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BACKGROUND: Cell-free DNA (cfDNA) is a source for liquid biopsy used for cancer diagnosis, therapy selection, and disease monitoring due to its non-invasive nature and ease of extraction. However, cfDNA also participates in cancer development and progression by horizontal transfer. In humans, cfDNA circulates complexed with extracellular vesicles (EV) and macromolecular complexes such as nucleosomes, lipids, and serum proteins. The present study aimed to demonstrate whether cfDNA not associated with EV induces cell transformation and tumorigenesis. METHODS: Supernatant of the SW480 human colon cancer cell line was processed by ultracentrifugation to obtain a soluble fraction (SF) and a fraction associated with EV (EVF). Primary murine embryonic fibroblast cells (NIH3T3) underwent passive transfection with these fractions, and cell proliferation, cell cycle, apoptosis, cell transformation, and tumorigenic assays were performed. Next, cfDNA was analyzed by electronic microscopy, and horizontal transfer was assessed by human mutant KRAS in recipient cells via PCR and recipient cell internalization via fluorescence microscopy. RESULTS: The results showed that the SF but not the EVF of cfDNA induced proliferative and antiapoptotic effects, cell transformation, and tumorigenesis in nude mice, which were reduced by digestion with DNAse I and proteinase K. These effects were associated with horizontal DNA transfer and cfDNA internalization into recipient cells. CONCLUSIONS: The results suggest pro-tumorigenic effects of cfDNA in the SF that can be offset by enzyme treatment. Further exploration of the horizontal tumor progression phenomenon mediated by cfDNA is needed to determine whether its manipulation may play a role in cancer therapy.
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Ácidos Nucleicos Livres , Humanos , Animais , Camundongos , Ácidos Nucleicos Livres/genética , Camundongos Nus , Células NIH 3T3 , Carcinogênese , DNARESUMO
The adhesion of initial colonizers such as Streptococcus mutans to collagen is critical for dentinal and root caries progression. One of the most described pathological and aging-associated changes in collagen-including dentinal collagen-is the generation of advanced glycation end-products (AGEs) such as methylglyoxal (MGO)-derived AGEs. Despite previous reports suggesting that AGEs alter bacterial adhesion to collagen, the biophysics driving oral streptococcal attachment to MGO-modified collagen remains largely understudied. Thus, the aim of this work was to unravel the dynamics of the initial adhesion of S. mutans to type I collagen in the presence and absence of MGO-derived AGEs by employing bacterial cell force spectroscopy with atomic force microscopy (AFM). Type I collagen gels were treated with 10 mM MGO to induce AGE formation, which was characterized with microscopy and enzyme-linked immunosorbent assay. Subsequently, AFM cantilevers were functionalized with living S. mutans UA 159 or Streptococcus sanguinis SK 36 cells and probed against collagen surfaces to obtain force curves displaying bacterial attachment in real time, from which the adhesion force, number of events, Poisson analysis, and contour and rupture lengths for each individual detachment event were computed. Furthermore, in silico computer simulation docking studies between the relevant S. mutans UA 159 collagen-binding protein SpaP and collagen were computed, in the presence and absence of MGO. Overall, results showed that MGO modification increased both the number and adhesion force of single-unbinding events between S. mutans and collagen, without altering the contour or rupture lengths. Both experimental and in silico simulations suggest that this effect is due to increased specific and nonspecific forces and interactions between S. mutans UA 159 and MGO-modified collagen substrates. In summary, these results suggest that collagen alterations due to aging and glycation may play a role in early bacterial adherence to oral tissues, associated with conditions such as aging or chronic hyperglycemia, among others.
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Colágeno Tipo I , Óxido de Magnésio , Colágeno Tipo I/metabolismo , Simulação por Computador , Óxido de Magnésio/metabolismo , Streptococcus , Streptococcus mutans , Aderência Bacteriana , Colágeno/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Biofilmes , Microscopia de Força Atômica/métodosRESUMO
Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05314790.
