RESUMO
OBJECTIVES: Prisoners' common mental disorders (CMDs) and their social contacts are a complex and significant concern. We have systematically investigated the relationship between social contacts (i.e. perceived, and objective social support, and loneliness) and prisoners' mental health. STUDY DESIGN: This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). METHODS: A protocol was developed and registered in PROSPERO (CRD42023372942). A search strategy was applied across four databases (namely MEDLINE [via OVID SP], APA PsycINFO, Scopus, and Web of Science). The quality assessment entailed the critical appraisal skills program (CASP) Checklist for cohort studies. The data were presented through a narrative synthesis. RESULTS: After screening, 32 studies that fulfilled the inclusion criteria were included in this review. Most were cross-sectional (k = 27), while five had a longitudinal design. The total number of study participants was 10,613. The majority of the studies reported negative correlations between perceived and objective social support and symptoms of common mental disorders (CMDs), specifically, depression, anxiety, and post-traumatic stress disorder (PTSD). The included studies appeared to indicate a correlation between loneliness and PTSD symptoms. CONCLUSIONS: The lack of social support was linked to the development or exacerbation of CMDs in prisoners. Initiatives, such as reducing visitation barriers and providing access to technology for remote communication, can assist prisoners in strengthening their support systems and enhancing their opportunities for reintegration into society.
Assuntos
Solidão , Transtornos Mentais , Saúde Mental , Prisioneiros , Apoio Social , Humanos , Prisioneiros/psicologia , Prisioneiros/estatística & dados numéricos , Solidão/psicologia , Transtornos Mentais/psicologia , Transtornos Mentais/epidemiologia , Saúde Mental/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologiaRESUMO
The replacement of bedding in compost dairy barns (CB) comprises a recurrent management practice, but bedding materials are often not readily available in all regions and the choice of alternative materials is necessary. The objective was to evaluate the thermal attributes of carnauba straw (CS) bedding in compost dairy barn facilities. Environmental monitoring operations were performed at a commercial farm located in Northeast Brazil. Mini weather stations were used to evaluate environmental variables. The THI was evaluated as one of the comfort parameters. Analysis of the spatial distribution of bed surface temperature (BST) in the CB was performed using geostatistical techniques. The cows remained out of the comfort zone according to THI results. The BST indicated satisfactory performance and from the thermal point of view can be used as alternative bedding material in CB facilities. However, it was observed that the CS showed fast biomass degradation compared to conventional materials, widely known. In addition, inadequate temperature values (< 45°C) were found in the deeper of the CS bed, signaling higher risks of pathogenic microbial activity. Additional studies are needed for searching the proper management plans that increase the life span of the bed formed by carnauba straw.(AU)
A reposição de cama na instalação Compost Barn (CB) compreende uma prática recorrente de manejo, porém os materiais de cama muitas vezes não estão facilmente disponíveis em todas as regiões, sendo necessária a adoção de materiais alternativos. Objetivou-se avaliar os atributos térmicos da cama à base de bagana de carnaúba (BC) para instalações CB. Foram realizadas operações de monitoramento ambiental em uma fazenda comercial situada no nordeste do Brasil. Miniestações meteorológicas foram utilizadas para avaliação de variáveis ambientais. O ITU foi avaliado como um dos parâmetros de conforto. A distribuição espacial da temperatura superficial da cama (TSC) no galpão foi analisada usando técnicas da geoestatística. As vacas mantiveram-se fora da zona de conforto, conforme resultados do ITU. A TSC indicou desempenho satisfatório e, do ponto de vista térmico, pode ser utilizada como material alternativo para cama em instalações CB. Entretanto, observou-se que a BC apresentou rápida degradação da biomassa em comparação a materiais convencionais, amplamente conhecidos. Além disso, valores inadequados de temperatura (< 45°C) foram encontrados nas camadas profundas da cama de BC, sinalizando maiores riscos de atividade microbiana patogênica. Estudos adicionais tornam-se necessários para a busca de planos de manejo que aumentem o tempo de vida útil da cama formada por bagana de carnaúba.(AU)
