RESUMEN
RATIONALE: A combination of stable carbon (δ13 C) and hydrogen (δ2 H) isotope ratios and carbon content (% C) was evaluated as a rapid, low-cost analytical approach to authenticate bioplastics, complementing existing radiocarbon (14 C) and Fourier transform infrared (FTIR) analytical methods. METHODS: Petroleum- and bio-based precursor materials and in-market plastics were analysed and their δ13 C, δ2 H and % C values were used to establish isotope criteria to evaluate plastic claims, and the source and biocontent of the samples. 14 C was used to confirm the findings of the isotope approach and FTIR analysis was used to vertify the plastic type of the in-market plastics. RESULTS: Distinctive carbon and hydrogen stable isotope ratios were found for authentic bio-based and petroleum-based precursor plastics, and it was possible to classify in-market plastics according to their source materials (petroleum, C3, C4, and mixed sources). An estimation of C4 biocontent was possible from a C4-petroleum isotope mixing model using δ13 C which was well correlated (R2 = 0.98) to 14 C. It was not possible to establish a C3-petroleum isotope mixing model due to δ13 C isotopic overlap with petroleum plastics; however, the addition of δ2 H and % C was useful to evaluate if petroleum-bioplastic mixes contained C3 bioplastics, and PLS-DA modelling reliably clustered each plastic type. CONCLUSIONS: A combined dual stable isotope and carbon content approach was found to rapidly and accurately identify C3 and C4 bio-based products from their petroleum counterparts, and identify instances of petroleum and bio-based mixes frequently found in mislabelled bioplastics. Out of 37 in-market products labelled as bioplastic, 19 were found to contain varying amounts of petroleum-based plastic and did not meet their bio-based claims.
Asunto(s)
Isótopos de Carbono/análisis , Deuterio/análisis , Fitoquímicos/análisis , Plásticos/análisis , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Radioisótopos de Carbono/análisis , Petróleo/análisisRESUMEN
The aim of this investigation was to determine the effect of dose and adjuvant on uptake of two phosphite products (Phos-A and Phos-B) into Pinus radiata needles. In experiment 1, uptake of 6 kg ha-1 phosphite, applied as Phos-A, in 100 liters of water, together with an organosilicone superspreader (0.2%), was high (>60%). Uptake at doses greater than 6 kg ha-1 (12, 15, 18, and 24 kg ha-1) and applied in volumes less than 100 liters of water (75 and 50 liters) was poor (1 to 30%). Using stability tests and NMR spectroscopy in experiment 2, this appeared to be linked to a concentration dependent reaction resulting in the degradation of the organosilicone adjuvant that facilitated uptake of Phos-A. In experiment 3, uptake of phosphite applied as Phos-B, between 6 and 24 kg ha-1 in 100 liters of water, was tested alone and with four adjuvants (an organosilicone, alcohol ethoxylate, lecithin, and esterified seed oil). Uptake of Phos-B without any adjuvant was high (>50%) across all doses, indicating the formulation was optimized for P. radiata needles. Uptake of Phos-B increased with concentration up to 72% at 24 kg ha-1 in 100 liters of water. Symptoms of phytotoxicity were observed at rates of ≥12 kg ha-1. This study highlighted the effect of formulation, dose, concentration, and adjuvant on the uptake of phosphite into P. radiata needles.
Asunto(s)
Fosfitos , Pinus , Hojas de la Planta , Transporte Biológico/efectos de los fármacos , Compuestos de Organosilicio/metabolismo , Compuestos de Organosilicio/farmacología , Fosfitos/metabolismo , Pinus/química , Pinus/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismoRESUMEN
A randomly assigned sample of 376 college students responded to a survey involving a between-subjects 2 × 3 experiment designed to assess the impact of age (older versus younger) and tattoo status (i.e., no tattoo, feminine tattoo, or masculine tattoo) on three dependent measures: credibility, attractiveness, and promiscuity. Older and younger women are perceived differently depending on tattoo status. Not wearing a tattoo may lead to a more favorable perception of older women than wearing one, but wearing a feminine tattoo may engender a more favorable impression of older women than having a masculine tattoo. But not having a tattoo may not be as helpful for the perception of younger women as it is for older women. Also, while younger women may be rewarded for gender role transgression with respect to tattoo status, this is not so for older women.
