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BACKGROUND: The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19). METHODS: In this international, double-blind, placebo-controlled trial, we randomly assigned health care workers to receive the BCG-Denmark vaccine or saline placebo and followed them for 12 months. Symptomatic Covid-19 and severe Covid-19, the primary outcomes, were assessed at 6 months; the primary analyses involved the modified intention-to-treat population, which was restricted to participants with a negative test for severe acute respiratory syndrome coronavirus 2 at baseline. RESULTS: A total of 3988 participants underwent randomization; recruitment ceased before the planned sample size was reached owing to the availability of Covid-19 vaccines. The modified intention-to-treat population included 84.9% of the participants who underwent randomization: 1703 in the BCG group and 1683 in the placebo group. The estimated risk of symptomatic Covid-19 by 6 months was 14.7% in the BCG group and 12.3% in the placebo group (risk difference, 2.4 percentage points; 95% confidence interval [CI], -0.7 to 5.5; P = 0.13). The risk of severe Covid-19 by 6 months was 7.6% in the BCG group and 6.5% in the placebo group (risk difference, 1.1 percentage points; 95% CI, -1.2 to 3.5; P = 0.34); the majority of participants who met the trial definition of severe Covid-19 were not hospitalized but were unable to work for at least 3 consecutive days. In supplementary and sensitivity analyses that used less conservative censoring rules, the risk differences were similar but the confidence intervals were narrower. There were five hospitalizations due to Covid-19 in each group (including one death in the placebo group). The hazard ratio for any Covid-19 episode in the BCG group as compared with the placebo group was 1.23 (95% CI, 0.96 to 1.59). No safety concerns were identified. CONCLUSIONS: Vaccination with BCG-Denmark did not result in a lower risk of Covid-19 among health care workers than placebo. (Funded by the Bill and Melinda Gates Foundation and others; BRACE ClinicalTrials.gov number, NCT04327206.).
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Adyuvantes Inmunológicos , Vacuna BCG , COVID-19 , Personal de Salud , Humanos , Vacuna BCG/uso terapéutico , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/uso terapéutico , Método Doble Ciego , SARS-CoV-2 , Adyuvantes Inmunológicos/uso terapéuticoRESUMEN
Cardiovascular complications are the most frequent cause of death in patients with the Hutchinson-Gilford progeria syndrome. However, due to its rarity, studying the course of cardiac abnormalities has been a challenge. The cardiovascular phenotype helps to provide greater insight into the natural history of these abnormalities.
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We report on a 50-year-old female patient, with several severe comorbidities and high-surgical risk, in whom we successfully performed a simultaneous transcatheter pulmonary and tricuspid valve-in-ring implantation to treat both bioprosthetic pulmonary valve dysfunction and native torrential tricuspid valve regurgitation, the latter previously managed with a Carpentier annuloplasty ring.
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Anuloplastia de la Válvula Cardíaca , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Tricúspide , Cateterismo Cardíaco , Femenino , Humanos , Persona de Mediana Edad , Diseño de Prótesis , Resultado del Tratamiento , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/cirugía , Insuficiencia de la Válvula Tricúspide/diagnóstico , Insuficiencia de la Válvula Tricúspide/cirugíaRESUMEN
Ruptured sinus of Valsalva aneurysm is a rare entity in children. To our knowledge, this is the youngest child reported in the literature with a sinus of Valsalva ruptured aneurysm being successfully treated percutaneously using an AmplatzerTM Duct Occluder II Additional Sizes device.
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Aneurisma de la Aorta , Rotura de la Aorta , Seno Aórtico , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/cirugía , Rotura de la Aorta/diagnóstico por imagen , Rotura de la Aorta/cirugía , Niño , Humanos , Lactante , Seno Aórtico/diagnóstico por imagen , Seno Aórtico/cirugíaRESUMEN
Superior-inferior ventricular arrangement with double-outlet left ventricle and malposition of the great arteries is an extremely rare congenital cardiac anomaly. The authors present the case of an infant who presented with cyanosis and respiratory distress. To the best of our knowledge, this is the first case reported.
