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1.
Braz J Med Biol Res ; 55: e11831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35976268

RESUMO

Candida albicans is the most frequently isolated opportunistic pathogen in the female genital tract, with 92.3% of cases in Brazil associated with vulvovaginal candidiasis (VVC). Linalool is a monoterpene compound from plants of the genera Cinnamomum, Coriandrum, Lavandula, and Citrus that has demonstrated a fungicidal effect on strains of Candida spp., but its mechanism of action is still unknown. For this purpose, broth microdilution techniques were applied, as well as molecular docking in a predictive manner for this mechanism. The main results of this study indicated that the C. albicans strains analyzed were resistant to fluconazole and sensitive to linalool at a dose of 256 µg/mL. Furthermore, the increase in the minimum inhibitory concentration (MIC) of linalool in the presence of sorbitol and ergosterol indicated that this molecule possibly affects the cell wall and plasma membrane integrity of C. albicans. Molecular docking of linalool with proteins that are key in the biosynthesis and maintenance of the cell wall and the fungal plasma membrane integrity demonstrated the possibility of linalool interacting with three important enzymes: 1,3-ß-glucan synthase, lanosterol 14α-demethylase, and Δ 14-sterol reductase. In silico analysis showed that this monoterpene has theoretical but significant oral bioavailability, low toxic potential, and high similarity to pharmaceuticals. Therefore, the findings of this study indicated that linalool probably causes damage to the cell wall and plasma membrane of C. albicans, possibly by interaction with important enzymes involved in the biosynthesis of these fungal structures, in addition to presenting low in silico toxic potential.


Assuntos
Candida albicans , Fluconazol , Monoterpenos Acíclicos , Antifúngicos/farmacologia , Farmacorresistência Fúngica , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Monoterpenos/farmacologia
2.
Braz. j. med. biol. res ; 55: e11831, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1394125

RESUMO

Candida albicans is the most frequently isolated opportunistic pathogen in the female genital tract, with 92.3% of cases in Brazil associated with vulvovaginal candidiasis (VVC). Linalool is a monoterpene compound from plants of the genera Cinnamomum, Coriandrum, Lavandula, and Citrus that has demonstrated a fungicidal effect on strains of Candida spp., but its mechanism of action is still unknown. For this purpose, broth microdilution techniques were applied, as well as molecular docking in a predictive manner for this mechanism. The main results of this study indicated that the C. albicans strains analyzed were resistant to fluconazole and sensitive to linalool at a dose of 256 µg/mL. Furthermore, the increase in the minimum inhibitory concentration (MIC) of linalool in the presence of sorbitol and ergosterol indicated that this molecule possibly affects the cell wall and plasma membrane integrity of C. albicans. Molecular docking of linalool with proteins that are key in the biosynthesis and maintenance of the cell wall and the fungal plasma membrane integrity demonstrated the possibility of linalool interacting with three important enzymes: 1,3-β-glucan synthase, lanosterol 14α-demethylase, and Δ 14-sterol reductase. In silico analysis showed that this monoterpene has theoretical but significant oral bioavailability, low toxic potential, and high similarity to pharmaceuticals. Therefore, the findings of this study indicated that linalool probably causes damage to the cell wall and plasma membrane of C. albicans, possibly by interaction with important enzymes involved in the biosynthesis of these fungal structures, in addition to presenting low in silico toxic potential.

3.
Phys Rev E ; 102(3-1): 032618, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33075900

RESUMO

Macromolecular diffusion in strongly confined geometries and crowded environments is still to a large extent an open subject in soft matter physics and biology. In this paper, we employ large-scale Langevin dynamics simulations to investigate how the diffusion of a tracer is influenced by the combined action of excluded-volume and weak attractive crowder-tracer interactions. We consider two species of tracers, standard hard-core particles described by the Weeks-Chandler-Andersen (WCA) repulsive potential and core-softened (CS) particles, which model, e.g., globular proteins, charged colloids, and nanoparticles covered by polymeric brushes. These systems are characterized by the presence of two length scales in the interaction and can show waterlike anomalies in their diffusion, stemming from the inherent competition between different length scales. Here we report a comprehensive study of both diffusion and structure of these two tracer species in an environment crowded by quenched configurations of polymers at increasing density. We analyze in detail how the tracer-polymer affinity and the system density affect transport as compared to the emergence of specific static spatial correlations. In particular, we find that, while hardly any differences emerge in the diffusion properties of WCA and CS particles, the propensity to develop structural order for large crowding is strongly frustrated for CS particles. Surprisingly, for large enough affinity for the crowding matrix, the diffusion coefficient of WCA tracers display a nonmonotonic trend as their density is increased when compared to the zero affinity scenario. This waterlike anomaly turns out to be even larger than what observed for CS particle and appears to be rooted in a similar competition between excluded-volume and affinity effects.

