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BACKGROUND: Persistent inflammation related to aging ("inflammaging") is exacerbated by chronic infections and contributes to frailty in older adults. We hypothesized associations between Toxoplasma gondii (T. gondii), a common parasite causing an oligosymptomatic unremitting infection, and frailty, and secondarily between T. gondii and previously reported markers of immune activation in frailty. METHODS: We analyzed available demographic, social, and clinical data in Spanish and Portuguese older adults [N = 601; age: mean (SD) 77.3 (8.0); 61% women]. Plasma T. gondii immunoglobulin G (IgG) serointensity was measured with an enzyme-linked immunosorbent assay. The Fried criteria were used to define frailty status. Validated translations of Mini-Mental State Examination, Geriatric Depression Scale, and the Charlson Comorbidity Index were used to evaluate confounders. Previously analyzed biomarkers that were significantly associated with frailty in both prior reports and the current study, and also related to T. gondii serointensity, were further accounted for in multivariable logistic models with frailty as outcome. RESULTS: In T. gondii-seropositives, there was a significant positive association between T. gondii IgG serointensity and frailty, accounting for age (p = .0002), and resisting adjustment for multiple successive confounders. Among biomarkers linked with frailty, kynurenine/tryptophan and soluble tumor necrosis factor receptor II were positively associated with T. gondii serointensity in seropositives (p < .05). Associations with other biomarkers were not significant. CONCLUSIONS: This first reported association between T. gondii and frailty is limited by a cross-sectional design and warrants replication. While certain biomarkers of inflammaging were associated with both T. gondii IgG serointensity and frailty, they did not fully mediate the T. gondii-frailty association.
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Fragilidade , Toxoplasma , Toxoplasmose , Humanos , Feminino , Idoso , Masculino , Estudos Transversais , Imunoglobulina G , Anticorpos Antiprotozoários , Biomarcadores , Imunoglobulina M , Fatores de RiscoRESUMO
In breast tomosynthesis, multiple low-dose projections are acquired in a single scanning direction over a limited angular range to produce cross-sectional planes through the breast for three-dimensional imaging interpretation. We built a next-generation tomosynthesis system capable of multidirectional source motion with the intent to customize scanning motions around "suspicious findings". Customized acquisitions can improve the image quality in areas that require increased scrutiny, such as breast cancers, architectural distortions, and dense clusters. In this paper, virtual clinical trial techniques were used to analyze whether a finding or area at high risk of masking cancers can be detected in a single low-dose projection and thus be used for motion planning. This represents a step towards customizing the subsequent low-dose projection acquisitions autonomously, guided by the first low-dose projection; we call this technique "self-steering tomosynthesis." A U-Net was used to classify the low-dose projections into "risk classes" in simulated breasts with soft-tissue lesions; class probabilities were modified using post hoc Dirichlet calibration (DC). DC improved the multiclass segmentation (Dice = 0.43 vs. 0.28 before DC) and significantly reduced false positives (FPs) from the class of the highest risk of masking (sensitivity = 81.3% at 2 FPs per image vs. 76.0%). This simulation-based study demonstrated the feasibility of identifying suspicious areas using a single low-dose projection for self-steering tomosynthesis.
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Neoplasias da Mama , Mamografia , Humanos , Feminino , Mamografia/métodos , Estudos Transversais , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Imageamento Tridimensional/métodosRESUMO
X-ray imaging results in inhomogeneous irradiation of the detector and distortion of structures in the periphery of the image; yet the spatial dependency of tomosynthesis image-quality metrics has not been extensively investigated. In this study, we use virtual clinical trials to quantify the spatial dependency of lesion detectability in our lab's next-generation tomosynthesis (NGT) system. Two geometries were analyzed: a conventional geometry with mediolateral source motion, and a NGT geometry with T-shaped motion. Breast parenchymal texture was simulated using an open-source library with Perlin noise using 400 random seeds and three breast densities. Spherical mass lesions were inserted in the central slice of the phantoms using the voxel additive method. Image acquisition was simulated using in-house ray-tracing software and simple backprojection was performed using commercial reconstruction software. Lesion detectability with Channelized Hotelling Observers (CHOs) was analyzed using receiver operating characteristic curves to measure the detectability index (d') at 154 unique locations for the lesions. We also divided images into three non-overlapping regions (differing in terms of distance from the chest wall). At the 0.05 level of significance, there was a statistically significant difference between the geometries in terms of d' in one of the three regions, with the T geometry offering superior detectability. Examining all 154 lesion locations, the T geometry was found to offer lower spread (standard deviation) in d' values throughout the image area, and superior d' at 83 of 154 locations (53.9%). In summary, the T geometry enables superior lesion detection and mitigates anisotropies.
