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1.
Sci Total Environ ; 912: 168901, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38042198

RESUMO

Use of nutrients recycled from societal waste streams in agriculture is part of the circular economy, and in line with organic farming principles. Nevertheless, diverse contaminants in waste streams create doubts among organic farmers about potential risks for soil health. Here, we gather the current knowledge on contaminant levels in waste streams and recycled nutrient sources, and discuss associated risks. For potentially toxic elements (PTEs), the input of zinc (Zn) and copper (Cu) from mineral feed supplements remains of concern, while concentrations of PTEs in many waste streams have decreased substantially in Europe. The same applies to organic contaminants, although new chemical groups such as flame retardants are of emerging concern and globally contamination levels differ strongly. Compared to inorganic fertilizers, application of organic fertilizers derived from human or animal feces is associated with an increased risk for environmental dissemination of antibiotic resistance. The risk depends on the quality of the organic fertilizers, which varies between geographical regions, but farmland application of sewage sludge appears to be a safe practice as shown by some studies (e.g. from Sweden). Microplastic concentrations in agricultural soils show a wide spread and our understanding of its toxicity is limited, hampering a sound risk assessment. Methods for assessing public health risks for organic contaminants must include emerging contaminants and potential interactions of multiple compounds. Evidence from long-term field experiments suggests that soils may be more resilient and capable to degrade or stabilize pollutants than often assumed. In view of the need to source nutrients for expanding areas under organic farming, we discuss inputs originating from conventional farms vs. non-agricultural (i.e. societal) inputs. Closing nutrient cycles between agriculture and society is feasible in many cases, without being compromised by contaminants, and should be enhanced, aided by improved source control, waste treatment and sound risk assessments.


Assuntos
Agricultura Orgânica , Poluentes do Solo , Animais , Humanos , Fertilizantes/análise , Plásticos , Agricultura/métodos , Solo/química , Medição de Risco , Nutrientes , Poluentes do Solo/análise , Esgotos/química
2.
Chemosphere ; 324: 138318, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36907485

RESUMO

The new EU regulations on maximum levels of cadmium (Cd) in cacao products sparked research on countermeasures to reduce Cd concentrations in cacao beans. This study was set up to test the effects of soil amendments in two established cacao orchards (soil pH 6.6 and 5.1) in Ecuador. Soil amendments included: 1) agricultural limestone at 2.0 and 4.0 Mg ha-1 y-1, 2) gypsum at 2.0 and 4.0 Mg ha-1 y-1 and 3) compost at 12.5 and 25 Mg ha-1 y-1, all amendments were applied at the surface during two subsequent years. Lime application increased the soil pH by one unit down to 20 cm depth. On the acid soil, leaf Cd concentrations decreased by lime application and the reduction factor gradually rose to 1.5 after 30 months. No effects of liming or gypsum on leaf Cd was found in the pH neutral soil. Compost application in the pH neutral soil reduced leaf Cd concentration with factor 1.2 at 22 months but that effect was absent at 30 months after application. Bean Cd concentrations were unaffected by any of the treatments at 22 months after application (acid soil) or 30 months (pH neutral soil) suggesting that any treatment effects on bean Cd might be even more delayed than in leaves. Soil columns experiments in the laboratory showed that mixing lime with compost largely enhanced the depth of lime penetration compared to lime only. Compost + lime reduced 10-3 M CaCl2 extractable Cd in soil without lowering extractable Zn. Our results suggest that soil liming has the potential to lower Cd uptake in cacao in the long term in acid soils and that the compost + lime treatment should be tested at field scale to accelerate the effects of the mitigation.


