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1.
Front Endocrinol (Lausanne) ; 15: 1282925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567303

RESUMO

Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls. Methods: Linear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients. Results: EPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively. Conclusion: High levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.


Assuntos
Calcinose , Hiperparatireoidismo , Fibrose Peritoneal , Humanos , Fibrose Peritoneal/etiologia , Cálcio , Fatores de Risco , Calcinose/etiologia , Minerais , Fosfatos
3.
Mol Pharm ; 21(2): 596-608, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38190605

RESUMO

New antimicrobials are urgently needed to combat the rising global health concern of antibiotic resistance. Antimicrobial peptides (AMPs) are one of the leading candidates as new antimicrobials since they target bacterial membranes and are therefore less prone to bacterial resistance. However, poor enzymatic stability, high production costs, and toxicity are drawbacks that limit their clinical use. Conjugation of AMPs to gold nanoparticles (NPs) may help to improve enzymatic stability and, thus, their overall antimicrobial efficiency. We did a one-pot synthesis of size-controlled (10 nm) gold NPs selectively conjugated to lipopeptides and determined their antibacterial activity. The conjugates exhibited potent (0.13-1.25 µM) antimicrobial activity against clinical isolates, including Gram-positive methicillin-resistant Staphylococcus aureus (S. aureus) ATCC33593, Gram-negative Escherichia coli (E. coli) CTX-M-14, multidrug-resistant Pseudomonas aeruginosa LESB58 and Acinetobacter baumannii ATCC19606, and showed promising activity (90% inhibition of initial biofilms and 80% reduction of preformed biofilms) against S. aureus and E. coli DH5α biofilms at low micromolar concentrations. The conjugates were stable in rat serum and not toxic to representative mammalian cell lines in vitro (≤64 µM) and in vivo (≤100 µM).


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Ratos , Animais , Staphylococcus aureus , Ouro/química , Peptídeos Antimicrobianos , Escherichia coli , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes , Mamíferos
4.
Int J Nurs Stud ; 150: 104647, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38056353

RESUMO

BACKGROUND: Given the health benefits of breastfeeding for infants and mothers, breastfeeding has become a significant public health issue. The global growth of mobile phone usage has created new options for breastfeeding promotion, including text messaging. OBJECTIVE: We aimed to evaluate the efficacy of text messaging interventions on breastfeeding outcomes and to identify the efficacy moderators of such interventions. METHODS: Ten electronic databases were searched from the inception of the databases to 5 July 2023. Studies were included if they used randomized controlled trials or quasi-experimental designs to evaluate the effect of text messaging interventions on breastfeeding outcomes. Two reviewers screened the included studies, assessed the risk of bias, and extracted the data. Pooled results were obtained by the random-effects model, and subgroup analyses were conducted on intervention characteristics to identify potential moderators. The protocol of this study was registered on PROSPERO (ID: CRD42022371311). RESULTS: Sixteen studies were included. Text messaging interventions could improve the exclusive breastfeeding rate (at <3 months: OR = 2.04; 95 % CI: 1.60-2.60, P < 0.001; at 3-6 months: OR = 1.66; 95 % CI: 1.18-2.33, P = 0.004; at ≥6 months: OR = 2.13; 95 % CI: 1.47-3.08, P < 0.001), and the breastfeeding self-efficacy (SMD = 0.30, 95 % CI: 0.14-0.45, P < 0.001). Text messaging interventions that covered antenatal and postnatal periods, delivered weekly were most effective in improving the exclusive breastfeeding rate. CONCLUSIONS: Text messaging interventions may improve breastfeeding practice compared with no or general health information. We suggest text messaging conducted from the pre- to postnatal periods in a weekly manner can effectively increase exclusive breastfeeding rates and breastfeeding self-efficacy. Further studies should investigate the relation between new theories (such as the health action process approach and the theory of message-framing) and efficacy of breastfeeding interventions, using text components.


Assuntos
Telefone Celular , Envio de Mensagens de Texto , Humanos , Feminino , Gravidez , Aleitamento Materno , Sistemas de Alerta , Mães
5.
Food Res Int ; 172: 113131, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689896

RESUMO

Studies have demonstrated avocado seeds are a good source of bioactive compounds. This study investigated the effects of roasting on the metabolites and anticancer activities of fermented avocado seeds. All three anti-cancer activities of fermented avocado seeds were higher at lower roasting temperature and time. The best inhibition effect was found against Hep G2 followed by the MDA-MB-231 and MCF-7 cancer cell lines. Untargeted metabolite profiling using gas chromatography-mass spectrometry resulted in identification of 208 metabolites. In total, 41 metabolites identified had VIP values more than 1 using PLS-R that were related to anticancer activities. All amino acids and most sugars were higher at lower roasting temperature and positively correlated to anticancer activity. The roasting conditions for optimal antioxidant and anticancer activities were determined to be 121 °C for 9 min. Findings showed that fermented avocado seed powder has the potential to become a functional food ingredient with beneficial bioctive properties.