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Our lab has built a next-generation tomosynthesis (NGT) system utilizing scanning motions with more degrees of freedom than clinical digital breast tomosynthesis systems. We are working toward designing scanning motions that are customized around the locations of suspicious findings. The first step in this direction is to demonstrate that these findings can be detected with a single projection image, which can guide the remainder of the scan. This paper develops an automated method to identify findings that are prone to be masked. Perlin-noise phantoms and synthetic lesions were used to simulate masked cancers. NGT projections of phantoms were simulated using ray-tracing software. The risk of masking cancers was mapped using the ground-truth labels of phantoms. The phantom labels were used to denote regions of low and high risk of masking suspicious findings. A U-Net model was trained for multiclass segmentation of phantom images. Model performance was quantified with a receiver operating characteristic (ROC) curve using area under the curve (AUC). The ROC operating point was defined to be the point closest to the upper left corner of ROC space. The output predictions showed an accurate segmentation of tissue predominantly adipose (mean AUC of 0.93). The predictions also indicate regions of suspicious findings; for the highest risk class, mean AUC was 0.89, with a true positive rate of 0.80 and a true negative rate of 0.83 at the operating point. In summary, this paper demonstrates with virtual phantoms that a single projection can indeed be used to identify suspicious findings.
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BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is associated with a very unfavorable prognosis. At this advanced stage of the disease, there are several therapeutic strategies approved in recent times, being one of them Radium-223 dichloride (Radium-223). However, its mechanisms of action and the process that conducts to cell death are not fully understood. Given this, our main goal is to characterize the radiobiological effects induced by Radium-223 and to evaluate its kinetics on metastatic Prostate Cancer (mPCa) cells. MATERIALS AND METHODS: In vitro studies were conducted using two mPCa cell lines, the LNCaP and PC3, the first being derived from lymph node metastasis and the second from bone metastasis. Kinetic studies were conducted to access the capacity of these cell lines to uptake, retain and internalize the Radium-223. For the assessment of radiobiological effects, cells were first exposed to different doses of Radium-223 and the clonogenic assay was done to evaluate cell survival and to determine lethal doses (LD50). Then, the effects were also evaluated in terms of proliferation, oxidative stress, morphological changes and cell damage. RESULTS: Radium-223 is uptaken by mPCa cells and reaches the nucleus, where it is retained over time. Irradiation decreases cell survival and proliferation, with LNCaP cells (LD50 = 1.73mGy) being more radiosensitive than PC3 cells (LD50 = 4.20mGy). Irradiated cells showed morphological changes usually associated with apoptosis and a dose-dependent increase in DNA damage. Moreover, activation of cell cycle checkpoints occurs through ATM/CHK2 pathway, which is involved in cell cycle arrest and cell death. CONCLUSIONS: The cytotoxic and anti-proliferative effects on both cell lines showed that Radium-223 can decrease the aggressiveness of tumor cells by decreasing the cell survival and proliferation and, also, by increasing the DNA damage. The similar results observed in both cell lines indicated that Radium-223 may have the potential to be used as a therapeutic option also for mCRPC patients with lymph node metastasis. The activation of DNA Damage Response pathways allows the possibility to understand the importance of these checkpoints as targets for new combined therapies.
