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1.
Environ Res ; 233: 116450, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37343761

RESUMO

Perchlorate and chlorate are endocrine disruptors considered emerging contaminants (ECs). Both oxyanions are commonly associated with anthropogenic contamination from fertilizers, pesticides, explosives, and disinfection byproducts. However, the soils of the Atacama Desert are the most extensive natural reservoirs of perchlorate in the world, compromising drinking water sources in northern Chile. Field campaigns were carried (2014-2018) to assess the presence of these ECs in the water supply networks of twelve Chilean cities. Additionally, the occurrence of perchlorate, chlorate and other anions typically observed in drinking water matrices of the Atacama Desert (i.e., nitrate, chloride, sulfate) was evaluated using a Spearman correlation analysis to determine predictors for perchlorate and chlorate. High concentrations of perchlorate (up to 114.48 µg L-1) and chlorate (up to 9650 µg L-1) were found in three northern cities. Spatial heterogeneities were observed in the physicochemical properties and anion concentrations of the water supply network. Spearman correlation analysis indicated that nitrate, chloride, and sulfate were not useful predictors for the presence of perchlorate and chlorate in drinking water in Chile. Hence, this study highlights the need to establish systematic monitoring, regulation, and treatment for these EC of drinking water sources in northern Chilean cities for public health protection.


Assuntos
Água Potável , Poluentes Químicos da Água , Água Potável/química , Cloratos/análise , Chile , Nitratos/análise , Percloratos , Cidades , Cloretos/análise , Poluentes Químicos da Água/análise
2.
Int J Mol Sci ; 23(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36077163

RESUMO

Developing a therapeutic antibody is a long, tedious, and expensive process. Many obstacles need to be overcome, such as biophysical properties (issues of solubility, stability, weak production yields, etc.), as well as cross-reactivity and subsequent toxicity, which are major issues. No in silico method exists today to solve such issues. We hypothesized that if we were able to properly measure the similarity between the CDRs of antibodies (Ab) by considering not only their evolutionary proximity (sequence identity) but also their structural features, we would be able to identify families of Ab recognizing similar epitopes. As a consequence, Ab within the family would share the property to recognize their targets, which would allow (i) to identify off-targets and forecast the cross-reactions, and (ii) to identify new Ab specific for a given target. Testing our method on 238D2, an antagonistic anti-CXCR4 nanobody, we were able to find new nanobodies against CXCR4 and to identify influenza hemagglutinin as an off-target of 238D2.


Assuntos
Influenza Humana , Anticorpos de Domínio Único , Anticorpos , Epitopos , Hemaglutininas , Humanos
3.
Rev Med Chil ; 148(11): 1652-1658, 2020 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-33844772

RESUMO

Climate change is associated with negative health outcomes, such as cardiovascular and respiratory diseases. This article analyses the threat of climate change on population health and the urgent need to implement measures to avoid this damage. Heat vulnerability, heatwave exposures, and wildfire exposure to forest fires have increased in Chile. In 2018, the annual mean concentration of fine particulate matter (PM2.5) exceeded the safe level proposed by the World Health Organization, increasing the risk of negative health outcomes. Thus, multidisciplinary and intersectoral mitigation and adaptation policies are needed. Among other elements, mental health impacts of climate change, health education provided by health workers to reduce negative health impacts of climate change, greater engagement of academia to generate evidence useful for policy-making processes and a better articulation between central and local governments should be considered. Finally, achieving a healthy population should be the aim of all these policies and efforts.


