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1.
Pain Med ; 20(10): 1980-1988, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496510

RESUMO

INTRODUCTION: Rib fractures are an important health issue worldwide, with significant, pain, morbidity, and disability for which only symptomatic treatment exists. OBJECTIVES: Based on our previous experimental model, the objective of the current study was to assess for the first time whether pulsed ultrasound (PUS) application could have beneficial effects on humans. METHODS: Prospective, double-blinded, randomized, controlled trial of 51 patients. Four were excluded, and 47 were randomized into the control group (N = 23) or PUS group (N = 24). The control group received a PUS procedure without emission, and the PUS group received 1 Mhz, 0.5 W/cm2 for 1 min/cm2. Pain level, bone callus healing rate, physical and work activity, pain medication intake, and adverse events were blindly evaluated at baseline and one, three, and six months. RESULTS: There were no significant differences at baseline between groups. PUS treatment significantly decreased pain by month 1 (P = 0.004), month 3 (P = 0.005), and month 6 (P = 0.025), significantly accelerated callus healing by month 1 (P = 0.013) and month 3 (P < 0.001), accelerated return to physical activity by month 3 (P = 0.036) and work activity (P = 0.001) by month 1, and considerably reduced pain medication intake by month 1 (P = 0.057) and month 3 (P = 0.017). No related adverse events were found in the PUS group. CONCLUSIONS: This study is the first evidence that PUS treatment is capable of improving rib fracture outcome, significantly accelerating bone callus healing, and decreasing pain, time off due to both physical activity and convalescence period, and pain medication intake. It is a safe, efficient, and low-cost therapy that may become a new treatment for patients with stable rib fractures.


Assuntos
Consolidação da Fratura , Manejo da Dor/métodos , Dor/etiologia , Fraturas das Costelas/terapia , Terapia por Ultrassom/métodos , Ondas Ultrassônicas , Adulto , Idoso , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Retorno ao Trabalho , Fraturas das Costelas/complicações , Resultado do Tratamento , Terapia por Ultrassom/efeitos adversos , Ondas Ultrassônicas/efeitos adversos
2.
J Biol Chem ; 292(23): 9774-9786, 2017 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-28404816

RESUMO

MicroRNAs (miRNAs) are important regulators of localized mRNA translation in neuronal dendrites. The presence of RNA-induced silencing complex proteins in these compartments and the dynamic miRNA expression changes that occur in response to neuronal stimulation highlight their importance in synaptic plasticity. Previously, we demonstrated a novel interaction between the major RNA-induced silencing complex component Argounaute-2 (Ago2) and the BAR (bin/amphiphysin/rvs) domain protein PICK1. PICK1 recruits Ago2 to recycling endosomes in dendrites, where it inhibits miRNA-mediated translational repression. Chemical induction of long-term depression via NMDA receptor activation causes the dissociation of Ago2 from PICK1 and a consequent increase in dendritic miRNA-mediated gene silencing. The mechanism that underlies the regulation of PICK1-Ago2 binding is unknown. In this study, we demonstrate that the PICK1-Ago2 interaction is directly sensitive to Ca2+ ions so that high [Ca2+]free reduces PICK1 binding to Ago2. Mutating a stretch of C-terminal Ca2+-binding residues in PICK1 results in a complete block of NMDA-induced PICK1-Ago2 disassociation in cortical neurons. Furthermore, the same mutant also blocks NMDA-stimulated miRNA-mediated gene silencing. This study defines a novel mechanism whereby elevated [Ca2+] induced by NMDA receptor activation modulates Ago2 and miRNA activity via PICK1. Our work suggests a Ca2+-dependent process to regulate miRNA activity in neurons in response to the induction of long-term depression.


Assuntos
Sinalização do Cálcio/fisiologia , Proteínas de Transporte/metabolismo , Dendritos/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Biossíntese de Proteínas/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Cálcio/metabolismo , Proteínas de Transporte/genética , Córtex Cerebral/metabolismo , Proteínas do Citoesqueleto , Células HEK293 , Humanos , MicroRNAs/genética , Proteínas Nucleares/genética , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/genética
3.
Proc Natl Acad Sci U S A ; 110(51): 20807-12, 2013 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-24297929