Asunto(s)
Deseabilidad Social , Percepción Social , Estereotipo , Tatuaje , Adulto , Actitud Frente a la Salud , Femenino , Humanos , Persona de Mediana Edad , Estudiantes , Adulto JovenRESUMEN
Selenium (Se) is required for synthesis of selenocysteine (Sec), an amino acid expressed in the active sites of Se-dependent enzymes (selenoenzymes), including forms with essential functions in fetal development, brain activities, thyroid hormone metabolism, calcium regulation, and to prevent or reverse oxidative damage. Homeostatic mechanisms normally ensure the brain is preferentially supplied with Se to maintain selenoenzymes, but high methylmercury (CH3Hg) exposures irreversibly inhibit their activities and impair Sec synthesis. Due to Hg's high affinity for sulfur, CH3Hg initially binds with the cysteine (Cys) moieties of thiomolecules which are selenoenzyme substrates. These CH3Hg-Cys adducts enter selenoenzyme active sites and transfer CH3Hg to Sec, thus irreversibly inhibiting their activities. High CH3Hg exposures are uniquely able to induce a conditioned Se-deficiency that impairs synthesis of brain selenoenzymes. Since the fetal brain lacks Se reserves, it is far more vulnerable to CH3Hg exposures than adult brains. This prompted concerns that maternal exposures to CH3Hg present in seafood might impair child neurodevelopment. However, typical varieties of ocean fish contain far more Se than CH3Hg. Therefore, eating them should augment Se-status and thus prevent Hg-dependent loss of fetal selenoenzyme activities. To assess this hypothesis, umbilical cord blood and placental tissue samples were collected following delivery of a cohort of 100 babies born on Oahu, Hawaii. Dietary food frequency surveys of the mother's last month of pregnancy identified groups with no (0 g/wk), low (0-12 g/wk), or high (12 + g/wk) levels of ocean fish consumption. Maternal seafood consumption increased Hg contents in fetal tissues and resulted in â¼34% of cord blood samples exceeding the EPA Hg reference level of 5.8 ppb (0.029 µM). However, Se concentrations in these tissues were orders of magnitude higher and ocean fish consumption caused cord blood Se to increase â¼9.4 times faster than Hg. Therefore, this study supports the hypothesis that maternal consumption of typical varieties of ocean fish provides substantial amounts of Se that protect against Hg-dependent losses in Se bioavailability. Recognizing the pivotal nature of the Hg:Se relationship provides a consilient perspective of seafood benefits vs. risks and clarifies the reasons for the contrasting findings of certain early studies.
Asunto(s)
Mercurio , Selenio , Adulto , Animales , Niño , Humanos , Femenino , Embarazo , Salud Infantil , Placenta/metabolismo , Alimentos Marinos/análisis , Peces/metabolismo , Selenocisteína/metabolismo , CisteínaRESUMEN
This clinical practice guideline is based on a series of systematic reviews of published studies in the available literature on the diagnosis and treatment of osteochondritis dissecans of the knee. None of the 16 recommendations made by the work group is graded as strong; most are graded inconclusive; two are graded weak; and four are consensus statements. Both of the weak recommendations are related to imaging evaluation. For patients with knee symptoms, radiographs of the joint may be obtained to identify the lesion. For patients with radiographically apparent lesions, MRI may be used to further characterize the osteochondritis dissecans lesion or identify other knee pathology.
Asunto(s)
Articulación de la Rodilla , Osteocondritis Disecante/diagnóstico , Osteocondritis Disecante/terapia , Terapia por Estimulación Eléctrica , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Articulación de la Rodilla/cirugía , Imagen por Resonancia Magnética , Procedimientos Ortopédicos , Aparatos Ortopédicos , RadiografíaRESUMEN
Of the 31 recommendations made by the work group, 19 were determined to be inconclusive because of the absence of definitive evidence. Of the remaining recommendations, four were classified as moderate grade, six as weak, and two as consensus statements of expert opinion. The four moderate-grade recommendations include suggestions that exercise and nonsteroidal anti-inflammatory drugs be used to manage rotator cuff symptoms in the absence of a full-thickness tear, that routine acromioplasty is not required at the time of rotator cuff repair, that non-cross-linked, porcine small intestine submucosal xenograft patches not be used to manage rotator cuff tears, and that surgeons can advise patients that workers' compensation status correlates with less favorable outcomes after rotator cuff surgery.
