RESUMO
Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease caused by the protozoa Trypanosoma cruzi, affecting nearly 7 million people only in the Americas. Polyamines are essential compounds for parasite growth, survival, and differentiation. However, because trypanosomatids are auxotrophic for polyamines, they must be obtained from the host by specific transporters. In this investigation, an ensemble of QSAR classifiers able to identify polyamine analogs with trypanocidal activity was developed. Then, a multi-template homology model of the dimeric polyamine transporter of T. cruzi, TcPAT12, was created with Rosetta, and then refined by enhanced sampling molecular dynamics simulations. Using representative snapshots extracted from the trajectory, a docking model able to discriminate between active and inactive compounds was developed and validated. Both models were applied in a parallel virtual screening campaign to repurpose known drugs as anti-trypanosomal compounds inhibiting polyamine transport in T. cruzi. Montelukast, Quinestrol, Danazol, and Dutasteride were selected for in vitro testing, and all of them inhibited putrescine uptake in biochemical assays, confirming the predictive ability of the computational models. Furthermore, all the confirmed hits proved to inhibit epimastigote proliferation, and Quinestrol and Danazol were able to inhibit, in the low micromolar range, the viability of trypomastigotes and the intracellular growth of amastigotes.
Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Putrescina/uso terapêutico , Ligantes , Danazol/uso terapêutico , Quinestrol/uso terapêutico , Poliaminas/química , Poliaminas/uso terapêutico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Proteínas de Membrana Transportadoras/uso terapêutico , Tripanossomicidas/farmacologia , Tripanossomicidas/químicaRESUMO
PURPOSE: To evaluate the clinical performance of refurbished resin composite restorations compared to untreated (negative control) restorations over a period of 10 years. METHODS: 26 subjects (having a total of 52 composite restorations) were recruited. All restorations in the refurbished group showed clinical features rated bravo according to modified USPHS criteria. Untreated restorations were those that had been deemed acceptable (alpha or bravo rated); these were used as controls. Two examiners performed assessments at baseline and during the 5th and 10th years after the intervention. Wilcoxon tests were performed for within-group comparisons, Friedman tests were used for multiple within-group comparisons, and Mann Whitney tests were used for between-groups comparisons. Kaplan-Meier survival curves were calculated, and the Mantel-Cox test was used to compare curves. P < 0.05 was considered statistically significant. RESULTS: In both groups, 10-year scores were significantly different from baseline scores in all clinical parameters except secondary caries. There were no statistically significant differences in the survival analysis of groups (log-rank test, P = 0.376). Refurbishing treatment improved the anatomy, roughness, luster, and marginal adaptation of restorations with a short-term effect, with most properties rated acceptable after 10 years of clinical service. The clinical characteristics were similar for all groups at the 10th year.
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Resinas Compostas , Restauração Dentária Permanente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to evaluate the effect of an adhesive loaded with 0.2 % copper (Cu) and 5 % zinc oxide (ZnO) nanoparticles (Nps) on its adhesive properties and enzymatic activity at the hybrid layer ex vivo in a randomized clinical model. METHODS: Fifteen patients participated in this study, and a total of 30 third molars were used. Occlusal cavities (4 × 4 × 2 mm) were made in each tooth, and randomly divided into 2 groups: (i) Experimental group: commercial adhesive loaded with 0.2wt % CuNps and 5wt % ZnONps; and (ii) Control Group: non-loaded commercial adhesive. Teeth were restored with resin composite. Thirty days later, extractions were performed. Extracted teeth were longitudinally sectioned. Nps in powder were characterized by field emission scanning electron microscope (FE-SEM) and energy dispersive X-ray (EDX) analysis. Microtensile bond strength (µTBS), degree of conversion (DC), and nanoleakeage (NL) tests were executed. In situ zymography (Zym) was performed to evaluate the gelatinolytic activity at the hybrid layer. Student's t-test (α = 0.05) was applied for all tests. RESULTS: µTBS and DC did not show significant differences (p > 0.05) between both groups. However, NL and gelatinolytic activity at the hybrid layer showed significant values (p < 0.05) for experimental group in comparison with control group. CONCLUSION: The addition of 0.2 % CuNps and 5 % ZnONps to a universal adhesive decreases NL and gelatinolytic activity at the hybrid layer, without jeopardizing its adhesive properties. SIGNIFICANCE: This randomized clinical trial with ex vivo analysis demonstrate that a commercial adhesive modified with 0.2wt % Cu and 5wt % ZnO Nps that does not affect its adhesive properties, reducing gelatinolytic activity and nanoleakage at the hybrid layer, which should contribute to an improvement of long term bonding-dentine clinical performance.
