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1.
Stress ; 27(1)2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022295

RESUMO

Objective: People living with HIV (PLWH) experience high rates of childhood trauma exposure, which is a significant risk factor for the development of posttraumatic stress disorder (PTSD). Because Black Americans living in urban environments are exposed to high levels of trauma, suffer from chronic PTSD, and are at increased risk for HIV infection, it is important to understand how HIV status interacts with childhood maltreatment to influence PTSD symptom severity and underlying psychophysiology. Methods: The current cross-sectional study assessed whether HIV status interacts with childhood maltreatment to influence PTSD symptom severity and heart rate variability during a dark-enhanced startle (DES) task in 88 Black women with (n=30) and without HIV (n=58). Results: HIV was associated with greater PTSD symptom severity only in women with low levels of childhood maltreatment (p=.024). Startle potentiation during DES was highest in women living without HIV and with high childhood maltreatment (p=.018). In women who had experienced low levels of childhood maltreatment, respiratory sinus arrhythmia (RSA) was lower during the dark phase of DES in women living without HIV than women living with HIV (WLWH), (p=.046). RSA during the light phase of DES was lower in WLWH than in women living without HIV (p=.042). Conclusion: In the current sample of Black women, HIV status was associated with PTSD symptom severity in a manner dependent on level of childhood maltreatment, suggesting that HIV status may be an important factor to consider for behavioral and pharmacological treatment strategies for PTSD. Additionally, HIV status is associated with lower percent potentiation to darkness and lower RSA during the light phase of DES, suggesting physiological mechanisms by which HIV may contribute to PTSD symptoms in individuals exposed to low levels of childhood maltreatment.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Negro ou Afro-Americano , Infecções por HIV , Frequência Cardíaca , Reflexo de Sobressalto , Transtornos de Estresse Pós-Traumáticos , Humanos , Feminino , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Frequência Cardíaca/fisiologia , Adulto , Estudos Transversais , Reflexo de Sobressalto/fisiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/psicologia , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Psicofisiologia , Arritmia Sinusal Respiratória/fisiologia
2.
Am J Perinatol ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38307105

RESUMO

Gestational metabolic diseases adversely impact the health of pregnant persons and their offspring. Pregnant persons of color are impacted disproportionately by gestational metabolic disease, highlighting the need to identify additional risk factors contributing to racial-ethnic pregnancy-related health disparities. Trauma exposure and posttraumatic stress disorder (PTSD) are associated with increased risk for cardiometabolic disorders in nonpregnant persons, making them important factors to consider when identifying contributors to gestational metabolic morbidity and mortality health disparities. Here, we review current literature investigating trauma exposure and posttraumatic stress disorder as psychosocial risk factors for gestational metabolic disorders, inclusive of gestational diabetes, low birth weight and fetal growth restriction, gestational hypertension, and preeclampsia. We also discuss the physiological mechanisms by which trauma and PTSD may contribute to gestational metabolic disorders. Ultimately, understanding the biological underpinnings of how trauma and PTSD, which disproportionately impact people of color, influence risk for gestational metabolic dysfunction is critical to developing therapeutic interventions that reduce complications arising from gestational metabolic disease. KEY POINTS: · Gestational metabolic diseases disproportionately impact the health of pregnant persons of color.. · Trauma and PTSD are associated with increased risk for cardiometabolic disorders in nonpregnant per.. · Trauma and PTSD impact physiological cardiometabolic mechanisms implicated in gestational metabolic..

3.
Genet Mol Biol ; 45(2): e20210354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35671453

RESUMO

Brazil has one of the highest rates of scientific production, occupying the ninth position among countries with genome-sequencing projects. Considering the rapid development of this research area and the diversity of professionals involved, the present study aims to understand the expectations, past experiences and the current scenario of Brazilian research in bioinformatics and genomics. The present research was carried out by analyzing the perceptions of 576 researchers in genomics and bioinformatics in Brazil through content and sentiment analysis techniques. This group of participants is equivalent to 48% of the members of the research community. The results suggest that most researchers have a positive perception of the potential of this research area. However, there is concern about the lack of funding for investing in equipment and professional training. As part of a wish list for the future, researchers highlighted the need for higher funding, formal education, and collaboration among research networks. When asked about genomics and bioinformatics in other countries, the participants recognize that sequencing technologies and infrastructure are more accessible, allowing better data volume expansion.

