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1.
Food Funct ; 15(9): 4983-4999, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38606532

RESUMO

Propolis is a resinous mixture produced by honeybees which has been used since ancient times for its useful properties. However, its chemical composition and bioactivity may vary, depending on the geographical area of origin and the type of tree bees use for collecting pollen. In this context, this research aimed to investigate the total phenolic content (using the Folin-Ciocalteu assay) and the total antioxidant capacity (using the FRAP, DPPH, and ABTS assays) of three black poplar (Populus nigra L.) propolis (BPP) solutions (S1, S2, and S3), as well as the chemical composition (HPLC-ESI-MSn) and biological activities (effect on cell viability, genotoxic/antigenotoxic properties, and anti-inflammatory activity, and effect on ROS production) of the one which showed the highest antioxidant activity (S1). The hydroalcoholic BPP solution S1 was a prototype of an innovative, research-type product by an Italian nutraceutical manufacturer. In contrast, hydroalcoholic BPP solutions S2 and S3 were conventional products purchased from local pharmacy stores. For the three extracts, 50 phenolic compounds, encompassing phenolic acids and flavonoids, were identified. In summary, the results showed an interesting chemical profile and the remarkable antioxidant, antigenotoxic, anti-inflammatory and ROS-modulating activities of the innovative BPP extract S1, paving the way for future research. In vivo investigations will be a possible line to take, which may help corroborate the hypothesis of the potential health benefits of this product, and even stimulate further ameliorations of the new prototype.


Assuntos
Anti-Inflamatórios , Antioxidantes , Populus , Própole , Própole/química , Própole/farmacologia , Populus/química , Antioxidantes/farmacologia , Antioxidantes/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Animais , Antimutagênicos/farmacologia , Antimutagênicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos , Humanos , Fenóis/química , Fenóis/farmacologia , Fenóis/análise , Sobrevivência Celular/efeitos dos fármacos
2.
Artigo em Inglês | MEDLINE | ID: mdl-36429544

RESUMO

Senecio vulgaris L. is a herbaceous species found worldwide. The demonstrated occurrence of pyrrolizidine alkaloids in this species and its ability to invade a great variety of habitats result in a serious risk of contamination of plant material batches addressed to the herbal teas market; this presents a potential health risk for consumers. In light of the above, this work aimed to assess the cytotoxic and genotoxic activity of S. vulgaris extracts in HepG2 cells. Dried plants were ground and extracted using two different methods, namely an organic solvent-based procedure (using methanol and chloroform), and an environmentally friendly extraction procedure (i.e., aqueous extraction), which mimicked the domestic preparation of herbal teas (5, 15, and 30 min of infusion). Extracts were then tested in HepG2 cells for their cytotoxic and genotoxic potentialities. Results were almost superimposable in both extracts, showing a slight loss in cell viability at the highest concentration tested, and a marked dose-dependent genotoxicity exerted by non-cytotoxic concentrations. It was found that the genotoxic effect is even more pronounced in aqueous extracts, which induced primary DNA damage after five minutes of infusion even at the lowest concentration tested. Given the broad intake of herbal infusions worldwide, this experimental approach might be proposed as a screening tool in the analysis of plant material lots addressed to the herbal infusion market.


Assuntos
Senécio , Chás de Ervas , Humanos , Células Hep G2 , Dano ao DNA , Fígado
3.
Artigo em Inglês | MEDLINE | ID: mdl-34948629

