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Acute Alveolar Injury: Experimental Models
Published in Joan Gil, Models of Lung Disease, 2020
The possibility that neutrophils are involved in the pathogenesis of AAI began to attract serious attention with the observation that transient marked neutropenia consistently occurs in patients during hemodialysis and that decreased pulmonary diffusing capacity and mild hypoxemia occur in some of them. This effect was shown to depend upon activation of complement via the alternative pathway when plasma comes into contact with the cellophane dialyzer membrane. Animal experiments in which complement was activated by exposure of plasma to dialyzer membranes demonstrated that the neutropenia which developed was due to sequestration of neutrophils in small vessels of the lung (Craddock et al., 1977a, 1977b). A similar chain of events also occurs in patients during nylon fiber leukaphoresis, a method used to separate neutrophils from blood for donation to neutropenic patients (Hammerschmidt et al., 1978). In this procedure, as in hemodialysis, plasma is exposed to a foreign polymeric surface and activation of complement, as well as sequestration of neutrophils in the vessels of the lung, occurs (Nusbacher et al., 1978). Some patients experience transient mild pulmonary dysfunction during leukaphoresis. Gel filtration, ultrafiltration, and antiserum inhibition studies have demonstrated that C5A is the complement fragment responsible for the leukostasis in the lung under these circumstances (Nusbacher et al., 1978). These observations in humans, together with the animal experiments to which they led, have suggested not only that neutrophils may cause acute lung dysfunction but that systemic activation of complement may initiate the pulmonary leukoaggregation.
Phototherapy Using Nanomaterials
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
A. N. Resmi, V. Nair Resmi, C. R. Rekha, V. Nair Lakshmi, Shaiju S. Nazeer, Ramapurath S. Jayasree
Biodegradable nanoparticles are made from polymers that degrade after PS release. Biodegradable polymer-based nanoparticles have gained a lot of attention because of their advantages in regulating drug release, flexibility in processes of material processing, less toxicity, and high drug loading [167]. The polymeric surface properties, morphologies, and structure can be designed to achieve the desired biocompatibility, regulate rate of degradation, and kinetics of drug release. Also, polymer’s chemical composition and structure can be adapted to fit photosensitizers with varying degrees of hydrophobicity, molecular weight, charge, and pH. Synthetic polymers, such as aliphatic polylactide (PLA), polyglycolide (PGA), and their copolymer polymer poly(d,l-lactide-co-glycolide) (PLGA), are also used as drug delivery carriers because of their favorable properties such as strong biocompatibility, biodegradability, bioresorbability, and mechanical power [168, 169]. For example, a photosensitizer meso-tetra(hydroxyphenyl)porphyrin (p-THPP) was encapsulated with submicronic nanoparticles of poly(d,l-lactide-co-glycolide) (50:50 and 75:25 PLGA) and poly(d,l-lactide) (PLA) with drug loading of up to 7% (m/m) using emulsification-diffusion technique. The photodynamic activity was evaluated on EMT-6 mammary tumor cells as compared to free p-THPP. Irrespective of the nature of the delivery system, the cell viability of the drug was concentration dependent. The photo induced cytotoxicity of the dye was strongly affected by the PDT parameters, such as drug concentration, light dose, drug–light time interval, and copolymer molar ratio. It was observed that the copolymer molar ratios influence the rate of carrier uptake and consequently, the intracellular drug concentration [169].
Biomedical Fourier Transform Infrared Spectroscopy: Applications To Proteins
Published in R. Michael Gendreau, Spectroscopy in the Biomedical Sciences, 1986
Figure 3 shows the current flow cell used for aqueous ATR experimentation at the National Center for Biomedical Infrared Spectroscopy. This cell design is similar to previous designs that we and others have used, and it represents a compromise between optimal spectral performance and reasonable hydrodynamic flow conditions within the cell. This particular cell design is intended for studies of macromolecules; studies for which this cell was designed include enzyme interactions with substrates or inhibitors and protein deposition to surfaces. Biocompatibility studies in which whole blood is allowed to interact with polymeric surfaces coated onto the crystal have been one of the primary applications. This cell has several attractive features. It is a narrow-gap flow cell. The total height of the flow chamber is roughly 0.8 mm, allowing shear rates in the neighborhood of 500 to 700 sec-1 for volumetric flow rates in the neighborhood of 75 ml/min. The cell is relatively long with a narrowed aspect so that laminar-type flow rapidly develops inside the cell, and only the first 10 to 20% of the entrance region experiences turbulent flow conditions. The ATR crystal is 105 × 10 × 2 mm, and only one of the two available surfaces is utilized. Polymers of interest can be deposited on the active surface or the crystal can be precoated with other materials to study surface interactions. Flowing substrates or products are pumped into the cell to react or adsorb onto the coated or uncoated ATR crystal surface. The crystals themselves are germanium, 45° degree ATR crystals, designed to provide approximately 50 reflections while still allowing an energy throughout in the range of 10 to 15%. The cell is further designed to mount on a pair of guidebars which allow the cell to slide back and forth inside a focusing accessory. This provides for experiments in a dual channel configuration in which one channel can be used as a control for experiments performed in the other channel, or two separate experiments can be conducted simultaneously. This cell is the basis for the majority of the surface protein adsorption, biocompatibility, and enzyme-antigen denaturation and substrate studies that our group has carried out over the last 5 years. Related cells are in use at the Universities of Wisconsin and Utah, and a similar cell has been used for fluorescence studies at Stanford, Michigan, and Utah, and is discussed elsewhere in this volume.9
