 2015 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-25311524

RESUMEN

PTBs polymers with thieno[3,4-b]thiophene [TT] and benzodithiophene [BDT] units have particular properties, which demonstrate it as one of the best group of donor materials in organic solar cells. In the present work, density functional theory (DFT) is applied to investigate the optimized structure, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), band gap and dihedral angle of PTB7 at B3LYP/6-31G(d). Two different approaches are applied to carry out these investigations: Oligomer extrapolation technique and periodic boundary condition (PBC) method. The results obtained from PBC-DFT method are in fair agreement with experiments. Based on these reliable outcomes; the investigations continued to perform some derivatives of PTB7. In this study, sulfur is substituted by nitrogen, oxygen, silicon, phosphor or selenium atoms in pristine PTB7. Due to the shift of HOMO and LUMO levels, smaller band gaps are predicted to appear in some derivatives in comparison with PTB7. Maximum theoretical efficiencies, η, of the mentioned derivatives as well as local difference of dipole moments between the ground and excited states (Δµge) are computed. The results indicate that substitution of sulfur by nitrogen or oxygen in BDT unit, and silicon or phosphor in TT unit of pristine PTB7 leads to a higher η as well as Δµge.


Asunto(s)
Electrónica , Fenómenos Ópticos , Polímeros/química , Teoría Cuántica , Energía Solar , Tiofenos/química , Electrones , Modelos Moleculares , Conformación Molecular , Termodinámica
19.
Iran J Public Health ; 44(2): 244-53, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25905059

RESUMEN

BACKGROUND: Food security is a multi-dimensional phenomenon. The objective of this study was to identify and prioritize major indices for determining food insecurity in Iran. METHODS: Descriptive study using the Delphi method was conducted through an email-delivered questionnaire. Forty-three senior experts at national or provincial level were selected based on their work experience and educational background through study panel consultation and snowballing from Tehran and other cities of Iran. During two rounds of Delphi, participants were asked to identify priority indicators for food security at provincial level in Iran. RESULTS: Sixty five percent of Delphi panel participated in the first round and eighty-nine percent of them participated in the second round of Delphi. Initially, 243 indices were identified through review of literature; after excluding indictors, which was not available or measurable at provincial level in Iran, 103 indictors remained. The results of study showed that experts identified "percentage of individuals receiving less than 70% of daily energy requirement" with a median score of 90, as the most influential index for determining food insecurity. "Food expenses as a proportion of the overall expenses of the family", "per capita of dietary energy supply", and "provision of micro-nutrient supply requirement per capita" with median of 80 were in the second rank of food security priority indicators. CONCLUSION: Out of 243 identified indicators for food security, 38 indicators were selected as the most priority indicators for food security at provincial level in Iran.

20.
Artículo en Inglés | MEDLINE | ID: mdl-21096738

RESUMEN

Nervous system conveys information by electrical signals called 'spikes', therefore, spikes detection and sorting are challenging topics in the neural data processing. The principal component analysis (PCA) is a convenient tool for clustering spikes; however it has some disadvantages for closely shaped and overlapped spikes. For such the cases, an algorithm based on the combination of the principal component analysis and undecimated wavelet transform, is proposed to enhance the cluster formation from the spikes mapping. These results indicate that the principal component analysis used in combination with the undecimated wavelet has a better performance in the spike sorting. This can lead to more compact and separate clusters in comparison with the PCA clustering and more efficient spike sorting.


Asunto(s)
Neurofisiología/métodos , Análisis de Componente Principal/métodos , Procesamiento de Señales Asistido por Computador , Algoritmos , Humanos
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