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1.
Med. clín. soc ; 7(2)ago. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1440489

RESUMO

El síndrome de DRESS (por sus siglas en inglés Drug Reaction with Eosinophilia and Systemic Symptoms) representa una farmacodermia grave con diferentes manifestaciones clínicas y paraclínicas secundarias a una reacción de hipersensibilidad farmacológica. Su incidencia exacta es desconocida pero se estima entre 1 a 1000 y 1 a 10000 casos de exposición a fármacos asociados. Se caracteriza por dermatosis generalizada extensa en conjunto con afección orgánica, linfadenopatia, eosinofilia y linfocitosis atípica. Entre los fármacos comúnmente asociados se encuentran anticomiciales aromáticos, carbamazepina, sulfonamidas y el alopurinol. Mediante el uso de la puntuación RegiSCAR es posible confirmar o descartar una sospecha de diagnóstico. El tratamiento depende de la severidad de presentación incluyendo esteroides tópicos hasta esteroide sistémico de duración variable dependiendo respuesta clínica y bioquímica. Se reporta tasas de mortalidad del 10 al 20% siendo la insuficiencia hepática la principal causa de muerte en estos pacientes. Se presenta el caso de un paciente femenino de 71 años de edad que, posterior a tratamiento con alopurinol, debuta con eritrodermia secundaria a Síndrome de DRESS.


DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) represents severe pharmacodermia with different clinical and paraclinical manifestations secondary to a drug hypersensitivity reaction. The exact incidence is unknown, but it is estimated to be between 1 in 1,000 and 1 in 10,000 cases of exposure to associated drugs. It is characterized by extensive generalized dermatosis, in conjunction with organic involvement, lymphadenopathy, eosinophilia, and atypical lymphocytosis. Commonly associated drugs include aromatic anticonvulsants, carbamazepine, sulfonamides, and allopurinol. By using the RegiSCAR score, it is possible to confirm or rule out a suspected diagnosis. Treatment depends on the severity of presentation, including topical steroids to systemic steroids of variable duration, depending on clinical and biochemical responses. Mortality rates of 10 - 20% have been reported, with liver failure being the main cause of death in these patients. We present the case of a 71-year-old female patient who, after treatment with allopurinol, developed erythroderma secondary to DRESS Syndrome.

2.
Interv Neuroradiol ; 29(2): 189-195, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35234070

RESUMO

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a known predictor of poor outcomes in critically ill patients. We sought to examine the role ARDS plays in outcomes in subarachnoid hemorrhage (SAH) patients. Prior studies investigating the incidence of ARDS in SAH patients did not control for SAH severity. Hence, we sought to determine the incidence ARDS in patients diagnosed with aneurysmal SAH and investigate the predisposing risk factors and impact upon outcomes. METHODS: A retrospective cohort study was conducted using the National Inpatient Sample (NIS) database for the years 2008 to 2014. Multivariate stepwise regression analysis was performed to identify the risk factors and outcome associated with developing ARDS in the setting of SAH. RESULTS: We identified 170,869 patients with non-traumatic subarachnoid hemorrhage, of whom 6962 were diagnosed with ARDS and of those 4829 required mechanical ventilation. ARDS more frequently developed in high grade SAH patients (1.97 ± 0.05 vs. 1.15 ± 0.01; p < 0.0001). Neurologic predictors of ARDS included cerebral edema (OR 1.892, CI 1.180-3.034, p = 0.0035) and medical predictors included cardiac arrest (OR 4.642, CI 2.273-9.482, p < 0.0001) and cardiogenic shock (OR 2.984, CI 1.157-7.696, p = 0.0239). ARDS was associated with significantly worse outcomes (15.5% vs. 52.9% discharged home, 63.0% vs. 40.8% discharged to rehabilitation facility and 21.5% vs. 6.3% in-hospital mortality). CONCLUSION: Patients with SAH who developed ARDS were less likely to be discharged home, more likely to need rehabilitation and had a significantly higher risk of mortality. The identification of risk factors contributing to ARDS is helpful for improving outcomes and resource utilization.