Assuntos
Antineoplásicos , Persea , Aminoácidos , Antioxidantes/farmacologia , Sementes
6.
BJS Open ; 7(5)2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37757753

RESUMO

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Feminino , Masculino , Feocromocitoma/cirurgia , Adrenalectomia/efeitos adversos , Neoplasias das Glândulas Suprarrenais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Estudos de Coortes
7.
Biomed Rep ; 19(1): 46, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37324167

RESUMO

Gemcitabine is a chemotherapeutic agent for pancreatic cancer treatment. It has also been demonstrated to inhibit human pancreatic cancer cell lines, MIA PaCa-2 and PANC-1. The aim of the present study was to investigate the suppressive effect of fucoxanthin, a marine carotenoid, in combination with gemcitabine on pancreatic cancer cells. MTT assays and cell cycle analysis using flow cytometry were performed to study the mechanism of action. The results revealed that combining a low dose of fucoxanthin with gemcitabine enhanced the cell viability of human embryonic kidney cells, 293, while a high dose of fucoxanthin enhanced the inhibitory effect of gemcitabine on the cell viability of this cell line. In addition, the enhanced effect of fucoxanthin on the inhibitory effect of gemcitabine on PANC-1 cells was significant (P<0.01). Fucoxanthin combined with gemcitabine also exerted significant enhancement of the anti-proliferation effect in MIA PaCa-2 cells in a concentration dependent manner (P<0.05), compared with gemcitabine treatment alone. In conclusion, fucoxanthin improved the cytotoxicity of gemcitabine on human pancreatic cancer cells at concentrations that were not cytotoxic to non-cancer cells. Thus, fucoxanthin has the potential to be used as an adjunct in pancreatic cancer treatment.

8.
Eur J Surg Oncol ; 49(2): 497-504, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36602554

RESUMO

BACKGROUND: Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring. METHODS: Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score. RESULTS: PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p < 0.001), preoperative catecholamine level (p < 0.001), open surgery (p < 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CI95%, 1.09-3.13, p = 0.02), preoperative catecholamine level (OR: 3.11, CI95%, 1.74-5.55, p < 0.001), open surgery (OR: 3.31, CI95%, 1.57-6.97, p = 0.002) and preoperative mean arterial blood pressure (OR: 0.59, CI95%, 0.48-1.02, p = 0.08) were independently associated with PH, and were incorporated into a clinical risk score (AUROC 0.69, C-statistic 0.69). The risk of PH was 25% and 68% in low and high risk patients, respectively. CONCLUSION: The derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hipotensão , Laparoscopia , Feocromocitoma , Humanos , Feminino , Feocromocitoma/cirurgia , Estudos Retrospectivos , Adrenalectomia , Neoplasias das Glândulas Suprarrenais/cirurgia , Fatores de Risco , Catecolaminas
9.
Sensors (Basel) ; 22(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298389

RESUMO

Traditionally, pavement safety performance in terms of texture, friction, and hydroplaning speed are measured separately via different devices with various limitations. This study explores the feasibility of using a novel 0.1 mm 3D Safety Sensor for pavement safety evaluation in a non-contact and continuous manner with a single hardware sensor. The 0.1 mm 3D images were collected for pavement safety measurement from 12 asphalt concrete (AC) and Portland cement concrete (PCC) field sites with various texture characteristics. The results indicate that the Safety Sensor was able to measure pavement texture data as traditional devices do with better repeatability. Moreover, pavement friction numbers can be estimated using 0.1 mm 3D data via the proposed 3D texture parameters with good accuracy using an artificial neural network, especially for asphalt pavement. Lastly, a case study of pavement hydroplaning speed prediction was performed using the Safety Sensor. The results demonstrate the potential of using ultra high-resolution 3D imaging to measure pavement safety, including texture, friction, and hydroplaning, in a non-contact, continuous, and accurate manner.


Assuntos
Hidrocarbonetos , Imageamento Tridimensional , Lasers , Tecnologia
10.
ACS Omega ; 7(41): 36848-36855, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36278103

RESUMO

Two-dimensional materials have exhibited great potential in mitigating climate change through sensing and capturing carbon dioxide. The interaction of CO2 on orthorhombic silicon diphosphide remains unexplored in spite of its interesting properties such as high carrier mobility, piezoelectricity, and mechanical stability. Here, using density functional theory, the adsorption of CO2 on pristine and Ti-, V-, and Cr-doped monolayer SiP2 is investigated. Doped systems exhibited significantly stronger adsorption (-0.268 to -0.396 eV) than pristine SiP2 (-0.017 to -0.031 eV) and have the possibility of synthesis with low defect formation energies. Our results on adsorption energy, band structure, partial density of states, and charge transfer conclude that titanium- and vanadium-doped SiP2 monolayers would be promising materials for CO2 capture and removal.