4.
Chaos ; 28(11): 113101, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30501219

RESUMO

Two experimental bifurcation diagrams were obtained with two different control parameters. One parameter was the faucet opening and the other one, keeping fixed the faucet opening, was an electrical voltage (V) applied to a metallic cylinder that surrounds the pendant water column. In this way, the drops are formed in an electrical field gradient that polarizes the water column altering the effective surface tension that is consistent with the observed decreasing of the drop mass as the potential is increased, while the water flow rate remains constant. We observed that the two bifurcations are similar for S ≲ 65 and V ≲ 2.05 kV ; otherwise, the bifurcation evolutions are quite different.

5.
Transplant Proc ; 50(10): 3840-3844, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30385044

RESUMO

OBJECTIVE: Ischemic preconditioning (IPC) was developed to diminish ischemia-reperfusion injury (IRI). There are two main ways of performing it: direct ischemic-preconditioning (DIP) and remote ischemic-preconditioning (RIP). The objectives of this study were to investigate local and systemic effects of DIP and RIP in liver IRI. METHODS: Thirty-two weaning rats (50-70 g body weight; 21 days old) were divided into 4 groups: control (C); ischemia followed by reperfusion (IR); DIP followed by ischemia and reperfusion; and RIP followed by ischemia and reperfusion. In the IR group, the vascular pedicles of medial and left lateral liver lobes were clamped for 60 minutes and then unclamped. In the DIP group, a 10-minute cycle of ischemia followed by a 10-minute reperfusion of the same lobes was performed before 60 minutes of ischemia. In the RIP group, three 5-minute cycles of clamping and unclamping of the femoral vessels were performed before liver ischemia. The animals were euthanized 24 hours after the surgical procedures. RESULTS: The serum levels of liver enzymes were significantly lower in the RIP group compared to the control and IR groups and to the DIP group. The scores of histologic hepatic lesions were significantly lower in RIP animals than those of IR animals (P = .002) and similar to the C group animals. The Bax/BCl-xl relation was lower in the DIP group than that in the RIP group (P = .045) and no differences were observed in histologic analyses of kidney, lung, intestine, and heart. CONCLUSION: In young animals, the beneficial effects of RIP are more evident than those of DIP.


Assuntos
Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Fígado/patologia , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia
6.
Med Oral Patol Oral Cir Bucal ; 23(2): e132-e137, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29476675

RESUMO

BACKGROUND: Facial disfigurement has been considered one of the most challenging consequences of the surgical treatment for head and neck cancer patients, mainly due to the importance of the facial region for the personal identity, body self-image and interpersonal interactions, which might affect negatively the quality of life. The aim of this study was to assess factors associated with the quality of life of subjects with facial disfigurement due to surgical treatment. MATERIAL AND METHODS: Clinical data were retrieved from 103 patient's medical records and quality of life data were collected using the Functional Assessment of Cancer Therapy (FACT-H&N) questionnaire. Moreover, the degree of facial disfigurement was classified by means of a specific ordinal scale. RESULTS: Data from the FACT-H&N questionnaire showed that the domain directly related to head and neck symptoms was considered the most impacted, while emotional domain was the least affected. Lower quality of life was associated with sequels in the neck and/or lower third of the face (ß=-0.39; p=0.001), a higher level of disfigurement (ß=-0.29; p=0.016) and female gender (ß=-0.20; p=0.038). CONCLUSIONS: Disfigurement due to surgical treatment was significantly associated with the functional dimension of the patients, especially in extensive sequels in the cervical and lower regions of the face.


Assuntos
Face/anormalidades , Neoplasias de Cabeça e Pescoço/cirurgia , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Oral Rehabil ; 45(4): 301-307, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29356092

RESUMO

The aim of this study was to test the reliability of a method to measure the masticatory performance of complete denture wearers employing a colour-mixing ability test and assessment by visual and electronic colourimetric analysis. A sample of 75 subjects was selected from patients who received new conventional complete dentures. Masticatory tests were performed using a two-colour chewing gum that was masticated for 5, 10, 20, 30 and 50 chewing cycles, performed in a random order. The mixing level of the two colours of the chewed gum was assessed visually by two independent raters based on a 5-point ordinal scale. The specimens were flattened into a 1-mm-width wafer, scanned and saved as a two-sided digital image. Each pair of images was submitted to an electronic colourimetric analysis to assess the level of colour mixture, measured by the circular variance of hue (VOH). Overall inter- and intra-rater agreements in visual analysis were 64% and 68%, respectively (almost 99% of scores ranged within ±1 point), whilst overall weighted kappa was >0.80. A proportional increase in the level of mixture occurred with increased number of chewing cycles (P < .001). Similarly, VOH and the visual analysis were highly correlated (r = -.89; P < .001). Bland-Altman plots revealed excellent agreement and extremely low systematic error between duplicated VOH measures. It was concluded that the two-colour chewing gum test is a reliable method to assess the masticatory performance in complete denture wearers using both visual and electronic colourimetric analyses.