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Photocatalytic degradation of phenylmercury was studied using TiO2 in aqueous suspension assisted by UV-A irradiation. Reaction conditions, such as pH and amount of TiO2 were set using a factorial design of experiments resulting in a greater influence of pH on phenylmercury degradation. Hg (II) reduction and simultaneous oxidation of aromatic group was observed. Optimum reaction conditions were obtained under nitrogen atmosphere at pH 10 and 0.35 g/L(-1) TiO2. Under these conditions almost 100% reduction of mercury was reached after 30 min UV irradiation. Total mercury reduction was achieved after 40 min reaction under saturated oxygen. Furthermore, phenol and diphenylmercury were identified as intermediate products of oxidation. It was observed that a major fraction of the reduced mercury was removed as metallic vapor by gas stripping, whereas a minor fraction was adsorbed on the catalyst surface, probably as Hg(OH)2. Under optimal conditions obtained by multivariable analysis, total mineralization of organic matter was achieved after about 60-min irradiation.
Assuntos
Compostos de Fenilmercúrio/química , Compostos de Fenilmercúrio/efeitos da radiação , Titânio/química , Raios Ultravioleta , Poluentes Químicos da Água/química , Poluentes Químicos da Água/efeitos da radiação , Fungicidas Industriais/química , Fungicidas Industriais/efeitos da radiação , Cromatografia Gasosa-Espectrometria de Massas , Microscopia Eletrônica de Varredura , Modelos Teóricos , Fotólise , Espectrometria por Raios XRESUMO
Artificial light at night (ALAN) is a pervasive but still under-recognized driver of global change. In coastal settings, a large majority of the studies assessing ALAN impacts has focused on individual species, even though it is unclear whether results gathered from single species can be used to predict community-wide responses. Similarly, these studies often treat species as single life-stage entities, ignoring the variation associated with distinct life stages. This study addresses both limitations by focusing on the effects of ALAN on a sandy beach community consisting of species with distinct early- and late-life stages. Our hypothesis was that ALAN alters community structure and these changes are mediated by individual species and also by their ontogenetic stages. A field experiment was conducted in a sandy beach of north-central Chile using an artificial LED system. Samples were collected at different night hours (8-levels in total) across the intertidal (9-levels) over several days in November and January (austral spring and summer seasons). The abundance of adults of all species was significantly lower in ALAN treatments. Early stages of isopods showed the same pattern, but the opposite was observed for the early stages of the other two species. Clear differences were detected in the zonation of these species during natural darkness versus those exposed to ALAN, with some adult-juvenile differences in this response. These results support our hypothesis and document a series of changes affecting differentially both early and late life stages of these species, and ultimately, the structure of the entire community. Although the effects described correspond to short-term responses, more persistent effects are likely to occur if ALAN sources become established as permanent features in sandy beaches. The worldwide growth of ALAN suggests that the scope of its effect will continue to grow and represents a concern for sandy beach systems.
Assuntos
Ecossistema , Poluição Luminosa , Chile , Estações do Ano , LuzRESUMO
Artificial Light at Night (ALAN) is expanding worldwide, and the study of its influence remains limited mainly to documenting impacts, overlooking the variation in key characteristics of the artificial light such as its intensity. The potential dose-response of fitness-related traits to different light intensities has not been assessed in sandy beach organisms. Hence, this study explored dose-responses to ALAN by exposing the intertidal sandy beach isopod Tylos spinulosus to a range of light intensities at night: 0 (control), 20, 40, 60, 80 and 100 lx. We quantified the response of this species at the molecular (RNA:DNA ratios), physiological (absorption efficiency) and organismal (growth rate) levels. Linear and non-linear regressions were used to explore the relationship between light intensity and the isopod response. The regressions showed that increasing light intensity caused an overall ~ threefold decline in RNA:DNA ratios and a ~ threefold increase in absorption efficiency, with strong dose-dependent effects. For both response variables, non-linear regressions also identified likely thresholds at 80 lx (RNA:DNA) and 40 lx (absorption efficiency). By contrast, isopod growth rates were unrelated (unaltered) by the increase in light intensity at night. We suggest that ALAN is detrimental for the condition of the isopods, likely by reducing the activity and feeding of these nocturnal organisms, and that the isopods compensate this by absorbing nutrients more efficiently in order to maintain growth levels.
