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1.
Proc Natl Acad Sci U S A ; 120(34): e2302738120, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37579159

RESUMO

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by various disabling symptoms including exercise intolerance and is diagnosed in the absence of a specific cause, making its clinical management challenging. A better understanding of the molecular mechanism underlying this apparent bioenergetic deficiency state may reveal insights for developing targeted treatment strategies. We report that overexpression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), here identified in a 38-y-old woman suffering from long-standing fatigue and exercise intolerance, can disrupt mitochondrial respiratory supercomplex formation and is associated with endoplasmic reticulum (ER) stress. Increased expression of WASF3 in transgenic mice markedly decreased their treadmill running capacity with concomitantly impaired respiratory supercomplex assembly and reduced complex IV levels in skeletal muscle mitochondria. WASF3 induction by ER stress using endotoxin, well known to be associated with fatigue in humans, also decreased skeletal muscle complex IV levels in mice, while decreasing WASF3 levels by pharmacologic inhibition of ER stress improved mitochondrial function in the cells of the patient with chronic fatigue. Expanding on our findings, skeletal muscle biopsy samples obtained from a cohort of patients with ME/CFS showed increased WASF3 protein levels and aberrant ER stress activation. In addition to revealing a potential mechanism for the bioenergetic deficiency in ME/CFS, our study may also provide insights into other disorders associated with fatigue such as rheumatic diseases and long COVID.


Assuntos
COVID-19 , Síndrome de Fadiga Crônica , Animais , Feminino , Humanos , Camundongos , COVID-19/metabolismo , Síndrome de Fadiga Crônica/diagnóstico , Mitocôndrias/metabolismo , Síndrome de COVID-19 Pós-Aguda , Respiração , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo , Camundongos Transgênicos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38922982

RESUMO

This study aimed to assess the impact of protein supplementation and its interaction with calf sex (CS) on the performance, metabolism and physiology of pregnant beef cows. Fifty-two multiparous Zebu beef cows carrying female (n = 22) and male (n = 30) fetuses were used. Cows were individually housed from day 100 to 200 of gestation and randomly assigned to restricted (RES, n = 26) or supplemented (SUP, n = 26) groups. The RES cows were ad libitum fed a basal diet (corn silage + sugarcane bagasse + mineral mixture), achieving 5.5% crude protein (CP), while SUP cows received the same basal diet plus a protein supplement (40% CP, at 3.5 g/kg of body weight). All cows were fed the same diet during late gestation. Differences were declared at p < 0.05. No significant interaction between maternal nutrition and calf sex was found for maternal outcomes (p ≥ 0.34). The SUP treatment increased the total dry matter (DM) intake (p ≤ 0.01) by 32% and 19% at mid- and late-gestation respectively. The total tract digestibility of all diet components was improved by SUP treatment at day 200 of gestation (p ≤ 0.02), as well as the ruminal microbial CP production (p ≤ 0.01). The SUP treatment increased (p ≤ 0.03) the cows' body score condition, ribeye area, the average daily gain (ADG) of pregnant components (PREG; i.e., weight accretion of cows caused by pregnancy) and the ADG of maternal tissues (i.e., weight accretion discounting the gain related to gestation) in the mid-gestation. The SUP cows exhibited a lower maternal ADG (p < 0.01) compared to RES cows in late pregnancy. There was a 24% additional gain (p < 0.01) in the PREG components for SUP cows during late gestation, which in turn improved the calf birthweight (p = 0.05). The uterine arterial resistance and pulsatility indexes (p ≤ 0.01) at mid-gestation were greater for RES cows. In conclusion, protein supplementation during mid-gestation is an effective practice for improving maternal performance, growth of the gravid uterus and the offspring's birth weight.