Assuntos
Mudança Climática , Saúde da População , Chile , Humanos , Material Particulado
4.
Rev Med Chil ; 148(6): 746-754, 2020 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-33480372

RESUMO

BACKGROUND: The presence of toxic metals in human populations is strongly associated with chronic diseases. AIM: To determine levels of lead, chromium, cadmium, mercury and inorganic arsenic (AsIn) in the general population aged over 5 years in Antofagasta, Chile. MATERIAL AND METHODS: People living in Urban Antofagasta for at least five years were considered eligible. Biological samples were obtained to measure heavy metals. RESULTS: One thousand two hundred three participants with a median age of 43 years (656 women) were studied. Their mean time of residence in the city was 30 years, and 52% smoked. Eight percent of the adult population and 12% of children had AsIn values above 35 µg/L, while 75% of the population had levels below 21.9 µg/L. The other metals were below the risk levels defined by the health authority (10 µg/L for chromium, 10 µg/L for mercury, 2 µg/L for cadmium, 5 and 10 µg/dL for blood lead for children and adults, respectively). The factors associated with high levels of AsIn in adults were male sex, living more than 200 meters from monitoring points, and low schooling. In children, the associated variables were high intake of seafood products and having a caregiver with less than 8 years of schooling. Contrary to expectations, the greatest risk of presenting altered levels of the metals occurred in the population living more than 500 meters from the identified risk sources (90% of the population). CONCLUSIONS: The findings of this study suggest that all potential sources of exposure to AsIn should be evaluated, and surveillance actions should be established to reduce involuntary exposure to this metalloid.


Assuntos
Chumbo/sangue , Metais Pesados/urina , Adulto , Chile/epidemiologia , Monitoramento Ambiental , Feminino , Humanos , Masculino
5.
Environ Geochem Health ; 41(6): 2505-2519, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31049755

RESUMO

The occurrence of toxic metals and metalloids associated with mine tailings is a serious public health concern for communities living in mining areas. This work explores the relationship between metal occurrence (e.g., spatial distribution in street dusts), human health indicators (e.g., metals in urine samples, lifestyle and self-reported diseases) and socioeconomic status (SES) using Chañaral city (in northern Chile) as study site, where a copper mine tailing was disposed in the periurban area. This study model may shed light on the development of environmental and health surveillance plans on arid cities where legacy mining is a sustainability challenge. High concentrations of metals were found in street dust, with arsenic and copper concentrations of 24 ± 13 and 607 ± 911 mg/kg, respectively. The arsenic concentration in street dust correlated with distance to the mine tailing (r = - 0.32, p-value = 0.009), suggesting that arsenic is dispersed from this source toward the city. Despite these high environmental concentrations, urinary levels of metals were low, while 90% of the population had concentrations of inorganic arsenic and its metabolites in urine below 33.2 µg/L, copper was detected in few urine samples (< 6%). Our results detected statistically significant differences in environmental exposures across SES, but, surprisingly, there was no significant correlation between urinary levels of metals and SES. Despite this, future assessment and control strategies in follow-up research or surveillance programs should consider environmental and urinary concentrations and SES as indicators of environmental exposure to metals in mining communities.


Assuntos
Poeira/análise , Exposição Ambiental/análise , Metais/urina , Mineração , Adolescente , Adulto , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/urina , Arsênio/análise , Arsênio/urina , Chile , Cidades , Cobre/análise , Cobre/urina , Estudos Transversais , Saúde Ambiental , Monitoramento Ambiental/métodos , Feminino , Humanos , Masculino , Metaloides/análise , Metais/análise , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto Jovem
6.
Protein Expr Purif ; 145: 94-99, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29366963

RESUMO

Using a cell-free expression system, we produced the Kv1.3 protein embedded in one step within detergent micelles. The protein was then purified and relipidated into mixed lipid bilayers. These proteoliposomes held an average of 0.8 protein per liposome. We examined channel forming activity using an oxonol VI fluorescent probe and verified its inhibition using margatoxin and ShK toxins. This assay was automatized and optimized so as to get a Z' statistical factor acceptable for venom fraction screening. We obtained a sensible amount of membrane protein using the cell-free assay, that proved to be active when embedded in liposomes. These findings emphasize the quality of the cell-free produced KV1.3 proteoliposomes and the usefulness of a fluorescent probe. This method can benefit the field of channel characterization, as well as provide tools for the development of new inhibitors, so as to reinforce our therapeutic arsenal against autoimmune diseases.