Assuntos
Cacau , Poluentes do Solo , Solo , Equador , Cádmio/análise , Sulfato de Cálcio , Poluentes do Solo/análise
3.
Sci Rep ; 12(1): 8092, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35577865

RESUMO

Layered double hydroxides (LDHs) of magnesium (Mg) and aluminium (Al) are ion exchangers that can be used as slow release phosphorus (P) fertilisers. These LDHs can be used successfully to concentrate P from waste streams such as urine. This study was set up to test the fertiliser potential of P derived from urine and concentrated on LDHs. Ryegrass was grown in a pot trial using a P- and N-deficient soil where different urine derived fertilisers, i.e. LDH-P, stored urine and urine mixed with sludge as a source of P were compared to different mineral N and P doses in a full factorial design. Plants were grown for 75 days with four cuttings and did not exhibit salinity stress in stored urine treatments. Plant growth and P uptake responded to N, P doses in mineral fertilizer treatments with significant N-P interaction. The fertiliser use efficiency of urine fertilisers was lower than that of mineral fertilisers at equivalent total nutrient input for stored urine, due to lower N availability, and for urine mixed with sludge due to lower P availability. In contrast, the yield and P uptake of ryegrass grown on LDH loaded with P from urine (LDH-P) showed equal fertiliser P use as mineral fertiliser. Interestingly, the residual soil P after harvest, scored by the sum of isotopically exchangeable P in soil and the P uptake, was higher for LDH-P than for mineral P, confirming slow release properties of LDH that limit loss of P by fixation in soil.


Assuntos
Fertilizantes , Solo , Fertilizantes/análise , Hidróxidos , Minerais , Fósforo , Esgotos
4.
J Environ Radioact ; 233: 106588, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33773364

RESUMO

The Neogene-Paleogene glauconite sands are investigated for radionuclide sorption in the framework of the Belgian radioactive waste disposal program. This study was set up to measure the adsorption of radiostrontium (85Sr) on the sands and on glauconite fractions to identify factors explaining variable sorption among different formations. Batch 85Sr sorption experiments were set up with 45 different glauconite sands and glauconite fractions (125-250 µm) in a background solution of 1 mM CaCl2.H2O and 0.5 mM KCl. The distribution coefficients (KD) for 85Sr2+ ranged 23-65 L kg-1 for the intact sands and ranged 50-144 L kg-1 for the glauconite fractions. The KD values strongly correlated with the CEC (R2 = 0.62 for sands and 0.82 for glauconite fractions) and corresponded well with CEC based predictions based on two existing models calibrated to soils. The KD on the complete sand is proportional to the glauconite content and the KD of the glauconite fraction if no other clay minerals are present in significant amounts. Sorption equilibrium was reached within 48 h in the complete sands, in milled complete sands, in glauconite fractions and in milled glauconite fractions, suggesting no diffusive boundaries in the glauconite pellets. It is concluded that glauconite sands have a suitably high retention of radiostrontium and the sorption strength is in line with that of other geological barriers when judged from the CEC.


Assuntos
Monitoramento de Radiação , Areia , Adsorção , Bélgica , Minerais , Solo
5.
Sci Total Environ ; 720: 137392, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32145613

RESUMO

The Neogene-Paleogene glauconite sands of Belgium cover the Boom Clay deposits that are candidate host for radioactive waste disposal. It is unclear if the highly permeable sand formations may act as an additional barrier for radiocesium (137Cs) or could be added as a complementary sorption sink in a surface disposal concept. Glauconite is an Fe-rich phyllosilicate that is mainly present as 250-125 µm sized pellets in sand, it is unknown to what extent and how fast these pellets may bind 137Cs. Pelletized clays embedded in sand may have poorly accessible high affinity sites for 137Cs. The 137Cs sorption on 11 different glauconite sands was measured in batch in a background solution of 0.1 M CaCl2 and 0.5 mM KCl. The log transformed 137Cs distribution coefficient Kd (L kg-1) after 30 days reaction ranged 3.4-4.3, surprisingly close to the Kd of the Boom Clay (3.5). Isolated glauconite fractions exhibited similar 137Cs sorption potentials (log Kd 4.1-4.3) as the reference Illite du Puy (4.4). The small Kd variation among the Neogene-Paleogene sands was explained by its glauconite content (r = 0.82). The 137Cs sorption kinetics (1-57 days) of milled pellets (<2 µm) confirmed slower reaction with intact pellets than with milled samples. Additionally, the Kd values of milled samples (57 days) sorption are 1.1-1.5 fold larger than the corresponding intact pellets, suggesting that not all Cs binding sites are accessible in intact pellets. Strongly weathered pellets exhibited cracks (visible with SEM). In these pellets the Kd was similar for milled and intact pellets suggesting that cracks increase the accessibility of the inner sorption sites. After 8.5 months the Kd values were 1.6-1.8-fold above corresponding 1 month data and these long-term reactions were more pronounced as total sand K content was larger. An adsorption-desorption experiment illustrated that 137Cs sorption is not fully reversible.

