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1.
Food Res Int ; 174(Pt 1): 113466, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986409

RESUMO

The impact of primary cooling on beef microbiota was investigated on six beef carcasses consecutively processed with the parallel use of metataxonomic and culture-dependent analysis. Samples were collected immediately after slaughtering (AS) and after the 24th-hour post-cooling (PC) from three different surfaces, namely neck, flank and thigh. The main objective was to examine whether the microbiota composition of beef carcasses changes as function of the surface sampled, primary cooling (from AS to PC) and animal's origin (breeder). The outcomes underline that primary cooling did not affect qualitatively the composition of the potentially active microbiota or the carcass superficial counts. Although slight changes in chemical-physical parameters like volatile organic compounds (VOCs) were observed after cooling, the carcasses microbiota and its inferred metabolic pathways varied among animals as a function of their origin. Co-occurrence and co-exclusion analyses underlined competition for the colonisation of the carcass surface between Brochothrix-Psychrobacter and Carnobacterium-Serratia-Pseudomonas. Once integrated in a comprehensive monitoring of the supply chain, the metataxonomic characterisation of the beef carcasses microbiota might represent a valid integrative approach to define the cuts' perishability and their appropriateness to specific packaging and storage methods. These new bits of knowledge could be the base to define good strategies for the prevention of meat spoilage.


Assuntos
Microbiologia de Alimentos , Microbiota , Animais , Bovinos , Carne , Temperatura Baixa
2.
Microbiol Res ; 260: 127012, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35430488

RESUMO

Recent advances have highlighted probiotic role in preventing colorectal cancer, by promoting differentiation, inhibiting proliferation, and inducing apoptosis in colonocytes. Here, three ascertained probiotics (L. rhamnosus GG ATCC 53103, L. reuterii DSM 17938 and L. johnsonii LC1) and four food-isolated putative probiotics (L. plantarum S2, L. plantarum O2, L. pentosus S3, L. rhamnosus 14E4) were investigated for their ability to adhere to HT29 cancer cells and to inhibit their and the chemoresistant counterpart (HT29-dx cells) proliferation. Three putative probiotics (S2, S3 and 14E4) were able to decrease viability of both sensitive and chemo-resistant HT-29 cells. Supposing this effect related to secreted metabolites (namely short chain fatty acids (SCFA), exopolysaccharides (EPS) and extracellular proteins) we tested the efficacy of extracellular extracts and butyrate with or without the chemotherapeutic agent doxorubicin (DOXO) (10 µM, 4 h). Increased production of mitochondrial reactive oxygen species (ROS) in HT29 and HT29-dx cells was observed. Moreover, cell exposure to DOXO (10 µM, 24 h) and extracellular extracts (48 h) reduced cell viability. Comparative phenotypic and secretome analyses on the effective/non effective strains, revealed quantitative/qualitative differences in EPS content and protein profiles, suggesting that P40, phage-tail-like and capsid-like proteins may be also involved. These results suggest that food-isolated bacteria releasing bioactive compounds (butyrate, EPS and peculiar proteins) may control cancer cell proliferation and improve their response to chemotherapy.


Assuntos
Neoplasias , Probióticos , Butiratos/farmacologia , Sobrevivência Celular , Células HT29 , Humanos , Extratos Vegetais , Probióticos/farmacologia
3.
Eur Rev Med Pharmacol Sci ; 26(1): 270-277, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35049004

RESUMO

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.


