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1.
PLoS One ; 15(9): e0237977, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915802

RESUMO

The objective of this study was to determine the radiocesium transfer rates of pigs fed haylage contaminated with low levels of cesium at different growth stages. We measured the body weight of juvenile and adult pigs during the treatment period to confirm their health status. We also performed pig blood hematologic and biochemical analyses at both growth stages. To our knowledge, this is the first study to report pig radiocesium transfer coefficient rates after 1 month of chronic oral treatment, which is the period assumed to be required for body equilibrium under a diet of radiocesium-contaminated food. The results showed higher radiocesium retention rates in the kidneys, liver, spleen, genitals, psoas major, bladder, thyroid, and urine than in the blood and bone (tibia and femur) of pigs at both growth stages. The radiocesium retention levels were generally higher in juvenile pigs than in adult pigs, with the highest transfer coefficient ratio in the kidneys (16.2%).


Assuntos
Radioisótopos de Césio/metabolismo , Contaminação Radioativa de Alimentos/análise , Administração Oral , Animais , Peso Corporal , Radioisótopos de Césio/sangue , Rim/química , Rim/metabolismo , Fígado/química , Fígado/metabolismo , Suínos
2.
Phys Rev Lett ; 125(3): 038003, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32745423

RESUMO

Experiments and theory have shown that cell monolayers and epithelial tissues exhibit solid-liquid and glass-liquid transitions. These transitions are biologically relevant to our understanding of embryonic development, wound healing, and cancer. Current models of confluent epithelia have focused on the role of cell shape, with less attention paid to cell extrusion, which is key for maintaining homeostasis in biological tissue. Here, we use a multiphase field model to study the solid-liquid transition in a confluent monolayer of deformable cells. Cell overlap is allowed and provides a way for modeling the precursor for extrusion. When cells overlap rather than deform, we find that the melting transition changes from continuous to first order like, and that there is an intermittent regime close to the transition, where solid and liquid states alternate over time. By studying the dynamics of five- and sevenfold disclinations in the hexagonal lattice formed by the cell centers, we observe that these correlate with spatial fluctuations in the cellular overlap, and that cell extrusion tends to initiate near fivefold disclinations.


Assuntos
Células Epiteliais/química , Células Epiteliais/citologia , Rim/química , Rim/citologia , Modelos Biológicos , Animais , Fenômenos Biofísicos , Movimento Celular/fisiologia , Forma Celular/fisiologia , Cães , Transição Epitelial-Mesenquimal , Células Madin Darby de Rim Canino , Transição de Fase
3.
Environ Sci Pollut Res Int ; 27(27): 34557-34566, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32557022

RESUMO

The indigenous population is one of the most vulnerable to suffer from contaminated environments. One of the target organs to suffer early deterioration from exposure to toxins is the kidney. The objective of this article was to evaluate biomarkers of exposure to organic and inorganic toxins and biomarkers of early kidney damage in urine from an indigenous Tenek population in Mexico. The biomarkers of exposure were Li, Be, Al, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Mo, Sn, Ba, and Pb evaluated by ICP-MS and hippuric acid for toluene exposure evaluated by UV-coupled with liquid chromatography; the biomarkers of kidney damage were cystatin C (Cys-C), osteopontin (OPN), retinol-binding protein-4 (RPB-4), and neutrophil gelatinase-associated lipocalin (NGAL). Thirty-one urine samples were obtained from indigenous people; 16, 42, 45.1, and 45.2% of the population exceeded the reference values for Pb, Zn, As, and hippuric acid respectively. Our results demonstrate significant correlations between the metals tested and the proteins associated with renal damage; Cys-C, OPN, and RPB4 showed a significant correlation with Li, B, and Mo, as well as hippuric acid in the case of Cys-C and Zn in OPN and RPB-4; NGAL did not present significant correlations with any of the pollutants of the study. This pilot study contributes to the evidence of great inequity in health associated to environmental pollution matters faced by indigenous people and addresses the need of initiatives for mitigation under the perspective that health is a fundamental human right.


