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1.
Am J Physiol Heart Circ Physiol ; 327(3): H601-H613, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38995211

RESUMO

Nighttime blood pressure (BP) and BP dipping (daytime-nighttime BP) are prognostic for cardiovascular disease. When compared with other racial/ethnic groups, Black Americans exhibit elevated nighttime BP and attenuated BP dipping. Neighborhood deprivation may contribute to disparities in cardiovascular health, but its effects on resting and ambulatory BP patterns in young adults are unclear. Therefore, we examined associations between neighborhood deprivation with resting and nighttime BP and BP dipping in young Black and White adults. We recruited 19 Black and 28 White participants (23 males/24 females, 21 ± 1 yr, body mass index: 26 ± 4 kg/m2) for 24-h ambulatory BP monitoring. We assessed resting BP, nighttime BP, and BP dipping (absolute dip and nighttime:daytime BP ratio). We used the area deprivation index (ADI) to assess average neighborhood deprivation during early and mid-childhood and adolescence. When compared with White participants, Black participants exhibited higher resting systolic and diastolic BP (Ps ≤ 0.029), nighttime systolic BP (114 ± 9 vs. 108 ± 9 mmHg, P = 0.049), diastolic BP (63 ± 8 vs. 57 ± 7 mmHg, P = 0.010), and attenuated absolute systolic BP dipping (12 ± 5 vs. 9 ± 7 mmHg, P = 0.050). Black participants experienced greater average ADI scores compared with White participants [110 (10) vs. 97 (22), P = 0.002], and select ADI scores correlated with resting BP and some ambulatory BP measures. Within each race, select ADI scores correlated with some BP measures for Black participants, but there were no ADI and BP correlations for White participants. In conclusion, our findings suggest that neighborhood deprivation may contribute to higher resting BP and impaired ambulatory BP patterns in young adults warranting further investigation in larger cohorts.NEW & NOTEWORTHY We demonstrate that young Black adults exhibit higher resting blood pressure, nighttime blood pressure, and attenuated systolic blood pressure dipping compared with young White adults. Black adults were exposed to greater neighborhood deprivation, which demonstrated some associations with resting and ambulatory blood pressure. Our findings add to a growing body of literature indicating that neighborhood deprivation may contribute to increased blood pressure.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea , Ritmo Circadiano , Adolescente , Feminino , Humanos , Masculino , Adulto Jovem , Negro ou Afro-Americano , Disparidades nos Níveis de Saúde , Hipertensão/diagnóstico , Hipertensão/etnologia , Fatores Raciais , Características de Residência , Brancos
2.
J Neuroinflammation ; 21(1): 281, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39487492

RESUMO

BACKGROUND: Secondary autoimmune disease (SAID) in the context of alemtuzumab treatment is one of the main safety concerns that may arise following administration in people with multiple sclerosis (pwMS). Contributing factors underlying this adverse event are not well understood. The purpose of this systematic review was to appraise the literature investigating the role of alemtuzumab in the development of SAID in pwMS following treatment and identify potential biomarkers/ risk factors that may be predictive of onset of this manifestation. METHODS: Relevant publications were retrieved from PubMed, Embase, and Web of Science using a three-pronged search strategy containing the following keywords: "multiple sclerosis"; "alemtuzumab"; and "autoimmunity". Studies that fulfilled the specified eligibility criteria and investigated SAID development after alemtuzumab in pwMS were included in the final analysis. RESULTS: 19 papers were included in the final review. Approximately, 47.92% of pwMS treated with alemtuzumab experienced SAID. A variety of biomarkers and risk factors were noted in the development of SAID, with a focus on immunological changes, including: increased homeostatic proliferation and T cell cycling, along with consistently elevated baseline serum IL-21 levels and thyroid autoantibodies. There was no significant association between known human leukocyte antigen (HLA) risk alleles, lymphocyte profile or dynamics and SAID development. CONCLUSIONS: While the mechanism underlying SAID following alemtuzumab is not fully understood, potential biomarkers and risk factors that may assist in elucidating mechanisms underlying this phenomenon have been documented in several independent studies. Following immunodepletion from alemtuzumab, an IL-21 driven increase in homeostatic proliferation and T cell cycling may disrupt tolerance mechanisms leading to an increase in the propensity toward alemtuzumab-induced autoimmunity. Further research is necessary to clarify the physiological changes after alemtuzumab therapy that trigger SAID in pwMS.