RESUMO

BACKGROUND: Healthcare-associated infections caused by multi-drug resistant (MDR) pathogens are associated with increased mortality and morbidity among hospitalized patients. Inanimate surfaces, and in particular high-touch surfaces, have often been described as the source for outbreaks of nosocomial infections. The present work aimed to evaluate the efficacy of a last-generation mobile (robotic) irradiation UV-C light device R2S on MDR microorganisms in inanimate surfaces and its translation to hospital disinfection. METHODS: The efficacy of R2S system was evaluated in environmental high-touch surfaces of two separate outpatient rooms of Perugia Hospital in Italy. The static UV-C irradiation effect was investigated on both the bacterial growth of S. aureus, MRSA, P. aeruginosa, and K. pneumoniae KPC and photoreactivation. The antimicrobial activity was also tested on different surfaces, including glass, steel, and plastic. RESULTS: In the environmental tests, the R2S system decreased the number of bacteria, molds, and yeasts of each high-touch spot surface (HTSs) compared with manual sanitization. UV-C light irradiation significantly inhibits in vitro bacterial growth, also preventing photoreactivation. UV-C light bactericidal activity on MDR microorganisms is affected by the type of materials of inanimate surfaces. CONCLUSIONS: The last-generation mobile R2S system is a more reliable sanitizing procedure compared with its manual counterpart.


Assuntos
Infecção Hospitalar , Preparações Farmacêuticas , Procedimentos Cirúrgicos Robóticos , Desinfecção , Humanos , Staphylococcus aureus , Raios Ultravioleta
4.
Int J Infect Dis ; 105: 391-396, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33647511

RESUMO

OBJECTIVES: To compare the Lumipulse® SARS-CoV-2 antigen test with the gold standard real-time reverse transcription-polymerase chain reaction (RT-PCR) for diagnosis of SARS-CoV-2 infection and to evaluate its role in screening programs. METHODS: Lumipulse® SARS-CoV-2 antigen assay was compared with the gold standard RT-PCR test in a selected cohort of 226 subjects with suspected SARS-CoV-2 infection, and its accuracy was evaluated. Subsequently, the test was administered to a real-life screening cohort of 1738 cases. ROC analysis was performed to explore test features and cutoffs. All tests were performed in the regional reference laboratory in Umbria, Italy. RESULTS: A 42.0% positive result at RT-PCR was observed in the selected cohort. The Lumipulse® system showed 92.6% sensitivity (95% CI 85.4-97.0%) and 90.8% specificity (95% CI 84.5-95.2%) at 1.24 pg/mL optimal cutoff. In the screening cohort, characterized by 5.2% prevalence of infection, Lumipulse® assay showed 100% sensitivity (95% CI 96.0-100.0%) and 94.8% specificity (95% CI 93.6-95.8%) at 1.645 pg/mL optimal cutoff; the AUC was 97.4%, NPV was 100% (95% CI 99.8-100.0%) and PPV was 51.1% (95% CI 43.5-58.7%). CONCLUSIONS: The Lumipulse® SARS-CoV-2 antigen assay can be safely employed in the screening strategies in small and large communities and in the general population.


Assuntos
Antígenos Virais/análise , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/análise , Programas de Rastreamento/métodos , SARS-CoV-2/imunologia , Teste de Ácido Nucleico para COVID-19/métodos , Estudos de Coortes , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Humanos , Itália , Nasofaringe/virologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade
5.
J Ethnopharmacol ; 268: 113614, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33246119