Assuntos
Poluentes Ambientais , Humanos , Rim/química , Metais/análise , México , Projetos Piloto
4.
Metabolism ; 109: 154283, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32497536

RESUMO

BACKGROUND: Absolute dietary fat intake but even more so fatty acid pattern is discussed to be critical in the development of non-alcoholic fatty liver disease (NAFLD). Here, we determined if switching a butterfat enriched diet to a rapeseed oil (RO) enriched diet affects progression of an existing NAFLD and glucose intolerance in mice. METHODS: For eight weeks, female C57Bl/6J mice were either fed a liquid control (C) or a butterfat-, fructose- and cholesterol-rich diet (BFC, 25E% butterfat) to induce early signs of steatohepatitis and glucose intolerance in mice. For additional five weeks mice received either BFC or C or a fat-, fructose- and cholesterol-rich and control diet, in which butterfat was replaced with RO (ROFC and CRO). Markers of glucose metabolism, liver damage and intestinal barrier were assessed. RESULTS: Exchanging butterfat with RO attenuated the progression of BFC diet-induced NAFLD and glucose intolerance. Beneficial effects of RO were associated with lower portal endotoxin levels and an attenuation of the induction of the toll-like receptor-4-dependent signaling cascades in liver. Peroxisome proliferator-activated receptor γ activity was induced in small intestine of ROFC-fed mice. CONCLUSION: Taken together, exchanging butterfat with RO attenuated the progression of diet-induced steatohepatitis and glucose intolerance in mice.


Assuntos
Manteiga/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Óleo de Brassica napus/uso terapêutico , Animais , Progressão da Doença , Endotoxinas/metabolismo , Feminino , Rim/química , Camundongos , Camundongos Endogâmicos C57BL , Receptor 4 Toll-Like
5.
PLoS Genet ; 16(5): e1008786, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32392242

RESUMO

Allele-specific expression (ASE) analysis, which quantifies the relative expression of two alleles in a diploid individual, is a powerful tool for identifying cis-regulated gene expression variations that underlie phenotypic differences among individuals. Existing methods for gene-level ASE detection analyze one individual at a time, therefore failing to account for shared information across individuals. Failure to accommodate such shared information not only reduces power, but also makes it difficult to interpret results across individuals. However, when only RNA sequencing (RNA-seq) data are available, ASE detection across individuals is challenging because the data often include individuals that are either heterozygous or homozygous for the unobserved cis-regulatory SNP, leading to sample heterogeneity as only those heterozygous individuals are informative for ASE, whereas those homozygous individuals have balanced expression. To simultaneously model multi-individual information and account for such heterogeneity, we developed ASEP, a mixture model with subject-specific random effect to account for multi-SNP correlations within the same gene. ASEP only requires RNA-seq data, and is able to detect gene-level ASE under one condition and differential ASE between two conditions (e.g., pre- versus post-treatment). Extensive simulations demonstrated the convincing performance of ASEP under a wide range of scenarios. We applied ASEP to a human kidney RNA-seq dataset, identified ASE genes and validated our results with two published eQTL studies. We further applied ASEP to a human macrophage RNA-seq dataset, identified genes showing evidence of differential ASE between M0 and M1 macrophages, and confirmed our findings by results from cardiometabolic trait-relevant genome-wide association studies. To the best of our knowledge, ASEP is the first method for gene-level ASE detection at the population level that only requires the use of RNA-seq data. With the growing adoption of RNA-seq, we believe ASEP will be well-suited for various ASE studies for human diseases.


Assuntos
Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Locos de Características Quantitativas , Análise de Sequência de RNA/métodos , Alelos , Feminino , Regulação da Expressão Gênica , Genética Populacional , Humanos , Rim/química , Macrófagos/química , Modelos Genéticos , Software
6.
Chemosphere ; 252: 126583, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32443269