RESUMO

NMDA-type glutamate receptors (NMDARs) guide the activity-dependent remodeling of excitatory synapses and associated dendritic spines during critical periods of postnatal brain development. Whereas mature NMDARs composed of GluN1 and GluN2 subunits mediate synapse plasticity and promote spine growth and stabilization, juvenile NMDARs containing GluN3A subunits are thought to inhibit these processes via yet unknown mechanisms. Here, we report that GluN3A binds G protein-coupled receptor kinase-interacting protein (GIT1), a postsynaptic scaffold that assembles actin regulatory complexes, including the Rac1 guanine nucleotide exchange factor ßPIX, to promote Rac1 activation in spines. Binding to GluN3A limits the synaptic localization of GIT1 and its ability to complex ßPIX, leading to decreased Rac1 activation and reduced spine density and size in primary cultured neurons. Conversely, knocking out GluN3A favors the formation of GIT1/ßPIX complexes and increases the activation of Rac1 and its main effector p21-activated kinase. We further show that binding of GluN3A to GIT1 is regulated by synaptic activity, a response that might restrict the negative regulatory effects of GluN3A on actin signaling to inactive synapses. Our results identify inhibition of Rac1/p21-activated kinase actin signaling pathways as an activity-dependent mechanism mediating the inhibitory effects of GluN3A on spine morphogenesis.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Fosfoproteínas/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais/fisiologia , Coluna Vertebral/embriologia , Sinapses/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Proteínas de Ciclo Celular/genética , Células Cultivadas , Ativação Enzimática/fisiologia , Morfogênese/fisiologia , Fosfoproteínas/genética , Ligação Proteica/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/genética , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismo , Coluna Vertebral/citologia , Sinapses/genética , Proteínas rac1 de Ligação ao GTP/genética
4.
Lung ; 192(3): 441-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24647564

RESUMO

BACKGROUND: Post-pneumonectomy bronchopleural fistulas (BPFs) are associated with high morbidity and mortality. Currently, since the management of BPFs is difficult to assess, the best therapeutic approach is prevention. Our objective was to evaluate the effects of adipose-derived stem cells (ASCs) on the healing of the bronchial stump in an experimental animal model. METHODS: Left pneumonectomy was performed in 37 Sprague-Dawley rats. Animals were randomly assigned to a control group (n = 13), an ASC group (n = 12), and an ASC plus Tissucol(®) group (ASCT) (n = 12). The ASCs and ASCTs were locally administered at the bronchial stump after surgical pneumonectomy. Animals were killed at 10 and 20 days. We analyzed histological changes and changes in the expression of relevant genes involved in wound repair in the bronchial stump. RESULTS: Two control animals, one animal from the ASC group, and one from the ASCT group died from early BPF. All the remaining animals had an adequate postoperative outcome. ASCs and ASCTs significantly decreased the necrosis and ulcerations of the bronchial stump at 10 and 20 days. ASCs significantly decreased mRNA expression of Igf1 at 10 days and Igf1, Tgfb1, Vegfa, and Col2a1 at 20 days, whereas there was increased expression of Agc1 and Col2a1 at 10 days and Sox6 at 20 days. CONCLUSIONS: Our findings indicate that local ASCs protected the bronchial stump after pneumonectomy and induced local changes in gene expression related to their protective action. These results could lead to a potential new therapeutic modality for the prevention of BPF.


Assuntos
Tecido Adiposo/transplante , Agrecanas/metabolismo , Colágeno Tipo II/metabolismo , Pneumonectomia , Fatores de Transcrição SOXD/metabolismo , Transplante de Células-Tronco , Tecido Adiposo/citologia , Agrecanas/genética , Animais , Brônquios/metabolismo , Brônquios/patologia , Brônquios/cirurgia , Células Cultivadas , Colágeno Tipo II/genética , Masculino , Modelos Animais , Necrose , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fatores de Transcrição SOXD/genética , Fatores de Tempo , Regulação para Cima , Cicatrização
5.
J Surg Res ; 183(1): 68-74, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23433719

RESUMO

BACKGROUND: Necrosis of the bronchial stump is a very important trigger for bronchopleural fistula. The administration of local autologous platelet-poor plasma (PPP) could protect the bronchial stump. MATERIALS AND METHODS: Left pneumonectomy was performed in 25 Sprague-Dawley rats. Animals were randomly assigned to a control group (n=13) and PPP group (n=12). PPP was locally administered on the bronchial stump after pneumonectomy. We analyzed histologic changes in the bronchial stump and messenger RNA expression changes of genes involved in wound repair at 10 and 20 d. RESULTS: Local PPP treatment produced a mass of fibrous tissue surrounding the bronchial stump and significantly decreased the presence of necrosis at 20 d. PPP increased the expression of insulin like growth factor 1 at 10 d although it did not reach statistical significance. CONCLUSIONS: Our findings indicate that local PPP treatment of the bronchial stump after pneumonectomy decreased necrosis and could have a protective effect on the bronchial stump.