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Artropatías/terapia , Lesiones del Manguito de los Rotadores , Manguito de los Rotadores/cirugía , Articulación Acromioclavicular/cirugía , Corticoesteroides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Artroscopía/métodos , Terapia por Ejercicio , Humanos , Artropatías/cirugía , Lesiones del Hombro , Articulación del Hombro/cirugía , Traumatismos de los Tendones/terapiaRESUMEN
This protocol describes the application of breath testing and ex vivo fermentations to study the association between breath methane and the composition and functionality of the gut microbiome. The protocol provides a useful systems biology approach for studying the gut microbiome in humans, which combines standardized methods in human breath testing and fecal sampling. The model described is accessible and easy to repeat, but its relative simplicity means that it can deviate from human physiological conditions.
Asunto(s)
Heces/microbiología , Microbioma Gastrointestinal , Pruebas Respiratorias , HumanosRESUMEN
This technology overview addressed four questions that compared the difference in outcomes between patients undergoing cervical disc arthroplasty with patients undergoing anterior cervical diskectomy fusion. Most studies did not either report or conduct the appropriate statistical analyses to examine predictive characteristics in patients with successful clinical outcomes. Most studies were inconclusive or unreliable regarding clinical outcomes and revision and/or complication rates in patients who present with neck and/or arm pain. No significant difference in the length of hospital stay was reported; however, two studies included in the overview reported that patients treated with cervical disc arthroplasty returned to work in significantly fewer days (range, 14 to 16 days) than did patients treated with anterior cervical diskectomy fusion.
Asunto(s)
Artroplastia/métodos , Vértebras Cervicales/cirugía , Discectomía/métodos , Disco Intervertebral/cirugía , Dolor de Cuello/cirugía , Artroplastia/economía , Evaluación de la Discapacidad , Discectomía/economía , Humanos , Dimensión del Dolor , Selección de PacienteRESUMEN
This clinical practice guideline is based on a series of systematic reviews of published studies in the available literature on the diagnosis and treatment of acute Achilles tendon rupture. None of the 16 recommendations made by the work group was graded as strong; most are graded inconclusive; four are graded weak; two are graded as moderate strength; and two are consensus statements. The two moderate-strength recommendations include the suggestions for early postoperative protective weight bearing and for the use of protective devices that allow for postoperative mobilization.
Asunto(s)
Tendón Calcáneo/lesiones , Traumatismos de los Tendones/diagnóstico , Traumatismos de los Tendones/cirugía , Humanos , Modalidades de Fisioterapia , Cuidados Posoperatorios , Rotura , Traumatismos de los Tendones/rehabilitación , Soporte de PesoRESUMEN
This clinical practice guideline is based on a systematic review of published studies on the treatment of glenohumeral osteoarthritis in the adult patient population. Of the 16 recommendations addressed, nine are inconclusive. Two were reached by consensus-that physicians use perioperative mechanical and/or chemical venous thromboembolism prophylaxis for shoulder arthroplasty patients and that total shoulder arthroplasty not be performed in patients with glenohumeral osteoarthritis who have an irreparable rotator cuff tear. Four options were graded as weak: the use of injectable viscosupplementation; total shoulder arthroplasty and hemiarthroplasty as treatment; avoiding shoulder arthroplasty by surgeons who perform fewer than two shoulder arthroplasties per year (to reduce the risk of immediate postoperative complications); and the use of keeled or pegged all-polyethylene cemented glenoid components. The single moderate-rated recommendation was for the use of total shoulder arthroplasty rather than hemiarthroplasty. Management of glenohumeral osteoarthritis remains controversial; the scientific evidence on this topic can be significantly improved.
