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1.
Nutr Neurosci ; 25(11): 2442-2457, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34514962

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/complicações
2.
Reprod Fertil Dev ; 33(6): 392-400, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33685580

RESUMO

Spix's cavy is a potentially good experimental model for research on reproductive biology and sexual development. The aim of the present study was to evaluate the ontogeny of the steroidogenic enzymes involved in testicular androgen synthesis during prenatal development. Testes were investigated on Days 25, 30, 40 and >50 of gestation. Immunohistochemistry and immunoblotting were used to establish the site and relative amount of androgenic enzymes, including 5α-reductase, cytosolic 17ß-hydroxysteroid dehydrogenase (17ß-HSDI) and mitochondrial microsomal 3ß-hydroxysteroid dehydrogenase (3ß-HSDII), throughout prenatal development. The testicular parenchyma began to organise on Day 25 of gestation, with the development of recognisable testicular cords. The mesonephros was established after Day 25 of gestation and the ducts differentiated to form the epididymis, as testicular cords were beginning to proliferate and the interstitium to organise by Day 30 of gestation, continuing thereafter. The androgen-synthesising enzymes 5α-reductase, 17ß-HSDI and 3ß-HSDII were evident in Leydig cells as they differentiated at all subsequent gestational ages studied. In addition, immunoblotting showed an increase in immunoreactivity for the enzymes at Days 30 and 40 of gestation (P<0.05) and a decrease at Day 50 of gestation (P<0.05). It is concluded that the increase in androgenic enzymes in Leydig cells coincides with the functional differentiation of the testes, and with the stabilisation and differentiation of mesonephric ducts forming the epididymis.


Assuntos
Androgênios/biossíntese , Cobaias/embriologia , Testículo/embriologia , Testículo/metabolismo , 17-Hidroxiesteroide Desidrogenases/análise , Animais , Colestenona 5 alfa-Redutase/análise , Feminino , Idade Gestacional , Imuno-Histoquímica/veterinária , Células Intersticiais do Testículo/enzimologia , Masculino , Gravidez , Progesterona Redutase/análise
3.
J Chem Phys ; 153(7): 074305, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32828076

RESUMO

The ratios of single, double, and triple ionizations to the total photoionization of the halothane (C2HBrClF3) molecule have been investigated by a single-photon ionization in the energy range from 21.21 eV to 320 eV. In the valence region, the multiple ionization results can be described by a sum of contributions generated from the shake-off and the two-step one models. At low photon energies (from the threshold of triple ionization up to 100 eV), the triple photoionization dynamics of halothane can be reasonably well described by a model involving a classical electron impact double ionization of the singly ionized parent ion.

4.
Med Oral Patol Oral Cir Bucal ; 25(2): e283-e290, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31967981

RESUMO

BACKGROUND: The purpose of this experimental study was to compare the immunohistochemical expression of SOX2 and BCL-2 in Odontogenic Keratocyst (OKC) and Ameloblastoma (AB) specimens, and to identify a possible correlation in their expression. MATERIAL AND METHODS: Immunohistochemical analysis was performed to evaluate SOX2 and BCL-2 expression in OKC (n = 20) and AB (n = 20). The immunoexpression was analyzed by a quantitative and qualitative scoring system. The comparison between the immunoexpression of SOX 2 and BCL-2 was assessed by the Mann-Whitney U-test. Spearman's correlation coefficient evaluated the correlation between SOX2 and BCL-2 expressions. RESULTS: SOX2 and BCL-2 expression was observed in all specimens of OKC in the full thickness of the epithelium lining. SOX2 immunostaining was higher in OKC, in comparison with AB samples (P<0.05). BCL-2 immunostaining between OKC and AB was not statistically significant. There was no significant correlation between SOX2 and BCL-2 in OKC and AB specimens. CONCLUSIONS: SOX2 and BCL-2 expressions in OKC may suggest their relationship with the biological behavior of this lesion, and the higher expression of SOX2 might be an upstream influence on the Hh signaling pathway.