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Cardiopatías Congénitas , Transposición de los Grandes Vasos , Arterias , Cianosis , Cardiopatías Congénitas/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Lactante , Transposición de los Grandes Vasos/diagnóstico por imagen , Transposición de los Grandes Vasos/cirugíaRESUMEN
Fipronil is an insecticide widely used in agriculture, veterinary medicine and public health that has recently been listed as a potential endocrine disrupter. In the present study we evaluated the effects of perinatal exposure to fipronil during the period of sexual brain differentiation and its later repercussions on reproductive parameters in male rats. Pregnant rats were exposed (via gavage) to fipronil (0.03, 0.3 or 3mgkg-1) from Gestational Day 15 until Postnatal Day 7. Fipronil exposure did not compromise the onset of puberty. In adulthood, there was no effect on organ weight or sperm production. Furthermore, there were no adverse effects on the number of Sertoli cells per seminiferous tubule, testicular and epididymal histomorphometry or histopathology or expression patterns of androgen receptor in the testis. Similarly, no changes were observed in the sexual behaviour or hormone levels. However, in rats exposed to fipronil, changes in sperm motility were observed, with a decrease in motile spermatozoa and an increase in non-mobile spermatozoa, which can compromise sperm quality in these rats. Perinatal exposure to fipronil has long-term effects on sperm parameters, and the epididymis can be a target organ. Additional studies should be undertaken to identify the mechanisms by which fipronil affects sperm motility.
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Astenozoospermia/inducido químicamente , Disruptores Endocrinos/toxicidad , Epidídimo/efectos de los fármacos , Insecticidas/toxicidad , Lactancia , Exposición Materna/efectos adversos , Pirazoles/toxicidad , Administración Oral , Animales , Astenozoospermia/patología , Forma de la Célula/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Disruptores Endocrinos/administración & dosificación , Epidídimo/patología , Femenino , Desarrollo Fetal/efectos de los fármacos , Insecticidas/administración & dosificación , Masculino , Neurogénesis/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Pirazoles/administración & dosificación , Ratas Wistar , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/patología , Motilidad Espermática/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Testículo/patologíaRESUMEN
Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation and decreasing mortality. Previous studies in rats reported male programming and alteration in sperm parameters and sexual behavior following intrauterine betamethasone exposure. The impact on the female reproductive development is not known. In this study, rat female offspring was assessed for sexual development, morphophysiology of the reproductive tract and fertility after maternal exposure to 0.1 mg kg-1 of betamethasone or vehicle on gestational days 12, 13, 18 and 19. The treatment promoted reduction of litter weight on postnatal day 1, morphological masculinization in females, delay in the age of puberty onset, reduction in estrus number, increase in estrous cycle length and increase in luteinizing hormone serum levels and uterus weight. The females from the betamethasone group showed an increase of myometrial uterine area and decrease in endometrial uterine area. These animals also performed less lordosis during the sexual behavior test and showed impaired reproductive performance. The uterus showed higher contraction in the treated group as shown by a pharmacological assay. In conclusion, prenatal betamethasone exposure in rats promoted female masculinization, altered sexual development and reproductive parameters. Copyright © 2017 John Wiley & Sons, Ltd.