3.
Bull Entomol Res ; 113(6): 814-828, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37997933

RESUMO

Climate factors, pesticides, and landscape in coffee agroecosystems directly affect the populations of the coffee leaf miner and its parasitoids. This study aimed to investigate the effects of climate factors, insecticide use, and landscape on natural parasitism, parasitoid diversity, and infestation of L. coffeella in coffee plantations in the Planalto region, Bahia, Brazil. Mined leaves were collected monthly in six coffee plantations with varying edge density, vegetation cover, landscape diversity in scales of 500 to 3000 m of radius, insecticide use, and climate factors. Closterocerus coffeellae, and Proacrias coffeae (Eulophidae) predominated in the pest's natural parasitism. Our record is the first for the occurrence of Stiropius reticulatus, Neochrysocharis sp. 1, Neochrysocharis sp. 2, and Zagrammosoma sp. in Bahia. Higher temperature and larger forest cover increased the coffee leaf miner infestation. Higher rainfall values, insecticide use, and landscape diversity decreased the pest infestations. Natural parasitism and species diversity are favoured by increase in temperature, forest cover, and edge density, while increase in rainfall, insecticide use, and landscape diversity lead them to decrease.The natural parasitism and diversity of parasitoid species of the coffee leaf miner have been enhancing in the areas with greater forest cover and edge density associated with low use of insecticides. The areas composed of different lands with annual croplands surrounding the coffee plantations showed less natural parasitism and parasitoid species diversity. The ecosystem services provided by C. coffeellae and P. coffeae in coffee crops areas require conservation and these species are potential bioproducts for applied biological control programmes.


Assuntos
Coffea , Inseticidas , Mariposas , Animais , Ecossistema , Florestas
4.
Bioprocess Biosyst Eng ; 46(11): 1651-1664, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37728765

RESUMO

This study aimed to immobilize trypsin on activated carbon submitted to different surface modifications and its application in casein hydrolysis. With the aim of determining which support can promote better maintenance of the immobilized enzyme. Results showed that pH 5.0 was obtained as optimal for immobilization and pH 9.0 for the casein hydrolysis reaction for activated carbon and glutaraldehyde functionalized carbon. Among the supports used, activated carbon modified with iron ions in the presence of a chelating agent was the one that showed best results, under the conditions evaluated in this study. Presenting an immobilization yield of 95.15% and a hydrolytic activity of 4.11 U, same as soluble enzyme (3.76 U). This derivative kept its activity stable at temperatures above 40 °C for1 h and when stored for 30 days at 5 °C. Furthermore, it was effective for more than 6 reuse cycles (under the same conditions as the 1st cycle). In general, immobilization of trypsin on metallized activated carbon can be an alternative to biocatalysis, highlighting the advantages of protease immobilization.


Assuntos
Caseínas , Carvão Vegetal , Hidrólise , Estabilidade Enzimática , Tripsina/metabolismo , Concentração de Íons de Hidrogênio , Enzimas Imobilizadas/metabolismo , Temperatura
5.
J Therm Biol ; 114: 103562, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37344024

RESUMO

This research aimed to evaluate the impact of temperature and energy status on the thermal indices, physiological parameters, and ruminal papilla mRNA expression levels of Zebu beef heifers (Bos taurus indicus). In this trial, we used six ruminal-cannulated Nellore females. The experimental design was a 6 × 6 Latin square, with six treatments and six periods. The research used a 2 × 2 + 2 factorial scheme. The arrangement comprised: two thermal conditions [thermoneutrality (TN; 21.6 °C) or heat stress (HS, 34 °C)]; two dietary energy levels (low or high-energy); and two additional treatments, with heifers exposed to the TN, but pair-fed with females exposed to HS (PFTN). For our purposes, body temperature, heart and respiratory rates were measured and the relative mRNA expression was quantified using the PCR-RT technique. Compared to TN or PFTN, the HS increased the body temperature measurements in the morning and evening (p ≤ 0.04). Heart rate was 22% greater for heifers under HS than for TN (p < 0.01) and 13% higher for those under HS than PFTN (p = 0.03) in the morning. Respiratory rates increased with HS exposure compared to TN or PFTN (p < 0.01). Heifers submitted to HS and fed low-energy diets had and tended to have lower caspase 3 (CASP3, p 0.001) and sodium-glucose cotransporter type 1 (SGLT1; p = 0.17) mRNA expressions, respectively. Heat-stressed heifers fed low-energy diets also increased the putative anion transporter (PAT1; p ≤ 0.01) mRNA expressions by 60%. Heifers under HS-fed high-energy diets had greater kallikrein-related peptidase (KLK) 9 expressions (p = 0.02), while KLK10 (p = 0.11) tended to be up-regulated in heifers in TN-fed a low-energy diets. In conclusion, heat stress down-regulated the mRNA expression of rumen markers related to short-chain fatty acids transport and pH modulation.


