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The digitalization and adoption of advanced technologies in supply chain and logistics not only change the business model but also transfer logistics infrastructure to a service-oriented architecture and introduce new avenues concerning supply chain 4.0 (SC4.0). Sharing logistic assets between various businesses leads to improving logistics work, enhancing work productivity, and reducing logistics expenses and environmental impact. However, due to the lack of a secure, trustworthy, and open sharing platform, the companies are not willing to rely on sharing economics. Aiming to improve trust-ability, openness, and interoperability in the SC4.0, this paper presents a blockchain-enabled hyperconnected logistics platform. Firstly, the Open Logistic platform (OL) is proposed, and the key characteristics of this platform are explained. Secondly, the concept of proof of delivery (PoD) based on smart contracts is defined and developed to explore its rule-based management and control among the dynamic assets sharing. Thirdly, the Blockchain asset sharing service is designed and discussed in the context of asset sharing. Fourthly to evaluate the feasibility of the proposed platform, a simulation environment is developed, and OL is implemented based on the case study.
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Blockchain , Registros Eletrônicos de Saúde , Tecnologia , ConfiançaRESUMO
Aim: Elabela (ELA) is a peptide of the apelinergic system and is known to play a role in endothelial homeostasis and vascular pathobiology. In this study, the relationship between carotid artery stenosis, which is the main culprit, and ELA level in patients with non-cardioembolic ischemic stroke was investigated. Materials & methods: Cross-sectional observation included two groups of 40 patients with critical carotid artery stenosis and 40 patients with age-sex matched noncritical carotid artery stenosis. Results: ELA levels were significantly higher in the noncritical stenosis group. ELA had a significantly moderate negative correlation with the carotid score (r = -0.334, p = 0.003), maximal carotid plaque length (r = -0.413, p < 0.001) and degree of stenosis (r = -0.397, p < 0.001). Conclusions: There is a significant inverse correlation between critical carotid artery disease and ELA level in patients with non-cardioembolic ischemic stroke.
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Estenose das Carótidas , AVC Isquêmico , Acidente Vascular Cerebral , Estenose das Carótidas/complicações , Constrição Patológica/complicações , Estudos Transversais , Humanos , Fatores de Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
The purpose of this pilot study was to investigate the effects of the transfusion of one erythrocyte concentrate on the number of circulating red blood cell extracellular vesicles (RBC-EVs) and their clearance time. Six, healthy volunteers donated their blood and were transfused with their RBC concentrate after 35-36 days of storage. One K2 EDTA and one serum sample were collected before donation, at four timepoints after donation and at another six timepoints after transfusion. RBC-EVs were analyzed on a Cytek Aurora flow cytometer. A highly significant increase (p < 0.001) of RBC-EVs from an average of 60.1 ± 19.8 (103 /µL) at baseline to 179.3 ± 84.7 (103 /µL) in the first 1-3 h after transfusion could be observed. Individual differences in the response to transfusion became apparent with one volunteer showing no increase and another an increased concentration at one timepoint after donation due to an influenza infection. We concluded that in an individualized passport approach, increased RBC-EVs might be considered as additional evidence when interpreting suspicious Athletes Biological Passport (ABPs) but for this additional research related to sample collection and transport processes as well as method development and harmonization would be necessary.
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Dopagem Esportivo , Vesículas Extracelulares , Humanos , Projetos Piloto , Eritrócitos , Transfusão de SangueRESUMO
Cystic echinococcosis (CE) is a zoonotic disease caused by a complex of species known as Echinococcus granulosus sensu lato. CE is endemic in Argentina, Chile, Peru, Uruguay and the South part of Brazil. In contrast, little is known regarding the presence of CE in Bolivia. In this study, 35 cysts isolated from livestock (mostly from the Department of La Paz) and 3 from humans (La Paz, Oruro and Potosi) were genetically characterized analysing the sequence of the cox1 gene (1609 bp). In total, 30 cysts (from La Paz, Cochabamba and Beni) were characterized as E. granulosus sensu stricto (3 fertile and 4 non-fertile cysts from sheep, 8 fertile and 12 non-fertile cysts from cattle and 3 fertile cysts from humans). A detailed analysis of the cox1 haplotypes of E. granulosus s.s. is included. Echinococcus ortleppi (G5) was found in 5 fertile cysts from cattle (from La Paz and Cochabamba). Echinococcus intermedius (G7) was identified in 3 fertile cysts from pigs (from Santa Cruz). Additionally, E. granulosus s.s. was detected in 4 dog faecal samples, while E. ortleppi was present in other two dog faecal samples. The implications of these preliminary results in the future implementation of control measures are discussed.
