RESUMO
Objectives: The mechanism behind the progression of Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) remains poorly understood. However some evidence pointed out that the co-occurrence of metabolic conditions affecting glucose homeostasis, as type 2 diabetes mellitus (T2DM), may be an important catalyst in this context. Notably, candidate drugs which modulate common pathways in the development of MCI-to-AD mediated by T2DM may offer likely therapy for AD. Nonetheless, limited pharmacological alternatives that modulate common pathways in T2DM, MCI, and AD are available. In the recent decades, studies have shown that resveratrol may act as a neuroprotective compound, but little is known about its potential in improving cognitive and metabolic aspects associated with AD progression mediated by the co-association between TDM2-MCI.Methods: In this review, we discuss possible protective mechanisms of resveratrol on shared pathways associated with AD progression mediated by T2DM-MCI co-occurrence.Results: Some studies indicated that insulin resistance and hyperglycemia may be also a T2DM risk factor for the progression of MCI-to-AD, promoting alterations in metabolic pathways associated with neuronal plasticity, and increasing pro-inflammatory environment. Interestingly, basic research and clinical trials indicate that resveratrol may modulate those pathways, showing a potential neuroprotective effect of this polyphenol.Conclusion: Therefore, there is not enough clinical data supporting the translational therapeutic use of resveratrol in this scenario.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Doenças Neurodegenerativas , Humanos , Resveratrol/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/complicações , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/complicaçõesRESUMO
BACKGROUND: Local fat accumulation is a health risk and this has raised interest in the development of aesthetic treatments, such as cryo-radiofrequency (CRF). OBJECTIVE: To evaluate the consequences of CRF in adipose tissue remodeling in a model system. MATERIALS AND METHODS: Lean and high-fat diet-induced obese mice were assessed 7 days after one CRF application; and lean mice were assessed 0, 3, 6 and 12 h after one application of CRF. Assessments included histology, DNA degradation, gene expression, ELISA of cytokines, serum analysis and neutrophil presence. RESULTS: Unchanged fat mass was found 7 days after CRF in obese and lean mice. However, lean mice showed smaller adipocyte size with areas resembling a browning process. TNF levels, apoptotic cells, and UCP-1 expression increased 7 days after CRF in inguinal adipose tissue of lean mice. Although no differences were found in fat mass, adipocyte size decreased just after CRF and this changed was maintained until 12 h, with cells resembling beige adipocytes. CONCLUSION: We suggest that CRF therapy is capable of inducing thermogenic adipocytes in lean mice.
Assuntos
Tecido Adiposo Marrom , Tecido Adiposo Branco , Crioterapia , Obesidade/terapia , Terapia por Radiofrequência , Adipócitos , Tecido Adiposo Marrom/citologia , Tecido Adiposo Branco/citologia , Animais , Camundongos , Camundongos Endogâmicos C57BL , TermogêneseRESUMO
PURPOSE OF REVIEW: In 2016, the World Health Organization declared the Zika virus (ZIKV) outbreak a Public Health Emergency of International Concern following a cluster of associated neurological disorders and neonatal malformations. Our aim is to review the clinical and neuroimaging findings seen in congenital Zika syndrome. RECENT FINDINGS: ZIKV injures neural progenitor cells in the hippocampus, a brain region important for learning, memory, cognition, and emotion/stress response. Positron emission tomography has revealed global neuroinflammation in ZIKV infection in animal models. Congenital Zika syndrome is associated with a spectrum of brain abnormalities, including microcephaly, parenchymal calcifications, malformations of cortical development and defective neuronal migration, corpus callosum abnormalities, ventriculomegaly, and brainstem and cerebellar abnormalities.
