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1.
Toxicol Lett ; 332: 82-87, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32569803

RESUMO

BACKGROUND: Glycidol, a probable human carcinogen, is a reactive chemical released in the gastrointestinal tract from glycidyl fatty acid esters, which are heat-induced dietary contaminants. OBJECTIVES: To investigate the prenatal transfer of glycidol, a specific hemoglobin adduct was measured as a biomarker for internal glycidol exposure in paired cord and maternal blood samples. METHODS: In 100 mother-newborn pairs from the Belgian ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort, we studied the correlation between levels of the glycidol-derived hemoglobin adduct N-(2,3-dihydroxypropyl)-valine (2,3-diHOPr-Val) in paired cord and maternal blood samples. The adduct levels were determined after cleavage with a modified Edman degradation by using ultra-high performance liquid chromatography-tandem mass spectrometry and an isotope-labeled reference standard. RESULTS: 2,3-DiHOPr-Val was detectable in all 100 maternal blood samples and in 96 cord blood samples (LOD =0.5 pmol 2,3-diHOPr-Val/g hemoglobin), with medians of 5.4 (range: 2.3-29.2) and 1.6 (range: LOD - 8.9) pmol/g hemoglobin), respectively. In blood samples of mothers who smoked during pregnancy and in the cord blood samples of their newborns (n = 6), the median 2,3-diHOPr-Val levels were 16.7 (range: 6.4-29.2) and 6.2 (range: LOD - 8.6) pmol/g hemoglobin, respectively. The median ratio of 2,3-diHOPr-Val levels of cord to maternal blood was 0.35 (range: 0.19-1.14) (n = 49). The Spearman correlation coefficient between 2,3-diHOPr-Val levels in cord and maternal blood samples was 0.63 (p < 0.001) among all mother-newborn pairs and 0.59 (p < 0.001) among mother-newborn pairs of non-smoking mothers. DISCUSSION: Maternal data confirm widespread exposure to glycidol, also in non-smokers. Neonatal levels indicate prenatal exposure to glycidol, due to an obviously relatively unhindered passive transfer through the placental barrier. Possible health effects of fetal (and postnatal) glycidol exposure in children may be addressed in epidemiological studies.


Assuntos
Compostos de Epóxi/metabolismo , Sangue Fetal/química , Hemoglobinas/metabolismo , Troca Materno-Fetal , Propanóis/metabolismo , Valina/análogos & derivados , Adulto , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Estudos de Coortes , Eritrócitos/química , Feminino , Hemoglobinas/análise , Humanos , Recém-Nascido , Gravidez , Fumar/sangue , Espectrometria de Massas em Tandem , Valina/sangue
2.
Proc Natl Acad Sci U S A ; 117(26): 15018-15027, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32527859

RESUMO

The pathology of sickle cell disease is caused by polymerization of the abnormal hemoglobin S upon deoxygenation in the tissues to form fibers in red cells, causing them to deform and occlude the circulation. Drugs that allosterically shift the quaternary equilibrium from the polymerizing T quaternary structure to the nonpolymerizing R quaternary structure are now being developed. Here we update our understanding on the allosteric control of fiber formation at equilibrium by showing how the simplest extension of the classic quaternary two-state allosteric model of Monod, Wyman, and Changeux to include tertiary conformational changes provides a better quantitative description. We also show that if fiber formation is at equilibrium in vivo, the vast majority of cells in most tissues would contain fibers, indicating that it is unlikely that the disease would be survivable once the nonpolymerizing fetal hemoglobin has been replaced by adult hemoglobin S at about 1 y after birth. Calculations of sickling times, based on a recently discovered universal relation between the delay time prior to fiber formation and supersaturation, show that in vivo fiber formation is very far from equilibrium. Our analysis indicates that patients survive because the delay period allows the majority of cells to escape the small vessels of the tissues before fibers form. The enormous sensitivity of the duration of the delay period to intracellular hemoglobin composition also explains why sickle trait, the heterozygous condition, and the compound heterozygous condition of hemoglobin S with pancellular hereditary persistence of fetal hemoglobin are both relatively benign conditions.