Assuntos
Isoxazóis/metabolismo , Canal de Potássio Kv1.3/antagonistas & inibidores , Canal de Potássio Kv1.3/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Sistema Livre de Células , Venenos de Cnidários/farmacologia , Humanos , Proteolipídeos/metabolismo , Proteínas Recombinantes/metabolismo , Venenos de Escorpião/farmacologia
7.
Analyst ; 143(9): 2165-2173, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29667660

RESUMO

A new prototype of a membrane protein biochip is presented in this article. This biochip was created by the combination of novel technologies of peptide-tethered bilayer lipid membrane (pep-tBLM) formation and solid support micropatterning. Pep-tBLMs integrating a membrane protein were obtained in the form of microarrays on a gold chip. The formation of the microspots was visualized in real-time by surface plasmon resonance imaging (SPRi) and the functionality of a GPCR (CXCR4), reinserted locally into microwells, was assessed by ligand binding studies. In brief, to achieve micropatterning, P19-4H, a 4 histidine-possessing peptide spacer, was spotted inside microwells obtained on polystyrene-coated gold, and Ni-chelating proteoliposomes were injected into the reaction chamber. Proteoliposome binding to the peptide was based on metal-chelate interaction. The peptide-tethered lipid bilayer was finally obtained by addition of a fusogenic peptide (AH peptide) to promote proteoliposome fusion. The CXCR4 pep-tBLM microarray was characterized by surface plasmon resonance imaging (SPRi) throughout the building-up process. This new generation of membrane protein biochip represents a promising method of developing a screening tool for drug discovery.


Assuntos
Bicamadas Lipídicas/química , Fosfolipídeos/química , Análise Serial de Proteínas , Receptores CXCR4/química , Ouro , Membranas , Proteolipídeos/química , Ressonância de Plasmônio de Superfície
8.
Biochim Biophys Acta Biomembr ; 1859(12): 2373-2380, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28888365

RESUMO

The study of ion channel activity and the screening of possible inhibitor molecules require reliable methods for production of active channel proteins, their insertion into artificial membranes and for the measurement of their activity. Here we report on cell-free expression of soluble and active Kv1.1 and Kv1.3 channels and their efficient insertion into liposomes. Two complementary methods for the determination of the electrical activity of the proteoliposome-embedded channels were compared using Kv1.1 as a model system: (1) single channel recordings in droplet interface bilayers (DIB) and (2) measurement of the membrane voltage potential generated by a potassium ion diffusion potential using the voltage-sensitive fluorescent dye oxonol VI. Single channel recordings in DIBs proved unreliable because of the non-reproducible fusion of proteoliposomes with an artificial membrane. Therefore, the use of the optical indicator oxonol VI was adapted for 96 well microtiter plates using the ionophore valinomycin as a positive control. The activity of Kv1.1 and Kv1.3 channels was then monitored in the absence and presence of different venom toxins, demonstrating that fluorescent dyes can be used very efficiently when screening small molecules for their channel blocking activity.


Assuntos
Canal de Potássio Kv1.1/metabolismo , Canal de Potássio Kv1.3/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Proteolipídeos/efeitos dos fármacos , Venenos Elapídicos/farmacologia , Escherichia coli/genética , Escherichia coli/metabolismo , Corantes Fluorescentes/química , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Isoxazóis/química , Canal de Potássio Kv1.1/genética , Canal de Potássio Kv1.3/genética , Fosfatidilcolinas/química , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/química , Fosfatidilserinas/metabolismo , Proteolipídeos/química , Proteolipídeos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Frações Subcelulares/metabolismo , Valinomicina/farmacologia
9.
Langmuir ; 33(39): 10385-10401, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28877444