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Hipotireoidismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Hipotireoidismo/tratamento farmacológico , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tiroxina/uso terapêuticoRESUMO
It is estimated that up to 10% of gastric carcinomas show familial aggregation. In contrast, around 1-3 % (approximately 33,000 yearly) are genuinely hereditary. Hereditary diffuse gastric cancer (HDGC) is a rare malignancy characterized by autosomal dominant inheritance of pathological variants of the CDH1 and CTNNA1 genes encoding the adhesion molecules E-cadherin and α-catenin, respectively. The multifocal nature of the disease and the difficulty of visualizing precursor lesions by endoscopy underscore the need to be aware of this malignancy as surgical prevention can be fully protective. Here, we provide an overview of the main epidemiological, clinical, genetic, and pathological features of HDGC, as well as updated guidelines for its diagnosis, genetic testing, counseling, surveillance, and management. We conclude that HDGC is a rare, highly penetrant disease that is difficult to diagnose and manage, so it is necessary to correctly identify it to offer patients and their families' adequate management following the recommendations of the IGCL. A critical point is identifying a mutation in HDGC families to determine whether unaffected relatives are at risk for cancer.
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Adenocarcinoma , Neoplasias Gástricas , Caderinas/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Mutação , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genéticaRESUMO
INTRODUCTION: Headache is common in the general population and a frequent reason for medical consultation. OBJECTIVES: To describe the characteristics of patients attending the Emergency Department (ED) for headache. METHODS: A descriptive study with prospective collection of 100 consecutive patients over 15 years old who attended our ED due to headache as the main complaint. RESULTS: Headache accounted for 1,4% of ED visits. The most common age range is between 31 and 45 years and the majority of the patients are females (61%). We diagnosed 67 primary and 33 secondary headaches. The most frequent diagnosis was migraine, with 36% of cases. One out of 3 patients had a history of headache and 4 out of 5 consulted by their own decision. Only a small percentage of patients were admitted as inpatients (12%), and 3 out of 5 were referred to Primary Care. Complementary tests were performed on 84% of the patients. One CT scan was performed for every 3 patients. A total of 80% patients was correctly diagnosed by the ED physicians. CONCLUSIONS: Headache is a frequent complaint in the ED, where primary headaches are the most common with migraine being the most frequent reason for consultation. In our setting, there is a good screening and diagnosis of headaches, as well as an adequate use of the available resources in the ED for their diagnosis and management.
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In this study the LCA methodology is applied in order to satisfy two goals: i) to evaluate the hot spots in site-specific production chain of biodiesel from terrestrial and micro-algae feedstock; ii) to compare quantitatively, utilizing primary data, the impacts of the first generation in respect to the third generation bio-fuels. Results show that micro-algae are neither competitive yet with traditional oil crops nor with fossil fuel. The use of renewable technologies as photovoltaics and biogas self production might increase the competitiveness of micro-algae oil. Further investigations are however necessary to optimize their production chain and to increase the added value of co-products.
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Biocombustíveis , Produtos Agrícolas , Meio Ambiente , Combustíveis Fósseis , TecnologiaRESUMO
La disfagia es una alteración del proceso deglutorio que afecta la seguridad, eficacia y calidad de la alimentación. Una de las estrategias más utilizadas para su intervención es la modificación de la viscosidad de los alimentos, sin embargo, la metodología empleada para determinarla es subjetiva y no está estandarizada. Esta investigación buscó establecer el dominio de los fonoaudiólogos para determinar el tipo de viscosidad. Se utilizaron 12 muestras de alimentos líquidos, cuyas viscosidades fueron determinadas objetivamente con un viscosímetro rotacional, clasificándolos bajo las categorías: fino, néctar, miel y pudín. Posteriormente, cuarenta fonoaudiólogos que se desempeñan en el área de los trastornos de la deglución en centros de salud de la Región Metropolitana en Santiago de Chile, evaluaron subjetivamente las 12 muestras. Con esta información se realizó un estudio comparativo objetivo/subjetivo para establecer el dominio de los profesionales. Los participantes lograron 66,87 por ciento de efectividad en la valoración del grado de viscosidad de las muestras, con un mejor rendimiento para aquellas viscosidades tipo fino y pudín. La repetibilidad intrasujeto fue superior a 75 por ciento para el 60 por ciento de la muestra. Existen además indicadores de que el tiempo de ejercicio profesional incidiría positivamente en estas capacidades, no así el nivel de perfeccionamiento. Por último, se establece que los fonoaudiólogos evaluados poseen un dominio regular para determinar el grado de viscosidad de alimentos líquidos, pero este no es homogéneo. Se hace necesario incentivar el conocimiento y manejo adecuado en este tema, en búsqueda de consensuar procedimientos y criterios que permitan una mayor estandarización al respecto.
