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1.
Environ Toxicol ; 36(8): 1544-1556, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33885224

RESUMO

Gastric cancer is the fifth most common malignancy worldwide. Serjania marginata Casar. (SM) displays anti-inflammatory properties and has been used to treat gastrointestinal disorders. In the current study, we examined whether the hydroethanolic extract of SM leaves exerted cytotoxic, mutagenic, and protective effects in non-tumor gastric epithelium cells (MNP01) and gastric adenocarcinoma cells (ACP02) in vitro and analyzed whether its action was selective. Initially, cell viability (MTT assay), cell cycle kinetics (flow cytometry), and cell proliferation (total protein content) were analyzed. In addition, genomic instability (cytokinesis-block micronucleus cytome assay), anti/pro-oxidant status (CM-H2 DCFDA probe), and transcriptional expression (RT-qPCR) of genes related to cell cycle, cell death, and antioxidant defense were also evaluated. The SM extract was cytotoxic toward MNP01 and ACP02 cells at concentrations greater than 300 and 100 µg·ml-1 , respectively, and decreased protein content only toward ACP02 cells at 200 µg ml-1 . In ACP02 cells, the SM extract at 100 µg·ml-1 associated with doxorubicin (DXR; 0.2 µg ml-1 ) clearly promoted cell cycle arrest at the G2/M phase. The extract alone was not mutagenic to either cell type and reversed DXR-induced DNA damage and H2 O2 -induced oxidative stress in MNP01 cells. The gene expression experiments showed that SM hydroethanolic extract exerts an antioxidant response via NFE2L2 activation in non-tumor gastric cells, and cell cycle arrest (G2/M) in ACP02 gastric cancer cells via the TP53 pathway. The selective action of SM indicates that it is a promising therapeutic agent to treat gastric diseases and merits further studies.


Assuntos
Antioxidantes , Sapindaceae , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Extratos Vegetais , Folhas de Planta
2.
J Toxicol Environ Health A ; 82(5): 321-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30940006

RESUMO

Achyrocline satureioides (LAM) D.C. is a species plant used in folk medicine with several medicinal properties; however, few studies have focused on its potential adverse effects. The aim of this study was to examine the effects of ethanolic extract of A. satureioides flowers administered during pre-mating, mating, pregnancy and postpartum period on reproductive and developmental parameters in rats. Male and female rats received by gavage 0, 250, 500 or 750 mg/kg of extract. The animals were treated from pre-mating until 13 days post-partum. Phytochemical analysis revealed the presence of important flavonoids (quercetin, luteolin, caffeic acid, rutin, and ferulic acid). In females, biochemical, hematological or gestational parameters were not markedly altered by the extract. However, an increase in calcium and thyroid stimulating hormone (TSH) levels was found in treated-dams. Although TSH and T4 levels were not significantly altered in pups, there was a rise in body weight of pups whose mothers were treated with the extract. All males treated were able to successfully copulate with treated-females. However, rats exposed to 500 and 750 mg/kg of extract exhibited a significant decrease in daily testicular sperm production and delay in sperm transit time in the epididymis. The ethanolic extract of A. satureioides flowers produced adverse effects in the male reproductive system as evidenced by diminished sperm production and transport. In addition, the extract elevated TSH levels of exposed mothers which may consequently affect the development of pups but this requires further evaluation.


Assuntos
Achyrocline/química , Extratos Vegetais/toxicidade , Reprodução/efeitos dos fármacos , Animais , Feminino , Flores/química , Masculino , Ratos/crescimento & desenvolvimento , Ratos Wistar , Testes de Toxicidade
3.
Scand J Med Sci Sports ; 29(10): 1537-1545, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31112342

