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1.
Structure ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31918960

RESUMO

How proteins with a stable globular fold acquire the amyloid state is still largely unknown. RepA, a versatile plasmidic DNA binding protein from Pseudomonas savastanoi, is functional as a transcriptional repressor or as an initiator or inhibitor of DNA replication, the latter via assembly of an amyloidogenic oligomer. Its N-terminal domain (WH1) is responsible for discrimination between these functional abilities by undergoing insufficiently understood structural changes. RepA-WH1 is a stable dimer whose conformational dynamics had not been explored. Here, we have studied it through NMR {1H}-15N relaxation and H/D exchange kinetics measurements. The N- and the C-terminal α-helices, and the internal amyloidogenic loop, are partially unfolded in solution. S4-indigo, a small inhibitor of RepA-WH1 amyloidogenesis, binds to and tethers the N-terminal α-helix to a ß-hairpin that is involved in dimerization, thus providing evidence for a priming role of fraying ends and dimerization switches in the amyloidogenesis of folded proteins.

2.
N Biotechnol ; 56: 123-129, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31953202

RESUMO

Microbial oil biosynthesis is envisaged as a promising technology for sustainable production of chemicals and fuels. Sugar-based substrates are the most typical carbon sources used for this purpose where metabolic pathways and stoichiometry are well known. However, the use of low-cost substrates is crucial for the economic viability of the process. Volatile fatty acids (VFAs) are considered to be a novel low-cost carbon source for microbial lipid production. They can be utilized by oleaginous yeasts to produce and store fatty acids in form of intracellular lipid bodies. In this work, Yarrowia lipolytica growth and substrate consumption were evaluated using the major VFAs present in anaerobic effluents. Individual VFAs as well as synthetic mixtures were tested at different concentrations to determine uptake rates and potential toxicity. Increasing VFA chain length resulted in greater biomass yield although, when added individually, 4 g Carbon/L VFA (e.g. 6.45 g/L of caproic and 10 g/L of acetic acid) caused inhibitory effects. Remarkably, biomass growth increased by 2.5-fold on real anaerobic fermentation effluent compared with synthetic mixtures. When real digestate was supplemented with synthetic VFAs up to 26.5 g/L, the inhibitory effect of the acids was counterbalanced. The results provided evidence of robustness of Y. lipolytica towards low-cost fermentation effluents and present this yeast as a promising candidate for the sustainable production of microbial oil using real digestates.

3.
Crit Rev Biotechnol ; : 1-14, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931630

RESUMO

Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, often pose a serious risk not only when delivered in the bloodstream but also in air, the environment and several industrial fields such as pharmaceutics or food. LPS is constituted of three regions; the O-specific chain, the core region and the lipid A, which is the responsible segment of the toxicity. Previous literature dealt with the study of lipid A, its potential ligands as well as the mechanisms of Lipid A interactions that, among other applications, establish the basis for detection methods such as Limulus Amebocyte Lysate (LAL) assays and emerging biosensoring techniques. However, quantifying LPS binding affinity is an urgent need that still requires thorough studies. In this context, this work reviews the molecules that bind LPS, highlighting quantitative affinity parameters. Moreover, state of the art methods to analyze the affinity and kinetics of lipid-ligand interactions are also reviewed and different techniques have been briefly described. Thus, first, we review existing information on LPS ligands, classifying them into three main groups and targeting the comparison of molecules in terms of their interaction affinities and, second, we establish the basis for further research aimed at the development of effective methods for LPS detection and removal.

4.
Waste Manag ; 102: 222-230, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683078

RESUMO

In the present study, anaerobic sludge was subjected to thermal and chemical pretreatments to favour VFAs production from a protein-rich waste (i.e. microalgae biomass). Sludge pretreatments have been previously used in hydrogen production; however, information about how they can affect VFAs production from microalgae is still lacking. Thermal pretreatment was studied at: (i) 80 °C for 10 and 30 min; (ii) 120 °C for 10 and 30 min; and (iii) 100 °C for 20 min. 2-bromoethanesulfonate (BES) at 10 mM and 30 mM was used as chemical pretreatment. Besides, a combination of both pretreatment methods (80 °C and 120 °C at 10 mM and 30 mM BES) was also tested. Thermal pretreatment increased organic matter conversions into VFAs (up to 71% COD-VFAs/CODin) when compared to control values (40% in the untreated anaerobic sludge). Acetic acid was the most abundant VFAs at high temperatures (120 °C) and when BES was employed (up to 60% and 40%, respectively, in terms of COD). On the other hand, propionic acid was the most abundant product at low temperatures and in the untreated anaerobic sludge (up to 60% in terms of COD). This research work might set guidelines in order to choose a suitable sludge pretreatment for VFAs production from microalgae.