6.
HIV Med ; 19(3): 216-226, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29194939

RESUMO

OBJECTIVES: Direct-acting antivirals (DAAs) for treatment of chronic hepatitis C virus (HCV) infection can cause drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) and non-cART co-medication. We mapped how physicians manage DDIs between DAAs and co-medication and analysed treatment outcomes. METHODS: Data were prospectively collected as part of the ATHENA HIV observational cohort and retrospectively analysed. Dutch patients with HIV/HCV coinfection who initiated treatment with DAAs between January 2015 and May 2016 were included. Co-medication 3 months prior to and during DAA therapy was identified. Potential DDIs with the DAAs were checked using http://hep-druginteractions.org. DDIs were categorized as: (1) no interaction expected; (2) potential interaction; (3) contra-indication; (4) no recommendation. These categories were used to determine which patients switched or had a DDI during DAA therapy with co-medication. RESULTS: A total of 423 patients were treated with DAAs, of whom 418 (99%) used cART and 251 (59%) used non-cART co-medication. Before commencing DAA treatment, in 17 of 84 (20%) patients the non-cART co-medication which could result in a category 2/3 DDI was discontinued before DAA initiation, including two of six (33%) prescriptions of category 3 drugs. A total of 196 of 418 (47%) patients had a category 2/3 DDI between their DAA regimen and cART. Category 2/3 DDIs were prevented by switching cART in 78 of 147 (53%) and 47 of 49 (98%) patients. Overall, 367 of 423 (87%) patients have achieved a sustained virological response (33 in follow-up). CONCLUSIONS: Prescription patterns suggest that physicians are aware of potential DDIs between co-medication and DAAs, in particular potential DDIs with cART. Greater awareness is needed concerning category 3 interactions between non-cART co-medication and DAAs.


Assuntos
Antivirais/uso terapêutico , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Antivirais/farmacologia , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Observacionais como Assunto , Padrões de Prática Médica , Estudos Prospectivos , Estudos Retrospectivos , Resposta Viral Sustentada
7.
Trop Med Int Health ; 23(3): 295-305, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29247579

RESUMO

OBJECTIVE: In Thailand, 7.2% of HIV patients are co-infected with hepatitis C virus (HCV), and these patients are treated with peg-interferon + ribavirin (PR) for their HCV infection. This study evaluates efficacy and safety of PR treatment and pharmacokinetics of ribavirin in this population. METHODS: HIV/HCV co-infected Thai patients were treated with PR for 24 or 48 weeks. Sustained virological response 24 weeks after the end of treatment (SVR24) was used to describe efficacy. (laboratory) safety parameters and ribavirin plasma concentrations were evaluated during study visits. Ribavirin concentrations were compared with t-tests for patients with and without anaemia (haemoglobin <10 g/dl) and SVR24. RESULTS: A total of 101 HIV/HCV co-infected patients were included; 88% were male (n = 88), and 46% were infected with genotype 3. The median (IQR) start dose was 14.28 mg/kg/day. SVR24 rate was 56%. All patients reported at least one (serious) adverse event, of which 28% of patients developed anaemia. Seven patients discontinued treatment due to toxicity issues. Geometric mean (IQR) ribavirin concentration was 1.81 (1.42-2.32) mg/l at week 8 of treatment. At week 8, patients with and without anaemia and SVR had ribavirin concentrations of 2.29 and 1.63 mg/l and 1.91 and 1.74 mg/l, respectively. CONCLUSIONS: PR treatment has comparable response rates and toxicity profile in Thai HIV/HCV co-infected patients as in Western HIV/HCV patients. However, ribavirin plasma concentrations were comparable with previously published studies in HIV/HCV co-infected patients, but both, just as SVR rate, were lower than in mono-infected patients.