RESUMO

This study aimed at examining the suitability of a standard treadmill test (TT), popular intermittent field tests, and small-sided football matches to induce maximal heart rate (HRmax ) in recreational football players. Sixty-six inactive untrained male subjects (age: 39.3 ± 5.8 years, VO2max : 41.2 ± 6.2 mL kg-1  min-1 , body mass: 81.9 ± 10.8 kg, height: 173.2 ± 6.4 cm) were evaluated. On separate occasions, the players were randomly submitted to a progressive VO2max TT, to the Yo-Yo intermittent endurance level 1 (YYIE1) and level 2 (YYIE2) tests, to the Yo-Yo intermittent recovery level 1 (YYIR1) test, and to 7v7 (43 × 27 m pitch, 83 m2 /player) football matches (45 minutes; 2-4 matches/player). To ensure data consistency, exercise HR was recorded using the same HR monitors in all the experimental conditions. A total of 73%, 24%, 18%, 17%, and 30% of the players achieved their HRmax during the YYIE1, YYIE2, YYIR1, TT, and the small-sided football matches, respectively. The probability of achieving HRmax increased proportionally to test duration, with 7.8 minutes as the cutoff time. Variations in HRpeak of ±2 b min-1 should be regarded as of practical relevance. YYIE1 HRpeak provided the most accurate estimation of a subject's individual HRmax and much higher probability of reaching HRmax . Nevertheless, the results of this study suggest caution in considering a reference test for HRmax assessment in this population. The use of confirmation tests is still highly advisable when the test duration is shorter than 7.8 minutes. In this regard, field tests seem to be suitable and accurate for individual HRmax assessment in recreational football players.


Assuntos
Teste de Esforço/métodos , Frequência Cardíaca , Futebol/fisiologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Aptidão Física
4.
J Mater Sci Mater Med ; 30(2): 27, 2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30747338

RESUMO

Guided tissue regeneration (GTR) is a surgical procedure applied in the reconstruction of periodontal defects, where an occlusive membrane is used to prevent the fast-growing connective tissue from migrating into the defect. In this work, silk fibroin (SF) membranes were developed for periodontal guided tissue regeneration. Solutions of SF with glycerol (GLY) or polyvinyl alcohol (PVA) where prepared at several weight ratios up to 30%, followed by solvent casting and thermal annealing at 85 °C for periods of 6 and 12 h to produce high flexible and stable membranes. These were characterized in terms of their morphology, physical integrity, chemical structure, mechanical and thermal properties, swelling capability and in vitro degradation behavior. The developed blended membranes exhibited high ductility, which is particular relevant considering the need for physical handling and adaptability to the defect. Moreover, the membranes were cultured with human periodontal ligament fibroblast cells (hPDLs) up to 7 days. Also, the higher hydrophilicity and consequent in vitro proteolytic degradability of these blends was superior to pure silk fibroin membranes. In particular SF/GLY blends demonstrated to support high cell adhesion and viability with an adequate hPDLs' morphology, make them excellent candidates for applications in periodontal regeneration.


Assuntos
Fibroínas/química , Regeneração Tecidual Guiada Periodontal/métodos , Animais , Bombyx , Adesão Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Fibroblastos/metabolismo , Glicerol/química , Temperatura Alta , Humanos , Membranas Artificiais , Ligamento Periodontal/efeitos dos fármacos , Álcool de Polivinil/química , Regeneração , Estresse Mecânico , Propriedades de Superfície , Resistência à Tração , Alicerces Teciduais/química
5.
Fish Physiol Biochem ; 45(3): 1051-1065, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31089991

RESUMO

The aim of this study was to assess the leaf aqueous extract composition of Serjania marginata and the effects of its inclusion on the diet of Nile tilapia (Oreochromis niloticus), with respect to the activity of digestive enzymes and enzymes associated with the metabolism of the liver and intestine and liver histopathology. Fish (initial mean weight, 54.36 ± 17.04 g) were divided into groups: fasting (without feeding), control (commercial feed), and treatment (commercial feed with leaf aqueous extract of Serjania marginata), and in each aquarium, there were five individuals and the fish fed ad libitum for 15 days. Treatment fish had ingested on average 224.3 mg of extract/kg of fish/day. In the extract analysis by mass spectrometry, quercitrin, isoquercitrin, A-type proanthocyanidin trimer, and quinic acid were identified. In the enzymatic activity, fish from the treatment group showed higher level of alkaline phosphatase, while the hepatotoxic markers (AST and ALT) and levels of lipase, amylase, and nonspecific protease did not differ (p > 0.05). In liver histopathological analysis, it was observed that fish from the treatment showed normal structure, while abnormalities were associated with control (fibrosis, loss of cordonal architecture, vacuolated hepatocytes with nucleus displaced to the periphery) and fasting (reduction in hepatocyte size and sinusoidal space). The intestine histopathology evidenced that the extract favored the development of goblet cells and intestinal fold height. The results indicated that the leaf aqueous extract of S. marginata assists in the structural maintenance of the liver and intestine and stimulates intestinal alkaline phosphatase production in Nile tilapia, suggesting that the identified compounds act on the liver and intestine, showing hepatoprotective effects and stimulating intestinal digestion.