Assuntos
Microalgas , Anaerobiose , Archaea , Ácidos Graxos Voláteis , Fermentação , Esgotos
5.
Bioresour Technol ; 297: 122486, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31796382

RESUMO

This study evaluated the feasibility of the anaerobic digestion as a sustainable valorisation strategy for volatile fatty acids production from agroindustrial waste (cucumber, tomato and lettuce). High bioconversion efficiencies were reached by operating the reactors at 25 °C, 3 g VS·d-1·L-1 with pH adjustment. Cucumber fermentation achieved the highest bioconversion (52.6%), whereas tomato degradation was the least efficient bioprocess (40.1%) due to the low pH (5.6) that partially inhibited the hydrolytic and acidogenic activities. In all cases, carboxylic acid profiles were mainly composed of volatile fatty acids with even carbon number. The developed microbial community exhibited high hydrolytic and acidogenic activities associated to carbohydrates degradation. This microbial population was dominated by Firmicutes phylum and showed a lack of acetogenic bacteria related with CH4 production, resulting in a remarkably high VFAs accumulation.


Assuntos
Ácidos Graxos Voláteis , Esgotos , Anaerobiose , Reatores Biológicos , Fermentação , Concentração de Íons de Hidrogênio , Hidrólise
7.
Biotechnol Bioeng ; 117(1): 238-250, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31544974

RESUMO

Microbial oils are proposed as a suitable alternative to petroleum-based chemistry in terms of environmental preservation. These oils have traditionally been studied using sugar-based feedstock, which implies high costs, substrate limitation, and high contamination risks. In this sense, low-cost carbon sources such as volatile fatty acids (VFAs) are envisaged as promising building blocks for lipid biosynthesis to produce oil-based bioproducts. VFAs can be generated from a wide variety of organic wastes through anaerobic digestion and further converted into lipids by oleaginous yeasts (OYs) in a fermentation process. These microorganisms can accumulate in the form of lipid bodies, lipids of up to 60% wt/wt of their biomass. In this context, OY is a promising biotechnological tool for biofuel and bioproduct generation using low-cost VFA media as substrates. This review covers recent advances in microbial oil production from VFAs. Production of VFAs via anaerobic digestion processes and the involved metabolic pathways are reviewed. The main challenges as well as recent approaches for lipid overproduction are also discussed.

8.
Reumatol Clin ; 2019 Dec 08.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31826829

RESUMO

OBJECTIVE: To determine and analyse the organisational approach adopted by Spanish rheumatologists to osteoporosis (OP) to define strategic priorities. MATERIAL AND METHOD: A group of experts designed a questionnaire on OP in the rheumatologist practice. The survey was sent to the Spanish Society of Rheumatology (SER) members. Through the Delphi round, strategic priorities were agreed upon in OP. RESULTS: The priorities are: 1) The SER should promote the inclusion of OP in 100% of the services and expand the training offer; 2) Rheumatology services should promote the role of the nurse in OP, promote quality indicators and referral protocols agreed with primary care in addition to promoting their training in this area; 3) The SER and Rheumatology services should promote electronic consultation, OP monographic clinics and participation in Fracture Liaison Service units. CONCLUSIONS: Strategic priorities in OP help identify areas of improvement at organisational, structural and quality standards level in this pathology.

9.
Molecules ; 24(23)2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810301

RESUMO

Volatile fatty acids (VFAs) are chemical building blocks for industries, and are mainly produced via the petrochemical pathway. However, the anaerobic fermentation (AF) process gives a potential alternative to produce these organic acids using renewable resources. For this purpose, waste streams, such as microalgae biomass, might constitute a cost-effective feedstock to obtain VFAs. The present review is intended to summarize the inherent potential of microalgae biomass for VFA production. Different strategies, such as the use of pretreatments to the inoculum and the manipulation of operational conditions (pH, temperature, organic loading rate or hydraulic retention time) to promote VFA production from different microalgae strains, are discussed. Microbial structure analysis using microalgae biomass as a substrate is pointed out in order to further comprehend the roles of bacteria and archaea in the AF process. Finally, VFA applications in different industry fields are reviewed.

