Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents ...with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems.
The potential of exogenous ethylene and sulfur (S) in reversal of cadmium (Cd)-inhibited photosynthetic and growth responses in mustard (
L. cv. Pusa Jai Kisan) were studied. Plants grown with 50 μM ...Cd showed increased superoxide and H
O
accumulation and lipid peroxidation together with increased activity of 1-aminocyclopropane carboxylic acid synthase (ACS) and ethylene production and inhibition of photosynthesis and growth. Application of 1 mM SO
or 200 μL L
ethephon (ethylene source) influenced photosynthetic and growth performance equally in presence or absence of Cd. However, their combined application synergistically improved photosynthetic performance more in presence of Cd and reduced oxidative stress (lower superoxide and H
O
accumulation) by decreasing ethylene and glucose sensitivity with the increase in cysteine and methionineand a non-proteinogenic thiol (reduced glutathione; GSH) contents. The central role of ethylene in potentiating S-mediated reversal of Cd-induced oxidative stress was evident with the use of ethylene action inhibitor, norbornadiene (NBD). The application of NBD resulted in decreased thiol production and photosynthetic responses. This suggests that ethylene promotes the effects of S in reversal of adverse effects of Cd, and thus, ethylene modulation may be considered as potential tool to substantiate the S effects in reversal of Cd inhibited photosynthesis and growth in mustard.
Photoacoustic imaging is an emerging imaging modality that is based upon the photoacoustic effect. In photoacoustic tomography (PAT), the induced acoustic pressure waves are measured by an array of ...detectors and used to reconstruct an image of the initial pressure distribution. A common challenge faced in PAT is that the measured acoustic waves can only be sparsely sampled. Reconstructing sparsely sampled data using standard methods results in severe artifacts that obscure information within the image. We propose a modified convolutional neural network (CNN) architecture termed fully dense UNet (FD-UNet) for removing artifacts from two-dimensional PAT images reconstructed from sparse data and compare the proposed CNN with the standard UNet in terms of reconstructed image quality.
Fuel cells represent a clean alternative to current technologies for utilizing hydrocarbon fuel resources. Polymer electrolyte membrane fuel cells (PEMFCs) have acquired due importance as they are ...best suited for applications where a quick start up is required such as in automobiles. The prime requirements of fuel cell membranes are high proton conductivity, low methanol/water permeability, good mechanical and thermal stability and moderate price. Membranes and the operating parameters together have a profound influence on performance of PEMFCs. Perfluorinated ionomers, hydrocarbon and aromatic polymers and acid–base complexes have been described in the review. The performance of this special class of polymers, considering their structure–property relationship and the current research involving their applicability in fuel cell systems are presented. Modifications made to Nafion
® membranes, the conceptual design of substitutes for perfluorosulfonic acid materials and modifications made to aromatic membranes to render them suitable for this application have been summarized. Promising avenues for further research in this area have been identified.
Aims
The aim of this study is to investigate the antibacterial activity of aluminium oxide nanoparticles (Al2O3 NPs) against multidrug‐resistant clinical isolates of Escherichia coli and their ...interaction with cell envelope biomolecules.
Methods and Results
Al2O3 NPs were characterized by scanning electron microscope (SEM), high‐resolution transmission electron microscope (HR‐TEM) and X‐ray diffraction (XRD) analyses. Antibacterial activity and interaction of Al2O3 NPs with E. coli and its surface biomolecules were assessed by spectrophotometry, SEM, HR‐TEM and attenuated total reflectance/Fourier transform infrared (ATR‐FTIR). Of the 80 isolates tested, about 64 (80%) were found to be extended spectrum β‐lactamase (ESBL) positive and 16 (20%) were non‐ESBL producers. Al2O3 NPs at 1000 μg ml−1 significantly inhibited the bacterial growth. SEM and HR‐TEM analyses revealed the attachment of NPs to the surface of cell membrane and also their presence inside the cells due to formation of irregular‐shaped pits and perforation on the surfaces of bacterial cells. The intracellular Al2O3 NPs might have interacted with cellular biomolecules and caused adverse effects eventually triggering the cell death. ATR‐FTIR studies suggested the interaction of lipopolysaccharide (LPS) and L‐α‐Phosphatidyl‐ethanolamine (PE) with Al2O3 NPs. Infrared (IR) spectral changes revealed that the LPS could bind to Al2O3 NPs through hydrogen binding and ligand exchange. The Al2O3 NPs‐induced structural changes in phospholipids may lead to the loss of amphiphilic properties, destruction of the membrane and cell leaking.
Conclusions
The penetration and accumulation of NPs inside the bacterial cell cause pit formation, perforation and disorganization and thus drastically disturb its proper function. The cell surface biomolecular changes revealed by ATR‐FTIR spectra provide a better understanding of the cytotoxicity of Al2O3 NPs.