Assuntos
Anemia Falciforme/metabolismo , Hemoglobina Falciforme/química , Oxigênio/metabolismo , Regulação Alostérica , Eritrócitos/química , Eritrócitos/metabolismo , Hemoglobina Fetal/química , Hemoglobina Fetal/metabolismo , Hemoglobina Falciforme/metabolismo , Humanos , Cinética , Oxigênio/química
3.
South Med J ; 113(4): 156-163, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32239227

RESUMO

OBJECTIVES: Studies have examined the association between tobacco use and folate levels in pregnancy, yet few have assessed this relation using objective and accurate measures of both smoking and folate. In this study, we evaluated the association between maternal cotinine levels and periconceptional red blood cell (RBC) folic acid reserves in a cohort of low-income pregnant mothers. METHODS: Smoking information, based on salivary cotinine, a highly sensitive and specific tobacco smoke exposure biomarker, was used. Furthermore, folate was assessed using RBC folate, an indicator of long-term folate storage. Participants were early to mid-trimester pregnant women who received antenatal care between 2011 and 2015 at the Genesis Clinic of Tampa (Florida). A total of 496 women were enrolled in the study. Associations between smoking status/maternal salivary cotinine concentrations, sociodemographic factors, and folate concentrations were investigated using Tobit regression analyses. RESULTS: The mean folate level of the participants was 718.3 ± 183.2 ng/mL, and only 2 (0.4%) participants were deficient in folate. We observed no significant difference in folate levels by smoking status. In contrast, salivary cotinine levels were significantly associated with decreased RBC folate concentrations (ß -11.43, standard error 5.45, P = 0.032). Prepregnancy maternal body mass index, gestational age, stress, and depression also were associated with folate levels. CONCLUSIONS: Low RBC folate is associated with perinatal factors, including high maternal cotinine levels, body mass index, stress, and depression. The effect of low folate levels among smokers cannot be overemphasized, considering that tobacco products not only reduce folate levels but also decrease the bioutilization of folate.


Assuntos
Cotinina/análise , Eritrócitos/química , Fertilização/fisiologia , Ácido Fólico/análise , Ácido Fólico/sangue , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Coortes , Cotinina/sangue , Feminino , Florida , Humanos , Gravidez , Poluição por Fumaça de Tabaco/análise
4.
BMC Bioinformatics ; 21(Suppl 2): 90, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32164547

RESUMO

BACKGROUND: For optimization of microfluidic devices for the analysis of blood samples, it is useful to simulate blood cells as elastic objects in flow of blood plasma. In such numerical models, we primarily need to take into consideration the movement and behavior of the dominant component of the blood, the red blood cells. This can be done quite precisely in small channels and within a short timeframe. However, larger volumes or timescales require different approaches. Instead of simplifying the simulation, we use a neural network to predict the movement of the red blood cells. RESULTS: The neural network uses data from the numerical simulation for learning, however, the simulation needs only be run once. Alternatively, the data could come from video processing of a recording of a biological experiment. Afterwards, the network is able to predict the movement of the red blood cells because it is a system of bases that gives an approximate cell velocity at each point of the simulation channel as a linear combination of bases.In a simple box geometry, the neural network gives results comparable to predictions using fluid streamlines, however in a channel with obstacles forming slits, the neural network is about five times more accurate.The network can also be used as a discriminator between different situations. We observe about two-fold increase in mean relative error when a network trained on one geometry is used to predict trajectories in a modified geometry. Even larger increase was observed when it was used to predict trajectories of cells with different elastic properties. CONCLUSIONS: While for uncomplicated box channels there is no advantage in using a system of bases instead of a simple prediction using fluid streamlines, in a more complicated geometry, the neural network is significantly more accurate. Another application of this system of bases is using it as a comparison tool for different modeled situations. This has a significant future potential when applied to processing data from videos of microfluidic flows.


Assuntos
Eritrócitos/fisiologia , Aprendizado de Máquina , Microfluídica/métodos , Fenômenos Biomecânicos , Circulação Sanguínea/fisiologia , Eritrócitos/química , Humanos , Dispositivos Lab-On-A-Chip , Fluidez de Membrana , Microfluídica/instrumentação
5.
Zhonghua Er Ke Za Zhi ; 58(3): 201-205, 2020 Mar 02.
Artigo em Chinês | MEDLINE | ID: mdl-32135591