10.
Sci Rep ; 9(1): 18411, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804526

RESUMO

Information on temporal variations in stock reproductive potential (SRP) is essential in fisheries management. Despite this relevance, fundamental understanding of egg production variability remains largely unclear due to difficulties in tracking the underlying complex fluctuations in early oocyte recruitment that determines fecundity. We applied advanced oocyte packing density theory to get in-depth, quantitative insights across oocyte stages and seasons, selecting the commercially valuable European hake (Merluccius merluccius) as a case study. Our work evidenced sophisticated seasonal oocyte recruitment dynamics and patterns, mostly driven by a low-cost predefinition of fecundity as a function of fish body size, likely influenced also by environmental cues. Fecundity seems to be defined at a much earlier stage of oocyte development than previously thought, implying a quasi-determinate - rather than indeterminate - fecundity type in hake. These results imply a major change in the conceptual approach to reproductive strategies in teleosts. These findings not only question the current binary classification of fecundity as either determinate or indeterminate, but also suggest that current practices regarding potential fecundity estimation in fishes should be complemented with studies on primary oocyte dynamics. Accordingly, the methodology and approach adopted in this study may be profitably applied for unravelling some of the complexities associated with oocyte recruitment and thereby SRP variability.

11.
Sci Rep ; 9(1): 18374, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804573

RESUMO

Volatile fatty acids (VFAs) are regarded as building blocks with a wide range of applications, including biofuel production. The traditional anaerobic digestion used for biogas production can be alternatively employed for VFAs production. The present study aimed at maximizing VFAs productions from Chlorella vulgaris through anaerobic digestion by assessing the effect of stepwise organic loading rates (OLR) increases (3, 6, 9, 12 and 15 g COD L-1 d-1). The biological system was proven to be robust as organic matter conversion efficiency into VFAs increased from 0.30 ± 0.02 COD-VFAs/CODin at 3 g COD L-1 d-1 to 0.37 ± 0.02 COD-VFAs/CODin at 12 g COD L-1d-1. Even though, the hydrolytic step was similar for all studied scenario sCOD/tCOD = 0.52-0.58), the highest OLR (15 g COD L-1 d-1) did not show any further increase in VFAs conversion (0.29 ± 0.01 COD-VFAs/CODin). This fact suggested acidogenesis inhibition at 15 g COD L-1d-1. Butyric (23-32%), acetic (19-26%) and propionic acids (11-17%) were the most abundant bioproducts. Population dynamics analysis revealed microbial specialization, with a high presence of Firmicutes followed by Bacteroidetes. In addition, this investigation showed the microbial adaptation of Euryarchaeota species at the highest OLR (15 g COD L-1d-1), evidencing one of the main challenges in VFAs production (out-competition of archaea community to avoid product consumption). Stepwise OLR increase can be regarded as a tool to promote VFAs productions. However, acidogenic inhibition was reported at the highest OLR instead of the traditional hydrolytic barriers. The operational conditions imposed together with the high VFAs and ammonium concentrations might have affected the system yields. The relative abundance of Firmicutes (74%) and Bacteroidetes (20%), as main phyla, together with the reduction of Euryarchaeota phylum (0.5%) were found the best combination to promote organic matter conversion into VFAs.

12.
Dig Dis Sci ; 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31858325

RESUMO

BACKGROUND: Increasing the interval of administration of anti-TNF agents over the duration specified in the data sheet is not common in inflammatory bowel disease (IBD). AIM: To evaluate the outcomes of IBD patients treated with this strategy. METHODS: Patients with IBD who were treated with infliximab or adalimumab at intervals > 8 weeks or > 2 weeks, respectively, because of persistent clinical remission, were identified at local databases of the ENEIDA registry (a nationwide registry promoted by the Spanish Working Group in Crohn's disease and Ulcerative Colitis-GETECCU) of two referral centers. Treatment success was considered if patients remained in clinical remission with the same schedule or without biological therapy at the end of follow-up, and if no return to the conventional schedule, dose-escalation, change in biological agent, or a course of systemic corticosteroids or surgery were required. RESULTS: Eighty-five patients were included, 60 treated with infliximab and 25 with adalimumab. The spaced schedule was initiated after a median of 25 months on anti-TNF treatment (IQR 14-49). Throughout a median follow-up of 34 months (IQR 21-47), fifty patients (59%) fulfilled the success criteria of the spaced strategy. No differences were found regarding type of IBD or anti-TNF agent. Baseline C-reactive protein levels and disease duration at the time of starting anti-TNF treatment were the only factors associated with treatment success. CONCLUSIONS: Anti-TNF administration at longer intervals than those provided in the data sheet may be an efficacious, convenient, and cheaper treatment option, particularly in patients in whom anti-TNF treatment was initiated early.