4.
Nucleic Acids Res ; 47(14): 7430-7443, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31147703

RESUMO

Clonal expansion of mitochondrial DNA (mtDNA) deletions is an important pathological mechanism in adults with mtDNA maintenance disorders, leading to a mosaic mitochondrial respiratory chain deficiency in skeletal muscle. This study had two aims: (i) to determine if different Mendelian mtDNA maintenance disorders showed similar pattern of mtDNA deletions and respiratory chain deficiency and (ii) to investigate the correlation between the mitochondrial genetic defect and corresponding respiratory chain deficiency. We performed a quantitative analysis of respiratory chain deficiency, at a single cell level, in a cohort of patients with mutations in mtDNA maintenance genes. Using the same tissue section, we performed laser microdissection and single cell genetic analysis to investigate the relationship between mtDNA deletion characteristics and the respiratory chain deficiency. The pattern of respiratory chain deficiency is similar with different genetic defects. We demonstrate a clear correlation between the level of mtDNA deletion and extent of respiratory chain deficiency within a single cell. Long-range and single molecule PCR shows the presence of multiple mtDNA deletions in approximately one-third of all muscle fibres. We did not detect evidence of a replicative advantage for smaller mtDNA molecules in the majority of fibres, but further analysis is needed to provide conclusive evidence.


Assuntos
DNA Mitocondrial/genética , Genes Mitocondriais/genética , Mitocôndrias Musculares/genética , Doenças Mitocondriais/genética , Fibras Musculares Esqueléticas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Deleção de Sequência , Análise de Célula Única
5.
Entropy (Basel) ; 23(2)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33670017

RESUMO

The high proportion of CO2/CH4 in low aggregated value natural gas compositions can be used strategically and intelligently to produce more hydrocarbons through oxidative methane coupling (OCM). The main goal of this study was to optimize direct low-value natural gas conversion via CO2-OCM on metal oxide catalysts using robust multi-objective optimization based on an entropic measure to choose the most preferred Pareto optimal point as the problem's final solution. The responses of CH4 conversion, C2 selectivity, and C2 yield are modeled using the response surface methodology. In this methodology, decision variables, e.g., the CO2/CH4 ratio, reactor temperature, wt.% CaO and wt.% MnO in ceria catalyst, are all employed. The Pareto optimal solution was obtained via the following combination of process parameters: CO2/CH4 ratio = 2.50, reactor temperature = 1179.5 K, wt.% CaO in ceria catalyst = 17.2%, wt.% MnO in ceria catalyst = 6.0%. By using the optimal weighting strategy w1 = 0.2602, w2 = 0.3203, w3 = 0.4295, the simultaneous optimal values for the objective functions were: CH4 conversion = 8.806%, C2 selectivity = 51.468%, C2 yield = 3.275%. Finally, an entropic measure used as a decision-making criterion was found to be useful in mapping the regions of minimal variation among the Pareto optimal responses and the results obtained, and this demonstrates that the optimization weights exert influence on the forecast variation of the obtained response.