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Isópodes , Poluição Luminosa , Animais , Causalidade , DNA , Isópodes/efeitos da radiação , RNARESUMO
This study focuses on examining the isomerization of allyl alcohol using ruthenium (Ru) supported on alumina as a heterogeneous catalyst. The synthesized Ru/Al solids were characterized by various characterization techniques. The content of Ru was estimated by the energy dispersive x-ray technique. The x-ray diffraction (XRD) confirmed the presence of phases in the support and active species in the catalysts. The surface area of the support after Ru impregnation and the pore volume were determined by nitrogen physisorption. The analysis of programmed temperature (TPR and TPO) shows different redox sites which is confirmed by XPS. The catalytic results suggest a dependence on the amount of available metallic Ru, as well as the importance of the continuous regeneration of the metal using H2 to achieve a good conversion of the allyl alcohol. For comparison purposes, the commercial Ru on alumina 5% (CAS 908142) was used. The results show up to 68% alcohol conversion and 27% yield of the isomerization product using Ru(1,5.4h)/Al catalyst in comparison with 86% conversion and 39% yield of the isomerization product using CAS 908142. In contrast, our catalysts always presented higher TOF values (149-160) in comparison with CAS 908142 (101).
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Many coastal processes are regulated by day/night cycles and are expected to be altered by Artificial Light at Night (ALAN). The goal of this study was to assess the influence of ALAN on the settlement rates of intertidal barnacles. A newly designed settlement plate equipped with a small central LED light source was used to quantify settlement rates in presence/absence of ALAN conditions. "ALAN plates" as well as regular settlement plates were deployed in the mid rocky intertidal zone. Both ALAN and control plates collected early and late settlers of the barnacles Notochthamalus scabrosus and Jehlius cirratus. Early settlers (pre-metamorphosis cyprids) were not affected by ALAN. By contrast, the density of late settlers (post-metamorphosis spats) was significantly lower in ALAN than in control plates for both species, suggesting detrimental ALAN impacts on the settlement process. The new ALAN plates represent an attractive and alternative methodology to study ALAN effects.
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Thoracica , Animais , Ecossistema , Luz , Metamorfose BiológicaRESUMO
In this work, thermoplastic polyurethane (TPU) composites incorporated with 1.0 wt% Cu particles were synthesized by the melt blending method. The effect of the incorporated copper particle size on the antibacterial, thermal, rheological, and mechanical properties of TPU was investigated. The obtained results showed that (i) the addition of copper particles increased the thermal and mechanical properties because they acted as co-stabilizers of polyurethane (PU) (ii) copper nanoparticles decreased the viscosity of composite melts, and (iii) microparticles > 0.5 µm had a tendency to easily increase the maximum torque and formation of agglomerates. SEM micrographics showed that a good mixture between TPU and copper particles was obtained by the extrusion process. Additionally, copper-TPU composite materials effectively inhibited the growth of the Gram-negative Escherichia coli and the Gram-positive Staphylococcus aureus. Considering that the natural concentration of copper in the blood is in the range of 0.7-0.12 mg/L and that the total migration value of copper particles from TPU was 1000 times lower, the results suggested that TPU nanocomposites could be adequately employed for biomedical applications without a risk of contamination.
