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This paper focuses on the preparation and characterization of antibacterial alginate microparticles containing silver@hydroxyapatite functionalized calcium carbonate composites for tissue engineering. Microparticles were prepared by cross-linking a silver@composite sodium alginate dispersion with CaCl2. This method showed a very good silver efficiency loading and the presence of silver chloride nanoparticles was detected. Silver free microparticles, containing hydroxyapatite functionalized calcium carbonates and neat alginate microparticles were prepared as well. All microparticles were characterized for water absorption and for in vitro bioactivity by immersion in simulated body fluid (SBF). Finally, antimicrobial and antibiofilm activities as well as cytotoxicity were evaluated. Microparticles containing silver@composites exhibited good antimicrobial and antibiofilm activities against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans, but exerted a certain cytotoxicity against the tested cell models (fibroblasts and osteoblasts). Microparticles containing hydroxyapatite functionalized calcium carbonates were found to be always less cytotoxic, also in comparison to neat alginate microparticles, proving that the presence of the inorganic matrices exerts a protective effect on microparticle cytotoxicity.
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Alginatos , Antibacterianos , Carbonato de Cálcio , Durapatita , Prata , Alginatos/química , Durapatita/química , Prata/química , Prata/farmacologia , Carbonato de Cálcio/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Fibroblastos/efeitos dos fármacos , Animais , Linhagem Celular , Humanos , Compostos de Prata/química , Compostos de Prata/farmacologia , Candida albicans/efeitos dos fármacos , CamundongosRESUMO
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.
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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 fármacosRESUMO
Wounds represent a major global health challenge. Acute and chronic wounds are sensitive to bacterial infection. The wound environment facilitates the development of microbial biofilms, delays healing, and promotes chronic inflammation processes. The aim of the present work is the development of chitosan films embedded with bud poplar extract (BPE) to be used as wound dressing for avoiding biofilm formation and healing delay. Chitosan is a polymer with antimicrobial and hydrating properties used in wound dressing, while BPE has antibacterial, antioxidative, and anti-inflammatory properties. Chitosan-BPE films showed good antimicrobial and antibiofilm properties against Gram-positive bacteria and the yeast Candida albicans. BPE extract induced an immunomodulatory effect on human macrophages, increasing CD36 expression and TGFß production during M1/M2 polarization, as observed by means of cytofluorimetric analysis and ELISA assay. Significant antioxidant activity was revealed in a cell-free test and in a human neutrophil assay. Moreover, the chitosan-BPE films induced a good regenerative effect in human fibroblasts by in vitro cell migration assay. Our results suggest that chitosan-BPE films could be considered a valid plant-based antimicrobial material for advanced dressings focused on the acceleration of wound repair.
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Anti-Infecciosos , Quitosana , Humanos , Quitosana/farmacologia , Quitosana/metabolismo , Bandagens/microbiologia , Cicatrização , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Extratos Vegetais/farmacologiaRESUMO
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.
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Senécio , Chás de Ervas , Humanos , Células Hep G2 , Dano ao DNA , FígadoRESUMO
Down syndrome (DS), which is due to triplication of chromosome 21, is constantly associated with intellectual disability (ID). ID can be ascribed to both neurogenesis impairment and dendritic pathology. These defects are replicated in the Ts65Dn mouse, a widely used model of DS. While neurogenesis impairment in DS is a fetal event, dendritic pathology occurs after the first postnatal months. Neurogenesis alterations across the life span have been extensively studied in the Ts65Dn mouse. In contrast, there is scarce information regarding dendritic alterations at early life stages in this and other models, although there is evidence for dendritic alterations in adult mouse models. Thus, the goal of the current study was to establish whether dendritic alterations are already present in the neonatal period in Ts65Dn mice. In Golgi-stained brains, we quantified the dendritic arbors of layer II/III pyramidal neurons in the frontal cortex of Ts65Dn mice aged 2 (P2) and 8 (P8) days and their euploid littermates. In P2 Ts65Dn mice, we found a moderate hypotrophy of the apical and collateral dendrites but a patent hypotrophy of the basal dendrites. In P8 Ts65Dn mice, the distalmost apical branches were missing or reduced in number, but there were no alterations in the collateral and basal dendrites. No genotype effects were detected on either somatic or dendritic spine density. This study shows dendritic branching defects that mainly involve the basal domain in P2 Ts65Dn mice and the apical but not the other domains in P8 Ts65Dn mice. This suggests that dendritic defects may be related to dendritic compartment and age. The lack of a severe dendritic pathology in Ts65Dn pups is reminiscent of the delayed appearance of patent dendritic alterations in newborns with DS. This similarly highlights the usefulness of the Ts65Dn model for the study of the mechanisms underlying dendritic alterations in DS and the design of possible therapeutic interventions.