Assuntos
ChAdOx1 nCoV-19/efeitos adversos , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Vacinação/efeitos adversos , COVID-19/prevenção & controle , ChAdOx1 nCoV-19/imunologia , Fibrina , Humanos , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/imunologia , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Tecido Parenquimatoso/patologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/imunologia
4.
Microbiol Spectr ; 9(3): e0175121, 2021 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-34787437

RESUMO

A low initial contamination level of the meat surface is the sine qua non to extend the subsequent shelf life of ground beef for as long as possible. Therefore, the short- and long-term effects of a pregrinding treatment with electrolyzed water (EW) on the microbiological and physicochemical features of Piedmontese steak tartare were here assessed on site, by following two production runs through storage under vacuum packaging conditions at 4°C. The immersion of muscle meat in EW solution at 100 ppm of free active chlorine for 90 s produced an initial surface decontamination with no side effects or compositional modifications, except for an external color change that was subsequently masked by the grinding step. However, the initially measured decontamination was no longer detectable in ground beef, perhaps due to a quick recovery by bacteria during the grinding step from the transient oxidative stress induced by the EW. We observed different RNA-based metataxonomic profiles and metabolomic biomarkers (volatile organic compounds [VOCs], free amino acids [FAA], and biogenic amines [BA]) between production runs. Interestingly, the potentially active microbiota of the meat from each production run, investigated through operational taxonomic unit (OTU)-, oligotyping-, and amplicon sequence variant (ASV)-based bioinformatic pipelines, differed as soon as the early stages of storage, whereas microbial counts and biomarker dynamics were significantly distinguishable only after the expiration date. Higher diversity, richness, and abundance of Streptococcus organisms were identified as the main indicators of the faster spoilage observed in one of the two production runs, while Lactococcus piscium development was the main marker of shelf life end in both production runs. IMPORTANCE Treatment with EW prior to grinding did not result in an effective intervention to prolong the shelf life of Piedmontese steak tartare. Our RNA-based approach clearly highlighted a microbiota that changed markedly between production runs but little during the first shelf life stages. Under these conditions, an early metataxonomic profiling might provide the best prediction of the microbiological fate of each batch of the product.


Assuntos
Contaminação de Alimentos/análise , Lactococcus/crescimento & desenvolvimento , Microbiota/efeitos dos fármacos , Carne Vermelha/microbiologia , Streptococcus/crescimento & desenvolvimento , Água/farmacologia , Animais , Bovinos , Manipulação de Alimentos/métodos , Microbiologia de Alimentos , Armazenamento de Alimentos/métodos , Lactococcus/efeitos dos fármacos , Lactococcus/isolamento & purificação , Streptococcus/efeitos dos fármacos , Streptococcus/isolamento & purificação , Água/química , Microbiologia da Água
5.
Eur Rev Med Pharmacol Sci ; 25(24): 7997-8003, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34982463

RESUMO

OBJECTIVE: The ongoing Coronavirus pandemic (COVID-19) showed similar characteristics with the severe acute respiratory syndrome (SARS). In the most compromised cases, COVID-19 infection leads to death due to severe respiratory complications. COVID-19-related acute respiratory distress syndrome (ARDS) is the primary cause of death in these patients. In the present study, we show an ultrastructural analysis on the lungs of a patient affected by COVID-19. PATIENTS AND METHODS: Lung specimens obtained at autopsy from a 63-years old patient affected by COVID-19 were fixed in 1% paraformaldehyde. Slices of 300 µm thickness were dehydrated and dried by Critical Point Drying in CO2. Slices were covered with a conductive gold film approximately 30 nm thick and observed at a Zeiss Sigma 300 SEM FEG in the secondary electron (SE) and backscattered electron (BSE) modes. As case control a lung biopsy from a 60-year-old man was considered. RESULTS: At low power in all COVID-19 lung specimens severe changes in the pulmonary architecture were found, due to the collapse of air spaces. Moreover, alveolar cavities were covered by large membranes. At high power, alveolar membranes showed a fibrillar structure, suggestive of a loose network of fibrin. It has been also found that intra-alveolar red blood cells were frequently present in the alveolar spaces, surrounded by a reticular fibrin network, suggestive for fibrin-hemorrhagic alveolitis. Alveolar changes were constantly associated with pathological features related to the pulmonary vessels. Vascular changes were prominent, including endothelial damage and thrombosis of large pulmonary vessels. Fibrinous microthrombi were frequently detected in the inter-alveolar septal capillaries. In addition, it has been frequently detected capillary proliferation in the alveolar septa with finding suggestive for intussusceptive neo-angiogenesis. CONCLUSIONS: In conclusion, our electron microscopy analysis showed that COVID-19-related lung disease is characterized by a substantial architectural distortion, with the interactions between alveolar and vascular changes. Intra-alveolar hyaline membranes are associated with macro- and micro-thrombotic angiopathy, ending with capillary proliferation. The new blood vessel formation originates from the septa and extends into the surrounding parenchyma. Our findings confirm previous reports on the specificity of the multiple and complex morphological pattern typical, and apparently specific, of COVID-19-related lung disease.