RESUMO

Membrane proteins exhibiting extra- and intracellular domains require an adequate near-native lipid platform for their functional reconstitution. With this aim, we developed a new technology enabling the formation of a peptide-tethered bilayer lipid membrane (pep-tBLM), a lipid bilayer grafted onto peptide spacers, by way of a metal-chelate interaction. To this end, we designed an original peptide spacer derived from the natural α-laminin thiopeptide (P19) possessing a cysteine residue in the N-terminal extremity for grafting onto gold and a C-terminal extremity modified by four histidine residues (P19-4H). In the presence of nickel, the use of this anchor allowed us to bind liposomes of variable compositions containing a 2% molar ratio of a chelating lipid, 1,2-dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl)iminodiacetic acid)succinyl] so-called DOGS-NTA, and to form the planar bilayer by triggering liposome fusion by an α-helical (AH) peptide derived from the N-terminus of the hepatitis C virus NS5A protein. The formation of pep-tBLMs was characterized by surface plasmon resonance imaging (SPRi), and their continuity, fluidity, and homogeneity were demonstrated by fluorescence recovery after photobleaching (FRAP), with a diffusion coefficient of 2.5 × 10-7 cm2/s, and atomic force microscopy (AFM). By using variable lipid compositions including phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol 4,5-bisphosphate (PIP2), sphingomyelin (SM), phosphatidic acid (PA), and cholesterol (Chol) in various ratios, we show that the membrane can be formed independently from the lipid composition. We made the most of this advantage to reincorporate a transmembrane protein in an adapted complex lipid composition to ensure its functional reinsertion. For this purpose, a cell-free expression system was used to produce proteoliposomes expressing the functional C-X-C motif chemokine receptor 4 (CXCR4), a seven-transmembrane protein belonging to the large superfamily of G-protein-coupled receptors (GPCRs). We succeeded in reinserting CXCR4 in pep-tBLMs formed on P19-4H by the fusion of tethered proteoliposomes. AFM and FRAP characterization allowed us to show that pep-tBLMs inserting CXCR4 remained fluid, homogeneous, and continuous. The value of the diffusion coefficient determined in the presence of reinserted CXCR4 was 2 × 10-7 cm2/s. Ligand binding assays using a synthetic CXCR4 antagonist, T22 ([Tyr5,12, Lys7]-polyphemusin II), revealed that CXCR4 can be reinserted in pep-tBLMs with functional folding and orientation. This new approach represents a method of choice for investigating membrane protein reincorporation and a promising way of creating a new generation of membrane biochips adapted for screening agonists or antagonists of transmembrane proteins.


Assuntos
Fosfolipídeos/química , Bicamadas Lipídicas , Fosfatidilcolinas , Receptores Acoplados a Proteínas G
10.
Environ Res ; 153: 99-105, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27918984

RESUMO

BACKGROUND: A growing number of studies have identified an association between exposure to inorganic arsenic and hypertension. However, results have not been consistent across studies. Additional studies are warranted, given the global prevalence of both arsenic exposure and morbidity attributable to hypertension. METHODS: We analyzed data collected from October 2007-December 2010 for a population-based cancer case-control study in northern Chile. Data included lifetime individual arsenic exposure estimates and information on potential confounders for a total of 1266 subjects. Those self-reporting either a physician diagnosis of hypertension or use of an anti-hypertensive medication were classified as having hypertension (n=612). The association between hypertension and drinking water arsenic exposure was analyzed using logistic regression models. RESULTS: Compared to those in the lowest category for lifetime highest 5-year average arsenic exposure (<60µg/L), those in the middle (60-623µg/L) and upper (>623µg/L) exposure categories had adjusted hypertension ORs of 1.49 (95% CI: 1.09, 2.05) and 1.65 (95% CI: 1.18, 2.32), respectively. Similar results were observed in analyses of lifetime cumulative exposures and analyses restricted to exposures from the distant past. CONCLUSIONS: We identified evidence of increased odds of hypertension with exposure to arsenic in drinking water among study participants. Our findings add to the growing body of research supporting this association, which could have important public health implications.