Assuntos
Goma de Mascar , Cor , Prótese Total , Mastigação/fisiologia , Adulto , Idoso , Força de Mordida , Colorimetria , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tamanho da Partícula , Reprodutibilidade dos Testes , Fatores de Tempo
8.
J Oral Rehabil ; 44(12): 1004-1016, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28805255

RESUMO

The single-implant mandibular overdenture (SIMO) has been proposed as an alternative for edentulous patients who are poorly adapted to their dentures due to low retention and stability of the conventional mandibular complete denture (CD). However, there is a lack of evidence regarding the effectiveness of SIMO, which can be measured by examining patient perception of treatment effects. The aim of this systematic review was to assess the comparative results of CD and SIMO treatments using patient-reported outcome measures. A literature search was carried out in PubMed, Scopus and Cochrane Central databases. The search included studies published up to July 2017. The focus question was: 'Do single-implant mandibular overdentures improve patient-reported outcomes compared to conventional complete dentures in edentulous patients?' Eligible studies were randomised clinical trials (RCT) and prospective studies. After initial screening for eligibility and full-text analysis, 11 studies were included for data extraction and quality assessment (five parallel-group RCTs, two crossover RCTs and four prospective studies). All studies reported marked improvement in satisfaction with the dentures and quality of life measures after SIMO treatment, irrespective of variations in implant treatment protocols and retention systems. Methodological considerations revealed a lack of evidence from RCTs on the comparative effectiveness of the two treatment strategies. Hence, although available evidence suggests considerable improvement in patient-reported outcomes following the insertion of a single implant to retain a mandibular denture, further well-designed comparative studies between SIMO and CD are required to improve the level of evidence and to support the indication of SIMO treatment in routine practice.


Assuntos
Prótese Total Inferior , Revestimento de Dentadura , Medidas de Resultados Relatados pelo Paciente , Humanos , Saúde Bucal , Satisfação do Paciente/estatística & dados numéricos , Qualidade de Vida , Resultado do Tratamento
10.
Genet Mol Res ; 15(4)2016 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-27813611

RESUMO

Moquiniastrum polymorphum subsp floccosum (Cabrera) G. Sancho is used in traditional Brazilian medicine to treat inflammation and infection, which is supported by scientific data. However, only one study has been conducted on the mutagenic activity of the extract, which has important safety implications. This study evaluated the mutagenic/antimutagenic activity of M. polymorphum ethanolic extract (MPEE) in Allium cepa meristematic cells. Commercial A. cepa seeds were cultured for 120 h. Treatments were performed for 48 h with MPEE (10 mg/mL), methyl methanesulfonate (MMS; 0.01 mg/mL), or in combination (MPEE + MMS). All of the experiments were performed in triplicate. A total of 15,000 cells per treatment were analyzed for chromosomal aberrations and the mitotic index. The results showed that MPEE was not mutagenic. In combination with MMS, MPEE decreased the number of damaged cells and the mitotic index. Interestingly, the most pronounced effect was observed post-treatment when the mitotic index also decreased, suggesting that MPEE may affect the cell cycle. MPEE exhibited antimutagenic activity, and may induce cell cycle arrest in A. cepa.


Assuntos
Antimutagênicos/farmacologia , Infecções/genética , Inflamação/genética , Mutagênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antimutagênicos/química , Asteraceae/química , Asteraceae/genética , Brasil , Ciclo Celular/efeitos dos fármacos , Aberrações Cromossômicas/efeitos dos fármacos , Infecções/tratamento farmacológico , Inflamação/tratamento farmacológico , Medicina Tradicional , Índice Mitótico , Cebolas/efeitos dos fármacos , Extratos Vegetais/química
11.
Horm Cancer ; 6(4): 176-81, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26021762

RESUMO

Incidentally discovered adrenal masses are common and the clinical evaluation and surveillance aims to diagnose hormone excess and malignancy. Adrenocortical cancer (ACC) is a very rare malignancy. This study aims to define the imaging characteristics of adrenal tumors preceding the diagnosis of ACC. Patients with prior (>5 months) adrenal tumors (<6 cm) subsequently diagnosed with ACC were identified in a large registry at a tertiary referral center. Retrospective chart and image review for patient characteristics and initial, interval, and diagnostic imaging characteristics (size, homogeneity, borders, density, growth rate, etc.) was conducted. Twenty patients with a diagnosis of ACC and a prior adrenal tumor were identified among 422 patients with ACC. Of these, 17 patients were initially imaged with CT and 3 with MR. Only 2 of the 20 patients had initial imaging characteristics suggestive of a benign lesion. Of initial tumors, 25% were <2 cm in size. Surveillance led to the diagnosis of ACC within 24 months in 50% of patients. The growth pattern was variable with some lesions showing long-term stability (up to 8 years) in size. In conclusion, antecedent lesions in patients with a diagnosis of ACC are often indeterminate by imaging criteria and can be small. Surveillance over 2 years detected only 50% of ACCs. Current practice and guidelines are insufficient in diagnosing ACCs. Given the rarity of ACC, the increased risk and health care costs of additional evaluation may not be warranted.