Assuntos
COVID-19/patologia , Pulmão/ultraestrutura , COVID-19/diagnóstico , COVID-19/virologia , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade
7.
Environ Sci Pollut Res Int ; 25(14): 13292-13311, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-27761862

RESUMO

The aim of this study was to jointly show the results of three independent ecotoxicological studies performed to investigate pollutants in three Brazilian tropical reservoirs undergoing accelerated eutrophication. In order to accomplish this goal, the full toxicity identification and evaluation procedure (TIE approach) was performed, at Pampulha (Minas Gerais State) and Salto Grande and Barra Bonita reservoirs (São Paulo State). Acute and chronic toxicity tests were performed using the cladocerans Daphnia similis and Ceriodaphnia dubia (exotic) and Daphnia laevis and Ceriodaphnia silvestrii (native) as test organisms. Results from TIE procedure stage I indicated the existence of nonpolar organic and filterable compounds in the water from Pampulha, probably cyanotoxins, and oxidants as part of the toxic agents. TIE results for sediments identified ammonia (Pampulha and Salto Grande), organic compounds (Pampulha), metals (Pampulha, Barra Bonita, and Salto Grande), and acidity (Salto Grande) as responsible for toxicity. Whole-sediment remediation experiments for Pampulha reservoir confirmed, through reproduction decrease, ammonia and organic compounds as contaminants. Such pollutants represent threats to aquatic biota and must be prevented. Higher temperatures as predicted from global climate change will severely affect tropical shallow reservoirs, accelerating eutrophication, the release of contaminants from sediments, and increasing toxicity.


Assuntos
Eutrofização , Água Doce/análise , Sedimentos Geológicos/química , Animais , Brasil , Cladocera/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Ecotoxicologia , Clima Tropical , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
8.
Leukemia ; 32(4): 1003-1015, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29158557

RESUMO

Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their microRNA (miRNA) network. By analyzing six different miRNA-profiling data sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients. In DCs co-cultured with MM cells, enforced expression of miR-29b counteracted pro-inflammatory pathways, including signal transducer and activator of transcription 3 and nuclear factor-κB, and cytokine/chemokine signaling networks, which correlated with patients' adverse prognosis and development of bone disease. Moreover, miR-29b downregulated interleukin-23 in vitro and in the SCID-synth-hu in vivo model, and antagonized a Th17 inflammatory response. All together, these effects translated into strong anti-proliferative activity and reduction of genomic instability of MM cells. Our study demonstrates that MM reprograms the DCs functional phenotype by downregulating miR-29b whose reconstitution impairs DCs ability to sustain MM cell growth and survival. These results underscore miR-29b as an innovative and attractive candidate for miRNA-based immune therapy of MM.


Assuntos
Células Dendríticas/patologia , Inflamação/genética , MicroRNAs/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Animais , Medula Óssea/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos SCID , NF-kappa B/genética , Fator de Transcrição STAT3/genética , Regulação para Cima/genética
9.
Blood Cancer J ; 6(12): e511, 2016 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-27983725

RESUMO

Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients' survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Inflamação/genética , Mieloma Múltiplo/genética , Proteínas de Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Progressão da Doença , Feminino , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Proteínas de Neoplasias/biossíntese , Transdução de Sinais/genética , Transcriptoma/genética
10.
Cell Death Discov ; 2: 16025, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27752361

RESUMO

The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients.