Dysphagia is a disruption in the swallowing process which hinders movement of food, affecting the safety, efficiency and quality of feeding. Treatment includes different strategies, with viscosity modification being one of the most used strategies nowadays. However, the methodology used to determine food viscosity is subjective and not standardized. In this regard, this study seeks to establish the speech pathologists skills in determining the different types of food viscosity. Twelve samples of liquid foods were used, whose viscosities were determined objectively with a rotational viscometer. Then, the samples of liquid foods were classified into four categories: thin liquid, nectar, honey, and pudding. Forty speech pathologists working with patients diagnosed with dysphagia at health centers in the Metropolitan Region, Chile, subjectively evaluated the samples of liquid foods. Finally, an objective/subjective comparative study was performed to determine their competence in identifying the different types of food viscosity. Near 66,87 percent of the participants performed well in the task. Participants performed better in determining thin and pudding viscosities. Over 75 percent of intra-subject repeatability was obtained for 60 percent of the sample. Unlike postgraduate studies, it could be observed that professional experience has a positive impact on these skills. Finally, the results of this study indicate that the participants have intermediate skills in determining the degree of viscosity of liquid food. However, this is not homogeneous, and therefore, it is necessary to enhance our understanding and proper management of dysphagia. Agreement on standard procedures is also necessary.
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Humanos , Manipulação de Alimentos , Competência Profissional , Reologia , Fonoaudiologia , Transtornos de Deglutição/terapia , ViscosidadeRESUMO
The transport properties at finite temperature of crystalline organic semiconductors are investigated, within the Su-Schrieffer-Heeger model, by combining an exact diagonalization technique, Monte Carlo approaches, and a maximum entropy method. The temperature-dependent mobility data measured in single crystals of rubrene are successfully reproduced: a crossover from super- to subdiffusive motion occurs in the range 150≤T≤200 K, where the mean free path becomes of the order of the lattice parameter and strong memory effects start to appear. We provide an effective model, which can successfully explain features of the absorption spectra at low frequencies. The observed response to slowly varying electric field is interpreted by means of a simple model where the interaction between the charge carrier and lattice polarization modes is simulated by a harmonic interaction between a fictitious particle and an electron embedded in a viscous fluid.
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Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1 and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wildtype MDA-MB-231 cells, to demonstrate its effects as a chemo or radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo or radiosensitizing agent regardless of the BRCA1 status in breast cancer.
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Neoplasias da Mama/metabolismo , Cisplatino/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Niacinamida/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Apoptose , Proteína BRCA1/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Dano ao DNA , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Radiação IonizanteRESUMO
A system for time-discretized spectroscopic measurements of the vacuum ultraviolet (VUV) emission from spark discharges in the 60-160 nm range has been developed for the study of early plasma-forming phenomena. The system induces a spark discharge in an environment close to atmospheric conditions created using a high speed puff value, but is otherwise kept at high vacuum to allow for the propagation of VUV light. Using a vertical slit placed 1.5 mm from the discharge the emission from a small cross section of the discharge is allowed to pass into the selection chamber consisting of a spherical grating, with 1200 grooves/mm, and an exit slit set to 100 µm. Following the exit slit is a photomultiplier tube with a sodium salicylate scintillator that is used for the time discretized measurement of the VUV signal with a temporal resolution limit of 10 ns. Results from discharges studied in dry air, Nitrogen, SF6, and Argon indicate the emission of light with wavelengths shorter than 120 nm where the photon energy begins to approach the regime of direct photoionization.