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia officinalis L. (sage), and Chamaemelum nobile (L.) (chamomile) have been used traditionally to treat various inflammatory conditions. AIMS: Our study aims to investigate the anti-inflammatory properties of both plant extracts in IL-1ß-stimulated neuroblastoma cells (SK-N-SH) and human subcutaneous mature adipocytes, as well as their potential protective effects against mature adipocytes conditioned media (ACM)-induced neuro-inflammation. MATERIALS AND METHODS: Human subcutaneous mature adipocytes and neuroblastoma cells were treated with 5 µg/ml (low dose: LD) and 50 µg/ml (high dose: HD) of each extract, with or without 0.5 ng/ml of human recombinant IL-1ß. To understand the cross talk between fat tissue and neuronal cells, SK-N-SH cell line was incubated with ACM 10%, in presence or absence of both extracts LD and HD. Following 4, and 24 h incubation, the released MCP-1, IL-6, IL-8, TNF-α, ICAM-1, VCAM-1 and SAA levels were measured using MSD Cytokines and Chemokines assay kits, and the cells were used for gene expression. RNA was quantified using Qubit™ RNA HS Assay. RNA aliquots were shipped to Eurofins Genomics (Aarhus, Denmark) for expression analysis on the human Clariom™ GO Screen Assay (952,361; ThermoFisher). RESULTS: Chamomile showed stronger effects compared to sage in both cell lines, at 4 and 24 h. Adipocytes acute treatment with sage decreased MCP-1, IL-6, IL-8 (p < 0.001), and TNF-α (p < 0.05) basal levels. This was mirrored at MCP-1 transcriptional level. Chronic treatment with both extracts resulted in a significant reduction in ICAM-1, VCAM-1 and SAA (p < 0.001) levels, in IL-1ß-stimulated adipocytes. However, in SK-N-SH cells, sage increased the basal levels of many cytokines and chemokines on both protein and transcriptional levels. This was also observed in IL-1ß-stimulated cells. In chamomile treated SK-N-SH cells, acute and chronic treatments decreased MCP-1 (p < 0.001), IL-6 (p < 0.01), TNF-α (p < 0.01), and IL-8 (p < 0.001) basal levels. In IL1-ß-stimulated SK-N-SH cells, chamomile HD induced a significant reduction in TNF-α after both acute and chronic treatments respectively, by 52% and 81%. At transcriptional level, this effect was only reflected at 4 h. ICAM-1, VCAM-1 and SAA levels were reduced in most of the studied conditions. In IL-1ß treated adipocytes, chamomile showed stronger reduction in MCP-1, ICAM-1 and VCAM-1 expression, however no significant reduction in TNF-α and IL-8 was observed, despite the decrease in basal levels. In SK-N-SH cells, ACM increased MCP-1, IL-6, IL-8, TNF-α, VCAM-1 and SAA levels. Sage HD acute treatment resulted in a reduction of ACM effect on IL-6, IL-8 and VCAM-1, with greater effect of chamomile on MCP-1 (p < 0.05); IL-6 (p < 0.001); TNF-α (p < 0.001); VCAM-1 (p < 0.001); and SAA (p < 0.001). This protective effect was also observed after chronic treatment. However, both extracts potentiated significantly the ACM-pro-inflammatory effect on IL-8 (p < 0.001). CONCLUSIONS: Sage decreased the pro-inflammatory markers mostly in human adipocytes, whereas chamomile showed a strong reduction in both cell populations. Both extracts reduced the ACM-induced inflammation effect and might be used as a preventive treatment for late-life cognitive impairment related to low-grade chronic inflammation associated with obesity. Further studies are needed to investigate their combination on other chronic inflammation-related diseases such as type 2 diabetes or rheumatoid arthritis.


Assuntos
Adipócitos/metabolismo , Anti-Inflamatórios/uso terapêutico , Chamaemelum , Neuroblastoma/metabolismo , Extratos Vegetais/uso terapêutico , Salvia officinalis , Adipócitos/efeitos dos fármacos , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Neuroblastoma/tratamento farmacológico , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-33321868

RESUMO

Many subjects perceive venous blood collection as too invasive, and thus moving to better-accepted procedures for leukocytes collection might be crucial in human biomonitoring studies (e.g., biomonitoring of occupational or residential exposure to genotoxins) management. In this context, primary DNA damage was assessed in buccal lymphocytes (BLs), fresh whole venous, and capillary blood leukocytes, and compared with that in peripheral blood lymphocytes (PBLs)-the most frequently used cells-in 15 young subjects. Mouthwashes were collected after the volunteers rinsed their mouths with normal saline, and BLs were isolated by density gradient centrifugation. Blood samples were collected by venipuncture or by lancet. Anthropometric and lifestyle information was obtained by the administration of a structured questionnaire. As shown in the Bland-Altman plots, the level of agreement between BLs and PBLs lied within the accepted range, we thus enrolled a wider population (n = 54) to assess baseline DNA damage in BLs. In these cells, mean values of tail length (µm), tail intensity (%), and tail moment were 25.7 ± 0.9, 6.7 ± 0.4 and 1.0 ± 0.1, respectively. No significant association was observed between sex and smoking habit with any of the DNA damage parameters. Conversely, underweight subjects displayed significantly higher genomic instability compared with normal weight group (p < 0.05). In conclusion, we successfully managed to set up and update a non-invasive and well-accepted procedure for the isolation of BLs from saliva that could be useful in upcoming biomonitoring studies.