11.
Eur J Histochem ; 60(3): 2678, 2016 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-27734990

RESUMO

The surfactant complex, thanks to its multiple actions including decrease of surface- tension and antimicrobial activity, plays a fundamental role in newborn survival, lowering the risk of respiratory distress syndrome. The aim of this work was to determine if the synthesis of two surfactant proteins (SP), SPA and pro-SPB, shows some inter-individual variability during lung development in the intrauterine life. Immunoreactivity for SPA and pro-SPB was investigated in the lungs of  40 subjects, including 15 fetuses, ranging from 14 to 22 weeks of gestation, and 25 neonates, from 24 to 41 weeks. Lung samples were formalin fixed, paraffin-embedded and routinely processed. SPA and pro-SPB were detected utilizing commercial antibodies.  A semi-quantitative grading system (1 to 4) was applied, based on the number of reactive cells and the intensity of immunostaining. Surfactant protein immunostaining was found in  three compartments: bronchi, bronchioles and alveoli, starting from 14 weeks of gestation in the bronchial epithelium and from the 21st week in the alveolar spaces. Differences were found regarding SPA and pro-SPB expression in the vast majority of subjects: in some lungs, SPA was more expressed whereas in others pro-SPB showed an higher degree of immunoreactivity. The expression of both surfactant proteins was not strictly correlated with gestational age. Whereas the highest levels of reactivity were detected in at term neonates, on the other hand one case with grade 3 was detected at 22 weeks and one negative case for both proteins was observed at 31 weeks. Our data clearly show a marked inter-individual variability regarding the production of SPA and pro-SPB and suggest the existence of other epigenetic factors, acting during gestation, that might influence surfactant production and, consequently, the survival potential of  neonates at birth.


Assuntos
Feto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Pulmão/embriologia , Proteína A Associada a Surfactante Pulmonar/biossíntese , Proteína B Associada a Surfactante Pulmonar/biossíntese , Pré-Escolar , Feminino , Feto/citologia , Humanos , Lactente , Pulmão/citologia , Masculino
13.
Phys Chem Chem Phys ; 18(27): 18289-96, 2016 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-27334668

RESUMO

The combination of continuum and ultrafast pump-probe spectroscopy with DFT and TDDFT calculations, in viscous and non-viscous environments, is effective in unraveling important features of the twisted intramolecular charge transfer mechanism in a new push-pull molecule that possesses aggregation induced emission properties. Long-living optical gain is found when this mechanism is inhibited, highlighting the importance of the environment rigidity in the design of materials for photonic applications.

14.
Transplant Proc ; 48(2): 349-51, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27109953

RESUMO

BACKGROUND: Kidney transplant recipients are at higher risk of developing pulmonary complications related to immunosuppression, and inhibitor of the mammalian target of rapamycin (mTORi) has been reported as a potential cause. METHODS: Five hundred kidney-transplanted patients were retrospectively analyzed for pulmonary complications on the basis of clinical and instrumental data (chest radiography, high-resolution computed tomography, broncho-alveolar lavage, oximetry). RESULTS: We found 26 interstitial lung diseases (ILD) (16%): 12 cases (46.2%) were from infections (42.8% by Pneumocystis jirovecii) and 14 cases of ILD (53.8%) resulted as drug-induced ILD (DI-ILD). According to anti-rejection protocols, DI-ILD occurred in 8 patients (57%) while on triple regimen including steroids, everolimus (EVL), and cyclosporine (CyA) and in 6 patients on double regimen with steroids and mTORi: EVL or sirolimus (43%). In ILD+ patients, everolimus trough-concentration (EVL(TLC)) and cyclosporine (2nd-hour concentration: CyA(C2)) levels were higher than in patients in the same regimen but with ILD- (EVL(TLC) [ng/mL] 9.84 versus 6.85; CyA(C2) [ng/mL] 303.97 versus 298.56). The formula that used the combined blood levels of both drugs (EVL(TLC) + CyA(C2)/100) resulted in a significant difference between groups of patients (12.88 ± 1.61 versus 9.83 ± 1.91). Applying receiver operator characteristic curve (ROC) analysis to detect risk of developing ILD when on combined protocol with EVL and CyA, we obtained an area under the curve of 0.8622 (P = .0081) and 0.9082 (P = .0028), respectively, when using EVL(TLC) or the combination formula with both drugs. CONCLUSIONS: In renal transplant patients, we obtained a relationship of ILD to specific drug concentration. On the basis of ROC analysis, patients on EVL and CyA combined protocol are at risk of ILD when EVL(TLC) is >9.03 ng/mL or >11.41 when a formula with summation of EVL(TLC) and CyA(C2) is used.