Assuntos
Alemtuzumab , Esclerose Múltipla , Alemtuzumab/efeitos adversos , Alemtuzumab/uso terapêutico , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Autoimunidade/efeitos dos fármacos , Autoimunidade/imunologia , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico
3.
J Med Virol ; 95(7): e28955, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37465865

RESUMO

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence-Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27-2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP-associated factors [granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-ß, interleukin (IL)-1ß, IL-2, IL-8, IL-13, tumor necrosis factor (TNF)-α, IL-1α, IL-1RA, IL-7, IL-15, C-X-C motif chemokine ligand 10 (IP-10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL-1α, IP-10, and placental growth factor 1 (PIGF-1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral-induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C , Humanos , Feminino , HIV/metabolismo , Hepacivirus/metabolismo , Quimiocina CXCL10 , Nitratos , Fator de Crescimento Placentário , Biomarcadores/metabolismo , Fator de Necrose Tumoral alfa , Coinfecção/patologia
4.
World J Urol ; 41(12): 3829-3838, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37966505

RESUMO

PURPOSE: To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). METHODS: We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. RESULTS: After a median follow-up of 104 months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. CONCLUSION: This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.


Assuntos
Adenocarcinoma , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/radioterapia , Adenocarcinoma/tratamento farmacológico , Antígeno Prostático Específico
5.
J Sex Marital Ther ; 49(6): 643-658, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36735842

RESUMO

Decreased sexual pleasure is a common problem in women with breast cancer. The aim of this study was to evaluate the effect of psychoeducation vs. acceptance and commitment therapy to improve sexual pleasure according to the predictive role of physical, cognitive and emotional factors. Results of 139 Hispanic women (Mexico and Spain) diagnosed with breast cancer reveal that only the emotional factor of depression predicts decreased sexual pleasure. Although women who participated in the psychoeducation program presented greater physical symptomatology, body image distortions and emotional distress, the results seem to indicate that psychoeducational guidelines are relevant to improve sexual pleasure in those women who manifest higher levels of previous depression. Future research is required to clarify these issues.


Assuntos
Terapia de Aceitação e Compromisso , Neoplasias da Mama , Hispânico ou Latino , Disfunções Sexuais Psicogênicas , Feminino , Humanos , Imagem Corporal/psicologia , Neoplasias da Mama/complicações , Neoplasias da Mama/etnologia , Neoplasias da Mama/psicologia , Hispânico ou Latino/psicologia , Prazer , Comportamento Sexual/psicologia , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/psicologia , Disfunções Sexuais Psicogênicas/terapia , Educação de Pacientes como Assunto , Psicoterapia/métodos , Depressão/etnologia , Depressão/etiologia , Depressão/psicologia , Emoções
6.
Neurol Sci ; 43(1): 441-452, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33907941