12.
Molecules ; 27(9)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35566037

RESUMO

Tamarillo fruit contains many phytochemicals that have beneficial therapeutic and nutritional properties. Spray-drying is widely used to preserve fruit puree in powder form. However, to obtain high-quality fruit powder, the optimisation of spray-drying conditions is necessary, as a high drying temperature can damage sensitive bioactive compounds. This study investigated the effects of spray-drying on the microstructure, polyphenolics, total flavonoids, total carotenoids, antioxidant activity, and anticancer capacity of tamarillo powder. Response surface methodology (RSM) was used to optimise the spray-drying process to produce tamarillo powder. The independent variables were inlet drying temperature (120-160 °C), flow rate (1-5 g/mL), and maltodextrin concentration (0-10%). These variables influenced the microstructural attributes, bioactive components, and cytotoxicity of the spray-dried tamarillo powder. The increase in polyphenols and antioxidant activities were favoured under high-temperature spray drying conditions and a low carrier concentration. The optimised spray-drying conditions for producing tamarillo powder with high antioxidant and anticancer activities, high yield, and stable bioactive compounds were found to be at 146.8 °C inlet temperature, and a flow rate of 1.76 g/mL.


Assuntos
Antioxidantes , Dessecação , Antioxidantes/química , Antioxidantes/farmacologia , Dessecação/métodos , Nova Zelândia , Pós/química , Secagem por Atomização
14.
Materials (Basel) ; 14(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34640166

RESUMO

Pavement micro- and macro-texture have significant effects on roadway friction and driving safety. The influence of traffic polish on pavement texture has been investigated in many laboratory studies. This paper conducts field evaluation of pavement micro- and macro-texture under actual traffic polishing using three-dimensional (3D) areal parameters. A portable high-resolution 3D laser scanner measured pavement texture from a field site in 2018, 2019, and 2020. Then, the 3D texture data was decomposed to micro- and macro-texture using Fourier transform and Butterworth filter methods. Twenty 3D areal parameters from five categories, including height, spatial, hybrid, function, and feature parameters, were calculated to characterize pavement micro- and macro-texture. The results demonstrate that the 3D areal parameters provide an alternative to comprehensively characterize the evolution of pavement texture under traffic polish from different aspects.

15.
Gut ; 70(6): 1061-1069, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33547182

RESUMO

OBJECTIVE: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection. DESIGN: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups. RESULTS: 1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection. CONCLUSION: Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.


Assuntos
COVID-19 , Pancreatite , COVID-19/diagnóstico , COVID-19/epidemiologia , Estudos de Coortes , Comorbidade , Progressão da Doença , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Cooperação Internacional , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Mortalidade , Escores de Disfunção Orgânica , Avaliação de Resultados em Cuidados de Saúde , Pancreatite/diagnóstico , Pancreatite/mortalidade , Pancreatite/fisiopatologia , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
16.
Molecules ; 25(24)2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33334031

RESUMO

Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Lipopeptídeos/química , Lipopeptídeos/farmacologia , Biofilmes/crescimento & desenvolvimento , Géis , Proteínas Imobilizadas/química , Proteínas Imobilizadas/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia
17.
Heliyon ; 6(7): e04357, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32685714

RESUMO

Molluscan extracts confer a wide range of health promoting properties, one of them is cytotoxicity. Extraction and processing can affect the efficacy and properties of bioactive molecules. New Zealand (NZ) surf clams have never been thoroughly studied for bioactives until recently. However, the effect of cold and heat extraction procedure on biochemical composition and cytotoxic activities of NZ surf clam remains unanswered. The objective is to compare the effects on cytotoxicity of three NZ surf clams (Diamond shell, Crassula aequilatera; Storm shell, Mactra murchisoni; and Deepwater Tua tua, Paphies donacina) extracts via cold or heat process across cancer cell lines to find out which process can preserve bioactivity better. Fractions of extracts prepared via cold or heat procedures were tested for cell growth inhibition, apoptosis induction and cell cycle arrest in seven cancer cell lines. Apoptosis was induced through all cell lines, as further evidenced in Caspase-3/7 activities. Cell cycle arrest was focused on G2/M- and S- phases. Petroleum ether and ethyl acetate fractions, with the greatest bioactivity in this study, are rich in lipids and proteins, indicating likely bioactive sources. Cold preparation was responsible for the lowest cancer cell viability and induced greater apoptosis. Cold process retained better bioactivity/cytotoxicity than that of heat-processed extracts. This information may guide future health/nutraceutical clam product development.

