Development of spray-dried N-acetylcysteine dry powder for inhalation.

N-acetylcysteine (NAC) has both antioxidant and immunomodulatory activities and has been used as adjuvant therapy in several viral infections. Recently, NAC attracted attention for its possible role in reducing the affinity of the spike protein receptor binding domain to angiotensin-converting enzyme (ACE2) receptors. Since only NAC solutions are available for inhalation, the purpose of the work was to develop a NAC dry powder for inhalation using mannitol or leucine as excipient. The powder was successfully produced using co-spray-drying with leucine. ATR-FTIR analyses evidenced spectral variations ascribed to the formation of specific interactions between NAC and leucine. This effect on the NAC environment was not evident for NAC-mannitol powders, but mannitol was in a different polymorphic form compared to the supplied material. Both the feedstock concentration and the leucine content have an impact on the powder aerodynamic features. In particular, to maximize the respirable fraction, it is preferable to produce the powder starting from a 0.5 % w/v feedstock solution using 33 to 50 % w/w leucine content. The NAC-leucine powder was stable for ten months maintaining NAC content of 50 % (w/w) and about 200 µg of NAC was able to deposit on a transwell insert, useful for future in vitro studies.

A perspective on iron (Fe) in the atmosphere: air quality, climate, and the ocean.

As scientists engage in research motivated by climate change and the impacts of pollution on air, water, and human health, we increasingly recognize the need for the scientific community to improve communication and knowledge exchange across disciplines to address pressing and outstanding research questions holistically. Our professional paths have crossed because our research activities focus on the chemical reactivity of Fe-containing minerals in air and water, and at the air-sea interface. (Photo)chemical reactions driven by Fe can take place at the surface of the particles/droplets or within the condensed phase. The extent and rates of these reactions are influenced by water content and biogeochemical activity ubiquitous in these systems. One of these reactions is the production of reactive oxygen species (ROS) that cause damage to respiratory organs. Another is that the reactivity of Fe and organics in aerosol particles alter surficial physicochemical properties that impact aerosol-radiation and aerosol-cloud interactions. Also, upon deposition, aerosol particles influence ocean biogeochemical processes because micronutrients such as Fe or toxic elements such as copper become bioavailable. We provide a perspective on these topics and future research directions on the reactivity of Fe in atmospheric aerosol systems, from sources to short- and long-term impacts at the sinks with emphasis on needs to enhance the predictive power of atmospheric and ocean models.

[Distribution of surface components in spray-dried powder of binary system of berberine hydrochloride and dextran based on hydrodynamic size].

The present study explored the correlation between the hydrodynamic size(i.e., hydrated particle size) and the surface component distribution of spray-dried powder based on the binary system model of berberine hydrochloride and dextran. A variety of mixture solutions containing substances of different proportions were prepared, and the hydrated particle sizes of the solutions were measured by laser light scattering technique. Then the effects of molecular weight and mixing proportion on the particle size were analyzed. After the solutions were spray-dried, the surface components of spray-dried powder were determined by X-ray photoelectron spectroscopy. The changes of hydrated particle size of the two substances in different solutions were measured with the altered solution environments, and the distribution of surface components after spray-drying was observed. The results of particle size measurement showed that different solution environments would change the hydrodynamic size of substances. Specifically, the particle size of berberine hydrochloride increased with the increase in ionic strength and solution pH, while the particle size of dextran decreased with the increase in ionic strength and increased with the increase in solution pH. The results of surface components of the spray-dried powder indicated that berberine hydrochloride was prone to accumulate on the surface of particles during spray-drying because of its large hydrodynamic size. Therefore, hydrodynamic size is considered an important factor affecting the surface component distribution of spray-dried powder. As revealed by scanning electron microscopy of the particle morphology of spray-dried powder, the particles of berberine hydrochloride spray-dried powder were irregularly elliptic, and the particles of dextran and mixture spray-dried powders were irregularly spherical with the shrunken surface. Finally, the FT4 powder rheometer and DVS instrument were used to determine the stability, adhesion, and hygroscopicity of the powder. The results showed that when berberine hydrochloride was enriched on the surface, the adhesion of the mixture increased and the fluidity became worse, but the hygroscopicity was improved to a certain extent. In addition, as found by hygroscopic kinetic curve fitting of spray-dried powder, the hygroscopic behaviors of all spray-dried powder conformed to the double exponential function.