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Neoplasias Ósseas/secundário , Neoplasias de Próstata Resistentes à Castração/patologia , Rádio (Elemento)/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Dano ao DNA , Humanos , Cinética , Metástase Linfática , MasculinoRESUMO
This work proposes the application of a new electroencephalogram (EEG) signal processing tool - the lacsogram - to characterize the Alzheimer's disease (AD) activity and to assist on its diagnosis at different stages: Mild Cognitive Impairment (MCI), Mild and Moderate AD (ADM) and Advanced AD (ADA). Statistical analyzes are performed to lacstral distances between conventional EEG subbands to find measures capable of discriminating AD in all stages and characterizing the AD activity in each electrode. Cepstral distances are used for comparison. Comparing all AD stages and Controls (C), the most important significances are the lacstral distances between subbands θ and α ( p = 0.0014 0.05). The topographic maps show significant differences in parietal, temporal and frontal regions as AD progresses. Machine learning models with a leave-one-out cross-validation process are applied to lacstral/cepstral distances to develop an automatic method for diagnosing AD. The following classification accuracies are obtained with an artificial neural network: 95.55% for All vs All, 98.06% for C vs MCI, 95.99% for C vs ADM, 93.85% for MCI vs ADM-ADA. In C vs MCI, C vs ADM and MCI vs ADM-ADA, the proposed method outperforms the state-of-art methods by 5%, 1%, and 2%, respectively. In All vs All, it outperforms the state-of-art EEG and non-EEG methods by 6% and 2%, respectively. These results indicate that the proposed method represents an improvement in diagnosing AD.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Eletroencefalografia , Humanos , Aprendizado de Máquina , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: The systematic evaluation of the results of time-series studies of air pollution is challenged by differences in model specification and publication bias. METHODS: We evaluated the associations of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) and fine PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) with daily all-cause, cardiovascular, and respiratory mortality across multiple countries or regions. Daily data on mortality and air pollution were collected from 652 cities in 24 countries or regions. We used overdispersed generalized additive models with random-effects meta-analysis to investigate the associations. Two-pollutant models were fitted to test the robustness of the associations. Concentration-response curves from each city were pooled to allow global estimates to be derived. RESULTS: On average, an increase of 10 µg per cubic meter in the 2-day moving average of PM10 concentration, which represents the average over the current and previous day, was associated with increases of 0.44% (95% confidence interval [CI], 0.39 to 0.50) in daily all-cause mortality, 0.36% (95% CI, 0.30 to 0.43) in daily cardiovascular mortality, and 0.47% (95% CI, 0.35 to 0.58) in daily respiratory mortality. The corresponding increases in daily mortality for the same change in PM2.5 concentration were 0.68% (95% CI, 0.59 to 0.77), 0.55% (95% CI, 0.45 to 0.66), and 0.74% (95% CI, 0.53 to 0.95). These associations remained significant after adjustment for gaseous pollutants. Associations were stronger in locations with lower annual mean PM concentrations and higher annual mean temperatures. The pooled concentration-response curves showed a consistent increase in daily mortality with increasing PM concentration, with steeper slopes at lower PM concentrations. CONCLUSIONS: Our data show independent associations between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality in more than 600 cities across the globe. These data reinforce the evidence of a link between mortality and PM concentration established in regional and local studies. (Funded by the National Natural Science Foundation of China and others.).
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Poluição do Ar/efeitos adversos , Exposição Ambiental/análise , Mortalidade , Material Particulado/efeitos adversos , Poluição do Ar/análise , Doenças Cardiovasculares/mortalidade , Causas de Morte , Exposição Ambiental/efeitos adversos , Exposição Ambiental/legislação & jurisprudência , Saúde Global , Humanos , Tamanho da Partícula , Material Particulado/análise , Doenças Respiratórias/mortalidade , RiscoRESUMO
Air pollution is, increasingly, a concern to our society given the threats to human health and the environment. Concerted actions to improve air quality have been taken at different levels, such as through the development of Air Quality Plans (AQPs). However, air quality impacts associated with the implementation of abatement measures included in AQPs are often neglected. In order to identify the major gaps and strengths in current knowledge, a literature review has been performed on existing methodologies to estimate air pollution-related health impacts and subsequent external costs. Based on this review, the Impact Pathway Approach was adopted and applied within the context of the MAPLIA research project to assess the health impacts and benefits (or avoided external costs) derived from improvements in air quality. Seven emission abatement scenarios, based on individual and combined abatement measures, were tested for the major activity sectors (traffic, residential and industrial combustion and production processes) of a Portuguese urban area (Grande Porto) with severe particular matter (PM10) air pollution problems. Results revealed a strong positive correlation between population density and health benefits obtained from the assessed reduction scenarios. As a consequence, potential health benefits from reduction scenarios are largest in densely populated areas with high anthropic activity and, thus, where air pollution problems are most alarming. Implementation of all measures resulted in a reduction in PM10 emissions by almost 8%, improving air quality by about 1% and contributing to a benefit of 8.8 million /year for the entire study domain. The introduction of PM10 reduction technologies in industrial units was the most beneficial abatement measure. This study intends to contribute to policy support for decision-making on air quality management.