Assuntos
Arsênio/toxicidade , Água Potável , Hipertensão/induzido quimicamente , Poluentes Químicos da Água/toxicidade , Idoso , Arsênio/análise , Índice de Massa Corporal , Chile , Água Potável/efeitos adversos , Água Potável/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Poluentes Químicos da Água/análise
11.
Protein Expr Purif ; 118: 83-91, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26477501

RESUMO

Using a cell-free expression system we produced the p7 viroporin embedded into a lipid bilayer in a single-step manner. The protein quality was assessed using different methods. We examined the channel forming activity of p7 and verified its inhibition by 5-(N,N-Hexamethylene) amiloride (HMA). Fourier transformed infrared spectroscopy (FTIR) experiments further showed that when p7 was inserted into synthetic liposomes, the protein displayed a native-like conformation similar to p7 obtained from other sources. Photoactivable amino acid analogs used for p7 protein synthesis enabled oligomerization state analysis in liposomes by cross-linking. Therefore, these findings emphasize the quality of the cell-free produced p7 proteoliposomes which can benefit the field of the hepatitis C virus (HCV) protein production and characterization and also provide tools for the development of new inhibitors to reinforce our therapeutic arsenal against HCV.


Assuntos
Sistema Livre de Células/metabolismo , Hepacivirus/metabolismo , Proteínas Virais/metabolismo , Sistema Livre de Células/química , Escherichia coli/química , Escherichia coli/genética , Hepacivirus/química , Hepacivirus/genética , Lipossomos/metabolismo , Dobramento de Proteína , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/isolamento & purificação
12.
BMC Public Health ; 16: 122, 2016 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-26847446

RESUMO

BACKGROUND: Maule Cohort (MAUCO), a Chilean cohort study, seeks to analyze the natural history of chronic diseases in the agricultural county of Molina (40,000 inhabitants) in the Maule Region, Chile. Molina´s population is of particular interest because in the last few decades it changed from being undernourished to suffering excess caloric intake, and it currently has the highest national rates of cardiovascular diseases, stomach cancer and gallbladder cancer. Between 2009 and 2011 Molina´s poverty rate dropped from 24.1 % to 13.5 % (national average 20.4 %); in this period the county went from insufficient to almost complete basic sanitation. Despite these advances, chemical pollutants in the food and air are increasing. Thus, in Molina risk factors typical of both under-developed and developed countries coexist, generating a unique profile associated with inflammation, oxidative stress and chronic diseases. METHODS/DESIGN: MAUCO is the core project of the recently established Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Católica de Chile. In this study, we are enrolling and following 10,000 adults aged 38 to 74 years over 10 years. All eligible Molina residents will be enrolled. Participants were identified through a household census. Consenting individuals answer an epidemiological survey exploring risk factors (psycho-social, pesticides, diet, alcohol, and physical activity), medical history and physical and cognitive conditions; provide fasting blood, urine, and saliva samples; receive an electrocardiogram, abdominal ultrasound and bio-impedance test; and take a hand-grip strength test. These subjects will be re-interviewed after 2, 5 and 7 years. Active surveillance of health events is in place throughout the regional healthcare system. The MAUCO Bio-Bank will store 30 to 50 aliquots per subject using an NIH/NCI biorepository system for secure and anonymous linkage of samples with data. DISCUSSION: MAUCO´s results will help design public health interventions tailored to agricultural populations in Latin America.


Assuntos
Doença Crônica/epidemiologia , Saúde Pública , Adulto , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Chile/epidemiologia , Dieta , Ingestão de Energia , Exercício Físico , Feminino , Neoplasias da Vesícula Biliar/epidemiologia , Humanos , América Latina , Masculino , Pessoa de Meia-Idade , Praguicidas/análise , Pobreza/estatística & dados numéricos , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , População Rural , Fatores Socioeconômicos , Neoplasias Gástricas/epidemiologia
13.
BMC Pediatr ; 16: 31, 2016 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-26956385

RESUMO

BACKGROUND: The current study aims to evaluate the association between neck circumference (NC) and several cardio-metabolic risk factors, to compare it with well-established anthropometric indices, and to determine the cut-off point value of NC for predicting children at increased risk of metabolic syndrome, insulin resistance and low-grade systemic inflammation. METHODS: A total of 669 school children, aged 8-14, were recruited. Demographic, clinical, anthropometric and biochemical data from all patients were collected. Correlations between cardio-metabolic risk factors and NC and other anthropometric variables were evaluated using the Spearman's correlation coefficient. Multiple linear regression analysis was applied to further examine these associations. We then determined by receiver operating characteristic (ROC) analyses the optimal cut-off for NC for identifying children with elevated cardio-metabolic risk. RESULTS: NC was positively associated with fasting plasma glucose and triglycerides (p = 0.001 for all), and systolic and diastolic blood pressure, C-reactive protein, insulin and HOMA-IR (p < 0.001 for all), and negatively with HDL-C (p = 0.001). Whereas, other anthropometric indices were associated with fewer risk factors. CONCLUSIONS: NC could be used as clinically relevant and easy to implement indicator of cardio-metabolic risk in children.