Assuntos
Ameloblastoma , Cistos Odontogênicos , Tumores Odontogênicos , Humanos , Proteínas Proto-Oncogênicas c-bcl-2 , Fatores de Transcrição SOXB1
5.
Inflamm Res ; 68(5): 359-368, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30874869

RESUMO

OBJECTIVE: The present study aimed to evaluate and clarify how the age at which the intake of a high-fat and high-fructose diet begins can affect animals' livers. METHODS: Thirty-eight male wistar rats aged 6 and 12 weeks were fed a high-fat and high-fructose diet for 13 weeks. Inflammatory cytokines, hepatic glycogen, serum and hepatic triacylglycerol and pAkt protein content in the liver were assessed. Percentage of weight gained, and visceral adiposity were also evaluated. RESULTS: Young animal presented increased hepatic triacylglycerol and decreased glycogen, while adult animals had no significant alterations regarding its contents. IL6 and IL10 to IL6 ratio were also altered in young animals exposed to HFHF, while adult animals fed with HFHF had only increases in TNF-α. Both groups which received HFHF had increased serum triacylglycerol and visceral adiposity. However, only young animals gained more relative weight and had greater final body weight, gains which were related to alterations found in hepatic triacylglycerol and glycogen. CONCLUSION: Age of which consumption begins interferes in how the liver deals with an excess of nutrient and subsequent proinflammatory stimulation, leading to different phenotypes.


Assuntos
Envelhecimento/metabolismo , Dieta Hiperlipídica , Açúcares da Dieta/administração & dosagem , Frutose/administração & dosagem , Fígado/metabolismo , Animais , Citocinas/metabolismo , Glicogênio/metabolismo , Masculino , Ratos Wistar , Triglicerídeos/metabolismo
6.
J Phys Chem A ; 123(24): 5164-5170, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31136176

RESUMO

We have performed an experimental investigation into the interaction of vacuum-ultraviolet synchrotron radiation with pyridine molecules in the gas phase. Specifically, a double-ion chamber spectrometer was used to measure the absolute photoabsorption cross sections and the photoionization quantum yields from the ionization threshold to 21.5 eV. Moreover, photoionization and neutral-decay cross sections in absolute scale were derived from these data. In addition, the fragmentation pattern was investigated as a function of the photon energy by using a time-of-flight mass spectrometer and the photoelectron-photoion coincidence technique. Thus, the absolute partial ionization cross sections for each ionic fragment were obtained. Comparisons are made with experimental data available in the literature.

7.
Environ Geochem Health ; 41(6): 2875-2892, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31230341

RESUMO

Soils from the old Mortórios uranium mine area were studied to look for contamination, as they are close to two villages, up to 3 km away, and used for agriculture. They are mainly contaminated in U and As and constitute an ecological threat. This study attempts to outline the degree to which soils have been affected by the old mining activities through the computation of significant hot clusters, Traditional geostatistical approaches commonly use raw data (concentrations) accepting that the analyzed elements represent the soil's entirety. However, in geochemical studies these elements are just a fraction of the total soil composition. Thus, considering compositional data is pivotal. The spatial characterization, considering raw and compositional data together, allowed a broad discussion about not only the concentrations' spatial distribution, but also a better understanding on the possibility of trends of "relative enrichment" and, furthermore an insight in U and As fate. The highest proportions (compositional data) on U (up to 33%), As (up to 35%) and Th (up to 13%) are reached in the south-southeast segment. However, the highest concentrations (raw data) occur in north and northwest of the studied area, pointing out to a "relative enrichment" toward the south-southeast zone. The Mondego Sul area is mainly contaminated in U and As, but also in Co, Cu, Pb and Sb. The Mortórios area is less contaminated than the Mondego Sul area.