6.
Clin Genet ; 97(2): 276-286, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31600844

RESUMO

Autosomal dominant progressive external ophthalmoplegia (adPEO) is a late-onset, Mendelian mitochondrial disorder characterised by paresis of the extraocular muscles, ptosis, and skeletal-muscle restricted multiple mitochondrial DNA (mtDNA) deletions. Although dominantly inherited, pathogenic variants in POLG, TWNK and RRM2B are among the most common genetic defects of adPEO, identification of novel candidate genes and the underlying pathomechanisms remains challenging. We report the clinical, genetic and molecular investigations of a patient who presented in the seventh decade of life with PEO. Oxidative histochemistry revealed cytochrome c oxidase-deficient fibres and occasional ragged red fibres showing subsarcolemmal mitochondrial accumulation in skeletal muscle, while molecular studies identified the presence of multiple mtDNA deletions. Negative candidate screening of known nuclear genes associated with PEO prompted diagnostic exome sequencing, leading to the prioritisation of a novel heterozygous c.547G>C variant in GMPR (NM_006877.3) encoding guanosine monophosphate reductase, a cytosolic enzyme required for maintaining the cellular balance of adenine and guanine nucleotides. We show that the novel c.547G>C variant causes aberrant splicing, decreased GMPR protein levels in patient skeletal muscle, proliferating and quiescent cells, and is associated with subtle changes in nucleotide homeostasis protein levels and evidence of disturbed mtDNA maintenance in skeletal muscle. Despite confirmation of GMPR deficiency, demonstrating marked defects of mtDNA replication or nucleotide homeostasis in patient cells proved challenging. Our study proposes that GMPR is the 19th locus for PEO and highlights the complexities of uncovering disease mechanisms in late-onset PEO phenotypes.


Assuntos
DNA Mitocondrial/genética , GMP Redutase/genética , Transtornos de Início Tardio/genética , Músculo Esquelético/enzimologia , Oftalmoplegia/genética , Adenina/metabolismo , Idoso , Células Cultivadas , Deficiência de Citocromo-c Oxidase/metabolismo , Replicação do DNA , DNA Mitocondrial/metabolismo , Feminino , Fibroblastos/enzimologia , GMP Redutase/deficiência , GMP Redutase/metabolismo , Guanina/metabolismo , Células HEK293 , Células HeLa , Heterozigoto , Humanos , Transtornos de Início Tardio/metabolismo , Transtornos de Início Tardio/patologia , Músculo Esquelético/patologia , Oftalmoplegia/enzimologia , Oftalmoplegia/fisiopatologia , Fosforilação Oxidativa , Splicing de RNA , Deleção de Sequência , Sequenciamento do Exoma
7.
J Stroke Cerebrovasc Dis ; 29(8): 104971, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689585

RESUMO

BACKGROUND AND PURPOSE: Mean Platelet Volume (MPV) is a marker of platelet activity and it is an independent predictor for long-term outcome in stroke patients. The aim of this study was to evaluate the association between baseline MPV value and clinical outcome at 90-days in anterior circulation stroke and large vessel occlusion (LVO) patients submitted to mechanical thrombectomy (MT). METHODS: We conducted a prospective observational cohort study in acute ischemic stroke (AIS) patients submitted to MT between January 2017 and May 2018. MPV was measured at admission. Patients were initially stratified into two groups according to the mean MPV level. We also compared groups that were stratified according to the MPV cut-off obtained by Peng F et al (10,4 fL) and performed analyses among MPV terciles. RESULTS: A total of 129 patients were included. Mean level of MPV was 10,9 fL. Patients with embolic stroke of undetermined source (ESUS) had significantly higher rates of good outcome at 3 months compared with large-artery atherosclerotic disease and cardioembolism [(82,9%) vs (78,3%) vs (55,2%); p=0,009]. There were no statistically significant differences in the mean MPV value (p=0,222), successful recanalization (p=0,464) and mortality (p=0,343) when evaluated for all TOAST etiologies. There were no statistically significant differences between the two groups according to the MPV level (10,4 and 10,9 fL) or between the terciles (lowest tertile <10,3 fL, median 10,3 - 11,3 fL, highest >11,3fL) concerning functional outcome at 3 months (p=0,357; p=0,24 and p=0,558, respectively), successful recanalization (p=0,108; p=0,582 and p=0,899, respectively) or mortality at 3 months (p=0,465; p=0,061 and p=0,484, respectively). CONCLUSION: Our study did not find an association between elevated MPV and worse outcome at 3 months in patients with acute anterior circulation stroke and LVO treated with MT. Since ischemic strokes have different pathophysiologic mechanisms, MPV may have distinct prognostic value according to each stroke etiology.