Assuntos
Ciclosporina/uso terapêutico , Everolimo/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Doenças Pulmonares Intersticiais/etiologia , Complicações Pós-Operatórias/etiologia , Quimioterapia Combinada , Feminino , Humanos , Falência Renal Crônica/cirurgia , Doenças Pulmonares Intersticiais/diagnóstico , Masculino , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sirolimo/uso terapêutico
15.
Leukemia ; 29(11): 2173-83, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25987254

RESUMO

Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral vectors or transfection with synthetic mimics impaired growth and survival of MM cells and overcame the protective role of bone marrow stromal cells in vitro. Apoptotic and autophagy-associated cell death were triggered in MM cells on miR-125b-5p ectopic expression. Importantly, we found that the anti-MM activity of miR-125b-5p was mediated via direct downregulation of IRF4 and its downstream effector BLIMP-1. Moreover, inhibition of IRF4 translated into downregulation of c-Myc, caspase-10 and cFlip, relevant IRF4-downstream effectors. Finally, in vivo intra-tumor or systemic delivery of formulated miR-125b-5p mimics against human MM xenografts in severe combined immunodeficient/non-obese diabetic mice induced significant anti-tumor activity and prolonged survival. Taken together, our findings provide evidence that miR-125b, differently from other hematologic malignancies, has tumor-suppressor activity in MM. Furthermore, our data provide proof-of-concept that synthetic miR-125b-5p mimics are promising anti-MM agents to be validated in early clinical trials.


Assuntos
Fatores Reguladores de Interferon/genética , MicroRNAs/fisiologia , Mieloma Múltiplo/terapia , Animais , Apoptose , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Genes Supressores de Tumor/fisiologia , Humanos , Masculino , Camundongos , Mieloma Múltiplo/patologia
16.
Chem Commun (Camb) ; 51(47): 9686-9, 2015 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-25977948

RESUMO

By means of confocal photoluminescence measurements and fs pump-probe spectroscopy, we observe the optical properties of phase separation in a mixture of polyfluorene and Liquid Crystals (LCs). The boundaries of LC-rich micro-domains display a large polarized gain region from keto defects stemming from the single-chain nature of this defect.