13.
Molecules ; 24(24)2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31842312

RESUMO

Disturbances in anaerobic digestion (AD) negatively impact the overall reactor performance. These adverse effects have been widely investigated for methane generation. However, AD recently appeared as a potential technology to obtain volatile fatty acids (VFAs) and thus, the impact of process disturbances must be evaluated. In this sense, microbial response towards a starvation period of two weeks was investigated resulting in a conversion of organic matter into VFAs of 0.39 ± 0.03 COD-VFAs/CODin. However, the lack of feeding reduced the yield to 0.30 ± 0.02 COD-VFAs/CODin. Microbial analysis revealed that the starvation period favored the syntrophic acetate-oxidizing bacteria coupled with hydrogenotrophic methanogens. Finally, the system was fed at 9 g COD/Ld resulting in process recovery (0.39 ± 0.04 COD-VFAs/CODin). The different microbiome obtained at the end of the process was proved to be functionally redundant, highlighting the AD robustness for VFAs production.

15.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31780424

RESUMO

INTRODUCTION AND OBJECTIVES: Current guidelines recommend centralizing the care of patients with cardiogenic shock in high-volume centers. The aim of this study was to assess the association between hospital characteristics, including the availability of an intensive cardiac care unit, and outcomes in patients with ST-segment elevation myocardial infarction (STEMI)-related cardiogenic shock (CS). METHODS: Discharge episodes with a diagnosis of STEMI-related CS between 2003 and 2015 were selected from the Minimum Data Set of the Spanish National Health System. Centers were classified according to the availability of a cardiology department, catheterization laboratory, cardiac surgery department, and intensive cardiac care unit. The main outcome measured was in-hospital mortality. RESULTS: A total of 19 963 episodes were identified. The mean age was 73.4±11.8 years. The proportion of patients with CS treated at hospitals with a catheterization laboratory and cardiac surgery department increased from 38.4% in 2005 to 52.9% in 2015 (P <.005). Crude- and risk-adjusted mortality rates decreased over time, from 82% to 67.1%, and from 82.7% to 66.8%, respectively (both P <.001). Coronary revascularization, either percutaneous or coronary artery bypass grafting, was independently associated with a lower mortality risk (OR, 0.29 and 0.25; both P <.001, respectively). Intensive cardiac care unit availability was associated with lower adjusted mortality rates (65.3%±7.9 vs 72±11.7; P <.001). CONCLUSIONS: The proportion of patients with STEMI-related CS treated at highly specialized centers increased while mortality decreased during the study period. Better outcomes were associated with the increased performance of revascularization procedures and access to intensive cardiac care units over time.

16.
Med. clín (Ed. impr.) ; 153(10): 380-386, nov. 2019. graf, tab
Artigo em Inglês | IBECS-Express | ID: ibc-ET2-4092

RESUMO

Background and objectives: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. Material and methods: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. Results: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). Conclusions: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule


Antecedentes y objetivos: La vacunación antigripal está recomendada en pacientes con enfermedades autoinmunes sistémicas que reciben tratamientos biológicos. Evaluar si la terapia biológica puede perjudicar la inmunización después de la administración de la vacuna contra la gripe estacional. Material y métodos: Los pacientes con artropatías inflamatorias, psoriasis, enfermedad inflamatoria intestinal o enfermedades del tejido conectivo, que estaban en tratamiento o que iban a iniciar tratamiento con terapia biológica, fueron incluidos en el estudio y vacunados durante la temporada de influenza 2014-2015. Se utilizó ELISA para medir los anticuerpos contra los antígenosA y B de la gripe, antes y después de la vacunación. Se registraron los datos demográficos, diagnósticos y el tipo de tratamiento y se estudió su influencia sobre el estado serológico final contra la influenza. Resultados: Se analizaron 253 sujetos. Después de la vacunación, el 77% de los participantes presentaron anticuerpos detectables contra el antígeno A y el 50,6% de ellos tenían anticuerpos detectables contra el antígeno B. La tasa de seropositividad final de anticuerpos contra el antígeno B aumentó desde los valores basales (50,6% frente a 43,5%, p<0,001). Los fármacos anti-TNF se asociaron con la mejor respuesta y rituximab con la peor (79,2% vs. 55,0% para la seropositividad final contra el antígeno A, p=0,020). La respuesta a la vacuna en el grupo de rituximab tuvo tendencia a mejorar cuando el intervalo entre la administración del fármaco y la vacunación fue por lo menos de 12 semanas (tasa de seropositividad del 80,0% en aquellos con el intervalo más largo frente al 25% en el otro grupo, p=0.054). Conclusiones: Entre los pacientes en terapia biológica vacunados contra la influenza, la terapia anti-TNF se identificó como un factor predictivo de la seropositividad final. Rituximab presentó una tasa más baja de seropositividad final, que podría aumentarse con un programa de administración preciso