RESUMO

Birds are bioindicators for research on the relationship between environmental heavy metal concentration levels and accumulation levels in bird tissues. We use roadkill samples, collected by citizen science participants, to investigate the accumulation levels and associations of seven heavy metals in internal organs (heart, liver, and kidney), feathers (primary and breast), and bones (sternum and femur) of two focal species, Amaurornis phoenicurus and Gallinula chloropus. We found that heavy metal accumulation varied by target tissue, and that variables are associated with bird species and heavy metal type. Although Zn and Cu were highest by concentration among both species, Cu was mostly accumulated in internal organs, As in feathers, and Pb in bones. Concentrations of As, Ni, and Pb in feathers of both focal species were lower than those reported in literature, whereas Cd and Cr were above toxic levels. The results also showed that spatial correlation for heavy metal concentration among bird tissues were weaker than non-spatial correlation, suggesting low spatial autocorrelations and variability. In addition, multiple regression analysis revealed significant correlation for Cr, As, and Pb estimations in A. phoenicurus heart, sternum, and kidney, respectively; and potentially Cr in G. chloropus femur by using feathers. These results support the feasibility of using feathers as indicators of As, Cr, and Pb heavy metal contamination to enhance our understanding of heavy metal accumulation in birds, although caution is required for feather-based estimations of Cd, Cu, and Ni concentration.


Assuntos
Aves/metabolismo , Monitoramento Ambiental/métodos , Metais Pesados/metabolismo , Animais , Crowdsourcing , Biomarcadores Ambientais , Plumas/química , Rim/química , Fígado/química , Metais Pesados/análise
7.
Bull Environ Contam Toxicol ; 104(5): 559-567, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185428

RESUMO

Nineteen loggerhead sea turtles (Caretta caretta) stranded along the southwestern Mediterranean coastline (Andalusia) were used in this study. A total of 68 samples of fat (n = 18), liver (n = 15), kidney (n = 13), pectoral muscle (n = 19), and brain (n = 3) were analysed for total mercury (Hg) and organochlorine pesticides [OC: ∑Dichlorodiphenyltrichloroethanes (∑DDT), ∑Hexachlorocyclohexane (∑HCH), ∑Heptachlor, ∑Drins and ∑Endosulfan]. These loggerhead sea turtles showed tissue Hg and OC concentrations similar to or lower than those reported in other studies. Few growth-related variations in Hg or OC levels in relation to straight carapace length were found, probably because the specimens were mostly juveniles. This study will help to fill the gap on spatio-temporal exposure data and ascertain the real world-wide picture of the contamination levels in loggerhead sea turtles.


Assuntos
Hidrocarbonetos Clorados/análise , Mercúrio/análise , Praguicidas/análise , Tartarugas , Poluentes Químicos da Água/análise , Animais , Monitoramento Biológico , Rim/química , Fígado/química , Mar Mediterrâneo , Músculos/química , Espanha
8.
J Vet Diagn Invest ; 32(2): 291-300, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32052705

RESUMO

We compared inductively coupled plasma-mass spectrometry (ICP-MS) test results for the analysis of heavy metals (As, Ba, Cd, Hg, Pb, and Se) in pet foods and routine veterinary diagnostic specimens using intralaboratory and interlaboratory comparisons. Four laboratories, 1 principal laboratory and 3 collaborating laboratories, conducted instrument comparison (limit of detection [LOD], limit of quantification [LOQ], and linear dynamic range [LDR] on 24 data sets), in-house method comparison (accuracy and precision on 120 data sets), and interlaboratory comparison (reproducibility on 528 data sets using Horwitz equation analysis). Matrices tested included 2 types of pet food jerky treats (chicken and sweet potato), bovine blood, and bovine liver and kidney. The instrument comparison study confirmed that ICP-MS provided the sensitivity necessary for the analysis of all heavy metals tested at concentrations below the level of concern for routine diagnostic testing. The "in-house" method comparison samples, spiked at low (0.04 µg/g), medium (0.4 µg/g), and high (8.0 µg/g; note: the high validation level spike for mercury was 2 µg/g) concentration levels, indicated that ICP-MS can meet U.S. FDA acceptance criteria for both accuracy (90-105% recovery) and precision (< 6% coefficient of variation). The interlaboratory comparison studies showed that ICP-MS is a reproducible method for the analysis of heavy metals (HorRat value of 0.5-2.0) except for mercury in one laboratory, which used a different sample preparation method (open block rather than microwave digestion). Overall, our study showed that ICP-MS is a reproducible method for the analysis of heavy metals in spite of minor differences in methodology.