Assuntos
Antivirais/administração & dosagem , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Antivirais/farmacocinética , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Interferon-alfa/farmacocinética , Masculino , Ribavirina/farmacocinética , Tailândia , Resultado do Tratamento , Carga Viral
8.
Aliment Pharmacol Ther ; 46(9): 864-872, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28881031

RESUMO

BACKGROUND: In the era of highly effective direct-acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients. AIM: To assess the association between RBV steady-state plasma levels and sustained virological response (SVR). METHODS: Consecutive HCV-infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady-state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady-state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses. RESULTS: A total of 183 patients were included, of whom 85% had one or more difficult-to-cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir-based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2-14.7) mg/kg/d, and median RBV steady-state plasma level was 2.66 (1.95-3.60) mg/L. In multivariable analyses, higher RBV steady-state plasma level (adjusted odds ratio 1.79 [95% CI 1.09-2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut-off for achieving SVR and 3.61 mg/L was the upper cut-off for preventing significant anaemia (Haemoglobin < 10 g/dL). CONCLUSION: In this cohort of mainly difficult-to-cure patients treated with DAAs plus RBV, higher RBV steady-state plasma level was an independent predictor of SVR.


Assuntos
Antivirais/sangue , Antivirais/uso terapêutico , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Ribavirina/sangue , Ribavirina/uso terapêutico , Adulto , Antivirais/farmacocinética , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ribavirina/farmacocinética , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada
9.
Clin Pharmacol Ther ; 102(3): 391-394, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28160270

RESUMO

During clinical development of medicines, manufacturers are obliged to assess the risk of drug-drug interactions (DDIs) with their new drug. There is no doubt that product labels of drugs that are nowadays introduced to the market contain much more information on DDIs than in the past. Indeed, the drug label is often the first source for DDIs available to physicians and pharmacists. But how informative are the data presented in the drug labels?


Assuntos
Desenho de Fármacos , Interações Medicamentosas , Rotulagem de Medicamentos , Humanos , Assistência ao Paciente/métodos , Preparações Farmacêuticas/administração & dosagem , Farmacêuticos/organização & administração , Médicos/organização & administração , Papel Profissional
10.
Int J Antimicrob Agents ; 49(3): 379-382, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28185946

RESUMO

Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were simultaneously treated with direct-acting antivirals (DAAs) for their chronic HCV infection. No pharmacokinetic drug-drug interactions (DDIs) were expected between tacrolimus and the selected DAAs. However, in both patients, tacrolimus plasma concentrations decreased during HCV treatment. We hypothesise that decreased plasma concentrations were not caused by a DDI but were an indirect result of the clearance of the HCV infection. During chronic HCV infection, pro-inflammatory cytokines may inhibit cytochrome P450 (CYP) enzymes, which are primarily responsible for tacrolimus metabolism. If this is true, then with clearance of the virus the activity of these enzymes will normalise and tacrolimus metabolism will increase. These changes were clinically relevant because the tacrolimus dosage needed to be adjusted. Therefore, physicians should be aware that CYP substrates with narrow therapeutic ranges might require dose adaption during HCV therapy with DAAs.


Assuntos
Antivirais/administração & dosagem , Interações Medicamentosas , Hepatite C Crônica/tratamento farmacológico , Imunossupressores/sangue , Plasma/química , Tacrolimo/sangue , Idoso , Antivirais/farmacocinética , Sistema Enzimático do Citocromo P-450/metabolismo , Hepatite C Crônica/cirurgia , Humanos , Imunossupressores/farmacocinética , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Tacrolimo/farmacocinética , Transplantados
11.
J Antimicrob Chemother ; 72(2): 486-489, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27798211