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IL-10 is a pleiotropic cytokine with immunoregulatory functions affecting various cell types. In a model of experimental infection with the protozoan Trypanosoma cruzi (T. cruzi), we found increased morbidity and lower parasite control in IL-10 deficient mice (IL-10 KO) compared to wild-type (WT) mice. Despite enhanced MÏ function and dendritic cell activation, IL-10 KO mice were more susceptible to infection. The kinetics of T cells in spleen and peripheral blood revealed that infected IL-10 KO mice failed to increase the number of spleen and circulating total CD8+ T cells, a phenomenon observed from the second week of infection in WT mice. Total CD8+ T cells from IL-10 KO mice exhibited diminished proliferation, cytotoxic potential and IFN-γ production than their WT counterparts and T. cruzi-specific CD8+ T cells displayed reduced in vivo cytotoxicity. The absence of IL-10 selectively affected expansion, survival, and increased PD-1 expression of CD8+ T cells without altering these same parameters on CD4+ T cells. Increased inhibitory receptors expression and down-modulation of T-bet by CD8+ T cells from IL-10 KO infected mice were compatible with a T cell exhaustion phenotype. Collectively, these findings reveal that during acute infection, IL-10 plays a previously unrecognized stimulatory role on CD8+ T cells, the most relevant lymphocyte population for the control of intracellular T. cruzi stages. A clear knowledge of the underlying mechanisms that drive effector functions of cytotoxic T cells is critical to understand pathogen persistence and rational design of prophylactic strategies against T. cruzi.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Interleucina-10/metabolismo , Ativação Linfocitária/imunologia , Trypanosoma cruzi/patogenicidade , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Interleucina-2/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Camundongos Endogâmicos BALB C , Camundongos Knockout , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Fenótipo , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Interleucina-10/metabolismo , Proteínas Recombinantes/farmacologia , Baço/patologia , VirulênciaRESUMO
Coastal habitats, in particular sandy beaches, are becoming increasingly exposed to artificial light pollution at night (ALAN). Yet, only a few studies have this far assessed the effects of ALAN on the species inhabiting these ecosystems. In this study we assessed the effects of ALAN on Tylos spinulosus, a prominent wrack-consumer isopod living in sandy beaches of north-central Chile. This species burrows in the sand during daylight and emerges at night to migrate down-shore, so we argue it can be used as a model species for the study of ALAN effects on coastal nocturnal species. We assessed whether ALAN alters the distribution and locomotor activity of this isopod using a light system placed in upper shore sediments close to the edge of the dunes, mimicking light intensities measured near public lighting. The response of the isopods was compared to control transects located farther away and not exposed to artificial light. In parallel, we measured the isopods' locomotor activity in the laboratory using actographs that recorded their movement within mesocosms simulating the beach surface. Measurements in the field indicated a clear reduction in isopod abundance near the source of the light and a restriction of their tidal distribution range, as compared to control transects. Meanwhile, the laboratory experiments showed that in mesocosms exposed to ALAN, isopods exhibited reduced activity and a circadian rhythm that was altered and even lost after a few days. Such changes with respect to control mesocosms with a natural day/night cycle suggest that the changes observed in the field were directly related to a disruption in the locomotor activity of the isopods. All together these results provide causal evidence of negative ALAN effects on this species, and call for further research on other nocturnal sandy beach species that might become increasingly affected by ALAN.
Assuntos
Ritmo Circadiano/efeitos da radiação , Poluição Ambiental/efeitos adversos , Isópodes/fisiologia , Iluminação/efeitos adversos , Locomoção/efeitos da radiação , Animais , Chile , EcossistemaRESUMO
Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.
Assuntos
Transporte Biológico/efeitos dos fármacos , Putrescina/metabolismo , Tripanossomicidas/antagonistas & inibidores , Tripanossomicidas/química , Tripanossomicidas/isolamento & purificação , Doença de Chagas/dietoterapia , Cinarizina/antagonistas & inibidores , Clofazimina/antagonistas & inibidores , Avaliação Pré-Clínica de Medicamentos/métodos , Reposicionamento de Medicamentos , Imidazóis/antagonistas & inibidores , Meclizina/antagonistas & inibidores , Proteínas de Membrana Transportadoras , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/metabolismoRESUMO
OBJECTIVE: To characterize and compare the population of public service drivers of a transport company in Armenia, Colombia. MATERIALS AND METHODS: Taxi and bus drivers from a transport company of Armenia, Colombia participated in an Analytical cross-sectional study. The analysis of the variables was made through Statgraphics Centurion XVI. The comparison of variables as well as multiple and logistic regression were carried out. RESULTS: 125 individuals participated, 8 were removed, and finally there were 117 male drivers as aim of research. The 28.21 % of individuals have driven small buses and the 71.79 % have driven cars. The increase in alcohol consumption was remarkable compared to tobacco. The 60.69 % of subjects did not get exercise. Besides, the BMI average and abdominal circumference was 28.03 kg/m2 and 100.09 cm respectively. The triglyceride average and serum HDL-C were 207.53 mg/dL to 33.12 mg/dL. 49.57 % of all drivers, fulfilled the Metabolic Syndrome diagnostic criteria. Statistically significant differences were found in the values of BMI, waist circumference, systolic blood pressure, diastolic blood pressure, weekly exercise, triglycerides and fasting glucose between individuals with and without Metabolic Syndrome. CONCLUSION: Public service drivers have a profile risk for developing Metabolic Syndrome. Obesity, hypertriglyceridemia and low HDL-C were the main alarm parameters of the presence of Metabolic Syndrome.