Asunto(s)
Artroplastia de Reemplazo/métodos , Osteoartritis/cirugía , Articulación del Hombro/cirugía , Anticoagulantes/administración & dosificación , Contraindicaciones , Humanos , Osteoartritis/fisiopatología , Diseño de Prótesis , Lesiones del Manguito de los Rotadores , Articulación del Hombro/fisiopatología , Tromboembolia/etiología , Tromboembolia/prevención & controlRESUMEN
The clinical practice guideline is based on a systematic review of published studies on the treatment of distal radius fractures in adults. None of the 29 recommendations made by the work group was graded as strong; most are graded as inconclusive or consensus; seven are graded as weak. The remaining five moderate-strength recommendations include surgical fixation, rather than cast fixation, for fractures with postreduction radial shortening >3 mm, dorsal tilt >10 degrees , or intra-articular displacement or step-off >2 mm; use of rigid immobilization rather than removable splints for nonsurgical treatment; making a postreduction true lateral radiograph of the carpus to assess dorsal radial ulnar joint alignment; beginning early wrist motion following stable fixation; and recommending adjuvant treatment with vitamin C to prevent disproportionate pain.
Asunto(s)
Procedimientos Ortopédicos/métodos , Fracturas del Radio/terapia , Adulto , Factores de Edad , Anciano , Artroscopía , Trasplante Óseo , Moldes Quirúrgicos , Humanos , Inmovilización/métodos , Persona de Mediana Edad , Radiografía , Fracturas del Radio/diagnóstico por imagen , Férulas (Fijadores)RESUMEN
Measuring the amount of mercury present in the environment or food sources may provide an inadequate reflection of the potential for health risks if the protective effects of selenium are not also considered. Selenium's involvement is apparent throughout the mercury cycle, influencing its transport, biogeochemical exposure, bioavailability, toxicological consequences, and remediation. Likewise, numerous studies indicate that selenium, present in many foods (including fish), protects against mercury exposure. Studies have also shown mercury exposure reduces the activity of selenium dependent enzymes. While seemingly distinct, these concepts may actually be complementary perspectives of the mercury-selenium binding interaction. Owing to the extremely high affinity between mercury and selenium, selenium sequesters mercury and reduces its biological availability. It is obvious that the converse is also true; as a result of the high affinity complexes formed, mercury sequesters selenium. This is important because selenium is required for normal activity of numerous selenium dependent enzymes. Through diversion of selenium into formation of insoluble mercury-selenides, mercury may inhibit the formation of selenium dependent enzymes while supplemental selenium supports their continued synthesis. Further research into mercury-selenium interactions will help us understand the consequences of mercury exposure and identify populations which may be protected or at greater risk to mercury's toxic effects.
Asunto(s)
Mercurio , Selenio , Animales , Peces/metabolismo , Mercurio/toxicidadRESUMEN
BACKGROUND: Methylmercury (CH3Hg) toxicity causes irreversible inhibition of selenium (Se)-dependent enzymes, including those that are required to prevent and reverse oxidative damage in the brain. Fish consumption provides numerous essential nutrients required for optimal health, but is also associated with CH3Hg exposure risks, especially during fetal development. Therefore, it is necessary to assess the amounts of both elements in seafood to evaluate relative risks or benefits. Consumption of ocean fish containing Se in molar excess of CH3Hg will prevent interruption of selenoenzyme activities, thereby alleviating Hg-exposure risks. Because dietary Se is a pivotal determinant of CH3Hg's effects, the Selenium Health Benefit Value (HBV) criterion was developed to predict risks or benefits as a result of seafood consumption. A negative HBV indicates Hg is present in molar excess of Se and may impair Se availability while a positive HBV indicates consumption will improve the Se status of the consumer, thus negating risks of Hg toxicity. OBJECTIVE: This study examined the Hg and Se contents of varieties of seafood to establish those with positive HBV's offering benefits and those having negative HBVs indicating potential consumption risks. METHODS: The Hg and Se molar concentrations in samples of meat from pilot whale, mako shark, thresher shark, swordfish, bigeye tuna, and skipjack tuna were used to determine their HBV's in relation to body weight. RESULTS: The HBVs of pilot whale, mako shark, and swordfish were typically negative and inversely related to body weight, indicating their consumption may impair Se availability. However, the HBV's of thresher shark, bigeye tuna, and skipjack tuna were uniformly positive regardless of body weights, indicating their consumption counteracts Hg-dependent risks of selenoenzyme impairment. CONCLUSIONS: The HBV criterion provides a reliable basis for differentiating seafoods whose intake should be limited during pregnancy from those that should be consumed to obtain health benefits.