Assuntos
Dieta , Temperatura Alta , Bovinos , Animais , Feminino , Dieta/veterinária , Resposta ao Choque Térmico , Epitélio , RNA Mensageiro , Ração Animal/análise , Rúmen/fisiologia
6.
Adv Physiol Educ ; 46(3): 351-357, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35549509

RESUMO

The COVID-19 pandemic affected almost all aspects of our lives, including the education sector and the way of teaching and learning. In March 2020, health authorities in Brazil imposed social isolation and the interruption of on-site activities in schools and universities. In this context, the Federal University of Minas Gerais (UFMG), one of the largest universities in Brazil and Latin America, developed an emergency remote learning (ERL) plan that allowed the return of classes in an online format and supported students to obtain access to equipment and internet network. Within this new perspective, the Undergraduate Teaching Assistant (UTA) program of the Department of Physiology and Biophysics (DFIB) explored strategies to minimize the impact of the absence of face-to-face classes. Using different available tools in online platforms and social media such as Microsoft Teams, YouTube animated video classes, and Instagram, the UTA program assisted >500 undergraduate students and strongly supported professors during ERL. In just over a year, our video classes on YouTube Channel reached ∼40,000 views. Most of the students reported that their questions were fully and quickly solved by the UTA program. Collectively, our results indicate that the strategies implemented by the UTA program helped the undergraduate students and professors to adapt to a remote learning format.


Assuntos
COVID-19 , Educação a Distância , Biofísica , Educação a Distância/métodos , Humanos , Pandemias , Estudantes
7.
FASEB J ; 34(6): 7644-7660, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32281181

RESUMO

Mitochondrial function, largely regulated by the dynamics of this organelle, is inextricably linked to the oocyte health. In comparison with most somatic cells, mitochondria in oocytes are smaller and rounder in appearance, suggesting limited fusion. The functional implications of this distinct morphology, and how changes in the mitochondrial shape translate to mitochondrial function in oogenesis is little understood. We, therefore, asked whether the pro-fusion proteins mitofusins 1 (MFN1) and 2 (MFN2) are required for the oocyte development. Here we show that oocyte-specific deletion of Mfn1, but not Mfn2, prevents the oocyte growth and ovulation due to a block in folliculogenesis. We pinpoint the loss of oocyte growth and ovulation to impaired PI3K-Akt signaling and disrupted oocyte-somatic cell communication. In support, the double loss of Mfn1 and Mfn2 partially rescues the impaired PI3K-Akt signaling and defects in oocyte development secondary to the single loss of Mfn1. Together, this work demonstrates that the mitochondrial function influences the cellular signaling during the oocyte development, and highlights the importance of distinct, nonredundant roles of MFN1 and MFN2 in oogenesis.


Assuntos
Comunicação Celular/fisiologia , GTP Fosfo-Hidrolases/metabolismo , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Oócitos/fisiologia , Oogênese/fisiologia , Ovulação/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia
8.
Chem Rec ; 21(10): 2702-2738, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34170622

RESUMO

Diverse structural frameworks are found in natural compounds and are well known for their chemical and biological properties; such compounds include the imidazoles and oxazoles. Researchers worldwide are continually working on the development of methods for synthesizing new molecules bearing these basic moiety and evaluating their properties and applications. To expand the knowledge related to azoles, this review summarizes important examples of imidazole and oxazole derivatives from 1,2-dicarbonyl compounds, such as lapachones and phenanthrene-9,10-diones, not only regarding their synthesis and biological applications but also their photophysical properties and uses. The data concerning the latter are particularly scarce in the literature, which leads to underestimation of the potential applications that can be envisaged for these compounds.