Assuntos
Microcefalia , Complicações Infecciosas na Gravidez , Infecção por Zika virus , Zika virus , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Microcefalia/diagnóstico por imagem , Microcefalia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico por imagem , Infecção por Zika virus/epidemiologiaRESUMO
AIM: To evaluate the activity and effectiveness of impregnated central venous catheters (CVC) against Klebsiella pneumoniae biofilms. METHODS AND RESULTS: The antimicrobial activity and durability of impregnated-CVCs were evaluated over time and the size of zones of inhibition (ZI) was measured. Biofilm formation was observed by quantitative culture and also by scanning electron microscopy. The catheters impregnated with chlorhexidine/silver sulfadiazine (CHX/SS) reduced bacteria counts by 0·3 log and were most effective (P < 0·01) against Klebsiella pneumoniae biofilms N-acetylcysteine/levofloxacin (NAC/LEV) catheters. It was observed that the catheter impregnated with NAC/LEV had initially the largest average ZI size being statistically significant (P < 0·01). The NAC/LEV combination remained active until day 30, whereas the combination of CHX/SS was completely inactivated from day 15 on. CONCLUSIONS: The NAC/LEV combination showed greater durability on the catheters, but it was the CHX/SS combination that had the greater initial efficacy in bacterial inhibition. It was also observed that NAC/LEV-impregnated catheters do not prevent the emergence of resistant subpopulations inside the inhibition halos during antimicrobial susceptibility tests. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results highlighted that the in vitro efficacy of antimicrobial-impregnated CVCs is limited by time and that their colonization occurred earlier than expected. Our data also demonstrated that NAC/LEV remained active until day 30 of evaluation and CHX/SS combination was completely inactivated from day 15 on. Our findings suggested that implantable devices should be carefully used by medical community.
Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Catéteres/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Acetilcisteína/farmacologia , Biofilmes/crescimento & desenvolvimento , Clorexidina/farmacologia , Farmacorresistência Bacteriana , Klebsiella pneumoniae/fisiologia , Levofloxacino/farmacologia , Sulfadiazina de Prata/farmacologia , Fatores de TempoRESUMO
Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). METHODS: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). RESULTS: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. CONCLUSIONS: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome.
Assuntos
Portador Sadio/virologia , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Paraparesia Espástica Tropical/diagnóstico , Provírus/fisiologia , Carga Viral , Adulto , Idoso , Doenças Assintomáticas , Brasil , Estudos de Coortes , Feminino , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Paraparesia Espástica Tropical/etiologia , Paraparesia Espástica Tropical/virologia , Provírus/genéticaRESUMO
Genetic improvement is essential to achieve increments in maize (Zea mays L.) grain yield components. It may be obtained through crosses, which enable to exploit the effects of intervarietal heterosis, allelic complementarity, as well as gene actions and effects. This study estimated the components of variance and genetic parameters (REML/BLUP) of an intervarietal diallel to select and predict the best genotypes for maize yield components. The experimental design was randomized blocks containing 60 intervarietal maize hybrids arranged in three repetitions. They were obtained through intervarietal crosses and evaluated in a diallel scheme, where 14 open-pollinated varieties were designated as parentals. Thus, 10 crosses were performed for each hybrid combination to obtain the number of seeds necessary for the competition test. The measured traits were: grain volume relative index, the mass of one hundred grains, and grain yield. The male parents and the additive genetic fraction were determinants for grain volume relative index. Mass of one hundred grains and grain yield were defined by the specific combining ability, and female parents revealed low narrow sense heritability. The female parent Taquarão and male parent Argentino Amarelo presented the best general combining abilities for the measured traits. The specific combining abilities were expressed for crosses AL 25 x Dente de Ouro Roxo, AL 25 x BRS Pampeano, and Taquarão x Argentino Branco. Genetic estimates and predictions were consistent and applicable to breeding programs and could be applied in future quantitative genetic studies of maize.
Assuntos
Hibridização Genética , Modelos Genéticos , Melhoramento Vegetal/métodos , Polimorfismo Genético , Zea mays/genética , Alelos , Genótipo , Característica Quantitativa Herdável , Sementes/genética , Sementes/crescimento & desenvolvimento , Zea mays/crescimento & desenvolvimentoRESUMO
The REML/BLUP statistics are analyses that can be used as selective criteria in the routine of maize breeding programs. The present study aims to determine the genetic potential in crosses of landrace populations applying the REML/BLUP methodology, and to identify populations for the synthesis of new populations and intrapopulation selection for family farming systems, as well as genetic constitutions for use in maize breeding programs. Nine top cross hybrids obtained in the 2012/2013 harvest were evaluated along with their testator, the landraces used as parents, and four commercial hybrids, in a randomized block design, with information taken from the average of each plot. The evaluated traits were: leaf angle, number of ramifications of the tassel, spike insertion height, plant height, spike diameter, number of grains per spike, mass of grains per spike, spike mass, spike length, prolificity, mass of one hundred grains, and grain yield per plot. The data were analyzed using the Selegen-REML/BLUP software. The top cross hybrids Cateto Branco x Planalto, Amarelão x Planalto and the population Cateto Branco are ranked among the ten best crosses, simultaneously, for the traits: leaf angle, number of ramifications of the tassel, spike insertion height, and plant height (Cateto Branco x Planalto), and leaf angle, spike insertion height, and plant height (Amarelão x Planalto and Cateto Branco). The top cross hybrids Criolão x Planalto, Branco 8 Carreiras x Planalto, Caiano Rajado x Planalto, Amarelão x Planalto, Branco Roxo Índio x Planalto stand out for their high genotypic value of the individual BLUP mean components among the ten best genotypes for grain yield, and by combining three or more traits of interest together, being, for effects of selection, the most indicated.