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Síndrome de Down , Neocórtex , Animais , Modelos Animais de Doenças , Síndrome de Down/tratamento farmacológico , Síndrome de Down/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese , Células Piramidais/patologiaRESUMO
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.
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Infecção Hospitalar , Preparações Farmacêuticas , Procedimentos Cirúrgicos Robóticos , Desinfecção , Humanos , Staphylococcus aureus , Raios UltravioletaRESUMO
BACKGROUND: In SARS-CoV-2 infection, viral RNA may persist in respiratory samples for several weeks after the resolution of symptoms. Criteria to assess the end of infectivity are not unequivocally defined. In some countries, time from diagnosis is the unique criterion used, in addition to symptom cessation. This study evaluates the role of the Lumipulse® Antigen Assay (LAA) for the safe end of isolation of patients ≥21 days after the diagnosis of infection. METHODS: A total of 671 nasopharyngeal swabs from patients diagnosed with infection at least 21 days before were assessed by RT-PCR and LAA, and the role of LAA in predicting the absence of infectivity was evaluated by virus cell culture. RESULTS: Viable virus was present in 10/138 cultured samples. Eight out of ten infective patients suffered from a concomitant disease, predisposing them to long-term shedding of infective virus. In particular, infectious virus was isolated from 10/20 RT-PCR+/LAA+ cultured samples, whereas no viable virus was found in all 118 RT-PCR+/LAA- cultured swabs. LLA and RT-PCR agreed in 484/671 (72.1%) samples, with 100% and 26.7% concordance in RT-PCR negative and positive samples, respectively. CONCLUSIONS: Viable virus can be found ≥21 days after diagnosis in immunocompromised or severely ill patients. LAA better than RT-PCR predicts non-infectivity of patients and can be safely used to end isolation in cases with long persistence of viral RNA in the respiratory tract.
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AIM: To investigate the impact of smartphone distraction on the quality and safety of care provided by the nursing population during work. BACKGROUND: About 80% of nurses use the smartphone in the workplace both for personal purposes and as a useful support to improve the quality of care. Distraction from smartphones during care is a phenomenon that should be known and managed within each health service. METHODS: A systematic review of the literature was conducted using the PRISMA methodology. The sources included in the review study were subjected to a qualitative assessment using the GRADE method. RESULTS: Sixteen articles were included in the review. Studies included highlight the positive and negative consequences of using mobile devices during nursing practice. Findings identify the smartphone as a generator of stimuli capable of diverting the attention of the person from the priority activities and absorbing the cognitive resources useful for carrying out these activities. Some studies aimed to show the restriction policies and/or the strategies for reducing disruptions. This review highlights how the free and indiscriminate use of the smartphone can negatively affect patient safety and the nurse-patient relationship through the dehumanization and depersonalization of care. CONCLUSIONS: Mobile technology can improve nurses' performance and the quality of care provided. However, the application of regulations and policies by healthcare facilities is desirable to avoid inappropriate use of these devices by nurses. The available data do not provide a precise estimate of the effect that distraction from smartphones has on the outcomes of nursing care.
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Cuidados de Enfermagem , Smartphone , Humanos , Relações Enfermeiro-Paciente , Segurança do Paciente , Local de TrabalhoRESUMO
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.