OBJETIVO: Caracterizar y comparar la población de conductores de servicio público de una empresa de transporte en Armenia, Colombia. MATERIALES Y MÉTODOS: Estudio analítico de corte transversal en el cual participaron conductores de taxi y colectivo en una empresa de servicio público de Armenia, Colombia. El análisis de las variables se realizó por medio de Statgraphics Centurion XVI. Se de criben las variables, se lleva a cabo una regresión múltiple y una regresión logística. RESULTADOS: Participaron 125 conductores, de los cuales, ocho se retiraron y finalmente quedaron 117 de sexo masculino como objeto de investigación. El 28,21 % ha conducido colectivo y 71,79 % taxi. Se observó un mayor consumo de alcohol respecto al de tabaco. El 60,69 % no realizaba ningún tipo de ejercicio físico. El promedio de IMC y perímetro abdominal fue de 28,03 kg/m2 y 100,09 cm, respectivamente. La media de triglicéridos y HDL-c en suero fue de 207,53 mg/dL y 33,12 mg/dL. Del total de conductores, el 49,57 % cumplía con los criterios diagnósticos de METS. Se encontraron diferencias estadísticamente significativas en los valores de IMC, perímetro abdominal, presión arterial sistólica, presión arterial diastólica, ejercicio semanal, triglicéridos y glicemia en ayunas entre individuos con Síndrome Metabólico y sin éste. CONCLUSIONES: Los conductores de servicio público presentan un perfil de riesgo aumentado para desarrollar Síndrome Metabólico. La obesidad, la hipertrigliceridemia y los bajos niveles de HDL-c fueron los principales parámetros de alarma para la presencia de Síndrome Metabólico.
Assuntos
Condução de Veículo , Síndrome Metabólica/epidemiologia , Doenças Profissionais/epidemiologia , Adulto , Colômbia/epidemiologia , Estudos Transversais , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Veículos Automotores , Doenças Profissionais/etiologia , Fatores de RiscoRESUMO
La parálisis facial periférica es un trastorno neurológico que tiene consecuencias motoras y sensoriales y que afecta al nervio facial. Ocasiona alteraciones en la acción de los músculos del rostro, en la secreción de saliva, lágrimas y en el sentido del gusto.El objetivo de esta publicación es dar cuenta de un caso en el que se realizó un tratamiento con terapias combinadas mínimamente invasivas junto con el uso de láserterapia de baja potencia, en un paciente femenino, 52 años de edad, con antecedentes médicos relevantes, derivada para evaluación estética. La paciente presenta una parálisis facial moderada sin resolver. Fue sometida a láserterapia con longitud de onda (808 nm) y una energía de 3 Joules por sesión en el lado afectado, complementada con toxina botulinica Tipo A, en el lado sano.El tratamiento de parálisis facial periférica con terapias combinadas mínimamente invasivas ha mostrado ser una herramienta útil terapéutica de las secuelas faciales. A su vez, la terapia de fotobiomodulación con láser de baja potencia es prometedora como coadyuvante en el proceso de reparación nerviosa lo que permitiría la recuperación funcional del nervio facial a mediano y largo plazo.
Peripheral Facial Palsy is a neurological disorder that has motor and sensory consequences and affects the facial nerve. It causes alterations in the action of the muscles of the face, in the secretion of saliva, tears, and in the sense of taste.The objective of this publication is to report a case in which a treatment with minimally invasive combined therapies was performed together with the use of low-level laser therapy, in a 52-year-old female patient. With relevant medical history, referred for aesthetic evaluation and with unresolved moderate facial paralysis. She was subjected to laser therapy with wavelength (808 nm) and an energy of 3 Joules per session on the affected side, supplemented with Botulinum Toxin Type A, on the healthy side.The treatment of peripheral facial paralysis with minimally invasive combined therapies has proven to be a useful therapeutic tool for facial sequelae. In turn, low-level laser photobiomodulation therapy is promising as an adjunct in the nerve repair process, which would allow functional recovery of the facial nerve in the medium and long term.