Assuntos
Monitoramento Biológico , Ensaio Cometa , Dano ao DNA , Linfócitos , Monitoramento Biológico/métodos , Feminino , Humanos , Leucócitos/patologia , Linfócitos/patologia , Masculino , Mucosa Bucal/citologia
7.
Toxicol In Vitro ; 69: 105001, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32942007

RESUMO

It has been hypothesized that high glucose concentrations might contribute to the overall intracellular oxidative stress either by the direct generation of reactive oxygen species (ROS) or by altering the redox balance. Moreover, it has also been suggested that high glucose concentration can increase the susceptibility of DNA to genotoxic effects of xenobiotics. The aim of this approach was to test high glucose concentrations for pro-genotoxicity in human liver cells by setting up an in vitro model for hyperglycaemia. The experimental design included performing of tests on both human HepG2 tumour cells and HepaRG immortalized cells. Increased cell susceptibility to genotoxic xenobiotics was tested by challenging cell cultures with 4-nitroquinoline-N-oxide (4NQO) and evaluating the extent of primary DNA damage by comet assay. Moreover, we evaluated the relationship between glucose concentration and intracellular ROS, as well as the effects of glucose concentration on the induction of Nrf2-dependent genes such as Glutathione S-transferases, Heme­oxygenase-1, and Glutathione peroxidase-4. To investigate the involvement of ROS in the induced pro-genotoxic activity, parallel experimental sets were set up by considering co-treatment of cells with the model mutagen 4NQO and the antioxidant, glutathione precursor N-acetyl-L-cysteine. High glucose concentrations caused a significant increase in the levels of primary DNA damage, with a pro-genotoxic condition closely related to the concentration of glucose in the culture medium when cells were exposed to 4NQO. High glucose concentrations also stimulated the production of ROS and down-regulated genes involved in contrasting of the effects of oxidative stress. In conclusion, in the presence of high concentrations of glucose, the cells are in unfavourable conditions for the maintenance of genome integrity.


Assuntos
Hiperglicemia/genética , Hiperglicemia/metabolismo , Fígado/citologia , Mutagênicos/toxicidade , 4-Nitroquinolina-1-Óxido/toxicidade , Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Ensaio Cometa , Dano ao DNA , Glucose , Glutationa Transferase/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo
8.
Int J Mol Sci ; 19(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127248

RESUMO

Diabetic retinopathy (DR) has been classically considered a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is also an early event in the pathogenesis of DR. Citicoline has been successfully used as a neuroprotective agent in the treatment of glaucoma but their effects on DR remain to be elucidated. On this basis, the main aim of the present study was to evaluate the effect of topical administration of citicoline in liposomal formulation on retinal neurodegeneration in db/db mouse and to investigate the underlying mechanisms of action. The treatment (citicoline or vehicle) was topically administered twice daily for 15 days. Retinal analyses were performed in vivo by electroretinography and ex vivo by using Western blot and immunofluorescence measurements. We found that the liposomal formulation of citicoline prevented glial activation and neural apoptosis in the diabetic retina. The main mechanism implicated in these beneficial effects were the inhibition of the downregulation of synaptophysin and its anti-inflammatory properties by means of preventing the upregulation of NF-κB and TNF-α (Tumor Necrosis Factor α) induced by diabetes. Overall, these results suggest that topical administration of citicoline in liposomal formulation could be considered as a new strategy for treating the early stages of DR.