Assuntos
Metaloides/análise , Metais/análise , Mineração , Poluentes do Solo/análise , Solo/química , Monitoramento Ambiental/métodos , Monitoramento Ambiental/estatística & dados numéricos , Modelos Teóricos , Portugal , Urânio
8.
J Phys Chem A ; 122(51): 9755-9760, 2018 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-30520626

RESUMO

The photofragmentation dynamics of 1,1,1,2-tetrafluoroethane (R134a) with photon energies from 12 eV up to 320 eV, surrounding the C 1s edge is discussed. The ionic moieties were measured in coincidence with the ejected electrons (PEPICO mode), and detected as a function of the photon energy. Around the C K core edge, the fragmentation profiles are examined regarding the site specific excitation of the CH2FCF3 molecule. In the present case, site-selectivity is favored by the distinct chemical environments surrounding both C atoms. NEXAFS spectrum at the C 1s edge simulation has been obtained at the TDDFT level and excited state geometry optimization calculations have been performed at the inner-shell multiconfigurational self-consistent field level. Our observations indicate that the C(H2F) 1s excitation to a highly repulsive potential expels a fluorine atom leaving the heavier radical fragment C2F3H2* which relaxes to the fundamental state of the ion C2F3H2+. On the other hand, the excitation from the C(F3) 1s carbon to a repulsive state in the C-C bond, leads to a C-C bond cleavage, explaining the observed site specific fragmentation.

9.
J Chem Phys ; 149(5): 054303, 2018 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-30089389

RESUMO

Autoionization spectra of CH2Cl2 and CD2Cl2 molecules after Cl 2p excitation are studied. The two molecular and atomic Auger transitions are examined and assigned. The contribution of atomic Auger transitions is lower in the deuterated molecule. In addition, to support the presence of the ultrafast dissociation mechanism in the dichloromethane molecule, a series of high-level ab initio quantum mechanical calculations were performed at multiconfigurational self-consistent field (MCSCF) and multireference configuration interaction (MRCI) levels of theory. Minimum energy pathways for the dissociation of the dichloromethane molecule have been calculated by taking into account the spin-orbit splitting between the singlet and triplet transitions in the Cl 2p edge.

10.
J Public Health (Oxf) ; 40(3): 476-484, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28977577

RESUMO

Background: It has been reported that early menarche is associated with high blood pressure and hypertension. However, some studies have failed to observe such association. We carried out a systematic review and meta-analysis on the association of early menarche with hypertension and high blood pressure in adulthood. Methods: PUBMED, SciELO, Scopus and LILACS databases were searched. Studies that evaluated the association of early menarche with hypertension or high blood pressure, among women aged 20 years or more were included. Random effects models were used to pool the estimates. Meta-regression was used to evaluate the contribution of different co-variables to heterogeneity. Results: We identified 17 studies with 18 estimates on the association of early menarche with hypertension and high blood pressure. The odds of hypertension/high blood pressure was higher among women with early menarche [pooled (OR):1.25; 95% confidence interval (CI): 1.17-1.34; P < 0.001]. In the meta-regression analysis, studies evaluating 1500 subjects or more had a higher pooled OR [1.27; 95%CI (1.19;1.36)] than those with less participants. Although funnel plots showed some asymmetry, Egger tests were not statistically significant. Therefore, it is unlikely that the observed association was to publication bias. Conclusions: Early menarche is associated with hypertension among adult woman.


Assuntos
Hipertensão/etiologia , Menarca/fisiologia , Adolescente , Fatores Etários , Pressão Sanguínea/fisiologia , Criança , Feminino , Humanos , Fatores de Risco , Adulto Jovem
12.
Neural Plast ; 2018: 9303674, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30275823