Optimization of Particle Properties of Nanocrystalline Solid Dispersion Based Dry Powder for Inhalation of Voriconazole.

A one-step spray drying based process was employed to generate ready-to-use nanocrystalline solid dispersion (NCSD) dry powder for inhalation (DPI) of voriconazole (VRC). The solid dispersion was prepared by spray drying VRC, MAN (mannitol) and soya lecithin (LEC) from mixture of methanol-water. Various formulation and process related parameters were screened, including LEC, inlet temperature, total solid content and feed flow rate to generate particles of geometric size ≤5 µm. Aerosil® 200 was explored as the quaternary excipient either during spray drying or by physically mixing with the optimized ternary NCSD. The powders were extensively characterized for solid form, primary particle size, assay, embedded nanocrystal size, morphology, porosity, density and moisture content. Aerodynamic properties were studied using next generation impactor (NGI), while surface elemental composition and topography were investigated using SEM-EDS (scanning electron microscopy- energy dispersive spectroscopy) and AFM (atomic force microscopy), respectively. At selected inlet temperature of 120 ˚C, total solid content and feed flow rate significantly impacted the size of primary NCSD particles. Size of primary particles increased with increase in total solid content and feed flow rate of the solution. VRC nanocrystals were obtained in polymorphic Form B whereas the matrix of MAN consisted of mixture of polymorphic Forms α, ß and δ. SEM-EDS analysis confirmed deposition of Aerosil® 200 on surface of spray dried particles. In addition to increased porosity and reduced density, increase in surface roughness of particles (evident from AFM topographic analysis) contributed to enhanced powder deposition at stages 3 and 4 in NGI. In comparison, physical blending of NCSD with Aerosil® 200 showed improvement in aerosolization due to flow enhancement property.

Amino acids improve aerosolization and chemical stability of potential inhalable amorphous Spray-dried ceftazidime for Pseudomonas aeruginosa lung infection.

Pseudomonas aeruginosa infection is common in cystic fibrosis as well as non-cystic fibrosis bronchiectasis. The pathogen presents challenges for treatment due to its adaptive antibiotic-resistance, mainly pertaining to its biofilm-forming ability, as well as limitations associated with conventional drug delivery in achieving desired therapeutic concentration in the infection site. Hence, therapeutic approach has shifted towards the inhalation of antibiotics. Ceftazidime is a potent antibiotic against the pathogen; however, it is currently only available as a parenteral formulation. Here, spray dryer was employed to generate inhalable high dose ceftazidime microparticles. In addition, the use of amino acids (valine, leucine, methionine, phenylalanine, and tryptophan) to improve aerosolization as well as chemical stability of amorphous ceftazidime was explored. The particles were characterized using X-ray diffraction, infrared (IR) spectroscopy, calorimetry, electron microscopy, particle size analyzer, and next generation impactor. The chemical stability at 25 °C/<15% was assessed using chromatography. All co-spray dried formulations were confirmed as monophasic amorphous systems using calorimetry. In addition, principal component analysis of the IR spectra suggested potential interaction between tryptophan and ceftazidime in the co-amorphous matrix. Inclusion of amino acids improved aerosolization and chemical stability in all cases. Increase in surface asperity was clear with the use of amino acids which likely contributed to the improved aerosol performance, and potential interaction between amino acids and ceftazidime was plausibly the reason for improved chemical stability. Leucine offered the best aerosolization enhancement with a fine particle fraction of 78% and tryptophan showed stabilizing superiority by reducing chemical degradation by 51% over 10 weeks in 1:1 M ratio. The protection against ceftazidime degradation varied with the nature of amino acids. Additionally, there was a linear relationship between degradation protection and molar mass of amino acids or percentage weight of amino acids in the formulations. None of the amino acids were successful in completely inhibiting degradation of ceftazidime in amorphous spray-dried powder to prepare a commercially viable product with desired shelf-life. All the amino acids and ceftazidime were non-toxic to A549 alveolar cell line.

High dose nanocrystalline solid dispersion powder of voriconazole for inhalation.