Assuntos
Citidina Difosfato Colina/uso terapêutico , Diabetes Mellitus Experimental/complicações , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Fármacos Neuroprotetores/uso terapêutico , Retina/efeitos dos fármacos , Administração Tópica , Animais , Citidina Difosfato Colina/administração & dosagem , Retinopatia Diabética/patologia , Lipossomos , Masculino , Camundongos , Fármacos Neuroprotetores/administração & dosagem , Nootrópicos/administração & dosagem , Nootrópicos/uso terapêutico , Retina/patologia
9.
Cardiovasc Revasc Med ; 19(1 Pt B): 106-111, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28651834

RESUMO

BACKGROUND: Reducing readmissions and improving metrics of care are a national priority. Supplementing traditional care with care management may improve outcomes. The Bridges program was an initial evaluation of a care management platform (CareLinkHub), supported by information technology (IT) developed to improve the quality and transition of care from hospital to home after Coronary Artery Bypass Surgery (CABG) and reduce readmissions. METHODS: CareLink is comprised of care managers, patient navigators, pharmacists and physicians. Information to guide care management is guided by a middleware layer to gather information, PLR (ColdLight Solutions, LLC) and presented to CareLink staff on a care management platform, Aerial™ (Medecision). In addition there is an analytic engine to help evaluate and guide care, Neuron™ (Coldlight Solutions, LLC). RESULTS: The "Bridges" program enrolled a total of 716 CABG patients with 850 admissions from April 2013 through March 2015. The data of the program was compared with those of 1111 CABG patients with 1203 admissions in the 3years prior to the program. No impact was seen with respect to readmissions, Blood Pressure or LDL control. There was no significant improvement in patients' reported outcomes using either the CTM-3 or any of the SAQ-7 scores. Patient follow-up with physicians within 1week of discharge improved during the Bridges years. CONCLUSIONS: The CareLink hub platform was successfully implemented. Little or no impact on outcome metrics was seen in the short follow-up time.


Assuntos
Ponte de Artéria Coronária , Prestação Integrada de Cuidados de Saúde , Gestão da Informação em Saúde , Infarto do Miocárdio/cirurgia , Administração dos Cuidados ao Paciente , Equipe de Assistência ao Paciente , Cuidados Pós-Operatórios/métodos , Melhoria de Qualidade , Indicadores de Qualidade em Assistência à Saúde , Idoso , Comportamento Cooperativo , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/normas , Prestação Integrada de Cuidados de Saúde/normas , Feminino , Gestão da Informação em Saúde/normas , Humanos , Comunicação Interdisciplinar , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Enfermeiras e Enfermeiros , Administração dos Cuidados ao Paciente/normas , Equipe de Assistência ao Paciente/normas , Navegação de Pacientes , Readmissão do Paciente , Intervenção Coronária Percutânea , Farmacêuticos , Médicos , Cuidados Pós-Operatórios/efeitos adversos , Cuidados Pós-Operatórios/normas , Avaliação de Programas e Projetos de Saúde , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Assistentes Sociais , Fatores de Tempo , Resultado do Tratamento
10.
Cardiovasc Revasc Med ; 18(2): 95-99, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27866747