RESUMO

Objective: To explore the predictive values of routine blood test results for iron deficiency (ID) screening in children. Methods: Routine blood test results and serum ferritin (SF) levels from 1 443 healthy children (862 boys, 581 girls) aged 6 months to 18 years, who were seen for well-child visits between June 2017 and May 2019 in Children's Hospital, Zhejiang University School of Medicine, were retrospectively analyzed. ID was defined as SF<20 µg/L, iron deficiency anemia (IDA) as ID with anemia (hemoglobin(Hb)<110 g/L at 6 months-5 years of age, Hb<120 g/L at 6-18 years of age), non-anemia ID as ID without anemia, non-ID anemia as SF≥20 µg/L with anemia, and healthy control subjects as those with SF≥20 µg/L but without anemia. The blood test results including Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), and the percentage of low hemoglobin density (LHD) of healthy control, non-anemia ID, non-ID anemia, and IDA groups were compared by analysis of variance (ANOVA) or non-parametric test, quantitative data were described as x±s or M(interquartile range), and receiver operating characteristic curve (ROC) analysis was applied to assess predictive values of routine blood test results and LHD for detecting IDA and ID. Results: Among 1 443 children with median age of 2.1(3.3) years, 1 061 children were in healthy control group, 292 in non-anemia ID group, 43 in non-ID anemia group and 47 in IDA group. The prevalence of ID was much higher than that of anemia (23.5% (339/1 443) vs. 6.2% (90/1 443) , χ(2)=169.76, P<0.01). Compared with control group, non-anemia ID group showed higher LHD (0.088 (0.093) vs.0.073 (0.068), P<0.01) and RDW (0.131±0.013 vs. 0.126±0.008, P<0.01), lower MCV ((80±4) vs. (83±4) fl, P<0.01) and MCHC values ((326±9) vs. (329±8) g/L, P<0.01). IDA group showed higher LHD (0.322(0.544)) and RDW (0.151±0.018), lower MCV ((73±6) fl) and MCHC values((309±14) g/L) than non-anemia ID group (all P<0.01). The area under curve (AUC) values of MCHC, LHD, RDW and MCV for detecting ID were 0.63 (95%CI: 0.60-0.67), 0.63 (95%CI:0.60-0.67), 0.67 (95%CI: 0.63-0.70) and 0.73 (95%CI: 0.69-0.76) respectively. With cutoff limits (MCV<80.2 fl, RDW>0.131 or MCHC<322 g/L), MCV, RDW and MCHC showed higher sensitivity for screening ID than hemoglobin (0.540, 0.469 and 0.336 vs. 0.139, χ(2)=121.70, 87.47, 35.56, all P<0.01). Conclusion: MCV, RDW and MCHC can be used to screen ID in primary health care settings.


Assuntos
Anemia Ferropriva/diagnóstico , Anemia/diagnóstico , Adolescente , Anemia/epidemiologia , Anemia Ferropriva/sangue , Anemia Ferropriva/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Índices de Eritrócitos , Eritrócitos/química , Feminino , Hemoglobinas/química , Humanos , Lactente , Ferro/sangue , Ferro/deficiência , Masculino , Estudos Retrospectivos
6.
Subcell Biochem ; 94: 297-322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32189305

RESUMO

Sickle cell hemoglobin (HbS) is an example of a genetic variant of human hemoglobin where a point mutation in the ß globin gene results in substitution of glutamic acid to valine at sixth position of the ß globin chain. Association between tetrameric hemoglobin molecules through noncovalent interactions between side chain residue of ßVal6 and hydrophobic grooves formed by ßAla70, ßPhe85 and ßLeu88 amino acid residues of another tetramer followed by the precipitation of the elongated polymer leads to the formation of sickle-shaped RBCs in the deoxygenated state of HbS. There are multiple non-covalent interactions between residues across intra- and inter-strands that stabilize the polymer. The clinical phenotype of sickling of RBCs manifests as sickle cell anemia, which was first documented in the year 1910 in an African patient. Although the molecular reason of the disease has been understood well over the decades of research and several treatment procedures have been explored to date, an effective therapeutic strategy for sickle cell anemia has not been discovered yet. Surprisingly, it has been observed that the oxy form of HbS and glutathionylated form of deoxy HbS inhibits polymerization. In addition to describe the residue level interactions in the HbS polymer that provides its stability, here we explain the mechanism of inhibition in the polymerization of HbS in its oxy state. Additionally, we reported the molecular insights of inhibition in the polymerization for glutathionyl HbS, a posttranslational modification of hemoglobin, even in its deoxy state. In this chapter we briefly consider the available treatment procedures of sickle cell anemia and propose that the elevation of glutathionylation of HbS within RBCs, without inducing oxidative stress, might be an effective therapeutic strategy for sickle cell anemia.