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Doenças dos Bovinos/parasitologia , Doenças do Cão/parasitologia , Equinococose/parasitologia , Equinococose/veterinária , Echinococcus/isolamento & purificação , Doenças dos Ovinos/parasitologia , Doenças dos Suínos/parasitologia , Animais , Bolívia , Bovinos , Cães , Fezes/parasitologia , Humanos , Ovinos , Carneiro Doméstico , Sus scrofa , SuínosRESUMO
Although continuous researches are going on for the discovery of new chemotherapeutic agents, resistance to these anticancer agents has made it really difficult to reach the fruitful results. There are many causes for this resistance that are being studied by the researchers across the world, but still, success is far because there are several factors that are going along unattended or have been studied less. Drug-metabolizing enzymes (DMEs) are one of these factors, on which less study has been conducted. DMEs include Phase I and Phase II enzymes. Cytochrome P450s (CYPs) are major Phase I enzymes while glutathione-S-transferases (GSTs), UDP-glucuronosyltransferases (UGTs), dihydropyrimidine dehydrogenases are the major enzymes belonging to the Phase II enzymes. These enzymes play an important role in detoxification of the xenobiotics as well as the metabolism of drugs, depending upon the tissue in which they are expressed. When present in tumorous tissues, they cause resistance by metabolizing the drugs and rendering them inactive. In this review, the role of these various enzymes in anticancer drug metabolism and the possibilities for overcoming the resistance have been discussed.
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Antineoplásicos/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias/tratamento farmacológico , Catálise , Sistema Enzimático do Citocromo P-450/fisiologia , Di-Hidrouracila Desidrogenase (NADP)/fisiologia , Glucuronosiltransferase/fisiologia , Glutationa Transferase/fisiologia , Humanos , Inativação MetabólicaRESUMO
The polypyrrole/polyaniline-based electrode (Ppy/Pan/TiO2/rGO) was fabricated via the electrophoretic deposition technique on fluorine-doped tin oxide (FTO)-coated glass. Physico-electrochemical adsorption/desorption of epigallocatechin gallate (EgCg) as an electroactive species was enhanced by the fabricated electrode compared to the electroless technique extraction using the same electrode. EgCg was electrochemically extracted using chronoamperometry by electrophoretically deposited Ppy/Pan/TiO2/rGO film. Isolated EgCg was qualified and quantified by the voltammetry and high-performance liquid chromatography (HPLC) techniques. It was found that the extracted EgCg values were 3.38 and 0.72 ppm from a 10 ppm prepared solution using the electrochemically and physically based techniques, respectively. Morphology/elemental analysis and crystal structure of the prepared electrodes were characterized by field emission scanning electron microscopy/energy-dispersive X-ray (FESEM/EDX) and X-ray diffraction (XRD), respectively. The conductivity of the fabricated electrode was investigated by electrochemical impedance spectroscopy (EIS) and was calculated as 1.124 S/cm for the electrophoretically deposited electrodes (EPD).
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BACKGROUND & OBJECTIVES: In India, kala-azar surveillance is weak and no public-private partnership exists for disease containment. Estimate of disease burden is not reliably available and still cases are going to private providers for the treatment. The present study aimed to assess the magnitude of kala-azar cases actually detected and managed at private set-up and unreported to existing health management information system. METHODS: Institution based cross-sectional prospective pilot study was conducted. List of facilities was created with the help of key informants. The information about incidence of kala-azar cases were captured on monthly basis from July 2010 to June 2011. Rapid diagnostic strip test (rk-39) or bone marrow/splenic puncture were applied as laboratory methods for the diagnosis of kala-azar. Descriptive statistics as well as chi-square test for comparison between proportions was conducted. RESULTS: Overall availability of private practitioners (PPs) was 4.59/1,00,000 population and maximum PPs (46; 93.9%) were from qualified category. The median years of medical practice was 25 yr (inter quartile-range [18, 28]). Interestingly, only a small proportion (240; 19%) of cases was managed by PPs. Amongst the PPs, only low proportion (32; 18.2%) managed >2 cases per month. The mean number of kala-azar suspects and cases identified varied significantly between different PPs' professions with p <0.048 and p <0.032, respectively. A highly significant difference (p <0.0001) was observed for kala-azar case load between qualified and unqualified practitioners. A small proportion (38; 15.8%) of kala-azar cases was not present in the public health system record. INTERPRETATION & CONCLUSION: Still sizeable proportions of cases are going to PPs and unrecorded into government surveillance system. A mechanism need to be devised to involve at least qualified PPs in order to reduce treatment delay and increase case detection in the region.
