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1.
Risk Anal ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329012

RESUMO

Recent research documents that exposure to air pollution can trigger various behavioral reactions. This article presents novel empirical evidence on the causal effect of pollution risk on life insurance decisions. We create a unique dataset by linking microgeographic air quality information to the confidential UK Wealth and Assets Survey. We identify an inverse N-shape relationship between pollution risk and life insurance adoption by exploiting the orthogonal variations in meteorological conditions. Over a given range above a threshold of exposure, rising pollution is associated with rising demand for life insurance, whereas at lower than the threshold levels of pollution, higher exposure risk reduces demand for insurance. Our findings indicate-for the first time-a nonlinear relationship between local pollution risk and life insurance demand.

2.
Curr Med Res Opin ; 37(7): 1079-1084, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33813997

RESUMO

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is the main genetic modulator of homocysteine. Data suggest a potential association of homozygosity for the TT MTHFR genotype with premature myocardial infarction (MI). We explored whether TT homozygosity is associated with long-term prognosis in patients with premature ST-segment elevation MI (STEMI). METHODS: A total of 265 consecutive patients who had survived their first STEMI ≤35 years of age were followed for a median of 8 years (5-12). Primary endpoints were cardiac death and secondary endpoints were hospitalizations for acute coronary syndrome, myocardial revascularization, arrhythmic event or ischemic stroke. Serum lipids, homocysteine, folate levels were measured at baseline and all patients were also tested for the MTHFR C677T polymorphism. RESULTS: During follow-up 14 patients died (cardiac death) [5.3%] while 84 (31.7%) met the secondary endpoints. In univariate Cox regression analysis TT homozygosity predicted the occurrence of cardiac death (Hazard ratio (HR): 4.071; 95% confidence interval (CI): 1.404-11.809, p = .010) but not the occurrence of secondary endpoints (HR: 0.877; 95% CI: 0.479-1.605, p = .669). TT homozygosity remained an independent predictor of cardiac death after adjustment for conventional risk factors (i.e., sex, diabetes mellitus, hypertension, family history of premature coronary artery disease [CAD]) [HR: 4.350; 95% CI: 1.472-12.856, p = .008]. The association also remained after adjustment for left ventricular ejection fraction or the presence of significant CAD. CONCLUSIONS: Homozygosity for the TT MTHFR is an independent long-term predictor of cardiac death in patients with premature STEMI.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2) , Infarto do Miocárdio , Criança , Pré-Escolar , Morte , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Infarto do Miocárdio/genética , Fatores de Risco , Volume Sistólico , Função Ventricular Esquerda
3.
Sci Rep ; 3: 2421, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23939372

RESUMO

We report on integrated geomorphological, mineralogical, geochemical and biological investigations of the hydrothermal vent field located on the floor of the density-stratified acidic (pH ~ 5) crater of the Kolumbo shallow-submarine arc-volcano, near Santorini. Kolumbo features rare geodynamic setting at convergent boundaries, where arc-volcanism and seafloor hydrothermal activity are occurring in thinned continental crust. Special focus is given to unique enrichments of polymetallic spires in Sb and Tl (±Hg, As, Au, Ag, Zn) indicating a new hybrid seafloor analogue of epithermal-to-volcanic-hosted-massive-sulphide deposits. Iron microbial-mat analyses reveal dominating ferrihydrite-type phases, and high-proportion of microbial sequences akin to "Nitrosopumilus maritimus", a mesophilic Thaumarchaeota strain capable of chemoautotrophic growth on hydrothermal ammonia and CO2. Our findings highlight that acidic shallow-submarine hydrothermal vents nourish marine ecosystems in which nitrifying Archaea are important and suggest ferrihydrite-type Fe(3+)-(hydrated)-oxyhydroxides in associated low-temperature iron mats are formed by anaerobic Fe(2+)-oxidation, dependent on microbially produced nitrate.


