Here, we present new antimicrobial nanoparticles based on silica nanoparticles (SNPs) coated with a quaternary ammonium cationic surfactant, didodecyldimethylammonium bromide (DDAB). Depending on the ...initial concentration of DDAB, SNPs immobilize between 45 and 275 μg of DDAB per milligram of nanoparticle. For high concentrations of DDAB adsorbed to SNP, a bilayer is formed as confirmed by zeta potential measurements, thermogravimetry, and diffuse reflectance infrared Fourier transform (DRIFT) analyses. Interestingly, these nanoparticles have lower minimal inhibitory concentrations (MIC) against bacteria and fungi than soluble surfactant. The electrostatic interaction of the DDAB with the SNP is strong, since no measurable loss of antimicrobial activity was observed after suspension in aqueous solution for 60 days. We further show that the antimicrobial activity of the nanoparticle does not require the leaching of the surfactant from the surface of the NPs. The SNPs may be immobilized onto surfaces with different chemistry while maintaining their antimicrobial activity, in this case extended to a virucidal activity. The versatility, relative facility in preparation, low cost, and large antimicrobial activity of our platform makes it attractive as a coating for large surfaces.
For many decades, cancer treatment has been strongly directed toward the development of cytotoxic and cytostatic drugs, quite often leading to disappointing results due to the inter- and ...intra-tumoral heterogeneity. Lately, this intra-cellular look has given way to the understanding of the tumor microenvironment, thus enabling modification of the immunological dynamics between tumor cells and their host. An era of new drugs aiming to unlock the host immune system against tumor cells is steadily increasing. Strategies involving adoptive cell therapy, therapeutic vaccines, immune checkpoint inhibitors and so on have provided spectacular clinical responses and increased survival in previously refractory settings and “hard-to-treat” cancers. Based on a comprehensive search in the main scientific databases, annals of recent renowned oncology congresses and platforms of ongoing trials, the clinical pharmacology characteristics of the main classes of immunotherapeutic agents, as well as the new treatment strategies related to immunotherapy in solid tumors, are carefully discussed throughout this review.
It was investigated how many cattle become infected with Trypanosoma vivax by subcutaneous (SC), intramuscular (IM) and intravenous (IV) routes, using the same syringe and needle from an animal with ...acute T. vivax infection. Besides, the T. vivax viability in 109 injectable veterinary drugs (antibiotics, antiparasitics, reproductive hormones, vitamin complex and derivatives, vaccines, anaesthetics, anti-inflammatory/antipyretics, antitoxics). In the field assay, four groups were performed: T01, T02 and T03 animals that received saline solution with the same syringe and needle contaminated with T. vivax via SC, IM and IV routes, respectively, and T04 control animals that received only saline solution with the same syringe and needle IV. In the laboratory, drugs had their pH measured and T. vivax viability verified. The number of cattle infected with T. vivax via SC (3/20) was lower (P ≤ 0.05) compared to via IM (9/20), which was lower (P ≤ 0.05) compared to IV (15/20). The solution pH did not influence T. vivax viability. In 44% (48/109) of the products, T. vivax remained viable regardless of time, stooding out that in 100% of oxytocins the protozoan was verified, at some evaluation times. The mean of T. vivax quantified in foot-and-mouth and brucellosis vaccines and in doramectin-based products were higher (P ≤ 0.05) than found in blood + saline solution.
Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates ...neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles.
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•NiII complexes are capable of binding in the minor groove of DNA.•DNA cleavage was observed.•Two NiII complexes were more active than cisplatin toward cancer cell lines.•Two NiII ...complexes induced late apoptosis.
