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1.
Int J Drug Policy ; 123: 104281, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056222

RESUMO

INTRODUCTION: This study aimed to evaluate the feasibility of molecular point-of-care testing for STIs, the prevalence of STIs and associated factors, and testing and treatment uptake among street-based female sex workers (FSWs) attending a mobile harm reduction unit in Madrid, Spain. METHODS: This was a prospective, longitudinal study. From August 15th to December 6th, 2022, participants were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis using molecular testing (Xpert) on self-collected urine samples at a mobile harm reduction unit. Additionally, rapid tests were used to screen participants for HIV, hepatitis C virus (HCV), and syphilis. On-site same-day results and treatment for those infected were offered. RESULTS: Among 77 FSWs included the median age was 40 (range, 33-48), 64 % were homeless, and 84 % reported drug use in the past six months. Four participants self-reported having HIV, of whom all were on antiretroviral therapy, and 14 (18 %) had HCV antibodies, including three with current infection. The prevalence of at least one STI was 66 %. When categorized by type of STI, the prevalences were as follows: 15 % for CT, 15 % for NG, 51 % for TV, and 21 % for syphilis. Notably, the prevalence of STIs was higher among FSW with recent drug use, with no cases of CT or NG detected among FSWs who did not recently use drugs. In adjusted analysis, drug use was associated an increased odds of having an STI (adjusted odds ratio, 10.47; 95 % CI: 1.67-65.42). All participants consented to screening, and all but one received on-site result-based linkage to treatment. CONCLUSIONS: This study demonstrates the feasibility, high STI prevalence, and high linkage to testing and treatment following point-of-care molecular testing among street-based FSWs who have recently used drugs in Madrid, Spain.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Profissionais do Sexo , Infecções Sexualmente Transmissíveis , Sífilis , Feminino , Humanos , Adulto , Sífilis/diagnóstico , Sífilis/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Redução do Dano , Espanha/epidemiologia , Estudos Prospectivos , Estudos Longitudinais , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/terapia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Testes Imediatos , Prevalência
2.
Heliyon ; 9(10): e20148, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37822633

RESUMO

HRSV is responsible for many acute lower airway infections and hospitalizations in infants, the elderly and those with weakened immune systems around the world. The strong inflammatory response that mediates viral clearance contributes to pathogenesis, and is positively correlated with disease severity. There is no specific effective therapy on hand. Antiviral synthetic stigmastanes (22S, 23S)-22,23-dihydroxystigmast-4-en-3-one (Compound 1) and 22,23-dihydroxystigmasta-1,4-dien-3-one (Compound 2) have shown to be active inhibiting unrelated virus like Herpes Simplex type 1 virus (HSV-1) and Adenovirus, without cytotoxicity. We have also shown that Compound 1 modulates the activation of cell signaling pathways and cytokine secretion in infected epithelial cells as well as in inflammatory cells activated by nonviral stimuli. In the present work, we investigated the inhibitory effect of both compounds on HRSV replication and their modulatory effect on infected epithelial and inflammatory cells. We show that compounds 1 and 2 inhibit in vitro HRSV replication and propagation and reduce cytokine secretion triggered by HRSV infection in epithelial and inflammatory cells. The compounds reduce viral loads and inflammatory infiltration in the lungs of mice infected with HRSV.

3.
Rev Esp Quimioter ; 36(3): 236-258, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37017117

RESUMO

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.


Assuntos
Antineoplásicos , Neoplasias Hematológicas , Humanos , Antifúngicos/efeitos adversos , Voriconazol , Azóis/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico
4.
Benef Microbes ; : 1-14, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37078124

RESUMO

Among the isoflavones and isoflavone-derived metabolites, equol, which in the human gut is synthesised from daidzein by minority bacterial populations, shows the strongest estrogenic and antioxidant activity. The beneficial effects on human health of isoflavone consumption might be partially or indeed totally attributable to this equol. Although some of the bacterial strains involved in its formation have been identified, the interplay between the composition and functionality of the gut microbiota and equol producer phenotype has hardly been studied. In this study, after shotgun metagenomic sequencing, different pipelines for the taxonomic and functional annotation of sequencing data were used in the search for similarities and differences in the faecal metagenome of equol-producing (n=3) and non-producing (n=2) women, with special focus on equol-producing taxa and their equol-associated genes. The taxonomic profiles of the samples differed significantly depending on the analytical method followed, although the microbial diversity detected by each tool was very similar at the phylum, genus and species levels. Equol-producing taxa were detected in both equol producers and non-producers, but no correlation between the abundance of equol-producing taxa and the equol producing/non-producing phenotype was found. Indeed, functional metagenomic analysis was unable to identify the genes involved in equol production, even in samples from equol producers. By aligning equol operons with the collected metagenomics data, a small number of reads mapping to equol-associated sequences were recognised in samples from both equol producers and equol non-producers, but only two reads mapping onto equol reductase-encoding genes in a sample from an equol producer. In conclusion, the taxonomic analysis of metagenomic data might not be suitable for detecting and quantifying equol-producing microbes in human faeces. Functional analysis of the data might provide an alternative. However, to detect the genetic makeup of the minority gut populations, more extensive sequencing than that achieved in the present study might be required.