RESUMO

BACKGROUND: Reducing readmissions following hospitalization is a national priority. Identifying patients at high risk for readmission after coronary artery bypass graft surgery (CABG) early in a hospitalization would enable hospitals to enhance discharge planning. METHODS: We developed different models to predict 30-day inpatient readmission to our institution in patients who underwent CABG between January 2010 and April 2013. These models used data available: 1) at admission, 2) at discharge 3) from STS Registry data. We used logistic regression and assessed the discrimination of each model using the c-index. The models were validated with testing on a different patient cohort who underwent CABG between May 2013 and September 2015. Our cohort included 1277 CABG patients: 1159 in the derivation cohort and 1018 in the validation cohort. RESULTS: The discriminative ability of the admission model was reasonable (C-index of 0.673). The c-indices for the discharge and STS models were slightly better. (C-index of 0.700 and 0.714 respectively). Internal validation of the models showed a reasonable discriminative admission model with slight improvement with adding discharge and registry data (C-index of 0.641, 0.659 and 0.670 respectively). Similarly validation of the models on the validation cohort showed similar results (C-index of 0.573, 0.605 and 0.595 respectively). CONCLUSIONS: Risk prediction models based on data available early on admission are predictive for readmission risk. Adding registry data did not improved the performance of these models. These simplified models may be sufficient to identify patients at highest risk of readmission following coronary revascularization early in the hospitalization.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária/métodos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Valor Preditivo dos Testes , Sistema de Registros , Fatores de Risco , Fatores de Tempo
11.
Regen Med ; 11(5): 459-63, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27346565

RESUMO

AIM: Bone osteoradionecrosis is a serious complication of radiation treatment. Current treatment approaches are not curative and treatment response is often poor leading to high social and healthcare costs. CASE REPORT: We report on the first case of osteoradionecrosis with successful restitutio ab integro by repeated administration of platelet gel (PLT-gel) and surgery in a critically ill patient. The administration of PLT-gel during a severe septic episode helped regeneration of bone and soft tissues, shortening the hospital stay of the patient. It was also noted that following applications of PLT-gel, both the use of morphine and the numbers of infective episodes were reduced. CONCLUSION: Additional studies are needed to confirm the promising effect of PLT-gel for the treatment of osteoradionecrosis.


Assuntos
Doenças Mandibulares/terapia , Osteorradionecrose/terapia , Plasma Rico em Plaquetas , Doenças do Tecido Conjuntivo/terapia , Fístula/terapia , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço , Transfusão de Plaquetas , Regeneração , Medicina Regenerativa , Cicatrização
12.
Innate Immun ; 21(3): 314-21, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25128692

RESUMO

LL-37 is a cationic peptide belonging to the cathelicidin family that has antimicrobial and immune-modulatory properties. Here we show that the mammalian mono-ADP-ribosyltransferase-1 (ART1), which selectively transfers the ADP-ribose moiety from NAD to arginine residues, ADP-ribosylates LL-37 in vitro. The incorporation of ADP-ribose was first observed by Western blot analysis and then confirmed by MALDI-TOF. Mass-spectrometry showed that up to four of the five arginine residues present in LL-37 could be ADP-ribosylated on the same peptide when incubated at a high NAD concentration in the presence of ART1. The attachment of negatively charged ADP-ribose moieties considerably alters the positive charge of the arginine residues thus reducing the cationicity of LL-37. The cationic nature of LL-37 is key for its ability to interact with cell membranes or negatively charged biomolecules, such as DNA, RNA, F-actin and glycosaminoglycans. Thus, the ADP-ribosylation of LL-37 is expected to have the potential to modulate LL-37 biological activities in several physiological and pathological settings.


Assuntos
ADP Ribose Transferases/metabolismo , Peptídeos Catiônicos Antimicrobianos/metabolismo , NAD/metabolismo , Adenosina Difosfato Ribose/metabolismo , Animais , Arginina/metabolismo , Linhagem Celular , Membrana Celular/metabolismo , Proteínas Ligadas por GPI/metabolismo , Humanos , Imunomodulação , Espectrometria de Massas , Catelicidinas
13.
PLoS One ; 9(6): e99830, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24918938

RESUMO

Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics.


