Different medications for the treatment of Ménière’s disease by intratympanic injection: a systematic review and network meta-analysis

Background: It is generally accepted that intratympanic injection provides an effective approach to manage severe vertigo in Ménière’s disease. Although there are several medications available, that which is the most effective is still subject to debate. Objective: To assess the effectiveness and safety of the different medications used in treatment of Ménière’s disease by intratympanic injection using a network meta-analysis. Methods: PubMed, EMBASE, CINAHL and CENTRAL were searched. Only randomized controlled trials that compared the effectiveness of medications used for intratympanic injection to treat Ménière’s disease with each other or a placebo were included. The primary outcome assessed was the effectiveness of medication in the management of vertigo symptoms. The effectiveness was expressed in terms of risk ratio (RR) with a 95% credible interval (CrI) for individual studies analyzed. Network meta-analyses was performed by Stata version 15.0 using the network package. Results: Nine studies involving 314 patients treated with 5 different medications were included in the present analysis. Number of injections given varied from 1 to 10 and follow-up time from 3 to 28 months. When compared to each other or to a placebo, Gentamicin was found to be the most efficacious medication, followed by Methylprednisolone, Latanoprost, Dexamethasone and Ganciclovir in order of effectiveness. However, no significant difference in efficacy was found between Gentamicin and Methylprednisolone when outcomes from studies with a follow-up time equal to or more than 24 months were analyzed. It was not possible to conduct subgroup and sensitivity analysis because of the limited number of studies that were included. Conclusion: All medications are more effective than a placebo in the treatment of Ménière’s disease by intratympanic injection. According to the SUCRA, Gentamicin ranked the most effective, with Gentamicin and Methylprednisolone equally effective in the long-term. When the potential risk of hearing loss induced by Gentamicin is taken into consideration, Methylprednisolone may be the best choice for treatment of Ménière’s disease by intratympanic injection

Phase behavior of supported lipid bilayers: A systematic study by coarse-grained molecular dynamics simulations

Solid-supported lipid bilayers are utilized by experimental scientists as models for biological membranes because of their stability. However, compared to free standing bilayers, their close proximity to the substrate may affect their phase behavior. As this is still poorly understood, and few computational studies have been performed on such systems thus far, here we present the results from a systematic study based on molecular dynamics simulations of an implicit-solvent model for solid-supported lipid bilayers with varying lipid-substrate interactions. The attractive interaction between the substrate and the lipid head groups that are closest to the substrate leads to an increased translocation of the lipids from the distal to the proximal bilayer-leaflet. This thereby leads to a transbilayer imbalance of the lipid density, with the lipid density of the proximal leaflet higher than that of the distal leaflet. Consequently, the order parameter of the proximal leaflet is found to be higher than that of the distal leaflet, the higher the strength of lipid interaction is, the stronger the effect. The proximal leaflet exhibits gel and fluid phases with an abrupt melting transition between the two phases. In contrast, below the melting temperature of the proximal leaflet, the distal leaflet is inhomogeneous with coexisting gel and fluid domains. The size of the fluid domains increases with increasing the strength of the lipid interaction. At low temperatures, the inhomogeneity of the distal leaflet is due to its reduced lipid density

Inherited Glutathione Reductase Deficiency and Plasmodium falciparum Malaria—A Case Study

In Plasmodium falciparum-infected red blood cells (RBCs), the flavoenzyme glutathione reductase (GR) regenerates reduced glutathione, which is essential for antioxidant defense. GR utilizes NADPH produced in the pentose phosphate shunt by glucose-6-phosphate dehydrogenase (G6PD). Thus, conditions affecting host G6PD or GR induce increased sensitivity to oxidants. Hereditary G6PD deficiency is frequent in malaria endemic areas and provides protection against severe malaria. Furthermore, GR deficiency resulting from insufficient saturation of the enzyme with its prosthetic group FAD is common. Based on these naturally occurring phenomena, GR of malaria parasites and their host cells represent attractive antimalarial drug targets. Recently we were given the opportunity to examine invasion, growth, and drug sensitivity of three P. falciparum strains (3D7, K1, and Palo Alto) in the RBCs from three homozygous individuals with total GR deficiency resulting from mutations in the apoprotein. Invasion or growth in the GR-deficient RBCs was not impaired for any of the parasite strains tested. Drug sensitivity to chloroquine, artemisinin, and methylene blue was comparable to parasites grown in GR-sufficient RBCs and sensitivity towards paraquat and sodium nitroprusside was only slightly enhanced. In contrast, membrane deposition of hemichromes as well as the opsonizing complement C3b fragments and phagocytosis were strongly increased in ring-infected RBCs of the GR-deficient individuals compared to ring-infected normal RBCs. Also, in one of the individuals, membrane-bound autologous IgGs were significantly enhanced. Thus, based on our in vitro data, GR deficiency and drug-induced GR inhibition may protect from malaria by inducing enhanced ring stage phagocytosis rather than by impairing parasite growth directly