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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 EspecificidadeRESUMO
The increasing use of nanomaterials in a variety of industrial, commercial, medical products, and their environmental spreading has raised concerns regarding their potential toxicity on human health. Titanium dioxide nanoparticles (TiO2 NPs) represent one of the most commonly used nanoparticles. Emerging evidence suggested that exposure to TiO2 NPs induced reproductive toxicity in male animals. In this in vitro study, porcine prepubertal Sertoli cells (SCs) have undergone acute (24 h) and chronic (from 1 up to 3 weeks) exposures at both subtoxic (5 µg/ml) and toxic (100 µg/ml) doses of TiO2 NPs. After performing synthesis and characterization of nanoparticles, we focused on SCs morphological/ultrastructural analysis, apoptosis, and functionality (AMH, inhibin B), ROS production and oxidative DNA damage, gene expression of antioxidant enzymes, proinflammatory/immunomodulatory cytokines, and MAPK kinase signaling pathway. We found that 5 µg/ml TiO2 NPs did not induce substantial morphological changes overtime, but ultrastructural alterations appeared at the third week. Conversely, SCs exposed to 100 µg/ml TiO2 NPs throughout the whole experiment showed morphological and ultrastructural modifications. TiO2 NPs exposure, at each concentration, induced the activation of caspase-3 at the first and second week. AMH and inhibin B gene expression significantly decreased up to the third week at both concentrations of nanoparticles. The toxic dose of TiO2 NPs induced a marked increase of intracellular ROS and DNA damage at all exposure times. At both concentrations, the increased gene expression of antioxidant enzymes such as SOD and HO-1 was observed whereas, at the toxic dose, a clear proinflammatory stress was evaluated along with the steady increase in the gene expression of IL-1α and IL-6. At both concentrations, an increased phosphorylation ratio of p-ERK1/2 was observed up to the second week followed by the increased phosphorylation ratio of p-NF-kB in the chronic exposure. Although in vitro, this pilot study highlights the adverse effects even of subtoxic dose of TiO2 NPs on porcine prepubertal SCs functionality and viability and, more importantly, set the basis for further in vivo studies, especially in chronic exposure at subtoxic dose of TiO2 NPs, a condition closer to the human exposure to this nanoagent.
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Nanopartículas Metálicas/toxicidade , Células de Sertoli/efeitos dos fármacos , Titânio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Masculino , Tamanho da Partícula , Células de Sertoli/patologia , Transdução de Sinais/efeitos dos fármacos , Sus scrofaRESUMO
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.
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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/farmacologiaRESUMO
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.
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Monitoramento Biológico , Ensaio Cometa , Dano ao DNA , Linfócitos , Monitoramento Biológico/métodos , Feminino , Humanos , Leucócitos/patologia , Linfócitos/patologia , Masculino , Mucosa Bucal/citologiaRESUMO
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.
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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/metabolismoRESUMO
Objective: Clinical and psychological HIV-related problems peak during adolescence, which coincides with transition of children and adolescents infected from mothers from pediatric to adult reference centers for HIV infection. Transition often is done without specific programs. We wanted to explore transition as an opportunity to increase the efficacy of care and the psychological well-being through a specific program. Methods: Thirteen vertically infected patients aged 13-20 years were followed up for 24 months by pediatricians, infectious disease specialists, a psychologist, and a nurse. Interventions consisted in joint clinic, simplification of therapy, patient group discussions, HIV infection explanations, and psychological support, lasting 12 months. Efficacy was measured by viro-immunological outcomes and adherence to therapy and psychological tests. Clinical, viro-immunological, and psychological evaluations were performed at 0 (T0) and 12 months (T12) and 6 months after transition to an adult center (T18). Psychological outcomes were assessed using standardized questionnaires for quality of life and self-esteem. Results: In 11/13 participants, pills administrations/day were significantly reduced. Patients with undetectable viral load and CD4+ >25% increased from 61 to 77% and from 61 to 74%, respectively. Six months after transition, all patients exhibited an undetectable viral load. Adolescents' awareness of the severity of the disease and the risk of sexual transmission was generally poor. Patients classified with "severe" psychological distress according to the quality of life index decreased from 38 to 15% and well-being increased. Similar results were observed 6 months after the transition to adult care. No effect was observed on self-esteem index. Conclusions: Specific protocols for transition should be developed to optimize resilience and psychological well-being, including routine psychological support for adolescents with HIV infection transiting from pediatric to adult centers for HIV infection.