Assuntos
Brônquios/patologia , Fístula Brônquica/prevenção & controle , Plasma , Doenças Pleurais/prevenção & controle , Pneumonectomia/efeitos adversos , Animais , Transfusão de Sangue Autóloga , Fístula Brônquica/etiologia , Expressão Gênica , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Necrose/etiologia , Necrose/prevenção & controle , Doenças Pleurais/etiologia , Ratos , Ratos Sprague-Dawley , Cicatrização
6.
Diabetes ; 71(3): 497-510, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35040477

RESUMO

Colorectal cancer (CRC) and diabetes are two of the most prevalent chronic diseases worldwide with dysregulated receptor tyrosine kinase signaling and strong co-occurrence correlation. Plasma autoantibodies represent a promising early diagnostic marker for both diseases before symptoms appear. In this study, we explore the value of autoantibodies against receptor-type tyrosine-protein phosphatase-like N (PTPRN; full-length or selected domains) as diagnostic markers using a cohort of individuals with type 2 diabetes (T2D), CRC, or both diseases or healthy individuals. We show that PTPRN autoantibody levels in plasma discriminated between patients with T2D with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of patients with CRC. Mechanistically, PTPRN depletion significantly reduced invasiveness of CRC cells in vitro and liver homing and metastasis in vivo by means of a dysregulation of the epithelial-mesenchymal transition and a decrease of the insulin receptor signaling pathway. Therefore, PTPRN autoantibodies may represent a particularly helpful marker for the stratification of patients with T2D at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidence that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in patients with CRC.


Assuntos
Autoanticorpos/sangue , Neoplasias Colorretais/imunologia , Diabetes Mellitus Tipo 2/imunologia , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/imunologia , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/fisiologia , Adulto , Animais , Biomarcadores/sangue , Linhagem Celular Tumoral , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Fatores de Risco
7.
J Biol Chem ; 285(38): 29387-97, 2010 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-20622015

RESUMO

Corynebacteria grow by wall extension at the cell poles, with DivIVA being an essential protein orchestrating cell elongation and morphogenesis. DivIVA is considered a scaffolding protein able to recruit other proteins and enzymes involved in polar peptidoglycan biosynthesis. Partial depletion of DivIVA induced overexpression of cg3264, a previously uncharacterized gene that encodes a novel coiled coil-rich protein specific for corynebacteria and a few other actinomycetes. By partial depletion and overexpression of Cg3264, we demonstrated that this protein is an essential cytoskeletal element needed for maintenance of the rod-shaped morphology of Corynebacterium glutamicum, and it was therefore renamed RsmP (rod-shaped morphology protein). RsmP forms long polymers in vitro in the absence of any cofactors, thus resembling eukaryotic intermediate filaments. We also investigated whether RsmP could be regulated post-translationally by phosphorylation, like eukaryotic intermediate filaments. RsmP was phosphorylated in vitro by the PknA protein kinase and to a lesser extent by PknL. A mass spectrometric analysis indicated that phosphorylation exclusively occurred on a serine (Ser-6) and two threonine (Thr-168 and Thr-211) residues. We confirmed that mutagenesis to alanine (phosphoablative protein) totally abolished PknA-dependent phosphorylation of RsmP. Interestingly, when the three residues were converted to aspartic acid, the phosphomimetic protein accumulated at the cell poles instead of making filaments along the cell, as observed for the native or phosphoablative RsmP proteins, indicating that phosphorylation of RsmP is necessary for directing cell growth at the cell poles.


Assuntos
Proteínas de Bactérias/metabolismo , Corynebacterium glutamicum/metabolismo , Corynebacterium glutamicum/ultraestrutura , Proteínas do Citoesqueleto/metabolismo , Proteínas de Bactérias/genética , Corynebacterium glutamicum/genética , Proteínas do Citoesqueleto/genética , Eletroforese em Gel Bidimensional , Evolução Molecular , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano/genética , Microscopia Eletrônica de Transmissão , Mutagênese Sítio-Dirigida , Fosforilação , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
8.
Lung ; 189(3): 251-5, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21437727

RESUMO

Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.


Assuntos
Estradiol/toxicidade , Rejeição de Enxerto/prevenção & controle , Lesão Pulmonar/etiologia , Transplante de Pulmão/efeitos adversos , Pulmão/efeitos dos fármacos , Traumatismo por Reperfusão/etiologia , Animais , Antioxidantes/administração & dosagem , Distribuição de Qui-Quadrado , Desferroxamina/administração & dosagem , Modelos Animais de Doenças , Estradiol/administração & dosagem , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/efeitos dos fármacos , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Melatonina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Edema Pulmonar/etiologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Índice de Gravidade de Doença , Fatores de Tempo
9.
Complement Ther Med ; 59: 102724, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33964405