Assuntos
Ração Animal/análise , Bovinos/metabolismo , Rim/química , Fígado/química , Espectrometria de Massas/veterinária , Metais Pesados/análise , Animais , Bovinos/sangue
9.
J Am Soc Mass Spectrom ; 31(2): 326-335, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32031384

RESUMO

First results for a new atmospheric-pressure matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging source operating at 213 nm laser wavelength are presented. The activation of analytes in the 213 nm MALDI process at atmospheric pressure was evaluated and compared to results for 337 nm MALDI and electrospray ionization using thermometer molecules. Different sample preparation techniques for nicotinic acid, the matrix with the highest ionization efficiency at 213 nm of all tested matrices, were evaluated and optimized to obtain small crystal sizes, homogenous matrix layer sample coverage, and high ion signal gains. Mass spectrometry imaging experiments of phospholipids in mouse tissue sections in positive- and negative-ion mode with different lateral resolutions and the corresponding pre-/post-mass spectrometry imaging workflows are presented. The use of custom-made objective lenses resulted in sample ablation spot diameters of on average 2.9 µm, allowing mass spectrometry imaging experiments to be performed with 3 µm pixel size without oversampling. The ion source was coupled to an orbital trapping mass spectrometer offering high mass resolution (>100.000), high mass accuracy (≤ ±2 ppm), and high sensitivity (single pixel on-tissue tandem MS from 6.6 µm2 ablation area). The newly developed 213 nm atmospheric-pressure MALDI source combines the high mass resolution and high mass accuracy performance characteristics of orbital trapping mass spectrometers with high lateral resolution (pixel size ∼3 µm) mass spectrometry imaging.


Assuntos
Química Encefálica , Rim/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Pressão Atmosférica , Lasers , Camundongos , Fosfolipídeos/análise
10.
J Nutr ; 150(5): 1135-1143, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32006016

RESUMO

BACKGROUND: Ex vivo studies suggest that increased renal prostanoids can mediate effects of high-protein (HP) compared with low-protein (LP) diets on normal and diseased kidneys. However, a short-term HP feeding study in normal male rats failed to demonstrate higher renal prostanoids in vivo. OBJECTIVES: The aim of the present study was to investigate whether long-term HP feeding alters renal prostanoids in male and female mice, with and without kidney disease. METHODS: Weanling normal mice (CD1) and mice with kidney disease (CD1-pcy/pcy mice) were fed standard diets with normal protein [NP, 20% of energy (%E)] or HP (35%E) for 13 wk. Renal disease was assessed by histomorphometric analysis of cysts and fibrosis, and measurement of serum urea nitrogen (SUN) and creatinine concentrations. Targeted analysis of renal oxylipins was performed by HPLC-MS/MS. RESULTS: The HP diet increased kidney size and water content of normal kidneys, and worsened disease in CD1-pcy/pcy mice as indicated by higher (P < 0.05) kidney weights (8-31%), water content (8-10%), cyst volume (36-60%), fibrous volume (44-53%), and SUN (47-55%). Diseased compared with normal kidneys had higher (P < 0.05) concentrations of 6 of 11 prostanoids and lower (P < 0.05) concentrations of 33 of 54 other oxylipins. This is consistent with previously known effects of dietary HP and disease effects on the kidney. However, the HP diet did not alter renal prostanoids and other renal oxylipins in either normal or diseased kidneys (P < 0.05), despite having the expected physiological effects on normal and diseased kidneys. This study also showed that females have higher concentrations of renal prostanoids [9 of 11 prostanoids higher (P < 0.05) in females], but lower concentrations of other oxylipins [28 of 54 other oxylipins lower (P < 0.05) in females]. CONCLUSIONS: The effects of HP diets on normal and diseased kidneys in CD1 and CD1-pcy/pcy mice are independent of renal oxylipin alterations.