5.
BMC Biol ; 20(1): 233, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36266680

RESUMO

BACKGROUND: Lipid homeostasis is an evolutionarily conserved process that is crucial for energy production, storage and consumption. Drosophila larvae feed continuously to achieve the roughly 200-fold increase in size and accumulate sufficient reserves to provide all energy and nutrients necessary for the development of the adult fly. The mechanisms controlling this metabolic program are poorly understood. RESULTS: Herein we identified a highly conserved gene, orsai (osi), as a key player in lipid metabolism in Drosophila. Lack of osi function in the larval fat body, the regulatory hub of lipid homeostasis, reduces lipid reserves and energy output, evidenced by decreased ATP production and increased ROS levels. Metabolic defects due to reduced Orsai (Osi) in time trigger defective food-seeking behavior and lethality. Further, we demonstrate that downregulation of Lipase 3, a fat body-specific lipase involved in lipid catabolism in response to starvation, rescues the reduced lipid droplet size associated with defective orsai. Finally, we show that osi-related phenotypes are rescued through the expression of its human ortholog ETFRF1/LYRm5, known to modulate the entry of ß-oxidation products into the electron transport chain; moreover, knocking down electron transport flavoproteins EtfQ0 and walrus/ETFA rescues osi-related phenotypes, further supporting this mode of action. CONCLUSIONS: These findings suggest that Osi may act in concert with the ETF complex to coordinate lipid homeostasis in the fat body in response to stage-specific demands, supporting cellular functions that in turn result in an adaptive behavioral response.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Metabolismo dos Lipídeos , Animais , Humanos , Trifosfato de Adenosina/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Corpo Adiposo/metabolismo , Flavoproteínas/metabolismo , Larva , Lipase/genética , Lipase/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos , Espécies Reativas de Oxigênio/metabolismo
6.
Sci Total Environ ; 846: 157434, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-35863565

RESUMO

It is known that any environmental remediation process must be approached as a system and that the transport of materials is key to determining its sustainability. The aim of this work is to establish how far it was possible to transport plant material from a phytoextraction process in such a way that the environmental gain of the remediation process is not compromised. In the absence of a general methodology to answer our question, a new methodology based on spatial analysis and the life cycle perspective is proposed to calculate, under different hypotheses and depending on the type of remediation, the maximum distance that a lorry can travel, taking as a limit the distance in which the environmental benefit would be equal to 0. The results obtained show that there are significant differences depending on the type of optimisation proposed for the transport route as well as the type of valorization of the plant material to be carried out. Thus, in the case of bioethanol, biomass could be transported up to 25 km. For biodiesel, it can be shipped over distances between 255 and 415 km and finally, if it is valorized by anaerobic co-digestion, biodigesters up to 267 km away could be sought for the most favourable case.


Assuntos
Biocombustíveis , Recuperação e Remediação Ambiental , Biodegradação Ambiental , Biomassa
7.
J Phys Condens Matter ; 34(33)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35654034

RESUMO

Surface nanopatterning induced by ion beam irradiation (IBI) has emerged as an effective nanostructuring technique since it induces patterns on large areas of a wide variety of materials, in short time, and at low cost. Nowadays, two main subfields can be distinguished within IBI nanopatterning depending on the irrelevant or relevant role played by the surface composition. In this review, we give an up-dated account of the progress reached when surface composition plays a relevant role, with a main focus on IBI surface patterning with simultaneous co-deposition of foreign atoms. In addition, we also review the advances in IBI of compound surfaces as well as IBI systems where the ion employed is not a noble gas species. In particular, for the IBI with concurrent metal co-deposition, we detail the chronological evolution of these studies because it helps us to clarify some contradictory early reports. We describe the main patterns obtained with this technique as a function of the foreign atom deposition pathway, also focusing in those systematic studies that have contributed to identify the main mechanisms leading to the surface pattern formation and development. Likewise, we explain the main theoretical models aimed at describing these nanopattern formation processes. Finally, we address two main special features of the patterns induced by this technique, namely, the enhanced pattern ordering and the possibility to produce both morphological and chemical patterns.