Assuntos
Cloretos/metabolismo , Enterócitos/metabolismo , Estresse Oxidativo/fisiologia , Infecções por Rotavirus/microbiologia , Rotavirus/metabolismo , Saccharomyces/metabolismo , Acetilcisteína/metabolismo , Antioxidantes/metabolismo , Células CACO-2 , Linhagem Celular Tumoral , Enterócitos/microbiologia , Enterócitos/virologia , Glutationa/metabolismo , Glicoproteínas/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Intestinos/virologia , Espécies Reativas de Oxigênio/metabolismo , Infecções por Rotavirus/metabolismo , Infecções por Rotavirus/virologia , Toxinas Biológicas/metabolismo , Proteínas não Estruturais Virais/metabolismo
14.
Blood ; 117(21): 5683-91, 2011 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-21487111

RESUMO

TLR7 and TLR8 are intracellular sensors activated by single-stranded RNA species generated during viral infections. Various synthetic small molecules can also activate TLR7 or TLR8 or both through an unknown mechanism. Notably, direct interaction between small molecules and TLR7 or TLR8 has never been shown. To shed light on how small molecule agonists target TLRs, we labeled 2 imidazoquinolines, resiquimod and imiquimod, and one adenine-based compound, SM360320, with 2 different fluorophores [5(6) carboxytetramethylrhodamine and Alexa Fluor 488] and monitored their intracellular localization in human plasmacytoid dendritic cells (pDCs). All fluorescent compounds induced the production of IFN-α, TNF-α, and IL-6 and the up-regulation of CD80 and CD86 by pDCs showing they retained TLR7-stimulating activity. Confocal imaging of pDCs showed that, similar to CpG-B, all compounds concentrated in the MHC class II loading compartment (MIIC), identified as lysosome-associated membrane protein 1(+), CD63, and HLA-DR(+) endosomes. Treatment of pDCs with bafilomycin A, an antagonist of the vacuolar-type proton ATPase controlling endosomal acidification, prevented the accumulation of small molecule TLR7 agonists, but not of CpG-B, in the MIIC. These results indicate that a pH-driven concentration of small molecule TLR7 agonists in the MIIC is required for pDC activation.


Assuntos
Adenina/análogos & derivados , Aminoquinolinas/farmacocinética , Células Dendríticas/metabolismo , Corantes Fluorescentes , Genes MHC da Classe II/fisiologia , Imidazóis/farmacocinética , Receptor 7 Toll-Like/agonistas , Adenina/farmacocinética , Antineoplásicos/farmacocinética , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Imunofluorescência , Humanos , Imiquimode , Macrolídeos/farmacologia , ATPases Translocadoras de Prótons/antagonistas & inibidores , Quinolinas/química , Quinolinas/farmacocinética , Receptor 7 Toll-Like/metabolismo
15.
Ann Fam Med ; 4(5): 410-6, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17003140

RESUMO

PURPOSE: We wanted to estimate excess risk of in-hospital mortality associated with medical injuries identified using an injury surveillance system, after controlling for risk of death resulting from comorbidities. METHODS: The Wisconsin Medical Injuries Prevention Program (WMIPP) screening criteria were used to identify medical injuries, defined as "any untoward harm associated with a therapeutic or diagnostic healthcare intervention," among discharge diagnoses for all 562,317 patients discharged from 134 acute care hospitals in Wisconsin in 2002. We then derived estimates for crude and adjusted relative risk of in-hospital mortality associated with the presence of a medical injury diagnosis. Logistic regression adjusted for baseline risk of mortality using a comorbidity index, age, sex, Diagnosis Related Groups, hospital characteristics, and clustering within hospital. RESULTS: There were 77,666 discharges that met WMIPP criteria for at least 1 medical injury (13.8%). Crude risk ratios for death ranged from 1.27 to 2.4 for those with medical injuries within 1 of 4 categories: drugs/biologics; devices, implants, and grafts; procedures; and radiation. After adjustment, estimates of excess mortality decreased, and significance persisted only for injuries related to procedures (39%; 95% confidence interval [CI], 28%-52%) and devices, implants, and grafts (16%; 95% CI, 3%-30%). CONCLUSIONS: Estimates of excess mortality that do not account for baseline mortality risk may be exaggerated. Findings have implications for the care family physicians provide in the hospital and for the advice they give their patients who are concerned about the risks of hospitalization.