Assuntos
Ciclídeos/metabolismo , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Sapindaceae/química , Estômago/efeitos dos fármacos , Animais , Suplementos Nutricionais , Fígado/enzimologia , Extratos Vegetais/química , Substâncias Protetoras/química
6.
Adv Exp Med Biol ; 1059: 209-217, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736575

RESUMO

Osteochondral lesions represent one of the major causes of disabilities in the world. These defects are due to degenerative or inflammatory arthritis, but both affect the articular cartilage and the underlying subchondral bone. Defects from trauma or degenerative pathology frequently cause severe pain, joint deformity, and loss of joint motion. Osteochondral defects are a significant challenge in orthopedic surgery, due to the cartilage complexity and unique structure, as well as its exposure to high pressure and motion. Although there are treatments routinely performed in the clinical practice, they present several limitations. Tissue engineering can be a suitable alternative for osteochondral defects since bone and cartilage engineering had experienced a notable advance over the years. Allied with nanotechnology, osteochondral tissue engineering (OCTE) can be leveled up, being possible to create advanced structures similar to the OC tissue. In this chapter, the current strategies using nanoparticles-based systems are overviewed. The results of the studies herein considered confirm that advanced nanomaterials will undoubtedly play a crucial role in the design of strategies for treatment of osteochondral defects in the near future.


Assuntos
Doenças Ósseas/terapia , Doenças das Cartilagens/terapia , Nanopartículas/uso terapêutico , Engenharia Tecidual/métodos , Rastreamento de Células/métodos , Sistemas de Liberação de Medicamentos , Humanos , Veículos Farmacêuticos , Alicerces Teciduais
7.
Aust Crit Care ; 31(5): 284-290, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29153826

RESUMO

BACKGROUND AND AIMS: The phase angle (PA), derived from bioelectrical impedance analysis (BIA), has been interpreted as a cell membrane integrity indicator, while handgrip strength (HGS) has been used as a prognostic indicator in certain clinical situations, such as in cardiac, oncologic patients with renal disease, hemodialysis patients, HIV-positive patients, and liver disease patients. In addition to prognostic scores, body changes due to surgical procedures indicate the importance of measuring muscle function and cell integrity. This study aimed to evaluate the behaviour of PA and HGS in patients undergoing cardiac surgery and associate these factors with clinical outcomes and prognosis. METHODS: This was a prospective cohort study of 50 consecutively recruited patients (aged ≥18 years) undergoing cardiac surgery. Measures PA and HGS were at three set points: preoperative, at hospital discharge and three months postoperative. The following data were collected: time of cardiopulmonary bypass (CPB), ischemia, mechanical ventilation (MV), Intensive Care Unit (ICU) length of stay (LOS) and hospital LOS after surgery; the EuroSCORE was also calculated. RESULTS: A decrease in PA was observed between the preoperative and the two postoperative stages (p<0.001). There was a reduction in HGS between the preoperative and hospital discharge assessments (p<0.001) and a recovery three months postoperative (p<0.001). The MV and EuroSCORE were inversely associated with PA and HGS in all three assessments. The PA was correlated with EuroSCORE in the first assessment (p=0.007) and in the second and third assessments (p<0.001), as well as with MV in all three assessments (p<0.001). The HGS was correlated with EuroSCORE and MV in the first and second assessments (p<0.001) and in the third assessment (p=0.010 and p=0.018, respectively). CONCLUSION: PA and HGS appear to be related to MV time, ICU LOS and hospital LOS after surgery in patients undergoing cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Força da Mão , Impedância Elétrica , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
8.
JAMA ; 318(14): 1335-1345, 2017 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-28973363

RESUMO

Importance: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. Objective: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. Design, Setting, and Participants: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. Interventions: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. Main Outcomes and Measures: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. Results: A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Conclusions and Relevance: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT01374022.