Assuntos
Síndrome do Desconforto Respiratório , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia , Estudos Retrospectivos , Incidência , Pacientes Internados , Fatores de Risco , Síndrome do Desconforto Respiratório/complicações
3.
Interv Neuroradiol ; 29(4): 363-370, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35354315

RESUMO

BACKGROUND: Heparin induced thrombocytopenia Type II (HIT-II) is a dangerous thromboembolic complication of heparin therapy. The current literature on incidence and outcomes of HIT-II in aneurysmal subarachnoid hemorrhage (aSAH) patients remains sparse. OBJECTIVE: We report our institution's incidence and outcomes of HIT-II in aSAH patients. METHODS: We performed a retrospective cohort study at an academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography. Diagnosis of HIT-II was determined by positive results on both heparin PF4-platelet antibody ELISA (anti-PF4) and serotonin release assay (SRA). RESULTS: 204 patients met inclusion criteria. Seven patients (7/204, 3.5%) underwent laboratory testing, three of whom met clinical criteria. HIT-II incidence was confirmed in two of these seven patients (2/204, 0.98%), who had high BMI and T4 scores. CONCLUSION: Our institution's report of HIT-II incidence in aSAH patients is lower than previously reported in this population and more closely parallels HIT-II incidence in the general and surgical ICU setting. Widely-accepted American College of Chest Physicians (ACCP) clinical diagnostic criteria in conjunction with anti-PF4 and SRA testing is the gold standard of clinical diagnosis of HIT-II in aSAH patients.


Assuntos
Hemorragia Subaracnóidea , Trombocitopenia , Trombose , Humanos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/tratamento farmacológico , Estudos Retrospectivos , Trombocitopenia/induzido quimicamente , Heparina/efeitos adversos , Anticoagulantes/efeitos adversos
4.
Mol Neurobiol ; 58(11): 5494-5516, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34341881

RESUMO

Spinal cord injury (SCI) is a devastating condition that affects approximately 294,000 people in the USA and several millions worldwide. The corticospinal motor circuitry plays a major role in controlling skilled movements and in planning and coordinating movements in mammals and can be damaged by SCI. While axonal regeneration of injured fibers over long distances is scarce in the adult CNS, substantial spontaneous neural reorganization and plasticity in the spared corticospinal motor circuitry has been shown in experimental SCI models, associated with functional recovery. Beneficially harnessing this neuroplasticity of the corticospinal motor circuitry represents a highly promising therapeutic approach for improving locomotor outcomes after SCI. Several different strategies have been used to date for this purpose including neuromodulation (spinal cord/brain stimulation strategies and brain-machine interfaces), rehabilitative training (targeting activity-dependent plasticity), stem cells and biological scaffolds, neuroregenerative/neuroprotective pharmacotherapies, and light-based therapies like photodynamic therapy (PDT) and photobiomodulation (PMBT). This review provides an overview of the spontaneous reorganization and neuroplasticity in the corticospinal motor circuitry after SCI and summarizes the various therapeutic approaches used to beneficially harness this neuroplasticity for functional recovery after SCI in preclinical animal model and clinical human patients' studies.


Assuntos
Plasticidade Neuronal , Tratos Piramidais/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Interfaces Cérebro-Computador , Terapia Combinada , Terapia por Estimulação Elétrica , Humanos , Locomoção/fisiologia , Terapia com Luz de Baixa Intensidade , Córtex Motor/fisiopatologia , Regeneração Nervosa , Crescimento Neuronal , Fármacos Neuroprotetores/uso terapêutico , Fotoquimioterapia , Qualidade de Vida , Recuperação de Função Fisiológica , Riluzol/uso terapêutico , Medula Espinal/fisiopatologia , Doenças da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/terapia , Transplante de Células-Tronco , Estimulação Transcraniana por Corrente Contínua , Estimulação Elétrica Nervosa Transcutânea
5.
Front Neurol ; 12: 615593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613432

RESUMO

Glioblastoma multiforme (GBM), the most common malignant brain tumor, universally carries a poor prognosis. Despite aggressive multimodality treatment, the median survival is ~18-20 months, depending on molecular subgroups. A long history of observations suggests antitumor effects of bacterial infections against malignant tumors. The present review summarizes and critically analyzes the clinical data providing evidence for or against the survival benefit of post-operative bacterial infections in GBM patients. Furthermore, we explore the probable underlying mechanism(s) from basic science studies on the topic. There are plausible explanations from immunobiology for the mechanism of the "favorable effect" of bacterial infections in GBM patients. However, available clinical literature does not provide a definitive association between postoperative bacterial infection and prolonged survival in GBM patients. The presently available, single-/multi-center and national database retrospective case-control studies on the topic provide conflicting results. A prospective randomized study on the subject is clearly not possible. Immunobiology literature supports development of genetically modified bacteria as part of multimodal regimen against GBM.

