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1.
Int J Stroke ; : 1747493019879662, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581930

RESUMO

AIM: In this narrative review we aimed to describe how stroke affects emotions and update the readers on the emotional disturbances that occur after stroke. METHODS: We searched Medline from 1.1.2013 to 1.7.2019, personal files and references of selected publications. All retrieved systematic reviews and randomized controlled trials were included. Other references were selected by relevance. SUMMARY OF REVIEW: The emotional response includes a reactive behavior with arousal, somatic, motivational and motor components, and a distinctive cognitive and subjective affective experience. Emotional category responses and experiences after stroke can show dissociations between the behavioral response and the cognitive and affective experiences. Emotional disturbances that often occur after stroke include fear, anger, emotional indifference, lack of understanding of other emotions, and lack of control of emotional expression. Emotional disturbances limit social reintegration of the persons with stroke and are a source of caregiver burnout. The evidence to support the management of the majority of emotional disorders in stroke survivors is currently weak and of low or very low methodologic quality. An exception are the disorders of emotional expression control where antidepressants can have a strong beneficial effect, by reducing the number and duration of the uncontrollable episodes of crying or laughing. CONCLUSION: Our current knowledge of the emotional disorders that occurs in acute stroke patients and in stroke survivors is heterogeneous and limited. Joint efforts of different research approaches, methodologies and disciplines will improve our current understanding on emotional disorder after stroke and indicate rational pathways to manage them.

2.
J Adolesc Health ; 65(4): 558-563, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377165

RESUMO

PURPOSE: Early timing of pubertal development is associated with worse cardiometabolic health in adulthood. We aimed to evaluate this association in 10-year-old girls and boys and clarify if it is independent of previous body mass index (BMI). METHODS: Pubertal development was evaluated through the Tanner scale in 4,548 children from the birth cohort Generation XXI. Data on anthropometrics, body composition, blood pressure, lipid profile, fasting plasma glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein were collected. Bonferroni correction was applied, using an alpha of .004 for statistical significance. Regression coefficients and 99.6% confidence intervals were computed using linear regression models. RESULTS: Girls with a Tanner stage ≥2 presented statistically significant higher values of BMI, waist circumference (WC), waist-to-height ratio, fat mass index, blood pressure, glucose, insulin, HOMA-IR, triglycerides, and high-sensitivity C-reactive protein and lower values of high-density lipoprotein cholesterol. Boys with a Tanner stage ≥2 presented statistically significant higher values of BMI, WC, systolic blood pressure, and HOMA-IR and lower values of high-density lipoprotein cholesterol. After adjustment, including previous BMI, a Tanner stage ≥2 remained associated with BMI z-score (girls ß = .41 [.32, .50]; boys ß = .10 [.01, .19]) and WC (girls ß = 2.64 cm [1.86, 3.43]; boys ß = .81 cm [.11, 1.51]), and only in girls with waist-to-height ratio (ß = .01 [.00, .01]), fat mass index (ß = .31 kg/m2 [.08; .54]), glucose (ß = 1.59 mg/dL [.85, 2.33]), insulin (ß = 1.73 µU/mL [.68, 2.78]), and HOMA-IR (ß = .40 [.16, .64]). CONCLUSIONS: Independently of previous BMI, preteens with early puberty already had more adiposity at age 10 years. In addition, girls had higher glucose, insulin, and HOMA-IR, which may predict a worse glucose metabolism. These preteens should be a target for public health interventions.

3.
JAMA ; 321(17): 1702-1715, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063572

RESUMO

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação , Complicações na Gravidez , Resultado da Gravidez , Adulto , Peso ao Nascer , Cesárea/estatística & dados numéricos , Diabetes Gestacional , Feminino , Humanos , Hipertensão Induzida pela Gravidez , Recém-Nascido , Obesidade , Gravidez , Nascimento Prematuro
4.
Neurosci Biobehav Rev ; 103: 163-177, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31100297

RESUMO

The objective of this meta-analytic review was to systematically assess the effects of working memory training on healthy older adults. We identified 552 entries, of which 27 experiments met our inclusion criteria. The final database included 1130 participants. Near- and far-transfer effects were analysed with measures of short-term memory, working memory, and reasoning. Small significant and long-lasting transfer gains were observed in working memory tasks. Effects on reasoning was very small and only marginally significant. The effects of working memory training on both near and far transfer in older adults were moderated by the type of training tasks; the adopted outcome measures; the training duration; and the total number of training hours. In this review, we provide an updated review of the literature in the field by carrying out a robust multi-level meta-analysis focused exclusively on working memory training in healthy older adults. Recommendations for future research are suggested.