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Betametasona/toxicidad , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Reproducción/efectos de los fármacos , Animales , Peso Corporal , Ciclo Estral/efectos de los fármacos , Estro/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Hormona Luteinizante/sangre , Masculino , Exposición Materna/efectos adversos , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Conducta Sexual Animal/efectos de los fármacos , Útero/efectos de los fármacosRESUMEN
The global interest in edible insects as sustainable protein sources raises concerns about the bioaccumulation of contaminants, including polycyclic aromatic hydrocarbons (PAHs), to problematic levels. Understanding the accumulation dynamics of PAHs in edible insects is highly relevant due to the widespread sources and toxicological profiles; however, the bioaccumulative potential of PAHs in edible insects is unexplored. This study examined the uptake and elimination dynamics of benzo(a)pyrene (B(a)P), a representative and carcinogenic PAH, in yellow mealworm larvae (YMW, Tenebrio molitor). Larvae were exposed to feeding substrate with varying B(a)P concentrations (0.03, 0.3, and 3 mg kg-1), and uptake (21 days in B(a)P-contaminated substrate) and elimination (21 days in B(a)P-free substrate) kinetics were subsequently assessed. The results showed that YMW can eliminate B(a)P, revealing dose-dependent B(a)P bioaccumulation in these insects. Larvae fed on a substrate with 0.03 mg kg-1 accumulated B(a)P over 21 days, presenting values of 0.049 (Standard deviation - 0.011) mg kg-1 and a kinetic-based (BAFkinetic) of 1.93 g substrate g organism-1, exceeding the EU regulatory limits for food. However, with a B(a)P half-life (DT50) of 4.19 days in the larvae, an EU legislation safety criterion was met after a 13-day depuration period in clean substrate. Larvae exposed to substrates with 0.3 and 3 mg kg-1 showed B(a)P accumulation, with BAFkinetic values of 3.27 and 2.09 g substrate g organism-1, respectively, not meeting the current legal standards for food consumption at the end of the exposure to B(a)P. Although the B(a)P half-life values after 35 days were 4.30 and 10.22 days (DT50s), the larvae retained B(a)P levels exceeding permitted food safety limits. These findings highlight a significant oversight in regulating PAHs in animal feed and the need for comprehensive safety evaluations of PAH hazards in edible insects for improved PAH feeding guidelines.
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Benzo(a)pireno , Larva , Tenebrio , Animales , Benzo(a)pireno/metabolismo , Benzo(a)pireno/toxicidad , Larva/efectos de los fármacos , Toxicocinética , Insectos Comestibles , Bioacumulación , Contaminación de AlimentosRESUMEN
BACKGROUND: Preterm birth and congenital heart defects are two major causes of neonatal and infant mortality. However, the relationship between them has not yet been fully clarified. OBJECTIVE: To determine the prevalence and spectrum of congenital heart defects in preterms, the specific associations between categories of congenital heart defects and preterm birth and to establish the influence on outcomes. METHODS: Observational, case-control analysis that included 448 live births with congenital heart defects born between 2003 and 2017. Preterm with congenital heart defects were the case subjects and term neonates with congenital heart defects the control subjects. RESULTS: Of the newborns with congenital heart defects, 23% were preterm. The odds of congenital heart defects in preterm were twofold higher than for term neonates (p<0.0001), even when considering only those with severe congenital heart defects (p=0.0002). The odds in preterm were 9.2-fold higher for abnormalities of the atria and atrial septum (p<0.0001) and two-fold higher for abnormalities of the ventricles and ventricular septum (p<0.0001) compared with term neonates. The neonatal mortality rate in the preterm group was not statistically different from that of the term group with congenital heart defects (p=0.799) or severe congenital heart defects (p=0.554). CONCLUSION: Preterm have more than twice as many congenital heart defects as term neonates. Although the etiology of prematurity between infants with congenital heart defects is still uncertain, our findings highlight a possible relationship between prematurity and congenital heart defects.
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Cardiopatías Congénitas , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Recien Nacido Prematuro , Prevalencia , Derivación y Consulta , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/epidemiologíaRESUMEN
Layered double hydroxides (LDHs) are innovative nanomaterials (NMs) with a typical nanoclay structure (height <40 nm) consisting of layers of metallic cations and hydroxides stabilized by anions and water molecules. Upon specific triggers, anions can exchange by others in the surrounding environment. Due to this stimuli-responsive behavior, LDHs are used as carriers of active ingredients in the industrial or pharmaceutical sectors. Available technical guidelines to evaluate the ecotoxicity of conventional substances do not account for the specificities of NMs, leading to inaccuracies and uncertainty. The present study aimed to assess two different exposure methodologies (serial dilutions of the stock dispersion vs. direct addition of NM powder to each concentration) on the ecotoxicological profile of different powder grain sizes of Zn-Al LDH-NO3 and Cu-Al LDH-NO3 (bulk, <25, 25-63, 63-125, 125-250, and >250 µm) in the growth of the freshwater microalgae Raphidocelis subcapitata. Results revealed that the serial dilutions methodology was preferable for Zn-Al LDH-NO3, whereas for Cu-Al LDH-NO3 both methodologies were suitable. Thus, the serial dilutions methodology was selected to assess the ecotoxicity of different grain sizes for both LDHs. All Zn-Al LDH-NO3 grain sizes yielded similar toxicity, while Cu-Al LDH-NO3 powders with smaller grain sizes caused a higher effect on microalgae growth; thus, grain size separation might be advantageous for future applications of Cu-Al LDH-NO3s. Considering the differences between exposure methodologies for the Zn-Al LDH-NO3, further research involving other NMs and species must be carried out to achieve harmonization and validation for inter-laboratory comparison.