RESUMO

Hearing aids (HAs) are an effective strategy for auditory rehabilitation in patients with peripheral hearing deficits. Yet, the neurophysiological mechanisms behind HA use are still unclear. Thus far, most studies have focused on changes in the auditory system, although it is expected that hearing deficits affect a number of cognitive systems, notably speech. In the present study, we used audiometric evaluations in 14 patients with bilateral hearing loss before and after one year of continuous HA use and functional magnetic resonance imaging (fMRI) and cortical thickness analysis in 12 and 10 of them compared with a normal hearing control group. Prior to HA fitting, fMRI activity was found reduced in the auditory and language systems and increased in visual and frontal areas, expanding to multimodal integration cortices, such as the superior temporal gyrus, intraparietal sulcus, and insula. One year after rehabilitation with HA, significant audiometric improvement was observed, especially in free-field Speech Reception Threshold (SRT) test and functional gain, a measure of HA efficiency. HA use increased fMRI activity in the auditory and language cortices and multimodal integration areas. Individual fMRI signal changes from all these areas were positively correlated with individual SRT changes. Before rehabilitation, cortical thickness was increased in parts of the prefrontal cortex, precuneus, fusiform gyrus, and middle temporal gyrus. It was reduced in the insula, supramarginal gyrus, medial temporal gyrus, occipital cortex, posterior cingulate cortex, and claustrum. After HA use, increased cortical thickness was observed in multimodal integration regions, particularly the very caudal end of the superior temporal sulcus, the angular gyrus, and the inferior parietal gyrus/superior temporal gyrus/insula. Our data provide the first evidence that one year of HA use is related to functional and anatomical brain changes, notably in auditory and language systems, extending to multimodal cortices.


Assuntos
Córtex Auditivo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Auxiliares de Audição , Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Neurossensorial/reabilitação , Adulto , Idoso , Mapeamento Encefálico , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Percepção da Fala/fisiologia
13.
Public Health ; 158: 31-36, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29533835

RESUMO

OBJECTIVE: The objective of this study was to evaluate the direct and indirect costs of tuberculosis (TB) (active and latent TB [LTB]) and HIV co-infection from the patient perspective. STUDY DESIGN: Costing study conducted alongside a pragmatic clinical trial. METHODS: The study was conducted in Brazil in a referral service for HIV/AIDS. We applied a standardised questionnaire to collect data about out-of-pocket expenses and indirect cost. The questionnaire was applied at every patient's appointment in the referral service after TB or LTB diagnosis. We followed all patients' pathways during the prediagnosis period and treatment period. For patients on sickness benefit due to TB/HIV, income loss was calculated as the difference between an employee's wages forgone and the sickness benefit received. The monetary value of the time loss was calculated based on the Brazilian minimum wage/2015. RESULTS: Among 239 people living with HIV recruited in the first year of the trial, 31 patients were included into the costing study, 26 patients who were diagnosed and treated for TB/HIV and five patients who were diagnosed and treated for LTB/HIV. TB/HIV patients incurred higher total costs than LTB/HIV (US$ 1,429 vs US$ 166). The main cost component for TB/HIV was indirect costs, especially income loss (US$ 749). CONCLUSIONS: Public health policies may address ways to prevent high patients' costs through the introduction of more accurate algorithms for TB diagnosis to prevent delays in the diagnosis and treatment.


Assuntos
Efeitos Psicossociais da Doença , Infecções por HIV/epidemiologia , Gastos em Saúde/estatística & dados numéricos , Tuberculose Latente/economia , Tuberculose/economia , Adolescente , Adulto , Brasil/epidemiologia , Coinfecção , Custos e Análise de Custo , Feminino , Humanos , Tuberculose Latente/terapia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Tuberculose/terapia , Adulto Jovem
14.
J Fish Biol ; 92(6): 1866-1887, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29624681

RESUMO

Astyanax anai, a new species of characid fish, is described from the Sixaola River basin, eastern Costa Rica-western Panama, Central America. The new species can be distinguished from all other congeners by the following combination of characters: premaxillary teeth 4-5 at the inner series and 4-6 at the outer series; maxillary teeth tricuspid, 2-4; predorsal scale series irregular and incomplete, with an unscaled space behind tip of supraoccipital process and 12-14 scales; lateral line scales 34-39; humeral region with a conspicuous black and rounded to horizontally ovate spot and two diffuse brown and vertically elongate bars (the first through the rounded to horizontally ovate spot, the second 2-4 scales behind the first); body depth 36·6-42·3% of standard length (LS ); midlateral stripe formed by a series of 10-14 anteriorly-directed dermal herringbone, or chevron-shaped, marks, most apparent in juveniles and in preserved specimens, extending above the lateral line from the black humeral spot or just behind it (from the second vertical bar) to the caudal peduncle; scale rows from lateral line to base of first dorsal-fin ray 8-9; scale rows from lateral line to base of pelvic fin 7-8; pre-anal distance 53·9-61·9% of LS ; total anal-fin elements 29-33; caudal spot elongated, rhomboid or rectangular, with its anterior margin surpassing the middle of the caudal peduncle, usually reaching the anal-fin insertion, posteriorly covering 4-7 principal caudal-fin rays and not extending onto the ventral and dorsal margins of the caudal peduncle, covering 3-5 horizontal scale rows. In order to test the phylogenetic relationships of the new taxon in relation to the other North and Central American species of the genus, a new phylogenetic hypothesis based on a reanalysis of the morphological matrix by Schmitter-Soto (2016) is proposed. A key to the lower Central American (southern Nicaragua to eastern Panama) species of Astyanax is also provided.