17.
Nat Metab ; 1(8): 775-789, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31579886

RESUMO

The humoral immune response demands that B cells undergo a sudden anabolic shift and high cellular nutrient levels which are required to sustain the subsequent proliferative burst. Follicular lymphoma (FL) originates from B cells that have participated in the humoral response, and 15% of FL samples harbor point, activating mutations in RRAGC, an essential activator of mTORC1 downstream of the sensing of cellular nutrients. The impact of recurrent RRAGC mutations in B cell function and lymphoma is unexplored. RRAGC mutations, targeted to the endogenous locus in mice, confer a partial insensitivity to nutrient deprivation, but strongly exacerbate B cell responses and accelerate lymphomagenesis, while creating a selective vulnerability to pharmacological inhibition of mTORC1. This moderate increase in nutrient signaling synergizes with paracrine cues from the supportive T cell microenvironment that activates B cells via the PI3K-Akt-mTORC1 axis. Hence, Rragc mutations sustain induced germinal centers and murine and human FL in the presence of decreased T cell help. Our results support a model in which activating mutations in the nutrient signaling pathway foster lymphomagenesis by corrupting a nutrient-dependent control over paracrine signals from the T cell microenvironment.

18.
Aten. prim. (Barc., Ed. impr.) ; 51(8): 479-485, oct. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-185750

RESUMO

Objetivo: Estimar la prevalencia de uso de anticoncepción hormonal de solo gestágenos (AHSG) entre las mujeres demandantes de anticoncepción reversible en atención primaria (AP). Diseño: Estudio descriptivo transversal multicéntrico. Emplazamiento: AP de la Comunidad de Madrid. Participantes: Mujeres entre 16-50 años, usuarias de anticoncepción reversible, que hablen español y hubieran acudido en el último año a consulta de AP. Mediciones principales: Encuesta telefónica. Variable principal: método anticonceptivo utilizado: solo gestágenos (sí/no). Edad, paridad, país de origen, tipo de método anticonceptivo (MAC) utilizado, motivo de elección, duración, fuente de información, lugar de obtención, satisfacción con el método. Resultados: 417 mujeres. Edad: media 30,3 años (DE: 7,7). Españolas: 69%, estudios secundarios y universitarios: 82%, nulíparas: 57%. Tipo de MAC utilizado: AHSG 14%, hormonal combinado (AHC): 74%, DIU cobre: 2%, preservativo: 10%. La prevalencia de uso de AHSG fue del 13,9% (IC95%: 10,6-17,2). Entre los AHSG el método más utilizado fue el inyectable trimestral de acetato de medroxiprogesterona (4,6%), píldora oral de desogestrel (4,1%), DIU-LNG (3,9%), implante subdérmico de etonogestrel (1,9%). El médico de familia fue el prescriptor del MAC en el 71% de las mujeres. Satisfacción: alta (mediana 10 sobre 10). Utilizar AHSG se asoció con mayor edad, ser extranjera y motivos de prescripción: lactancia y tener contraindicación médica para AHC (p < 0,05). Conclusiones: La prevalencia de uso para la AHSG fue del 14%, la satisfacción fue muy alta para todos los MAC. El perfil de usuaria para la AHSG corresponde a mujer de mayor edad, extranjera y con condiciones como la lactancia o la contraindicación para otros MAC