In this work, three nickel(II) complexes, namely, Ni(η2-NO3)(bta)(phen) (I), Ni(η2-NO3)(btc)(phen) (II), and Ni(η2-NO3)(btf)(phen) (III) (bta = 4,4,4-trifluoro-1-phenyl-1,3-butanedione anion, btc = 1-(4-chlorophenyl)-4,4,4-trifluoro-1,3-butanedione anion, btf = 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione anion, phen = 1,10-phenanthroline) were prepared and fully characterized by magnetic susceptibility measurements, spectroscopic methods and single-crystal X-ray diffraction. The spectral and structural data confirm that the β-diketones anions coordinate via the oxygen atoms, whilst the heterocyclic base coordinates through the nitrogen atoms. A nitrate coordinated in bidentate mode completes the coordination sphere around the metal center. The anticancer activity of chelating ligands and their nickel complexes was evaluated against two tumor cell lines, MCF-7 (a hormone responsive cancer cell) and MDA-MB-231 (triple negative breast cancer cell). The complexes I and II were more active than cisplatin and interacted more effectively with DNA, with Kb values in the range of 103 –104 M−1. According to data from circular dichroism (CD) and fluorescence spectroscopy, these complexes appear to bind to the DNA groove and/or by electrostatic forces. Molecular docking followed by semiempirical simulations reinforce that they are capable of binding in the minor groove of the double helix of ct-DNA in an A-T rich region. DNA cleavage studies indicated that the complex II cleaves the plasmid DNA in the presence of H2O2. Subsequently, we found that I and II induce late apoptosis in MCF-7 cells.
Cardiac magnetic resonance has become a reliable imaging modality providing structural and functional data, and fundamental information about tissue composition. Cardiac magnetic resonance imaging ...with late gadolinium enhancement, T1-mapping, T2-mapping, T2*-imaging, and extracellular volume, has proved to be a valuable tool in investigating the etiology of heart failure. Such analysis is helpful for the diagnostic evaluation of both ischemic and non-ischemic cardiomyopathies. As primary heart muscle diseases, the ability to characterize the myocardial substrate is essential. Determining the heart failure etiology is fundamental and has implications regarding the prognosis prediction and best treatment. Investigation in cardiac magnetic resonance in heart failure patients has grown in the past decade, and the true value of this imaging modality to detect early disease likely remains underestimated. This review describes the importance of cardiac magnetic resonance for the diagnosis and prognosis of non-ischemic cardiomyopathies, particularly hypertrophic, infiltrative, and arrhythmogenic cardiomyopathies.
Overdrive pacing may play a role in the termination of VAs, by inducing an extrastimuli and stopping the reentrant circuit. ...Ito currents are less prominent at faster heart rates; thus, by ...increasing the basal heart rate, rapid pacing may have a role in decreasing the risk of arrhythmia generation. In this case, there seems to be a direct myocardial insult. ...the patient reported mild chest pain after PCI of a proximal RCA lesion, suggesting reperfusion injury and justifying the involvement of the RV. Interestingly, a recent case series suggested that CAD‐related but non‐ischemia‐driven drug‐refractory VAs may have a similar background to BrS (and other arrhythmogenic syndromes with a structurally normal heart) and display a remarkable response to quinidine, although in this study there is no mention of a BrP preceding the VAs. 5 This case highlights the importance of early recognition of the precipitating mechanisms of electrical storm and raises the possibility that reperfusion injury may precipitate VAs in patients with BrS.
Cardiac Computed Tomography (CCT) has become a reliable imaging modality in cardiology providing robust information on the morphology and structure of the heart with high temporal and isotropic ...spatial resolution. For the past decade, there has been a paradigm shift in the management of valvular heart disease since previously unfavorable candidates for surgery are now provided with less-invasive interventions. Transcatheter heart valve interventions provide a real alternative to medical and surgical management and are often the only treatment option for valvular heart disease patients. Successful transcatheter valve interventions rely on comprehensive multimodality imaging assessment. CCT is the mainstay imaging technique for preprocedural planning of these interventions. CCT is critical in guiding patient selection, choice of procedural access, device selection, procedural guidance, as well as allowing postprocedural follow-up of complications. This article aims to review the current evidence of the role of CCT in the preprocedural planning of patients undergoing transcatheter valvular interventions.
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