Assuntos
Animais , Feminino , Bovinos , Bem-Estar do Animal , Transtornos de Estresse por Calor/prevenção & controle , Transtornos de Estresse por Calor/veterinária , ArecaceaeRESUMO
An impacted third molar is one of the most common dental abnormalities. Among the reasons for impaction the most common are: insufficient space, time of eruption, improper position of the tooth bud, and genetic disruptions. To investigate if runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), and msh homeobox 1 (MSX1) are differently expressed depending on the position of the molar, we studied 32 patients who had been referred for surgical removal. An orthopantomogram was used to separate them according to Winter's, and Pell & Gregory's, classifications. Bone samples were harvested during the operation for gene expression assay. The Kruskal-Wallis, Dunn's post hoc, and Spearman's correlation, tests were used to assess the significance of differences. No correlations were found in expression of the genes, and no differences between expression in maxillary and mandibular third molars, nor were they expressed differently according to Winter's or Pell and Gregory's classifications or in relation to impaction of the mandibular ramus. However, MSX1 was expressed differently when account was taken of the depth of impaction in maxillary third molars (pâ¯=â¯0.029), but there was no difference in expression of RUNX2, BMP2, and MSX1 for the Pell and Gregory classification of depth of impaction (pâ¯>â¯0.05). We conclude that MSX1 is expressed differently depending on the depth of maxillary impaction phenotypes.
Assuntos
Dente Serotino , Dente Impactado , Humanos , Fator de Transcrição MSX1 , Mandíbula , Dente Molar , Erupção DentáriaRESUMO
This manuscript presents a model and the methodology to understand and define the ethical management of the large-scale implementation of ICT solutions for Active and Healthy Ageing. Based on project expertise, including experience from the Pharaon project Horizon 2020, this model includes an understanding of the main ethical challenges and the development of the necessary guidelines, measures, and tools for different stakeholder profiles. This model extends beyond conventional ethical guidelines, providing a methodology to actively discuss ethical and societal challenges within a project based on interactive and iterative dialogue between the entire value-chain of stakeholders. One of the cornerstones in the analysis of challenges is focused attention on policy and societal issues that emerge during a project. Accordingly, the model includes targeted reflections and tools delivered in the context of the recent Covid-19 pandemic. The tools developed in this process are organised in a guide that can be actively used throughout large-scale implementation projects related to ICT solutions.
RESUMO
BACKGROUND AND PURPOSE: Remyelination represents an area of great therapeutic interest in multiple sclerosis but currently lacks a robust imaging marker. The purpose of this study was to use high-gradient diffusion MRI and macromolecular tissue volume imaging to obtain estimates of axonal volume fraction, myelin volume fraction, and the imaging g-ratio in patients with MS and healthy controls and to explore their relationship to neurologic disability in MS. MATERIALS AND METHODS: Thirty individuals with MS (23 relapsing-remitting MS, 7 progressive MS) and 19 age-matched healthy controls were scanned on a 3T MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Macromolecular tissue volume imaging was performed to quantify the myelin volume fraction. Diffusion data were fitted to a 3-compartment model of white matter using a spheric mean approach to yield estimates of axonal volume fraction. The imaging g-ratio was calculated from the ratio of myelin volume fraction and axonal volume fraction. Imaging metrics were compared between groups using 2-sided t tests with a Bonferroni correction. RESULTS: The mean g-ratio was significantly elevated in lesions compared with normal-appearing WM (0.74 vs 0.67, P < .001). Axonal volume fraction (0.17 vs 0.23, P < .001) and myelin volume fraction (0.17 vs 0.25, P < .001) were significantly lower in lesions than normal-appearing WM. Myelin volume fraction was lower in normal-appearing WM compared with that in healthy controls (0.25 vs 0.27, P = .009). Disability, as measured by the Expanded Disability Status Scale, was significantly associated with myelin volume fraction (ß = -40.5, P = .001) and axonal volume fraction (ß = -41.0, P = .016) in normal-appearing WM. CONCLUSIONS: The imaging g-ratio may serve as a biomarker for the relative degree of axonal and myelin loss in MS.
Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Neuroimagem/métodos , Substância Branca/diagnóstico por imagem , Adulto , Algoritmos , Axônios/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Bainha de Mielina/patologia , Substância Branca/patologia , Adulto JovemRESUMO
Leishmania amazonensis is one of leishmaniasis' causative agents, a disease that has no cure and leads to the appearance of cutaneous lesions. Recently, our group showed that heme activates a Na+/K+ ATPase in these parasites through a signaling cascade involving hydrogen peroxide (H2O2) generation. Heme has a pro-oxidant activity and signaling capacity, but the mechanism by which this molecule increases H2O2 levels in L. amazonensis has not been elucidated. Here we investigated the source of H2O2 stimulated by heme, ruling out the participation of mitochondria and raising the possibility of a role for a NADPH oxidase (Nox) activity. Despite the absence of a classical Nox sequence in trypanosomatid genomes, L. amazonensis expresses a surface ferric iron reductase (LFR1). Interestingly, Nox enzymes are thought to have evolved from ferric iron reductases because they share same core domain and are very similar in structure. The main difference is that Nox catalyses electron flow from NADPH to oxygen, generating reactive oxygen species (ROS), while ferric iron reductase promotes electron flow to ferric iron, generating ferrous iron. Using L. amazonensis overexpressing or knockout for LFR1 and heterologous expression of LFR1 in mammalian embryonic kidney (HEK 293) cells, we show that this enzyme is bifunctional, being able to generate both ferrous iron and H2O2. It was previously described that protozoans knockout for LFR1 have their differentiation to virulent forms (amastigote and metacyclic promastigote) impaired. In this work, we observed that LFR1 overexpression stimulates protozoan differentiation to amastigote forms, reinforcing the importance of this enzyme in L. amazonensis life cycle regulation. Thus, we not only identified a new source of ROS production in Leishmania, but also described, for the first time, an enzyme with both ferric iron reductase and Nox activities.
Assuntos
FMN Redutase/metabolismo , Peróxido de Hidrogênio/metabolismo , Ferro/metabolismo , Leishmania/enzimologia , Leishmaniose/parasitologia , NADPH Oxidases/metabolismo , Proteínas de Protozoários/metabolismo , Células HEK293 , Heme/metabolismo , Humanos , Leishmania/crescimento & desenvolvimento , Leishmaniose/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/parasitologia , NADPH Oxidases/genética , Oxirredução , Proteínas de Protozoários/genéticaRESUMO
BACKGROUND & AIMS: Resting energy expenditure (REE) and respiratory quotient (RQ) as measured by indirect calorimetry (IC) may correlate with muscle mass and represent prognostic indicators in treating patients with liver cirrhosis. We aimed to assess the correlation of IC-measured REE and RQ with skeletal muscle mass (SM), mortality, and REE values as estimated by Harris-Benedict, European guidelines (EG), and Brazilian guidelines-DITEN (BG) equations in patients with liver cirrhosis. METHODS: In this prospectively designed study, REE was measured in 126 male patients with liver cirrhosis by IC and predicted by Harris-Benedict, EG (35 kcal/kg current weight), and BG (30 kcal/kg current weight) guidelines. Measurements were obtained at the time of admission to the study. Body composition was determined by whole-body dual-energy X-ray absorptiometry. The association between REE and 3-year survival was investigated. RESULTS: Cirrhosis etiology was classified as alcohol related (59.0%), viral (20.1%), cryptogenic (11.8%), or other (9.0%). Mean Child-Pugh and MELD indexes were 8.30 ± 2.0 and 14.38 ± 6.12, respectively. RQ showed a moderate correlation with SM (r = 0.64), while IC-measured REE was inversely associated with mortality (multivariate Cox Regression, HR = 0.88, 95% CI: 0.78; 1, p = 0.04). Among the predictive equations for REE, only Harris-Benedict yielded values close to the IC, with a positive Pearson correlation (r = 0.77), excellent accuracy (Cb = 0.98), and positive Lin's concordance correlation (CCC = 0.75). However, a large standard deviation was observed; HB-measured REE did not correlate with mortality. CONCLUSIONS: RQ and REE, as measured by IC, may be valuable tools for evaluating the severity of cirrhosis, by reflecting SM and predicting mortality, respectively. The predictive equations for REE included in this study cannot replace IC for this purpose. REGISTERED AT: www.clinicalTrials.gov (NCT02421848).