Assuntos
Isquemia Encefálica/terapia , Volume Plaquetário Médio , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Bases de Dados Factuais , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Trombectomia/efeitos adversos , Trombectomia/mortalidade , Fatores de Tempo , Resultado do Tratamento
8.
Gen Dent ; 68(4): 36-41, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32597776

RESUMO

The aim of this case-control study was to evaluate the association between denture-related oral mucosal lesions and Alzheimer disease (AD) in older adults (60 years and older). Seventy elderly adults (35 with AD and 35 classified as mentally healthy) were included in this study, which was carried out in a Brazilian medical center. Clinical data on oral lesions and mucosal findings were recorded, including alterations in the color or appearance of any lesions, if present. The influence of possible confounding factors, including sex, age, race, education level, health conditions, harmful habits, gait speed, and oral status (use of removable prostheses and denture hygiene), was analyzed. There was no statistically significant difference between groups in the frequency of denture-related oral mucosal lesions. Logistic regression analysis showed a higher prevalence of AD among individuals aged 80 years and older, those who were illiterate, users of tobacco, and patients with a slower gait. These results suggest that AD is not a risk factor for denture-related oral mucosal lesions.


Assuntos
Doença de Alzheimer , Estomatite sob Prótese , Idoso , Idoso de 80 Anos ou mais , Brasil , Estudos de Casos e Controles , Dentaduras , Humanos , Fatores Sexuais
9.
Ann Neurol ; 83(1): 115-130, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29283441

RESUMO

OBJECTIVE: Single, large-scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large-scale mtDNA deletions in skeletal muscle. METHODS: We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large-scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction. RESULTS: We have defined 3 "classes" of single, large-scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class. INTERPRETATION: Combining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex-specific protein-encoding genes. Furthermore, removal of mt-tRNA genes impacts specific complexes only at high deletion levels, when complex-specific protein-encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115-130.


Assuntos
DNA Mitocondrial/genética , Doenças Mitocondriais/genética , Deleção de Sequência/genética , Adulto , Idoso , Biópsia , Estudos de Coortes , Complexo I de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Deleção de Genes , Dosagem de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/patologia , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Fosforilação Oxidativa , Adulto Jovem
10.
Ann Neurol ; 84(2): 289-301, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30014514

RESUMO

OBJECTIVE: In patients with mitochondrial DNA (mtDNA) maintenance disorders and with aging, mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to identify the sub-cellular origin and potential mechanisms underlying this process. METHODS: Serial skeletal muscle cryosections from patients with multiple mtDNA deletions were subjected to subcellular immunofluorescent, histochemical, and genetic analysis. RESULTS: We report respiratory chain-deficient perinuclear foci containing mtDNA deletions, which show local elevations of both mitochondrial mass and mtDNA copy number. These subcellular foci of respiratory chain deficiency are associated with a local increase in mitochondrial biogenesis and unfolded protein response signaling pathways. We also find that the commonly reported segmental pattern of mitochondrial deficiency is consistent with the three-dimensional organization of the human skeletal muscle mitochondrial network. INTERPRETATION: We propose that mtDNA deletions first exceed the biochemical threshold causing biochemical deficiency in focal regions adjacent to the myonuclei, and induce mitochondrial biogenesis before spreading across the muscle fiber. These subcellular resolution data provide new insights into the possible origin of mitochondrial respiratory chain deficiency in mitochondrial myopathy. Ann Neurol 2018;84:289-301.