Assuntos
Oxazóis , Fenantrenos , Imidazóis
9.
Soft Matter ; 17(26): 6352-6361, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34086028

RESUMO

Hydrogels have been used as matrices for the topical delivery of nitric oxide (NO) for achieving vasodilation, wound healing and analgesic actions. More recently, supramolecular hydrogels comprised of poly(acrylic acid) (PAA) and micellar Pluronic F127 (F127), prepared by thermal reaction, emerged as a suitable matrix for the incorporation of hydrophilic NO donors, such as S-nitrosoglutathione (GSNO). Herein, we describe an innovative method for the three-dimensional (3D) printing of cellulose nanocrystal (CNC)-containing and semi-interpenetrating PAA/F127 hydrogels by PAA photopolymerization via digital light processing (DLP), in the absence of organic solvents. Scanning electron microscopy showed that, differently from typical porous PAA-based hydrogels, the 3D printed PAA/F127/CNC hydrogels have dense morphology. By using transmission electron microscopy we confirmed for the first time the presence of F127 micelles in the printable resin, and their preservation after the photopolymerization process. The F127 micelles conferred compressive recoverability to the 3D printed PAA/F127/CNC hydrogels, widening their potential applications as soft biomaterials. PAA/F127/CNC hydrogels charged with GSNO are shown to release NO spontaneously upon hydration at initial rates that depend on the GSNO charge and are higher in the presence of CNC. As local NO release may exert cell proliferation action, 3D printed PAA/F127/CNC/GSNO hydrogels may serve as a versatile soft biomaterial for local NO delivery in regenerative medicine and other biomedical applications.


Assuntos
Hidrogéis , Nanopartículas , Resinas Acrílicas , Celulose , Óxido Nítrico , Polietilenos , Polipropilenos , Impressão Tridimensional
10.
Artigo em Inglês | MEDLINE | ID: mdl-33406983

RESUMO

The objective of this study was to evaluate the productivity of shoot dry biomass and the capacity of nitrogen (N), phosphorus (P) and potassium (K) extraction by the Vetiver and Tifton 85 grasses when cultivated in horizontal subsurface flow constructed wetlands (HSSF-CWs) whose porous medium was saturated with solutions containing different nutrient availability. The grass shoots were cut every 30 days to determine the productivity and N, P and K contents in the plant tissue. Models of productivity and the extraction capacity of each nutrient were obtained as a function of the nutrient concentration. Based on the results obtained, it was verified that the productivity of shoot dry biomass and the extractions of N, P and K by the Vetiver grass increased linearly with the nutrient availability of the nutritive solution. In relation to Tifton 85, quadratic models of productivity and N and K extraction were adjusted. The maximum productivity, N, P and K extraction by Vetiver grass were 513.4, 8.2, 1.9 and 10.39 g m-2 month-1, respectively. In relation to Tifton 85 grass, these values were 739.4, 30.8, 3.0 and 15.59 g m-2 month-1 for productivity, N, P and K extraction, respectively.


Assuntos
Vetiveria/metabolismo , Cynodon/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo , Potássio/metabolismo , Biomassa , Vetiveria/crescimento & desenvolvimento , Cynodon/crescimento & desenvolvimento , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Áreas Alagadas
11.
Beilstein J Org Chem ; 17: 1849-1938, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386103

RESUMO

Several valuable biologically active molecules can be obtained through C-H activation processes. However, the use of expensive and not readily accessible catalysts complicates the process of pharmacological application of these compounds. A plausible way to overcome this issue is developing and using cheaper, more accessible, and equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C-H activation processes to obtain potentially (or proved) biologically active compounds.

12.
Mol Hum Reprod ; 26(12): 938-952, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-33118034

RESUMO

Offspring born to obese and diabetic mothers are prone to metabolic diseases, a phenotype that has been linked to mitochondrial dysfunction and endoplasmic reticulum (ER) stress in oocytes. In addition, metabolic diseases impact the architecture and function of mitochondria-ER contact sites (MERCs), changes which associate with mitofusin 2 (MFN2) repression in muscle, liver and hypothalamic neurons. MFN2 is a potent modulator of mitochondrial metabolism and insulin signaling, with a key role in mitochondrial dynamics and tethering with the ER. Here, we investigated whether offspring born to mice with MFN2-deficient oocytes are prone to obesity and diabetes. Deletion of Mfn2 in oocytes resulted in a profound transcriptomic change, with evidence of impaired mitochondrial and ER function. Moreover, offspring born to females with oocyte-specific deletion of Mfn2 presented increased weight gain and glucose intolerance. This abnormal phenotype was linked to decreased insulinemia and defective insulin signaling, but not mitochondrial and ER defects in offspring liver and skeletal muscle. In conclusion, this study suggests a link between disrupted mitochondrial/ER function in oocytes and increased risk of metabolic diseases in the progeny. Future studies should determine whether MERC architecture and function are altered in oocytes from obese females, which might contribute toward transgenerational transmission of metabolic diseases.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Oócitos/metabolismo , Animais , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Feminino , GTP Fosfo-Hidrolases/genética , Homeostase/fisiologia , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/fisiologia , Músculo Esquelético/metabolismo , Transdução de Sinais
13.
Artigo em Inglês | MEDLINE | ID: mdl-32067564