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La hemorragia intraventricular (HIV) es una causa importante de daño cerebral en los recién nacidos prematuros. Su impacto negativo en el resultado del desarrollo neurológico se relaciona no sólo a su impacto directo, sino que también a las lesiones asociadas, como la hidrocefalia posthemorrágica (HPH). En la mayoría de los casos, la hidrocefalia es causada por la alteración de la reabsorción del líquido cefalorraquídeo (LCR) debido a la inflamación de las vellosidades subaracnoideas por el contacto con la sangre. El drenaje ventricular se utiliza a menudo como un procedimiento temporal para manejo de la HPH y algunos pacientes tratados con drenaje ventricular no requieren una derivación permanente; de no ser así, las derivaciones más usadas en los prematuros incluyen la ventriculoperitoneal (DVP), seguida por las derivaciones ventriculosubgaleal y ventriculoatrial. Las derivativas se consideran el tratamiento definitivo para la HPH; pero puede asociarse a complicaciones, tales como la infección, obstrucción, rechazo y el drenaje insuficiente. Otra alternativa, es la derivación ventrículopleural. Sin embargo, esta alternativa de derivación se vincula a otras complicaciones específicas, principalmente el neumotórax y el derrame pleural. Se presenta el caso clínico de EAV, quien a raíz de un parto prematuro, complicado con Hemorragia intraventricular, desarrolló Hidrocefalia y un quiste de Fosa Posterior, debiendo intervenirse en 36 oportunidades, por múltiples complicaciones. Durante su evolución se instalaron catéteres en prácticamente todos los sitios posibles, lográndose finalmente la solución del problema. Se revisa la literatura
Ventricular haemorrhage is an important cause of neurologic damage in preterm babies. Its negative impact in the final neurologic damage is not just related with the direct impact, but also with associated lesions like posthaemorrhagic hydrocephalus (PHH). In most of cases, hydrocephalus is caused by impaired cerebrospinal fluid (CEF) resorption due to the inflammation of the Arachnoid granulations because of the contact with blood. Ventricular drainage system is often used as a temporal procedure for the management of the PHH in children who have not a good response to serials lumbar punctures. Some patients treated with ventricular drainage don't need a permanent derivation, but if they do the most used in preterm babies include ventriculoperitoneal derivation (VPD) followed by ventriculosubgaleal and ventriculoatrial derivation. Derivation is considered the definitive treatment for PHH, but it can be associated with some complications as infection, obstruction and insufficient drainage. Another option is ventriculopleural derivation but this alternative is related to other complications like pneumothorax and pleural effusion. The presentation is about the case of the newborn EAV, who after preterm birth, complicated with intraventricular haemorrhage, developed hydrocephalus and a posterior fossa cyst, requiring 36 surgical interventions because of multiple complications. During its evolution he needed catheters installations in almost every possible sites, finally getting the problem solved. The literature is reviewed
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Humanos , Masculino , Ventrículos Cerebrais , Drenagem/métodos , Fossa Craniana Posterior , Hemorragias Intracranianas , Hemorragias Intracranianas/complicações , Hidrocefalia , Diagnóstico por ImagemRESUMO
Environmental profiles of mineral nitrogen fertilizers were used to evaluate the environmental disturbances related to their use in cultivation systems in Europe. Since the production of mineral fertilizers requires a large amount of energy, the present study of bioenergy systems is relevant in order to achieve crop yields less dependent on fossil fuels and to reduce the environmental impact due to fertilization. In this study, the suitability of the LCA methodology to analyze the environmental impact of sunflower cultivation systems with different forms of mineral nitrogen fertilizers urea and ammonium nitrate was investigated. Effects on climate change were estimated by the use of Ecoinvent 2.2 database default value for soil N2O emission factor (1%) and local emission data (0.8%) of mineral nitrogen applied to soils. LCA analysis showed a higher impact on environmental categories (human health and ecosystem quality) for the system in which urea was used as a nitrogen source. Use of urea fertilizer showed a higher impact on resource consumption due to fossil fuel consumption. Use of mineral nitrogen fertilizers showed a higher environmental burden than other inputs required for sunflower cultivation systems under study. Urea and ammonium nitrate showed, respectively, a 7.8% and 4.9% reduced impact of N2O as greenhouse gas by using direct field data of soil N2O emission factor compared to the default soil emission factor of 2006 IPCC Guidelines. Use of ammonium nitrate as mineral nitrogen fertilizer in sunflower cultivation would have a lower impact on environmental categories considered. Further environmental analysis of available technologies for fertilizer production might be also evaluated in order to reduce the environmental impacts of each fertilizer.