Assuntos
Metabolismo Energético/fisiologia , Cirrose Hepática , Adulto , Composição Corporal/fisiologia , Calorimetria Indireta , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
The effects of doping of ZnO and Nb2O5 solids with Fe2O3 (1.4 wt%) and Ag2O (1.4 wt%) on its surface and catalytic properties were investigated, as well as its photocatalytic performance on the degradation of a pulp and paper wastewater (PPW). The catalysts were characterized by XRD, SEM, photoacoustic spectroscopy (PAS), NH3-TPD and textural analysis. The results obtained revealed that Fe2O3 doping of Nb2O5 conducted at 500 °C resulted in an increase of about 116% for SBET while Ag2O treatment exerted a decrease of 33% for SBET of the doped adsorbents. Doping ZnO with Fe2O3 or Ag2O led to an increase of 80% for SBET. Iron and silver doping also led to a decrease in band gap energy of at least 6%. The addition of 1.4 wt% Ag2O on ZnO followed by calcination at 500 °C resulted in an increase of 11% in the value of the reaction rate constant (kap) for COD reduction under UV radiation. The treatment of Nb2O5 with 1.4 wt% Ag2O increased by a factor of 2.04 the value of kap for the reaction taking place under VIS radiation. The catalysts partially reduced the organic load and the real colour of the wastewater, allowing the achievement of the specifications for release into rivers, so photocatalysis could be an alternative for pulp and paper wastewater final polishing.
Assuntos
Compostos Férricos/química , Águas Residuárias , Catálise , Óxidos/química , PapelRESUMO
The present work, involves the simulation of the transport of a vitamin C derivative, Ascorbyl Tetraisopalmitate (ATI), through human skin by molecular dynamics. Percutaneous absorption of the ATI molecule through the infundibulum, an important route of absorption into the hair follicle of the human skin, has been modeled and compared with the stratum corneum membrane. The comparative study was done using molecular dynamics with Martini force field. In infundibulum, a single ATI molecule require more time to penetrate, and the data obtained suggested that a high concentration of ATI molecule accelerated the process of penetration. In conclusion, the ATI molecule was found to have more affinity towards the stratum corneum as compared with the infundibulum, and it followed a straight pathway to penetrate (until 600ns of simulation). In the infundibulum, it showed less affinity, more mobility and followed a lateral pathway. Thus, this work contributes to a better understanding of the different molecular interactions during percutaneous absorption of active molecules in these two different types of biological membranes.
Assuntos
Ácido Ascórbico/análogos & derivados , Membrana Celular/química , Simulação de Dinâmica Molecular , Ácido Ascórbico/química , Ácido Ascórbico/farmacocinética , Membrana Celular/metabolismo , Folículo Piloso/química , Folículo Piloso/metabolismo , Humanos , Absorção CutâneaRESUMO
O objetivo do presente estudo foi caracterizar as propriedades leiteiras da região do Vale do Braço do Norte, sul de Santa Catarina, Brasil, quanto à qualidade do leite e ao perfil em infraestrutura, manejo e alimentação dos animais. Foram coletadas informações de 50 propriedades leiteiras, obtidas por meio da aplicação de um questionário estruturado, abrangendo questões socioeconômicas dos produtores, manejo do rebanho, estrutura da propriedade, caracterização dos animais, alimentação das vacas além de manejo e higiene da ordenha. As amostras de leite foram submetidas a análises de composição, contagem bacteriana total, contagem de células somáticas e estabilidade do leite ao teste do álcool. Os dados foram analisados pela análise fatorial, discriminante, canônica, e de agrupamento. As propriedades têm como principal característica a agricultura familiar, com área média de 30 hectares; destes, 15,1 são destinados à pecuária leiteira, com média de 23,1 vacas ordenhadas. Na análise fatorial, o primeiro fator representa as relações entre as práticas de higiene na ordenha e de controle/prevenção de mastite, o segundo fator compreende a infraestrutura da fazenda com o nível de produção e o terceiro fator demonstra a relação entre a suplementação concentrada, a produção e a estabilidade do leite ao teste do álcool. A análise de agrupamento formou três grupos, sendo dois compostos por produtores com maior nível tecnológico e outro constituído por pequenos produtores com menor infraestrutura e nível de tecnologia. As propriedades que apresentam infraestrutura mais adequada para a produção, maior adoção das práticas recomendadas de manejo de ordenha e critérios de alimentação mais adequados produzem leite com melhor qualidade.