Assuntos
Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/terapia , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Respiração com Pressão Positiva/efeitos adversos , Síndrome do Desconforto Respiratório/mortalidade , Volume de Ventilação Pulmonar , Falha de Tratamento
9.
J Intensive Care Med ; 31(8): 544-52, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26112759

RESUMO

INTRODUCTION: Tissue hypoperfusion and hypoxia markers predict mortality in critically ill patients. This study evaluates the ability of serum lactate, central venous oxygen saturation (Scvo 2), and venous-arterial carbon dioxide difference (GapCo 2) to predict mortality in patients with postcardiac arrest (post-CA) syndrome. METHODS: A prospective observational study of patients with post-CA in a tertiary teaching hospital. Serial assessments of lactate, lactate clearance (Clac), GapCo 2, and Scvo 2 in the first 72 hours post-CA were analyzed. Adults (≥18 years) patients resuscitated from CA were included. The primary end point was 28-day mortality and secondary end points were 24- and 72-hour mortality. RESULTS: A total of 54 patients were recruited, 33 (61,1%) of 54 were men, with a 28-day mortality of 75.9%. Cardiac arrest occurred in-hospital in 84.6% of survivors and 97.5% of nonsurvivors. Lactate and Clac were significantly associated with mortality at 28 days, yielding an area under the receiver-operating characteristic curve of 0.797 (lactate 6 hours) and 0.717 (Clac 6 hours) with a positive predictive value of 96% for lactate 6 hours (> 2.5 mmol/L) and 89.5% for Clac 6 hours (<50%). Survival analysis confirmed the difference between the groups from the 24th hour post-CA. Considering mortality at 24 hours, lactate, Clac, and Scvo 2 (immediately post-CA, 6 and 18 hours) were different between the groups. In mortality at 72 hours, lactate, Clac, Scvo 2 (48 hours), and GapCo 2 (36 and 48 hours) were associated with mortality. CONCLUSION: In post-CA syndrome, serum lactate and Clac were consistently able to predict mortality.


Assuntos
Dióxido de Carbono/sangue , Parada Cardíaca/sangue , Parada Cardíaca/mortalidade , Ácido Láctico/sangue , Idoso , Gasometria , Débito Cardíaco , Feminino , Parada Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Estudos Prospectivos , Curva ROC , Ressuscitação/mortalidade
10.
J Cell Mol Med ; 19(6): 1253-61, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25854285

RESUMO

Patients undergoing mechanical ventilation (MV) often experience respiratory muscle dysfunction, which complicates the weaning process. There is no simple means to predict or diagnose respiratory muscle dysfunction because diagnosis depends on measurements in muscle diaphragmatic fibre. As oxidative stress is a key mechanism contributing to MV-induced respiratory muscle dysfunction, the aim of this study was to determine if differences in blood measures of oxidative stress in patients who had success and failure in a spontaneous breathing trial (SBT) could be used to predict the outcome of MV. This was a prospective analysis of MV-dependent patients (≥72 hrs; n = 34) undergoing a standard weaning protocol. Clinical, laboratory and oxidative stress analyses were performed. Measurements were made on blood samples taken at three time-points: immediately before the trial, 30 min. into the trial in weaning success (WS) patients, or immediately before return to MV in weaning failure (WF) patients, and 6 hrs after the trial. We found that blood measures of oxidative stress distinguished patients who would experience WF from patients who would experience WS. Before SBT, WF patients presented higher oxidative damage in lipids and higher antioxidant levels and decreased nitric oxide concentrations. The observed differences in measures between WF and WS patients persisted throughout and after the weaning trial. In conclusion, WF may be predicted based on higher malondialdehyde, higher vitamin C and lower nitric oxide concentration in plasma.


Assuntos
Biomarcadores/sangue , Estresse Oxidativo , Respiração Artificial/métodos , Desmame do Respirador/métodos , Idoso , Idoso de 80 Anos ou mais , Ácido Ascórbico/sangue , Catalase/sangue , Feminino , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Glutationa Peroxidase/sangue , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Nitritos/sangue , Avaliação de Resultados em Cuidados de Saúde/métodos , Valor Preditivo dos Testes , Superóxido Dismutase/sangue
11.
Anesthesiology ; 122(1): 29-38, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25401417

RESUMO

BACKGROUND: Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients, but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer. METHODS: In a randomized, controlled, parallel-group, double-blind (patients and outcome assessors) superiority trial in the intensive care unit of a tertiary oncology hospital, the authors evaluated whether a restrictive strategy of erythrocyte transfusion (transfusion when hemoglobin concentration <7 g/dl) was superior to a liberal one (transfusion when hemoglobin concentration <9 g/dl) for reducing mortality and severe clinical complications among patients having major cancer surgery. All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and randomly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy. The primary outcome was a composite endpoint of mortality and morbidity. RESULTS: A total of 198 patients were included as follows: 101 in the restrictive group and 97 in the liberal group. The primary composite endpoint occurred in 19.6% (95% CI, 12.9 to 28.6%) of patients in the liberal-strategy group and in 35.6% (27.0 to 45.4%) of patients in the restrictive-strategy group (P = 0.012). Compared with the restrictive strategy, the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16% (3.8 to 28.2%) and a number needed to treat of 6.2 (3.5 to 26.5). CONCLUSION: A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.