Assuntos
Mortalidade Hospitalar , Erros Médicos/mortalidade , Adolescente , Adulto , Idoso , Criança , Comorbidade , Feminino , Humanos , Modelos Logísticos , Masculino , Erros de Medicação , Pessoa de Meia-Idade , Razão de Chances , Qualidade da Assistência à Saúde , Medição de Risco , Índice de Gravidade de Doença , Wisconsin
16.
An. bras. dermatol ; 78(5): 553-560, set.-out. 2003.
Artigo em Português, Inglês | LILACS | ID: lil-348789

RESUMO

FUNDAMENTOS: As características do melanoma acrolentiginoso (MAL) diagnosticado no Brasil säo pouco estudadas. OBJETIVOS: Avaliar as características do MAL diagnosticado na Unidade de Melanoma da Santa Casa de Säo Paulo - UMSC, comparando essa manifestaçäo com outros subtipos e verificar se as possíveis diferenças entre eles teriam importância na determinaçäo do diagnóstico, tratamento e prognóstico. MÉTODO: A Casuística da UMSC foi subdividida em dois grupos, um de melanoma acrolentiginoso (MAL) e outro de melanoma näo acrolentiginoso (NAL), que foram comparados quanto a sexo, cor, idade, espessura e nível de invasäo da lesäo primária, estadiamento, tempo decorrido entre a percepçäo do tumor e o atendimento pelo médico. RESULTADOS: A casuística correspondente ao MAL mostrou freqüência significativa de pacientes näo brancos, com faixa etária mais elevada, com a lesäo primária em média, mais espessa e ulcerada. Näo ocorreram diferenças significativas quanto ao sexo e estadiamento, bem como com relaçäo ao tempo decorrido entre perceber a neoplasia e procurar o médico. CONCLUSÖES: O MAL diagnosticado na UMSC ocorre, principalmente, em pacientes que normalmente näo säo alertados para câncer da pele (näo brancos) e pertencem a uma faixa etária mais elevada (portanto, do ponto de vista teórico, poderiam estar menos atentos ao início da doença). A maioria apresentou lesäo espessa e ulcerada, conseqüentemente de maior risco para metástases. Essa forma de câncer é desconhecida do público em geral e mesmo por boa parcela da classe médica.


Assuntos
Humanos , Melanoma
17.
An. bras. dermatol ; 77(2): 163-170, mar.-abr. 2002. tab
Artigo em Português, Inglês | LILACS | ID: lil-343236

RESUMO

A epidemiologia do melanoma cutâneo no Brasil é pouco estudada. Sendo um país de dimensões continentais e com complexa etnia, quais seriam seus padrões epidemiológicos? Para tentar responder a essa questão, foram comparadas casuísticas do tipo assistencial e de clínica privada, e, em seguida, discutidas em relacão à literatura brasileira e internacional. A casuística assistencial no geral mostrou freqüencia significativa de pacientes não brancos, faixa etária mais elevada e percentagem alta de melanoma acrolentiginoso, enquanto a clínica privada mostrou predominância de pacientes brancos, faixa etária não elevada e pequena percentagem de melanoma acrolentiginoso. Os resultados da casuística assistencial contrapuseram-se, significativamente, aos da clínica privada e da literatura mundial, porém foram concordantes com a maioria dos autores brasileiros. Assim sendo, é possível dizer que a elevada freqüência do melanoma acrolentiginoso, encontrada na casuística assistencial (maioria da população brasileira), poderia caracterizar a epidemiologia do melanoma cutâneo no país e provavelmente seria decorrente da diferença racial e étnica do Brasil em relação aos países de população predominantemente branca. Essas diferenças, entretanto, não aconteceram quando foram comparadas as casuísticas na faixa etária abaixo de 50 anos. A diversificação dos resultados determina (de acordo com a faixa etária), possivelmente, uma variação epidemiológica do melanoma cutâneo, considerando grupos sociais diferentes em uma mesma localização geográfica


Assuntos
Humanos , Masculino , Feminino , Adulto , Melanoma
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