Assuntos
Envelhecimento/genética , DNA Mitocondrial/genética , DNA Mitocondrial/ultraestrutura , Deleção de Genes , Músculo Esquelético/fisiologia , Músculo Esquelético/ultraestrutura , Envelhecimento/patologia , Humanos , Fibras Musculares Esqueléticas/patologia , Fibras Musculares Esqueléticas/ultraestrutura , Músculo Esquelético/patologia , Frações Subcelulares/patologia , Frações Subcelulares/ultraestrutura
11.
J Theor Biol ; 460: 134-141, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30315812

RESUMO

The Minnaert model, which can account for the reaction kinetics between cytochrome oxidase and cytochrome c (Cytc), has been used to justify equal binding rate constants for reduced and oxidized Cytc. Here we extend the model beyond reversible binding of Cytc and its irreversible oxidation to include CuA, heme a and the oxidation cycle of the binuclear center. The model reproduces the experimental reduction of CuA and heme a during turnover and the low population of the ferryl and ferrous heme a3. It predicts that the off rate constants for reduced and oxidized Cytc can be unequal and that the non-Nernst response of CuA and heme a is due to disequilibrium between free Cytc and CuA rather than redox anticooperativity.


Assuntos
Citocromos c/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Transporte de Elétrons , Modelos Químicos , Cinética , Oxirredução , Ligação Proteica
12.
J Org Chem ; 84(17): 11042-11053, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31419129

RESUMO

The strange tautomeric equilibrium behavior exhibited by a new o-hydroxyphenyl diazepine derivative when the compound is analyzed both in solution and solid state opens the structural study of the enol-imino-keto-enamine forms and the influence of the intermolecular interactions in their equilibrium. The expected enol-imino form, in which the enol is part of a phenyl system and a strong O-H···N intramolecular hydrogen bond is established, results the most stable tautomer in gas phase (theoretical calculations) and was detected by NMR spectroscopy when the compound was dissolved in aprotic solvents. Nevertheless, the keto-enamine form ,in which the keto group integrates a cyclohexadienone moiety and the aromaticity of the phenol is lost, was the only tautomer in the crystal lattice according to single-crystal X-ray diffraction, vibrational spectroscopy, and diffuse reflectance results. The last form was also found as the main tautomer in UV-vis and NMR spectroscopy when a protic solvent was employed.

13.
Oecologia ; 191(4): 919-929, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31624960

RESUMO

Recently, community ecology has emphasized the multi-facetted aspects of biological diversity by linking species traits and the environment. Here, we explored environmental correlates of taxonomically-based and traits-based compositional distances using a comprehensive data set of diatom and macroinvertebrate communities. We also explored the responses of different beta diversity components (i.e., overall beta diversity, turnover, and nestedness) of beta diversity facets (i.e., taxonomically and traits-based beta diversity) to environmental distances. Partial Mantel tests were used to test the relationships between beta diversity and environmental distance (while controlling for spatial distances). Taxonomically-based beta diversity varied much more than traits-based beta diversity, indicating strong functional convergence. We found that taxonomically-based beta diversity was largely driven by the turnover component. However, the nestedness component contributed more to overall traits-based beta diversity than the turnover component. Taxonomically-based beta diversity was significantly correlated with environmental distances for both diatoms and macroinvertebrates. Thus, we found support for the role of environmental filtering as a driver of community dissimilarities of rather different biological groups. However, the strength of these relationships between beta diversity and environmental distances varied depending on the biological group, facet, component, and the way which the environmental variables were selected to calculate the explanatory (distance) matrix. Our results indicated that both taxonomically and traits-based approaches are still needed to better understand patterns and mechanisms affecting the organization of biological communities in streams. This is because different facets of biological communities may be driven by different mechanisms.


Assuntos
Diatomáceas , Rios , Biodiversidade , Ecologia
14.
J Stroke Cerebrovasc Dis ; 28(3): 627-631, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30472174