Assuntos
Neoplasias Abdominais/cirurgia , Transfusão de Eritrócitos/métodos , Transfusão de Eritrócitos/estatística & dados numéricos , Brasil/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Hemoglobinas/análise , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Risco
12.
J Nat Prod ; 78(1): 77-84, 2015 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-25517504

RESUMO

A phytochemical study of a Serjania marginata leaf extract with antiulcer activity afforded 15 compounds, including the new 3-O-α-l-arabinopyranosyl(1→3)-α-l-rhamnopyranosyl(1→2)[ß-d-glucopyranosyl(1→4)]-α-l-arabinopyranosyloleanolic acid (1) and 7,5″-anhydroapigenin 8-C-α-(2,6-dideoxy-5-hydroxy-ribo-hexopyranosyl)-4'-O-ß-d-glucopyranoside (4). The structures of the new compounds were determined by spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry, and chemical methods. Compound 4 is a C-hexopyranosylapigenin with an unusual cyclic ether linkage between C-5″ and C-7 of apigenin. The isolated proanthocyanidins have high antioxidant activities, and these compounds are probably responsible for the gastroprotective effect of the extract.


Assuntos
Antiulcerosos/química , Apigenina/química , Glicosídeos/isolamento & purificação , Ácido Oleanólico/isolamento & purificação , Sapindaceae/química , Antiulcerosos/isolamento & purificação , Antiulcerosos/farmacologia , Apigenina/isolamento & purificação , Apigenina/farmacologia , Brasil , Glicosídeos/química , Glicosídeos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Folhas de Planta/química , Saponinas/química , Triterpenos/química
13.
BMC Biol ; 12: 47, 2014 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-24923837

RESUMO

BACKGROUND: In the adult central nervous system, axonal regeneration is abortive. Regulators of microtubule dynamics have emerged as attractive targets to promote axonal growth following injury as microtubule organization is pivotal for growth cone formation. In this study, we used conditioned neurons with high regenerative capacity to further dissect cytoskeletal mechanisms that might be involved in the gain of intrinsic axon growth capacity. RESULTS: Following a phospho-site broad signaling pathway screen, we found that in conditioned neurons with high regenerative capacity, decreased glycogen synthase kinase 3ß (GSK3ß) activity and increased microtubule growth speed in the growth cone were present. To investigate the importance of GSK3ß regulation during axonal regeneration in vivo, we used three genetic mouse models with high, intermediate or no GSK3ß activity in neurons. Following spinal cord injury, reduced GSK3ß levels or complete neuronal deletion of GSK3ß led to increased growth cone microtubule growth speed and promoted axon regeneration. While several microtubule-interacting proteins are GSK3ß substrates, phospho-mimetic collapsin response mediator protein 2 (T/D-CRMP-2) was sufficient to decrease microtubule growth speed and neurite outgrowth of conditioned neurons and of GSK3ß-depleted neurons, prevailing over the effect of decreased levels of phosphorylated microtubule-associated protein 1B (MAP1B) and through a mechanism unrelated to decreased levels of phosphorylated cytoplasmic linker associated protein 2 (CLASP2). In addition, phospho-resistant T/A-CRMP-2 counteracted the inhibitory myelin effect on neurite growth, further supporting the GSK3ß-CRMP-2 relevance during axon regeneration. CONCLUSIONS: Our work shows that increased microtubule growth speed in the growth cone is present in conditions of increased axonal growth, and is achieved following inactivation of the GSK3ß-CRMP-2 pathway, enhancing axon regeneration through the glial scar. In this context, our results support that a precise control of microtubule dynamics, specifically in the growth cone, is required to optimize axon regrowth.