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Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Saúde da População Urbana , Adolescente , Idoso , Poluição do Ar/prevenção & controle , Criança , Pré-Escolar , Habitação , Humanos , Material Particulado , Portugal , Melhoria de Qualidade , Saúde da População Urbana/economiaRESUMO
This review will focus on published human studies on oxidative stress and DNA damage in inflammatory bowel disease (IBD), both ulcerative colitis and Crohn's disease, assessing their role in the pathophysiology of these diseases. Search was performed over PubMed and ScienceDirect databases to identify relevant bibliography, using keywords including "oxidative stress," "DNA damage," "IBD," and "oxidative DNA damage." Whether as cause or effect, mechanisms underlying oxidative stress have the potential to condition the course of various pathologies, particularly those driven by inflammatory scenarios. IBDs are chronic inflammatory relapsing conditions. Oxidative stress has been associated with some of the characteristic clinical features exhibited in IBD, namely tissue injury and fibrosis, and also to the ulcerative colitis-associated colorectal cancer. The possible influence of oxidative stress over therapeutic behavior and response, as well as their contribution to the oxidative burden and consequences, is also addressed. Due to the high prevalence and incidence of IBD worldwide, and also to its associated morbidity, complications, and disease and treatment costs, it is of paramount importance to better understand the pathophysiology of these diseases.
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Dano ao DNA , Doenças Inflamatórias Intestinais/metabolismo , Estresse Oxidativo , Antioxidantes/uso terapêutico , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Doença de Crohn/genética , Doença de Crohn/metabolismo , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , OxirreduçãoRESUMO
Formaldehyde (FA) is a commonly used chemical in anatomy and pathology laboratories as a tissue preservative and fixative. Because of its sensitising properties, irritating effects and cancer implication, FA accounts probably for the most important chemical-exposure hazard concerning this professional group. Evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting, particularly in regard to the ability of inhaled FA to induce toxicity on other cells besides first contact tissues, such as buccal and nasal cells. To evaluate the effects of exposure to FA in human peripheral blood lymphocytes, a group of 84 anatomy pathology laboratory workers exposed occupationally to FA and 87 control subjects were tested for chromosomal aberrations (CAs) and DNA damage (comet assay). The level of exposure to FA in the workplace air was evaluated. The association between genotoxicity biomarkers and polymorphic genes of xenobiotic-metabolising and DNA repair enzymes were also assessed. The estimated mean level of FA exposure was 0.38±0.03 ppm. All cytogenetic endpoints assessed by CAs test and comet assay % tail DNA (%TDNA) were significantly higher in FA-exposed workers compared with controls. Regarding the effect of susceptibility biomarkers, results suggest that polymorphisms in CYP2E1 and GSTP1 metabolic genes, as well as, XRCC1 and PARP1 polymorphic genes involved in DNA repair pathways are associated with higher genetic damage in FA-exposed subjects. Data obtained in this study show a potential health risk situation of anatomy pathology laboratory workers exposed to FA (0.38 ppm). Implementation of security and hygiene measures may be crucial to decrease risk. The obtained information may also provide new important data to be used by health care programs and by governmental agencies responsible for occupational health and safety.