17.
Ecotoxicol Environ Saf ; 117: 155-63, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25868152

RESUMO

This study aimed to analyze laboratory and field data to assess the ecotoxicological risks of calcium nitrate exposure to freshwater tropical biota. Short-term laboratorial tests resulted in estimated EC50 values of 76.72 (67.32-86.12)mg N-NO3₋ L(-1) for C. silvestrii and 296.46 (277.16-315.76) mg N-NO3₋ L(-1) for C. xanthus. Long-term laboratorial tests generated IC25 values of 5.05 (4.35-5.75) and 28.73 (26.30-31.15) mg N-NO3₋ L(-1) for C. silvestrii and C. xanthus, respectively. The results from in situ mesocosm experiments performed in the Ibirité reservoir (a tropical eutrophic urban water body located in SE Brazil) indicated that C. silvestrii and C. xanthus were not under severe deleterious acute impact due to the treatment because the higher nitrate concentrations determined were 5.2 mg N-NO3₋ L(-1) (t=24 h; sediment-water interface) and 17.5 mg N-NO3₋ L(-1) (t=600 h; interstitial water). However, an abrupt decrease in the densities of Cyanophyceae members and other benthic taxa was observed. In summary, the present work contributes greatly to the toxicity data linked to two taxonomically distinct organisms that have never been screened for calcium nitrate sensitivity. Furthermore, considering the problem of the management and restoration of eutrophic environments, our study reports a comprehensive field assessment that allows the elucidation of the possible toxic impacts caused by the addition of calcium nitrate (a remediation technique) on aquatic and benthic organisms as well as the implications on the aquatic ecosystem as a whole, which may greatly allow expanding the current knowledgebase on the topic.


Assuntos
Compostos de Cálcio/toxicidade , Nitratos/toxicidade , Animais , Organismos Aquáticos , Brasil , Cladocera , Ecossistema , Ecotoxicologia , Água Doce , Risco , Testes de Toxicidade , Clima Tropical
18.
Chem Commun (Camb) ; 50(91): 14225-8, 2014 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-25283160

RESUMO

The unexpected and acido-triggered reversible luminescence and nonlinear optical properties of (2-pyrene-1-yl-vinyl)pyridine, a simple and highly transparent chromophore, are studied both in solution and in the solid state. Remarkably, for the first time the acidomodulation of the NLO response of a poled thin film is reported.

19.
Transplant Proc ; 46(7): 2263-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25242766

RESUMO

INTRODUCTION: Thrombotic microangiopathy (TMA) is characterized by endothelial cell injury and formation of fibrin thrombi within capillary and arterioles. In renal allograft recipients, TMA mainly presents as hemolytic uremic syndrome. Its occurrence is rare, and diagnosis requires a high degree of suspicion. Drug toxicity, in particular from calcineurin inhibitors (CNIs) and mTOR inhibitors (mTORi), is the most common cause posttransplant and has recently been emphasized in the setting of lung transplantation. OBJECTIVE: The goal of this study was to investigate the role of mTORi as an added risk factor in the development of TMA to propose strategies for modulation of immunosuppressive (IS) therapy. PATIENTS AND METHODS: From a database of 496 renal graft recipients, we analyzed 350 renal graft biopsy specimens gathered at our center from 1998 to 2012. In patients undergoing combined therapy with mTORi and CNI, we compared drugs levels in TMA-affected and TMA-free groups, using mTORi and CNI TLC and the summation of [everolimus TLC+(cyclosporine C2/100)] (Σ) as a surrogate marker of combined exposition to 2 drugs. Receiver-operating characteristic analysis of association of EVL TLC+(C2/100) was performed for patients exposed to mTORi. RESULTS: Histologic features of TMA were found in 36 patients (prevalence of 7.3%). The caseload was divided into 2 groups: not drug-related TMA (n=19) and drug-related TMA (n=17). Despite the prevalence of TMA in patients exposed to mTORi being greater (8 of 153; prevalence, 5.3%) compared with therapies without mTORi (9 of 324; prevalence, 2.8%), statistical difference was not reached. Patients treated with mTORi who developed de novo drug-related TMA had higher blood levels of IS drugs compared with those who did not develop TMA. Receiver-operating characteristic analysis found a significant threshold of 12.5 ng/mL (area under the curve, 0.803; P=.006). CONCLUSIONS: Results confirm the pivotal role of IS drugs in the onset of de novo TMA. On the basis of literature, we could speculate a sequence of endothelial damage by CNI, on which everolimus fits hindering the repair of endothelial injury. Therefore, high blood levels of CNI and mTORi seem to predispose patients to posttransplant TMA. Combined monitoring of these 2 drugs might be used to prevent the complication. Σ [everolimus TLC + (cyclosporine C2/100)]>12.5 ng/mL should be avoided as a surrogate risk factor for adverse effects.