Assuntos
Anemia Falciforme/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Anemia Falciforme/genética , Anemia Falciforme/patologia , Anemia Falciforme/terapia , Eritrócitos/química , Eritrócitos/metabolismo , Eritrócitos/patologia , Hemoglobinas/genética , Humanos , Polimerização
8.
Proc Natl Acad Sci U S A ; 117(7): 3509-3517, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32019879

RESUMO

Personalized medicine offers great potential benefits for disease management but requires continuous monitoring of drugs and drug targets. For instance, the therapeutic window for lithium therapy of bipolar disorder is very narrow, and more frequent monitoring of sodium levels could avoid toxicity. In this work, we developed and validated a platform for long-term, continuous monitoring of systemic analyte concentrations in vivo. First, we developed sodium microsensors that circulate directly in the bloodstream. We used "red blood cell mimicry" to achieve long sensor circulation times of up to 2 wk, while being stable, reversible, and sensitive to sodium over physiologically relevant concentration ranges. Second, we developed an external optical reader to detect and quantify the fluorescence activity of the sensors directly in circulation without having to draw blood samples and correlate the measurement with a phantom calibration curve to measure in vivo sodium. The reader design is inherently scalable to larger limbs, species, and potentially even humans. In combination, this platform represents a paradigm for in vivo drug monitoring that we anticipate will have many applications in the future.


Assuntos
Monitoramento de Medicamentos/métodos , Eritrócitos/química , Sódio/sangue , Animais , Circulação Sanguínea , Monitoramento de Medicamentos/instrumentação , Fluorescência , Camundongos , Camundongos Nus , Mimetismo Molecular , Ratos
9.
PLoS One ; 15(1): e0227862, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995595

RESUMO

BACKGROUND: The effect of phase-change material blood containers on the quality of stored red blood cells (RBCs) transported in the Qinghai-Tibet Plateau remains to be studied. STUDY DESIGN AND METHODS: RBCs stored in a phase-change material blood container were transported from Chengdu to Tibet and then back to Chengdu. The detection time points were the 1st day of fresh-collected RBCs (group 1), the 14th day of resting refrigerated storage (group 2), and the 14th day of plateau transportation under refrigerated storage in the container (group 3). RBC counts, hemoglobin (HGB) content, free hemoglobin (FHb) content, blood biochemical indexes, hemorheologic indexes and 2,3-DPG content were detected. RESULTS: Compared with group 2, RBC counts and HGB were decreased, and the mean corpuscular volume (MCV), FHb and K+ content were increased in group 3. The glucose consumption and lactic acid production were significantly increased in groups 2 and 3. Compared with group 2, the 2,3-DPG content and whole blood viscosity were decreased in group 3. After resting refrigerated storage and plateau transportation, the RBC quality still met the national standard (GB18469-2012 whole blood and component blood quality requirements). CONCLUSION: The phase-change material blood container can be maintained at a constant temperature under plateau environmental conditions, ensuring that the quality of the stored RBCs is compliant with GB18469-2012 whole blood and component blood quality requirements.


Assuntos
Preservação de Sangue/instrumentação , Eritrócitos/química , Manejo de Espécimes/instrumentação , Transportes , 2,3-Difosfoglicerato/sangue , Contagem de Eritrócitos , Glucose/metabolismo , Sistema Hematopoético/metabolismo , Hemoglobinas/metabolismo , Humanos , Ácido Láctico/sangue , Tibet
10.
Lipids ; 55(1): 53-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31943229

RESUMO

The interest in the amount of polyunsaturated fatty acids (PUFA) in the umbilical cord blood (UCB) is increasing, but the stability of erythrocyte PUFA in these samples during storage and washing of the erythrocytes has not been directly evaluated. The purpose of this study was to analyze the effect of the lapse of time on the fatty acid (FA) content from UCB sample collection and maintained at 4 °C (0-12 h) until erythrocyte separation and washing. Palmitic acid (16:0), stearic acid (18:0), 18:1n-7/n-9, linoleic acid (18:2n-6), arachidonic acid (20:4n-6), 22:4n-6, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), and docosahexaenoic acid (22:6n-3) together accounted for 87% of the FA profile in the umbilical vein erythrocytes. No difference was observed in the concentration of any of the FA studied, nor in the sum of saturated fatty acids (SFA), PUFA, or LC-PUFA in umbilical erythrocytes obtained at delivery and stored up to 12 h before the separation of erythrocytes. However, if a washing step was included in the processing of the erythrocytes, a decrease in the concentration of 16:0, 18:0, 18:3n-3, 20:4n-6, 22:4n-6, total SFA, PUFA, LC-PUFA, and n-6 LC-PUFA was evidenced, compared to unwashed erythrocytes. The FA concentration in umbilical cord erythrocytes did not change between samples stored from 0 to 12 h until erythrocyte separation. Erythrocyte washing before storage decreased the concentration of significant individual and total SFA, PUFA, and LC-PUFA. These results should be considered when planning the collection of UCB samples for the study of fatty acid concentration due to the nonscheduled timing of deliveries.