Assuntos
Characidae/anatomia & histologia , Characidae/classificação , Animais , Biodiversidade , Caraciformes , Costa Rica , Feminino , Masculino , Panamá , Filogenia , Rios
15.
Environ Geochem Health ; 40(1): 521-542, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28343275

RESUMO

The Alto da Várzea radium mine (AV) exploited ore and U-bearing minerals, such as autunite and torbernite. The mine was exploited underground from 1911 to 1922, closed in 1946 without restoration, and actually a commercial area is deployed. Stream sediments, soils and water samples were collected between 2008 and 2009. Stream sediments are mainly contaminated in As, Th, U and W, which is related to the AV radium mine. The PTEs, As, Co, Cr, Sr, Th, U, W, Zn, and electrical conductivity reached the highest values in soils collected inside the mine influence. Soils are contaminated with As and U and must not be used for any purpose. Most waters have pH values ranging from 4.3 to 6.8 and are poorly mineralized (EC = 41-186 µS/cm; TDS = 33-172 mg/L). Groundwater contains the highest Cu, Cr and Pb contents. Arsenic occurs predominantly as H2(AsO4)- and H(AsO4)2-. Waters are saturated in goethite, haematite and some of them also in lepidocrocite and ferrihydrite, which adsorbs As (V). Lead is divalent in waters collected during the warm season, being mobile in these waters. Thorium occurs mainly as Th(OH)3(CO3)-, Th(OH)2(CO3) and Th(OH)2(CO3) 22- , which increase water Th contents. Uranium occurs predominantly as UO2CO3, but CaUO2(CO3) 32- and CaUO2(CO3)3 also occur, decreasing its mobility in water. The waters are contaminated in NO2-, Mn, Cu, As, Pb and U and must not be used for human consumption and in agricultural activities. The water contamination is mainly associated with the old radium mine and human activities. A restoration of the mining area with PTE monitoring is necessary to avoid a public hazard.


Assuntos
Sedimentos Geológicos/química , Mineração , Rádio (Elemento)/análise , Solo/química , Poluentes Radioativos da Água/análise , Arsênio/análise , Monitoramento Ambiental/métodos , Metais/análise , Portugal , Rios
16.
Int J Obes (Lond) ; 41(4): 533-541, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28028320

RESUMO

BACKGROUND/OBJECTIVES: The role of Protein Intake (PI) at preschool age on later adiposity is understudied, and prospective studies also examining Dietary Glycemic Load (GL) are lacking. The current study evaluated the association of PI and GL at 4 years with adiposity and Fasting Serum Insulin (FSI) 3 years later, and examined the possible interaction between PI and GL on these associations, by sex. DESIGN: This prospective study included 1999 singleton children enrolled in the population-based birth cohort, Generation XXI (Porto, Portugal, 2005-2006). Diet at 4 years was assessed by 3-days food diaries. Energy-adjusted PI and GL (g per day) were converted into sex-specific tertiles (T). At 7 years, Body Mass Index (BMI) z-scores were defined according to the World Health Organization. Sample's sex-specific z-scores were computed for Fat Mass Index (FMI), Waist-to-Height ratio (W/Ht) and FSI. Associations were estimated by linear regression coefficients (ß) and 95% confidence intervals (95% CI). RESULTS: After adjustment for confounders, PI was positively associated with BMI in girls (T2 vs T1: ß=0.187; 95% CI: 0.015, 0.359) and boys (T3 vs T1: ß=0.205; 95% CI: 0.003, 0.406), being associated with FSI only in boys (T3 vs T1: ß=0.207; 95% CI: 0.011, 0.404; P-interaction=0.026). Also, GL was associated with BMI only in boys (T3 vs T1: ß=0.362; 95% CI: 0.031, 0.693; P-interaction=0.006), in whom significant interactions between PI and GL were found on the association with FMI (P=0.019) and W/Ht (P=0.039). Boys within the third T of both PI and GL at 4 years had higher FMI (ß=0.505; 95% CI: 0.085, 0.925) and W/Ht (ß=0.428; 95% CI: 0.022, 0.834) at 7 years. CONCLUSIONS: In both girls and boys, PI at preschool age is positively associated with later BMI, being positively associated with FSI only in boys. Dietary GL is associated with adiposity only in boys, in whom it seems to interact with PI enhancing increased adiposity.