RESUMO

INTRODUCTION: Orolingual angioedema (OA) after intravenous thrombolysis (IVT) with alteplase in acute stroke can be a life-threatening complication. Our aim was to describe its incidence, clinical features, and related factors. PATIENTS AND METHODS: We analyzed a single-center cohort of stroke patients treated with IVT in an 8-year period. We compared patients with (OA+) and without OA (OA-). A meta-analysis of previous studies was performed to identify factors related with OA. RESULTS: OA occurred in 7 out of 512 patients (1.37%; 95% CI 0.86-1.88%). Previous hypertension, diabetes, and treatment with ACE inhibitors were more frequent in OA+ compared to OA- patients (100% vs 58%, p = 0.045; 71.4% vs 21.8%, p = 0.008; and 71.4% vs. 16.6%, p = 0.002). Three out of 4 cases with unilateral OA had a contralateral insular infarct. The meta-analysis included 13 studies: 5720 stroke patients treated with IVT and 209 cases of OA. Factors related with OA were ACE inhibitor treatment (RR 5.33 [95% CI 3.07-9.26]) female sex (RR 1.94 [95% CI 1.24-3.03]), hypertension (RR 2.64 [95% CI 1.79-3.90]), diabetes (RR 1.60 [95% CI 1.16-2.21]), and dyslipidemia (RR 1.46 [95% CI 1.00-2.12]). The effect of insular infarct was inconclusive: positive when considering complete infarcts (RR 1.97 [95% CI 1.18-3.29]) and absent when partial infarcts were also included. CONCLUSIONS: OA occurred in 1.37% of the IVT-treated stroke patients. Previous treatment with ACE inhibitors, hypertension, diabetes, dyslipidemia, and female sex were associated with OA. The effect of insular infarct needs to be clarified in further studies.


Assuntos
Angioedema , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Angioedema/induzido quimicamente , Angioedema/epidemiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
7.
Breast J ; 2022: 1507881, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051467

RESUMO

Background: Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods: A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results: A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions: In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).


Assuntos
Neoplasias da Mama , Biópsia de Linfonodo Sentinela , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Terapia Neoadjuvante/métodos , Neoplasia Residual/patologia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos
8.
Gac Med Mex ; 158(1): 55-62, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35404923

RESUMO

INTRODUCTION: Using diffusion tensor imaging (DTI), 11 biomarkers have been reported in different glioblastoma (GB) regions. OBJECTIVE: To compare the efficacy of GB biomarkers using "zombie plots". METHODS: Retrospective cohort of 29 subjects with GB who underwent 3-Tesla brain magnetic resonance imaging. DTI major, intermediate and minor eigenvalues were used to calculate biomarkers at five tumor regions: normal-appearing white matter (NAWM), proximal and distal edema, tumor tissue and necrosis. Contingency tables with true and false positive and negative results allowed the calculation of zombie plots based on the Bayes factor and previously unreported diagnostic tests. RESULTS: The MD, FA, q, L, Cl, Cp and RA biomarkers had a good performance at the optimal zone for NAWM diagnosis. The proximal and distal edema, enhancing rim and necrosis regions do not have biomarkers that identify them with an optimal performance level. CONCLUSIONS: Zombie plots allow simultaneous comparison of biomarkers based on likelihood ratios. MD, FA, q, L, Cl, Cp, RA discriminated NAWM normal brain tissue at the optimal zone, but performance for other regions was at the mediocre, diagnostic inclusion and diagnostic exclusion zones.


INTRODUCCIÓN: Han sido reportados 11 biomarcadores de imágenes con tensor de difusión (DTI) en las regiones tumorales del glioblastoma. OBJETIVO: Comparar la eficacia de biomarcadores de glioblastoma mediante gráficos de zombie, que permiten la comparación simultánea en función de razones de verosimilitud. MÉTODOS: Cohorte retrospectiva de 29 sujetos con glioblastoma a quienes se efectuó resonancia magnética cerebral de 3 T. Los eigenvalores mayor, intermedio y menor de ITD se utilizaron para calcular 11 biomarcadores en cinco regiones tumorales: sustancia blanca de apariencia normal (NAWM), edema proximal y distal, tumoral viable y necrosis. Las tablas de contingencia con resultados verdaderos y falsos positivos y negativos permitieron calcular gráficos de zombie basados en el factor de Bayes y pruebas diagnósticas previamente no reportadas. RESULTADOS: Los biomarcadores DM, AF, q, L, Cl, Cp, AR actúan en la zona óptima para el diagnóstico de NAWM. Las regiones de edema proximal y distal, tejido tumoral que se realza con contraste y necrosis no poseen biomarcadores que las identifiquen en un nivel de rendimiento óptimo. CONCLUSIONES: Los biomarcadores DM, AF, q, L, Cl, Cp, AR discriminan el tejido cerebral normal en la zona óptima, pero el rendimiento de otras regiones tumorales se ubica en las zonas de inclusión diagnóstica, exclusión diagnóstica y mediocre.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Anisotropia , Teorema de Bayes , Biomarcadores , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Análise de Dados , Testes Diagnósticos de Rotina , Imagem de Tensor de Difusão/métodos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Necrose , Estudos Retrospectivos
9.
Eur J Neurol ; 28(10): 3339-3347, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33474816