RESUMO

OBJECTIVES: Surgery is the treatment of choice for symptomatic disc herniation after conservative management. Several studies have suggested the potential utility of intradiscal ozone infiltration in this pathology. The aim of this trial was to compare intradiscal ozone infiltration vs. oxygen infiltration vs. surgery. DESIGN AND INTERVENTIONS: This was a randomized, double-blinded, and controlled trial in patients on a waiting list for herniated disc surgery. There were three treatment groups: surgery; intradiscal ozone infiltration (plus foraminal infiltration of ozone, steroids, and anesthetic); intradiscal oxygen infiltration (plus foraminal infiltration of oxygen, steroids, and anesthetic). MAIN OUTCOME MEASURES: The requirements for surgery. RESULTS: Five years after the treatment of the last recruited patient (median follow-up: 78 months), the requirement for further surgery was 20 % for patients in the ozone group and 60 % for patients in the oxygen group. 11 % of patients initially treated with surgery also required a second surgery. Compared to the surgery group, the ozone group showed: 1) significantly lower number of inpatient days: median 3 days (interquartile range: 3-3.5 days) vs. 0 days (interquartile range: 0-1.5 days), p = 0.012; 2) significantly lower costs: median EUR 3702 (interquartile range: EUR 3283-7630) vs. EUR 364 (interquartile range: EUR 364-2536), p = 0.029. CONCLUSIONS: Our truncated trial showed that intradiscal ozone infiltrations decreased the requirements for conventional surgery, resulting in decreased hospitalization durations and associated costs. These findings and their magnitude are of interest to patients and health services providers. Further validation is ongoing.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Dor Lombar , Ozônio , Humanos , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Ozônio/uso terapêutico , Resultado do Tratamento
10.
Sci Rep ; 7(1): 12318, 2017 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-28951554

RESUMO

Global cerebral ischemia results in oxygen and glucose deprivation (OGD) and consequent delayed cell death of vulnerable neurons, with hippocampal CA1 neurons more vulnerable than cortical neurons. Most AMPA receptors (AMPARs) are heteromeric complexes of subunits GluA1/GluA2 or GluA2/GluA3, and the presence of GluA2 renders AMPARs Ca2+-impermeable. In hippocampal CA1 neurons, OGD causes the synaptic expression of GluA2-lacking Ca2+-permeable AMPARs, contributing to toxic Ca2+ influx. The loss of synaptic GluA2 is caused by rapid trafficking of GluA2-containing AMPARs from the cell surface, followed by a delayed reduction in GluA2 mRNA expression. We show here that OGD causes endocytosis, lysosomal targeting and consequent degradation of GluA2- and GluA3-containing AMPARs, and that PICK1 is required for both OGD-induced GluA2 endocytosis and lysosomal sorting. Our results further suggest that GluA1-containing AMPARs resist OGD-induced endocytosis. OGD does not cause GluA2 endocytosis in cortical neurons, and we show that PICK1 binding to the endocytic adaptor AP2 is enhanced by OGD in hippocampal, but not cortical neurons. We propose that endocytosis of GluA2/3, caused by a hippocampal-specific increase in PICK1-AP2 interactions, followed by PICK1-dependent lysosomal targeting, are critical events in determining changes in AMPAR subunit composition in the response to ischaemia.


Assuntos
Isquemia Encefálica/patologia , Região CA1 Hipocampal/patologia , Neurônios/patologia , Receptores de AMPA/metabolismo , Complexo 2 de Proteínas Adaptadoras/metabolismo , Animais , Apoptose , Região CA1 Hipocampal/citologia , Proteínas de Transporte/metabolismo , Células Cultivadas , Proteínas do Citoesqueleto , Endocitose , Glucose/metabolismo , Lisossomos/metabolismo , Proteínas Nucleares/metabolismo , Oxigênio/metabolismo , Cultura Primária de Células , Proteólise , Ratos , Ratos Wistar
11.
J Cell Biol ; 216(10): 3323-3338, 2017 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-28855251

RESUMO

Clathrin-mediated endocytosis (CME) is used to internalize a diverse range of cargo proteins from the cell surface, often in response to specific signals. In neurons, the rapid endocytosis of GluA2-containing AMPA receptors (AMPARs) in response to NMDA receptor (NMDAR) stimulation causes a reduction in synaptic strength and is the central mechanism for long-term depression, which underlies certain forms of learning. The mechanisms that link NMDAR activation to CME of AMPARs remain elusive. PICK1 is a BAR domain protein required for NMDAR-dependent reductions in surface GluA2; however, the molecular mechanisms involved are unclear. In this study, we show that PICK1 makes direct, NMDAR-dependent interactions with the core endocytic proteins AP2 and dynamin. PICK1-AP2 interactions are required for clustering AMPARs at endocytic zones in dendrites in response to NMDAR stimulation and for consequent AMPAR internalization. We further show that PICK1 stimulates dynamin polymerization. We propose that PICK1 is a cargo-specific endocytic accessory protein required for efficient, activity-dependent AMPAR endocytosis.