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Oral rehydration solutions (ORSs) is the key treatment of acute diarrhea in children, as it restores the electrolyte balance by stimulating the intestinal sodium/glucose transporter SGLT1 to induce fluid absorption. The World Health Organization (WHO) and The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) proposed ORSs with different chemical compositions. The main agent of childhood acute gastroenteritis is rotavirus (RV). We evaluate the effects of ORS with different concentration of glucose and sodium on RV induced secretion. Ussing chambers technique was used for electophysiology experiments to evaluate ion fluid flux. ESPGHAN ORS (sodium 60 mmol/L and glucose 111 mmol/L) induced a more potent proabsorptive effect in Caco-2 cells than WHO ORS, and this effect depended on the sodium/glucose ratio. Titration experiments showed that RV-induced fluid secretion can be reverted to a proabsorptive direction when sodium and glucose concentration fall in specific ranges, specifically 45-60 mEq/L and 80-110 mM respectively. The results were confirmed by testing commercial ORSs. These findings indicated that ORS proabsorptive potency depends on sodium and glucose concentrations. Optimal ORS composition should be tailored to reduce RV-induced ion secretion by also considering palatability. These in vitro data should be confirmed by clinical trials.
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Diarreia/terapia , Glucose/metabolismo , Soluções para Reidratação/farmacologia , Bicarbonatos/farmacologia , Células CACO-2 , Criança , Diarreia/metabolismo , Diarreia/prevenção & controle , Hidratação/métodos , Glucose/farmacologia , Humanos , Absorção Intestinal/efeitos dos fármacos , Concentração Osmolar , Potássio/metabolismo , Cloreto de Potássio/farmacologia , Solução Salina/farmacologia , Sódio/metabolismo , Cloreto de Sódio/farmacologia , Transportador 1 de Glucose-Sódio/genética , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
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.
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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/patologiaRESUMO
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 TratamentoRESUMO
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 percutaneous coronary intervention (PCI) 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). An additional analytic engine [Neuron™ (ColdLight Solutions, LLC)] helps, evaluates and guide care. RESULTS: The "Bridges" program enrolled a total of 2054 PCI patients with 2835 admission from April, 1st 2013 through March 1st, 2015. The data of the program was compared with those of 3691 PCI patients with 4414 admissions in the 3years prior to the program. No impact was seen with respect to inpatient and observation readmission, or emergency department visits. Similarly no change was noticed in LDL control. There was minimal improvement in BP control and only in the CTM-3 and SAQ-7 physical limitation scores in the patients' reported outcomes. 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. The Bridges program suggests that population health management must be a long-term goal, improving preventive care in the community.
RESUMO
BACKGROUND: Rotavirus (RV) induces diarrhoea through a sequence of enterotoxic and cytotoxic effects. The former are NSP4-dependent, induce calcium-dependent chloride secretion and involve oxidative stress. Diosmectite (DS) is a natural clay that has been recommended as an active therapy for diarrhoea, but the mechanism of its effect is not clear. Electrical parameters may be used to measure the direct enterotoxic and cytotoxic effects in polar epithelial intestinal cells. To investigate the effects of DS on RV-induced enterotoxic and cytotoxic damage. Caco-2 cells were used as a model of RV infection to evaluate chloride secretion, epithelial integrity, oxidative stress and viral infectivity in Ussing chambers. RESULTS: Diosmectite reduced the expression of NSP4 and oxidative stress, resulting in a strong inhibition of chloride secretion. Preincubating RV with DS reduced the cytotoxic effect. Finally, the viral load was reduced by DS but not by control clay. This result suggests that DS specifically affects the early events of RV infection protecting the enterocyte, whereas it does not restore already-established cell damage. CONCLUSION: These findings indicate that DS exerts an anti-diarrhoeal effect by inhibiting viral replication and the expression of NSP4. Both ion secretion and cell damage induced by RV are strongly inhibited consequent to the antiviral effect, which explains its clinical efficacy.
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.