RESUMO

OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.


Assuntos
COVID-19 , Doenças do Sistema Nervoso , Neurologia , Teste para COVID-19 , Humanos , Doenças do Sistema Nervoso/epidemiologia , Pandemias , Estudos Prospectivos , Sistema de Registros , SARS-CoV-2
10.
Proc Natl Acad Sci U S A ; 115(37): E8642-E8651, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30150414

RESUMO

We used fluorescence spectroscopy and EM to determine how binding of ATP, nucleation-promoting factors, actin monomers, and actin filaments changes the conformation of Arp2/3 complex during the process that nucleates an actin filament branch. We mutated subunits of Schizosaccharomyces pombe Arp2/3 complex for labeling with fluorescent dyes at either the C termini of Arp2 and Arp3 or ArpC1 and ArpC3. We measured Förster resonance energy transfer (FRET) efficiency (ETeff) between the dyes in the presence of the various ligands. We also computed class averages from electron micrographs of negatively stained specimens. ATP binding made small conformational changes of the nucleotide-binding cleft of the Arp2 subunit. WASp-VCA, WASp-CA, and WASp-actin-VCA changed the ETeff between the dyes on the Arp2 and Arp3 subunits much more than between dyes on ArpC1 and ArpC3. Ensemble FRET detected an additional structural change that brought ArpC1 and ArpC3 closer together when Arp2/3 complex bound actin filaments. VCA binding to Arp2/3 complex causes a conformational change that favors binding to the side of an actin filament, which allows further changes required to nucleate a daughter filament.


Assuntos
Citoesqueleto de Actina/metabolismo , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Proteína da Síndrome de Wiskott-Aldrich/metabolismo , Citoesqueleto de Actina/química , Complexo 2-3 de Proteínas Relacionadas à Actina/química , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Trifosfato de Adenosina/química , Transferência Ressonante de Energia de Fluorescência , Microscopia Eletrônica de Transmissão , Mutação , Ligação Proteica , Conformação Proteica , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/genética , Proteína da Síndrome de Wiskott-Aldrich/química
15.
Biochim Biophys Acta Bioenerg ; 1858(12): 975-981, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28919501

RESUMO

Ustilago maydis is an aerobic basidiomycete that fully depends on oxidative phosphorylation for its supply of ATP, pointing to mitochondria as a key player in the energy metabolism of this organism. Mitochondrial F1F0-ATP synthase occurs in supramolecular structures. In this work, we isolated the monomer (640kDa) and the dimer (1280kDa) and characterized their subunit composition and kinetics of ATP hydrolysis. Mass spectrometry revealed that dimerizing subunits e and g were present in the dimer but not in the monomer. Analysis of the ATPase activity showed that both oligomers had Michaelis-Menten kinetics, but the dimer was 7 times more active than the monomer, while affinities were similar. The dimer was more sensitive to oligomycin inhibition, with a Ki of 24nM, while the monomer had a Ki of 169nM. The results suggest that the interphase between the monomers in the dimer state affects the catalytic efficiency of the enzyme and its sensitivity to inhibitors.