Assuntos
Imunossupressores/efeitos adversos , Transplante de Rim , Microangiopatias Trombóticas/etiologia , Adulto , Idoso , Ciclosporina/efeitos adversos , Everolimo , Feminino , Síndrome Hemolítico-Urêmica/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores
20.
Rev. calid. asist ; 28(1): 28-35, ene.-feb. 2013.
Artigo em Espanhol | IBECS | ID: ibc-109771

RESUMO

Objetivos. Describir los errores de medicación en el circuito de uso de medicamentos en una sala general de internación de un Hospital Público de referencia, e identificar estrategias de intervención en relación a la detección y prevención de estos errores. Método. Estudio descriptivo, transversal. Hospital público general, de 190 camas, en Rosario (Argentina). Recolección de datos en forma diaria y sistemática del circuito de uso de medicamentos en una sala de internación general durante mayo 2009. Una vez identificados y caracterizados los errores, un grupo interdisciplinar aplicó en forma secuencial herramientas de gestión de calidad para reconocer causas y proponer y ponderar soluciones. (Flujograma, diagrama de causa y efecto, tormenta de ideas, grupo nominal y matriz de decisión). Resultados. En el período de estudio se obtiene información de 60 pacientes, con detección de 506 errores de medicación. Los indicadores de incidencia mostraron los siguientes valores: 8,4 errores/paciente y 88,6 errores/100 pacientes-día. De las causas identificadas se definieron como relevantes: «la doble prescripción» y «la falta de normativas claras». De las diferentes soluciones propuestas se planteó como estrategia de intervención incluir en la Historia Clínica una planilla de «prescripción/indicación/administración» con un diseño diferente, habilitando actualización diaria, con un duplicado para la dispensación en Farmacia. Se genera un procedimiento operativo estándar para normatizar esta nueva modalidad de trabajo. Conclusiones. Este trabajo logra, a través de la gestión de la calidad, el compromiso del equipo de salud para generar cambios que buscan tanto la seguridad del paciente como mejorar la calidad de las prestaciones que brinda el hospital(AU)


Objectives. To describe the medication errors in the medication use cycle in a general public hospital, and to identify intervention strategies in relation to the detection and prevention of these errors. Methods. Descriptive study with cross-sectional design. General public hospital of 190 beds, in Rosario (Argentina). Daily and systematic data collection of the circuit of use of medicines during May 2009. Once the errors were identified and classified, an interdisciplinary group sequentially applied different quality management tools to recognize and weigh causes, and propose solutions. (Flowchart, Cause Effect Diagram, Brainstorming, Nominal Group and Matrix Decision). Results. Information on 60 patients was retrieved during the study period, with 506 medication errors detected. The impact indicators showed the following values: 8.4 errors/patient and 88.6 errors/100 patients-day. From the causes identified, two were defined as relevant: “Double prescription” and “Lack of clear policy”. Of the various solutions proposed, an intervention strategy was defined to include a differently designed form for “prescription/indication/administration” in the clinical history which could be updated daily, with a duplicate to Pharmacy for the distribution, as well as a Standard Operating Procedure to standardize this new way of working. Conclusion. This work achieved, through quality management, the commitment of a team of health professionals to seek and make changes for patient safety, and to improve the quality of services provided by the hospital(AU)


Assuntos
Humanos , Masculino , Feminino , Segurança do Paciente/legislação & jurisprudência , Segurança do Paciente/normas , Erros de Medicação/prevenção & controle , Erros de Medicação/tendências , 34002 , Sistemas de Medicação/organização & administração , Sistemas de Medicação/normas , Segurança do Paciente , Assistência Farmacêutica/organização & administração , Assistência Farmacêutica/tendências , Estudos Transversais/métodos , Estudos Transversais/tendências
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