Assuntos
Adiposidade/fisiologia , Glicemia/metabolismo , Fenômenos Fisiológicos da Nutrição Infantil/fisiologia , Ingestão de Energia/fisiologia , Carga Glicêmica/fisiologia , Insulinas/sangue , Índice de Massa Corporal , Criança , Pré-Escolar , Proteínas Alimentares , Feminino , Índice Glicêmico/fisiologia , Humanos , Masculino , Inquéritos Nutricionais , Portugal/epidemiologia , Estudos Prospectivos
17.
Int J Obes (Lond) ; 41(2): 268-278, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27733761

RESUMO

OBJECTIVE: To investigate whether the Cdc2-like kinase 2 (CLK2) is expressed in hypothalamic neurons and if it is, whether the hypothalamic CLK2 has a role in the regulation of energy balance. SUBJECTS: Swiss mice on chow or high-fat diet (HFD) and db/db mice on chow diet were used to address the role of CLK2 in the hypothalamus. RESULTS: Hypothalamic CLK2Thr343 phosphorylation, which induces CLK2 activity, is regulated in vivo by refeeding, insulin and leptin, in a PI3K (phosphoinositide 3-kinase)-dependent manner. The reduction of CLK2 expression in the hypothalamus, by chronic pharmacological inhibition with TG003 or by chronic knockdown with small interfering RNA was sufficient to abolish the anorexigenic effect of insulin and leptin, to increase body weight, fat mass, food intake and to decrease energy expenditure in mice on chow. In contrast, CLK2Thr343 phosphorylation in the hypothalamus in response to insulin, leptin or refeeding was impaired in mice on HFD or in db/db mice. Chronic CLK2 inhibition in the hypothalamus was associated with a slight increase in the fasting blood glucose levels, reduction in PEPCK (phosphoenolpyruvate carboxykinase) expression in the liver and enhanced glucose production from pyruvate, suggesting a regulation of hepatic glucose production. Further, overexpressing CLK2 in the mediobasal hypothalami of mice on HFD or in db/db mice by adenovirus partially reversed the obese phenotype. CONCLUSIONS: Thus, our results suggest that protein CLK2 integrates some important hypothalamic pathways, and may be a promising molecule for new therapeutic approaches for obesity and diabetes.


Assuntos
Quinases relacionadas a CDC2 e CDC28/metabolismo , Diabetes Mellitus Tipo 2/patologia , Metabolismo Energético/fisiologia , Hipotálamo/metabolismo , Resistência à Insulina/fisiologia , Obesidade/patologia , Fosforilação/fisiologia , Animais , Quinases relacionadas a CDC2 e CDC28/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Ingestão de Alimentos , Metabolismo Energético/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Metabolismo dos Lipídeos , Masculino , Camundongos , Transdução de Sinais
18.
J Phys Chem A ; 121(22): 4233-4241, 2017 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-28514147