6.
World Neurosurg ; 148: 141-162, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33482414

RESUMO

OBJECTIVE: The present systematic review and meta-analysis analyzes the available clinical literature on post-intracerebral hemorrhage (ICH) cognitive impairment. METHODS: We conducted a systematic review with meta-analysis following PRISMA guidelines. A search of bibliographic databases up to July 31, 2020 yielded 2155 studies. Twenty articles were included in our final qualitative systematic review and 18 articles in quantitative meta-analysis. RESULTS: Based on analysis of data from 18 studies (3270 patients), we found prevalence of post-ICH cognitive impairment to be 46% (confidence interval, 35.9-55.9), with a follow-up duration ranging from 8 days to 4 years. The estimated pooled prevalence of cognitive decline decreased over longitudinal follow-up, from 55% (range, 37.7%-71.15%) within 6 months of ICH to 35% (range, 27%-42.7%) with >6 months to 4 years follow-up after ICH. The modalities used to evaluate cognitive performance after ICH in studies varied widely, ranging from global cognitive measures to domain-specific testing. The cognitive domain most commonly affected included nonverbal IQ, information processing speed, executive function, memory, language, and visuoconstructive abilities. Prognostic factors for poor cognitive performance included severity of cortical atrophy, age, lobar ICH location, and higher number of hemorrhages at baseline. CONCLUSIONS: The prevalence of post-ICH cognitive impairment is high. Despite the heterogeneity among studies, the present study identified cognitive domains most commonly affected and predictors of cognitive impairment after ICH. In future, prospective cohort studies with larger sample sizes and standardized cognitive domains testing could more accurately determine prevalence and prognostic factors of post-ICH cognitive decline.


Assuntos
Disfunção Cognitiva/etiologia , Hemorragias Intracranianas/complicações , Angiopatia Amiloide Cerebral , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Humanos , Hemorragias Intracranianas/epidemiologia , Hemorragias Intracranianas/psicologia , Testes Neuropsicológicos , Prevalência , Prognóstico
7.
J Insect Sci ; 20(4)2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32770249

RESUMO

Insect predators are seldom considered during toxicological trophic assessments for insecticide product development. As a result, the ecological impact of novel insecticides on predators is not well understood, especially via the food chain, i.e., when their prey is exposed to insecticides. Neonicotinoids are systemic insecticides widely used in agriculture to control herbivorous insects, but their effects on predatory insects via the food chain have not been well characterized. In this study, we documented the time-course effects of the neonicotinoid thiamethoxam on the survival of two predators, the insidiosus flower bug Orius insidiosus (Say) and the convergent lady beetle Hippodamia convergens Guérin-Méneville, when preying upon the aphids Aphis glycines Matsumura (Hemiptera: Aphididae), Aphis gossypii Glover (Hemiptera: Aphididae), and Myzus persicae (Sulzer) (Hemiptera: Aphididae). Aphids were exposed to thiamethoxam-treated or untreated plants every week over the course of 5 wk. After transferring aphids to Petri dishes, predators were allowed to feed on aphids. We found that the survival of the insidiosus flower bug, but not the convergent lady beetle, was reduced after consuming aphids reared on thiamethoxam-treated plants compared to untreated plants. Survival reduction of the insidiosus flower bug was observed only during the first weeks after thiamethoxam application; no reduction occurred 28 d after treatment or beyond. These results demonstrate that a systemic application of thiamethoxam could be compatible with convergent lady beetles and insidiosus flower bugs, if the time of predator release does not coincide with thiamethoxam activity. These findings are critical for the development of future pest control programs that integrate biological and chemical control.