Assuntos
Neoplasias do Córtex Suprarrenal/diagnóstico , Glândulas Suprarrenais/patologia , Neoplasias do Córtex Suprarrenal/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
12.
Genet Mol Res ; 14(1): 269-76, 2015 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-25729959

RESUMO

Agronomic performance and external and internal appearance of watermelon (Citrullus lanatus) fruit are important traits that should be taken into consideration during the development of a new cultivar, as well as being the principal identification elements used by the consumer, which are based on the external appearance and quality of the fruit. Externally, the fruit can be characterized in terms of the shape, the color of the lower rind, and the presence of grooves and stripes, the stripes can be classified as clearly defined or diffuse. The objective of this study was to identify microsatellite markers linked to the stripe pattern of watermelon fruit to support watermelon improvement programs, with the selection of this characteristic in the plantlet stage. F1 and F2 populations, result of a cross between the cultivars BRS Opara (clearly defined stripes) and Pérola (diffuse stripes), were phenotyped for their fruit stripe pattern. The CTAB 2X protocol was used for DNA extraction and 116 microsatellite markers were examined in a group of F2 plants that had fruit with well-defined stripes and fruit with diffuse stripes. The microsatellite loci MCPI_05 and MCPI_16 exhibited a linkage to the stripe pattern at a distance of 1.5 and 1.8 cM, respectively, with LOD scores of 39.28 and 38.11, respectively, which were located on chromosome six of the watermelon genome. These markers can be used in marker-assisted selection in watermelon improvement programs, by various research institutions.


Assuntos
Citrullus/genética , Frutas/genética , Ligação Genética , Loci Gênicos , Repetições de Microssatélites/genética , Alelos , Fenótipo
13.
Int J Legal Med ; 129(2): 245-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25516412

RESUMO

The majority of STR loci are not ideal for the analysis of forensic samples with degraded and/or low template DNA. One alternative to overcome these limitations is the use of bi-allelic markers, which have low mutation rates and shorter amplicons. Human identification (HID) InDel marker panels have been described in several countries, including Brazil. The commercial kit available is, however, mostly suitable for Europeans, with lower discrimination power for other population groups. Recently, a combination of 49 InDel markers used in four different ethnic groups in the USA has been shown to be more informative than another panel from Portugal, already tested in a Rio de Janeiro sample. However, these 49 InDels have yet to be applied to other admixed or isolated populations. We assessed the efficiency of this panel in two urban admixed populations (Rio de Janeiro, Brazil; Tripoli, Libya) and one isolated Native Brazilian community. All markers are in Hardy-Weinberg equilibrium (HWE) after the Bonferroni correction, and no Linkage disequilibrium was detected. Assuming loci independence and no substructure effect, cumulative RMP was 2.7×10(-18), 1.5×10(-20), and 4.5×10(-20) for Native Brazilian, Rio de Janeiro, and Tripoli populations, respectively. The overall Fst value was 0.05512. Rio de Janeiro and Tripoli showed similar admixture levels, however for Native Brazilians one parental cluster represented over 60 % of the total parental population. We conclude that this panel is suitable for HID on these urban populations, but is less efficient for the isolated group.


Assuntos
Etnicidade/genética , Mutação INDEL , Brasil , Frequência do Gene , Marcadores Genéticos , Humanos , Indígenas Sul-Americanos/genética , Líbia , População Urbana
14.
Neuroscience ; 277: 417-34, 2014 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-25047998

RESUMO

Amphetamine-type psychostimulants (ATS) are used worldwide by millions of patients for several psychiatric disorders. Amphetamine (AMPH) and "ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) are common drugs of abuse. The impact of chronic ATS exposure to neurons and brain aging is still undisclosed. Current neuronal culture paradigms are designed to access acute ATS toxicity. We report for the first time a model of chronic exposure to AMPH and MDMA using long-term rat cortical cultures. In two paradigms, ATS were applied to neurons at day 1 in vitro (DIV) (0, 1, 10 and 100 µM of each drug) up to 28 days (200 µM was applied to cultures up to 14 DIV). Our reincubation protocol assured no decrease in the neuronal media's drug concentration. Chronic exposure of neurons to concentrations equal to or above 100 µM of ATS up to 28 DIV promoted significant mitochondrial dysfunction and elicited neuronal death, which was not prevented by glutamate receptor antagonists at 14 DIV. ATS failed to promote accelerated senescence as no increase in ß-galactosidase activity at 21 DIV was found. In younger cultures (4 or 8 DIV), AMPH promoted mitochondrial dysfunction and neuronal death earlier than MDMA. Overall, AMPH proved more toxic and was the only drug that decreased intraneuronal glutathione levels. Meanwhile, caspase 3 activity increased for either drug at 200 µM in younger cultures at 8 DIV, but not at 14 DIV. At 8 DIV, ATS promoted a significant change in the percentage of neurons and astroglia present in culture, promoting a global decrease in the number of both cells. Importantly, concentrations equal to or below 10 µM of either drug did not promote neuronal death or oxidative stress. Our paradigm of neuronal cultures long-term exposure to low micromolar concentrations of ATS closely reproduces the in vivo scenario, being valuable to study the chronic impact of ATS.


Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Anfetamina/farmacologia , Córtex Cerebral/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Neurônios/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Astrócitos/fisiologia , Caspase 3/metabolismo , Contagem de Células , Técnicas de Cultura de Células , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Células Cultivadas , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glutationa/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Neurônios/patologia , Neurônios/fisiologia , Ratos Wistar , Receptores de Glutamato/metabolismo , Fatores de Tempo
15.
Arq. bras. med. vet. zootec ; 65(4): 1123-1130, Aug. 2013. tab
Artigo em Português | LILACS | ID: lil-684471

RESUMO

Objetivou-se analisar a viabilidade econômica da terceira ordenha em sistemas de produção de leite que utilizam ordenhadeira mecânica, do tipo circuito aberto, visando fornecer aos técnicos e pecuaristas informações que os auxiliem no processo de tomada de decisões. Especificamente pretendeu-se ainda: a) estimar o custo de uma ordenha; b) estimar, por meio de simulação, o custo da terceira ordenha; c) desenvolver uma equação matemática que permita estimar a quantidade mínima de leite produzido em duas ordenhas, a partir da qual será viável economicamente a realização da terceira ordenha. Os dados foram coletados em três sistemas de produção de leite, em uma rotina de duas ordenhas diárias, sendo realizadas três coletas de dados em cada um, perfazendo um total de nove. Considerando-se os dados médios, seria viável a realização da terceira ordenha se a produtividade média diária das vacas em lactação em duas ordenhas fosse igual ou superior a 38,13kg de leite. A equação matemática desenvolvida pode auxiliar o técnico e o pecuarista a estimarem a quantidade mínima de leite produzido por uma vaca em duas ordenhas, a partir da qual será viável economicamente a realização da terceira ordenha, com precisão e considerável rapidez.


This study aims to analyze the economic viability of the third milking in milk production systems using open circuit milking mechanics, aiming to provide technicians and farmers with information to help in the decision-making process. Specifically intend to a) estimate the cost of a milking; (b) estimate, by means of simulation, the cost of the third milking; (c) develop a mathematical equation that allows estimating the minimum amount of milk produced in two milkings, from which it will be economically feasible to hold the third milking. The data were collected in three milk production systems, in a routine of two milkings per day, with three collections of data in each, a total of nine collections. Considering the average data, it would be feasible to hold the third milking if the productivity of daily average lactating cows is equal or greater than 38.13 kg of milk. The mathematical equation developed may help the technician and the farmer to estimate the minimum quantity of milk produced by a cow in two milkings, from which it will be economically feasible to hold the third milking with precision and considerable speed.


Assuntos
Animais , Bovinos , Animais Domésticos , Economia , Leite , Bovinos/classificação
16.
Cell Death Differ ; 19(11): 1836-46, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22653339

RESUMO

Induction of the C/EBP homologous protein (CHOP) is considered a key event for endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is characterized by an autoimmune destruction of the pancreatic ß-cells. Pro-inflammatory cytokines are early mediators of ß-cell death in T1D. Cytokines induce ER stress and CHOP overexpression in ß-cells, but the role for CHOP overexpression in cytokine-induced ß-cell apoptosis remains controversial. We presently observed that CHOP knockdown (KD) prevents cytokine-mediated degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner caspases 9 and 3, and apoptosis. Nuclear factor-κB (NF-κB) is a crucial transcription factor regulating ß-cell apoptosis and inflammation. CHOP KD resulted in reduced cytokine-induced NF-κB activity and expression of key NF-κB target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased IκB degradation and p65 translocation to the nucleus. The present data suggest that CHOP has a dual role in promoting ß-cell death: (1) CHOP directly contributes to cytokine-induced ß-cell apoptosis by promoting cytokine-induced mitochondrial pathways of apoptosis; and (2) by supporting the NF-κB activation and subsequent cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo attraction of mononuclear cells to the islets during insulitis.


Assuntos
Apoptose/efeitos dos fármacos , Citocinas/farmacologia , Células Secretoras de Insulina/metabolismo , Fator de Transcrição CHOP/metabolismo , Animais , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Núcleo Celular/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Estresse do Retículo Endoplasmático , Quinase I-kappa B/metabolismo , Células Secretoras de Insulina/citologia , Interferon gama/farmacologia , Interleucina-1beta/farmacologia , Mitocôndrias/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Fator de Transcrição CHOP/antagonistas & inibidores , Fator de Transcrição CHOP/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
17.
J Thromb Haemost ; 9(10): 2057-66, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21794075