The aim of this study was to characterize the dairy farms of the Vale do Braço do Norte region, south of Santa Catarina State, Brazil, regarding milk quality and profile of the farms for infrastructure, management and nutrition of the animals. Information about 50 dairy farms was obtained through a survey regarding socio-economic conditions of the farmers, farm structure, characterization of animals, cow feeding and also milking management and hygiene. The milk samples were analyzed for total bacterial count, somatic cell count and stability of milk to ethanol. The data were analyzed in factorial, discriminant, canonical and cluster analysis. The main characteristic of farms is family farming with an average area of 30 hectares, of which 15.1 are destined for dairy farming, where an average of 23.1 cows are milked. On the factor analysis, the first factor represents the relation between hygiene practices during milking and control / prevention of mastitis, the second factor comprises the infrastructure of the farm with the level of production and the third factor shows the ratio of concentrate supplementation, production and stability of the milk to the ethanol test. The cluster analysis formed three groups, two composed of producers with higher technological level and another by small producers with lower infrastructure and level of technology. The dairy farms that have more adequate infrastructure for production, greater adoption of practices recommended for milking management and more appropriate criteria for cow feeding produce better quality milk.
Assuntos
Animais , Bovinos , Substitutos do Leite Humano , Bovinos , Criação de Animais Domésticos/organização & administração , Infraestrutura , Ejeção Láctea , Zonas Agrícolas , Qualidade dos Alimentos , Indústria AgropecuáriaRESUMO
AIM: The association between Helicobacter pylori infection and gastrointestinal symptoms is debatable in childhood. We examined the potential relationship between H. pylori infection and gastrointestinal symptoms in Brazilian children with nonulcer dyspepsia. METHODS: This prospective observational study analysed 240 Brazilian children and adolescents (68.7% girls) with chronic nonulcer dyspepsia, who underwent upper gastrointestinal endoscopy and biopsy. Their mean age was 9.8 years (range 4-17). Upper gastrointestinal symptoms, including abdominal pain, nausea, burning, early satiety, belching and weigh loss, were evaluated by a questionnaire and H. pylori infection was determined by histopathology of gastric biopsies. RESULTS: H. pylori infection was identified in 123/240 patients (52%). There was no significant association between the H. pylori infection and gastrointestinal symptoms and no relationship between the infection and abdominal pain or pain characteristics. However, nausea was significantly associated with the H. pylori infection, with an odds ratio of 1.76 and 95% confidence interval of 1.1-2.94 p < 0.03. Symptoms lasting longer than 12 months were significantly more frequent in children with pangastritis than in those with antral gastritis (p < 0.05). CONCLUSION: The prevalence of H. pylori infection was high in Brazilian children with nonulcer dyspepsia, but was not associated with specific signs and symptoms, except for nausea.
Assuntos
Dispepsia/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Dor Abdominal/microbiologia , Adolescente , Criança , Pré-Escolar , Doença Crônica , Dispepsia/diagnóstico por imagem , Dispepsia/patologia , Endoscopia Gastrointestinal , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Humanos , Modelos Logísticos , Masculino , Náusea/microbiologia , Prevalência , Estudos ProspectivosRESUMO
This paper presents a theoretical study using density functional theory to calculate thermodynamics properties of major molecules compounds at gas phase of fuels like gasoline, ethanol, and gasoline-ethanol mixture in thermal equilibrium on temperature range up to 1500 K. We simulated a composition of gasoline mixture with ethanol for a thorough study of thermal energy, enthalpy, Gibbs free energy, entropy, heat capacity at constant pressure with respect to temperature in order to study the influence caused by ethanol as an additive to gasoline. We used semi-empirical computational methods as well in order to know the efficiency of other methods to simulate fuels through this methodology. In addition, the ethanol influence through the changes in percentage fractions of chemical energy released in combustion reaction and the variations on thermal properties for autoignition temperatures of fuels was analyzed. We verified how ethanol reduces the chemical energy released by gasoline combustion and how at low temperatures the gas phase fuels in thermal equilibrium have similar thermodynamic behavior. Theoretical results were compared with experimental data, when available, and showed agreement. Graphical Abstract Thermodynamic analysis of fuels in gas phase.