Asunto(s)
Peces , Mercurio/análisis , Alimentos Marinos/análisis , Selenio/análisis , Animales , Humanos , Medición de RiesgoRESUMEN
Selenium (Se) supplementation in the nutritionally relevant range counteracts methylmercury (MeHg) toxicity. Since Se tends to be abundant in fish, MeHg exposures alone may not provide an accurate index of risk from fish consumption. Molar ratios of MeHg:Se in the diets and Hg:Se in tissues of exposed individuals may provide a more accurate index. This experiment compared MeHg toxicity in relation to MeHg exposure vs. Hg:Se molar ratios in diets and tissues. Diets were prepared using low-Se torula yeast basal diets supplemented with Na(2)SeO(4) to contain 0.1, 1.0, or 10.0 micromol Se/kg ( approximately 0.01, 0.08, or 0.8 ppm Se), reflecting low-, adequate-, or rich-Se intakes, respectively. Diets contained either low or high (0.5 micromol or 50 micromol MeHg/kg) ( approximately 0.10 or 10 ppm Hg). Sixty weanling male Long Evans rats were distributed into six weight-matched groups (three Se levels x two MeHg levels) that were supplied with water and their respective diets ab libitum for 18 weeks. No Se-dependent differences in growth were noted among rats fed low-MeHg diets, but growth impairments among rats fed high-MeHg were inversely related to dietary Se. After 3 weeks on the diet, growth impairments were evident among rats fed high-MeHg with low- or adequate-Se and after 10 weeks, rats fed low-Se, high-MeHg diets started to lose weight and displayed hind limb crossing. No weight loss or hind limb crossing was noted among animals fed high-MeHg, rich-Se diets. Methylmercury toxicity was not predictable by tissue Hg, but was inversely related to tissue Se (P<0.001) and directly related to Hg:Se ratios (P<0.001). Methylmercury-selenocysteine complexes (proposed name; pseudomethionine) appear likely to impair Se bioavailability, interrupting synthesis of selenium-dependent enzymes (selenoenzymes) that provide antioxidant protection in brain. Therefore, selenoenzymes may be the molecular target of methylmercury toxicity.
Asunto(s)
Antioxidantes/metabolismo , Intoxicación del Sistema Nervioso por Mercurio/dietoterapia , Compuestos de Metilmercurio/toxicidad , Selenio/metabolismo , Análisis de Varianza , Animales , Antioxidantes/administración & dosificación , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Dieta , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Miembro Posterior/efectos de los fármacos , Miembro Posterior/fisiopatología , Masculino , Intoxicación del Sistema Nervioso por Mercurio/etiología , Intoxicación del Sistema Nervioso por Mercurio/metabolismo , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Long-Evans , Selenio/administración & dosificación , Selenio/farmacología , Distribución TisularRESUMEN
BACKGROUND: Methylmercury (CH3Hg+) toxicity is characterized by challenging conundrums: 1) "selenium (Se)-protective" effects, 2) undefined biochemical mechanism/s of toxicity, 3) brain-specific oxidative damage, 4) fetal vulnerability, and 5) its latency effect. The "protective effects of Se" against CH3Hg+ toxicity were first recognized >50â¯years ago, but awareness of Se's vital functions in the brain has transformed understanding of CH3Hg+ biochemical mechanisms. Mercury's affinity for Se is ~1 million times greater than its affinity for sulfur, revealing it as the primary target of CH3Hg+ toxicity. SCOPE OF REVIEW: This focused review examined research literature regarding distinctive characteristics of CH3Hg+ toxicity to identify Se-dependent aspects of its biochemical mechanisms and effects. CONCLUSIONS: Research indicates that CH3Hg+ irreversibly inhibits the selenoenzymes that normally prevent/reverse oxidative damage in the brain. Unless supplemental Se is provided, consequences increase as CH3Hg+ approaches/exceeds equimolar stoichiometries with Se, thus forming HgSe and inducing a conditioned Se deficiency. As the biochemical target of CH3Hg+ toxicity, Se-physiology provides perspectives on the brain specificity of its oxidative damage, accentuated fetal vulnerability, and latency. This review reconsiders the concept that Se is a "tonic" that protects against CH3Hg+ toxicity and recognizes Se's role as Hg's molecular "target". As the most potent intracellular nucleophile, the selenoenzyme inhibition paradigm has broad implications in toxicology, including resolution of conundrums of CH3Hg+ toxicity. GENERAL SIGNIFICANCE: Mercury-dependent sequestration of selenium and the irreversible inhibition of selenoenzymes, especially those required to prevent and reverse oxidative damage in the brain, are primarily responsible for the characteristic effects of mercury toxicity.