5.
Braz J Psychiatry ; 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31116258

RESUMO

OBJECTIVE: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. METHODS: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. RESULTS: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10-5) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. CONCLUSION: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.

6.
J Oral Sci ; 61(1): 171-177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918214

RESUMO

This study evaluated the biocompatibility of a new silicone-based sealer (GuttaFlow Bioseal) in rat subcutaneous tissue and compared the results with those for GuttaFlow2 and AH Plus. Each of 16 Wistar rats received four subcutaneous tissue implants, namely, GuttaFlow Bioseal, GuttaFlow2, AH Plus, and one empty polyethylene tube. Eight rats were euthanized at day 8 and the remaining eight at day 30. Histological sections were stained with haematoxylin and eosin and analysed with a light microscope. Scores were established for inflammatory reaction, macrophage infiltrate, thickness of the fibrous capsule, and vascular changes. Differences between groups were assessed by using the Friedman test with Bonferroni correction. Histological analysis showed that GuttaFlow Bioseal had the lowest inflammatory reaction of all tested sealers at day 8. At day 30, the silicone-based sealers had similar inflammation profiles, but inflammation scores were nonsignificantly higher for AH Plus than for the negative control. The inflammatory reaction decreased from day 8 to day 30 in all sealers. GuttaFlow Bioseal had the most macrophage infiltrate. Under the present experimental conditions, GuttaFlow Bioseal induced limited inflammatory reactions at days 8 and 30, and initial inflammatory reactions to GuttaFlow2 and AH Plus subsided within 30 days. All tested sealers exhibited satisfactory biocompatibility at day 30 after subcutaneous implantation.


Assuntos
Materiais Biocompatíveis , Cerâmica , Cimentos de Resina , Silicones/química , Tela Subcutânea/metabolismo , Animais , Dimetilpolisiloxanos , Combinação de Medicamentos , Guta-Percha , Ratos , Ratos Wistar , Materiais Restauradores do Canal Radicular
7.
Expert Opin Drug Deliv ; 16(2): 143-151, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30632401

RESUMO

INTRODUCTION: Biotherapeutics are primarily delivered subcutaneously due to better compliance and prolonged rate of absorption compared to other parenteral administration routes. Recent research has allowed for the development of biotherapeutic formulations for subcutaneous delivery that require a lower frequency of administration by increasing drug half-life. Formulations determine shelf-life stability as well as features and transient behaviors that influence stability once implanted in the subcutaneous space. AREAS COVERED: This review provides an overview of the factors affecting subcutaneous absorption with a focus on transient effects at the injection site following administration of biotherapeutics and the subsequent impact on absorption and stability. EXPERT OPINION: Advances have been made in understanding subcutaneous tissue and the complex interplay of factors that regulate its homeostasis. The issue of poor stability after injection has been neglected, and many biotherapeutics are hampered by low bioavailability. With the advent of new in vitro techniques that account for properties of the injection site, stability studies evaluating subcutaneous tissues and impacts on pharmacokinetics of biotherapeutics may be useful in the development of new formulations.


Assuntos
Produtos Biológicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Disponibilidade Biológica , Humanos , Injeções Subcutâneas , Tela Subcutânea
8.
Artigo em Inglês | MEDLINE | ID: mdl-30411595