Assuntos
Trifosfato de Adenosina/metabolismo , ATPases Mitocondriais Próton-Translocadoras/química , Multimerização Proteica/genética , Subunidades Proteicas/química , Trifosfato de Adenosina/química , Sequência de Aminoácidos/genética , Metabolismo Energético/genética , Hidrólise/efeitos dos fármacos , Cinética , Espectrometria de Massas , Mitocôndrias/enzimologia , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Oligomicinas/farmacologia , Subunidades Proteicas/metabolismo , Ustilago/enzimologia
16.
J Neurol Neurosurg Psychiatry ; 88(8): 632-638, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28550069

RESUMO

OBJECTIVES: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry. BACKGROUND: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established. METHODS: Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases. RESULTS: NMOSD was confirmed in 81/170 (48%) cases referred. Capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. CONCLUSIONS: NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.


Assuntos
Aquaporina 4/imunologia , Neuromielite Óptica/epidemiologia , Adulto , Idoso , Povo Asiático , Austrália/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Prevalência
17.
Biochim Biophys Acta ; 1847(2): 143-152, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25444704

RESUMO

ATP-diphosphohydrolase is associated with human syncytiotrophoblast mitochondria. The activity of this enzyme is implicated in the stimulation of oxygen uptake and progesterone synthesis. We reported previously that: (1) the detergent-solubilized ATP-diphosphohydrolase has low substrate specificity, and (2) purine and pyrimidine nucleosides, tri- or diphosphates, are fully dephosphorylated in the presence of calcium or magnesium (Flores-Herrera 1999, 2002). In this study we show that ATP-diphosphohydrolase hydrolyzes first the nucleoside triphosphate to nucleoside diphosphate, and then to nucleotide monophosphate, in the case of all tested nucleotides. The activation energies (Ea) for ATP, GTP, UTP, and CTP were 6.06, 4.10, 6.25, and 5.26 kcal/mol, respectively; for ADP, GDP, UDP, and CDP, they were 4.67, 5.42, 5.43, and 6.22 kcal/mol, respectively. The corresponding Arrhenius plots indicated a single rate-limiting step for each hydrolyzed nucleoside, either tri- or diphosphate. In intact mitochondria, the ADP produced by ATP-diphosphohydrolase activity depolarized the membrane potential (ΔΨm) and stimulated oxygen uptake. Mitochondrial respiration showed the state-3/state-4 transition when ATP was added, suggesting that ATP-diphosphohydrolase and the F1F0-ATP synthase work in conjunction to avoid a futile cycle. Substrate selectivity of the ATP-diphosphohydrolase was modified by ΔΨm (i.e. ATP was preferred over GTP when the inner mitochondrial membrane was energized). In contrast, dissipation of ΔΨm by CCCP produced a loss of substrate specificity and so the ATP-diphosphohydrolase was able to hydrolyze ATP and GTP at the same rate. In intact mitochondria, ATP hydrolysis increased progesterone synthesis as compared with GTP. Although dissipation of ΔΨm by CCCP decreased progesterone synthesis, NADPH production restores steroidogenesis. Overall, our results suggest a novel physiological role for ΔΨm in steroidogenesis.


Assuntos
Apirase/metabolismo , Potencial da Membrana Mitocondrial , Mitocôndrias/enzimologia , Progesterona/biossíntese , Trofoblastos/metabolismo , Trifosfato de Adenosina/metabolismo , Antígenos CD , Catálise , Humanos , Especificidade por Substrato
18.
Biochim Biophys Acta ; 1850(1): 107-17, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25459514