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Agricultura/métodos , Monitoramento Ambiental/métodos , Fertilizantes/análise , Helianthus/crescimento & desenvolvimento , Compostos de Nitrogênio/metabolismo , Conservação dos Recursos Naturais , Europa (Continente) , Nitratos/metabolismo , Ureia/metabolismoRESUMO
PURPOSE: The antihypertensive hydralazine has recently been repositioned as DNA demethylating for the epigenetic therapy of cancer. As the acetylator phenotype is the key determinant of its plasma levels, the dose of hydralazine needs to be adjusted for the acetylation status of patients. METHODS: The pharmacokinetics of orally administered hydralazine was evaluated in 26 healthy volunteers (13 slow and 13 fast acetylators) after a single dose of 182 mg administered as a controlled-release tablet. Plasma levels of hydralazine were analyzed in 85 cancer patients treated with this formulation at a dose of 83 mg/day and 182 mg/day for slow and fast acetylators, respectively. RESULTS: The C(max) and t(max) of hydralazine for fast acetylators were 208.4 ± 56.9 SD ng/ml and 2.8 ± 2.5 h, respectively. The corresponding results for slow acetylators were 470.4 ± 162.8 ng/ml, and 4.4 ± 3.1 h. Healthy volunteers who were fast acetylators had no clinically significant changes in blood pressure and heart rate or any other side-effect, however, slow acetylators had transient episodes of headache, tachycardia and faintness. Among 85 cancer patients that received either 182 mg or 83 mg of hydralazine daily, according to their acetylator status, the mean concentrations of hydralazine in plasma were 239.1 ng/ml and 259.2 ng/ml for fast and slow acetylators, respectively. These differences were not significantly different, p = 0.3868. CONCLUSIONS: The administration of dose-adjusted controlled-release hydralazine according to the acetylation status of cancer patients yields similar levels of hydralazine.
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Anti-Hipertensivos/farmacocinética , Hidralazina/farmacocinética , Neoplasias/tratamento farmacológico , Acetilação , Administração Oral , Adolescente , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Estudos de Casos e Controles , Metilação de DNA/efeitos dos fármacos , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Feminino , Humanos , Hidralazina/administração & dosagem , Hidralazina/efeitos adversos , Masculino , Neoplasias/patologia , Fenótipo , Comprimidos , Adulto JovemRESUMO
Sub-Tenon anesthesia is an effective, well-tolerated technique for surgery in the anterior or posterior compartments of the eye. The advantages of this block are comparable to those of peribulbar and retrobulbar anesthesia and complications are minimal. Sub-Tenon anesthesia provides better analgesia than akinesia. Most studies suggest that sub-Tenon anesthesia is a good technique to choose, given that potential adverse effects are fewer than for other regional blocks and analgesia and akinesia are superior.
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Anestesia por Condução/métodos , Procedimentos Cirúrgicos Oftalmológicos , Anestesia por Condução/efeitos adversos , Anestesia por Condução/instrumentação , Desenho de Equipamento , Humanos , Procedimentos Cirúrgicos Oftalmológicos/métodosRESUMO
The Notch signalling pathway has recently been linked to T helper 1 (Th1)/T helper 2 (Th2) cell polarization via a mechanism involving differential expression of Notch ligands, Delta-like and Jagged, in antigen-presenting cells. However, whether stimuli other than pathogen-derived factors are involved in the regulation of Notch ligand expression in dendritic cells (DCs) remains unknown. Here, we address the effect of T helper cells (Th1 and Th2) on Delta-like 4 and Jagged 2 expression in bone marrow-derived DCs. We demonstrate that both Th1 and Th2 cells induce Delta-like 4 mRNA expression in DCs, in a process that is, in part, mediated by CD40 signalling. In contrast, only Th2 cells induce a significant increase in Jagged 2 mRNA levels in DCs. Additionally, we show that IL-4, a hallmark Th2 cytokine, plays a role in Jagged 2 expression, as evidenced by the fact that cholera toxin, a Th2-promoting stimulus, induces Jagged 2 mRNA expression in DCs only in the presence of IL-4. Finally, we demonstrate that DCs also express Notch 1 and that this expression is downregulated by IL-4. These data suggest that Notch ligands are differentially regulated in DCs: Delta-like 4 is regulated by T helper cells and by pathogen-derived Th1 stimuli, whereas Jagged 2 is regulated by Th2 cells and pathogen-derived Th2-promoting stimuli. Based on our results, we propose that the positive feedback loop that Th2 cells exert on T cell polarization may involve the induction of Jagged 2 expression in DCs.