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Leishmaniose Visceral/epidemiologia , Adolescente , Adulto , Estudos Transversais , Erradicação de Doenças , Feminino , Humanos , Incidência , Índia/epidemiologia , Leishmaniose Visceral/prevenção & controle , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Adulto JovemRESUMO
In the study, 130 honey bee colonies fed with different levels (5, 20, and 100 liters/colony) of various industrial commercial sugars, including High-Fructose Corn 85 (Fructose-85), High-Fructose Corn 55 (Fructose-55), Glucose Monohydrate (Glucose), Bee feed, and Sucrose syrups, for 2 mo were compared with colonies fed with no sugar (control) in terms of their colony development of worker bee population, hive weight, wax production, wintering ability, foraging behavior, and lifespan of worker bee. Utilization of industrial sugars by honey bee colonies showed differences in terms of colony performance and behavior parameters. Honey bees did not use Glucose heavily, resulting in 4% increase in worker bee loss in winter and 46% decrease in marked worker bee numbers over time when compared to the control. Sucrose syrup had a positive effect on wintering ability, wax production, and hive weight. While Sucrose had a positive effect (3-4%) on wintering ability, the 100 liters/colony sugar syrups of all other sugars had negative effects (6-15%). Sugars containing high levels of monosaccharide were not used effectively by honey bee colonies, whereas the sugars containing fructose and glucose at rates of 40 and 30% (Bee feed and Fructose-55), were utilized effectively. The lifespan of worker bees decreased over time in the 100 liters/colony of all sugars syrup. In conclusion, except Glucose, other industrial sugars can be used for promoting colonies at the beginning of the season (in spring). Industrial sugars except sucrose should not be used in order to meet carbohydrate needs of the colonies in winter.
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Criação de Abelhas , Abelhas/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Açúcares da Dieta/administração & dosagem , Longevidade/efeitos dos fármacos , Animais , Estações do AnoRESUMO
The urinary 'steroid profile' in doping control analysis is a powerful tool aimed at detecting intra-individual deviations related to the abuse of endogenous steroids. Factors altering the steroid profile include, among others, the excessive fluid intake leading to low endogenous steroids concentrations compared to an individual's normal values. Cases report the use of hyperhydration by athletes as a masking method during anti-doping urine sample collection. Seven healthy physically active non-smoking Caucasian males were examined for a 72-hour period using water and a commercial sports drink as hyperhydration agents (20 mL/kg body weight). Urine samples were collected and analyzed according to World Anti-Doping Agency (WADA) technical documents. Although, significant differences were observed on the endogenous steroid concentrations under the studied hyperhydration conditions, specific gravity adjustment based on a reference value of 1.020 can eliminate the dilution induced effect. Adjustment methods based on creatinine and urinary flow rate were also examined; however, specific gravity was the optimum method in terms of effectiveness to adjust concentrations close to the baseline steroid profile and practicability. No significant effect on the urinary steroid ratios was observed with variability values within 30% of the mean for the majority of data. Furthermore, no masking on the detection ability of endogenous steroids was observed due to hyperhydration. It can be concluded that any deviation on the endogenous steroid concentrations due to excessive fluid intake can be compensated by the specific gravity adjustment and therefore, hyperhydration is not effective as a masking method on the detection of the abuse of endogenous steroids.