Assuntos
Eritrócitos/química , Ácidos Graxos/sangue , Sangue Fetal/citologia , Ácido Araquidônico/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos/isolamento & purificação , Ácidos Graxos Insaturados/sangue , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Ácido Linoleico/sangue , Ácido Palmítico/sangue , Gravidez , Ácidos Esteáricos/sangue
11.
Malar J ; 19(1): 21, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941490

RESUMO

BACKGROUND: Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. METHODS: Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A-(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes. RESULTS: In children, HbAS was associated, compared to wild type, with a lower incidence of malaria (IRR = 0.78, 95% CI 0.66-0.92, p = 0.003), lower parasite density upon infection (PR = 0.66, 95% CI 0.51-0.85, p = 0.001), and lower body temperature for any given parasite density (- 0.13 â„ƒ, 95% CI - 0.21, - 0.05, p = 0.002). In children, HbSS was associated with a lower incidence of malaria (IRR = 0.17, 95% CI 0.04-0.71, p = 0.02) and lower parasite density upon infection (PR = 0.31, 95% CI 0.18-0.54, p < 0.001). α-/αα thalassaemia, was associated with higher parasite prevalence in both children and adults (RR = 1.23, 95% CI 1.06-1.43, p = 0.008 and RR = 1.52, 95% CI 1.04-2.23, p = 0.03, respectively). G6PD deficiency was associated with lower body temperature for any given parasite density only among male hemizygote children (- 0.19 â„ƒ, 95% CI - 0.31, - 0.06, p = 0.003). CONCLUSION: RBC variants were associated with non-severe malaria outcomes. Elucidation of the mechanisms by which they confer protection will improve understanding of genetic protection against malaria.


Assuntos
Eritrócitos/citologia , Malária/sangue , Adulto , Fatores Etários , Distribuição Binomial , Cuidadores , Criança , Pré-Escolar , Estudos de Coortes , Eritrócitos/química , Eritrócitos/classificação , Feminino , Humanos , Incidência , Lactente , Estudos Longitudinais , Malária/epidemiologia , Malária/genética , Malária/parasitologia , Masculino , Parasitemia/sangue , Parasitemia/epidemiologia , Parasitemia/genética , Parasitemia/parasitologia , Prevalência , Estudos Prospectivos , Fatores Sexuais , Uganda/epidemiologia , Adulto Jovem
12.
J Pharmacol Exp Ther ; 372(3): 355-365, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31924689

RESUMO

Many victims, after being extricated from a collapsed building as the result of a disaster, suffer from disaster nephrology, a term that is referred to as the crush syndrome (CS). Recommended treatments, which include dialysis or the continuous administration of massive amounts of fluid are not usually easy in cases of such mass natural disasters. In the present study, we examined the therapeutic performance of a biomimetic carbon monoxide (CO) delivery system, CO-enriched red blood cells (CO-RBCs), on experimental animal models of an acute kidney injury (AKI) induced by traumatic and nontraumatic rhabdomyolysis, including CS and rhabdomyolysis with massive hemorrhage shock. A single CO-RBC treatment was found to effectively suppress the pathogenesis of AKI with the mortality in these model rats being improved. In addition, in further studies using glycerol-induced rhabdomyolysis model rats, the pathogenesis of which is similar to that for the CS, AKI and mortality were also reduced as the result of a CO-RBC treatment. Furthermore, CO-RBCs were found to have renoprotective effects via the suppression of subsequent heme protein-associated renal oxidative injury; the oxidation of myoglobin in the kidneys, the generation of reactive oxygen species by free heme produced from degraded-cytochrome P450 and hemoglobin-associated renal injury. Because CO-RBCs can be prepared and used at both hospitals and at a disaster site, these findings suggest that CO-RBCs have the potential for use as a novel cell therapy against both nontraumatic and traumatic rhabdomyolysis including CS-induced AKI. SIGNIFICANCE STATEMENT: After mass natural and man-made disasters, people who are trapped in collapsed buildings are in danger of acute kidney injury (AKI), including crush syndrome (CS)-related AKI. This paper reports that carbon monoxide-enriched red blood cells (CO-RBCs), which can be prepared at both hospitals and disaster sites, dramatically suppressed the pathogenesis of CS-related AKI, thus improving mortality via suppressing heme protein-associated renal injuries. CO-RBCs have the potential for serving as a practical therapeutic agent against disaster nephrology associated with the CS.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Monóxido de Carbono/uso terapêutico , Síndrome de Esmagamento/complicações , Eritrócitos/química , Rim/efeitos dos fármacos , Rabdomiólise/complicações , Lesão Renal Aguda/etiologia , Animais , Apoptose/efeitos dos fármacos , Monóxido de Carbono/administração & dosagem , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Rim/metabolismo , Rim/patologia , Células LLC-PK1 , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Análise de Sobrevida , Suínos
13.
Artigo em Inglês | MEDLINE | ID: mdl-31926297