RESUMO

The dynamics of the photofragmentation pathways of tetrachloroethylene with photon energies from 15 up to 250 eV encompassing the Cl 2p edge is presented. In order to distinguish the fragmentation channels, the ionic fragments were separated according to their mass-to-charge ratio, measured in coincidence with the photoelectrons, and collected as a function of the incident photon energy. Distinct minima or maxima are found in the partial ion yield in the region between 40 and 50 eV. These features are believed to be associated with the Cooper minimum which results from a molecular orbital with a strong atomic 3p subshell character. In the shallow core region, some fragmentation patterns are considered in terms of fast fragmentation of the C2Cl4 molecule, despite the heavy mass of its fragments. In the present case, the fast fragmentation is favored by the very strong antibonding character of the LUMO, understandable in the frame of the core equivalent model for halogen-containing molecules. In addition, ab initio calculations were performed to obtain states at the Cl 2p edge. Singlet and triplet states at the Cl 2p edge of the C2Cl4 molecule, corresponding to the Cl(2p → 9b1u*) and Cl(2p → 8b2u*) transitions, were calculated in order to form a basis set of molecular states from which the spin-orbit splitting can be inferred. Multiconfigurational self-consistent field (MCSCF) calculation followed by multireference configuration interaction (MRCI) was the method chosen to establish a set of singlet and triplet states at the 2p excitation edge in addition to the ground state.

19.
J Chem Phys ; 146(21): 214306, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-28595419

RESUMO

The fragmentation of the tetrachloromethane molecule following core-shell photoexcitation and photoionization in the neighborhood of the chlorine K-edge has been studied by using time-of-flight mass spectroscopy and monochromatic synchrotron radiation. Branching ratios for ionic dissociation were derived for all the detected ions, which are informative of the decay dynamics and photofragmentation patterns of the core-excited species. In addition, the absorption yield has been measured with a new assignment of the spectral features. The structure that appears above the Cl 1s ionization potential in the photoionization spectrum has been ascribed to the existing connection with electron-CCl4 scattering through experimental data and calculations for low-energy electron-molecule cross sections. In addition, the production of the doubly ionized Cl fragment, Cl2+, as a function of the photon energy has been analysed in the terms of a simple and an appealing physical picture, the half-collision model.

20.
J Hum Nutr Diet ; 30(2): 193-202, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27611775

RESUMO

BACKGROUND: The association between obesity during adolescence and the increased risk of cardiometabolic diseases indicates the need to identify reproducible and cost effective methods for identifying individuals who are at increased risk of developing diseases. The present cross-sectional study investigated the occurrence of metabolic consequences of obesity in adolescents and the use of adiposity indicators as predictors of cardiometabolic risk. METHODS: A fasting blood sample was taken in 93 pubertal obese adolescents aged 13-18 years old (39 males, 54 females) for the assessment of cardiometabolic risk markers (glucose, lipid profiles, insulin resistence, and inflammatory and endothelial dysfunction markers). Together with anthropometry, total fat mass and lean mass were determined by dual-energy X-ray absorptiometry (DXA). RESULTS: The prevalence of dyslipidaemia and disorders in glucose metabolism are noticeably higher in the present study. There was no correlation between the percentage of body fat according to DXA and most indicators of adiposity. For boys, the arm circumference values predicted the increase in fasting insulin (r² = 0.200), homeostasis model assessment of insulin resistance (r² = 0.267) and cardiometabolic risk score (r² = 0.338). The percentage of body fat according to DXA predicted the inflammation score (r² = 0.172). For girls, body mass index was the parameter that best described the variability of fasting insulin (r² = 0.079) and inflammation score (r² = 0.263). The waist-to-stature ratio was able to predict the triglyceride values (r² = 0.090). CONCLUSIONS: Anthropometric measures of adiposity, such a body mass index, waist-to-stature ratio, arm circumference and waist circumference,should be considered in the clinical evaluation of obese adolescents.


Assuntos
Adiposidade , Composição Corporal , Doenças Cardiovasculares/sangue , Síndrome Metabólica/sangue , Obesidade Infantil/sangue , Absorciometria de Fóton , Adolescente , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/epidemiologia , Obesidade Infantil/complicações , Fatores de Risco , Triglicerídeos/sangue , Circunferência da Cintura
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