Assuntos
Inflamação/diagnóstico , Síndrome Metabólica/diagnóstico , Pescoço/anatomia & histologia , Adolescente , Biomarcadores/sangue , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Criança , Colômbia , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Insulina/sangue , Resistência à Insulina , Modelos Lineares , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Curva ROC , Fatores de Risco , Triglicerídeos/sangue
14.
J Clin Microbiol ; 53(4): 1164-71, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25631795

RESUMO

Liver diseases linked to hepatitis B-hepatitis D virus co- or superinfections are more severe than those during hepatitis B virus (HBV) monoinfection. The diagnosis of hepatitis D virus (HDV) infection therefore remains crucial in monitoring patients but is often overlooked. To integrate HDV markers into high-throughput viral hepatitis diagnostics, we studied the binding of anti-HDV antibodies (Abs) using surface plasmon resonance imaging (SPRi). We focused on the ubiquitous HDV genotype 1 (HDV1) and the more uncommon African-HDV6 and HDV8 genotypes to define an array with recombinant proteins or peptides. Full-length and truncated small hepatitis D antigen (S-HDAg) recombinant proteins of HDV genotype 1 (HDV1) and 11 HDV peptides of HDV1, 6, and 8, representing various portions of the delta antigen were grafted onto biochips, allowing SPRi measurements to be made. Sixteen to 17 serum samples from patients infected with different HDV genotypes were injected onto protein and peptide chips. In all, Abs against HDV proteins and/or peptides were detected in 16 out of 17 infected patients (94.12%), although the amplitude of the SPR signal varied. The amino-terminal part of the protein was poorly immunogenic, while epitope 65-80, exposed on the viral ribonucleoprotein, may be immunodominant, as 9 patient samples led to a specific SPR signal on peptide 65 type 1 (65#1), independently of the infecting genotype. In this pilot study, we confirmed that HDV infection screening based on the reactivity of patient Abs against carefully chosen HDV peptides and/or proteins can be included in a syndrome-based viral hepatitis diagnostic assay. The preliminary results indicated that SPRi studying direct physical HDAg-anti-HDV Ab interactions was more convenient using linear peptide epitopes than full-length S-HDAg proteins, due to the regeneration process, and may represent an innovative approach for a hepatitis syndrome-viral etiology-exploring array.


Assuntos
Anticorpos Anti-Hepatite/sangue , Hepatite D/imunologia , Vírus Delta da Hepatite/genética , Vírus Delta da Hepatite/imunologia , Antígenos da Hepatite delta/imunologia , Análise Serial de Proteínas/métodos , Adolescente , Adulto , Sequência de Aminoácidos , Hepatite D/virologia , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Projetos Piloto , Alinhamento de Sequência , Ressonância de Plasmônio de Superfície , Adulto Jovem
15.
Molecules ; 20(9): 15893-909, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26340616