Cold Induces Micro- and Nano-Scale Reorganization of Lipid Raft Markers at Mounds of T-Cell Membrane Fluctuations

Whether and how cold causes changes in cell-membrane or lipid rafts remain poorly characterized. Using the NSOM/QD and confocal imaging systems, we found that cold caused microscale redistribution of lipid raft markers, GM1 for lipid and CD59 for protein, from the peripheral part of microdomains to the central part on Jurkat T cells, and that cold also induced the nanoscale size-enlargement (1/3- to 2/3-fold) of the nanoclusters of lipid raft markers and even the colocalization of GM1 and CD59 nanoclusters. These findings indicate cold-induced lateral rearrangement/coalescence of raft-related membrane heterogeneity. The cold-induced re-distribution of lipid raft markers under a nearly-natural condition provide clues for their alternations, and help to propose a model in which raft lipids associate themselves or interact with protein components to generate functional membrane heterogeneity in response to stimulus. The data also underscore the possible cold-induced artifacts in early-described cold-related experiments and the detergent-resistance-based analyses of lipid rafts at 4°C, and provide a biophysical explanation for recently-reported cold-induced activation of signaling pathways in T cells. Importantly, our fluorescence-topographic NSOM imaging demonstrated that GM1/CD59 raft markers distributed and re-distributed at mounds but not depressions of T-cell membrane fluctuations. Such mound-top distribution of lipid raft markers or lipid rafts provides spatial advantage for lipid rafts or contact molecules interacting readily with neighboring cells or free molecules

Legumes as food ingredient: characterization, processing, and applications

Editores: Jiménez-López, José Carlos (CSIC); Clemente, Alfonso (CSIC

Complement Receptor 1 Is a Sialic Acid-Independent Erythrocyte Receptor of Plasmodium falciparum

Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1-coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine

Nanoparticles for Applications in Cellular Imaging

In the following review we discuss several types of nanoparticles (such as TiO2, quantum dots, and gold nanoparticles) and their impact on the ability to image biological components in fixed cells. The review also discusses factors influencing nanoparticle imaging and uptake in live cells in vitro. Due to their unique size-dependent properties nanoparticles offer numerous advantages over traditional dyes and proteins. For example, the photostability, narrow emission peak, and ability to rationally modify both the size and surface chemistry of Quantum Dots allow for simultaneous analyses of multiple targets within the same cell. On the other hand, the surface characteristics of nanometer sized TiO2allow efficient conjugation to nucleic acids which enables their retention in specific subcellular compartments. We discuss cellular uptake mechanisms for the internalization of nanoparticles and studies showing the influence of nanoparticle size and charge and the cell type targeted on nanoparticle uptake. The predominant nanoparticle uptake mechanisms include clathrin-dependent mechanisms, macropinocytosis, and phagocytosis

Benchmark numerical simulations of rarefied non-reacting gas flows using an open-source DSMC code

Validation and verification represent an important element in the development of a computational code. The aim is establish both confidence in the algorithm and its suitability for the intended purpose. In this paper, a direct simulation Monte Carlo solver, called dsmcFoam, is carefully investigated for its ability to solve low and high speed non-reacting gas flows in simple and complex geometries. The test cases are: flow over sharp and truncated flat plates, the Mars Pathfinder probe, a micro-channel with heated internal steps, and a simple micro-channel. For all the cases investigated, dsmcFoam demonstrates very good agreement with experimental and numerical data available in the literature