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Biomarcadores/metabolismo , Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA/genética , Formaldeído/efeitos adversos , Exposição Ocupacional/efeitos adversos , Hipersensibilidade Respiratória/induzido quimicamente , Hipersensibilidade Respiratória/patologia , Adulto , Estudos de Casos e Controles , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Enzimas Reparadoras do DNA/genética , Feminino , Seguimentos , Formaldeído/metabolismo , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Hipersensibilidade Respiratória/metabolismo , Adulto JovemRESUMO
House dust is a repository and concentrator of many chemical and biological agents including fungi. Considering that dust acts as a long-term reservoir of airborne fungi and that cumulative exposure is more relevant to potential health problems than single-day or short-term exposure, characterization of fungal communities in dust samples is of paramount importance. In the present study, the fungal composition of Portuguese house dust samples was determined. A total of 28 samples were obtained from vacuum cleaner deposits from households located in central Portugal. DNA was extracted from dust samples and fungal communities were analyzed using a culture-independent polymerase chain reaction (PCR)- denaturing gradient gel electrophoresis (DGGE) approach. Cultural analyses were also performed in order to identify the viable fungi species present in selected samples. Fungal diversity, reported as the number of operational taxonomic units (OTU), varied between 9 and 56 OTU. This analysis of viable fungi showed that Aspergillus was the most abundant genus, followed by Penicillium, Mucor, and Rhizomucor. Trichoderma, Chrysosporium, Fusarium, Rhizopus, and Stachybotrys were found in a limited number of houses. Our results demonstrated that dust is, in fact, home for a diverse and heterogeneous fungal community and that some of the species found are known allergic agents with severe negative impacts on human health.
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Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Fungos/isolamento & purificação , DNA Fúngico/isolamento & purificação , Fungos/classificação , Habitação , Reação em Cadeia da Polimerase , PortugalRESUMO
Several evidences suggest that enhanced oxidative stress is involved in the pathogenesis and/or progression of several neurodegenerative diseases. The aim of this study was to investigate for the first time whether both extracts from tomato plant (Lycopersicon esculentum Mill.) leaves and their isolated steroidal alkaloids (tomatine and tomatidine) afford neuroprotective effect against glutamate-induced toxicity in SH-SY5Y neuroblastoma cells and to elucidate the mechanisms underlying this protection. Steroidal alkaloids from tomato are well known for their cholinesterases' inhibitory capacity and the results showed that both purified extracts and isolated compounds, at non-toxic concentrations for gastric (AGS), intestinal (Caco-2) and neuronal (SH-SY5Y) cells, have the capacity to preserve mitochondria membrane potential and to decrease reactive oxygen species levels of SH-SY5Y glutamate-insulted cells. Moreover, the use of specific antagonists of cholinergic receptors allowed observing that tomatine and tomatidine can interact with nicotinic receptors, specifically with the α7 type. No effect on muscarinic receptors was noticed. In addition to the selective cholinesterases' inhibition revealed by the compounds/extracts, these results provide novel and important insights into their neuroprotective mechanism. This work also demystifies the applicability of these compounds in therapeutics, by demonstrating that their toxicity was overestimated for long time.
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Ácido Glutâmico/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Tomatina/análogos & derivados , Tomatina/farmacologia , Células CACO-2 , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Humanos , Neuroblastoma , Extratos Vegetais/farmacologia , Folhas de Planta/químicaRESUMO
Cationic solid lipid nanoparticles (cSLN) are colloidal carriers for genes or drugs, particularly lipophilic drugs. Several reports exist on their high efficiency, but only a few studies report the effect of cSLNs on living cells. In the present work, internalization, cell viability (alamar blue assay) and genotoxic potential (alkaline comet assay) of three cSLN formulations (A-C) were evaluated in HepG2 and Caco-2 cells. cSLN showed an average hydrodynamic diameter (z-ave) of 141-222 nm, zeta-potential of 55.0-72.5 mV and polidispersity indices (PdI) of 0.336-0.421. Dispersion in physiological buffers increased z-ave and PdI. 0.01 mg ml(-1) cSLN unaffected cell viability, but 1.0 mg ml(-1) significantly decreased it, being cSLN-C (Compritol-based) the most toxic and HepG2 the most affected. DNA damage was not significantly increased by 0.1 mg ml(-1) cSLN but damage was observed at 1.0 mg ml(-1) cSLN-C. Thus, no genotoxicity is to be expected at concentrations that do not reduce cell viability.