RESUMO

Maternal smoking-induced congenital heart and microvascular defects are closely associated with the impaired functioning of the in-utero feto-placental circulation system. Current groundbreaking facts revealed intimate crosstalk between circulating red blood cells (RBCs) and the vascular endothelium. Thus, RBCs have become the protagonists under varied pathological and adverse pro-oxidative cellular stress conditions. We isolated and screened fetal RBCs from the arterial cord blood of neonates, born to non-smoking (RBC-NS) and smoking mothers (RBC-S), assuming that parameters of fetal RBCs are blueprints of conditions experienced in-utero. Using atomic force microscopy and mass spectrometry-based shotgun lipidomics in the RBC-S population we revealed induced membrane stiffness, loss in intrinsic plastic activities and several abnormalities in their membrane-lipid composition, that could consequently result in perturbed hemodynamic flow movements. Altogether, these features are indicative of the outcome of neonatal microvascular complications and suggest unavailability for the potential rescue mechanism in cases of vascular endothelium impairment due to altered membrane integrity and rheological properties.


Assuntos
Eritrócitos/patologia , Sangue Fetal/citologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Fenômenos Biomecânicos , Membrana Eritrocítica/química , Membrana Eritrocítica/patologia , Eritrócitos/química , Feminino , Hemodinâmica , Humanos , Recém-Nascido , Peroxidação de Lipídeos , Fluidez de Membrana , Lipídeos de Membrana/análise , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia , Adulto Jovem
14.
J Int Soc Sports Nutr ; 17(1): 8, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996219

RESUMO

BACKGROUND: The present study aimed to determine changes occurring in the erythrocyte concentrations of Iron (Fe), Magnesium (Mg) and Phosphorous (P) of subjects with different levels of physical training living in the same area of Extremadura (Spain). METHODS: Thirty sedentary subjects (24.34 ± 3.02 years) without sports practice and a less active lifestyle, formed the control group (CG); 24 non-professional subjects (23.53 ± 1.85 years), who perform between 4 and 6 h/week of moderate sports practice without any performance objective and without following systematic training formed the group of subjects with a moderate level of training (MTG), and 22 professional cyclists (23.29 ± 2.73 years) at the beginning of their sports season, who performed more than 20 h/week of training, formed the high-level training group (HTG). Erythrocyte samples from all subjects were collected and frozen at - 80 °C until analysis. Erythrocyte analysis of Fe, Mg and P was performed by inductively coupled plasma mass spectrometry (ICP-MS). All results are expressed in µg/g Hb. RESULTS: The results showed that there were statistically significant lower concentrations of erythrocyte Fe, Mg and P in MTG and HTG than CG. All parameters (Fe, Mg and P concentrations in erythrocytes) correlated inversely with physical training. CONCLUSIONS: Physical exercise produces a decrease in erythrocyte concentrations of Fe, Mg and P. This situation could cause alterations in the performance of athletes given the importance of these elements. For this reason, we recommend an erythrocyte control at the beginning, and during the training period, to avoid harmful deficits.