RESUMO

BACKGROUND: Atazanavir is boosted with the cytochrome P450 (CYP) 3A4 inhibitor ritonavir. When combined with the CYP3A4 substrate daclatasvir, the daclatasvir dosage should be reduced from 60 to 30 mg once daily. Recently, cobicistat was licensed as a CYP3A booster and used with atazanavir. OBJECTIVES: To determine whether the fixed-dose combination of atazanavir/cobicistat has an influence on daclatasvir pharmacokinetics comparable to that of the separate agents atazanavir and ritonavir. METHODS: A prospective, open-label, two-period, randomized, cross-over trial was performed in 16 healthy subjects (NCT02565888). Treatment consisted of 300/100 mg of atazanavir/ritonavir plus 30 mg of daclatasvir once daily (reference) and a second period of 300/150 mg of atazanavir/cobicistat plus 30 mg of daclatasvir once daily (test). A 24 h pharmacokinetic, steady-state curve was recorded for all drugs. Geometric mean ratios (GMRs) with 90% CI were calculated for daclatasvir and atazanavir AUCτ and Cmax to compare the effect of both treatments (test versus reference). Laboratory safety and adverse events were evaluated throughout the trial. RESULTS: All 16 healthy subjects completed the study. Median (range) age and BMI were 48.5 (21-55) years and 24.5 (19.0-29.2) kg/m2, respectively. Pharmacokinetic parameters of ritonavir and cobicistat were comparable to those in the literature. The GMRs (90% CI) of daclatasvir AUCτ and Cmax (test versus reference) were 101% (92%-111%) and 97% (89%-106%), respectively. Atazanavir GMRs (90% CI) of AUCτ and Cmax were 82% (75%-79%) and 74% (68%-81%), respectively. No serious adverse events were reported. CONCLUSIONS: Atazanavir/cobicistat and atazanavir/ritonavir had a similar influence on daclatasvir pharmacokinetics in healthy volunteers. Daclatasvir at 30 mg once daily is the correct dose when combined with atazanavir/cobicistat.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Cobicistat/uso terapêutico , Infecções por HIV/tratamento farmacológico , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Adulto , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacocinética , Sulfato de Atazanavir/farmacocinética , Carbamatos , Cobicistat/farmacocinética , Estudos Cross-Over , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Inibidores do Citocromo P-450 CYP3A/uso terapêutico , Feminino , Humanos , Imidazóis/farmacocinética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirrolidinas , Ritonavir/farmacocinética , Ritonavir/uso terapêutico , Valina/análogos & derivados , Adulto Jovem
13.
Clin Pharmacokinet ; 55(12): 1471-1494, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27317413

RESUMO

Treatment options for chronic hepatitis C virus (HCV) infection have drastically changed since the development and licensing of new potent direct-acting antivirals (DAAs). The majority of DAAs are extensively metabolized by liver enzymes and have the ability to influence cytochrome P450 (CYP) enzymes. Additionally, these DAAs are both substrates and inhibitors of drug transporters, which makes the DAAs both possible victims or perpetrators of drug-drug interactions (DDIs). There is a high prevalence of mental illnesses such as depression or psychosis in HCV-infected patients; therefore, psychoactive medications are frequently co-administered with DAAs. The majority of these psychoactive medications are also metabolized by CYP enzymes but remarkably little information is available on DDIs between psychoactive medications and DAAs. Hence, the aim of this review is to provide an overview of the interaction mechanisms between DAAs and psychoactive agents. In addition, we describe evidenced-based interactions between DAAs and psychoactive drugs and identify safe options for the simultaneous treatment of mental illnesses and chronic HCV infection.


Assuntos
Antivirais/farmacologia , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Psicotrópicos/farmacologia , Antivirais/farmacocinética , Antivirais/uso terapêutico , Interações Medicamentosas , Humanos , Psicotrópicos/farmacocinética , Psicotrópicos/uso terapêutico
14.
Aquat Toxicol ; 173: 74-82, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26851570