RESUMO

Estimation of the Crop Evapotranspiration (ETC) in Horizontal Subsurface Flow Constructed Wetlands (HSSF-CWs) is of great importance for hydrological modeling of these systems. The objective of this work was to obtain the Crop Coefficient (KC) values of Vetiver (Chrysopogon zizanioides) and Tifton 85 (Cynodon spp.) grasses when grown in HSSF-CWs whose porous medium was saturated with solutions containing different nutrients concentrations. The water balance was performed every day in order to determine the KC of the grasses. It was verified that the KC values of the Vetiver grass were independent of the nutrient availability, expressed in terms of Electrical Conductivity (EC) of the nutrient solution. The KC value in the initial growth phase (Phase I) was 0.99, independent of the seasons. In Phase II, the KC were 0.95 and 1.36 for autumn and spring, respectively, and for Phase III were 1.12 in autumn and 1.60 in spring. In relation to the Tifton 85 grass, the KC values showed a quadratic behavior as a function of the EC, where the KC estimation models were obtained by the cluster analysis in Phase II and III. For Phase I, the KC value was 1.17, independent of the EC and the time of year.


Assuntos
Vetiveria/crescimento & desenvolvimento , Cynodon/crescimento & desenvolvimento , Áreas Alagadas , Brasil , Hidrodinâmica , Modelos Teóricos , Estações do Ano , Tempo (Meteorologia)
14.
BMC Genomics ; 20(1): 501, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208329

RESUMO

BACKGROUND: Feed efficiency is one of the most important parameters that affect beef production costs. The energy metabolism of skeletal muscle greatly contributes to variations in feed efficiency. However, information regarding differences in proteins involved in the energy metabolism of the skeletal muscle in beef cattle divergently identified for feed efficiency is scarce. In this study, we aimed to investigate energy metabolism of skeletal muscle of Nellore beef cattle, identified for low and high residual feed intake using a proteomics approach. We further assessed the expression of candidate microRNAs as a one of the possible mechanisms controlling the biosynthesis of the proteins involved in energy metabolism that were differentially abundant between high and low residual feed intake animals. RESULTS: A greater abundance of 14-3-3 protein epsilon (P = 0.01) was observed in skeletal muscle of residual feed intake (RFI) high animals (RFI-High). Conversely, a greater abundance of Heat Shock Protein Beta 1 (P < 0.01) was observed in the skeletal muscle of RFI-Low cattle. A greater mRNA expression of YWHAE, which encodes the 14-3-3 protein epsilon, was also observed in the skeletal muscle of RFI-High animals (P = 0.01). A lower mRNA expression of HSPB1, which encodes the Heat Shock Protein Beta 1, was observed in the skeletal muscle of RFI-High animals (P = 0.01). The miR-665 was identified as a potential regulator of the 14-3-3 protein epsilon, and its expression was greater in RFI-Low animals (P < .001). A greater expression of miR-34a (P = 0.01) and miR-2899 (P < .001) was observed in the skeletal muscle of RFI-High animals, as both miRNAs were identified as potential regulators of HSPB1 expression. CONCLUSION: Our results show that Nellore cattle divergently identified for feed efficiency by RFI present changes in the abundance of proteins involved in energy expenditure in skeletal muscle. Moreover, our data point towards that miR-665, miR34a and miR-2899 are likely involved in controlling both 14-3-3 epsilon and HSPB1 proteins identified as differentially abundant in the skeletal muscle of RFI-High and RFI-Low Nellore cattle.