Assuntos
Eritrócitos/química , Exercício Físico , Ferro/sangue , Magnésio/sangue , Fósforo/sangue , Adulto , Humanos , Masculino , Espectrometria de Massas , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-31923811

RESUMO

Long-chain polyunsaturated fatty acids (LC-PUFAs) are involved in the fetal growth in utero, and are essential for the development of visual and cognitive functions during infancy. The purpose of this study was to examine the associations of erythrocyte fatty acid compositions with FADS1 gene polymorphism in Japanese mothers and infants. The subjects were 383 mothers who participated in an adjunct birth cohort study of the Japan Environment and Children's Study (JECS). In maternal FADS1 SNP genotypes, the precursor fatty acids composition of the Δ5 desaturase in the maternal blood showed significant differences in levels among the groups, and showed increasing values in the order of TT < TC < CC genotype groups. On the other hand, many product fatty acids levels were significantly reduced in the order of TT > TC > CC genotype groups, and DHA levels were significantly lower in the CC genotype group relative to the other groups. Likewise, the relationship between fetal genotype group and fatty acid composition in cord blood was very similar to the maternal relationship. These results indicate the maternal and fetal blood fatty acid compositions are strongly influenced by the FADS1 genotypes. With respect to the cord blood DHA composition, the levels in the fetal CC genotype group showed a trend toward lower values in the maternal CC genotype group pair (p = 0.066) compared to the maternal TC genotype group pair. However, in the fetal TT and TC genotype groups (p = 0.131, p = 0.729, respectively), the maternal genotype did not have a significant effect. The DHA composition was more influenced by the maternal genotype in the fetal CC genotype group than in the fetal TT and TC genotype groups. It was shown that DHA transport via the placenta from the mother might be promoted in the fetal CC genotype compared to the other fetal genotype groups. In conclusion, differences in the FADS1 SNP genotypes of pregnant women and their children may greatly affect the supply of LC-PUFAs. Further studies on the involvement of the FADS1 polymorphisms and the fetal LC-PUFA levels in the fetal growth and development are warranted.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Eritrócitos/química , Ácidos Graxos Dessaturases/genética , Ácidos Graxos/sangue , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Coortes , Feminino , Sangue Fetal/química , Desenvolvimento Fetal , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Japão , Masculino , Mães , Gravidez
17.
J Pharm Biomed Anal ; 178: 112870, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31685266

RESUMO

The analysis of 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-mMP) in biological samples is not straight forward and requires pre-treatment of samples. There are no validated published methods for the analysis of azathioprine/6-mercaptopurine (AZA/6-MP) metabolites in dried blood spot (DBS) samples that study the correlation with red blood cells (RBC) concentrations. DBS was prepared by applying fifteen microliters of blood [spiked with analytes or samples obtained from patients] to a Guthrie card which was then dried at room temperature overnight. The sample treatment procedure used protein precipitation followed by a hydrolysis step in which, 6-mMP was converted into 4-amino-5-(methylthio)carbonyl imidazole (AMTCI) then analytes were transferred to a solid phase extraction cartridge. The extracted sample was chromatographed using a reversed phase system (C18) column preceded by a guard column of matching chemistry. The method gave a linear calibration over the range 0.5-15 µmol/L and 3.75-175 µmol/L for 6-TG and 6-mMP, respectively. The method has been applied successfully to the determination of 6-TG and 6-mMP concentrations in DBS finger-prick samples from 27 paediatric patients with IBD who were receiving (AZA/6-MP). Patient 6-TG and 6-mMP RBC concentrations, calculated from whole blood finger prick DBS samples and those measured in RBCs derived from matched venous samples (analyzed using conventional HPLC-UV technique) showed good agreement using the Bland-Altman test. This is the first published method for determining 6-TG and 6-mMP in DBS that studies their correlation with RBCs concentrations. It is applicable to a range of clinical studies such as adherence and pharmacokinetic studies involving AZA/6-MP.


Assuntos
Azatioprina/sangue , Teste em Amostras de Sangue Seco/métodos , Mercaptopurina/sangue , Adolescente , Criança , Cromatografia Líquida/métodos , Eritrócitos/química , Feminino , Humanos , Extração em Fase Sólida , Espectrometria de Massas em Tandem/métodos
18.
Talanta ; 206: 120174, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514890