RESUMO

Mechanical thrombectomy (MT) in combination with intravenous thrombolysis (IVT) is the standard of care for patients with acute ischemic stroke with anterior circulation large vessel occlusion. The particular benefit of IVT in these patients is unknown. We performed a retrospective analysis of patients submitted to MT at our center between January 2015 and June 2017. Functional outcome was prospectively assessed using modified Rankin scale (mRS) at 3 months. A total of 234 patients were enrolled, 152 (65%) in the combined treatment group and 82 (35%) in the direct MT group. Patients receiving combined treatment had a higher frequency of intracranial internal carotid artery occlusion (48 [31.6%] versus 16 [19.5%], P = .048) and significantly less strokes of cardioembolic etiology (72 [47.4%] versus 57 [69.5%], P = .01). Other baseline characteristics did not differ between the 2 groups. Good functional outcome at 3 months (mRS 0-2) was trending toward being higher in patients in the combined treatment group (98 [64.9%] versus 42 [52.5%], P = .066). Rates of symptomatic intracranial hemorrhage (5 [3.3%] versus 4 [4.9%], P = .723) and mortality (15 [9.9%] versus 14 [17.5%], P = .099) did not differ between groups. In multivariate logistic regression analysis, we did not find a statistically significant association between the use of IVT and any of the outcomes studied. Our results suggest that combined treatment carries similar effectiveness and safety than direct MT. Randomized controlled trials regarding this subject are warranted.


Assuntos
Isquemia Encefálica/terapia , Artéria Carótida Interna , Estenose das Carótidas/terapia , Fibrinolíticos/administração & dosagem , Infarto da Artéria Cerebral Média/terapia , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Terapia Trombolítica/métodos , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/fisiopatologia , Artéria Carótida Interna/fisiopatologia , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/mortalidade , Estenose das Carótidas/fisiopatologia , Terapia Combinada , Avaliação da Deficiência , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infarto da Artéria Cerebral Média/diagnóstico , Infarto da Artéria Cerebral Média/mortalidade , Infarto da Artéria Cerebral Média/fisiopatologia , Infusões Intravenosas , Hemorragias Intracranianas/etiologia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Trombectomia/efeitos adversos , Trombectomia/mortalidade , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Resultado do Tratamento
15.
Biochim Biophys Acta Bioenerg ; 1859(8): 555-566, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29704499

RESUMO

Cytochrome oxidase is the terminal oxidase of the mitochondrial electron transport chain and pumps 4 protons per oxygen reduced to water. Spectral shifts in the α-band of heme a have been observed in multiple studies and these shifts have the potential to shed light on the proton pumping intermediates. Previously we found that heme a had two spectral components in the α-band during redox titrations in living RAW 264.7 mouse macrophage cells, the classical 605 nm form and a blue-shifted 602 nm form. To confirm these spectral changes were not an artifact due to the complex milieu of the living cell, redox titrations were performed in the isolated detergent-solubilized bovine enzyme from both the Soret- and α-band using precise multiwavelength spectroscopy. This data verified the presence of the 602 nm form in the α-band, revealed a similar shift of heme a in the Soret-band and ruled out the reversal of calcium binding as the origin of the blue shift. The 602 nm form was found to be stabilized at high pH or by binding of azide, which is known to blue shift the α-band of heme a. Azide also stabilized the 602 nm form in the living cells. It is concluded there is a form of cytochrome oxidase in which heme a undergoes a blue shift to a 602 nm form and that redox titrations can be successfully performed in living cells where the oxidase operates in its authentic environment and in the presence of a proton motive force.


Assuntos
Detergentes/química , Complexo IV da Cadeia de Transporte de Elétrons/química , Heme/química , Macrófagos/enzimologia , Animais , Bovinos , Células Cultivadas , Detergentes/metabolismo , Transporte de Elétrons , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Heme/metabolismo , Concentração de Íons de Hidrogênio , Camundongos , Oxirredução
16.
Cerebrovasc Dis ; 46(1-2): 40-45, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30064126