Assuntos
Complexo 2 de Proteínas Adaptadoras/metabolismo , Proteínas de Transporte/metabolismo , Dinaminas/metabolismo , Endocitose/fisiologia , Proteínas Nucleares/metabolismo , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Complexo 2 de Proteínas Adaptadoras/genética , Animais , Proteínas de Transporte/genética , Proteínas do Citoesqueleto , Dinaminas/genética , Células HEK293 , Humanos , Proteínas Nucleares/genética , Ratos , Ratos Wistar , Receptores de AMPA/genética , Receptores de N-Metil-D-Aspartato/genética
12.
Eur J Cardiothorac Surg ; 29(1): 20-5, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16343923

RESUMO

INTRODUCTION: It has been hypothesized that medical procedures performed in high-volume units carry less risk and achieve a better outcome. OBJECTIVE: To determine the relationship between the number of interventions and the operative morbidity, mortality and long-term survival in the surgery of bronchogenic carcinoma (BC). PATIENTS AND METHOD: Prospective, multicenter Spanish study was conducted in 19 departments of thoracic surgery on 2994 patients operated on consecutively with the aim of curing BC. The thoracic surgery departments have been classified into three groups, according to the number of interventions performed per year: I (1-43 cases/year; centers=7; n=565; 18.9%), II (44-54 cases/year; centers=6; n=1044; 34.9%) and III (55 or more cases/year; centers=6; n=1385; 46.3%). RESULTS: When the three groups were compared, the frequency of complete surgery was found to be 84% for group I, 76% for group II and 83% for group III (p=0.001, for comparisons between groups I/II and II/III). The pathological stages were identical in the three groups. The overall morbidity and the mortality in all patients or above the age of 75 or in pneumonectomies were not different among the groups. When considering all the patients with prognostic information (n=2758), no differences were found regarding the 5-year survival among the groups. When only patients in postoperative stage I-II and complete resection were evaluated, excluding operative mortality (n=1128), 5-year survival was 0.58 for group I, 0.57 for group II and 0.50 for group III (p=0.06 between groups II and III; p=0.08 between groups I and III). CONCLUSIONS: No significant differences that do not favor the hypothesis that there is increased surgical risk and worse survival in centers having a lower volume were found in this Spanish multicenter study.


Assuntos
Carcinoma Broncogênico/epidemiologia , Neoplasias Pulmonares/epidemiologia , Toracotomia/mortalidade , Idoso , Carcinoma Broncogênico/mortalidade , Carcinoma Broncogênico/cirurgia , Feminino , Mortalidade Hospitalar , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Morbidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Análise de Sobrevida , Toracotomia/efeitos adversos , Toracotomia/estatística & dados numéricos , Resultado do Tratamento
13.
Rev Lat Am Enfermagem ; 24: e2691, 2016.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-27192416

RESUMO

OBJECTIVE: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. METHOD: cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. RESULTS: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). CONCLUSION: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics.


Assuntos
Antirretrovirais/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Tuberculose , Adulto , Estudos Transversais , Emprego , Feminino , Humanos , Masculino , Estado Civil , Fatores Sexuais
14.
Rev Lat Am Enfermagem ; 23(2): 183-91, 2015.
Artigo em Inglês, Português, Espanhol | MEDLINE | ID: mdl-26039287

RESUMO

OBJECTIVE: to analyze the quality of life (QoL) of men with AIDS from the perspective of the model of social determinants of health (MSDH). METHOD: cross-sectional study conducted in an outpatient infectious diseases clinic from a Brazilian university hospital over the course of one year with a sample of 138 patients. A form based on the MSDH was used to collect sociodemographic data addressing individual, proximal, intermediate determinants and the influence of social networks together with an instrument used to assess the QoL of people with HIV/AIDS. The project was approved by the Institutional Review Board (Protocol No. 040.06.12). RESULTS: according to MSDH, most men with AIDS were between 30 and 49 years old (68.1%), mixed race (59.4%), heterosexual (46.4%), single (64.5%), Catholic (68.8%), had a bachelor's degree (39.2%), had no children (61.6%), and had a formal job (71.0%). The perception of QoL in the physical, level of independence, environment, and spirituality domains was intermediate, while QoL was perceived to be superior in the domains of psychological and social relationship. A perception of lower QoL was presented by homosexual (p=0.037) and married men (p=0.077), and those with income below one times the minimum wage (p=0.042). A perception of greater QoL was presented by those without a religion (p=0.005), living with a partner (p=0.049), and those who had a formal job (p=0.045). CONCLUSION: social determinants influence the QoL of men with AIDS.