Assuntos
Ingestão de Alimentos , Metabolismo Energético/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Proteínas Musculares/genética , Músculo Esquelético/metabolismo , Carne Vermelha , Ração Animal , Animais , Bovinos , Masculino , Proteômica , RNA Mensageiro/genética
15.
An Acad Bras Cienc ; 90(4): 3685-3692, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30365707

RESUMO

The objective of this study was to evaluate NBPT, zeolite and humic acid in different concentrations as inhibitors of the activity of the enzyme urease. The activity of the urease enzyme was quantified by the methods proposed by May and Douglas (1976) and Witte and Medina-Escobar (2001). For this reason, two experiments were conducted in a completely randomized design in split plots, in which the incubation periods are the plots and the fertilizers with the inhibitors at the different concentrations are the subplots with three replications. Fifteen fertilizers based on NBPT-coated urea, humic acid and zeolite were used in different concentrations. The two methods of analysis used in the experiment confirmed the efficiency of NBPT in inhibiting the enzymatic action even at low concentration, with 0.02% (m/m) being sufficient to inhibit urease, with no difference between inhibitor concentrations. The addition of humic acid reduced the activity of urease after 36 hours of reaction when the activity of the enzyme was evaluated by the method proposed by May and Douglas (1976). Zeolite did not influence the activity of the urease enzyme when analyzed by the May and Douglas method (1976).


Assuntos
Inibidores Enzimáticos/farmacologia , Substâncias Húmicas , Compostos Organofosforados/farmacologia , Solo/química , Ureia/farmacologia , Urease/antagonistas & inibidores , Zeolitas/farmacologia , Fertilizantes
16.
Acta Neurol Scand ; 136(5): 407-413, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28181220

RESUMO

OBJECTIVE: To assess seizure control and tolerability of eslicarbazepine acetate (ESL) as adjunctive therapy to one baseline antiepileptic drug (AED), in adults with partial-onset seizures (POS) with or without secondary generalization. METHODS: Multicenter, non-interventional, prospective cohort study conducted between March 2012 and September 2014 at 12 neurology departments in Portugal. Adults with POS not controlled with one AED who had initiated ESL as adjunctive treatment were enrolled. Retention rate was defined at the final visit (Vfinal) 6-9 months of follow-up. Proportion of responders, seizure-free, changes in seizure frequency were evaluated using patients' diaries. Clinical Global Impression of Change (CGI-C) and Clinical Global Impression of Severity (CGI-S) were assessed by the neurologist. RESULTS: Fifty-two patients (48.1% male) were included with mean age 41.5±13.3 years. Mean epilepsy duration was 18.5±14.8 years; mean seizure frequency in the four previous weeks to baseline was 7.5±12.7. At Vfinal, retention rate was 73.0%; responder rate and seizure-free rates were 71.1% and 39.5%, respectively. The median relative reduction in seizure frequency between baseline and Vfinal was 82.2%. A reduction in epilepsy severity (CGI-S) was observed in 42.1%. According to CGI-C, 73.6% patients had their epilepsy "much improved" or "very much improved". Twelve patients (23.1%) had at least one adverse event (AE), two (3.9%) had one serious AE, and five (9.6%) discontinued due to AE. CONCLUSIONS: Eslicarbazepine acetate showed good retention rates, elicited a significant reduction in seizure frequency, and was well tolerated when used in the clinical practice.


Assuntos
Anticonvulsivantes/uso terapêutico , Dibenzazepinas/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Adulto , Anticonvulsivantes/efeitos adversos , Dibenzazepinas/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
17.
J Biol Chem ; 290(35): 21591-602, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26163517

RESUMO

Alzheimer disease (AD) is characterized by the extracellular accumulation of amyloid ß (Aß), which is accompanied by a robust inflammatory response in the brain. Both of these pathogenic processes are regulated by nuclear receptors, including the liver X receptors (LXRs) and peroxisome-proliferator receptor γ (PPARγ). Agonists of LXRs have been demonstrated previously to reduce Aß levels and improve cognitive deficits in AD mouse models by inducing the transcription and lipidation of apolipoprotein E (apoE). Agonists targeting PPARγ reduce the microglial expression of proinflammatory genes and have also been shown to modulate apoE expression. Here we investigate whether a combination therapy with both LXR and PPARγ agonists results in increased benefits in an AD mouse model. We found that the LXR agonist GW3965 and the PPARγ agonist pioglitazone were individually able to increase the levels of apoE and related genes, decrease the expression of proinflammatory genes, and facilitate Aß decreases in the hippocampus. Combined treatment with both agonists provoked a further increase in the expression of apoE and a decrease in the soluble and deposited forms of Aß. The decrease in plaques was associated with increased colocalization between microglia and plaques. In addition, the PPARγ agonist in the combined treatment paradigm was able to counteract the elevation in plasma triglycerides that is a side effect of LXR agonist treatment. These results suggest that combined LXR/PPARγ agonist treatment merits further investigation for the treatment of AD.


Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Comportamento Animal , Receptores Nucleares Órfãos/agonistas , PPAR gama/agonistas , Presenilina-1/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Apolipoproteínas E/metabolismo , Comportamento Animal/efeitos dos fármacos , Benzoatos/farmacologia , Benzilaminas/farmacologia , Biomarcadores/metabolismo , Transtornos Cognitivos/complicações , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Receptores X do Fígado , Masculino , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Receptores Nucleares Órfãos/metabolismo , PPAR gama/metabolismo , Tamanho da Partícula , Pioglitazona , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Proteólise/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Transcrição Gênica/efeitos dos fármacos , Triglicerídeos/sangue
18.
Int J Mol Sci ; 17(6)2016 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-27294923

RESUMO

The objective of the present review is to discuss the results of published studies that show how nutrition affects the expression of genes involved in lipid metabolism and how diet manipulation might change marbling and composition of fat in beef. Several key points in the synthesis of fat in cattle take place at the molecular level, and the association of nutritional factors with the modulation of this metabolism is one of the recent targets of nutrigenomic research. Within this context, special attention has been paid to the study of nuclear receptors associated with fatty acid metabolism. Among the transcription factors involved in lipid metabolism, the peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding proteins (SREBPs) stand out. The mRNA synthesis of these transcription factors is regulated by nutrients, and their metabolic action might be potentiated by diet components and change lipogenesis in muscle. Among the options for dietary manipulation with the objective to modulate lipogenesis, the use of different sources of polyunsaturated fatty acids, starch concentrations, forage ratios and vitamins stand out. Therefore, special care must be exercised in feedlot feed management, mainly when the goal is to produce high marbling beef.


Assuntos
Lipogênese , Nutrigenômica/métodos , Receptores Citoplasmáticos e Nucleares/genética , Animais , Bovinos , Gorduras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos , Receptores Citoplasmáticos e Nucleares/metabolismo , Carne Vermelha/análise , Vitaminas/farmacologia
19.
J Vasc Surg ; 59(5): 1456-61, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24767275

RESUMO

Fenestrated endovascular aortic repair has been used with increasing frequency to treat complex aortic aneurysms. The Zenith fenestrated stent graft system (Cook Medical Inc, Brisbane, Queensland, Australia) was approved for commercial use in the United States in April 2012, offering a custom-made design with up to three fenestrations to treat short-neck infrarenal and juxtarenal abdominal aortic aneurysms. This report and the Video presentation (online only) summarize the preoperative planning, stent graft design, and technique of implantation of a Zenith fenestrated stent graft using a totally percutaneous approach in an 80-year-old female patient with a 6-cm juxtarenal abdominal aortic aneurysm. The patient was dismissed home the next day without complications, and a computed tomography angiography at 12 months showed no endoleak or stent graft complications.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aortografia/métodos , Feminino , Humanos , Desenho de Prótese , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
J Vasc Surg ; 59(4): 1168-73, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24268717

RESUMO

Branched stent grafts have been widely applied to treat complex aortic aneurysms. The technique often requires brachial or axillary approach to provide antegrade access to directional branches, which are bridged to target visceral arteries by self-expandable stent grafts. Preloaded guidewire catheterization may facilitate access into directional branches, decreasing or eliminating catheter manipulations required during this step of the procedure. We describe the use of a physician-modified branched stent graft using preloaded guidewire catheterization to treat a patient with recurrent, type III thoracoabdominal aortic aneurysm. The procedure was performed with no complications, and total operative time was 300 minutes, fluoroscopy time was 81 minutes, and iodinated contrast dose was 210 mL. Computed tomographic angiography revealed no endoleak and widely patent branches at 2 months.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Desenho de Prótese , Stents , Dispositivos de Acesso Vascular , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia/métodos , Desenho de Equipamento , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Grau de Desobstrução Vascular
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