Assuntos
Etanol/química , Gasolina/análise , Modelos Teóricos , Termodinâmica , Pressão , Temperatura , VolatilizaçãoRESUMO
Recent models of semantic memory propose that the semantic representation of concepts is based, in part, on a network of features. In this view, a feature that is distinctive for an object (a zebra has stripes) is processed differently from a feature that is shared across many objects (a zebra has four legs). The goal of this paper is to determine whether there are hemispheric differences in such processing. In a feature verification task, participants responded 'yes' or 'no' following concepts which were presented to a single visual field (left or right) paired with a shared or distinctive feature. Both hemispheres showed faster reaction times to shared features than to distinctive features, although right hemisphere responses were significantly slower overall and particularly in the processing of distinctive features. These findings support models of semantic processing in which the dominant left hemisphere more efficiently performs highly discriminating 'fine' encoding, in contrast to the right hemisphere which performs less discriminating 'coarse' encoding.
Assuntos
Formação de Conceito/fisiologia , Dominância Cerebral/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Semântica , HumanosRESUMO
Theoretical and experimental bands have been assigned to the Fourier Transform Infrared (FT-IR) and FT-Raman spectra of the bis(diethyldithiocarbamate)Cd(II) complex, abbreviated as ([Cd(DDTC)2]). The calculations and spectral interpretation have been based on the DFT/B3LYP method, infrared and Raman second derivative spectra, and band deconvolution analysis to assist in the assignment of observed fundamentals. This study validated the unusual pseudo tetrahedral molecular structure formed around the Cd(II) cation. Surface-enhanced Raman scattering (SERS) was used to determine the interactions of the normal-modes of the diethyldithiocarbamate cadmium (II) complex on nano-structured silver surfaces. Natural bond orbital (NBO) analysis was also carried out to study the Cd(II) hybridization causing the pseudo tetrahedral geometry of the framework of the [Cd(DDTC)2] complex, and to confirm the charge transfer mechanisms through second order perturbation theory analysis of the Fox Matrix. In order to find out the electronic dispersion of the Mulliken atomic charges (MAC) in the normal modes, we calculated the MAC for each normal mode and correlated these values with the SERS effect. Experimental UV-Vis spectra were obtained and charge transfer bands were assigned. Good agreement between the calculated and experimental values for the vibrational and UV-Vis spectra was obtained.
Assuntos
Cádmio/química , Ditiocarb/química , Modelos Moleculares , Análise Espectral RamanRESUMO
The aim of this study was to more clearly define the clinical course of leptomeningeal carcinomatosis due to esophageal cancer. A single institution retrospective case series was conducted. Additionally, a systematic review of the literature was performed. We present a large case series (n = 7) of leptomeningeal carcinomatosis due to esophageal cancer. Our case series and systematic review of the literature report similar findings. In our series, we report a predominance of male patients (86%) with adenocarcinoma histology (77%). Variable onset of leptomeningeal involvement of esophageal cancer in relation to the original diagnosis of the primary disease (5 months to 3 years and 11 weeks) was noted. Disease progresses quickly and overall survival is poor, measured in weeks (2.5-16 weeks) from the diagnosis of leptomeningeal involvement. Four of our patients initiated whole-brain radiation therapy with only two completing the course prior to clinical deterioration. Our patient with the longest survival (16 weeks) received intrathecal topotecan and oral temozolomide. Leptomeningeal carcinomatosis secondary to esophageal cancer has a poor prognosis. A clearly beneficial treatment modality is lacking.