RESUMO

Despite palliative treatments, glioblastoma (GBM) remains a devastating malignancy with a mean survival of about 15 months after diagnosis. Programmed cell-death is de-regulated in almost all GBM and the re-activation of the mitochondrial apoptotic pathway through exogenous bioactive proteins may represent a powerful therapeutic tool to treat multidrug resistant GBM. We have reported that human Bak protein integrated in Liposomes (LB) was able, in vitro, to activate the mitochondrial apoptotic pathway in colon cancer cells. To evaluate the anti-tumor effects of LB on GBM, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and Western blot analysis were performed on GL26 murine cell line. LB treatment shows a dose-dependent inhibition of cell viability, followed by an up-regulation of Bax and a down-modulation of JNK1 proteins. In GL26-bearing mice, two different routes of administration were tested: intra-tumor and intravenous. Biodistribution, tumor growth and animal survival rates were followed. LB show long-lasting tumor accumulation. Moreover, the intra-tumor administration of LB induces tumor growth delay and total tumor regression in about 40% of treated mice, while the intravenous injection leads to a significant increased life span of mice paralleled by an increased tumor cells apoptosis. Our findings are functional to the design of LB with potentiated therapeutic efficacy for GBM.


Assuntos
Glioblastoma/tratamento farmacológico , Proteolipídeos/química , Proteína Killer-Antagonista Homóloga a bcl-2/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Lipossomos , Camundongos
16.
Am J Epidemiol ; 180(11): 1082-7, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25371173

RESUMO

Arsenic concentrations greater than 100 µg/L in drinking water are a known cause of cancer, but the risks associated with lower concentrations are less well understood. The unusual geology and good information on past exposure found in northern Chile are key advantages for investigating the potential long-term effects of arsenic. We performed a case-control study of lung cancer from 2007 to 2010 in areas of northern Chile that had a wide range of arsenic concentrations in drinking water. Previously, we reported evidence of elevated cancer risks at arsenic concentrations greater than 100 µg/L. In the present study, we restricted analyses to the 92 cases and 288 population-based controls who were exposed to concentrations less than 100 µg/L. After adjustment for age, sex, and smoking behavior, these exposures from 40 or more years ago resulted in odds ratios for lung cancer of 1.00, 1.43 (90% confidence interval: 0.82, 2.52), and 2.01 (90% confidence interval: 1.14, 3.52) for increasing tertiles of arsenic exposure, respectively (P for trend = 0.02). Mean arsenic water concentrations in these tertiles were 6.5, 23.0, and 58.6 µg/L. For subjects younger than 65 years of age, the corresponding odds ratios were 1.00, 1.62 (90% confidence interval: 0.67, 3.90), and 3.41 (90% confidence interval: 1.51, 7.70). Adjustments for occupation, fruit and vegetable intake, and socioeconomic status had little impact on the results. These findings provide new evidence that arsenic water concentrations less than 100 µg/L are associated with higher risks of lung cancer.


Assuntos
Arsênio/efeitos adversos , Neoplasias Pulmonares/induzido quimicamente , Poluentes Químicos da Água/efeitos adversos , Idoso , Arsênio/administração & dosagem , Estudos de Casos e Controles , Chile/epidemiologia , Água Potável/química , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Poluentes Químicos da Água/administração & dosagem
17.
Toxicol Appl Pharmacol ; 274(2): 225-31, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24296302

RESUMO

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., <200µg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99-3.67), and 3.26 (1.76-6.04) (p-trend <0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06-3.11), and 2.02 (1.15-3.54) (p-trend <0.001). In analyses confined to subjects only with arsenic water concentrations <200µg/L (median=60µg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08-5.68) and 2.37 (1.01-5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations.


Assuntos
Arsênio/urina , Água Potável/análise , Neoplasias Pulmonares/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Arsênio/metabolismo , Arsênio/toxicidade , Estudos de Casos e Controles , Chile/epidemiologia , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Metilação , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Inquéritos e Questionários , Neoplasias da Bexiga Urinária/epidemiologia , Poluentes da Água/metabolismo , Poluentes da Água/toxicidade , Poluentes da Água/urina
18.
Rev Med Chil ; 142(4): 443-50, 2014 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-25117034