RESUMO

BACKGROUND: The role of platelets in hemostasis is well known, but few papers have reported their role in pain and edema induced by inflammatory agents. OBJECTIVE: To evaluate the role of circulating platelets in the local injury induced by two diverse inflammatory agents, Bothrops jararaca venom (Bjv) and carrageenan. METHODS: Rats were (i) rendered thrombocytopenic by administration of polyclonal anti-rat platelet IgG (ARPI) or busulfan, or (ii) treated with platelet inhibitors (aspirin or clopidogrel). Edema formation, local hemorrhage and the pain threshold were assessed after intraplantar injection of Bjv or carrageenan in rat hind paws. Additionally, whole platelets or platelet releasate were tested whether they directly induced hyperalgesia. RESULTS: Platelet counts were markedly diminished in rats administered with either ARPI (± 88%) or busulfan (± 96%). Previous treatment with ARPI or busulfan slightly reduced edema induced by Bjv or carrageenan. Injection of Bjv, but not of carrageenan, induced a statistically significance increase in hemorrhage in the hind paws of thrombocytopenic rats. Remarkably, hyperalgesia evoked by Bjv or carrageenan was completely blocked in animals treated with ARPI or busulfan, or pre-treated with aspirin or clopidogrel. On the other hand, intraplantar administration of whole platelets or platelet releasate evoked hyperalgesia, which was inhibited by pre-incubation with alkaline phosphatase. CONCLUSIONS: Thrombocytopenia or inhibition of platelet function drastically reduced hyperalgesia induced by injection of carrageenan or Bjv; moreover, platelets per se secrete phosphorylated compounds involved in pain mediation. Thus, blood platelets are crucial cells involved in the pain genesis, and their role therein has been underestimated.


Assuntos
Plaquetas/citologia , Bothrops , Carragenina/farmacologia , Venenos de Crotalídeos/farmacologia , Hiperalgesia/induzido quimicamente , Animais , Aspirina/farmacologia , Plaquetas/enzimologia , Bussulfano/toxicidade , Clopidogrel , Ciclo-Oxigenase 1/efeitos dos fármacos , Hiperalgesia/prevenção & controle , Masculino , Ratos , Ratos Wistar , Trombocitopenia/induzido quimicamente , Ticlopidina/análogos & derivados , Ticlopidina/farmacologia
18.
Journal of Thrombosis and Haemostasis ; 9(10): 2057-2066, 2011.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP, SESSP-IBACERVO | ID: biblio-1064356

RESUMO

Background:The role of platelets in hemostasis is well known, but few papers have reported their role in pain and edema induced by inflammatory agents. Objective:To evaluate the role of circulating platelets in the local injury induced by two diverse inflammatory agents, Bothrops jararaca venom (Bjv) and carrageenan. Methods:Rats were (i) rendered thrombocytopenic by administration of polyclonal anti-rat platelet IgG (ARPI) or busulfan, or (ii) treated with platelet inhibitors (aspirin or clopidogrel). Edema formation, local hemorrhage and the pain threshold were assessed after intraplantar injection of Bjv or carrageenan in rat hind paws. Additionally, whole platelets or platelet releasate were tested whether they directly induced hyperalgesia. Results:Platelet counts were markedly diminished in rats administered with either ARPI (±88%) or busulfan (±96%). Previous treatment with ARPI or busulfan slightly reduced edema induced by Bjv or carrageenan. Injection of Bjv, but not of carrageenan, induced a statistically significance increase in hemorrhage in the hind paws of thrombocytopenic rats. Remarkably, hyperalgesia evoked by Bjv or carrageenan was completely blocked in animals treated with ARPI or busulfan, or pre-treated with aspirin or clopidogrel. On the other hand, intraplantar administration of whole platelets or platelet releasate evoked hyperalgesia, which was inhibited by pre-incubation with alkaline phosphatase. Conclusions:Thrombocytopenia or inhibition of platelet function drastically reduced hyperalgesia induced by injection of carrageenan or Bjv; moreover, platelets per se secrete phosphorylated compounds involved in pain mediation. Thus, blood platelets are crucial cells involved in the pain genesis, and their role therein has been underestimated.


Assuntos
Animais , Ratos , Bothrops , Serpentes/classificação , Venenos de Serpentes , Hemorragia , Inflamação
19.
Nutr Hosp ; 24(5): 558-67, 2009.
Artigo em Espanhol | MEDLINE | ID: mdl-19893866