RESUMEN
The influence of dietary selenium (Se) on mercury (Hg) toxicity was studied in weanling male Long Evans rats. Rats were fed AIN-93G-based low-Se torula yeast diets or diets augmented with sodium selenite to attain adequate- or rich-Se levels (0.1, 1.0 or 15 micromol/kg, respectively) These diets were prepared with no added methylmercury (MeHg) or with moderate- or high-MeHg (0.2, 10 or 60 micromol/kg, respectively). Health and weights were monitored weekly. By the end of the 9-week study, MeHg toxicity had impaired growth of rats fed high-MeHg, low-Se diets by approximately 24% (p < 0.05) compared to the controls. Growth of rats fed high-MeHg, adequate-Se diets was impaired by approximately 8% (p < 0.05) relative to their control group, but rats fed high-MeHg, rich-Se diets did not show any growth impairment. Low-MeHg exposure did not affect rat growth at any dietary Se level. Concentrations of Hg in hair and blood reflected dietary MeHg exposure, but Hg toxicity was more directly related to the Hg to Se ratios. Results support the hypothesis that Hg-dependent sequestration of Se is a primary mechanism of Hg toxicity. Therefore, Hg to Se molar ratios provide a more reliable and comprehensive criteria for evaluating risks associated with MeHg exposure.
Asunto(s)
Compuestos de Metilmercurio/toxicidad , Selenio/metabolismo , Animales , Encéfalo/metabolismo , Cabello/química , Masculino , Mercurio/sangre , Mercurio/metabolismo , Mercurio/toxicidad , Compuestos de Metilmercurio/sangre , Compuestos de Metilmercurio/metabolismo , Modelos Biológicos , Ratas , Ratas Long-Evans , Selenio/sangre , Factores de TiempoRESUMEN
Selenium (Se)-dependent enzymes (selenoenzymes) protect brain tissues against oxidative damage and perform other vital functions, but their synthesis requires a steady supply of Se. High methylmercury (CH3Hg) exposures can severely diminish Se transport across the placenta and irreversibly inhibit fetal brain selenoenzymes. However, supplemental dietary Se preserves their activities and thus prevents pathological consequences. The modified Se health benefit value (HBVSe) is a risk assessment criterion based on the molar concentrations of CH3Hg and Se present in a fish or seafood. It was developed to reflect the contrasting effects of maternal CH3Hg and Se intakes on fetal brain selenoenzyme activities. However, the original equation was prone to divide-by-zero-type errors whereby the calculated values increased exponentially in samples with low CH3Hg contents. The equation was refined to provide an improved index to better reflect the risks of CH3Hg exposures and the benefits provided by dietary Se. The HBVSe provides a biochemically based perspective that confirms and supports the FDA/EPA advice for pregnant and breast-feeding women regarding seafoods that should be avoided vs. those that are beneficial to consume. Since Se can be highly variable between watersheds, further evaluation of freshwater fish is needed to identify locations where fish with negative HBVSe may arise and be consumed by vulnerable subpopulation groups.