Assuntos
Síndrome da Imunodeficiência Adquirida , Qualidade de Vida , Determinantes Sociais da Saúde , Síndrome da Imunodeficiência Adquirida/diagnóstico , Adulto , Idoso , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Adulto Jovem
15.
J Cereb Blood Flow Metab ; 34(12): 1898-906, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25248834

RESUMO

Distinct neuronal populations show differential sensitivity to global ischemia, with hippocampal CA1 neurons showing greater vulnerability compared to cortical neurons. The mechanisms that underlie differential vulnerability are unclear, and we hypothesize that intrinsic differences in neuronal cell biology are involved. Dendritic spine morphology changes in response to ischemic insults in vivo, but cell type-specific differences and the molecular mechanisms leading to such morphologic changes are unexplored. To directly compare changes in spine size in response to oxygen/glucose deprivation (OGD) in cortical and hippocampal neurons, we used separate and equivalent cultures of each cell type. We show that cortical neurons exhibit significantly greater spine shrinkage compared to hippocampal neurons. Rac1 is a Rho-family GTPase that regulates the actin cytoskeleton and is involved in spine dynamics. We show that Rac1 and the Rac guanine nucleotide exchange factor (GEF) Tiam1 are differentially activated by OGD in hippocampal and cortical neurons. Hippocampal neurons express more Tiam1 than cortical neurons, and reducing Tiam1 expression in hippocampal neurons by shRNA enhances OGD-induced spine shrinkage. Tiam1 knockdown also reduces hippocampal neuronal vulnerability to OGD. This work defines fundamental differences in signalling pathways that regulate spine morphology in distinct neuronal populations that may have a role in the differential vulnerability to ischemia.


Assuntos
Córtex Cerebral/metabolismo , Espinhas Dendríticas/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Hipocampo/metabolismo , Isquemia/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Glicemia/metabolismo , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Morte Celular/fisiologia , Córtex Cerebral/patologia , Espinhas Dendríticas/patologia , Feminino , Fatores de Troca do Nucleotídeo Guanina/genética , Hipocampo/patologia , Isquemia/patologia , Masculino , Proteínas de Neoplasias/genética , Neurônios/metabolismo , Neurônios/ultraestrutura , Oxigênio/metabolismo , Gravidez , Ratos Wistar , Receptores de AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T , Proteínas rac1 de Ligação ao GTP/genética
16.
Int J Cell Biol ; 2012: 905832, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22481946

RESUMO

Although bacteria are considered the simplest life forms, we are now slowly unraveling their cellular complexity. Surprisingly, not only do bacterial cells have a cytoskeleton but also the building blocks are not very different from the cytoskeleton that our own cells use to grow and divide. Nonetheless, despite important advances in our understanding of the basic physiology of certain bacterial models, little is known about Actinobacteria, an ancient group of Eubacteria. Here we review current knowledge on the cytoskeletal elements required for bacterial cell growth and cell division, focusing on actinobacterial genera such as Mycobacterium, Corynebacterium, and Streptomyces. These include some of the deadliest pathogens on earth but also some of the most prolific producers of antibiotics and antitumorals.

17.
J Heart Lung Transplant ; 31(2): 213-21, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22305384

RESUMO

BACKGROUND: Chronic rejection (CR) is the main reason for the limited survival rates among lung transplant (LT) recipients. There remains no effective treatment for CR. The aim of this study was to identify new molecular mechanisms involved in CR by using DNA microarray analysis. METHODS: We performed 10 left LTs using the microsurgical cuff technique in inbred Sprague-Dawley rats. Lung isograft samples were obtained 3 months after surgery. We analyzed histologic, apoptotic and gene expression changes by DNA microarray and quantitative PCR analysis. RESULTS: Histologic analyses confirmed signs of CR in all lungs and positive labeling for apoptotic and anti-apoptotic markers. A total of 702 genes were regulated in the CR lungs: 317 genes were upregulated and 385 were downregulated. Significant changes for about 30 biologic processes, including regulation of the cytoskeleton, and 15 signaling pathways, such as adherens junctions, were observed. We found significantly increased mRNA expression of the Cldn5, Epas1, Tgfb1, Vegf, Selp1, Hsp27 and Igf1 genes. CONCLUSIONS: This is the first experimental study performed in an orthotopic model of LT using DNA microarray analysis. The individual genes, biologic process and pathways identified may represent novel targets that could be manipulated and contribute to the development of treatments capable of providing protection from CR.