Significance and Impact of the Study
Al2O3 NPs may serve as broad‐spectrum bactericidal agents to control the emergent pathogens regardless of their drug‐resistance mechanisms.
The phagocyte NADPH oxidase generates superoxide anion and downstream reactive oxidant intermediates in response to infectious threat, and is a critical mediator of antimicrobial host defense and ...inflammatory responses. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that are recruited by cancer cells, accumulate locally and systemically in advanced cancer, and can abrogate anti-tumor immunity. Prior studies have implicated the phagocyte NADPH oxidase as being an important component promoting MDSC accumulation and immunosuppression in cancer. We therefore used engineered NADPH oxidase-deficient (p47 (phox-/-)) mice to delineate the role of this enzyme complex in MDSC accumulation and function in a syngeneic mouse model of epithelial ovarian cancer. We found that the presence of NADPH oxidase did not affect tumor progression. The accumulation of MDSCs locally and systemically was similar in tumor-bearing wild-type (WT) and p47 (phox-/-) mice. Although MDSCs from tumor-bearing WT mice had functional NADPH oxidase, the suppressive effect of MDSCs on ex vivo stimulated T cell proliferation was NADPH oxidase-independent. In contrast to other tumor-bearing mouse models, our results show that MDSC accumulation and immunosuppression in syngeneic epithelial ovarian cancer is NADPH oxidase-independent. We speculate that factors inherent to the tumor, tumor microenvironment, or both determine the specific requirement for NADPH oxidase in MDSC accumulation and function.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary ...analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow-up is presented. After 19.4 (range: 0 to 27.7) months of median follow-up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; hazard ratio, 0.31; 95% confidence interval, 0.24-0.39; P <0.0001) and improved the overall response rate (83.8% versus 63.2%; P <0.0001) compared with bortezomib and dexamethasone alone. The progression-free survival benefit of daratumumab plus bortezomib and dexamethasone was most apparent in patients with 1 prior line of therapy (median: not reached versus 7.9 months; hazard ratio, 0.19; 95% confidence interval, 0.12-0.29; P <0.0001). Daratumumab plus bortezomib and dexamethasone was also superior to bortezomib and dexamethasone alone in subgroups based on prior treatment exposure (bortezomib, thalidomide, or lenalidomide), lenalidomide-refractory status, time since last therapy (≤12, >12, ≤6, or >6 months), or cytogenetic risk. Minimal residual disease-negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow-up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse.
clinicaltrials.gov identifier: NCT02136134.
Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT ...is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies.
This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006-December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm -61.26 g (±SE 24.12, P < 0.01), preterm -232.90 g (±SE 17.24, P < .001), near term -171.50 g (±SE 17.52, P < .001), and at term -101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm -61.54 g (±SE 28.62, P < .03), preterm -222.78 g (±SE 19.64, P < .001), near term -159.25 g (±SE 19.14, P < .001), and at term -91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: -220.18 g (±SE 21.43, P < .001), -140.68 g (±SE 23.09, P < .001), and -89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested.
In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: Different approaches have been used for preventing biofilm-related infections in health care settings. Many of these methods have their own de-merits, which include chemical-based ...complications; emergent antibiotic resistant strains, etc. The formation of biofilm is the hallmark characteristic of Staphylococcus aureus and S. epidermidis infection, which consists of multiple layers of bacteria encased within an exopolysachharide glycocalyx. Nanotechnology may provide the answer to penetrate such biofilms and reduce biofilm formation. Therefore, the aim of present study was to demonstrate the biofilm formation by methicillin resistance S. aureus (MRSA) and methicillin resistance S. epidermidis (MRSE) isolated from wounds by direct visualisation applying tissue culture plate, tube and Congo Red Agar methods. Materials and Methods: The anti-biofilm activity of AgNPs was investigated by Congo Red, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) techniques. Results: The minimum inhibitory concentration (MIC) was found to be in the range of 11.25-45 μg/ml. The AgNPs coated surfaces effectively restricted biofilm formation of the tested bacteria. Double fluorescent staining (propidium iodide staining to detect bacterial cells and fluorescein isothiocyanate concanavalin A (Con A-FITC) staining to detect the exopolysachharides matrix) technique using CLSM provides the visual evidence that AgNPs arrested the bacterial growth and prevent the glycocalyx formation. In our study, we could demonstrate the complete anti-biofilm activity AgNPs at a concentration as low as 50 μg/ml. Conclusions: Our findings suggested that AgNPs can be exploited towards the development of potential anti-bacterial coatings for various biomedical and environmental applications. In the near future, the AgNPs may play major role in the coating of medical devices and treatment of infections caused due to highly antibiotic resistant biofilm.
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