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Atletas , Dopagem Esportivo/métodos , Ingestão de Líquidos/fisiologia , Esteroides/urina , Adulto , Algoritmos , Bebidas , Voluntários Saudáveis , Humanos , Indicadores e Reagentes , Masculino , Padrões de Referência , Gravidade Específica , Detecção do Abuso de Substâncias/métodos , Adulto JovemRESUMO
Although the precise host-defence mechanisms are not completely understood, T-cell-mediated immune responses are believed to play a pivotal role in controlling parasite infection. In this study, the potential HLA*A2 restricted peptides were predicted and the ability of peptides to bind HLA-A*02 was confirmed by a MHC stabilization assay. Two of the peptides tested stabilized HLA-A*02: (a) LLATTVSGL (P1) and (b) LMTNGPLEV (P3). The potential of the peptides to generate protective immune response was evaluated in patients with treated visceral leishmaniasis as well as in healthy control subjects. Our data suggest that CD8+ T-cell proliferation against the selected peptide was significantly higher compared to unstimulated culture conditions. The stimulation of peripheral blood mononuclear cells with epitopes individually or as a cocktail upregulated IFN-γ production, which indicates its pivotal role in protective immune response. The IFN-γ production was mainly in a CD8+ T-cells-dependent manner, which suggested that these epitopes had an immunoprophylactic potential in a MHC class I-dependent manner. Moreover, no role of the CD3+ T cell was observed in the IL-10 production against the selected peptides, and no role was found in disease pathogenesis. Further studies on the role of these synthetic peptides may contribute significantly to developing a polytope vaccine idea towards leishmaniasis.
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Cisteína Proteases/imunologia , Epitopos de Linfócito T/imunologia , Antígeno HLA-A2/imunologia , Leishmania/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/imunologia , Adolescente , Adulto , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Cisteína Proteases/química , Epitopos de Linfócito T/química , Feminino , Antígeno HLA-A2/química , Humanos , Imunogenicidade da Vacina , Interleucina-10/metabolismo , Leishmania/enzimologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Leucócitos Mononucleares/imunologia , Masculino , Modelos Moleculares , Peptídeos/síntese química , Peptídeos/química , Peptídeos/imunologia , Adulto JovemAssuntos
Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Paromomicina/administração & dosagem , Fosforilcolina/análogos & derivados , Administração Oral , Adulto , Antiprotozoários/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Injeções Intramusculares , Leishmaniose Visceral/tratamento farmacológico , Masculino , Paromomicina/efeitos adversos , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Projetos Piloto , Resultado do TratamentoRESUMO
OBJECTIVE: To compare, through cone-beam computed tomography (CBCT), the root resorption and treatment efficiency of two different mini-implant-assisted modalities in intruding the maxillary incisors. MATERIALS AND METHODS: Thirty-two adults who had deep bite and elongated maxillary incisors were randomly allocated to two groups: anterior mini-implant group (AMG) and posterior mini-implant group (PMG). In the AMG, approximately 40 g of force was applied per side with elastic chains from mini-implants placed between the lateral incisors and canines and in the PMG, with beta-titanium wires from mini-implants placed between the second premolars and first molars. This study was conducted on CBCT scans taken before intrusion and after 4 months of intrusion. Data were analyzed by means of a paired t-test, independent t-test, and Pearson's correlation test. RESULTS: One patient was excluded from the AMG due to mini-implant loosening. While the incisors showed a significant reduction in length and volume, this amount was greater in the AMG, especially in the central incisors (P < .05). Together with the mean intrusion rates of 0.62 and 0.39 mm/mo in the AMG and PMG respectively, the center of resistance of the incisors showed distal movement with labial tipping; these changes were greater in the PMG (P < .001). Volumetric root resorption was correlated with the amount of intrusion (P < .05). CONCLUSIONS: Intrusion anchoring from posterior mini-implants is preferred in cases of upright incisors, as the use of such mechanics directs the roots into the spongiosa where they undergo less root resorption and more labial tipping.
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Incisivo , Procedimentos de Ancoragem Ortodôntica , Reabsorção da Raiz , Tomografia Computadorizada de Feixe Cônico , Humanos , Maxila , Distribuição Aleatória , Técnicas de Movimentação DentáriaRESUMO
This study investigated the effect of Ramadan on the haematological and steroid module of the Athletes Biological Passport (ABP) of the World Anti-Doping Agency (WADA). Nine healthy physically active subjects were tested in the morning and afternoon for two days before and three days during Ramadan. Sample collection and all analyses were performed according to WADA technical documents. Although there were significant changes in the haemoglobin concentration during Ramadan, especially during the first fasting week, none of the subjects in this study exceeded the individually calculated thresholds of the ABP. No significant effects on testosterone/epitestosterone (T/E) ratio were observed but only the afternoon specific gravity (SG) of the urine was elevated. Thus, when urinary steroid concentrations are required, SG corrections need to be performed. The haematological and the steroid module of the ABP can be reliably applied during Ramadan as the observed changes are only marginal.