Implantable drug delivery systems for the treatment of osteomyelitis
Published in Drug Development and Industrial Pharmacy, 2022
Megan Smith, Matthew Roberts, Raida Al-Kassas
To conclude, antibiotic loaded biomaterials are a promising future for the treatment of OM infections. They have many advantages over conventional treatment methods and can be easily modified to treat various applications. They have proven to be just as good or in some cases superior to non-biodegradable PMMA beads with the added advantage of not requiring a second surgery removal. Biodegradable polymers are considered the most advantageous biomaterial, composite materials of both natural and synthetic polymers provide both the excellent biocompatibility and mechanical strength required. Various types of implants for bone infection have been designed and discussed in this review. Scaffold implants are the most explored fabricated implant. Their porous structure provides an ideal framework for the incorporation of drugs for the treatment of osteomyelitis whilst also allowing the flow of nutrients essential for bone tissue regeneration. Biodegradable polymeric surface coatings offer the advantage of enhanced biocompatibility and biofilm prevention whilst also providing excellent mechanical strength from the steel implant which pure polymer implants would not provide. More recently, research into silica incorporated nanoparticles has been explored due to their benefits in modulating the drug release rate as well their size and flexibility to be molded into any desired shape. Many alternative treatment methods for OM have been explored but most new techniques are yet to reach clinical trials.
Anti-biofouling properties of poly(dimethyl siloxane) with RAFT photopolymerized acrylate/methacrylate surface grafts against model marine organisms
Published in Biofouling, 2021
Cary A. Kuliasha, Rebecca L. Fedderwitz, Shane J. Stafslien, John A. Finlay, Anthony S. Clare, Anthony B. Brennan
Engineering surface properties using polymeric grafts provides a way to address many of these concerns while offering new insights into the biofouling problem (Krishnan et al. 2008). The ability to test different surface chemistries using grafts of targeted molecular weight, thickness, roughness, and wettability offers an exciting opportunity to identify effective ABF surfaces using a multifaceted approach. Previous work by the authors focused on modifying poly(dimethyl siloxane) elastomers (PDMSe), a common low surface free energy (SFE) FR coating material, with engineered polymeric surface grafts (Kuliasha et al. 2017; 2018; 2020). Amphiphilic poly(co-acrylate) grafts composed of methyl acrylate, acrylic acid (AAc), and acrylamide (AAm) were demonstrated effective at inhibiting biofouling of two common marine microalgae (Kuliasha et al. 2017). However, additional marine organisms (e.g. barnacles and bacteria) were not tested, and the fabrication strategy employed resulted in low-density graft layers whose graft molecular weights and surface properties were not controlled adequately.
Multidrug-resistant Candida auris: an epidemiological review
Published in Expert Review of Anti-infective Therapy, 2020
Arunaloke Chakrabarti, Shreya Singh
Variable biofilm forming ability has been reported in different strains of C. auris. Studying the draft genome of C. auris revealed the presence of various proteins involved in biofilms formation, in addition to descriptions of aggregative and non-aggregative phenotypes [39]. The isolates, which fail to release daughter cells produce large aggregates that are difficult to physically disrupt. However, aggregating isolates demonstrate less pathogenicity than their non aggregating counterparts in-vivo [39]. Biofilm formation may help the organism to persist longer in the environment. A study by Sherry et al revealed differential adherence of C. auris to polymeric surfaces with biofilm formation associated with resistance to drugs with known activity against the planktonic yeast forms [40]. Importantly, caspofungin was inactive against C. auris biofilms and thus, biofilms not only contribute to environmental survival but also enhanced virulence and antifungal resistance. In a study describing the transcriptomic profile of temporally developing biofilms of C. auris, it was seen that antifungal class and phase (planktonic versus biofilm) determined the resistance profiles [41]. Upregulation of the glycosylphosphatidylinositol (GPI)-anchored, adhesion related cell wall genes was seen in all phases of biofilm formation but specific upregulation of efflux pumps (ABC and MFS transporter genes) was present in mature biofilms. In a recent study, investigating the mechanisms used by C. auris to evade antifungal activity in biofilms, extracellular matrix (ECM) sequesters were found to contribute 70% of antifungal resistance [42]. High content of mannan-glucan polysaccharide were also seen in ECM with elevated expression of glucan modifying genes which was also reported previously by Kean et al [41,42]. Apart from antifungal resistance, the analysis of a complex biofilms model in a panel of clinical C. auris isolates demonstrated reduced susceptibility to disinfectants- chlorhexidine and hydrogen peroxide, with evidence of complete eradication only on using povidone iodine [43].