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Células Dendríticas/imunologia , Proteínas de Membrana/biossíntese , Células Th1/imunologia , Células Th2/imunologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Antígenos CD40/imunologia , Proteínas de Ligação ao Cálcio , Células Dendríticas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Interleucina-4/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteína Jagged-2 , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Transdução de SinaisRESUMO
We construct a very simple epidemic model for influenza spreading in an age-class-distributed population, by coupling a lattice gas model for the population dynamics with a SIR stochastic model for susceptible, infected and removed/immune individuals. We use as a test case the age-distributed Italian epidemiological data for the novel influenza A(H1N1). The most valuable features of this model are its country-independent and virus-independent structure (few demographic, social and virological data are used to fix some parameters), its large statistic due to a very short run-time machine, and its easy generalizability to include mitigation strategies. In spite of its simplicity, the model presented reproduces the epidemiological Italian data, with sensible predictions for the reproduction number and theoretically interesting results for the generation time distribution.
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Gases , Vírus da Influenza A Subtipo H1N1/fisiologia , Influenza Humana/epidemiologia , Influenza Humana/transmissão , Modelos Biológicos , Pandemias , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Difusão , Humanos , Lactente , Recém-Nascido , Itália/epidemiologia , Pessoa de Meia-Idade , Método de Monte Carlo , Pandemias/estatística & dados numéricos , Reprodutibilidade dos Testes , Processos Estocásticos , Fatores de Tempo , Adulto JovemRESUMO
INTRODUCTION: This trial aimed to evaluate the safety and efficacy of epigenetic therapy associated with cisplatin chemoradiation in FIGO Stage IIIB patients. METHODS: Hydralazine containing either 182 mg for rapid-, or 83 mg for slow acetylators and magnesium valproate were administered at 30 mg/kg tid. Both drugs were taken until intracavitary therapy was finished. Pelvic external beam radiation and low-dose rate brachytherapy were administered at a total cumulative dose to point A of at least 85 Gy. Weekly cisplatin at 40 mg/m2 was delivered for six cycles. RESULTS: Twenty-two patients were included and 18 (82%) patients completed treatment. Mean dose to point A was 84.6 + 2.2. Median number of cisplatin cycles was 5.5 (range, 1-6). Brachytherapy was delayed for technical reasons; the mean overall treatment time was 11.8 weeks. Grade 3 anemia, leucopenia, neutropenia, and thrombocytopenia were observed in 9%, 45%, 45%, and 9% of patients, respectively. CONCLUSIONS: Hydralazine and valproate are well-tolerated and safe when administered with cisplatin chemoradiation. Unfortunately, the suboptimal administration of brachytherapy for technical reasons in this study, precluded assessing the efficacy of epigenetic therapy. However, the tolerability of this regimen administered concurrent to radiation needs to be further tested.