RESUMO

Previous studies have suggested that phosphorus (P) deficiency can increase the sensitivity of microalgae to toxic trace metals, potentially due to reduced metal detoxification at low cell P quota. The existing evidence is, however, inconsistent. This study was set up to determine the combined effects of zinc (Zn) and P supplies on Zn and P bioaccumulation and growth of the green microalgae Pseudokirchneriella subcapitata. Zinc toxicity was investigated in (i) a 24h growth rate assay with cells varying in initial cell P quota (0.5-1.7% P on cell dry weight) with no supplemental P during Zn exposure (Expt. 1) and in (ii) a 48h growth assay initiated with cells at the end of a 14-days steady state culture at three P addition rates (RARs) between 0.8 and 1.6day(-1) (Expt.2). The solution Zn concentrations required to reduce final cell density by 10% relative to control (EbC10) were 5-fold (Expt.1) or 2-fold (Expt.2) lower at the highest P supply than at the lowest P supply, i.e. Zn was more toxic at higher P supply, in contrast with the suggestions from previous studies. Cell P quota increased with increasing Zn in the exposure solution (Expt.2), thereby partially overcoming P deficiency under moderate Zn toxicity compared to low Zn exposure. Similarly, cell Zn increased with increasing P supply, potentially induced by Zn-P complexation or precipitation inside the cell. A dynamic growth model accounting for effects of external Zn and internal P on the specific growth rate was calibrated to all data. This model shows that the effect of solution Zn on specific growth rate (ErC50) was statistically unaffected by cell P quota. In contrast, this model predicts that the EbC10 (i.e. EC10 based on cell numbers) varies with P supply because cell P depends on external P and Zn. Moreover, scenario analysis predicts even contrasting trends of the EbC10 with increasing P supply depending on the duration of the growth assay and the P supply scenario. Our data at two experimental scenarios and the prediction under various relevant scenarios suggest a weaker effect of secondary stress factor (Zn) when nutrient deficiency (first stress factor) is prevailing.


Assuntos
Clorófitas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Zinco/toxicidade , Fosfatos/química , Fosfatos/metabolismo , Oligoelementos/metabolismo
15.
Br J Dermatol ; 172(2): 392-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25060063

RESUMO

BACKGROUND: Little is known about the impact of engineered nanoparticles (ENPs) on skin sensitization caused by chemicals. OBJECTIVES: We determined the ability of different ENPs (TiO2 , Ag and SiO2 ) and aged paint particles containing ENPs to modulate dermal sensitization by a known potent dermal sensitizer. METHODS: The fur of BALB/c mice in the area around the ears was cut with scissors 1 day prior to topical exposure to ENPs (0·4, 4 or 40 mg mL(-1) ), paint particles containing ENPs (4 mg mL(-1) ) or vehicle (day 0). On days 1, 2 and 3, the mice received dermal applications on the back of both ears of 2,4-dinitrochlorobenzene (DNCB) or vehicle. The stimulation index (SI) was calculated on day 6. RESULTS: Topical exposure to TiO2 , Ag or SiO2 ENPs, or aged paint particles followed by vehicle treatment as a control, did not influence the SI. When 4 mg mL(-1) TiO2 ENPs were applied prior to DNCB sensitization, we found an increased SI compared with vehicle-exposed mice prior to DNCB sensitization. Furthermore, an increased titanium concentration was found in the draining lymph node cells of this group. Topical exposure to Ag or SiO2 ENPs or aged paint particles prior to DNCB sensitization did not influence the SI. CONCLUSIONS: We have demonstrated that topical exposure to TiO2 ENPs increases chemical-induced dermal sensitization.


Assuntos
Dinitroclorobenzeno/toxicidade , Irritantes/toxicidade , Nanopartículas/administração & dosagem , Titânio/farmacologia , Administração Cutânea , Alérgenos/farmacologia , Animais , Dermatite Alérgica de Contato/etiologia , Masculino , Nanopartículas Metálicas/administração & dosagem , Camundongos Endogâmicos BALB C , Pintura , Dióxido de Silício/farmacologia , Pele/efeitos dos fármacos
16.
Sci Total Environ ; 485-486: 319-328, 2014 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-24727598