Assuntos
Axônios/fisiologia , Quinase 3 da Glicogênio Sintase/genética , Cones de Crescimento/metabolismo , Microtúbulos/metabolismo , Regeneração , Animais , Feminino , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fosforilação , Ratos , Ratos Wistar
14.
J Phys Ther Sci ; 27(6): 1945-50, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26180354

RESUMO

[Purpose] To evaluate pre-extubation variables and check the discriminative validity of age as well as its correlation with weaning failure in elderly patients. [Subjects and Methods] Two hundred thirty-nine consecutive patients (48% female) who were on mechanical ventilation and had undergone orotracheal intubation were divided into four subgroups according to their age: <59 years, 60-69 years, 70-79 years, and >80 years old. The expiratory volume (VE), respiratory frequency (f), tidal volume (VT), and respiratory frequency/tidal volume ratio (f/VT) were used to examine differences in weaning parameters between the four subgroups, and age was correlated with weaning failure. [Results] The rate of weaning failure was 27.8% in patients aged >80 years and 22.1% in patients aged <60 years old. Elderly patients presented higher f/VT and f values and lower VT values. The areas under the receiver operating characteristic curves for f/VT ratio were smaller than those published previously. [Conclusion] Our results indicate that aging influences weaning criteria without causing an increase in weaning failure.

15.
BMC Endocr Disord ; 14: 50, 2014 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-24941997

RESUMO

BACKGROUND: Obesity and diabetes mellitus are well-defined risk factors for cardiovascular mortality. The impact of antecedent hyperglycemia and body size on mortality in critical ill patients in intensive care units (ICUs) may vary across their range of values. Therefore, we prospectively analyzed the relationship between in-hospital mortality and preexisting hyperglycemia and body size in critically ill ICU patients to understand how mortality varied among normal, overweight, and obese patients and those with low, intermediate, and high glycated hemoglobin (HbA1c) levels. METHODS: Medical history, weight, height, physiologic variables, and HbA1c were obtained during the first 24 h for patients who were consecutively admitted to the high complexity ICU of Hospital de Clínicas de Porto Alegre, Brazil, from April to August 2011. The relationships between mortality and obesity and antecedent hyperglycemia were prospectively analyzed by cubic spline analysis and a Cox proportional hazards model. RESULTS: The study comprised 199 patients. The overall hospital mortality rate was 43.2% during a median 16 (8-28) days of follow-up. There was a progressive risk of in-hospital mortality with higher HbA1c levels, with the relationship becoming significant at HbA1c >9.3% compared with lower levels (hazard ratio 1.74; 95% confidence interval with Bonferroni correction 1.49-2.80). In contrast, mean body mass index (BMI) was higher in survivors than in nonsurvivors (27.2 kg/m2 ± 7.3 vs. 24.7 kg/m2 ± 5.0 P = 0.031, respectively). Cubic spline analysis showed that these relationships differed nonlinearly through the spectrum of BMI values. In a Cox proportional hazards model adjusted for Acute Physiology and Chronic Health Evaluation II score and HbA1c, the risk of in-hospital mortality progressively decreased with increasing BMI (BMI <20 vs. 20-23.9 kg/m2, P = 0.032; BMI <20 vs. 24-34.9 kg/m2, P = 0.010; BMI <20 vs. ≥35 kg/m2, P = 0.032). CONCLUSIONS: Our findings suggest that significant hyperglycemia prior to ICU admission is a risk factor for in-hospital mortality. Conversely, increasing BMI may confer an advantageous effect against mortality in critical illness independently of previous glycemic control.


Assuntos
Estado Terminal/mortalidade , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Hiperglicemia/fisiopatologia , Obesidade/fisiopatologia , Glicemia/análise , Índice de Massa Corporal , Tamanho Corporal , Brasil , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
16.
BMC Anesthesiol ; 13: 11, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23773812