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Microalgas , Nanoestructuras , Ecotoxicología , Polvos/farmacología , Hidróxidos/toxicidad , Hidróxidos/química , Agua Dulce , Nanoestructuras/toxicidadRESUMEN
Engineered nanoparticles released into surface water may accumulate in sediments, potentially threatening benthic organisms. This study determined the toxicokinetics in Chironomus riparius of Ag from pristine silver nanoparticles (Ag NPs), a simulating aged Ag NP form (Ag2S NPs), and AgNO3 as an ionic control. Chironomid larvae were exposed to these Ag forms through water, sediment, or food. The potential transfer of Ag from larvae to adult midges was also evaluated. Results revealed higher Ag uptake by C. riparius upon exposure to Ag2S NPs, while larvae exposed to pristine Ag NPs and AgNO3 generally presented similar uptake kinetics. Uptake patterns of the different Ag forms were generally similar in the tests with water or sediment exposures, suggesting that uptake from water was the most important route of Ag uptake in both experiments. For the sediment bioaccumulation test, uptake was likely a combination of water uptake and sediment particles ingestion. Ag uptake via food exposure was only significant for Ag2S NPs. Ag transfer to the terrestrial compartment was low. In our environmentally relevant exposure scenario, chironomid larvae accumulated relatively high Ag concentrations and elimination was extremely low in some cases. These results suggest that bioaccumulation of Ag in its nanoparticulate and/or ionic form may occur in the environment, raising concerns regarding chronic exposure and trophic transfer. This is the first study determining the toxicokinetics of NPs in Chironomus, providing important information for understanding chironomid exposure to NPs and their potential interactions in the environment.
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Chironomidae , Nanopartículas del Metal , Animales , Nanopartículas del Metal/toxicidad , Plata/toxicidad , Toxicocinética , SulfurosRESUMEN
The world population is experiencing colossal growth and thus demand for food, leading to an increase in the use of pesticides. Persistent pesticide contamination, such as carbendazim, remains a pressing environmental concern, with potentially long-term impacts on aquatic ecosystems. In the present study, Daphnia magna was exposed to carbendazim (5 µg L-1) for 12 generations, with the aim of assessing gene transcription alterations induced by carbendazim (using a D. magna custom microarray). The results showed that carbendazim caused changes in genes involved in the response to stress, DNA replication/repair, neurotransmission, ATP production, and lipid and carbohydrate metabolism at concentrations already found in the environment. These outcomes support the results of previous studies, in which carbendazim induced genotoxic effects and reproduction impairment (increasing the number of aborted eggs with the decreasing number of neonates produced). The exposure of daphnids to carbendazim did not cause a stable change in gene transcription between generations, with more genes being differentially expressed in the F0 generation than in the F12 generation. This could show some possible daphnid acclimation after 12 generations and is aligned with previous multigenerational studies where few ecotoxicological effects at the individual and populational levels and other subcellular level effects (e.g., biochemical biomarkers) were found.