8.
Clin. transl. oncol. (Print) ; 24(2): 227-246, febrero 2022. ilus
Artigo em Inglês | IBECS | ID: ibc-203429

RESUMO

Infertility is one of the main sequelae of cancer and its treatment in both children and adults of reproductive age. It is, therefore, essential that oncologists and haematologists provide adequate information about the risk of infertility and the possibilities for its preservation before starting treatment. Although many international clinical guidelines address this issue, this document is the first Spanish multidisciplinary guideline in paediatric and adult oncological patients. Experts from the Spanish Society of Medical Oncology, the Spanish Fertility Society, the Spanish Society of Haematology and Haemotherapy, the Spanish Society of Paediatric Haematology and Oncology and the Spanish Society of Radiation Oncology have collaborated to develop a multidisciplinary consensus.


Assuntos
Humanos , Masculino , Feminino , Ciências da Saúde , Fertilidade , Preservação da Fertilidade , Gravidez , Criopreservação , Neoplasias , Infertilidade Feminina , Infertilidade Masculina
9.
Clin Transl Oncol ; 24(2): 227-243, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34635959

RESUMO

Infertility is one of the main sequelae of cancer and its treatment in both children and adults of reproductive age. It is, therefore, essential that oncologists and haematologists provide adequate information about the risk of infertility and the possibilities for its preservation before starting treatment. Although many international clinical guidelines address this issue, this document is the first Spanish multidisciplinary guideline in paediatric and adult oncological patients. Experts from the Spanish Society of Medical Oncology, the Spanish Fertility Society, the Spanish Society of Haematology and Haemotherapy, the Spanish Society of Paediatric Haematology and Oncology and the Spanish Society of Radiation Oncology have collaborated to develop a multidisciplinary consensus.


Assuntos
Preservação da Fertilidade/normas , Infertilidade/prevenção & controle , Neoplasias , Humanos , Infertilidade/etiologia , Comunicação Interdisciplinar , Neoplasias/complicações
11.
J Infect ; 83(3): 306-313, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34302864

RESUMO

BACKGROUND: We aimed to describe the epidemiology, risk factors, and clinical outcomes of co-infections and superinfections in onco-hematological patients with COVID-19. METHODS: International, multicentre cohort study of cancer patients with COVID-19. All patients were included in the analysis of co-infections at diagnosis, while only patients admitted at least 48 h were included in the analysis of superinfections. RESULTS: 684 patients were included (384 with solid tumors and 300 with hematological malignancies). Co-infections and superinfections were documented in 7.8% (54/684) and 19.1% (113/590) of patients, respectively. Lower respiratory tract infections were the most frequent infectious complications, most often caused by Streptococcus pneumoniae and Pseudomonas aeruginosa. Only seven patients developed opportunistic infections. Compared to patients without infectious complications, those with infections had worse outcomes, with high rates of acute respiratory distress syndrome, intensive care unit (ICU) admission, and case-fatality rates. Neutropenia, ICU admission and high levels of C-reactive protein (CRP) were independent risk factors for infections. CONCLUSIONS: Infectious complications in cancer patients with COVID-19 were lower than expected, affecting mainly neutropenic patients with high levels of CRP and/or ICU admission. The rate of opportunistic infections was unexpectedly low. The use of empiric antimicrobials in cancer patients with COVID-19 needs to be optimized.


Assuntos
COVID-19 , Coinfecção , Neoplasias , Superinfecção , Estudos de Coortes , Coinfecção/epidemiologia , Humanos , Unidades de Terapia Intensiva , Neoplasias/complicações , Neoplasias/epidemiologia , SARS-CoV-2
12.
Toxicol In Vitro ; 72: 105071, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33352256