RESUMO

BACKGROUND: Studies suggest that in patients admitted to intensive care units (ICU), physical functional status (PFS) improves over time, but does not return to the same level as before ICU admission. The goal of this study was to assess physical functional status two years after discharge from an ICU and to determine factors influencing physical status in this population. METHODS: The study reviewed all patients admitted to two non-trauma ICUs during a one-year period and included patients with age ≥ 18 yrs, ICU stay ≥ 24 h, and who were alive 24 months after ICU discharge. To assess PFS, Karnofsky Performance Status Scale scores and Lawton-Instrumental Activities of Daily Living (IADL) scores at ICU admission (K-ICU and L-ICU) were compared to the scores at the end of 24 months (K-24mo and L-24mo). Data at 24 months were obtained through telephone interviews. RESULTS: A total of 1,216 patients were eligible for the study. Twenty-four months after ICU discharge, 499 (41.6%) were alive, agreed to answer the interview, and had all hospital data available. PFS (K-ICU: 86.6 ± 13.8 vs. K-24mo: 77.1 ± 19.6, p < 0.001) and IADL (L-ICU: 27.0 ± 11.7 vs. L-24mo: 22.5 ± 11.5, p < 0.001) declined in patients with medical and unplanned surgical admissions. Most strikingly, the level of dependency increased in neurological patients (K-ICU: 86 ± 12 vs. K-24mo: 64 ± 21, relative risk [RR] 2.6, 95% CI, 1.8-3.6, p < 0.001) and trauma patients (K-ICU: 99 ± 2 vs. K-24mo: 83 ± 21, RR 2.7, 95% CI, 1.6-4.6, p < 0.001). The largest reduction in the ability to perform ADL occurred in neurological patients (L-ICU: 27 ± 7 vs. L-24mo: 15 ± 12, RR 3.3, 95% CI, 2.3-4.6 p < 0.001), trauma patients (L-ICU: 32 ± 0 vs. L-24mo: 25 ± 11, RR 2.8, 95% CI, 1.5-5.1, p < 0.001), patients aged ≥ 65 years (RR 1.4, 95% CI, 1.07-1.86, p = 0.01) and those who received mechanical ventilation for ≥ 8 days (RR 1.48, 95% CI, 1.02-2.15, p = 0.03). CONCLUSIONS: Twenty-four months after ICU discharge, PFS was significantly poorer in patients with neurological injury, trauma, age ≥ 65 tears, and mechanical ventilation ≥ 8 days. Future studies should focus on the relationship between PFS and health-related quality of life in this population.

17.
Nutr Clin Pract ; 38(3): 617-627, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36351616

RESUMO

BACKGROUND: This study aimed to investigate the relationship between acute gastrointestinal injury (AGI) and hemodynamic and perfusion parameters in the first week of intensive care unit (ICU) admission and evaluate the association of AGI with ICU and hospital outcomes in patients with septic shock undergoing mechanical ventilation. METHODS: This retrospective cohort study applied the criteria proposed by the European Society of Intensive Medicine to classify the participants into risk/dysfunction group (AGI grade I and II) and failure group (AGI grade III and IV). Hemodynamic and perfusion parameters data previously collected in the first 48 h after ICU admission (admission, 12, 24, 48 h) were analyzed. RESULTS: A total of 163 were included and classified into AGI grades I (n = 79), II (n = 64), III (n = 20), and IV (none). Groups consisted of AGI risk/dysfunction (n = 143, 87.8%) and AGI failure (n = 20, 12.2%) patients. Patients with AGI failure had higher heart rate and mottling score (MS) at admission, lower mean arterial pressure, and an oliguria incidence at 12 h compared with those without AGI failure. Skin MS and abdominal primary site of infection were risk factors for AGI failure. AGI failure tended to be a risk factor for ICU mortality (risk ratio [95% CI]: 1.37 [0.99-1.89]; P = 0.053). CONCLUSION: AGI was frequently observed in patients with septic shock in the first week of ICU admission. Higher heart rate and MS and lower mean arterial pressure and incidence of oliguria were identified in patients with AGI failure compared with those without. AGI failure was associated with ICU mortality.


Assuntos
Gastroenteropatias , Enteropatias , Choque Séptico , Humanos , Choque Séptico/complicações , Estudos Retrospectivos , Oligúria , Gastroenteropatias/epidemiologia , Hemodinâmica , Perfusão , Unidades de Terapia Intensiva , Prognóstico
18.
Nutr Clin Pract ; 38(5): 1093-1103, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37302020