RESUMO

BACKGROUND: A 2013 consensus statement recommended the use of the modified Treatment In Cerebral Ischemia (mTICI) scale to evaluate angiographic revascularization after endovascular treatment (EVT) of acute ischemic stroke due to its higher inter-rater agreement and capacity of clinical outcome prediction. The current definition of successful revascularization includes the achievement of grades mTICI 2b or 3. However, mTICI 2b grade encompasses a large heterogeneity of revascularization states, and prior studies suggested that the magnitude of benefit derived from mTICI 2b and mTICI 3 does not seem to be equivalent. In a way to restrain the referred heterogeneity, Goyal et al. [J Neurointerv Surg 2014; 6: 83-86] proposed a revised mTICI scale that includes a 2c grade (rTICI). METHODS: Retrospective analysis of prospectively collected data from consecutive cases of EVT for anterior circulation large-vessel occlusion, performed between January 2015 and July 2017. Patients with mTICI 2b or 3 grades were reclassified according to the rTICI scale, and the outcomes between the 3 revascularization grades (rTICI 2b, 2c, 3) compared. RESULTS: Our study population of 226 patients (64 rTICI 2b, 30 rTICI 2c, 132 rTICI 3) has a mean age of 71 years, 48.2% males, median baseline NIHSS of 16 (13-19) and ASPECTS of 8 (7-9). The 3 revascularization grades are represented by homogeneous populations. Logistic regression analysis showed statistically significant higher rates of functional independence at 3 months (65.9 vs. 50.0%; adjusted OR 0.39, 95% CI 0.18-0.86), with lower rates of mortality (8.3 vs. 15.6%; adjusted OR 3.54, 95% CI 1.14-10.97) and intracranial hemorrhage (ICH) in rTICI 3 than 2b groups. When comparing rTICI 3 with 2c groups, there were only statistically significant differences in the total ICH rate (8.3 vs. 26.7%; adjusted OR 7.08, 95% CI 1.80-27.82) but not in symptomatic ICH. CONCLUSIONS: These results corroborate the scarce prior findings suggesting that patients with rTICI 2c grade should be reported separately, since they have similar outcomes to rTICI 3, and better than rTICI 2b patients. Therefore, we suggest resetting the angiographic revascularization endpoint to perfect revascularization (rTICI 2c or 3 grades), a target that neurointerventionalists should strive to achieve.


Assuntos
Isquemia Encefálica/cirurgia , Revascularização Cerebral/métodos , Procedimentos Endovasculares/métodos , Determinação de Ponto Final , Acidente Vascular Cerebral/cirurgia , Terminologia como Assunto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/classificação , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Angiografia Cerebral , Revascularização Cerebral/efeitos adversos , Revascularização Cerebral/normas , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/normas , Determinação de Ponto Final/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Indicadores de Qualidade em Assistência à Saúde , Recuperação de Função Fisiológica , Estudos Retrospectivos , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
17.
J Pathol ; 241(2): 236-250, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27659608

RESUMO

Mitochondria are double-membrane-bound organelles that are present in all nucleated eukaryotic cells and are responsible for the production of cellular energy in the form of ATP. Mitochondrial function is under dual genetic control - the 16.6-kb mitochondrial genome, with only 37 genes, and the nuclear genome, which encodes the remaining ∼1300 proteins of the mitoproteome. Mitochondrial dysfunction can arise because of defects in either mitochondrial DNA or nuclear mitochondrial genes, and can present in childhood or adulthood in association with vast clinical heterogeneity, with symptoms affecting a single organ or tissue, or multisystem involvement. There is no cure for mitochondrial disease for the vast majority of mitochondrial disease patients, and a genetic diagnosis is therefore crucial for genetic counselling and recurrence risk calculation, and can impact on the clinical management of affected patients. Next-generation sequencing strategies are proving pivotal in the discovery of new disease genes and the diagnosis of clinically affected patients; mutations in >250 genes have now been shown to cause mitochondrial disease, and the biochemical, histochemical, immunocytochemical and neuropathological characterization of these patients has led to improved diagnostic testing strategies and novel diagnostic techniques. This review focuses on the current genetic landscape associated with mitochondrial disease, before focusing on advances in studying associated mitochondrial pathology in two, clinically relevant organs - skeletal muscle and brain. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Encéfalo/patologia , DNA Mitocondrial/genética , Mitocôndrias/genética , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Músculo Esquelético/patologia , Humanos , Mitocôndrias/metabolismo , Mutação/genética
18.
Oecologia ; 186(1): 205-216, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29090405