Assuntos
Adenocarcinoma/patologia , Neoplasias Esofágicas/patologia , Carcinomatose Meníngea/secundário , Adenocarcinoma/terapia , Adulto , Idoso , Progressão da Doença , Neoplasias Esofágicas/terapia , Feminino , Humanos , Masculino , Carcinomatose Meníngea/terapia , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Modulation of the mitochondrial permeability transition pore (MPTP) and inhibition of the apoptotic signaling are critically associated with the cardioprotective phenotypes afforded by both intermittent hypobaric-hypoxia (IHH) and endurance-training (ET). We recently proposed that IHH and ET improve cardiac function and basic mitochondrial capacity, although without showing addictive effects. Here we investigate whether a combination of IHH and ET alters cardiac mitochondrial vulnerability to MPTP and related apoptotic signaling. METHODS: Male Wistar rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1h/day/5 week treadmill-running), hypoxic-sedentary (HS, 6000 m, 5h/day/5 weeks) and hypoxic-exercised (HE) to study susceptibility to calcium-induced cardiac MPTP opening. Mitochondrial cyclophilin D (CypD), adenine nucleotide translocator (ANT), Bax and Bcl-2 protein contents were semi-quantified by Western blotting. Cardiac caspase 3-, 8- and 9-like activities were measured. Mitochondrial aconitase and superoxide dismutase (MnSOD) activity and malondialdehyde (MDA) and sulphydryl group (-SH) content were determined. RESULTS: Susceptibility to MPTP decreased in NE and HS vs. NS and even further in HE. The ANT content increased in HE vs. NS. Bcl-2/Bax ratio increased in NE and HS compared to NS. Decreased activities in tissue caspase 3-like (HE vs. NS) and caspase 9-like (HS and HE vs. NS) were observed. Mitochondrial aconitase increased in NE and HS vs. NS. No alterations between groups were observed for caspase 8-like activity, MnSOD, CypD, MDA and -SH. CONCLUSIONS: Data confirm that IHH and ET modulate cardiac mitochondria to a protective phenotype characterized by decreased MPTP induction and apoptotic signaling, although without visible addictive effects as initially hypothesized.
Assuntos
Apoptose/fisiologia , Hipóxia/metabolismo , Mitocôndrias Cardíacas/fisiologia , Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Condicionamento Físico Animal/fisiologia , Transdução de Sinais/fisiologia , Animais , Masculino , Poro de Transição de Permeabilidade Mitocondrial , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/métodos , Ratos , Ratos WistarRESUMO
BACKGROUND: Intermittent hypobaric-hypoxia (IHH) and endurance-training (ET) are cardioprotective strategies against stress-stimuli. Mitochondrial modulation appears to be an important step of the process. This study aimed to analyze whether a combination of these approaches provides additive or synergistic effects improving heart-mitochondrial and cardiac-function. METHODS: Two-sets of rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5 weeks treadmill-running), hypoxic-sedentary (HS, 6000 m, 5h/day/5 weeks) and hypoxic-exercised (HE) to study overall cardiac and mitochondrial function. In vitro cardiac mitochondrial oxygen consumption and transmembrane potential were evaluated. OXPHOS subunits and ANT protein content were semi-quantified by Western blotting. HIF-1α, VEGF, VEGF-R1 VEGF-R2, BNP, SERCA2a and PLB expressions were measured by qRT-PCR and cardiac function was characterized by echocardiography and hemodynamic parameters. RESULTS: Respiratory control ratio (RCR) increased in NE, HS and HE vs. NS. Susceptibility to anoxia/reoxygenation-induced dysfunction decreased in NE, HS and HE vs. NS. HS decreased mitochondrial complex-I and -II subunits; however HE completely reverted the decreased content in complex-II subunits. ANT increased in HE. HE presented normalized ventricular-arterial coupling (Ea) and BNP myocardial levels and significantly improved myocardial performance as evaluated by increased cardiac output and normalization of the Tei index vs. HS CONCLUSION: Data demonstrates that IHH and ET confer cardiac mitochondria with a more resistant phenotype although without visible addictive effects at least under basal conditions. It is suggested that the combination of both strategies, although not additive, results into improved cardiac function.