RESUMO

BACKGROUND: Bioimpedance phase angle (PA) is a measure of cell membrane integrity, whereas handgrip strength (HGS) is an evaluation of functional capacity. Although both are related to the prognosis of patients undergoing cardiac surgery, their changes over time are less known. This study followed variations in PA and HGS for 1 year in these patients, determining associations with clinical outcomes. METHODS: This prospective cohort study included 272 cardiac surgery patients. PA and HGS were measured at six predetermined times. The evaluated outcomes were surgery type; bleeding; time of surgery, cardiopulmonary bypass, aortic cross-clamp, and mechanical ventilation; postoperative (PO) length of stay (LOS) in the intensive care unit (ICU) and hospital; and infections, hospital readmission, reoperation, and mortality. RESULTS: There were reductions in PA and HGS values after surgery, with total recovery beginning at 6 months for PA and 3 months for HGS. In the PA area under the curve (AUC), age, combined surgery, and sex (ß = -9.66, P < 0.001; ß = -252.85, P = 0.005; ß = -216.56, P < 0.001, respectively) were predictors for PA-AUC reduction. Stratified by sex, age (ß = -93.54, P < 0.001) and PO LOS (ß = -46.91, P = 0.003) were predictors for HGS-AUC reduction in women, but only age was a predictor in men (ß = -77.02, P = 0.010). PA and HGS had an effect in hospital LOS and ICU LOS. CONCLUSION: Age, combined surgery, and female sex were predictors of reduced PA-AUC, whereas reduced HGS-AUC was predicted by age in both sexes and PO hospital LOS in women, which suggests that these factors could interfere in prognosis.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Força da Mão , Masculino , Humanos , Feminino , Estudos Prospectivos , Tempo de Internação , Prognóstico
19.
Bioengineering (Basel) ; 10(4)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37106614

RESUMO

This work aims to engineer a new stable injectable Mn-based methacrylated gellan gum (Mn/GG-MA) hydrogel for real-time monitored cell delivery into the central nervous system. To enable the hydrogel visualization under Magnetic Resonance Imaging (MRI), GG-MA solutions were supplemented with paramagnetic Mn2+ ions before its ionic crosslink with artificial cerebrospinal fluid (aCSF). The resulting formulations were stable, detectable by T1-weighted MRI scans and also injectable. Cell-laden hydrogels were prepared using the Mn/GG-MA formulations, extruded into aCSF for crosslink, and after 7 days of culture, the encapsulated human adipose-derived stem cells remained viable, as assessed by Live/Dead assay. In vivo tests, using double mutant MBPshi/shi/rag2 immunocompromised mice, showed that the injection of Mn/GG-MA solutions resulted in a continuous and traceable hydrogel, visible on MRI scans. Summing up, the developed formulations are suitable for both non-invasive cell delivery techniques and image-guided neurointerventions, paving the way for new therapeutic procedures.

20.
J Ethnopharmacol ; 304: 116018, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36496043

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Serjania marginata Casar (Sapindaceae Family) Leaves are popularly used against abdominal pain. Antiulcer properties of S. marginata were scientifically described, however rare studies showed the antinociceptive effects of this plant. AIM OF STUDY: In this study, we investigated the antinociceptive and anti-inflammatory effects of aqueous extract obtained from Serjania marginata leaves (AESM) in nociception/inflammation models. MATERIAL AND METHODS: AESM was analyzed in FIA-ESI-IT-MS and Mass spectrometer LTQ XL. AESM oral administration (p.o.) (30, 100 and 300 mg/kg), dexamethasone subcutaneous injection (1 mg/kg, s.c.) and morphine (5 mg/kg, s.c.) were tested against the acetic acid-induced nociception, carrageenan-induced acute inflammatory paw edema/hyperalgesia, formalin-induced nociception and carrageenan-induced pleurisy in Swiss mice. RESULTS: Flavonoids rutin was detected in the phytochemical analysis of this extract. Oral treatment of AESM 300 mg/kg significantly reduced the number of acetic acid-induced abdominal writhing. AESM (100 and 300 mg/kg) significantly inhibited formalin-induced nociception, mechanical hyperalgesia and paw edema in carrageenan-model. Furthermore, AESM significantly inhibited leukocyte migration and protein exudation in the carrageenan-induced pleurisy test. CONCLUSION: This study confirms the antinociceptive, and anti-inflammatory activity of AESM, which may explain, in part, the popular use of this plant as a natural antinociceptive agent. This pharmacological action can be caused by flavonoids such as rutin and other compounds present in AESM.


Assuntos
Pleurisia , Sapindaceae , Camundongos , Animais , Carragenina , Analgésicos/efeitos adversos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Anti-Inflamatórios/efeitos adversos , Sapindaceae/química , Ácido Acético/uso terapêutico , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Formaldeído , Folhas de Planta/química
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