RESUMO

INTRODUCTION: As eating disorders include both psychological and physiological components, appropriate management of these disorders requires input from a number of disciplines working together in a coordinated manner, following an integrated Programme. The Eating Disorders-Nutrition Education Programme has as its purpose achieving healthier habits and modifying eating behaviour. The Programme should take place as one part of Eating Disorders treatment. OBJECTIVES: To determine the efficacy of a Nutrition Education Programme about nutritional state and eating patterns in a group of patients diagnosed with Eating Disorders who follow the usual check-up protocol in the clinic for nutrition and mental health. MATERIAL AND METHODS: 89 patients were included, including 5% men. They received individual nutritional education with weekly/fortnightly appointments during a period of 4-6 months. Educational counseling was carried out by a dietician. The mean age of the sample was 24 +/- 8 years and the diagnoses were: Anorexia Nervosa Restrictive (ANR) 32.5% Anorexia Nervosa Purgative (ANP) 26.5%, Bulimia Nervosa (BN) 18%, Eating Disorder Not Otherwise Specified (EDNOS) 21% and Binge Eating Disorder (BED) 2%. The average evolution time since the diagnosis was 4.8 +/- 5 years. An anthropometric assessment, assessment of daily oral intake, 24-hour dietary recall, and Eating Attitudes Test (EAT26) questionnaires were completed at the first appointment and again at the end of the programme. RESULTS: The mean score of the EAT26 questionnaire was 32 +/- 15 initially, and after 4-6 months the score was 23.7 +/- 14 (p < 0.001). This change represents a significant improvement in the patients' symptoms after the Programme. Furthermore there were significant differences in the evaluation of the questionnaire by scales and by diagnosis. After 4-6 months, there was a meaningful reduction in episodes of vomiting per week (from 7.5 +/- 10 to 1 +/- 1.8 p < 0.001) in ANP and BN binge-purging (8 +/- 9.7 vs 2.2 +/- 3.2 p < 0,01). In addition, a favourable trend in the number of binges per week was observed for both diagnoses. The percentage of subjects that ate less than 4 meals per day decreased from 70% to 19% after the Education Programme (p < 0.001). Some 67% of the patients dedicated a specific time for eating and a 54% started to have complete meals. These results that show a very favourable tendency with respect to the normalization of eating patterns. There was improvement in the intake of dairy products, vegetables, fruits, cereals and oil (p < 0.05). At the beginning, 34% consumed at least 3 of the 6 food groups within the recommended range, but at the end 70% did (p < 0.001). After the nutritional education programme, an important increase in energy ingestion and carbonhydrate consumption took place (p < 0.001), as much with ANR as with ANP. With respect to micronutrients, the ingestion of vitamin B2 significantly increased, as well as folic acid and calcium (p < 0.001) in ANP, and magnesium and calcium (p < 0.001) in ANR. In ANR, we found a significant improvement in nutritional status (p < 0.001). Variables including weight, BMI, muscular circumference of the arm and tricipetal fold were at the limit of significance. Regarding ANP and EDNOS, the initial evaluation demonstrated that they were within normal limits, and they were maintained after nutritional education. In BN, progress towards normalization of BMI took place, increasing from 26.4 +/- 6.6 to 25.5 +/- 5.7 (-2.3 kg). CONCLUSIONS: The Nutritional Education Programme carried out by qualified professionals should be a part of Eating Disorders treatment, along with medical and psychological monitoring and as part of an interdisciplinary, multiprofessional team effort.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Educação de Pacientes como Assunto , Feminino , Humanos , Masculino , Estado Nutricional , Avaliação de Programas e Projetos de Saúde , Adulto Jovem
20.
Nutr. hosp ; 24(5): 558-567, sept.-oct. 2009. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-76616

RESUMO

Introducción: Los Trastornos de la Conducta Alimentaria incluyen componentes psíquicos y físicos, por lo que para un adecuado abordaje de los mismos se debe trabajar dentro de un Programa integral con la participación de diferentes disciplinas. La Educación Nutricional busca la modificación de la conducta alimentaria hacia patrones más saludables y debe formar parte del Programa de tratamiento de esta enfermedad. Objetivo: Determinar el efecto de un programa de Educación Nutricional sobre el estado nutricional y el patrón alimentario de un grupo de pacientes con Trastornos de la Conducta Alimentaria que siguen con el protocolo habitual de seguimiento en consulta de Nutrición y deSalud Mental. Metodología: Se incluyeron 89 pacientes, 5% hombres, que recibieron Educación Nutricional individual con visitas semanales/quincenales por 4-6 meses, llevadas a cabo por una Dietista. La edad media 24 ± 8 años. La distribución por diagnóstico fue: Anorexia Nerviosa Restrictiva (ANR) 32,5% y Anorexia Nerviosa Purgativa (ANP) 26,5%, Bulimia Nerviosa (BN) 18%, Trastorno Alimentario No Específico (TANE) 21% y Trastorno por Atracón (TA) 2%. La media del tiempo de evolución desde el diagnóstico fue de 4,8 ± 5 años. Los pacientes completaban el cuestionario EAT26 (Eating Attitudes Test-26), se realizaba evaluación antropométrica, registro de 24 h y frecuencia habitual de consumo de alimentos en la primera consulta y tras recibir el programa de educación nutricional. Resultados: El valor medio del cuestionario EAT26 fue inicialmente 32 ± 15, tras la intervención fue 23,7 ± 14 (p < 0,001), lo que evidencia cambios significativos en la sintomatología de los pacientes muy positivos. También hubo diferencias significativas en el análisis del cuestionario por escalas y en la evaluación por diagnósticos. Tras los 4-6 meses del programa, disminuyó significativamente el número de vómitos/semana tanto en ANP (7,2 ± 10 vs 1 ± 1,8 p < 0,001) como en BN (8 ± 9,7 vs 2,2 ± 3,2 p < 0,01). También se observó una tendencia favorable en la disminución en el número de atracones/semana para ambos diagnósticos. El porcentaje de pacientes que consumían menos de 4 comidas/día se redujo de un 70% a un 19% (p < 0,001). El 67% de los pacientes logró dedicar un tiempo definido como correcto a comer y un 54% pasó a consumir una comida completa, resultados que muestran una tendencia muy favorable respecto a la normalización del patrón alimentario. Aumentó significativamente el consumo de lácteos, verduras, cereales, aceite (p < 0,001), carnes (p < 0,05) y frutas (p < 0,01). Inicialmente un 34% consumía por lo menos 3 de los 6 grupos de alimentos dentro del rango recomendado, al final lo hizo el 70% (p < 0,001). Tras la educación nutricional se produjo un incremento significativo en la ingesta energética y en el consumo de hidratos de carbono (p < 0,001) tanto en ANR como en ANP. Respecto a los micronutrientes aumentó significativamente la ingesta de vitamina B2, ácido fólico y calcio (p < 0,001) en ANP y de magnesio y calcio (p < 0,001) en ANR. Se produjo una mejoría significativa en el estado nutricional en ANR (p < 0,001) en las variables peso, IMC y circunferencia muscular del brazo y el pliegue tricipital estuvo en el límite de la significación. Para ANP y TANE su valoración inicial demostraba que se encontraban dentro de rangos de normalidad, situación que se mantuvo tras la educación nutricional. En BN se produjo una evolución hacia la normalización del IMC, que pasó de 26,4 ± 6,6 a 25,5 ± 5,7 (-2,3 kg). Conclusión: Los programas de educación nutricional llevados a cabo por profesionales cualificados y expertos, deben formar parte del tratamiento de los TCA, junto al seguimiento médico y psicológico y dentro del marco de la interdisciplina y el trabajo en equipo (AU)