RESUMO

BACKGROUND: STARD1 transports cholesterol into mitochondria of acutely regulated steroidogenic tissue. It has been suggested that STARD3 transports cholesterol in the human placenta, which does not express STARD1. STARD1 is proteolytically activated into a 30-kDa protein. However, the role of proteases in STARD3 modification in the human placenta has not been studied. METHODS: Progesterone determination and Western blot using anti-STARD3 antibodies showed that mitochondrial proteases cleave STARD3 into a 28-kDa fragment that stimulates progesterone synthesis in isolated syncytiotrophoblast mitochondria. Protease inhibitors decrease STARD3 transformation and steroidogenesis. RESULTS: STARD3 remained tightly bound to isolated syncytiotrophoblast mitochondria. Simultaneous to the increase in progesterone synthesis, STARD3 was proteolytically processed into four proteins, of which a 28-kDa protein was the most abundant. This protein stimulated mitochondrial progesterone production similarly to truncated-STARD3. Maximum levels of protease activity were observed at pH7.5 and were sensitive to 1,10-phenanthroline, which inhibited steroidogenesis and STARD3 proteolytic cleavage. Addition of 22(R)-hydroxycholesterol increased progesterone synthesis, even in the presence of 1,10-phenanthroline, suggesting that proteolytic products might be involved in mitochondrial cholesterol transport. CONCLUSION: Metalloproteases from human placental mitochondria are involved in steroidogenesis through the proteolytic activation of STARD3. 1,10-Phenanthroline inhibits STARD3 proteolytic cleavage. The 28-kDa protein and the amino terminal truncated-STARD3 stimulate steroidogenesis in a comparable rate, suggesting that both proteins share similar properties, probably the START domain that is involved in cholesterol binding. GENERAL SIGNIFICANCE: Mitochondrial proteases are involved in syncytiotrophoblast-cell steroidogenesis regulation. Understanding STARD3 activation and its role in progesterone synthesis is crucial to getting insight into its action mechanism in healthy and diseased syncytiotrophoblast cells.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/enzimologia , Peptídeo Hidrolases/metabolismo , Progesterona/biossíntese , Trofoblastos/metabolismo , Western Blotting , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Concentração de Íons de Hidrogênio , Mitocôndrias/metabolismo , Consumo de Oxigênio , Fenantrolinas/farmacologia , Placenta/citologia , Placenta/metabolismo , Gravidez , Inibidores de Proteases/farmacologia , Proteólise/efeitos dos fármacos , Espectrometria de Massas em Tandem
19.
J Sch Health ; 2024 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-39460463

RESUMO

BACKGROUND: We sought to determine the impact of school gardens and nutrition education on student fruit and vegetable consumption from limited-income communities in Alabama. METHODS: Third grade students at 99 Alabama schools with and without gardens on-site were randomized to receive either nutrition education or to a wait-list control group. Multi-level models were used to assess the effects of treatment and control with and without school gardens. RESULTS: Students attending schools with gardens demonstrated highest consumption of fruits and vegetables prior to treatment. Nutrition education alone translated into significant dietary improvements. Both gardens and education translated into greatest dietary improvements. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Devising financially accessible, practical, and culturally relevant ways to improve student health through garden and nutrition education may help improve student diet. Forming comprehensive Extension, SNAP-Ed, and school collaboration to support gardens, nutrition education, and healthy school policies and systems can be a way to support and sustain healthy student learning environments. CONCLUSIONS: Combined gardening and nutrition education is associated with increases in fruit and vegetable consumption among majority rural, Southern students from limited-resource communities.

20.
Clin Transl Oncol ; 26(7): 1798-1803, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38421563

RESUMO

PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.


Assuntos
Carboplatina , Dislipidemias , Hipertensão , Hipogonadismo , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Estudos Retrospectivos , Hipogonadismo/epidemiologia , Hipogonadismo/complicações , Dislipidemias/epidemiologia , Dislipidemias/complicações , Hipertensão/epidemiologia , Hipertensão/complicações , Adulto , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/patologia , Seminoma/complicações , Seminoma/epidemiologia , Seminoma/patologia , Pessoa de Meia-Idade , Incidência , Espanha/epidemiologia , Carboplatina/administração & dosagem , Adulto Jovem , Estadiamento de Neoplasias , Fatores de Risco , Idoso
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