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Antineoplásicos/uso terapêutico , Braquiterapia , Cisplatino/uso terapêutico , Epigênese Genética , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Braquiterapia/efeitos adversos , Cisplatino/efeitos adversos , Terapia Combinada , Feminino , Humanos , Hidralazina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Ácido Valproico/administração & dosagemRESUMO
UNLABELLED: The aim of our study is to observe the self-injured inflicted dimension in prisoners and to estimate the presence of one correlation with the anxiety-depressive syndrome. MATERIALS AND METHODS: From 15th of Oct 2006 till 31st Aug 2009 we have admitted to our department 150 patients that showed previous or recent evidences of self inflicted injuries and the use and abuse of tranquillizers and antidepressive drugs. The patients were classified in data base and we made an observation study. RESULTS: Out of 150 (100%) patients admitted to hospital, 55 (37%) patients had had a recent or previous episode of self-injured inflicted, 23 (15%) patients had taken antidepressive drugs and 72 (48%) patients had been in treatment with benzodiazepines. Among 55 patients that reported on medical history evidences of self-injured inflicted only 4 (7%) had taken antidepressive drugs and 18 (33%) had been in treatment with benzodiazepines. Among 18 patients in treatment with benzodiazepines, 12 (67%) patients had begun to use it during the detention regime. CONCLUSION: The phenomenon of self-injured inflicted among the patients that came to our department is very widespread and it resulted to be more frequent than in common people. We observed a correlation among the episodes of self-injured inflicted and the anxiety-depressive syndrome. Often the hardships is pre-existent to admittance in prison and the detention stresses that phenomenon. In fact, most of episodes of self-injured inflicted occurred during detention regime.
Assuntos
Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo/epidemiologia , Prisioneiros , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Transtornos de Ansiedade/complicações , Transtorno Depressivo/complicações , Feminino , Hospitalização , Humanos , Masculino , Cidade de Roma , Comportamento Autodestrutivo/etiologiaRESUMO
Organ transplantation success depends principally on avoiding rejection, a purpose almost accomplished with immunosuppressant therapy. Nevertheless, drug side effects have promoted the search for other mechanisms to restrain alloresponses. T-regulatory cells (Treg) might exert that function. Campath 1H (C1H) induces Treg proliferation in the period subsequent to T-cell depletion following C1H administration. In the present study, the status of Treg and de novo HLA antibody production was determined posttransplantation when T-cell repopulation had been completed. In 14 patients, the following parameters were analyzed: renal function, rejection, Treg, panel-reactive antibody (PRA), and HLA antibodies. Patient and graft survivals were 100%. At the moment of Treg determination (20 months following transplant) the mean tacrolimus level was 8.4 ng/mL. One patient experienced an antibody-mediated rejection at 15 months after transplantation while having 3.2% Treg, with excellent treatment responses. Mean leukocyte and lymphocyte counts were 5752 and 1183 cells/mm(3); the mean peripheral blood percentage of Treg of 7.1% +/- 5.9% was not different from that observed in subjects without induction (mean 5.5% +/- 2.5%). Three patients (21%) showed Treg greater than 8.0%. In seven patients, we compared Treg at 4 and 20 months posttransplant, observing a decline from a mean of 19.9% to 5.9% (P = .05). In seven recipients, posttransplant PRA was determined; five of them became "de novo" sensitized, three with a mean class I PRA of 16% and two with a mean class II PRA of 37%. In conclusion, patient and graft survivals were excellent, mean Treg percentage was not elevated with results lower than in the early posttransplant period. Rejection incidence was negligible. Late "de novo" sensitization occurred in 70% showing that B cell-mediated alloresponses were only partially controlled among recipients induced with C1H even when associated with sustained anticalcineurin treatment.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Transplante de Rim/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados , Azatioprina/uso terapêutico , Complexo CD3/sangue , Antígenos CD4/sangue , Cadáver , Ciclosporina/uso terapêutico , Feminino , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunossupressores/uso terapêutico , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Doadores de TecidosRESUMO
A theoretical and numerically study of dynamical properties in the sol-gel transition is presented. In particular, the complex phenomenology observed experimentally and numerically in gelling systems is reproduced in the framework of percolation theory, under simple assumptions on the relaxation of single clusters. By neglecting the correlation between particles belonging to different clusters, the quantities of interest (such as the self intermediate scattering function, the dynamical susceptibility, the Van-Hove function, and the non-Gaussian parameter) are written as superposition of those due to single clusters. Connection between these behaviors and the critical exponents of percolation are given. The theoretical predictions are checked in a model for permanent gels, where bonds between monomers are described by a finitely extendable nonlinear elastic potential. The data obtained in the numerical simulations are in good agreement with the analytical predictions.