Introduction: As eating disorders include both psychological and physiological components, appropriate management of these disorders requires input from a number of disciplines working together in a coordinated manner, following an integrated Programme. The Eating Disorders-Nutrition Education Programme has as its purpose achieving healthier habits and modifying eating behaviour. The Programme should take place as one part of Eating Disorders treatment. Objectives: To determine the efficacy of a Nutrition Education Programme about nutritional state and eating patterns in a group of patients diagnosed with Eating Disorders who follow the usual check-up protocol in the clinic for nutrition and mental health. Material and methods: 89 patients were included, including 5% men. They received individual nutritional education with weekly/fortnightly appointments during a period of 4-6 months. Educational counseling was carried out by a dietician. The mean age of the sample was 24 ± 8 years and the diagnoses were: Anorexia Nervosa Restrictive (ANR) 32.5% Anorexia Nervosa Purgative (ANP) 26.5%, Bulimia Nervosa (BN) 18%, Eating Disorder Not Otherwise Specified (EDNOS) 21% and Binge Eating Disorder (BED) 2%. The average evolution time since the diagnosis was 4.8 ± 5 years. An anthropometric assessment, assessment of daily oral intake, 24-hour dietary recall, and Eating Attitudes Test (EAT26) questionnaires were completed at the first appointment and again at the end of the programme. Results: The mean score of the EAT26 questionnaire was 32 ± 15 initially, and after 4-6 months the score was 23.7 ± 14 (p < 0.001). This change represents a significant improvement in the patients' symptoms after the Programme. Furthermore there were significant differences in the evaluation of the questionnaire by scales and by diagnosis. After 4-6 months, there was a meaningful reduction in episodes of vomiting per week (from 7.5 ± 10 to 1 ± 1.8 p < 0.001) in ANP and BN binge-purging (8 ± 9.7 vs 2.2 ± 3.2 p < 0,01). In addition, a favourable trend in the number of binges per week was observed for both diagnoses. The percentage of subjects that ate less than 4 meals per day decreased from 70% to 19% after the Education Programme (p < 0.001). Some 67% of the patients dedicated a specific time for eating and a 54% started to have complete meals. These results that show a very favourable tendency with respect to the normalization of eating patterns. There was improvement in the intake of dairy products, vegetables, fruits, cereals and oil (p < 0.05). At the beginning, 34% consumed at least 3 of the 6 food groups within the recommended range, but at the end 70% did (p < 0.001). After the nutritional education programme, an important increase in energy ingestion and carbonhydrate consumption took place (p < 0.001), as much with ANR as with ANP. With respect to micronutrients, the ingestion of vitamin B2 significantly increased, as well as folic acid and calcium (p < 0.001) in ANP, and magnesium and calcium (p < 0.001) in ANR. In ANR, we found a significant improvement in nutritional status (p < 0.001). Variables including weight, BMI, muscular circumference of the arm and tricipetal fold were at the limit of significance. Regarding ANP and EDNOS, the initial evaluation demonstrated that they were within normal limits, and they were maintained after nutritional education. In BN, progress towards normalization of BMI took place, increasing from 26.4 ± 6.6 to 25.5 ± 5.7 (-2.3 kg). Conclusions: The Nutritional Education Programme carried out by qualified professionals should be a part of Eating Disorders treatment, along with medical and psychological monitoring and as part of an interdisciplinary, multiprofessional team effort (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Educação de Pacientes como Assunto , Avaliação de Programas e Projetos de Saúde , Estado Nutricional
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