Assuntos
Dieta Rica em Proteínas/efeitos adversos , Nefropatias/genética , Nefropatias/metabolismo , Rim/química , Oxilipinas/análise , Prostaglandinas/análise , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Genótipo , Rim/patologia , Nefropatias/patologia , Doenças Renais Císticas/congênito , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Masculino , Camundongos , Tamanho do Órgão , Prostaglandina-Endoperóxido Sintases/metabolismo , Fatores Sexuais
11.
Food Chem Toxicol ; 137: 111127, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945393

RESUMO

The extensive use of doxycycline in aquaculture results in drug residue violations that negatively impact human food safety. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for doxycycline to predict drug residues and withdrawal times (WTs) in grass carp (Ctenopharyngodon idella) after daily oral administration for 3 days. Physiological parameters including cardiac output and organ weights were measured experimentally. Chemical-specific parameters were obtained from the literature or estimated by fitting to the observed data. The model properly captured the observed kinetic profiles of doxycycline in tissues (i.e., liver, kidney, muscle + skin and gill). The predicted WT in muscle + skin by Monte Carlo analysis based on sensitive parameters identified at 24 h after drug administration was 41 d, which was similar to 43 d calculated using the tolerance limit method. Sensitivity analysis identified two additional sensitive parameters at 6 weeks: intestinal transit rate constant and urinary elimination rate constant. The predicted WT in muscle + skin based on sensitive parameters identified at 6 weeks was 54 d. This model provides a useful tool to estimate tissue residues and withdrawal times for doxycycline in grass carp and also serves a foundation for extrapolation to other fish species and other tetracyclines.


Assuntos
Antibacterianos/análise , Carpas/metabolismo , Doxiciclina/análise , Resíduos de Drogas/análise , Animais , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Antibacterianos/farmacocinética , Doxiciclina/administração & dosagem , Doxiciclina/metabolismo , Doxiciclina/farmacocinética , Resíduos de Drogas/metabolismo , Resíduos de Drogas/farmacocinética , Inocuidade dos Alimentos , Brânquias/química , Brânquias/metabolismo , Rim/química , Rim/metabolismo , Fígado/química , Fígado/metabolismo , Músculos/química , Músculos/metabolismo
12.
Molecules ; 25(2)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963528

RESUMO

Metformin is the first-line drug for type 2 diabetes mellitus control. It is established that this drug traffics through OCT-2 and MATE-1 transporters in kidney tubular cells and is excreted in its unaltered form in the urine. Hereby, we provide evidence that points towards the metformin-dependent upregulation of OCT-2 and MATE-1 in the kidney via the transcription factor proliferator-activated receptor alpha (PPARα). Treatment of wild type mice with metformin led to the upregulation of the expression of OCT-2 and MATE-1 by 34% and 157%, respectively. An analysis in a kidney tubular cell line revealed that metformin upregulated PPARα and OCT-2 expression by 37% and 299% respectively. MK-886, a PPARα antagonist, abrogated the OCT-2 upregulation by metformin and reduced MATE-1 expression. Conversely, gemfibrozil, an agonist of PPARα, elicited the increase of PPARα, OCT-2, and MATE-1 expression by 115%, 144%, and 376%, respectively. PPARα knockout mice failed to upregulate both the expression of OCT-2 and MATE-1 in the kidney upon metformin treatment, supporting the PPARα-dependent metformin upregulation of the transporters in this organ. Taken together, our data sheds light on the metformin-induced mechanism of transporter modulation in the kidney, via PPARα, and this effect may have implications for drug safety and efficacy.


Assuntos
Rim/química , Metformina/administração & dosagem , Proteínas de Transporte de Cátions Orgânicos/genética , Transportador 2 de Cátion Orgânico/genética , PPAR alfa/genética , Animais , Linhagem Celular , Genfibrozila/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Indóis/farmacologia , Rim/efeitos dos fármacos , Masculino , Metformina/farmacologia , Camundongos , Regulação para Cima/efeitos dos fármacos
13.
Nat Biotechnol ; 38(3): 303-308, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31959954

RESUMO

Monitoring drug-target interactions with methods such as the cellular thermal-shift assay (CETSA) is well established for simple cell systems but remains challenging in vivo. Here we introduce tissue thermal proteome profiling (tissue-TPP), which measures binding of small-molecule drugs to proteins in tissue samples from drug-treated animals by detecting changes in protein thermal stability using quantitative mass spectrometry. We report organ-specific, proteome-wide thermal stability maps and derive target profiles of the non-covalent histone deacetylase inhibitor panobinostat in rat liver, lung, kidney and spleen and of the B-Raf inhibitor vemurafenib in mouse testis. In addition, we devised blood-CETSA and blood-TPP and applied it to measure target and off-target engagement of panobinostat and the BET family inhibitor JQ1 directly in whole blood. Blood-TPP analysis of panobinostat confirmed its binding to known targets and also revealed thermal stabilization of the zinc-finger transcription factor ZNF512. These methods will help to elucidate the mechanisms of drug action in vivo.