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Terapia com Luz de Baixa Intensidade , Paralisia Facial/radioterapiaRESUMO
Chagas disease is a major unsolved health issue in Latin America and an emerging threat worldwide. New drugs are urgently needed for chemotherapy as those available (benznidazole and nifurtimox) have variable efficacy and elevated toxicity. Efforts are actually oriented to improve tools and technologies (e.g. transgenic parasites, flow cytometry or image-based systems) for the screening of large numbers of candidate compounds for their activity against Trypanosoma cruzi (T. cruzi). Methods that test drug efficacy and selectivity in the same assay are suitable to accelerate the process of drug discovery. Here, we developed a GFP expressing T. cruzi from a moderate virulence stock and confirmed that the transgenic parasite retained the biological characteristics of the parental strain. With this tool, we established a flow cytometer-based method to simultaneously test drug activity against intracellular amastigotes and toxicity to the host cell. This one-step procedure allows determining the selectivity index of the tested compound in a sensitive and accurate manner even with low infection rates. This method can provide additional information on the interactions between drug, parasites and host cell and could be adapted to other trypanosomatids and protozoa with intracellular multiplication.
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Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Descoberta de Drogas/métodos , Nifurtimox/uso terapêutico , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma cruzi/efeitos dos fármacos , Citometria de Fluxo , HumanosRESUMO
Los implantes dentales son ampliamente usados para el reemplazo de piezas dentarias y se han convertido en el "gold standard" de las terapias protésicas en odontología. Dado el mayor uso de éstos, las investigaciones epidemiológicas recientes han demostrado elevadas tasas de prevalencia de enfermedad periimplantaria. En el presente estudio se presentan tres casos clínicos diagnosticados con periimplantitis. Todos los casos presentaron aumento de la profundidad al sondaje periimplantario en relación a controles anteriores, supuración, sangramiento al sondaje y pérdida ósea confirmada a través de tomografía computada cone beam. El tratamiento indicado para todos los casos fue una terapia conjunta entre un tratamiento mecánico mediante ultrasonido con la utilización de puntas plásticas (P.I EMS®, Suiza) y la terapia con láser. Para la laserterapia se utilizó un equipo de láser diodo de 940 nm (Biolase®, USA) con una potencia de 2 W en modo CW, utilizando una punta de 300 µm. El láser de diodo no daña la superficie de titanio y es capaz de descontaminar las superficies rugosas de los implantes. En este reporte, el uso de una terapia combinada mecánica y láser fue efectiva en todos los casos. En los controles clínicos, la mucosa periimplantaria no presentó signos de supuración ni sangramiento, y la profundidad al sondaje también se vió disminuída. El nivel óseo se controló a través de una tomografía computada cone beam y no se evidenciaron cambios significativos. En la actualidad, la evidencia clínica para el tratamiento periimplantario mediante la fototerapia todavía es limitada. Sin embargo, el láser ofrece un enfoque técnico novedoso que es completamente diferente de los instrumentos mecánicos y tiene varios efectos beneficiosos, por lo que puede desempeñar un papel importante, en la resolución de la peri-implantitis.