Assuntos
Besouros/efeitos dos fármacos , Heterópteros/efeitos dos fármacos , Inseticidas/efeitos adversos , Tiametoxam/efeitos adversos , Animais , Dieta , Feminino , Cadeia Alimentar , Longevidade/efeitos dos fármacos , Masculino , Comportamento Predatório , Especificidade da Espécie
8.
Water Environ Res ; 92(10): 1433-1439, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32574406

RESUMO

This article is a review of the scientific literature published in 2019 on topics relating to bioenergy from biofuel residues and waste. This literature review is divided into the following sections: Feedstocks, Biodiesel, Bioethanol, Hydrogen, Biohydrogen, Biofuel Residues, Microalgae, and Lignocelluloses.


Assuntos
Biocombustíveis , Microalgas
9.
Water Environ Res ; 92(10): 1418-1424, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32574412

RESUMO

This section presents a review of the scientific literature published in 2019 on topics relating to distributed treatment systems. This review is divided into the following sections: constituent removal, treatment technologies, planning and treatment management, and other topics. PRACTITIONER POINTS: Highlights changes and innovation in removal techniques and technologies in water treatment. Reviews management systems of distributed treatment systems. Discusses point-of-use treatment systems.


Assuntos
Eliminação de Resíduos Líquidos , Purificação da Água
10.
San Salvador; s.n; 2020. 41 p. Tab, Ilus, Graf.
Tese em Espanhol | LILACS, BISSAL | ID: biblio-1178966

RESUMO

Determinar el perfil epidemiológico de los donadores de dientes humanos extraídos en Unidades Comunitarias de Salud Familiar de Guaymango y Barra de Santiago en Ahuachapán, San Pedro Perulapán en Cuscatlán y Salcoatitán en Sonsonate, durante el año 2019. Metodología: Investigación observacional, descriptiva y transversal en 200 pacientes donadores entre las edades de 7 a más de 60 años a quienes se les entrevistó y efectuó un examen clínico para determinar los indicadores sociodemográficos, historia médica y clínico bucal del donador y las características físicas del diente extraído. Para el vaciado, análisis e interpretación de los datos se utilizó el programa SPSS versión 25. Resultados: Del total de los pacientes donadores un 62.5% fueron de sexo femenino, el 25% entre 21 y 30 años; 84.5% reside en el área rural; 13% padece de hipertensión arterial; 21.5% presentó bruxismo, 91% caries dental y 68.5% gingivitis/enfermedad periodontal. La principal causa de extracción fue caries dental con un 61% y la pieza más extraída fue la 4-6 de éstas el 63% presentaban caries extensa y un 99% raíz completa. Conclusión: Los donadores de dientes extraídos fueron en su mayoría del sexo femenino entre 21 y 30 años de edad, del sector rural. La condición bucal prevalente fue la higiene bucal regular, caries dental y gingivitis/enfermedad periodontal. La hipertensión fue la enfermedad más encontrada en los donadores y la causa principal de extracción fue la caries dental y sus secuelas siendo la pieza 4-6 la más extraída.


To determine the epidemiological profile of the donors of human teeth extracted in Community Family Health Units of Guaymango and Barra de Santiago in Ahuachapán, San Pedro Perulapán in Cuscatlán and Salcoatitán in Sonsonate, during 2019. Methodology: Observational, descriptive and cross-sectional investigation was carried out in 200 donor patients between the ages of 7 to more than 60 years who were interviewed and performed a former clinician to determine the donor´s sociodemographic indicators, medical history and oral history and the physical characteristics of the extracted tooth. The IBM SPSS version 25 program was used TO EMPTY, analyze and interpret the data. Results: Of the total of the donor patients, 62.5% were female, 25% were between 21 and 30 years old; 84.5% reside in the rural area; 13% have high blood pressure; 21.5% presented bruxism, 91% dental caries and 68.5% gingivitis / periodontal disease. The main cause of extraction was dental caries with 61% and the most extracted piece was 4-6, the 63% of these had extensive tooth decay and a 99% had his roots complete. Conclusion: The donors of extracted teeth were mostly female between 21 and 30 years old, from the rural sector. Regular oral hygiene, dental caries, and gingivitis / periodontal disease prevailed in the oral condition. Hypertension was the most found disease in donors and the main cause of extraction was dental caries, with piece 4-6 being the most extracted.