Assuntos
Bronquiolite Obliterante/etiologia , Perfilação da Expressão Gênica , Rejeição de Enxerto/genética , Transplante de Pulmão/efeitos adversos , Análise de Sequência com Séries de Oligonucleotídeos , Animais , Bronquiolite Obliterante/patologia , Modelos Animais de Doenças , Marcadores Genéticos , Masculino , RNA Mensageiro , Ratos , Ratos Sprague-Dawley
18.
Rev. latinoam. enferm. (Online) ; 24: e2691, 2016. tab
Artigo em Inglês | LILACS, BDENF - enfermagem (Brasil) | ID: biblio-961064

RESUMO

Objective: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. Method: cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. Results: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). Conclusion: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics.


Objetivo: avaliar os níveis de adesão à terapia antirretroviral em coinfectados pelo HIV/tuberculose e correlacionar esses níveis com as variáveis sociodemográficas e clínicas da população em estudo. Método: estudo transversal, com 74 pessoas adultas, de ambos os sexos, coinfectadas por HIV/tuberculose. Utilizou-se, para coleta de dados, um formulário de avaliação sociodemográfica e clínica e o Questionário de Avaliação da Adesão ao Tratamento Antirretroviral. A análise dos dados ocorreu mediante o uso do STATA, versão11, por meio de estatística descritiva, do teste qui-quadrado exato de Fisher e de probabilidade. Resultados: predominaram homens (79,7%), com idade entre 30 e 39 anos (35,1%), com baixa renda (75,7%) e tuberculose pulmonar (71,6%). A adesão à terapia antirretroviral mostrou-se inadequada em 78,1% dos homens; 61,0% dos solteiros; 47,0% dos desempregados e 76,5% entre pessoas com renda inferior a um salário-mínimo. Observou-se diferença significativa entre a adesão e o tempo de uso dos antirretrovirais (p=0,018), orientação sexual (p=0,024) e número de filhos (p=0,029). Conclusão: os coinfectados apresentaram adesão inadequada aos antirretrovirais, fato que repercute de modo negativo nas condições de saúde das pessoas que vivem com a coinfecção HIV/tuberculose. Constatou-se correlação estatisticamente significante entre os níveis de adesão e algumas características sociodemográficas e clínicas.


Objetivo: evaluar los niveles de adhesión a la terapia antiretroviral en coinfectados por el VIH/tuberculosis y correlacionar esos niveles con las variables sociodemográficas e clínicas de la población estudiada. Método: estudio trasversal con 74 personas adultas, de ambos sexos, coinfectadas por HIV/tuberculosis. Fue utilizado para recolectar los datos un formulario de evaluación sociodemográfica y clínica y el Cuestionario de Evaluación de la Adhesión al Tratamiento Antirretroviral. El análisis de los datos fue efectuado con el uso de STATA, versión 11, mediante estadística descriptiva, la prueba ji-cuadrado exacto de Fisher y de probabilidad. Resultados: predominaron hombres (79,7%), con edad entre 30 y 39 años (35,1%), baja renta (75,7%) y tuberculosis pulmonar (71,6%). La adhesión a la terapia antiretroviral se mostró inadecuada en 78,1% de los hombres; 61,0% de los solteros; 47,0% de los desempleados y 76,5% entre personas con renta inferior a un salario-mínimo. Se observó diferencia significativa entre la adhesión y el tiempo de uso de los antiretrovirales (p=0,018), orientación sexual (p=0,024) y número de hijos (p=0,029). Conclusión: los coinfectados presentaron adhesión inadecuada a los antiretrovirales, hecho que influye negativamente en las condiciones de salud de las personas que viven con la coinfección HIV/tuberculosis. Se constató correlación estadísticamente significante entre los niveles de adhesión y algunas características sociodemográficas y clínicas.


Assuntos
Humanos , Masculino , Feminino , Adulto , Tuberculose , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Coinfecção , Fatores Sexuais , Estudos Transversais , Estado Civil , Emprego
19.
Texto & contexto enferm ; 25(4): e2030015, 2016. tab
Artigo em Inglês | LILACS, BDENF - enfermagem (Brasil) | ID: biblio-962867

RESUMO

ABSTRACT The aim of this study was to evaluate the social support for people with AIDS. It was a cross-sectional study, with 215 outpatients at a University Hospital in Northeastern Brazil. Data were collected from August to December 2012, through interviews, using a Socio-demographic and Clinical Form and a Social Support Scale for People Living with HIV/AIDS. Statistical Package for the Social Science was used for data analysis. Results showed that average scores of social emotional and instrumental support were satisfactory and not influenced by sex (p=0.954; p=0.508), education (p=0.756; p=0.194), marital status (p=0.076; p=0.446) and length of antiretroviral therapy (p=0.480; p=0.120). People diagnosed for less than three years had more instrumental support (p=0.048) than those diagnosed over three years (p=0.370). Neighbors, employers and health professionals provided less support. The conclusion was that people with AIDS have satisfactory social support, especially from friends and family not living in the same household.