RESUMO

The gradual increase of soil cadmium concentrations in European soils during the 20th century has prompted environmental legislation to limit soil cadmium (Cd) accumulation. Mass balances (input-output) reflecting the period 1980-1995 predicted larger Cd inputs via phosphate (P) fertilizers and atmospheric deposition than outputs via crop uptake and leaching. This study updates the Cd mass balance for the agricultural top soils of EU-27+Norway (EU-27+1). Over the past 15 years, the use of P fertilizers in the EU-27+1 has decreased by 40%. The current mean atmospheric deposition of Cd in EU is 0.35 g Cd ha(-1) yr(-1), this is strikingly smaller than values used in the previous EU mass balances (~3 g Cd ha(-1) yr(-1)). Leaching of Cd was estimated with most recent data of soil solution Cd concentrations in 151 soils, which cover the range of European soil properties. No significant time trends were found in the data of net applications of Cd via manure, compost, sludge and lime, all being small sources of Cd at a large scale. Modelling of the future long-term changes in soil Cd concentrations in agricultural top soils under cereal or potato culture predicts soil Cd concentrations to decrease by 15% over the next 100 years in an average scenario, with decreasing trends in some scenarios being more prevalent than increasing trends in other scenarios. These Cd balances have reverted from the general positive balances estimated 10 or more years ago. Uncertainty analysis suggests that leaching is the most uncertain relative to other fluxes.


Assuntos
Agricultura , Cádmio/análise , Poluição Ambiental/estatística & dados numéricos , Poluentes do Solo/análise , Solo/química , Monitoramento Ambiental , Noruega
17.
Br J Cancer ; 109(7): 1805-12, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23969729

RESUMO

BACKGROUND: The expression of SMAD4, the central component of the transforming growth factor-ß (TGF-ß) and bone morphogenetic protein (BMP) signalling pathways, is lost in 50% of pancreatic cancers and is associated with a poor survival. Although the TGF-ß pathway has been extensively studied and characterised in pancreatic cancer, there is very limited data on BMP signalling, a well-known tumour-suppressor pathway. BMP signalling can be lost not only at the level of SMAD4 but also at the level of BMP receptors (BMPRs), as has been described in colorectal cancer. METHODS: We performed immunohistochemical analysis of the expression levels of BMP signalling components in pancreatic cancer and correlated these with survival. We also manipulated the activity of BMP signalling in vitro. RESULTS: Reduced expression of BMPRIA is associated with a significantly worse survival, primarily in a subset of SMAD4-positive cancers. In vitro inactivation of SMAD4-dependent BMP signalling increases proliferation and invasion of pancreatic cancer cells, whereas inactivation of BMP signalling in SMAD4-negative cells does not change the proliferation and invasion or leads to an opposite effect. CONCLUSION: Our data suggest that BMPRIA expression is a good prognostic marker and that the BMP pathway is a potential target for future therapeutic interventions in pancreatic cancer.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo I/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteína Smad4/metabolismo , Angiopoietina-1/biossíntese , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Neovascularização Patológica/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Pirazóis/farmacologia , Pirimidinas/farmacologia , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais , Proteína Smad4/genética , Sobrevida , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese
18.
Animal ; 7(4): 655-65, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23171501

RESUMO

Data from 113 Dutch organic farms were analysed to determine the effect of cross-breeding on production and functional traits. In total, data on 33 788 lactations between January 2003 and February 2009 from 15 015 cows were available. Holstein-Friesian pure-bred cows produced most kg of milk in 305 days, but with the lowest percentages of fat and protein of all pure-bred cows in the data set. Cross-breeding Holstein dairy cows with other breeds (Brown Swiss, Dutch Friesian, Groningen White Headed, Jersey, Meuse Rhine Yssel, Montbéliarde or Fleckvieh) decreased milk production, but improved fertility and udder health in most cross-bred animals. In most breeds, heterosis had a significant effect (P < 0.05) on milk (kg in 305 days), fat and protein-corrected milk production (kg in 305 days) and calving interval (CI) in the favourable direction (i.e. more milk, shorter CI), but unfavourably for somatic cell count (higher cell count). Recombination was unfavourable for the milk production traits, but favourable for the functional traits (fertility and udder health). Farm characteristics, like soil type or housing system, affected the regression coefficients on breed components significantly. The effect of the Holstein breed on milk yield was twice as large in cubicle housing as in other housing systems. Jerseys had a negative effect on fertility only on farms on sandy soils. Hence, breed effects differ across farming systems in the organic farming and farmers can use such information to dovetail their farming system with the type of cow they use.