Assuntos
Perfil de Saúde , Dente , Extração Dentária , Epidemiologia
11.
Water Environ Res ; 91(10): 1205-1209, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31517427

RESUMO

This section presents a review of the scientific literature published in 2018 on topics relating to distributed treatment systems. This review is divided into the following sections: constituent removal, treatment technologies, planning and treatment management, and other topics.


Assuntos
Reatores Biológicos , Eliminação de Resíduos Líquidos
12.
Int J Nanomedicine ; 14: 5271-5285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409989

RESUMO

Electrospun nanofibers have been widely studied for many medical applications. They can be designed with specific features, including mucoadhesive properties. This review summarizes the polymeric scaffolds obtained by the electrospinning process that has been applied for drug release in different mucosal sites such as oral, ocular, gastroenteric, vaginal, and nasal. We analyzed the electrospinning parameters that have to be optimized to create reproducible and efficient mucoadhesive nanofibers, among them are: electrical field, polymer concentration, viscosity, flow rate, needle-collector distance, solution conductivity, solvent, environmental parameters, and electrospinning setup. We also revised the mucoadhesive theories as well as the mucoadhesive properties of the polymers used. This review shows that the most studied mucosal site is the oral cavity, because it is accessible and easy to evaluate, while the rest are uncomfortable for the patient and difficult to assess in vivo. We found problems that need to be solved for mucoadhesive electrospun nanofibers, such as improving adhesion strength and mucosal permanence time, and the design of unidirectional release, multilayer systems for the treatment of several pathologies, to ensure the drug concentration in the tissue or target organ.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Muco/química , Nanofibras/química , Polímeros/química , Adesividade , Condutividade Elétrica , Humanos
13.
Water Environ Res ; 91(10): 1199-1204, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433529

RESUMO

This section presents a review of the scientific literature published in 2018 on topics relating to sustainable bioenergy from biofuel residues and waste. This review is divided into the following sections: Feedstocks, Bioethanol, Biodiesel, Biohydrogen, Hydrogen, Biofuel Residues, Microalgae, and Lignocelluloses.


Assuntos
Biocombustíveis , Microalgas , Hidrogênio
14.
J Pharm Pharm Sci ; 22(1): 313-331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31329535

RESUMO

The electrospinning technique is a useful and versatile approach for conversion of polymeric solutions into continuous fibers, ranging from a few micrometers (10-100 µm) to the scale of nanometers (10- 100 nm) in diameters. This technique can be used in a vast number of polymers, in some cases after modifying them to the required properties. The high surface-to-volume ratio of the fibers can improve some processes like cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents, to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into electrospun polymeric nanofibers to be used as drug delivery systems. These drugs are classified by their applications in pharmacy.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Nanofibras/química , Polímeros/química , Portadores de Fármacos/química , Eletricidade , Humanos , Tamanho da Partícula , Propriedades de Superfície
15.
Artigo em Inglês | MEDLINE | ID: mdl-30873405

RESUMO

Microalgae offer a promising biological platform for sustainable biomanufacturing of a wide range of chemicals, pharmaceuticals, and fuels. The model microalga Chlamydomonas reinhardtii is thus far the most versatile algal chassis for bioengineering and can grow using atmospheric CO2 and organic carbons (e.g., acetate and pure cellulose). Ability to utilize renewable feedstock like lignocellulosic biomass as a carbon source could significantly accelerate microalgae-based productions, but this is yet to be demonstrated. We observed that C. reinhardtii was not able to heterotrophically grow using wheat straw, a common type of lignocellulosic biomass, likely due to the recalcitrant nature of the biomass. When the biomass was pretreated with alkaline, C. reinhardtii was able to grow using acetate that was released from the biomass. To establish an eco-friendly and self-sustained growth system, we engineered C. reinhardtii to secrete a fungal acetylxylan esterase (AXE) for hydrolysis of acetylesters in the lignocellulosic biomass. Two transgenic strains (CrAXE03 and CrAXE23) secreting an active AXE into culture media were isolated. Incubation of CrAXE03 with wheat straw resulted in an eight-fold increase in the algal cell counts with a concomitant decrease of biomass acetylester contents by 96%. The transgenic lines showed minor growth defects compared to the parental strain, indicating that secretion of the AXE protein imposes limited metabolic burden. The results presented here would open new opportunities for applying low-cost renewable feedstock, available in large amounts as agricultural and manufacturing by-products, for microalgal cultivation. Furthermore, acetylesters and acetate released from them, are well-known inhibitors in lignocellulosic biofuel productions; thus, direct application of the bioengineered microalga could be exploited for improving renewable biofuel productions.