Assuntos
Coração/fisiologia , Hipóxia/fisiopatologia , Mitocôndrias Cardíacas/fisiologia , Condicionamento Físico Animal/fisiologia , Resistência Física/fisiologia , Adaptação Fisiológica/fisiologia , Altitude , Animais , Metabolismo Energético/fisiologia , Hemodinâmica/fisiologia , Masculino , Miocárdio/metabolismo , Consumo de Oxigênio/fisiologia , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , TranscriptomaRESUMO
Carbon nanotubes (CNTs) are formed by rolling up a single graphite sheet into a tube. Among the different types of CNTs, the multi-walled carbon nanotubes (MWCNTs) comprise a set of concentric nanotubes with perfect structures. Several uses for MWCNTs have been suggested to be included in biological applications such as manufacturing of biosensors, carriers of drugs. However, before these materials can be put on the market, it is necessary to know their genotoxic effects. Thus, this study aims to evaluate the mutagenicity of multi-walled carbon nanotubes (MWCNTs) functionalized in somatic cells of Drosophila melanogaster, using the somatic mutation and recombination test (SMART). This assay detects the loss of heterozygosity of marker genes expressed phenotypically on the wings of the fly. Larvae of three days were used, resulting from ST cross, with basal levels of the cytochrome P450 and larvae of high metabolic bioactivity capacity (HB cross). They were treated with different concentrations of MWCNTs functionalized. The MH descendants, analyzed in both ST and HB crosses, had no significant effects on the frequency of mutant. Based on the results and on the experimental conditions mentioned in this study, it was concluded that MWCNTs were not mutagenic in D. melanogaster.
Assuntos
Drosophila melanogaster/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Animais , Relação Dose-Resposta a Droga , Drosophila melanogaster/genética , Feminino , Larva/efeitos dos fármacos , Masculino , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Mutação , Recombinação Genética , Taxa de Sobrevida , Asas de Animais/citologia , Asas de Animais/efeitos dos fármacosRESUMO
The conformational preferences of a series of hydroxyflavones were studied by Raman and FTIR spectroscopies, coupled to Density Functional Theory calculations. Special attention was paid to the effect of hydroxyl substitution, due to its importance on the biological activity of these compounds. Their conformational preferences were found to be determined mainly by the orientation of the hydroxylic groups at C(7) and within the catechol moiety, leading to the occurrence of distinct conformers in the solid state. A complete assignment of the experimental spectra was carried out for these molecules, in the light of their most stable conformers and the corresponding predicted vibrational pattern.
Assuntos
Flavonas/química , Modelos Moleculares , Conformação Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral RamanRESUMO
Mitochondrial function is modulated by multiple approaches including physical activity, which can afford cross-tolerance against a variety of insults. We therefore aimed to analyze the effects of endurance-training (ET) and chronic-intermittent hypobaric-hypoxia (IHH) on liver mitochondrial bioenergetics and whether these effects translate into benefits against in vitro salicylate mitochondrial toxicity. Twenty-eight young-adult male rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE), hypoxic-sedentary (HS) and hypoxic-exercised (HE). ET consisted of 1h/days of treadmill running and IHH of simulated atmospheric pressure of 49.3 kPa 5h/days during 5weeks. Liver mitochondrial oxygen consumption, transmembrane-electric potential (ΔΨ) and permeability transition pore induction (MPTP) were evaluated in the presence and absence of salicylate. Aconitase, MnSOD, caspase-3 and 8 activities, SH, MDA, SIRT3, Cyp D, HSP70, and OXPHOS subunit contents were assessed. ET and IHH decreased basal mitochondrial state-3 and state-4 respiration, although no alterations were observed in ΔΨ endpoints evaluated in control mitochondria. In the presence of salicylate, ET and IHH decreased state-4 and lag-phase of ADP-phosphorylation. Moreover, ADP-lag phase in hypoxic was further lower than in normoxic groups. Neither ET nor IHH altered the susceptibility to calcium-induced MPTP. IHH lowered MnSOD and increased aconitase activities. ET and IHH decreased caspase 8 activity whereas no effect was observed on caspase 3. The levels of SIRT3 increased with ET and IHH and Cyp D decreased with IHH. Data suggest that ET and IHH do not alter general basal liver mitochondrial function, but may attenuate some adverse effects of salicylate.