RESUMO

BACKGROUND: High prevalence of vitamin D deficiency is well known around the world in risk populations. Although less is known about the athletic population, some studies report vitamin D deficiency amongst athletic population and adequate vitamin D levels are crucial for athletic population as it can prevent injuries such as stress fractures and might even have ergogenic effects for example on muscle function. The main objectives were to evaluate the basal serum levels of 25(OH)D and calcium in professional soccer athletes on the latitude 40 ̊N, to evaluate the effects in 25(OH)D and calcium serum levels following supplementation of 1667 IU/day of cholecalciferol during a period of 8 weeks and evaluate eventual toxicity arising from it. METHODS: 28 professional athletes were evaluated according to the skin type. Basal serum levels of 25(OH)D and calcium were evaluated during winter months. Athletes were then supplemented with cholecalciferol 25.000 IU every two weeks. Serum levels of 25(OH)D and calcium were evaluated after supplementation. RESULTS: 25(OH)D initially ranged between 9.9 ng/mL and 32.9 ng/mL with a median of 19.2 IQR 7.24 ng/mL. A statistically significant inverse correlation exists between vitamin D deficiency and the Fitzpatrick scale (ρ= - 0,555 p=0.003). After 8 weeks, 25(OH)D ranged between 10.6 ng/mL and 43.4 ng/mL with a median of 33.2 ng/mL IQR 6.1 ng/mL. We verified a statistically significant increase of serum 25(OH) D levels (11.74 ± 5.988; IC95% [9,02; 14,47]; p<0,001. In addition, there was a statistically significant reduction of calcium: -0,36 ± 0,457; IC95% [- 0,57; -0,15]; p=0,002. CONCLUSIONS: Professional athletes have a high prevalence of vitamin D. Supplementation with cholecalciferol in winter months during 8 weeks is safe and effective in raising 25(OH)D serum levels. However, it may not be sufficient for athletes to reach adequate vitamin D levels.

9.
Cancers (Basel) ; 10(9)2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30150555

RESUMO

The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs (n = 96) were cross-matched for age, gender, and district of residence with a control group (n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components' waist circumference, fasting triglycerides, and fasting plasma glucose (p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease.

10.
Colloids Surf B Biointerfaces ; 171: 566-578, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098535

RESUMO

The medicinal properties of essential oils from aromatic plants are known since antiquity. Currently, the technological innovation enabled the reinvention of the ancient plant knowledge leading to the identification and extraction of organic compounds present in essential oils. These organic compounds belong mainly to the terpene group and are accountable for the wide range of bioactive properties attributed to essential oils. Linalool (C10H18O), so-called 3,7-dimethyl-1,6-octadien-3-ol, is a monoterpene alcohol broadly present as a major constituent of plant essential oils, particularly lavender and coriander. Linalool per se is non-toxic and, according to recent in vitro and in vivo scientific studies, it has demonstrated to have a comprehensive range of bioactive properties, which can be exploited for pharmaceutic and cosmetic applications. The present review focuses on the anti-inflammatory, anticancer, anti-hyperlipidemic, antimicrobial, antinoceptive, analgesic, anxiolytic, antidepressive and neuroprotective properties of linalool. The advantages of the loading in nanotechnology-based drug delivery systems, with the purpose of enhancing its bioactive properties are also discussed.

11.
J Control Release ; 286: 301-314, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30077735

RESUMO

The convenience of subcutaneous (SC) administration and the increasing interest in monoclonal antibody (mAb)-based therapies for chronic diseases, hint their potential for SC delivery in a near future. In addition, there is a common interest among patients, clinicians and pharmaceutical industry in moving from intravenous to SC administration of mAbs due to benefits of improved patient compliance and reduced costs to the healthcare system. Despite the wide use of this route of administration in diseases like diabetes and rheumatoid arthritis, SC bioavailability of mAbs has been shown to be incomplete and variable in most preclinical and clinical studies. This evidences a gap in the understanding of SC absorption process of mAbs and in their drug development process. Likewise, challenges present in drug formulation, such as high viscosity and aggregation, and the inherent immunogenicity of mAbs have also been hampering the successful translation to clinical settings. This review provides a characterization of the subcutaneously delivered mAbs that have entered the market in the last 10 years as well as a snapshot of the landscape of currently undergoing clinical trials. Moreover, there is an overview of the factors influencing SC absorption of mAbs and the preclinical models in use to study SC pharmacokinetics. Considerations about drug formulation and immunogenicity of mAbs are also explored.