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Atletas , Dopagem Esportivo , Epitestosterona/urina , Jejum , Hemoglobinas/metabolismo , Islamismo , Substâncias para Melhoria do Desempenho , Detecção do Abuso de Substâncias/métodos , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Jejum/sangue , Jejum/urina , Humanos , Masculino , Substâncias para Melhoria do Desempenho/sangue , Substâncias para Melhoria do Desempenho/urina , Projetos Piloto , Valor Preditivo dos Testes , Contagem de Reticulócitos , Gravidade Específica , Fatores de Tempo , Urinálise , Adulto JovemRESUMO
In the present study, one hundred pure and adulterated honey samples obtained from feeding honeybee colonies with different levels (5, 20 and 100 L/colony) of various commercial sugar syrups including High Fructose Corn Syrup 85 (HFCS-85), High Fructose Corn Syrup 55 (HFCS-55), Bee Feeding Syrup (BFS), Glucose Monohydrate Sugar (GMS) and Sucrose Sugar (SS) were evaluated in terms of the δ(13)C value of honey and its protein, difference between the δ(13)C value of protein and honey (Δδ(13)C), and C4% sugar ratio. Sugar type, sugar level and the sugar type*sugar level interaction were found to be significant (P<0.001) regarding the evaluated characteristics. Adulterations could not be detected in the 5L/colony syrup level of all sugar types when the δ(13)C value of honey, Δδ(13)C (protein-honey), and C4% sugar ratio were used as criteria according to the AOAC standards. However, it was possible to detect the adulteration by using the same criteria in the honeys taken from the 20 and 100 L/colony of HFCS-85 and the 100L/colony of HFCS-55. Adulteration at low syrup level (20 L/colony) was more easily detected when the fructose content of HFCS syrup increased. As a result, the official methods (AOAC, 978.17, 1995; AOAC, 991.41, 1995; AOAC 998.12, 2005) and Internal Standard Carbon Isotope Ratio Analysis could not efficiently detect the indirect adulteration of honey obtained by feeding the bee colonies with the syrups produced from C3 plants such as sugar beet (Beta vulgaris) and wheat (Triticium vulgare). For this reason, it is strongly needed to develop novel methods and standards that can detect the presence and the level of indirect adulterations.
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Criação de Abelhas , Abelhas/metabolismo , Metabolismo dos Carboidratos , Isótopos de Carbono/análise , Contaminação de Alimentos/análise , Mel/análise , Animais , Carboidratos/química , Análise DiscriminanteRESUMO
The Harran Plain is located in the southeastern part of Turkey and has recently been developed for irrigation agriculture. It already faces soil salinity problems causing major yield losses. Management of the problem is hindered by the lack of information on the extent and geography of the salinization problem. A survey was carried out to delineate the spatial distribution of salt-affected areas by randomly selecting 140 locations that were sampled at two depths (0 to 30 and 30 to 60 cm) and analyzed for soil salinity variables: soil electrical conductivity (EC), soluble cations (Ca(2+,) Mg(2+), Na(+), and K(+)), soluble anions (SO (4) (2-) , Cl(-)), exchangeable Na(+) (me 100 g(-1)) and exchangeable sodium percentage. Terrain attributes (slope, topographical wetness index) were extracted from the digital elevation model of the study area. Variogram analyses after log transformation and ordinary kriging (OK) were applied to map spatial patterns of soil salinity variables. Multivariate geostatistical methods-regression kriging (RK) and kriging with external drift (KED)-were used using elevation and soil electrical conductivity data as covariates. Performances of the three estimation methods (OK, RK, and KED) were compared using independent validation samples randomly selected from the main dataset. Soils were categorized into salinity classes using disjunctive kriging (DK) and ArcGIS, and classification accuracy was tested using the kappa statistic. Results showed that soil salinity variables all have skewed distribution and are poorly correlated with terrain indices but have strong correlations among each other. Up to 65 % improvement was obtained in the estimations of soil salinity variables using hybrid methods over OK with the best estimations obtained with RK using EC(0-30) as covariate. DK-ArcGIS successfully classified soil samples into different salinity groups with overall accuracy of 75 % and kappa of 0.55 (p < 0.001).