RESUMEN Este estudio objetivó evaluar el apoyo social a personas con SIDA. Estudio transversal con muestra de 215 pacientes ambulatorios de un hospital universitario del nordeste de Brasil. Los datos recolectados entre agosto y diciembre de 2012, a través de entrevistas utilizando el formulario sociodemográfico y clínico y la Escala de Apoyo Social para las Personas que Viven con VIH/SIDA. El Statistical Package for the Social Science fue utilizado para análisis de datos. Los resultados evidenciaron que las puntuaciones medias de apoyo social emocionales e instrumentales fueron satisfactorios, y no influenciados por el sexo (p=0,954; p=0,508), educación (p=0,756; p=0,194), estado civil (p=0,076; p=0,446) y tiempo de terapia antirretroviral (p=0,480; p=0,120). Las personas diagnosticadas en menos de tres años tenían más apoyo instrumental (p=0,048) que los diagnosticados hace más de tres años (p=0,370). Los vecinos, jefe y profesionales de salud proporcionaban menos apoyo. Se concluyó que personas con SIDA tienen un apoyo social satisfactorio, principalmente por parte de amigos y familiares que no viven en el mismo hogar.


RESUMO Teve-se como objetivo avaliar o suporte social de pessoas com aids. Estudo transversal, com amostra de 215 pacientes ambulatoriais de um hospital universitário do Nordeste brasileiro. Dados coletados de agosto a dezembro de 2012, por meio de entrevista, utilizando formulário sociodemográfico e clínico e Escala de Suporte Social para Pessoas Vivendo com HIV/aids. O Statistical Package for the Social Science foi utilizado para análise de dados. Resultados mostraram que médias de escores de suporte social emocional e instrumental foram satisfatórias e não influenciadas pelo sexo (p=0,954; p=0,508), escolaridade (p=0,756; p=0,194), situação conjugal (p=0,076; p=0,446) e tempo de terapia antirretroviral (p=0,480; p=0,120). Pessoas diagnosticadas há menos de três anos tiveram mais suporte instrumental (p=0,048) que os diagnosticados há mais de três anos (p=0,370). Vizinhos, chefe e profissionais da saúde forneceram menos apoio. Concluiu-se que pessoas com aids possuem suporte social satisfatório, principalmente, de amigos e familiares que não moram no mesmo domicílio.


Assuntos
Humanos , Apoio Social , Síndrome da Imunodeficiência Adquirida , HIV
20.
J Thorac Cardiovasc Surg ; 141(5): 1253-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20708756

RESUMO

OBJECTIVES: Rib fractures are a frequent traumatic injury associated with a relatively high morbidity. Currently, the treatment of rib fractures is symptomatic. Since it has been reported that pulsed ultrasounds accelerates repair of limb fractures, we hypothesized that the application of pulsed ultrasounds will modify the course of healing in an animal model of rib fracture. METHODS: We studied 136 male Sprague-Dawley rats. Animals were randomly assigned to different groups of doses (none, 50, 100, and 250 mW/cm(2) of intensity for 3 minutes per day) and durations (2, 10, 20, and 28 days) of treatment with pulsed ultrasounds. In every subgroup, we analyzed radiologic and histologic changes in the bone callus. In addition, we examined changes in gene expression of relevant genes involved in wound repair in both control and treated animals. RESULTS: Histologic and radiologic consolidation was significantly increased by pulsed ultrasound treatment when applied for more than 10 days. The application of 50 mW/cm(2) was the most effective dose. Only the 100 and 250 mW/cm(2) doses were able to significantly increase messenger RNA expression of insulin-like growth factor 1, suppressor of cytokine signaling-2 and -3, and vascular endothelial growth factor and decrease monocyte chemoattractant protein-1 and collagen type II-alpha 1. CONCLUSIONS: Our findings indicate that pulsed ultrasound accelerates the consolidation of rib fractures. This study is the first to show that pulsed ultrasound promotes the healing of rib fractures. From a translational point of view, this easy, cheap technique could serve as an effective new therapeutic modality in patients with rib fractures.


Assuntos
Consolidação da Fratura , Fraturas das Costelas/terapia , Terapia por Ultrassom , Animais , Quimiocina CCL2/genética , Colágeno Tipo III/genética , Modelos Animais de Doenças , Consolidação da Fratura/genética , Regulação da Expressão Gênica , Fator de Crescimento Insulin-Like I/genética , Masculino , RNA Mensageiro/metabolismo , Radiografia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fraturas das Costelas/diagnóstico por imagem , Fraturas das Costelas/genética , Fraturas das Costelas/patologia , Fraturas das Costelas/fisiopatologia , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética
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