12.
Adv Colloid Interface Sci ; 257: 58-70, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29887382

RESUMO

Natural forming clay halloysite is an emerging nanomaterial carrier for sustained drug delivery. These 50 nm diameter aluminosilicate tubes, with inner - alumina and outer - silica surface layers, can be loaded with 10-30 wt% of drug molecules, DNA and enzymes. The opposite charge of the inner and outer halloysite surface allow for selective drug adsorption inside or outside the clay nanotubes. The drug loaded halloysite enhanced the zeta potential of minus 50-60 mV allowing for stable aqueous nanocolloids. Halloysite nanoformulations provide an extended 10-20 h release profile, and may be functionalized (e.g., clogging tubes' end with polymers extending release time to 1-2 weeks or allowing for triggered release), which renders these clay nanostructures as promising controlled delivery systems. Recent studies demonstrate the potential of abundantly available halloysite clay nanotubes for life science applications, from drug delivery via oral or topical administration, to tissue scaffolds and regenerative medicine, while assessing their cellular internalization, stability, biosafety and biocompatibility are featured. The benefits and limitations of halloysite clay nanotubes are discussed, as well as the directions for future developments.


Assuntos
Silicatos de Alumínio/química , Materiais Biocompatíveis/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Nanotubos/química , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Tecidos Suporte/química , Animais , Disciplinas das Ciências Biológicas/métodos , Argila , Liberação Controlada de Fármacos , Humanos , Tamanho da Partícula
13.
Skin Pharmacol Physiol ; 31(2): 59-73, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29262420

RESUMO

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options.


Assuntos
Dermatopatias/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Diferenciação Celular/fisiologia , Progressão da Doença , Humanos , Fatores de Risco
14.
Nicotine Tob Res ; 20(6): 674-680, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-28575495

RESUMO

Introduction: Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children. Methods: We evaluated 4295 of Generation XXI children, recruited at birth in 2005-2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children's BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children's BP. Results: Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child's body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (ß = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (ß = 0.08, 95% CI 0.03 to 0.13 before conception; ß = 0.07, 95%CI 0.02 to 0.12; ß = 0.04, 95%CI -0.02 to 0.10; and ß = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and ß = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels. Conclusion: Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged. Implications: Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking-before pregnancy, during pregnancy, and 4 years after delivery-was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.

15.
FEBS J ; 284(19): 3278-3301, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28783254

RESUMO

Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups upon oxidation. This produces metabolically active heme that is exchangeable between acceptor proteins, macromolecules and low molecular weight ligands, termed here labile heme. As it accumulates in plasma labile heme acts in a pro-oxidant manner and regulates cellular metabolism while exerting pro-inflammatory and cytotoxic effects that foster the pathogenesis of hemolytic diseases. Here, we developed and characterized a panel of heme-specific single domain antibodies (sdAbs) that together with a cellular-based heme reporter assay, allow for quantification and characterization of labile heme in plasma during hemolytic conditions. Using these approaches, we demonstrate that when generated during hemolytic conditions labile heme is bound to plasma molecules with an affinity higher than 10-7 m and that 2-8% (~ 2-5 µm) of the total amount of heme detected in plasma can be internalized by bystander cells, termed here bioavailable heme. Acute, but not chronic, hemolysis is associated with transient reduction of plasma heme-binding capacity, that is, the ability of plasma molecules to bind labile heme with an affinity higher than 10-7 m. The heme-specific sdAbs neutralize the pro-oxidant activity of soluble heme in vitro, suggesting that these maybe used to counter the pathologic effects of labile heme during hemolytic conditions. Finally, we show that heme-specific sdAbs can be used to visualize cellular heme. In conclusion, we describe a panel of heme-specific sdAbs that when used with other approaches provide novel insights to the pathophysiology of heme.


Assuntos
Anticorpos Monoclonais/química , Eritrócitos/química , Heme/análise , Biblioteca de Peptídeos , Anticorpos de Domínio Único/química , Sequência de Aminoácidos , Anemia Falciforme/sangue , Animais , Anticorpos Monoclonais/biossíntese , Afinidade de Anticorpos , Especificidade de Anticorpos , Biotina/química , Clonagem Molecular , Ensaio de Imunoadsorção Enzimática , Eritrócitos/parasitologia , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/virologia , Expressão Gênica , Heme/química , Heme/imunologia , Heme/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Hemólise , Humanos , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Plasmodium falciparum/crescimento & desenvolvimento , Ligação Proteica , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Anticorpos de Domínio Único/biossíntese , Tetrapirróis/química , Tetrapirróis/metabolismo
16.
Mol Syndromol ; 7(6): 344-348, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27920638