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Monitoramento Ambiental/métodos , Salinidade , Poluentes do Solo/análise , Solo/química , Agricultura/estatística & dados numéricos , Análise Espacial , TurquiaRESUMO
AIMS/HYPOTHESIS: Calorie restriction is an essential component in the treatment of obesity and associated diseases. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) act as natural hypolipidaemics, reduce the risk of cardiovascular disease and could prevent the development of obesity and insulin resistance. We aimed to characterise the effectiveness and underlying mechanisms of the combination treatment with LC n-3 PUFA and 10% calorie restriction in the prevention of obesity and associated disorders in mice. METHODS: Male mice (C57BL/6J) were habituated to a corn-oil-based high-fat diet (cHF) for 2 weeks and then randomly assigned to various dietary treatments for 5 weeks or 15 weeks: (1) cHF, ad libitum; (2) cHF with LC n-3 PUFA concentrate replacing 15% (wt/wt) of dietary lipids (cHF + F), ad libitum; (3) cHF with calorie restriction (CR; cHF + CR); and (4) cHF + F + CR. Mice fed a chow diet were also studied. RESULTS: We show that white adipose tissue plays an active role in the amelioration of obesity and the improvement of glucose homeostasis by combining LC n-3 PUFA intake and calorie restriction in cHF-fed mice. Specifically in the epididymal fat in the abdomen, but not in other fat depots, synergistic induction of mitochondrial oxidative capacity and lipid catabolism was observed, resulting in increased oxidation of metabolic fuels in the absence of mitochondrial uncoupling, while low-grade inflammation was suppressed, reflecting changes in tissue levels of anti-inflammatory lipid mediators, namely 15-deoxy-Δ(12,15)-prostaglandin J(2) and protectin D1. CONCLUSIONS/INTERPRETATION: White adipose tissue metabolism linked to its inflammatory status in obesity could be modulated by combination treatment using calorie restriction and dietary LC n-3 PUFA to improve therapeutic strategies for metabolic syndrome.
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Tecido Adiposo Branco/metabolismo , Restrição Calórica , Ácidos Graxos Ômega-3/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica , Gorduras na Dieta/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Metabolismo Energético/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Obesos , Prostaglandina D2/análogos & derivados , Prostaglandina D2/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
As one of the most studied protein hormones, insulin as well as its receptor have been known to play key roles in a variety of important biological processes. Detection of insulin and its receptor in the central nervous system (CNS) has led to a rapidly growing interest in the central effects of insulin. Insulin and its receptor are located in the specific area of the CNS with a diversity of region-specific functions different from its direct carbohydrate homeostasis in the periphery. The high density of insulin/insulin receptor in brain areas such as the hippocampus and cerebral cortex have shown to play an important role in higher cognitive functions, suggesting that insulin might be involved in the modulation of memory. Previous studies have offered controversial results regarding the effects of insulin on various types of memory. The aim of the present study is to determine whether intracerebroventricular (ICV) administration of insulin improves the water maze performance of rats. The experimental groups had pretraining insulin infusion (2, 4, 8, 16, and 32 mu) into the third ventricle, and then they were compared with a sham (saline) group. Insulin treatment caused an enhancing effect on spatial memory in a dose-dependent manner. The low doses (2, 4, and 8 mu) of insulin had no significant effect on the water maze achievement of rats, whereas higher doses (16 and 32 mu) significantly improved the rats' performance. These results suggest that ICV administration of insulin may result in a dose-dependent improvement of memory function in rats.