18.
Materials (Basel) ; 12(23)2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31766331

RESUMO

Skid resistance is an important surface characteristic that influences roadway safety. Various studies have been performed to understand the interaction between pavement and tires through numerical simulation for skid resistance prediction. However, the friction parameters required for simulation inputs are generally determined by objective assumptions. This paper develops a finite element method (FEM)-based skid resistance simulation framework using in-situ 3D pavement surface texture and skid resistance data. A 3D areal pavement model is reconstructed from high resolution asphalt pavement surface texture data. The exponential decay friction model is implemented in the simulation and the interface friction parameters required for the simulation are determined using the binary search back-calculation approach based on a trial process with the desired level of differences between simulated and observed skid numbers. To understand the influence of texture characteristics on interface friction parameters, the high-resolution 3D texture data is separated into macro- and micro-scales through Butterworth filtering and various areal texture indicators are calculated at both levels. Principal component analysis (PCA) regression analysis is conducted to quantify the relationship between various texture characteristics and the interface friction parameters. The results from this study can be used to better prepare the inputs of friction parameters for FEM simulation.

19.
Cancer Immunol Res ; 7(12): 1903-1909, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31658994

RESUMO

Ipilimumab is effective for patients with melanoma, but not for those with less immunogenic tumors. We report a phase II trial of ipilimumab with concurrent or sequential stereotactic ablative radiotherapy to metastatic lesions in the liver or lung (NCT02239900). Ipilimumab (every 3 weeks for 4 doses) was given with radiotherapy begun during the first dose (concurrent) or 1 week after the second dose (sequential) and delivered as 50 Gy in 4 fractions or 60 Gy in 10 fractions to metastatic liver or lung lesions. In total, 106 patients received ≥1 cycle of ipilimumab with radiation. Median follow-up was 10.5 months. Median progression-free survival time was 2.9 months (95% confidence interval, 2.45-3.40), and median overall survival time was not reached. Rates of clinical benefit of nonirradiated tumor volume were 26% overall, 28% for sequential versus 20% for concurrent therapy (P = 0.250), and 31% for lung versus 14% for liver metastases (P = 0.061). The sequential lung group had the highest rate of clinical benefit at 42%. There were no differences in treatment-related adverse events between groups. Exploratory analysis of nontargeted lesions revealed that lesions receiving low-dose radiation were more likely to respond than those that received no radiation (31% vs. 5%, P = 0.0091). This phase II trial of ipilimumab with stereotactic radiotherapy describes satisfactory outcomes and low toxicities, lending support to further investigation of combined-modality therapy for metastatic cancers.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Ipilimumab/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Terapia Combinada , Feminino , Humanos , Ipilimumab/efeitos adversos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Análise de Sobrevida , Adulto Jovem
20.
Biomacromolecules ; 20(7): 2515-2529, 2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31145611

RESUMO

Peptides can serve as versatile therapeutics with a highly modular structure and tunable biophysical properties. In particular, the efficacy of peptide antibiotics against drug-resistant pathogens is of great promise, as few new classes of antibiotics are being developed to overcome the ever-increasing bacterial resistance to contemporary drugs. This work reports biophysical and antimicrobial studies of a designed library of ultrashort peptides that self-assemble into hydrogels at concentrations as low as 0.5% w/v in buffered saline, as confirmed by rheology. The hydrogels are constituted by ß-sheet-rich nanofibril networks, as determined by biophysical techniques including spectroscopy (attenuated total reflectance Fourier transform infrared spectroscopy and Congo red binding assay), short- and wide-angle X-ray scattering, and electron microscopy. Both peptide solutions and self-assembled hydrogels show potent antimicrobial activity against S. aureus and Pseudomonas aeruginosa by membrane lysis. These peptides also displayed selectivity toward bacterial cells over human dermal fibroblasts in vitro, as determined from Live/Dead, scanning electron microscopy, and coculture assays. This work reports an antimicrobial self-assembling motif of only three residues comprising an aromatically acylated cationic d-Dab/Lys amino acid, a second cationic residue, and naphthylalanine that heavily influences the self-assembly of these peptides into hydrogels. The variations in the antimicrobial activity and self-assembly properties between analogues may have implications in future studies on the correlation between self-assembly and biological activity in ultrashort peptides.


Assuntos
Anti-Infecciosos , Hidrogéis , Nanoestruturas/química , Peptídeos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Linhagem Celular , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Nanoestruturas/ultraestrutura , Peptídeos/química , Peptídeos/farmacologia , Pseudomonas aeruginosa/ultraestrutura , Staphylococcus aureus/ultraestrutura
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