RESUMO

Inhalation is the main route of nanoparticles (NP) exposure during manufacturing. Although many mechanisms of toxicity have been described, the interaction of NP with relevant pneumocytes organelles is not widely understood. Considering that the physicochemical properties of NP influence their toxicological responses, the objective of this study was to evaluate whether exposure to different NP, crystalline Fe3O4 NP and amorphous SiO2 NP could alter pneumocytes organelles in alveolar epithelial cells. To achieve this goal, cell viability, ultrastructural changes, lysosomal damage, mitochondrial membrane potential (MMP), lipid droplets (LD) formation and cytokines production were evaluated by MTT, electron microscopy, lysotracker red staining, JC-1, Oil Red staining and Milliplex® assay respectively. Both NP were observed within lamellar bodies (LB), lysosomes, and cytoplasm causing morphological changes. Exposure to SiO2 NP at 6 h induced lysosomal activation, but not Fe3O4 NP. MMP decreased and LD increased at the highest concentrations after both NP exposure. Pro-inflammatory cytokines were released only after SiO2 NP exposure at 48 h. These results indicate that SiO2 NP have a greater impact than Fe3O4 NP on organelles responsible for energy, secretion, degradation and metabolism in pneumocytes leading to the development of respiratory disorders or the exacerbation of preexisting conditions. Therefore, the established biocompatibility for amorphous NP has to be reconsidered.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Óxido Ferroso-Férrico/toxicidade , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Células A549 , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Gotículas Lipídicas/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
13.
PLoS One ; 15(12): e0243997, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33347495

RESUMO

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Foliculite/epidemiologia , Paroniquia/epidemiologia , Fumar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Complacência (Medida de Distensibilidade) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Proto-Oncogênicas p21(ras)/genética , Resultado do Tratamento
14.
Blood Cancer J ; 10(7): 75, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32678078

RESUMO

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.


Assuntos
Suscetibilidade a Doenças , Variação Genética , Imunidade/genética , Leucemia Mieloide Aguda/etiologia , Adulto , Idoso , Alelos , Biomarcadores Tumorais , Suscetibilidade a Doenças/imunologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Imunomodulação/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Esteroides/metabolismo
15.
Int J Pharm ; 586: 119533, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32534160

RESUMO

Current efforts on inflammatory bowel diseases (IBD) treatment are focused on strategies for localised drug delivery at the intestinal mucosa. Despite the potential of curcumin (CC) for IBD treatment, its low solubility and stability limit its application. Thus, the design of nanocarriers that focus CC delivery at the intestinal epithelium is an area of interest. This work proposes α-tocopherol nanoemulsions (NE) stabilised by ascorbyl-2,6-dipalmitate (ADP) as intestinal CC-carriers. The antioxidant capacity of α-tocopherol and ADP could have a synergistic effect on IBD-affected tissues, characterised by an oxidative environment. We obtained nanoemulsions (NE-ADP) with size below 200 nm, negative surface charge, stable in gastrointestinal media and no toxic in the Caco-2 cell model. Intracellular retention of NE-ADP in Caco-2 cells was observed by confocal microscopy. The extremely low Papp values obtained for CC and α-tocopherol indicated the lack of transport across the Caco-2 monolayer. Control nanoemulsion stabilised by lecithin (NE-L) was greatly transported across the Caco-2 cells monolayer, confirming the relevance of ADP on the cellular retention of NE-ADP. The therapeutic potential of NE-ADP was shown by the significant decrease of intracellular ROS levels. Altogether, these results indicate the potential of NE-ADP as a novel approach for the treatment of IBD.


Assuntos
Ácido Ascórbico/química , Curcumina/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Palmitatos/química , alfa-Tocoferol/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Transporte Biológico , Células CACO-2 , Curcumina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Emulsões , Humanos , Lecitinas/química , Nanopartículas , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Solubilidade , alfa-Tocoferol/farmacologia
16.
Sci Rep ; 10(1): 4187, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144349

RESUMO

Plasmonic gallium (Ga) nanoparticles (NPs) are well known to exhibit good performance in numerous applications such as surface enhanced fluorescence and Raman spectroscopy or biosensing. However, to reach the optimal optical performance, the strength of the localized surface plasmon resonances (LSPRs) must be enhanced particularly by suitable narrowing the NP size distribution among other factors. With this purpose, our last work demonstrated the production of hexagonal ordered arrays of Ga NPs by using templates of aluminium (Al) shallow pit arrays, whose LSPRs were observed in the VIS region. The quantitative analysis of the optical properties by spectroscopic ellipsometry confirmed an outstanding improvement of the LSPR intensity and full width at half maximum (FWHM) due to the imposed ordering. Here, by engineering the template dimensions, and therefore by tuning Ga NPs size, we expand the LSPRs of the Ga NPs to cover a wider range of the electromagnetic spectrum from the UV to the IR regions. More interestingly, the factors that cause this optical performance improvement are studied with the universal plasmon ruler equation, supported with discrete dipole approximation simulations. The results allow us to conclude that the plasmonic coupling between NPs originated in the ordered systems is the main cause for the optimized optical response.