Dental implants are widely used for the replacement of teeth and have become the "gold standard" of prosthetic therapies in dentistry. Given the increased use of these, recent epidemiological investigations have shown high prevalence rates of peri-implant disease. In the present study, three clinical cases diagnosed with peri-implantitis are presented. All cases presented increased depth to peri-implant probing in relation to previous controls, suppuration, bleeding and bone loss confirmed by cone beam computed tomography. The treatment indicated for all cases was a joint therapy between a mechanical ultrasound treatment with the use of plastic tips (P.I EMS®, Switzerland) and laser therapy. For laser therapy, a 940 nm diode laser equipment was used (Biolase®, USA) with a power of 2W in continuous laser beam mode, using a 300 µm tip. The diode laser does not damage the titanium surface and is capable of decontaminating the rough surfaces of the implants. In this report, the use of a combined mechanical and laser therapy was effective in all cases. In clinical controls, the peri-implant mucosa did not show signs of suppuration or bleeding, and the depth on probing was decreased. The bone level was controlled through a cone beam computed tomography and no significant changes were evidenced. At present, the clinical evidence for peri-implant treatment using phototherapy is still limited. However, the laser offers a novel technical approach that is completely different from mechanical instruments and has several beneficial effects, so it can play an important role in the resolution of peri-implantitis.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Lasers Semicondutores/uso terapêutico , Peri-Implantite/radioterapia , Implantes DentáriosRESUMO
In mammals, the pleiotropic biological functions of tumor necrosis factor alpha (TNF-alpha) may include important effects on human reproductive physiology. Thus, chronic anovulation, oligo or amenorrhea, infertility, hyperandrogenism, obesity, insulin resistance and increased TNFalpha serum levels have been observed in women affected by polycystic ovary syndrome (PCOS). Whole blood short - term cell cultures (WBSC) are simple systems where the capacity to produce TNF-alpha by circulating leukocytes, mainly of the macrophage/monocyte lineage, can be accurately quantified. Given the relevance of monocytes/macrophages in the production of TNF-alpha, in this study, in a control-case approach, WBSC from women with PCOS were analyzed in their basal and lipolysaccharide (LPS)- stimulated capacity to produce the cytokine. These measurements did not correlate with the increased serum levels of the cytokine and the normal levels of cortisol, found in PCOS women. Increased serum TNF-alpha levels in PCOS women correlated positively with body mass index and negatively with insulin sensitivity. In spite of the increased serum TNF-alpha levels in PCOS women, basal and LPS stimulated production of the cytokine, by the ex vivo WBSC from these patients, were within normal values.
Assuntos
Síndrome do Ovário Policístico/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Adolescente , Adulto , Células Sanguíneas/imunologia , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Técnicas In Vitro , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologiaRESUMO
OBJECTIVE: To assess the incidence and type of laparoscopic complications. METHODS: A series of 2140 operative laparoscopies were reviewed in a retrospective study of patient records. The setting was a tertiary-care university hospital. Operative laparoscopy included minor procedures (minimal adhesiolysis, destruction of minimal endometriosis foci, ovarian biopsy, ovarian puncture, tubal sterilization), major laparoscopic surgery (extended adhesiolysis, tuboplasties, uterine suspension, treatment for ectopic pregnancy, salpingitis, ovarian cyst, moderate and severe endometriosis), and advanced laparoscopic surgery (hysterectomy, myomectomy, bladder neck suspension). RESULTS: Two major vascular complications, 3 intestinal injuries, 1 anesthesiological complication, and 4 urinary tract injuries occurred. Two minor and 5 postoperative complications were noted. The overall complication rate was 17/2140 (0.79%). The major complication rate was 10/2140 (0.46%). CONCLUSIONS: This review is useful for helping surgeons reduce the risk of injuries and to inform patients about potential complications. These rates are similar to those that have been previously reported.
Assuntos
Aorta/lesões , Obstrução Intestinal/etiologia , Complicações Intraoperatórias , Laparoscopia , Complicações Pós-Operatórias , Adulto , Aorta/cirurgia , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Doença de Chagas/tratamento farmacológico , Clofazimina/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Nitroimidazóis/uso terapêutico , Tripanossomicidas/uso terapêutico , Animais , Doença de Chagas/patologia , Chlorocebus aethiops , Doença Crônica , Clofazimina/química , Terapia Combinada , Di-Hidropiridinas/química , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C3H , Nitroimidazóis/química , Tripanossomicidas/química , Células VeroRESUMO
Anomalously high levels of mercury in sediment in the Lenga estuary, Chile are comparable to the most contaminated sites previously reported elsewhere. Total mercury (Hgtotal) concentrations range from 0.5 to 129 mg kg(-1) and organic mercury (Hgorg) from 11 to 53 µg kg(-1). The highest levels are in areas near the previous wastewater outfall of a chlo-alkali plant. The results show that the proportion of Hgorg/Hgtotal in the sediment varies by more than two orders of magnitude (0.02-5.7%) according to the concentration of Hgtotal. No correlation between the concentration of Hgorg and Hgtotal was found. The lack of correlation does contrast with the findings of other authors in culture media. Our results indicate that even at very high concentrations of Hgtotal and organic matter do not influence organic mercury formation in estuary sediments. The disparity in Hgtotal and Hgorg concentrations also attests to environmental differences in the formation.