Aim: To estimate the prevalence of use of progestin-only contraceptive among women who request reversible contraception in Primary Care (PC). Design: Multicentre cross-sectional study. Setting: Primary Care Health Care Centres (Madrid). Participants: Women aged 16-50 years old, users of reversible contraception, who speak Spanish, and had attended the Primary Care Centre in the last year. Main measurements: Primary outcome: contraceptive method used: Contraception with progestins-only (yes/no). Age, parity, country of origin, type of contraceptive method used, reason for choice, source of information, satisfaction with the contraceptive method. Telephone survey. Results: A total of 417 women were interviewed. The median age was 30.3 years (SD: 7.7). Spanish 69%, and 82% of participants had secondary or university studies. More than half (57%) were nulliparous. The type of contraceptive used included: progestins only: 14%, combined hormonal contraceptive: 74%, copper IUD: 2%, and condom 10%. The prevalence of use of "progestins-only" was 13.9% (95%CI: 10.6-17.2). Medroxyprogesterone acetate injection was the most progestin-only method used (4.6%), desogestrel oral pill (4.1%), IUD-levonorgestrel IUD (3.9%), and etonogestrel subdermal implant (1.9%). The family doctor was the prescriber in 71% of the women. Satisfaction: high (range 9-10). Using only progestogens was associated with older age, being non-Spanish, breastfeeding, and having a medical contraindication for combined contraception (P < 0.05). Conclusions: The prevalence of use for progestins was 14%, satisfaction was very high for all contraceptive methods. The user profile for the only progestins-only corresponds to older, and non-Spanish women with conditions such as breastfeeding or contraindications for other contraceptives


Assuntos
Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Progestinas/uso terapêutico , Atenção Primária à Saúde/métodos , Anticoncepção , Satisfação do Paciente , Estudos Transversais , Epidemiologia Descritiva , Telefone , Contraindicações de Medicamentos
19.
Int J Mol Sci ; 20(16)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412584

RESUMO

Melatonin exerts oncostatic actions and sensitizes tumor cells to chemotherapeutics or radiation. In our study, we investigated the effects of docetaxel, vinorelbine, and radiation on human breast fibroblasts and its modulation by melatonin. Docetaxel or vinorelbine inhibits proliferation and stimulates the differentiation of breast preadipocytes, by increasing C/EBPα and PPARγ expression and by downregulating tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-11 expression. Radiation inhibits both proliferation and differentiation through the downregulation of C/EBPα and PPARγ and by stimulating TNFα expression. In addition, docetaxel and radiation decrease aromatase activity and expression by decreasing aromatase promoter II and cyclooxygenases 1 and 2 (COX-1 and COX-2) expression. Melatonin potentiates the stimulatory effect of docetaxel and vinorelbine on differentiation and their inhibitory effects on aromatase activity and expression, by increasing the stimulatory effect on C/EBPα and PPARγ expression and the downregulation of antiadipogenic cytokines and COX expression. Melatonin also counteracts the inhibitory effect of radiation on differentiation of preadipocytes, by increasing C/EBPα and PPARγ expression and by decreasing TNFα expression. Melatonin also potentiates the inhibitory effect exerted by radiation on aromatase activity and expression by increasing the downregulation of promoter II, and COX-1 and COX-2 expression. Our findings suggest that melatonin modulates regulatory effects induced by chemotherapeutic drugs or radiation on preadipocytes, which makes it a promising adjuvant for chemotherapy and radiotherapy sensibilization.


Assuntos
Antineoplásicos/farmacologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/efeitos da radiação , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Melatonina/farmacologia , Radiação Ionizante , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/efeitos da radiação , Aromatase/metabolismo , Neoplasias da Mama , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Docetaxel/farmacologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Glândulas Mamárias Humanas/citologia , PPAR gama/genética , PPAR gama/metabolismo , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Vinorelbina/farmacologia
20.
HIV AIDS (Auckl) ; 11: 179-192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447590

RESUMO

Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions. Adding to the increasing body of evidence for newer two-drug combinations, phase II and phase III trial data to date demonstrate cabotegravir and rilpivirine combination injectable therapy to be non-inferior to selected oral triple-therapy alternatives. Most importantly, this therapy is reported to be acceptable to individuals taking the 4-weekly or 8-weekly injections, despite frequent injection-site reactions. Key outstanding questions include management of missed or delayed dosing, drug interactions and management of virological failure, as well as the efficacy of cabotegravir and rilpivirine in all HIV-1 subtypes. We describe clinical evidence to date and efficacy and challenges in selected populations, including women; those with prior virological failure; individuals with a history of difficulty adhering to oral therapy and individuals with co-infections. We await real-world data and longer-term evidence while moving forward to this new era of antiretroviral therapy.

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