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Insulina/administração & dosagem , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Comportamento Espacial/efeitos dos fármacos , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Cateteres de Demora , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Masculino , Microinjeções , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
AIMS/HYPOTHESIS: Fatty acids of marine origin, i.e. docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) act as hypolipidaemics, but they do not improve glycaemic control in obese and diabetic patients. Thiazolidinediones like rosiglitazone are specific activators of peroxisome proliferator-activated receptor gamma, which improve whole-body insulin sensitivity. We hypothesised that a combined treatment with a DHA and EPA concentrate (DHA/EPA) and rosiglitazone would correct, by complementary additive mechanisms, impairments of lipid and glucose homeostasis in obesity. METHODS: Male C57BL/6 mice were fed a corn oil-based high-fat diet. The effects of DHA/EPA (replacing 15% dietary lipids), rosiglitazone (10 mg/kg diet) or a combination of both on body weight, adiposity, metabolic markers and adiponectin in plasma, as well as on liver and muscle gene expression and metabolism were analysed. Euglycaemic-hyperinsulinaemic clamps were used to characterise the changes in insulin sensitivity. The effects of the treatments were also analysed in dietary obese mice with impaired glucose tolerance (IGT). RESULTS: DHA/EPA and rosiglitazone exerted additive effects in prevention of obesity, adipocyte hypertrophy, low-grade adipose tissue inflammation, dyslipidaemia and insulin resistance, while inducing adiponectin, suppressing hepatic lipogenesis and decreasing muscle ceramide concentration. The improvement in glucose tolerance reflected a synergistic stimulatory effect of the combined treatment on muscle glycogen synthesis and its sensitivity to insulin. The combination treatment also reversed dietary obesity, dyslipidaemia and IGT. CONCLUSIONS/INTERPRETATION: DHA/EPA and rosiglitazone can be used as complementary therapies to counteract dyslipidaemia and insulin resistance. The combination treatment may reduce dose requirements and hence the incidence of adverse side effects of thiazolidinedione therapy.
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Gorduras na Dieta/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Glicogênio/biossíntese , Insulina/fisiologia , Músculo Esquelético/metabolismo , Tiazolidinedionas/farmacologia , Animais , Óleo de Milho/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Intolerância à Glucose/metabolismo , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , RosiglitazonaRESUMO
Myocardial injury may complicate allergic reactions caused by several medications. We evaluated a case of a myocardial injury with transient ST segment elevation in a 72 year-old man presenting with collapse caused by sulbactam-ampicilllin assumption. The purpose of this report is to present this interesting case and revise the classification of Kounis syndrome.
Assuntos
Anafilaxia/induzido quimicamente , Anafilaxia/complicações , Antibacterianos/efeitos adversos , Doença da Artéria Coronariana/complicações , Infarto do Miocárdio/etiologia , Sulbactam/efeitos adversos , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Eletrocardiografia , Humanos , Masculino , Infarto do Miocárdio/diagnóstico por imagemRESUMO
BACKGROUND: Chronically elevated interleukin-6 (IL-6) is implicated in obesity-associated pathologies, where a proportion of this cytokine is derived from adipose tissue. Proinflammatory prostaglandins, which regulate this cytokine elsewhere, are also produced by this tissue. OBJECTIVE: To investigate whether constitutively active cyclooxygenase (COX)/prostaglandin (PG) pathway in white adipose tissue (WAT) is responsible for basal IL-6 production. DESIGN: The effect of acetylsalicylic acid (ASA), an inhibitor of COX, on IL-6 was assessed in human subjects and mice. COX, downstream PG synthase (PGS) activity and PG receptor signalling were determined in subcutaneous (SC), gonadal (GN) WAT and adipocytes. METHODS AND RESULTS: In obese humans, low-dose ASA (150 mg day(-1) for 10 days) inhibited systemic IL-6 and reduced IL-6 release from SC WAT ex vivo (0.2 mM). Similarly, in mice, ASA (0.2 and 2.0 mg kg(-1)) suppressed SC WAT 6-keto-PGF(1alpha) (a stable metabolite of prostacyclin) and IL-6 release. Although both COX isoforms are comparably expressed, prostacyclin synthase expression is higher in GN WAT, with levels of activity correlating directly with IL-6. Both ASA (5 mM) and NS-398 (COX-2 selective inhibitor Assuntos
Tecido Adiposo Branco/metabolismo
, Aspirina/administração & dosagem
, Inibidores de Ciclo-Oxigenase/administração & dosagem
, Interleucina-6/metabolismo
, Obesidade/metabolismo
, Adipócitos/metabolismo
, Idoso
, Animais
, Aspirina/farmacologia
, Estudos de Casos e Controles
, Inibidores de Ciclo-Oxigenase/farmacologia
, Feminino
, Gônadas/metabolismo
, Humanos
, Masculino
, Camundongos
, Camundongos Obesos
, Pessoa de Meia-Idade
, Prostaglandina-Endoperóxido Sintases/metabolismo
, Receptores de Prostaglandina/metabolismo
, Gordura Subcutânea/metabolismo
, Fator de Necrose Tumoral alfa/sangue