16.
J Econ Entomol ; 112(2): 712-719, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30715412

RESUMO

Thiamethoxam, an insecticide used in soybean seed treatments, effectively suppresses soybean aphids (Aphis glycines) Matsumura (Hemiptera: Aphididae) for a short time after planting. However, exactly when and how quickly soybean aphid populations could increase is unknown. Likewise, we lack data on virulent soybean aphid biotypes (that can overcome soybean resistance) when fed on seed-treated soybean. Determining the survival of soybean aphids over time on insecticidal seed-treated soybean is critical for improving soybean aphid management and may provide insights to manage aphid virulence to aphid resistant-soybean. In greenhouse and field experiments, aphid-susceptible soybean plants (with and without an insecticidal seed treatment) were infested at 7, 14, 21, 28, 35, and 42 days after planting (DAP). We compared aphid survival among biotypes 1 (avirulent) and 4 (virulent) and insecticide treatment 72 h after infestation. We also measured thiamethoxam concentrations in plant tissue using liquid chromatography-tandem mass spectrometry. As expected, soybean aphid survival was significantly lower on seed-treated soybean up to 35 DAP for both biotypes, which correlates with the decrease of thiamethoxam in the plant over time. Moreover, we found no significant difference between avirulent and virulent biotype survivorship on insecticidal seed-treated soybean plants, although we did find significantly greater survival for the virulent biotype compared with the avirulent biotype on untreated soybean in the field. In conclusion, our study further characterized the relative short duration of seed treatment effectiveness on soybean aphid and showed that survivorship of virulent aphids on seed-treated soybean is similar to avirulent aphids.


Assuntos
Afídeos , Inseticidas , Animais , Sementes , Sobrevivência
17.
Hum Mol Genet ; 28(4): 525-538, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30304524

RESUMO

Aminoacyl-tRNA synthetases (ARSs) are critical for protein translation. Pathogenic variants of ARSs have been previously associated with peripheral neuropathy and multisystem disease in heterozygotes and homozygotes, respectively. We report seven related children homozygous for a novel mutation in tyrosyl-tRNA synthetase (YARS, c.499C > A, p.Pro167Thr) identified by whole exome sequencing. This variant lies within a highly conserved interface required for protein homodimerization, an essential step in YARS catalytic function. Affected children expressed a more severe phenotype than previously reported, including poor growth, developmental delay, brain dysmyelination, sensorineural hearing loss, nystagmus, progressive cholestatic liver disease, pancreatic insufficiency, hypoglycemia, anemia, intermittent proteinuria, recurrent bloodstream infections and chronic pulmonary disease. Related adults heterozygous for YARS p.Pro167Thr showed no evidence of peripheral neuropathy on electromyography, in contrast to previous reports for other YARS variants. Analysis of YARS p.Pro167Thr in yeast complementation assays revealed a loss-of-function, hypomorphic allele that significantly impaired growth. Recombinant YARS p.Pro167Thr demonstrated normal subcellular localization, but greatly diminished ability to homodimerize in human embryonic kidney cells. This work adds to a rapidly growing body of research emphasizing the importance of ARSs in multisystem disease and significantly expands the allelic and clinical heterogeneity of YARS-associated human disease. A deeper understanding of the role of YARS in human disease may inspire innovative therapies and improve care of affected patients.