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Multiple factors, including vaccine platform and prior vaccinations, influence vaccine responses. We compared antibody responses to CoronaVac (Sinovac) and ChAdOx1-S (AstraZeneca-Oxford) vaccination in 874 healthcare workers in Brazil. As participants were randomised to BCG vaccination or placebo in the preceding 0-6 months as part of the BCG vaccination to reduce the impact of COVID-19 in healthcare workers (BRACE) trial, we also investigated the influence of recent BCG vaccination on antibody responses to these COVID-19 vaccines. Twenty-eight days after the second dose of each vaccine, ChAdOx1-S induced a stronger anti-spike IgG response than CoronaVac vaccination. Recent BCG vaccination did not impact IgG antibody responses to ChAdOx1-S or CoronaVac.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Vacuna BCG , Formación de Anticuerpos , COVID-19/prevención & control , Vacunación , ChAdOx1 nCoV-19 , Inmunoglobulina GRESUMEN
Mesocosms allow the simulation of environmentally relevant conditions and can be used to establish more realistic scenarios of organism exposure to nanoparticles. An indoor mesocosm experiment simulating an aquatic stream ecosystem was conducted to assess the toxicokinetics and bioaccumulation of silver sulfide nanoparticles (Ag2S NPs) and AgNO3 in the freshwater invertebrates Girardia tigrina, Physa acuta and Chironomus riparius, and determine if previous single-species tests can predict bioaccumulation in the mesocosm. Water was daily spiked at 10 µg Ag L-1. Ag concentrations in water and sediment reached values of 13.4 µg Ag L-1 and 0.30 µg Ag g-1 in the Ag2S NP exposure, and 12.8 µg Ag L-1 and 0.20 µg Ag g-1 in the AgNO3. Silver was bioaccumulated by the species from both treatments, but with approximately 1.5, 3 and 11 times higher body Ag concentrations in AgNO3 compared to Ag2S NP exposures in snails, chironomids and planarians, respectively. In the Ag2S NP exposures, the observed uptake was probably of the particulate form. This demonstrates that this more environmentally relevant Ag nanoform may be bioavailable for uptake by benthic organisms. Interspecies interactions likely occurred, namely predation (planarians fed on chironomids and snails), which somehow influenced Ag uptake/bioaccumulation, possibly by altering organisms´ foraging behaviour. Higher Ag uptake rate constants were determined for AgNO3 (0.64, 80.4 and 1.12 Lwater g-1organism day-1) than for Ag2S NPs (0.05, 2.65 and 0.32 Lwater g-1organism day-1) for planarians, snails and chironomids, respectively. Biomagnification under environmentally realistic exposure seemed to be low, although it was likely to occur in the food chain P. acuta to G. tigrina exposed to AgNO3. Single-species tests generally could not reliably predict Ag bioaccumulation in the more complex mesocosm scenario. This study provides methodologies/data to better understand exposure, toxicokinetics and bioaccumulation of Ag in complex systems, reinforcing the need to use mesocosm studies to improve the risk assessment of environmental contaminants, specifically NPs, in aquatic environments.
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Nanopartículas del Metal , Animales , Bioacumulación , Nanopartículas del Metal/toxicidad , Ecosistema , Toxicocinética , RíosRESUMEN
Bioaccumulation studies are critical in regulatory decision making on the potential environmental risks of engineered nanoparticles (NPs). The present study evaluated the toxicokinetics of silver, taken up from sulfide nanoparticles (Ag2S NPs; simulating an aged Ag NP form) and AgNO3 (ionic counterpart), in the pulmonate snail Physa acuta and the planarian Girardia tigrina. The snails were first exposed for 7 days to Ag-spiked water, along with the microalgae Raphidocelis subcapitata upon which they fed setting up a double route exposure, and subsequently provided as pre-exposed food to the planarians. Ag toxicokinetics and bioaccumulation were assessed in planarians and snails, and potential biomagnification from snail to planarian was evaluated. Gut depuration was also explored to understand whether it constitutes a factor likely to influence Ag toxicokinetics and internal concentrations in the test species. Both species revealed Ag uptake in Ag2S NP and AgNO3 treatments, with higher uptake from the latter. Uptake by the snails was probably via a combination of water exposure and ingested algae provided as food, but ingestion of algae possibly had higher relevance for Ag uptake from the Ag2S NPs compared to AgNO3. For planarians, diet probably was the most important exposure route since no Ag uptake was observed in previous waterborne exposures to Ag2S NPs. Kinetics and internal Ag concentrations did not significantly differ between depurated and non-depurated snails or planarians. The planarians fed on snails revealed no biomagnification. To the best of our knowledge this is the first study investigating the toxicokinetics and biomagnification of NPs in planarians, and with that providing important data on the kinetics and bioaccumulation of NPs in a relevant benthic species.