RESUMO

We report on a Brazilian patient with a 1.7-Mb interstitial microdeletion in chromosome 1q21.1. The phenotypic characteristics include microcephaly, a peculiar facial gestalt, cleft lip/palate, and multiple skeletal anomalies represented by malformed phalanges, scoliosis, abnormal modeling of vertebral bodies, hip dislocation, abnormal acetabula, feet anomalies, and delayed neuropsychological development. Deletions reported in this region are clinically heterogeneous, ranging from subtle phenotypic manifestations to severe congenital heart defects and/or neurodevelopmental findings. A few genes within the deleted region are associated with congenital anomalies, mainly the RBM8A, DUF1220, and HYDIN2 paralogs. Our patient presents with a spectrum of unusual malformations of 1q21.1 deletion syndrome not reported up to date.

17.
Alcohol Clin Exp Res ; 39(8): 1453-64, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26110492

RESUMO

BACKGROUND: Ethanol (EtOH) consumption is able to disturb the ovalbumin (OVA)-oral tolerance induction by interfering on the function of antigen presenting cells (APC), down-regulating dendritic cells (DCs) and macrophages and up-regulating B-lymphocytes and their function, which results in an overall allergic-type immune status. In this study, the potential of a priori administration of Lactococcus lactis (LL) in avoiding loss of oral tolerance in EtOH-treated mice was investigated. METHODS: Female C57BL/6 mice received, by oral route, ad libitum wild-type (WT) LL or heat-shock protein producer (Hsp65) LL for 4 consecutive days. Seven days later, mice were submitted to short-term high-dose EtOH treatment. After 24 hours, stomach, intestine, spleen, mesenteric lymph nodes (mLN) specimens were collected for biomarkers analysis. Following EtOH-treatment protocol, a group of animals underwent single-gavage OVA-tolerance protocol and sera samples collected for antibody analysis. RESULTS: The ingestion of WT LL or Hsp65 LL is able to restore oral tolerance to OVA in EtOH-treated mice, by reducing local and systemic allergic outcomes such as gastric mast cells and gut-interleukin-4, as well as serum IgE. WT LL treatment prevents the decrease of mLN regulatory T cells induced by the EtOH treatment. Moreover, LL treatment preserves APC hierarchy and antigen presentation commitment in EtOH-treated mice, with conserved DC and macrophage activity over B lymphocytes in mLN and preserved macrophage activity over DC and B-cell subsets in the spleen. CONCLUSIONS: The present findings suggest that a priori ingestion of LL preserves essential mechanisms associated with oral tolerance induction that are disturbed by EtOH ingestion. Maintenance of mucosal homeostasis by preserving APC hierarchy and antigen presentation commitment could be associated with T-regulatory subset activities in the gastrointestinal tract.


Assuntos
Apresentação do Antígeno/imunologia , Etanol/administração & dosagem , Trato Gastrointestinal/imunologia , Tolerância Imunológica/imunologia , Lactococcus lactis , Administração Oral , Animais , Apresentação do Antígeno/efeitos dos fármacos , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Tolerância Imunológica/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
18.
ACS Appl Mater Interfaces ; 7(22): 11972-83, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-25985366

RESUMO

Sonication-assisted layer-by-layer (LbL) self-assembly is a nanoencapsulation technique based on the alternate adsorption of oppositely charged polyelectrolytes, enabling the encapsulation of low solubility drugs. In this work, a top-down LbL technique was performed using a washless approach and ibuprofen (IBF) as a model class II drug. For each saturated layer deposition, polyelectrolyte concentration was determined by titration curves. The first layer was constituted by cationic poly(allylamine hydrochloride) (PAH), given the IBF negative surface charge, followed by anionic polystyrenesulfonate (PSS). This polyelectrolyte sequence was made up with 2.5, 5.5, and 7.5 bilayer nanoshells. IBF nanoparticles (NPs) coated with 7.5 bilayers of PAH/PSS showed 127.5 ± 38.0 nm of particle size, a PDI of 0.24, and a high zeta potential (+32.7 ± 0.6 mV), allowing for a stable aqueous nanocolloid of the drug. IBF entrapment efficiency of 72.1 ± 5.8% was determined by HPLC quantification. In vitro MTT assay showed that LbL NPs were biocompatible. According to the number of coating layers, a controlled release of IBF from LbL NPs was achieved under simulated intestinal conditions (from 5 h up to 7 days). PAH/PSS-LbL NPs constitute a potential delivery system to improve biopharmaceutical parameters of water low solubility drugs.