Assuntos
Archaea/isolamento & purificação , Fontes Hidrotermais/química , Fontes Hidrotermais/microbiologia , Metais/análise , Erupções Vulcânicas/análise , Grécia
4.
Environ Monit Assess ; 185(11): 9603-18, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23754146

RESUMO

Potentially toxic metals in the urban chemical environment impose risks to both ecosystem and human health. Here, we evaluate the labile pools and availabilities of non-anthropogenic Ni, Cr, Co and Mn in soil samples from Thiva town (central Greece) and investigate their associations with common soil properties and geochemical data obtained by the aqua regia and single selective dissolutions. Experimental work included the initial application of the sequential extraction protocol proposed by the European Community Bureau of Reference and chemical extractions with ethylenediamine tetraacetic acid solution and a modified physiologically based extraction test with the aim to obtain the operationally defined fractions of plant availability and human bioaccessibility, respectively. The leachate results demonstrated that despite the significant contribution of residual metal species especially for Ni and Cr, the studied serpentine soils provide chemically labile pools for all the considered elements. Nickel was found to be the most available metal with the order being Ni > Cr ∼ Co ∼ Mn for plant uptake and Ni > Cr > Co ∼ Mn for human bioaccessibility. The aqua regia extractable concentrations are not predictors of elemental availabilities except for Ni bioaccessible data interpreting however only a moderate percentage of the total variance. The incorporation of basic soil properties (mostly total organic carbon), geochemical data for the major elements Ca, Mg and Fe and ammonium oxalate extractable Cr significantly improved the estimations for individual elements entailing the strong influence of the chemistry and mineralogy of soil materials to the release of focus metals from the soil matrix. This study provides for the first time bioaccessible data for serpentine-derived soils that are more realistic for evaluating potential adverse effects on the human health.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química
5.
Platelets ; 22(5): 361-70, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21158497

RESUMO

Inhibition of platelet aggregation is indispensable for the treatment of acute arterial thrombotic episodes. We have previously reported the synthesis of a highly constrained cyclic peptide, that incorporates the -CDC- sequence, (S,S) PSRCDCR-NH(2), which potently inhibits aggregation and fibrinogen binding to human platelets in vitro. We have tested the safety and efficacy of the peptide on the electrically induced carotid artery thrombosis experimental rabbit model. The peptide's effects on carotid blood flow, thrombus weight, in vitro and ex vivo platelet aggregation, and bleeding and hemostatic parameters were evaluated. The peptide was administered via the femoral vein. Carotid blood flow was continuously monitored for 90 min after electrical thrombus formation. The peptide, at 12 mg/kg, prevented total artery occlusion and significantly preserved carotid artery's patency compared with placebo and eptifibatide. Furthermore, (S,S) PSRCDCR-NH(2) administration at 12 mg/kg reduced thrombus weight, whereas it inhibited ex vivo ADP, arachidonic acid (AA) and collagen-induced platelet aggregation. Moreover (S,S) PSRCDCR-NH(2) at 12 mg/kg presented significantly higher inhibitory effects on AA and collagen-induced ex vivo platelet aggregation compared to eptifibatide. The peptide at any dose did not affect the coagulation cascade, the bleeding times or the hemostatic response of the animals. Thus highly constrained cyclic peptides like (S,S) PSRCDCR-NH(2) that incorporate the -CDC- motif and fulfil certain conformational criteria represent novel compounds that potently inhibit thrombus formation, ex vivo platelet aggregation and carotid artery occlusion superiorly to other non-RGD peptides, such as YMESRADR, without causing hemorrhagic complications in a rabbit model of arterial thrombosis.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Trombose das Artérias Carótidas , Peptídeos Cíclicos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Trombose , Difosfato de Adenosina/antagonistas & inibidores , Difosfato de Adenosina/farmacologia , Sequência de Aminoácidos , Animais , Ácido Araquidônico/antagonistas & inibidores , Ácido Araquidônico/farmacologia , Tempo de Sangramento , Artérias Carótidas/patologia , Trombose das Artérias Carótidas/tratamento farmacológico , Trombose das Artérias Carótidas/patologia , Trombose das Artérias Carótidas/prevenção & controle , Colágeno/antagonistas & inibidores , Colágeno/farmacologia , Modelos Animais de Doenças , Estimulação Elétrica , Eptifibatida , Humanos , Masculino , Dados de Sequência Molecular , Peptídeos/farmacologia , Peptídeos Cíclicos/administração & dosagem , Peptídeos Cíclicos/síntese química , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/síntese química , Coelhos , Trombose/tratamento farmacológico , Trombose/prevenção & controle
6.
J Pharmacol Exp Ther ; 329(2): 634-40, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19244095