Assuntos
Criação de Animais Domésticos/métodos , Bovinos/fisiologia , Fertilidade , Hibridização Genética , Glândulas Mamárias Animais/fisiologia , Leite/metabolismo , Animais , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Feminino , Abrigo para Animais , Lactação , Países Baixos , Agricultura Orgânica/métodos , Solo/química
19.
Aquat Toxicol ; 124-125: 66-71, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22903064

RESUMO

The Free Ion Activity Model (FIAM) predicts that cadmium (Cd) uptake by organisms is identical for solutions with the same free Cd(2+) concentration and inorganic composition. Clear exceptions to the FIAM have been shown for Cd uptake by plant roots, periphyton and human cells where labile Cd complexes increase bioavailability and which has been attributed to their role in enhancing Cd diffusion towards the uptake cells. Here, we assessed the role of labile Cd complexes on Cd uptake by algae, for which diffusion limitations should be less pronounced due to their smaller size. Long-term (3 days) Cd uptake by the green algae Pseudokirchneriella subcapitata was measured in resin buffered solutions with or without synthetic ligands and at three Cd(2+) ion activities (pCd 8.2-5.7). The free Cd(2+) activity was maintained during the test using a metal-selective resin located in the algal bottles. Total dissolved Cd increased up to 35-fold by adding the synthetic ligands at constant Cd(2+) activity. In contrast, Cd uptake by algae increased maximally 2.8 fold with increasing concentration of the synthetic ligands and the availability of the complexes were maximally 5.2% relative to Cd(2+) for NTA and CDTA complexes. It is concluded that labile Cd complexes do not greatly enhance Cd bioavailability to the unicellular algae and calculations suggest that Cd transport from solution to these small cells is not rate limiting.


Assuntos
Cádmio/metabolismo , Clorófitas/metabolismo , Disponibilidade Biológica , Soluções Tampão , Cádmio/química , Ligantes , Resinas Sintéticas/química , Soluções
20.
Chemosphere ; 89(11): 1369-75, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22749126

RESUMO

Biodegradation of trichloroethene (TCE) near a Dense Non Aqueous Phase Liquid (DNAPL) can enhance the dissolution rate of the DNAPL by increasing the concentration gradient at the DNAPL-water interface. Two-dimensional flow-through sand boxes containing a TCE DNAPL and inoculated with a TCE dechlorinating consortium were set up to measure this bio-enhanced dissolution under anaerobic conditions. The total mass of TCE and daughter products in the effluent of the biotic boxes was 3-6 fold larger than in the effluent of the abiotic box. However, the mass of daughter products only accounted for 19-55% of the total mass of chlorinated compounds in the effluent, suggesting that bio-enhanced dissolution factors were maximally 1.3-2.2. The enhanced dissolution most likely primarily resulted from variable DNAPL distribution rather than biodegradation. Specific dechlorination rates previously determined in a stirred liquid medium were used in a reactive transport model to identify the rate limiting factors. The model adequately simulated the overall TCE degradation when predicted resident microbial numbers approached observed values and indicated an enhancement factor for TCE dissolution of 1.01. The model shows that dechlorination of TCE in the 2D box was limited due to the short residence time and the self-inhibition of the TCE degradation. A parameter sensitivity analysis predicts that the bio-enhanced dissolution factor for this TCE source zone can only exceed a value of 2 if the TCE self-inhibition is drastically reduced (when a TCE tolerant dehalogenating community is present) or if the DNAPL is located in a low-permeable layer with a small Darcy velocity.


Assuntos
Tricloroetileno/química , Poluentes Químicos da Água/química , Bactérias/metabolismo , Biodegradação Ambiental , Modelos Químicos , Tricloroetileno/análise , Tricloroetileno/metabolismo , Microbiologia da Água , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo
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