98 research outputs found
Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis.
BACKGROUND: Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials. METHODS: Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies. RESULTS: Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)). CONCLUSIONS: Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events
Haemocompatibility of iron oxide nanoparticles synthesized for theranostic applications: a high-sensitivity microfluidic tool
The poor heating efficiency of the most
reported magnetic nanoparticles (MNPs), allied to the
lack of comprehensive biocompatibility and haemodynamic
studies, hampers the spread of multifunctional
nanoparticles as the next generation of
therapeutic bio-agents in medicine. The present work
reports the synthesis and characterization, with special
focus on biological/toxicological compatibility, of
superparamagnetic nanoparticles with diameter
around 18 nm, suitable for theranostic applications
(i.e. simultaneous diagnosis and therapy of cancer).
Envisioning more insights into the complex nanoparticle-red
blood cells (RBCs) membrane interaction,
the deformability of the human RBCs in contact with
magnetic nanoparticles (MNPs) was assessed for the
first time with a microfluidic extensional approach,
and used as an indicator of haematological disorders in
comparison with a conventional haematological test,
i.e. the haemolysis analysis. Microfluidic results
highlight the potential of this microfluidic tool over
traditional haemolysis analysis, by detecting small
increments in the rigidity of the blood cells, when
traditional haemotoxicology analysis showed no significant
alteration (haemolysis rates lower than 2 %).
The detected rigidity has been predicted to be due to
the wrapping of small MNPs by the bilayer membrane
of the RBCs, which is directly related to MNPs size,
shape and composition. The proposed microfluidic
tool adds a new dimension into the field of
nanomedicine, allowing to be applied as a highsensitivity
technique capable of bringing a better understanding of the biological impact of nanoparticles
developed for clinical applications.This work was financially supported by:
Project POCI-01-0145-FEDER-006984 – Associate Laboratory
J Nanopart Res (2016) 18:194 Page 15 of 17 194
123 LSRE-LCM funded by FEDER funds through COMPETE2020 -
Programa Operacional Competitividade e Internacionalizac¸a˜o
(POCI) – and by national funds through FCT - Fundac¸a˜o para a
Cieˆncia e a Tecnologia. R.O.R. acknowledges the Ph.D.
scholarship SFRH/BD/97658/2013 Granted by FCT. A.M.T.S
acknowledges the FCT Investigator 2013 Programme (IF/01501/
2013), with financing from the European Social Fund and the
Human Potential Operational Programme. M.B. would like to
thank ERDF (European Regional Development Fund) under
grant PO Norte CCDR-N/ON.2 Programme. J.G. also thanks the
European Union’s Seventh Framework Programme for research,
technological development and demonstration under grant
agreement no. 600375.info:eu-repo/semantics/publishedVersio
The ocean sampling day consortium
Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits
Conjugating his-tagged proteins to magnetic nanoparticles: tips and challenges
Resumen del póster presentado al 5th Multistep Enzyme Catalyzed Processes Congress (MECPC), celebrado online del 13 al 16 de septiembre de 2021.The histidine tag (His-tag) is one of the most used affinity-tag for protein purification due to its small size and versatility. Agarose and sepharose beads containing nitriloacetic acid (NTA) transition metal derivatives are widely used for the purification of His-tagged proteins, thanks to their high affinity to the His-tag genetically fused to the protein of interest [1]. The same chemistry can be used to conjugate enzymes to magnetic nanoparticles (MNPs) with the aim of tuning their activity by magnetic heating [2, 3]. Within the frame of the FET-OPEN project HOTZYMES (https://www.hotzymes.eu), different MNPs have been synthetized and coated with polyacrylic acid and dimercaptosuccinic acid, and then were further functionalized with NTA-Cu2+ as His-tag chelating agent. Different proteins were expressed as His-tag variants and immobilized on the MNPs, including monomeric (superfolded GFP), dimeric (C. violaceum transaminase, CvTA; C. uda cellobiose phosphorylase, CuCbP), and tetrameric (B. stearothermophilus alcohol dehydrogenase, ADH) variants. While for the monomeric protein selected as model no difficulties in the bioconjugation processes were observed, when using dimeric or tetrameric enzymes the aggregation of the MNPs occurs very easily due to crosslinking between the nanoparticles. This colloidal destabilization of the MNPs is favored due to its high surface area and the presence of several tags per enzyme molecule. To avoid this situation, different strategies have been developed: saturation of the binding site of the nanoparticles, presence of a small percentage of imidazole in reaction, changes in the incubation conditions (pH, ionic strength, …). First positive results confirm that by playing with different factors it is possible to conjugate different His-tagged enzymes to very different MNPs in terms of size, shape, surface area, and colloidal stability. Actually, it is possible to avoid protein and MNPs aggregation while obtaining good activity yields for the conjugated enzymes and maintaining the magnetic heating capacity of the MNPs.The research for this work has received funding from the European Union (EU) project HOTZYMES (grant agreement n° 829162) under EU’s Horizon 2020 Programme Research and Innovation actions H2020-FETOPEN-2018-2019-2020-01. Authors also thank Spanish MINECO project BIO2017-84246-C2-1-R, DGA and Fondos Feder (Bionanosurf E15_17R).Peer reviewe
NADPH Phagocyte Oxidase Knockout Mice Control Trypanosoma cruzi Proliferation, but Develop Circulatory Collapse and Succumb to Infection
•NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91phox−/− or phox KO) were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-γ and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx) at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with •NO in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi
Nucleases as a barrier to gene silencing in the cotton boll weevil, Anthonomus grandis.
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