Assuntos
Sangue/metabolismo , Proteoma/química , Proteoma/metabolismo , Bibliotecas de Moléculas Pequenas/administração & dosagem , Animais , Azepinas/administração & dosagem , Azepinas/farmacologia , Células Hep G2 , Humanos , Rim/química , Rim/metabolismo , Fígado/química , Fígado/metabolismo , Pulmão/química , Pulmão/metabolismo , Masculino , Espectrometria de Massas , Camundongos , Especificidade de Órgãos , Panobinostat/administração & dosagem , Panobinostat/farmacologia , Estabilidade Proteica , Ratos , Bibliotecas de Moléculas Pequenas/farmacologia , Baço/química , Baço/metabolismo , Testículo/química , Testículo/metabolismo , Termodinâmica , Triazóis/administração & dosagem , Triazóis/farmacologia , Vemurafenib/administração & dosagem , Vemurafenib/farmacologia
14.
J Zoo Wildl Med ; 50(4): 956-965, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926528

RESUMO

Nephrolithiasis has been reported in several aquatic mammals including bottlenose dolphins (Tursiops truncatus), small clawed otters (Amblonyx cinereus), European river otters (Lutra lutra), North American river otters (Lontra canadensis), northern elephant seals (Mirounga angustirostris), Florida manatees (Trichechus manatus latirostris), and California sea lions (Zalophus californianus). Compositions of calculi in previous cases were predominantly calcium oxalate or ammonium acid urate. Xanthine urolithiasis is rare in veterinary medicine. Primary cases (without exposure to xanthine dehydrogenase inhibitors) occur as a consequence of hereditary xanthinuria, although the causal mutation has only been discovered in a subset of cases. Five captive juvenile giant otters (Pteronura brasiliensis) from two facilities were diagnosed with nephrolithiasis: three siblings from one set of parents and two siblings from another pair. Serum analyte assays revealed renal compromise in affected individuals. Computed tomography (CT) confirmed the presence of nephrolithiasis in one individual. Postmortem evaluation identified extensive bilateral nephrolithiasis on gross necropsy in four of five cases. Calculus analyses identified 100% xanthine composition. Histologic examination revealed marked nephrolithiasis with associated tubular necrosis and gastric mineralization. Nutrient composition of the diet including mineral and purine content was assessed. No association between diet and nephroliths was found in this study. This is the first report of xanthine nephrolithiasis in aquatic mammals. The potential role of diet and genetics in xanthine nephrolithiasis in the small inbred population of giant otters under human care needs further investigation to assess the implications of this disease process for the long-term captive management of this species.


Assuntos
Nefrolitíase/veterinária , Lontras , Xantina/química , Animais , Evolução Fatal , Feminino , Rim/química , Rim/patologia , Masculino , Nefrolitíase/mortalidade , Nefrolitíase/patologia
16.
Nanotoxicology ; 14(3): 420-432, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31994971