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Dano ao DNA , Portadores de Fármacos/toxicidade , Lipídeos/toxicidade , Nanopartículas/toxicidade , Células CACO-2 , Cátions , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Portadores de Fármacos/química , Estabilidade de Medicamentos , Células Hep G2 , Humanos , Lipídeos/química , Nanopartículas/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Manufacturing or using nanomaterials may result in exposure of workers to nanoparticles. Potential routes of exposure include skin, lung and gastrointestinal tract. The lack of health-based standards for nanomaterials combined with their increasing use in many different workplaces and products emphasize the need for a reliable temporary risk assessment tool. Therefore, the aim of this work was to explore the effects of different doses of titanium dioxide nanoparticles on human gastric epithelial cells in vitro. We analyzed proliferation by MTT assay, apoptosis by Tunel, migration by injury assay, oxidative stress by determining GSH/GSSG ratio and DNA damage by Comet assay on nanoparticle-treated AGS human gastric epithelial cell line in comparison to controls. We show and discuss the tumor-like phenotypes of nanoparticles-exposed AGS cells in vitro, as increased proliferation and decreased apoptosis. Our results demonstrate for the first time that nanoparticles induce tumor-like phenotypes in human gastric epithelial cells.
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Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/toxicidade , Titânio/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Células Epiteliais/patologia , Mucosa Gástrica/citologia , Mucosa Gástrica/patologia , Humanos , Estresse Oxidativo/efeitos dos fármacos , Medição de Risco/métodos , Titânio/administração & dosagemRESUMO
Brassica oleracea L. var. costata DC leaves and Pieris brassicae L. larvae aqueous extracts were assayed for their potential to prevent/induce DNA damage. None of them was mutagenic at the tested concentrations in the Ames test reversion assay using Salmonella His(+) TA98 strains, with and without metabolic activation. In the hypoxanthine-guanine phosphoribosyltransferase mutation assay using mammalian V79 fibroblast cell line, extracts at 500 µg/mL neither induced mutations nor protected against the mutagenicity caused by methyl methanesulfonate (MMS). In the comet assay, none of the extracts revealed to be genotoxic by itself, and both afforded protection, more pronounced for larvae extracts, against MMS-induced genotoxicity. As genotoxic/antigenotoxic effects of Brassica vegetables are commonly attributed to isothiocyanates, the extracts were screened for these compounds by headspace-solid-phase microextraction/gas chromatography-mass spectrometry. No sulfur compound was detected. These findings demonstrate that both extracts could be useful against damage caused by genotoxic compounds, the larvae extract being the most promising.
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Fatores Biológicos/farmacologia , Brassica/química , Borboletas/química , Dano ao DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Ensaio Cometa , Cricetinae , Larva/química , Pulmão/efeitos dos fármacos , Metanossulfonato de Metila/toxicidade , Mutagênicos/toxicidadeRESUMO
Ptaquiloside, a norsesquiterpene glycoside from bracken (Pteridium aquilinum), is a known carcinogen towards animals. Its genotoxicity is mainly attributed to its DNA-alkylating and clastogenic properties. This study analyses various modes of genotoxic action of ptaquiloside in human mononuclear blood cells. The alkaline comet assay was performed on cells exposed to 5µg/ml ptaquiloside for 5, 10, 20, 30, 40 or 50min. Tail length was used as a DNA-damage parameter. Assays to determine structural and numerical chromosomal aberrations and sister-chromatid exchange were conducted on cells exposed to 5, 10 or 20µg/ml ptaquiloside for 48h. The tail length showed maximum DNA damage at 20-30min, diminishing onwards. Highly significant (p<0.001) dose-dependent increases in structural and numerical chromosomal aberrations and SCE were observed in response to ptaquiloside. These results indicate that ptaquiloside is not only a DNA-alkylating agent, but expresses its genotoxicity through multiple mechanisms including clastogenesis, aneugenesis and the mechanism underlying SCE induction, which is not entirely understood. Recent studies support the role played by aneuploidy in oncogenesis, highlighting the importance of this endpoint for mutagenicity screening. SCE are thought to represent the long-term effects of mutagens and are an important genotoxicity biomarker. The present results also agree with data from epidemiological studies and from animal in vivo studies, further supporting the hypothesis that ptaquiloside may represent a significant threat to human health.