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Nanopartículas del Metal , Planarias , Animales , Bioacumulación , Agua Dulce , Nanopartículas del Metal/toxicidad , Compuestos de Plata , Nitrato de Plata , Caracoles , SulfurosRESUMEN
The fate of engineered nanomaterials in ecosystems is unclear. An aquatic stream mesocosm explored the fate and bioaccumulation of silver sulfide nanoparticles (Ag2S NPs) compared to silver nitrate (AgNO3). The aims were to determine the total Ag in water, sediment and biota, and to evaluate the bioavailable fractions of silver in the sediment using a serial extraction method. The total Ag in the water column from a nominal daily dose of 10 µg L-1 of Ag for the AgNO3 or Ag2S NP treatments reached a plateau of around 13 and 12 µg L-1, respectively, by the end of the study. Similarly, the sediment of both Ag-treatments reached ~380 µg Ag kg-1, and with most of it being acid-extractable/labile. The biota accumulated 4-59 µg Ag g-1 dw, depending on the type of Ag-treatment and organism. The oligochaete worm, Lumbriculus variegatus, accumulated Ag from the Ag2S exposure over time, which was similar to the AgNO3 treatment by the end of the experiment. The planarian, Girardia tigrina, and the chironomid larva, Chironomus riparius, showed much higher Ag concentrations than the oligochaete worms; and with a clearer time-dependent statistically significant Ag accumulation relative to the untreated controls. For the pulmonate snail, Physa acuta, bioaccumulation of Ag from AgNO3 and Ag2S NP exposures was observed, but was lower from the nano treatment. The AgNO3 exposure caused appreciable Ag accumulation in the water flea, Daphnia magna, but accumulation was higher in the Ag2S NP treatment (reaching 59 µg g-1 dw). In the rainbow trout, Oncorhynchus mykiss, AgNO3, but not Ag2S NPs, caused total Ag concentrations to increase in the tissues. Overall, the study showed transfer of total Ag from the water column to the sediment, and Ag bioaccumulation in the biota, with Ag from Ag2S NP exposure generally being less bioavailable than that from AgNO3.
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Nanopartículas del Metal , Oncorhynchus mykiss , Contaminantes Químicos del Agua , Animales , Colorantes , Daphnia , Ecosistema , Metales , Ríos , Compuestos de Plata , Nitrato de Plata , SulfurosRESUMEN
Sibutramine is a non-selective serotonin-norepinephrine reuptake inhibitor orally administered for weight loss. In a previous study, we showed pharmacological mechanisms involved in the reduction of sperm quality and fertility of rats exposed for 30 days to this anorexigen in the light phase of the light-dark (l/d) cycle. It is already known that rodents are nightlife animals, with higher metabolic activity during the dark phase than in the light phase of the light-dark (l/d) cycle. Thus, the present study aimed to investigate whether the deleterious effects on reproductive parameters after sibutramine administration would be enhanced after a shorter period of exposure during the dark phase of the l/d cycle. For this, adult male Wistar rats were treated with sibutramine (10 mg/kg/d) or vehicle for 15 days during the dark phase of the l/d cycle. Sibutramine treatment decreased final body and reproductive organ weights, as well as serum testosterone levels. Sperm transit time through the epididymis was accelerated, and sperm concentration and motility were diminished in the sibutramine-exposed rats. The decrease in sperm concentration was also verified in the epididymal histological sections. In conclusion, the deleterious effects of sibutramine on reproductive parameters of male rats were enhanced when the exposure occurred in the dark phase of the l/d cycle, even after a short exposure duration. Our results reinforce the impact of timing on drug therapeutic action.