Assuntos
Composição de Medicamentos , Ibuprofeno/química , Nanopartículas/química , Poliestirenos/química , Adsorção/efeitos dos fármacos , Alilamina/química , Eletrólitos/química , Eletrólitos/farmacologia , Humanos , Tamanho da Partícula , Poliestirenos/farmacologia , Solubilidade/efeitos dos fármacos , Sonicação
19.
Mov Disord Clin Pract ; 2(3): 260-266, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30363545

RESUMO

Background: Although aspiration is one of the main causes of death in SCA, such as SCA3/Machado Joseph disease (SCA3/MJD), clinical studies on dysphagia are lacking for these diseases. The aims of this study were to characterize dysphagia in SCA3/MJD through videofluoroscopy (VF) of swallowing, correlate VF with disease severity criteria and weight loss, and determine the clinical criteria cutoffs for performing VF in the clinical routine, in order to detect aspiration. Methods: A cross-sectional study on 34 SCA3/MJD patients was performed. Clinical and molecular data, as well as body mass index (BMI), were obtained. Neurological scales, such as the Scale for the Assessment and Rating of Ataxia (SARA), and the Swallowing Quality of Life (SWAL-QOL) questionnaire were applied. The VF scores, Dysphagia Outcome and Severity Scale (DOSS) and penetration/aspiration scale (PAS), were obtained: Moderate-to-severe scores were grouped as "significant dysphagia." Results: Overall, 31 of 34 individuals showed abnormal scores at VF. SARA, BMI, and the domain "eating duration" of SWAL-QOL correlated with VF: Their relation to significant dysphagia (DOSS <4 points or PAS >3) was evaluated through receiver operating characteristic curves. A sensitivity of 100% was equivalent to a cutoff of 15 points on SARA score, 23.72 kg/m2 on BMI, and 60% on eating duration-SWAL-QOL (P < 0.05). Conclusion: Significant dysphagia was not related to age at onset, disease duration, or CAG repeat expansion, but with SARA scores, lower BMI, and the domain eating duration of SWAL-QOL. As a guideline for preventing aspiration, we suggest that SARA scores greater than 15 or eating duration-SWAL-QOL lower than 60% should urge VF studies in SCA3/MJD.

20.
Cancer Nurs ; 38(4): 322-9, 2015 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25232958

RESUMO

BACKGROUND: Oral mucositis is a common inflammatory complication among patients undergoing hematopoietic stem cell transplantation (HSCT). Among its therapeutic properties, Chamomilla recutita has anti-inflammatory effects. OBJECTIVE: The aim of this study was to identify the dosage of the liquid extract of C recutita in mouthwash that is needed to reduce the incidence and intensity of oral mucositis in adult patients undergoing allogenic HSCT. METHODS: In a randomized phase II clinical trial, 40 patients were randomized to receive routine care plus mouthwash containing a liquid extract of C recutita at 0.5%, 1%, or 2% (experimental groups) or standard care alone (control group). Daily evaluation was performed using the measurement scale for oral toxicity defined by the World Health Organization. Statistical analysis was performed, in which the incidence, intensity, and duration of oral mucositis were compared between each experimental group and the control group. RESULTS: The experimental group at the 1% dosage demonstrated reduced incidence, intensity, and duration of oral mucositis compared with the control group. The formulation was well tolerated by patients and was safe, as no moderate or severe adverse effects were identified. CONCLUSIONS: In this study, the use of mouthwash containing 1% C recutita extract can be associated with reduced incidence, intensity, and duration of mucositis in adults patients undergoing allogenic HSCT. IMPLICATIONS FOR PRACTICE: The results of this investigation will help nurses and other professionals in selecting the C recutita dosage used to manage oral mucositis in patients undergoing HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Matricaria , Estomatite/tratamento farmacológico , Adulto , Anemia Aplástica/complicações , Anemia Aplástica/tratamento farmacológico , Feminino , Humanos , Leucemia Linfoide/complicações , Leucemia Linfoide/tratamento farmacológico , Leucemia Mieloide/complicações , Leucemia Mieloide/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Antissépticos Bucais/farmacologia , Antissépticos Bucais/uso terapêutico
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