RESUMO

The platelet integrin receptor alpha(IIb)beta(3) plays a critical role in thrombosis. We have shown previously that the octapeptide YMESRADR, corresponding to sequences 313 to 320 of the human alpha(IIb) subunit, inhibits human platelet activation and fibrinogen binding to alpha(IIb)beta(3), possibly interacting with the ligand. We investigated the effect of YMESRADR on electrically induced carotid artery thrombosis in New Zealand white rabbits. Peptide was administered via the femoral vein, starting 60 min before and continuing for 90 min after the electrical stimulation. Carotid blood flow was monitored for 90 min after the electrical stimulation. The peptide effects on platelet aggregation, in vitro and ex vivo, and on various coagulation, bleeding, and hemostatic parameters were evaluated. YMESRADR significantly inhibited rabbit platelet aggregation in vitro in a dose-dependent manner. It is important that peptide administration in vivo, at doses ranging from 3 to 15 mg/kg, prolonged the duration of the patency of the carotid artery, and no artery occlusion was observed until the end of the study (90 min after electrical stimulation). Furthermore, YMESRADR administration reduced platelet aggregation ex vivo and thrombus weight; however, these reductions reached statistical significance, compared with the control group, at the peptide doses of 12 and 15 mg/kg. YMESRADR did not affect any coagulation parameter studied and the hemostatic response observed in control animals. Thus, YMESRADR represents a novel antiplatelet agent that can inhibit thrombus formation effectively and carotid artery occlusion without causing hemorrhagic complications in a rabbit model of arterial thrombosis.


Assuntos
Trombose das Artérias Carótidas/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/fisiologia , Animais , Coagulação Sanguínea/efeitos dos fármacos , Trombose das Artérias Carótidas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Oligopeptídeos/síntese química , Oligopeptídeos/química , Fragmentos de Peptídeos/síntese química , Fragmentos de Peptídeos/química , Inibidores da Agregação Plaquetária/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/química , Coelhos
7.
Cancer Causes Control ; 19(4): 371-8, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18064534

RESUMO

OBJECTIVE: Thyroid disease has been associated with leukemia and lymphoma. No previous study using clinical and laboratory data has explored whether thyroid disease and especially autoimmune thyroid disease (ATD) is associated with myelodysplastic syndrome (MDS) risk. In this case-control study, we investigated the association of ATD with MDS. METHODS: Our study included 101 cases with incident primary MDS confirmed by histology and cytogenetics, and 101 controls matched on gender and age, admitted for non-neoplastic and non-infectious diseases. All subjects were submitted to clinical, ultrasound thyroid evaluation and serum free T3, free T4, TSH, thyroglobulin, and thyroperoxidase antibodies determination. RESULTS: Adjusting for age, gender, and body mass index, there was statistically significant evidence that ATD is associated with increased risk of MDS (OR = 2.58, 95% CI 1.29-5.16). Interestingly, ATD starting from the remote past (more than 10 years from MDS onset) was positively associated with MDS risk (OR = 5.73. 95% CI 2.03-16.16). Mean serum levels of fT3, fT4, and thyroid antibodies were significantly higher in MDS patients and mean TSH serum levels were significantly lower in MDS patients than in controls (p < 0.05). CONCLUSION: Biological plausibility and empirical evidence highlights the importance of ATD in MDS etiopathogenesis. Further studies are needed to explore underlying mechanisms associating thyroid autoimmunity with leukemogenesis.