RESUMO

BACKGROUND: Exposure to Biological Agents during work is an emergent type of occupational risk. AIM: To characterize occupational biological risk exposure among Chilean workers which have been registered by the Toxicology Information Center, between January 2006 and December 2009. MATERIAL AND METHODS: All incoming calls reporting exposure to biological agents during the studied period were analyzed. The information obtained from the caller was registered using the Communication Record Instrument of the WHO International Programme on Chemical Safety (IPCS INTOX). RESULTS: In the studied period, 77 calls were received. The mean age of exposed patients was 35 ± 15 years and 57% of them were females. The most common involved agents were vaccines for veterinary use (42%) followed by Loxosceles laeta bites in 16%. The main routes of exposure were injections, cuts and needle stick injuries in 39% and stings and bites in 38%. The highest exposure rates were observed in Southern Chile due to self-inoculation of veterinary vaccines used in the salmon industry (22.7/100.000 actual workers). Fifty-eight percent of calls were from health care workers, and 51% of them were from health care facilities. Sixty percent of exposures occurred during summer and spring. There was a fourfold higher risk of calls involving women exposed to bites or stings (odds ratio (OR) 4.5 (CI95 1.5-13.9, p < 0.01). Men had a fourfold higher risk of being exposed to vaccines or medications for veterinary use (OR 4.2, CI95 1.4-12.6 p < 0.01). CONCLUSIONS: Most calls involving an exposure to a biological agent were caused by self-inoculation of veterinary medications.


Assuntos
Fatores Biológicos/toxicidade , Exposição Ocupacional/estatística & dados numéricos , Adolescente , Adulto , Idoso , Chile/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/classificação , Fatores de Risco , Estações do Ano , Venenos de Serpentes/intoxicação , Adulto Jovem
19.
Artigo em Inglês | MEDLINE | ID: mdl-38053279

RESUMO

Air pollution in Chile presents unique challenges, exacerbated by inequalities and geographical and climatic diversity. Current policies have not succeeded in aligning air quality with international and national standards, nor have they significantly mitigated public health impacts, despite being more advanced than those in other Latin American countries. The evidence on the health damages caused by air pollution is compelling, showing harmful acute and chronic effects across various life stages. Yet, current measures do not effectively reduce exposure to pollutants. The monitoring network, which reports data from stationary and mobile sources, does not always detect early fugitive emissions and is limited to regulated pollutants, leaving areas without adequate monitoring coverage and without management plans for critical episodes outside of autumn and winter and for a reduced number of pollutants. In the context of climate change, which increases the frequency of forest fires, Chile is experiencing a deterioration of air quality, highlighting the need to expand critical episode management beyond the current Air Pollution Prevention and/or Atmospheric Decontamination Plans. Integrated intersectoral plans need to be improved and extended to address the high exposure to pollutants, due to the large number of people exposed, and a broad population health risks, including quality of life. Decarbonisation by 2040 based on the Sustainable Development Goals is an important pillar of the strategy, but a public debate is needed to establish additional actions for addressing environmental injustice, improving equity and reducing current exposure to air pollutants.

20.
Heliyon ; 9(7): e18191, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37519708

RESUMO

Achieving sustainability and resilience depends on the conciliation of environmental, social, and economic issues integrated into a long-term perspective to ensure communities flourish. Many nations are transitioning toward both objectives, while at the same time addressing structural concerns that have not allowed them to look after the environment in the past. Chile is one of these nations dealing with such challenges within a particular administrative context, an increasing environmental awareness, and a set of unique and complex geophysical boundaries that impose a plethora of hazards for cities, ecosystems, and human health. This paper presents recent accomplishments and gaps, mostly from an environmental perspective, on issues related to air pollution, the urban water cycle, and soil contamination, in the path being followed by Chile toward urban sustainability and resilience. The focus is on the bonds between cities and their geophysical context, as well as the relationships between environmental issues, the built environment, and public health. The description and diagnosis are illustrated using two cities as case studies, Temuco and Copiapó, whose socioeconomic, geographical, and environmental attributes differ considerably. Particulate matter pollution produced by the residential sector, drinking water availability, wastewater treatment, stormwater management, and soil contamination from the mining industry are discussed for these cities. Overall, the case studies highlight how tackling these issues requires coordinated actions in multiple areas, including regulatory, information, and financial incentive measures. Finally, the policy analysis discusses frameworks and opportunities for Chilean cities, which may be of interest when conceiving transitional paths toward sustainability and resilience for other cities elsewhere.

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