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Depresores del Apetito/toxicidad , Ciclobutanos/toxicidad , Epidídimo/efectos de los fármacos , Reproducción/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Depresores del Apetito/administración & dosificación , Ciclobutanos/administración & dosificación , Cronoterapia de Medicamentos , Epidídimo/patología , Masculino , Fotoperiodo , Ratas Wistar , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Espermatozoides/patología , Testículo/patología , Factores de TiempoRESUMEN
Statins are a class of drugs that act lowering lipid levels by inhibiting cholesterol biosynthesis. Additionally, statins can act by "pleiotropic effects", related to the inhibition of synthesis of the other mevalonate pathway products. Rosuvastatin is a third-generation statin and has shown better results in reducing cholesterol concentrations when compared to other statins. Recent studies suggest that rosuvastatin may act as an endocrine disruptor that potentially damages the hormonal axis and, consequently reproductive development and function of male rats. However, the effects of rosuvastatin exposure on rat female reproductive parameters remain unknown. In this study female rats were exposed to rosuvastatin at the doses of 0 (control), 3, or 10 mg/Kg.bw-1/day from pre-puberty to adulthood. No alterations in the female reproductive parameters were observed at a dose of 3 mg/Kg.bw-1. However, females exposed to 10 mg/Kg.bw-1 exhibited shorter estrous cycles, altered copulatory behavior, decreased serum prolactin level, and alterations in the liver, pituitary and placental weights, parameters to some extent influenced by the reproductive hormonal axis signaling pathway. On the other hand, pubertal onset, reproductive hormone levels, fertility, and histological parameters of the ovary, uterus, and placenta were unaltered by exposure to both doses of this statin. Thus, rosuvastatin exposure, at the higher dose, altered the reproductive function of female rats, probably due to the pleiotropic effects of this statin. Additional studies on the effects of this statin on female reproductive function and development are encouraged to better characterize its mode of action.
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In the last decades, the use of organic ultraviolet-filters (UV-filters) has increased worldwide, and these compounds are now considered emerging contaminants of many freshwater ecosystems. The present study aimed to assess the effects of 3-(4-methylbenzylidene) camphor (4-MBC) on a freshwater invertebrate community and on associated ecological functions. For that, artificial streams were used, and a natural invertebrate benthic community was exposed to sediments contaminated with two concentrations of 4-MBC. Effects were evaluated regarding macroinvertebrate abundance and community structure, as well as leaf decomposition and primary production. Results showed that the macroinvertebrate community parameters and leaf decomposition rates were not affected by 4-MBC exposure. On the other hand, primary production was strongly reduced. This study highlights the importance of higher tier ecotoxicity experiments for the assessment of the effects of low concentrations of organic UV-filters on freshwater invertebrate community structure and ecosystem functioning.
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Alcanfor/análogos & derivados , Invertebrados/efectos de los fármacos , Ríos , Contaminantes Químicos del Agua/toxicidad , Animales , Alcanfor/toxicidad , Ecosistema , Agua Dulce/química , Invertebrados/fisiologíaRESUMEN
The exposure to pesticides by nontarget soil biota has long been regarded as a serious downside of modern agricultural regimes and the subject of heated debate. Of utmost relevance is the exposure to pesticide mixtures because their effects have been shown to not necessarily reflect the individual toxicity of their components, and even the simple addition of effects may lead to consequences not clearly anticipated. In the present study, a multiple biomarker approach was employed to identify the mechanistic and time effects underlying several single and mixture treatments of chlorpyrifos (CPF) and mancozeb (MCZ) in juveniles and adults of the terrestrial isopod Porcellionides pruinosus. The effects of the individual pesticides and the mixtures at recommended doses were mostly transitory under these controlled conditions and one-pulse exposure. Whereas imbalances were identified on detoxification and oxidative stress-related enzymes, the isopods generally showed the ability to recover through the end of the experiment. However, juveniles displayed greater vulnerability than adults. Most of the differences between life stages occurred in energy-related parameters where distinct performances and stress-handling behaviors were observed, suggesting higher metabolic costs to juveniles. Our results stress that understanding the time dependence of the underlying mechanisms governing the joint effects of the pesticides can help in assessing and anticipating the effects of the pesticide mixtures. Moreover, we emphasize the importance of taking life stage-related differences into consideration when evaluating the environmental risks of pesticides and pesticide mixtures. Environ Toxicol Chem 2018;37:1446-1457. © 2018 SETAC.