Assuntos
Doenças Genéticas Inatas/genética , Predisposição Genética para Doença , Mutação com Perda de Função/genética , Tirosina-tRNA Ligase/genética , Adulto , Domínio Catalítico/genética , Pré-Escolar , Feminino , Doenças Genéticas Inatas/fisiopatologia , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/fisiopatologia , Heterozigoto , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Linhagem , Fenótipo , Índice de Gravidade de Doença , Sequenciamento do Exoma , Leveduras/genética
18.
Water Environ Res ; 90(10): 1073-1090, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30126479

RESUMO

This section presents a review of the scientific literature published in 2017 on topics relating to sustainable bioenergy from biofuel residues and waste. This review is divided into the following sections: Feedstocks, Bioethanol, Biodiesel, Biohydrogen, Hydrogen, Biofuel Residues, Microalgae, Lignocelluloses and other topics.


Assuntos
Biocombustíveis , Desenvolvimento Sustentável , Resíduos , Biomassa
19.
Curr Drug Deliv ; 15(10): 1360-1374, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30033869

RESUMO

Recently, electrospun polymeric nanofibers have proven to be an interesting strategy for drug delivery systems application. The high surface-to-volume ratio of the fibers can improve some processes, such as cell binding and proliferation, drug loading, and mass transfer processes. One of the most important and studied areas of electrospinning is in the drug delivery field, for the controlled release of active substances ranging from antibiotics and anticancer agents to macromolecules such as proteins and DNA. The advantage of this method is that a wide variety of low solubility drugs can be loaded into the fibers to improve their bioavailability or to attain controlled release. This review presents an overview of the reported drugs loaded into polymeric nanofibers, to be used as drug delivery systems. For instance, it presents the reports on drugs with different bioactivities such as antiinflammatory, anti-microbial, anticancer, cardiovascular, anti-histamine, gastrointestinal, palliative and contraceptive drugs, etc. It also analyzes the electrospinning techniques used in each system, as well as the polymers used as matrices for the preparation of the nanofibers; unfolding the advantages of electrospun polymeric nanofibers over other drug delivery systems. This review intends to enlist and summarize the reported literature concerning this topic. In addition, it proposes future research in the field.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Biopolímeros/química , Sistemas de Liberação de Medicamentos , Nanofibras/química , Animais , Humanos
20.
Plant Biotechnol J ; 15(9): 1214-1224, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28207991

RESUMO

Microalga-based biomanufacturing of recombinant proteins is attracting growing attention due to its advantages in safety, metabolic diversity, scalability and sustainability. Secretion of recombinant proteins can accelerate the use of microalgal platforms by allowing post-translational modifications and easy recovery of products from the culture media. However, currently, the yields of secreted recombinant proteins are low, which hampers the commercial application of this strategy. This study aimed at expanding the genetic tools for enhancing secretion of recombinant proteins in Chlamydomonas reinhardtii, a widely used green microalga as a model organism and a potential industrial biotechnology platform. We demonstrated that the putative signal sequence from C. reinhardtii gametolysin can assist the secretion of the yellow fluorescent protein Venus into the culture media. To increase the secretion yields, Venus was C-terminally fused with synthetic glycomodules comprised of tandem serine (Ser) and proline (Pro) repeats of 10 and 20 units [hereafter (SP)n , wherein n = 10 or 20]. The yields of the (SP)n -fused Venus were higher than Venus without the glycomodule by up to 12-fold, with the maximum yield of 15 mg/L. Moreover, the presence of the glycomodules conferred an enhanced proteolytic protein stability. The Venus-(SP)n proteins were shown to be glycosylated, and a treatment of the cells with brefeldin A led to a suggestion that glycosylation of the (SP)n glycomodules starts in the endoplasmic reticulum (ER). Taken together, the results demonstrate the utility of the gametolysin signal sequence and (SP)n glycomodule to promote a more efficient biomanufacturing of microalgae-based recombinant proteins.


Assuntos
Chlamydomonas reinhardtii/metabolismo , Metaloproteases/metabolismo , Processamento de Proteína Pós-Traducional , Sinais Direcionadores de Proteínas/genética , Proteínas Recombinantes de Fusão/metabolismo , Biotecnologia , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/crescimento & desenvolvimento , Meios de Cultura , Genes Reporter , Glicoproteínas/genética , Glicoproteínas/metabolismo , Glicosilação , Metaloproteases/genética , Plantas Geneticamente Modificadas , Transporte Proteico , Proteínas Recombinantes de Fusão/genética
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