Assuntos
Síndromes Mielodisplásicas/etiologia , Tireoidite Autoimune/complicações , Tireoidite Autoimune/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Autoimunidade , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Prevalência , Fatores de Risco , Inquéritos e Questionários , Glândula Tireoide/fisiopatologia , Tireoidite Autoimune/diagnóstico
8.
Clin Biochem ; 40(15): 1129-34, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17673194

RESUMO

OBJECTIVES: The aim of this study was to evaluate the extent of oxidative stress in patients with breast or ovarian cancer by analyzing the magnitude of serum oxidizability and the involvement of oxidized low-density lipoproteins (oxLDL) in the disease. DESIGN AND METHODS: The study was conducted on 32 patients diagnosed with breast or ovarian cancer but who had not undergone any kind of treatment and 30 healthy individuals of similar age. The evaluation of oxidative stress was assessed by: (a) the ex-vivo susceptibility of serum lipids to oxidation and (b) the detection of oxLDL and anti-oxLDL autoantibodies. Total cholesterol, LDL-cholesterol and HDL-cholesterol were co-estimated. RESULTS: The results indicated that the levels of oxLDL were increased among both breast and ovarian cancer patients as compared to the control subjects. Additionally in patients with breast cancer, serum total cholesterol, LDL-cholesterol, anti-oxLDL antibodies and the maximal rate of diene formation (RA), the index of oxidizable components load, were increased in comparison to controls. There is statistically significant evidence that serum oxLDL levels are associated with increased risk of breast and ovarian cancer. CONCLUSIONS: The findings exhibit a correlation between oxLDL and malignancy, supporting the contribution of oxidative stress to carcinogenesis and the possible involvement of oxLDL in the process of malignancy. The clinical evaluation of the oxLDL measurement is under investigation.


Assuntos
Neoplasias da Mama/sangue , Carcinoma/sangue , Lipídeos/sangue , Lipoproteínas LDL/sangue , Neoplasias Ovarianas/sangue , Soro/metabolismo , Idoso , Neoplasias da Mama/metabolismo , Carcinoma/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Oxirredução , Estresse Oxidativo/fisiologia
9.
Eur J Nucl Med Mol Imaging ; 34(11): 1804-14, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17594090

RESUMO

PURPOSE: The aim of this study was to evaluate the applicability of [(99m)Tc]Demotensin 5 and 6 [Formula: see text] in the targeted diagnostic imaging of neurotensin subtype 1 receptor (NTS1-R)-expressing tumours. METHODS: Labelling of Demotensin 5 and 6 with (99m)Tc was conducted by brief incubation with (99m)TcO(4) (-), SnCl(2) and citrate anions in alkaline medium at ambient temperature. Affinities of conjugates for the NTS1-R were determined by competition binding experiments in WiDr cell membranes using [(125)I-Tyr(3)]NT as the radioligand. Saturation binding assays were conducted for [(99m)Tc/(99g)Tc]Demotensin 6 in WiDr cell membranes. Internalisation of [(99m)Tc]Demotensin 5 and 6 was studied at 37 degrees C in WiDr cells. Biodistribution of [(99m)Tc]Demotensin 5 and 6 was performed in female Swiss nu/nu mice bearing human WiDr xenografts. RESULTS: Unlabelled conjugates showed a high affinity for the human NTS1-R (Demotensin 5 IC(50)=0.03+/-0.01 nM; Demotensin 6 IC(50)=0.08+/-0.02 nM), while high affinity was also exhibited by (radio)metallated [(99m)Tc/(99g)Tc]Demotensin 6 (K (d)=0.13+/-0.01 nM). [(99m)Tc]Demotensin 5 and 6 internalised rapidly and specifically in WiDr cells. After injection in WiDr tumour-bearing mice, radiopeptides, and especially the doubly stabilised [(99m)Tc]Demotensin 6, showed NTS1-R-mediated uptake in the intestines and in the implanted tumour (4.30+/-0.45%ID/g at 1 h post injection) and rapid renal excretion from non-target tissues into the urine. CONCLUSION: [(99m)Tc]Demotensin 6 shows a favourable preclinical profile and further testing in patients is warranted to monitor its eventual applicability as a radiotracer in the diagnostic imaging of NTS1-R-positive tumours.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/metabolismo , Neurotensina/farmacocinética , Receptores de Neurotensina/metabolismo , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Humanos , Masculino , Taxa de Depuração Metabólica , Camundongos , Neurotensina/química , Especificidade de Órgãos , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/química , Tecnécio/farmacocinética , Distribuição Tecidual
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