RESUMO

Silicon dioxide (silica, SiO2, SAS) and titanium dioxide (TiO2) are produced in high volumes and applied in many consumer and food products. As a consequence, there is a potential human exposure and subsequent systemic uptake of these particles. In this study we show the characterization and quantification of both total silicon (Si) and titanium (Ti), and particulate SiO2 and TiO2 in postmortem tissue samples from 15 deceased persons. Included tissues are liver, spleen, kidney and the intestinal tissues jejunum and ileum. Low-level analysis was enabled by the use of fully validated sample digestion methods combined with (single particle) inductively coupled plasma high resolution mass spectrometry techniques (spICP-HRMS). The results show a total-Si concentration ranging from <2 to 191 mg Si/kg (median values of 5.8 (liver), 9.5 (spleen), 7.7 (kidney), 6.8 (jejunum), 7.6 (ileum) mg Si/kg) while the particulate SiO2 ranged from <0.2 to 25 mg Si/kg (median values of 0.4 (liver), 1.0 (spleen), 0.4 (kidney), 0.7 (jejunum, 0.6 (ileum) mg Si/kg), explaining about 10% of the total-Si concentration. Particle sizes ranged from 150 to 850 nm with a mode of 270 nm. For total-Ti the results show concentrations ranging from <0.01 to 2.0 mg Ti/kg (median values of 0.02 (liver), 0.04 (spleen), 0.05 (kidney), 0.13 (jejunum), 0.26 (ileum) mg Ti/kg) while particulate TiO2 concentrations ranged from 0.01 to 1.8 mg Ti/kg (median values of 0.02 (liver), 0.02 (spleen), 0.03 (kidney), 0.08 (jejunum), 0.25 (ileum) mg Ti/kg). In general, the particulate TiO2 explained 80% of the total-Ti concentration. This indicates that most Ti in these organ tissues is particulate material. The detected particles comprise primary particles, aggregates and agglomerates, and were in the range of 50-500 nm with a mode in the range of 100-160 nm. About 17% of the detected TiO2 particles had a size <100 nm. The presence of SiO2 and TiO2 particles in liver tissue was confirmed by scanning electron microscopy with energy dispersive X-ray spectrometry.


Assuntos
Intestino Delgado/química , Rim/química , Fígado/química , Dióxido de Silício/análise , Baço/química , Titânio/análise , Idoso , Idoso de 80 Anos ou mais , Autopsia , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Tamanho da Partícula , Espectrometria por Raios X , Distribuição Tecidual
17.
J Agric Food Chem ; 68(6): 1563-1570, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927998

RESUMO

Ethanamizuril(N-{4-[4-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-2-methyl-phenoxy]-phenyl}-acetamide, EZL) is a new anticoccidiosis compound and belongs to the class of triazines. In this study, the metabolism, distribution, and excretion of EZL were evaluated in chickens after administration of EZL at a single dosage. According to the relevant drug biotransformation rules, the exact molecular mass detection, the fragmentation characteristics, and the retention times, a total of five metabolites were identified in vivo in chickens, including two phase I metabolites and three phase II conjugated metabolites. The major metabolic pathways of EZL in chickens were deacetylation, hydroxylation, and glucuronidation. Regarding 14C-tissue residues after administration, kidney was considered to be the target tissue, as 14C-tissue residues could be detected at 240 h postdose. DeacetylEZL (M3) was the main metabolite, accounting for 68.65% and 25.62% of 14C in kidney at 6 and 24 h, respectively. In heart, muscle, skin+fat, and lung tissues, EZL was the main radioactive substance accounting for 94.88%, 97.32%, 96.23%, and 91.3% of 14C, respectively. In the liver, EZL and M3 were 20.76% and 54.65% of 14C, respectively. In chicken tissues the ratio of M5 was too low to be quantitated and it was mainly detected in chicken fecal and bile samples. In chicken excreta, EZL, M3, and glucuronidation of EZL (M5) accounted for 7.02%, 12.33%, and 10.32% of the dose, respectively and were eliminated primarily. This study presents the first detection of EZL metabolites, which is helpful for further understanding of the metabolic mechanism and in vivo intermediate processes of EZL. The results of this study will be good bases for better understanding EZL's anticoccidiosis mechanism and will serve as a helpful reference for assessing the risks to animals and humans.


Assuntos
Coccidiostáticos/farmacocinética , Triazinas/farmacocinética , Animais , Biotransformação , Galinhas , Coccidiostáticos/administração & dosagem , Coccidiostáticos/metabolismo , Hidroxilação , Rim/química , Rim/metabolismo , Fígado/química , Fígado/metabolismo , Pulmão/química , Pulmão/metabolismo , Músculos/química , Músculos/metabolismo , Triazinas/administração & dosagem , Triazinas/metabolismo
18.
Arch Environ Contam Toxicol ; 78(2): 294-302, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31641780