RESUMO

A method of simultaneous cell counting and determination of metals in single cells using time-resolved inductively coupled plasma-mass spectrometry (ICP-MS) was reported. A facile, low cost and highly efficient single-cell introduction system of time-resolved ICP-MS consists of a flow cell, a visual contrast calibration device, a customized nebulizer and a fabricated spray chamber. The flow cell includes a cell sample tube, a sheath liquid tube and a flow chamber. The visual contrast calibration device was composed of a microscope with a 16 × microscope objective (160 × total magnification). The flow chamber was used to combine a flow of red blood cell suspension (0.800 µL/min) and a flow of PBS (4.40 µL/min) into the nebulizer. The intact cells were directly introduced with the single-cell introduction system into the plasma via nebulizing, and then ion plumes corresponding to single cells were individually detected with mass spectrometer. The frequency of the spikes directly reflects the number of cells, and the intensity of spikes is proportional to the concentration of copper within one cell. The single-cell introduction system can be transported into the ICP-MS via a customized transport system with 100% efficiency. A high cell introduction efficiency into the plasma supports for a reduction of cell consumption. The Cu signal frequency was about 120 cell events per minute. This single-cell introduction system simplifies the introduction of individual and intact cells. The copper content in single red blood cell was 0.20-0.40 fg.


Assuntos
Cobre/análise , Eritrócitos/química , Humanos , Limite de Detecção , Espectrometria de Massas/instrumentação , Espectrometria de Massas/métodos , Nebulizadores e Vaporizadores , Análise de Célula Única/instrumentação , Análise de Célula Única/métodos
19.
Am J Clin Nutr ; 111(3): 601-612, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31858145

RESUMO

BACKGROUND: RBC folate (RBF) is an indicator of folate status and risk of neural-tube defects. It is calculated from whole blood folate (WBF), serum folate (SFOL), and hematocrit (Hct). SFOL and/or Hct are sometimes unavailable; hemoglobin (Hb) is generally available in surveys. OBJECTIVES: We assessed the ability of different RBF approximations to generate population data in women aged 12-49 y. METHODS: Using SFOL, RBF, Hct, Hb, and mean corpuscular Hb content (MCHC) from prefortification (1988-1994) and postfortification (1999-2006, 2007-2010) NHANES we applied 6 approaches: #1) assume SFOL = 0; #2) impute SFOL (population median); #3) impute Hct (population median); #4) estimate Hct (Hb/MCHC); #5) assume SFOL = 0 and estimate Hct; and #6) predict SFOL (from WBF) and estimate Hct. For each approach, we calculated the paired percentage difference to the "true" RBF and estimated various statistics. RESULTS: For 2007-2010 (unweighted data), the median relative difference from "true" RBF was lowest for approaches #2 (-0.74%), #4 (-0.96%), and #6 (-1.15%), intermediate for #3 (-3.36%), and highest for #5 (4.96%) and #1 (5.78%). The 95% agreement limits were smallest for approach #1 (2.33%, 13.0%) and largest for #3 (-20.8%, 11.3%). Approach #2 showed concentration-dependence (negative compared with positive differences at low compared with high RBF). Using weighted data, we found similar patterns across approaches for mean relative differences by demographic subgroup for all 3 time periods. CONCLUSIONS: We obtained the best agreement between estimated and "true" RBF when we predicted SFOL using a regression equation obtained from a subset of samples (approach #6). Alternatively, the consistent overestimation of RBF when assuming SFOL = 0 (∼6%) could be addressed by adjusting the data (approach #5). Similar observations for pre- and postfortification periods suggest applicability to low and high folate status situations, but should be confirmed elsewhere. To estimate RBF, at least WBF and Hb are needed.


Assuntos
Eritrócitos/química , Ácido Fólico/sangue , Hemoglobinas/análise , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Adulto Jovem
20.
Sci Adv ; 5(11): eaax9250, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31763454

RESUMO

Despite being the mainstay of cancer treatment, chemotherapy has shown limited efficacy for the treatment of lung metastasis due to ineffective targeting and poor tumor accumulation. Here, we report a highly effective erythrocyte leveraged chemotherapy (ELeCt) platform, consisting of biodegradable drug nanoparticles assembled onto the surface of erythrocytes, to enable chemotherapy for lung metastasis treatment. The ELeCt platform significantly extended the circulation time of the drug nanoparticles and delivered 10-fold higher drug content to the lung compared with the free nanoparticles. In both the early- and late-stage melanoma lung metastasis models, the ELeCt platform enabled substantial inhibition of tumor growth that resulted in significant improvement of survival. Further, the ELeCt platform can be used to deliver numerous approved chemotherapeutic drugs. Together, the findings suggest that the ELeCt platform offers a versatile strategy to enable chemotherapy for effective lung metastasis treatment.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Nanopartículas/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Eritrócitos/química , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Microscopia Eletrônica de Varredura , Nanopartículas/química , Nanopartículas/ultraestrutura , Resultado do Tratamento
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