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Indanos/toxicidade , Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Sesquiterpenos/toxicidade , Troca de Cromátide Irmã/efeitos dos fármacos , Alquilantes/toxicidade , Aneugênicos/toxicidade , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Fatores de TempoRESUMO
Hairdressing is predominantly a female activity, in which several chemicals are handled, some of which are known to be allergenic and potentially carcinogenic. Several epidemiological studies showed an association between occupational exposure to chemicals in hairdressing salons and skin and respiratory-tract conditions. The aim of this study were to characterize the occupational exposure to total volatile organic compounds (VOC) and ammonia (NH3) in 50 Portuguese hairdressers' salons and to analyze the prevalence of respiratory and skin symptoms in 134 hairdressing professionals. Data indicated that internal sources of total VOC are mainly due to indoor sources, with average concentrations (1.4 mg/m³) above the Portuguese reference levels (0.6 mg/m³). Of the hairdressers' salons studied, 4% had a mean NH3 concentration higher than Portuguese (20 ppm) and American Conference of Industrial Hygienists (ACGIH) (25 ppm) reference levels. Hand dermatitis was the occupational symptom most reported by hairdressers (50%), followed by eye irritation (43%). The results of this study suggest that hairdressers' occupational activities are linked with higher risk of developing hand and wrist/arm dermatitis and symptoms in the upper respiratory tract. The proper use of disposable gloves, hands, wrists, and arms skin monitoring, and the frequent use of moisturizers in the workplace are effective measures to prevent the occurrence of dermatitis in these professionals. Displacement ventilation and/or local exhaust with adequate air exchange rate are recommended particularly in technical areas where hairdressing chemicals are mixed.
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Amônia/efeitos adversos , Exposição Ocupacional/efeitos adversos , Doenças Respiratórias/induzido quimicamente , Dermatopatias/induzido quimicamente , Compostos Orgânicos Voláteis/efeitos adversos , Adolescente , Adulto , Monitoramento Ambiental , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Doenças Respiratórias/epidemiologia , Dermatopatias/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Disseminated tuberculosis (TB) is a common cause of death among human immunodeficiency virus (HIV)-infected patients in developing countries. Blood culture offers a potential means to diagnose disseminated TB, but optimal blood culture methods have not been studied. METHODS: Two hundred and fifty-eight HIV-infected patients hospitalized in Tanzania with ≥2 weeks fever or cough had diagnostic studies for TB: 3 sputum samples for acid-fast bacilli smear and culture; 40 ml of blood for culture, randomized 1:1 to 40 ml × 1, or 20 ml × 2 collected 12-24 h apart. Blood was processed using automated MB BacT(®) broth and manual Isolator(®) lysis-centrifugation agar. Mortality was assessed at 2 months. RESULTS: TB was confirmed in 83 (32%) of 258 patients: by sputum only in 42 (51%, median CD4 = 72 cells/µl), blood only in 15 (18%, median CD4 = 44 cells/µl), and in sputum and blood in 26 (31%, median CD4 = 12 cells/µl). Blood was positive in 21 (16%) for 40 ml × 1 vs 20 (15%) for 20 ml × 1 (p = 0.83) vs 20 (16%) for 20 ml × 2 (p = 0.97). MB BacT was positive in 31 (76%) and Isolator was positive in 20 (49%) of 41 samples (p = 0.01). The mean colony-forming units/ml was 8 (range 3-14). Twenty-one (51%) patients with disseminated TB died; median survival was 6 days (range 0-58). CONCLUSIONS: Disseminated TB in HIV is characterized by persistent bacteraemia, delayed microbiological detection, and high mortality. Twenty millilitres of blood processed by automated broth is the optimal culture method to detect disseminated TB. Empiric TB therapy is warranted for HIV-infected patients from TB-endemic countries with prolonged cough or fever.
Assuntos
Bacteriemia/epidemiologia , Bacteriemia/patologia , Febre/epidemiologia , Infecções por HIV/complicações , Tuberculose/complicações , Tuberculose/epidemiologia , Adulto , Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Técnicas Bacteriológicas/métodos , Sangue/microbiologia , Feminino , Febre/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Escarro/microbiologia , Tanzânia , Tuberculose/diagnóstico , Tuberculose/patologiaRESUMO
Nanotoxicology link between India and European Nations (NanoLINEN) is a consortium of 7 European laboratories and Indian Institute of Toxicology Research (CSIR Laboratory) from India to strengthen the research ties in the area of Nanomaterial Toxicology. The goal of this project is to develop robust risk assessment methodologies that will be useful for the community manufacturing and using nano-products.