17.
Rev Esp Quimioter ; 33(2): 110-115, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32056418

RESUMO

OBJECTIVE: The fungal infections remain an important problem in the allogeneic stem cell trasnsplantation (allo-SCT) setting and thus, anti-fungal prophylaxis is commonly used. The antifungal drug should offer activity, at least against Candida and Aspergillus spp., a good safety profile and low probability interactions. Micafungin could theoretically fulfill these requisites. The aim of the study was to describe the experience with micafungin as primary prophylaxis in patients undergoing allo-SCT in a cohort of Spanish centres, and to evaluate its efficacy and tolerability in this population. METHODS: Retrospective multicentre observational study including all consecutive adult patients admitted for allo-SCT in participating centres of the Grupo Español de Trasplante Hematopoyético (GETH), from January 2010 to December 2013, who received micafungin as primary prophylaxis during the neutropenic period. RESULTS: A total of 240 patients from 13 centres were identified and 159 patients were included for the analysis. Most patients (95.6%) received 50 mg/day of micafungin. During the follow-up, 7 (4.4%) patients developed breakthrough invasive fungal disease, 1 proven and 6 probable; one patient discontinued the drug because of serious drug interactions. Prophylaxis with micafungin was considered effective in 151 (94.9%) patients. CONCLUSIONS: According to our experience, micafungin is an appropriate alternative for antifungal prophylaxis in patients undergoing an allo-HSCT, because its efficacy, its low profile of drug interactions and side-effects.


Assuntos
Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Micafungina/uso terapêutico , Micoses/prevenção & controle , Aloenxertos , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Interações Medicamentosas , Feminino , Humanos , Infecções Fúngicas Invasivas/epidemiologia , Masculino , Micafungina/administração & dosagem , Micafungina/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia
18.
Infect Immun ; 88(4)2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-31964743

RESUMO

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Aspergillus/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Receptor 1 de Quimiocina CX3C/genética , Predisposição Genética para Doença , Aspergilose Pulmonar Invasiva/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Genótipo , Doenças Hematológicas/complicações , Humanos , Medição de Risco
19.
Colloids Surf B Biointerfaces ; 186: 110740, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31869603

RESUMO

Nanoemulsions are vesicular systems with great potential for the delivery of drugs, which significantly depends on the appropriate selection of the components that constitute them. In this sense, the use of materials with adequate toxicity profiles for the oral route provides additional advantages in terms of safety concerns avoidance. This work describes the formulation of novel two-component nanoemulsions constituted by α-tocopherol and ascorbyl-palmitate derivatives. Among them, ascorbyl-dipalmitate allowed the formation of nanoemulsions with size values around 170 nm and negative charge; additionally, they showed strong antioxidant capacity. These nanoemulsions are proposed to the oral route, so their behaviour in intestinal conditions was evaluated by incubating the nanoemulsion in simulated intestinal fluid. This process led to the formation of an intestinal-protein corona (I-PC) at the colloidal surface that determined the interaction with the mucus barrier. The I-PC displaced the immobile-hindered particles towards a subdiffusive-diffusive population. These studies report for the first time the effect of the I-PC on the mucodiffusion behaviour of vesicular systems, a finding that may help to comprehend the performance of nanocarriers under intestinal conditions.


Assuntos
Ácido Ascórbico/análogos & derivados , Intestinos/química , Nanopartículas/química , Coroa de Proteína/química , Ácido Ascórbico/química , Difusão , Emulsões/química , Tamanho da Partícula , Propriedades de Superfície , alfa-Tocoferol/química
20.
Rev Esp Quimioter ; 33(1): 44-48, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865649

RESUMO

OBJECTIVE: Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocan-dins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haema-tological patients on chemotherapy. METHODS: A multicentre, observational retrospective study was performed in 7 Haematology Depart-ments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included. RESULTS: There were 5 cases of probable or proven fun-gal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 as-pergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. CONCLUSIONS: Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/prevenção & controle , Candidíase/prevenção & controle , Doenças Hematológicas/complicações , Micafungina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Aplástica/complicações , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Linfoma/complicações , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Estudos Retrospectivos , Adulto Jovem
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