Of huge importance now is to provide a fast, cost-effective, safe, and immediately available pharmaceutical solution to curb the rapid global spread of SARS-CoV-2. Recent publications on SARS-CoV-2 have brought attention to the possible benefit of chloroquine in the treatment of patients infected by SARS-CoV-2. Whether chloroquine can treat SARS-CoV-2 alone and also work as a prophylactic is doubtful. An effective prophylactic medication to prevent viral entry has to contain, at least, either a protease inhibitor or a competitive virus ACE2-binding inhibitor. Using bromhexine at a dosage that selectively inhibits TMPRSS2 and, in so doing, inhibits TMPRSS2-specific viral entry is likely to be effective against SARS-CoV-2. We propose the use of bromhexine as a prophylactic and treatment. We encourage the scientific community to assess bromhexine clinically as a prophylactic and curative treatment. If proven to be effective, this would allow a rapid, accessible, and cost-effective application worldwide.

In vitro studies have shown that human osteoclasts can corrode stainless steel and titanium leading to the production of metal ions responsible for inflammatory reactions. Moreover, traces of cellular activities on metal orthopaedic explants have recently been reported as inflammatory cell-induced (ICI) corrosion being the result of the cells sealing on the metal surfaces and releasing reactive oxygen species (ROS) through Fenton-like reactions. The extent and clinical relevance of this phenomenon has yet to be understood. We analysed a cohort of 100 CoCr alloy hips collected at our retrieval centre; we performed macroscopic and microscopic screening and used statistical analysis to correlate our findings with implant and clinical variables. We found that 59% of our implants had evidence of surface damage consistent with what has previously been described as cell-induced corrosion. There was a significant association between the patterns and aseptic loosening for the ASR modular (r = -0.488, p = 0.016) and the Durom modular (r = 0.454, p = 0.026). This is the largest implant retrieval study to examine the phenomena of so-called ICI corrosion and is the first to investigate its clinical relevance. We recommend further work to determine the role of cells in the damage patterns observed. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 155-164, 2017.

The ability of mesenchymal stromal cells (MSCs) to differentiate into adipocytes provides a cellular model of human origin to study adipogenesis in vitro. One of the major challenges in studying adipogenesis is the lack of tools to identify and monitor the differentiation of various subpopulations within the heterogeneous pool of MSCs. Cluster of differentiation (CD)36 plays an important role in the formation of intracellular lipid droplets, a key characteristic of adipocyte differentiation/maturation. The objective of this study was to develop a reproducible quantitative method to study adipocyte differentiation by comparing two lipophilic dyes [Nile Red (NR) and Bodipy 493/503] in combination with CD36 surface marker staining. We identified a subpopulation of adipose-derived stromal cells that express CD36 at intermediate/high levels and show that combining CD36 cell surface staining with neutral lipid-specific staining allows us to monitor differentiation of adipose-derived stromal cells that express CD36intermediate/high during adipocyte differentiation in vitro. The gradual increase of CD36intermediate/high/NRpositive cells during the 21 day adipogenesis induction period correlated with upregulation of adipogenesis-associated gene expression.

Interest in reactive oxygen species and adipocyte differentiation/adipose tissue function is steadily increasing. This is due in part to a search for alternative avenues for combating obesity, which results from the excess accumulation of adipose tissue. Obesity is a major risk factor for complex disorders such as cancer, type 2 diabetes, and cardiovascular diseases. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is often used as a model for studying adipogenesis in vitro. A key focus is the effect of both intra- and extracellular reactive oxygen species (ROS) on adipogenesis. The consensus from the majority of studies is that ROS, irrespective of the source, promote adipogenesis.The effect of ROS on adipogenesis is suppressed by antioxidants or ROS scavengers. Reactive oxygen species are generated during the process of adipocyte differentiation as well as by other cell metabolic processes. Despite many studies in this field, it is still not possible to state with certainty whether ROS measured during adipocyte differentiation are a cause or consequence of this process. In addition, it is still unclear what the exact sources are of the ROS that initiate and/or drive adipogenic differentiation in MSCs in vivo. This review provides an overview of our understanding of the role of ROS in adipocyte differentiation as well as how certain ROS scavengers and antioxidants might affect this process.

Coatings have been applied to all surfaces of hip implants with the majority performing well in the laboratory, but there are few reports of their performance in humans. The rationale for coating the metal-on-metal bearing surfaces includes a reduction in metal ion release and risk of adverse reaction to metal debris; yet there are no reports of retrieved coated metal-on-metal hip implants despite the concern that they may delaminate. The aim of this study was to better understand the performance of coated hip implants in humans through findings of three coated metal-on-metal hip resurfacings, retrieved after failure for unexplained pain. Analysis of these implants included quantification of the amount and mechanism of coating loss which was correlated with clinical, imaging and blood data. In all cases, there were large areas of complete coating loss in which the metal substrate was exposed and found to be rougher than the coated areas. The coating loss gave rise to third body abrasive wear of the coating and the exposed metal, the latter of which led to high blood levels of cobalt and chromium. Coating of the bearing surfaces of metal-on-metal hip resurfacings, therefore, do not prevent metal ion release when implanted into humans. This is an example of a need for increased retrieval analysis of newly introduced implants and expansion of laboratory testing regulations to better reflect the clinical environment.

In this study we found evidence of coating loss on metal femoral heads which was associated with increased wear of the corresponding polyethylene acetabular cups.

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Hypersensitivity reactions in patients receiving metal-on-metal hip replacements have been attributed to corrosion products as observed by elevated cobalt and chromium ions in the blood. Although the majority of cases are reported in metal-on-metal, incidences of these reactions have been reported in the metal-on-polyethylene patient population. To date, no in vitro study has considered cobalt release for this bearing combination. This study considered four 28 mm and seven 52 mm diameter metal-on-polyethylene bearings tested following ISO standard hip simulator conditions as well as under established abrasive conditions. These tests showed measurable cobalt in all bearings under standard conditions. Cobalt release, as well as polyethylene wear, increased with diameter, increasing from 52 to 255 ppb. The introduction of bone cement particles into the articulation doubled polyethylene wear and cobalt release while alumina particles produced significant damage on the heads demonstrated by cobalt levels of 70,700 ppb and an increased polyethylene wear from a mean value of 9–160 mm3/mc. Cobalt release was indicative of head damage and correlated with polyethylene wear at the next gravimetric interval. The removal of third body particles resulted in continued elevated cobalt levels in the 52 mm diameter bearings tested with alumina compared to standard conditions but the bearings tested with bone cement particles returned to standard levels. The polyethylene wear in the bone cement tested bearings also recovered to standard levels, although the alumina tested bearings continued to wear at a higher rate of 475 mm3/mc. Cobalt release was shown to occur in metal-on-polyethylene bearings indicating damage to the metal head resulting in increased polyethylene wear. While large diameter metal-on-polyethylene bearings may provide an increased range of motion and a reduced dislocation risk, increased levels of cobalt are likely to be released and this needs to be fully considered before being widely adopted.