RESUMO

Polychlorinated biphenyls (PCBs), which cause environmental pollution, are found in animal-based fatty foods. Due to their long half-life and lipophilic properties, they can accumulate in the fat tissues of cattle. The study was conducted to compare the PCB levels (PCB28, 52, 101, 118, 138, 153, and 180) in the different fat tissues (muscle, liver, kidney, spinal cord, lung, back fat, perihepatic fat, and perirenal fat) of cattle by age and gender. This information is also useful to evaluate the exposure risks for different bovine edible tissues. Therefore, 15 female and 15 male cattle under 24 months of age and 15 female and 15 male cattle over 24 months of age were used, and 480 samples were analyzed for target PCBs using gas chromatography-mass spectrometry. Of all the samples, two (50.2 µg/kg in perihepatic fat and 51.1 µg/kg in kidney) were found above the maximum residue limit; these samples were taken from the animals in the elderly female group (over 24 months). There were more PCBs in cattle older than 2 years. Muscle, kidney, and perihepatic fat presented higher PCB concentrations than other tissues, and perirenal fat presented lower PCB concentrations than other tissues. PCB101, PCB153, and PCB138 were found to have the highest contribution to the PCB concentration. Thus, it is concluded that perihepatic fat, muscle, or kidney should be sampled, particularly in routine residue monitoring, and specifically analyzed for PCB101, PCB153, and PCB138.


Assuntos
Tecido Adiposo/química , Bifenilos Policlorados/análise , Fatores Etários , Animais , Bovinos , Poluentes Ambientais/análise , Poluentes Ambientais/farmacocinética , Feminino , Contaminação de Alimentos/análise , Cromatografia Gasosa-Espectrometria de Massas , Rim/química , Fígado/química , Masculino , Músculos/química , Bifenilos Policlorados/farmacocinética , Distribuição Tecidual , Turquia
20.
N Z Vet J ; 68(1): 31-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31437418

RESUMO

Aims: To determine the pharmacokinetics and tissue depletion of 2 mg/kg marbofloxacin (MBX) in Bilgorajska geese (Anser anser domesticus) after I/V and oral administration, to calculate the daily dose from experimental data and to compare it with that calculated by allometric scaling.Methods: Eight clinically normal female Bilgorajska geese were used in a three-phase study with a 3-week wash-out period between phases. In the first phase birds received I/V administration of 2 mg/kg MBX; the same dose was given orally in the second and third phases. Blood samples were collected between 0 minutes and 48 hours in the first and second phases, and samples of liver, kidney, lung, muscle and heart were collected following slaughter of birds between 6 and 48 hours in the third phase. Concentrations of MBX in plasma and tissues were analysed using HPLC. Two additional birds served as controls. The optimal dose was calculated based on a minimal inhibitory concentration (MIC) of 0.125 µg/mL using the observed clearance, or using clearance calculated by allometric scaling.Results: Concentrations of MBX in plasma were detectable up to 24 hours following both I/V and oral administration. Mean oral bioavailability was 26.5 (SD 7.7)%. Concentrations of MBX in all tissues were highest at 6 hours and decreased constantly up to 34 hours. The mean optimal daily dose for oral administration of MBX, calculated using the observed clearance was 10.36 (SD 2.18) mg/kg, and using predicted clearance was 5.54 (SD 0.14) mg/kg. The preliminary withdrawal time for a maximum residue limit of 0.15 mg/kg calculated for muscle was 38.4 hours, heart 33.6 hours, kidney 48.3 hours, lung 47.7 hours and liver 49.3 hours.Conclusion and Clinical Relevance: There was insufficient evidence to recommend MBX orally administered to geese at a daily dose of 2 mg/kg for treatment of bacteria with an MIC of 0.125 µg/mL. Further pharmacokinetic/pharmacodynamic studies in geese are recommended to determine the MBX dose regimen and its clinical efficacy in geese.


Assuntos
Anseriformes/sangue , Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Administração Intravenosa/veterinária , Administração Oral , Animais , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Resíduos de Drogas , Escherichia coli/efeitos dos fármacos , Feminino , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/metabolismo , Rim/química , Fígado/química , Pulmão/química , Músculo Esquelético/química , Miocárdio/química , Consumo de Álcool por Menores
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