Assuntos
Cruzamento/métodos , Cruzamentos Genéticos , Zea mays/genética , Característica Quantitativa HerdávelRESUMO
OBJECTIVES: The objective of this study was to perform a systematic review and meta-analysis of the literature to evaluate the efficacy and safety of therapies for cerebral toxoplasmosis in HIV-infected adults. The pyrimethamine plus sulfadiazine (P-S) combination is considered the mainstay therapy for cerebral toxoplasmosis and pyrimethamine plus clindamycin (P-C) is the most common alternative treatment. Although trimethoprim-sulfamethoxazole (TMP-SMX) has potential advantages, its use is infrequent. METHODS: We searched PubMed and four other databases to identify randomized controlled trials (RCTs) and cohort studies. Two independent reviewers searched the databases, identified studies and extracted data. Risk ratios (RRs) were pooled across studies using random-effects models. RESULTS: Nine studies were included (five RCTs, three retrospective cohort studies and one prospective cohort study). In comparison to P-S, treatment with P-C or TMP-SMX was associated with similar rates of partial or complete clinical response [P-C: RR 0.87; 95% confidence interval (CI) 0.70-1.08; TMP-SMX: RR 0.97; 95% CI 0.78-1.21], radiological response (P-C: RR 0.92; 95% CI 0.82-1.03), skin rash (P-C: RR 0.81; 95% CI 0.56-1.17; TMP-SMX: RR 0.17; 95% CI 0.02-1.29), gastrointestinal impairment (P-C: RR 5.16; 95% CI 0.66-40.11), and drug discontinuation because of adverse events (P-C: RR 0.32; 95% CI 0.07-1.47). Liver impairment was more frequent with P-S than P-C (P-C vs. P-S: RR 0.48; 95% CI 0.24-0.97). CONCLUSIONS: The current evidence fails to identify a superior regimen in terms of relative efficacy or safety for the treatment of HIV-associated cerebral toxoplasmosis. Use of TMP-SMX as preferred treatment may be consistent with the available evidence and other real-world considerations. Larger comparative studies are needed.
Assuntos
Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Infecções por HIV/complicações , Toxoplasmose Cerebral/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Clindamicina/efeitos adversos , Clindamicina/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pirimetamina/efeitos adversos , Pirimetamina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfadiazina/efeitos adversos , Sulfadiazina/uso terapêuticoRESUMO
Quantitative real-time polymerase chain reaction (RT-qPCR) is a powerful tool used to measure gene expression. However, because of its high sensitivity, the method is strongly influenced by the quality and concentration of the template cDNA and by the amplification efficiency. Relative quantification is an effective strategy for correcting random and systematic errors by using the expression level of reference gene(s) to normalize the expression level of the genes of interest. To identify soybean reference genes for use in studies of flooding stress, we compared 5 candidate reference genes (CRGs) with the NormFinder and GeNorm programs to select the best internal control. The expression stability of the CRGs was evaluated in root tissues from soybean plants subjected to hypoxic conditions. Elongation factor 1-beta and actin-11 were identified as the most appropriate genes for RT-qPCR normalization by both the NormFinder and GeNorm analyses. The expression profiles of the genes for alcohol dehydrogenase 1, sucrose synthase 4, and ascorbate peroxidase 2 were analyzed by comparing different normalizing combinations (including no normalization) of the selected reference genes. Here, we have identified potential genes for use as references for RT-qPCR normalization in experiments with soybean roots growing in O2-depleted environments, such as flooding-stressed plants.
Assuntos
Regulação da Expressão Gênica de Plantas/genética , Glycine max/genética , Proteínas de Plantas/biossíntese , Reação em Cadeia da Polimerase em Tempo Real/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/fisiologia , Hipóxia , Proteínas de Plantas/genética , Raízes de PlantasRESUMO
BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival î¶6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.