Asunto(s)
Contaminación de Alimentos/análisis , Compuestos de Metilmercurio/análisis , Compuestos de Metilmercurio/envenenamiento , Alimentos Marinos/análisis , Alimentos Marinos/envenenamiento , Selenio/análisis , Selenio/envenenamiento , Animales , Peces , Humanos , Compuestos de Metilmercurio/administración & dosificación , Medición de Riesgo , Selenio/administración & dosificaciónRESUMEN
Cytochrome c oxidase (CCO) is the Cu-dependent, terminal respiratory complex of the mitochondrial electron transport chain. Inhibition of CCO can promote oxidative stress by increasing mitochondrial production of reactive oxygen species (ROS). Because mitochondria have an important role in apoptosis as both a target and source for ROS, enhanced ROS production resulting from inhibition of CCO by Cu deficiency may trigger apoptosis. The present study focuses on the mitochondrial effects of N,N'-bis(2-aminoethyl)-1,3-propanedi-amine (TET), which inhibits CCO by causing cellular Cu deficiency, and the antioxidants ascorbate and alpha-tocopherol in a human promyelocytic leukemia cell line (HL-60). The following effects were observed: (i) TET reduced both cell growth and viability only in the presence of ascorbate or alpha-tocopherol; (ii) TET reduced CCO activity and increased mitochondrial ROS production as indicated by increased expression of Mn super-oxide dismutase, but the induction of Mn superoxide dismutase was not affected by ascorbate or alpha-tocopherol; (iii) TET acted independently of ascorbate or alpha-tocopherol in disrupting mitochondrial membrane potential; (iv) TET did not increase caspase-8 activity in the absence of ascorbate or alpha-tocopherol; and (v) TET did not increase transfer of cytochrome c from mitochondria to the cytosol unless alpha-tocopherol was present. These findings indicate that reduction in CCO activity by TET-induced Cu deficiency increased oxidative stress in HL-60 cells sufficiently to disrupt the electrochemical gradient of the inner mitochondrial membrane but did not trigger cell death. Also, ascorbate and alpha-tocopherol did not alleviate oxidative stress but may have become pro-oxidants, adding to the oxidant burden sufficiently to trigger cell death in TET-treated cells.
Asunto(s)
Ácido Ascórbico/farmacología , Muerte Celular/efectos de los fármacos , Cobre/metabolismo , alfa-Tocoferol/farmacología , Secuencia de Bases , Medios de Cultivo , Cartilla de ADN , Complejo IV de Transporte de Electrones/antagonistas & inhibidores , Complejo IV de Transporte de Electrones/metabolismo , Inhibidores Enzimáticos/farmacología , Células HL-60 , Humanos , Estrés Oxidativo , Poliaminas/farmacología , ARN Mensajero/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismoRESUMEN
Autism and autism spectrum disorders (ASDs) are behaviorally defined, but the biochemical pathogenesis of the underlying disease process remains uncharacterized. Studies indicate that antioxidant status is diminished in autistic subjects, suggesting its pathology is associated with augmented production of oxidative species and/or compromised antioxidant metabolism. This suggests ASD may result from defects in the metabolism of cellular antioxidants which maintain intracellular redox status by quenching reactive oxygen species (ROS). Selenium-dependent enzymes (selenoenzymes) are important in maintaining intercellular reducing conditions, particularly in the brain. Selenoenzymes are a family of ~25 genetically unique proteins, several of which have roles in preventing and reversing oxidative damage in brain and endocrine tissues. Since the brain's high rate of oxygen consumption is accompanied by high ROS production, selenoenzyme activities are particularly important in this tissue. Because selenoenzymes can be irreversibly inhibited by many electrophiles, exposure to these organic and inorganic agents can diminish selenoenzyme-dependent antioxidant functions. This can impair brain development, particularly via the adverse influence of oxidative stress on epigenetic regulation. Here we review the physiological roles of selenoproteins in relation to potential biochemical mechanisms of ASD etiology and pathology.
RESUMEN
Animal studies indicate that the toxic effects of methylmercury (MeHg) exposures increase when selenium (Se) status is low. Toxicity is directly proportional to Hg/Se molar ratios in critical tissues such as brain and increase dramatically as molar ratios exceed 1:1. In this study, we examined the nail as a biomonitor of Hg/Se molar ratios in kidney, liver, and brain tissues of weanling male Long-Evans rats fed controlled diets containing varying amounts of Se and MeHg. Linear regression analyses indicate that the natural log transform of the Hg/Se ratio in the nails is strongly related to the Hg/Se molar ratio in kidney, liver, and brain (p < 0.01 in all cases). The nail appears to be a reliably accurate noninvasive biomonitor of the Hg/Se molar ratio in tissues and should, therefore, be considered for use in human studies.