RESUMO

The regional occupancy and local abundance of species are thought to be strongly correlated to their body size, niche breadth and niche position. The strength of the relationships among these variables can also differ between different organismal groups. Here, we analyzed data on stream diatoms and insects from a high-latitude drainage basin to investigate these relationships. To generate measures of niche position and niche breadth for each species, we used sets of local environmental and catchment variables separately, applying the outlying mean index analysis. Beta regression and negative binomial generalized linear models were run to predict regional occupancy and mean local abundance, respectively. We found a positive occupancy-abundance relationship in both diatoms and insects, and that niche-based variables were the main predictors of variation in regional occupancy and local abundance. This finding was mainly due to local environmental niche position, whereas the effects of niche breadth on regional occupancy and local abundance were less important. We also found a relationship between body size and local abundance or regional occupancy of diatoms. Our results thus add to current macroecological research by emphasizing the strong importance of niche position rather than niche breadth and body size for regional occupancy and local abundance in rarely studied organisms (e.g., diatoms and insects) and ecosystems (i.e., wilderness streams).


Assuntos
Diatomáceas , Rios , Animais , Tamanho Corporal , Ecossistema , Insetos
19.
Rheumatol Int ; 38(8): 1437-1442, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29907885

RESUMO

Absolute cardiovascular risk of an individual with rheumatoid arthritis (RA) is greater when compared to the general population, and several factors have proven to be important for the development of coronary artery disease (CAD) in these patients, including factors related to the underlying disease, such as the systemic inflammatory response, drugs used in its treatment, and a higher prevalence of traditional risk factors for CAD. Our aim is to describe the recognition and control frequencies of systemic arterial hypertension (SAH), dyslipidemia, and diabetes mellitus (DM) in RA patients. Patients with RA answered a questionnaire focused on their general knowledge of the risk factors for CAD, as well as on the recognition of the risk factors that they possess. The patient's information, collected from a structured medical record, was reviewed to evaluate the control of risk factors. Hundred and thirty-four patients were included in the study. One patient was excluded due to the impossibility of reviewing her medical records. Therefore, 133 patients remained in the study. Patients had a mean (SD) age of 57.3 (12.9) years. SAH was diagnosed in 88 subjects, with a recognition frequency of 89.8%, and 63.3% had desirable blood pressure control. Seventy-two patients were diagnosed with dyslipidemia; 68.1% recognized that they had dyslipidemia and 69.4% achieved desirable LDL-c control. Twenty-two patients had DM; 90.9% admitted being diabetic and 40.9% had desirable glycemic control. The frequencies of the CAD risk factor recognition and control were high in comparison to those described for the general population.


Assuntos
Artrite Reumatoide/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Idoso , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
20.
Molecules ; 23(11)2018 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-30453683

RESUMO

This paper describes a bioprocess to obtain omegas-6 and 9 from the hydrolysis of Açaí (Euterpe oleracea Martius) and Buriti (Mauritia flexuosa) oils by lipases immobilized on octyl-sepharose. For this, oils and butters were initially selected as the carbon source which resulted in higher production of lipases in Beauveria bassiana and Fusarium oxysporum cultures. The carbon source that provided secretion of lipase by B. bassiana was Açaí oil, and for F. oxysporum, Bacuri butter. Lipases obtained under these conditions were immobilized on octyl-sepharose, and both, the derivatives and the crude extracts were biochemically characterized. It was observed that the immobilization promoted an increase of stability in B. bassiana and F. oxysporum lipase activities at the given temperatures and pH. In addition, the immobilization promoted hyperactivation of B. bassiana and F. oxysporum lipase activities being 23.5 and 11.0 higher than free enzyme, respectively. The hydrolysis of Açaí and Buriti oils by the derivatives was done in a biphasic (organic/aqueous) system, and the products were quantified in RP-HPLC. The results showed the potential of these immobilized lipases to obtain omegas-6 and 9 from Brazilian natural oils. This work may improve the enzymatic methodologies for obtaining foods and drugs enriched with fatty acids.


Assuntos
Arecaceae/química , Carotenoides/química , Euterpe/química , Lipase/química , Óleos de Plantas/química , Carbono/química , Cromatografia Líquida , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Espectrometria de Massas em Tandem
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