In the current work, we aimed to deliver high dose of voriconazole (VRC) to lung through dry powder for inhalation (DPIs). Furthermore, the research tested the hypothesis that drug nanocrystals can escape the clearance mechanisms in lung by virtue of their size and rapid dissolution. High dose nanocrystalline solid dispersion (NCSD) based DPI of VRC was prepared using a novel spray drying process. Mannitol (MAN) and soya lecithin (LEC) were used as crystallization inducer and stabilizer, respectively. The powders were characterized for physicochemical and aerodynamic properties. Chemical interactions contributing to generation and stabilization of VRC nanocrystals in the matrix of MAN were established using computational studies. Performance of NCSD (VRC-N) was compared with microcrystalline solid dispersion (VRC-M) in terms of dissolution, uptake in A549 and RAW 264.7 cells. Plasma and lung distribution of VRC-N and VRC-M in Balb/c mice upon insufflation was compared with the intravenous product. In VRC-N, drug nanocrystals of size 645.86 ± 56.90 nm were successfully produced at VRC loading of 45%. MAN created physical barrier to crystal growth by interacting with N- of triazole and F- of pyrimidine ring of VRC. An increase in drug loading to 60% produced VRC crystals of size 4800 ± 200 nm (VRC-M). The optimized powders were crystalline and showed deposition at stage 2 and 3 in NGI. In comparison to VRC-M, more than 80% of VRC-N dissolved rapidly in around 5-10 mins, therefore, showed higher and lower drug uptake into A549 and RAW 264.7 cells, respectively. In contrast to intravenous product, insufflation of VRC-N and VRC-M led to higher drug concentrations in lung in comparison to plasma. VRC-N showed higher lung AUC0-24 due to escape of macrophage clearance.

Cannabis Vaping: Existing and Emerging Modalities, Chemistry, and Pulmonary Toxicology.

The outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) has been cause for concern to the medical community, particularly given that this novel illness has coincided with the COVID-19 pandemic, another cause of severe pulmonary illness. Though cannabis e-cigarettes tainted with vitamin E acetate were primarily associated with EVALI, acute lung injuries stemming from cannabis inhalation were reported in the literature prior to 2019, and it has been suggested that cannabis components or additives other than vitamin E acetate may be responsible. Despite these concerning issues, novel cannabis vaporizer ingredients continue to arise, such as Δ8-tetrahydrocannabinol, Δ10-tetrahydrocannabinol, hexahydrocannabinol, and cannabichromene. In order to address cannabis e-cigarette safety and vaping in an effective manner, we provide a comprehensive knowledge of the latest products, delivery modes, and ingredients. This perspective highlights the types of cannabis vaping modalities common to the United States cannabis market, with special attention to cartridge-type cannabis e-cigarette toxicology and their involvement in the EVALI outbreak, in particular, acute lung injurious responses. Novel ingredient chemistry, origins, and legal statuses are reviewed, as well as the toxicology of known cannabis e-cigarette aerosol components.

Clustering approach for the analysis of the fluorescent bioaerosol collected by an automatic detector.

Automatically operating particle detection devices generate valuable data, but their use in routine aerobiology needs to be harmonized. The growing network of researchers using automatic pollen detectors has the challenge to develop new data processing systems, best suited for identification of pollen or spore from bioaerosol data obtained near-real-time. It is challenging to recognise all the particles in the atmospheric bioaerosol due to their diversity. In this study, we aimed to find the natural groupings of pollen data by using cluster analysis, with the intent to use these groupings for further interpretation of real-time bioaerosol measurements. The scattering and fluorescence data belonging to 29 types of pollen and spores were first acquired in the laboratory using Rapid-E automatic particle detector. Neural networks were used for primary data processing, and the resulting feature vectors were clustered for scattering and fluorescence modality. Scattering clusters results showed that pollen of the same plant taxa associates with the different clusters corresponding to particle shape and size properties. According to fluorescence clusters, pollen grouping highlighted the possibility to differentiate Dactylis and Secale genera in the Poaceae family. Fluorescent clusters played a more important role than scattering for separating unidentified fluorescent particles from tested pollen. The proposed clustering method aids in reducing the number of false-positive errors.

Kuanxiong aerosol inhibits apoptosis and attenuates isoproterenol-induced myocardial injury through the mitogen-activated protein kinase pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kuanxiong aerosol (KXA) is a common clinical drug based on Fangxiang Wentong (FXWT) therapy in the treatment of angina pectoris. However, the pharmacological mechanism of KXA in the prevention and treatment of myocardial injury (MI) is not clear. AIM OF THE STUDY: The purpose of this study was to explore the protective effect of KXA on isoproterenol (ISO)-induced MI in rats. MATERIALS AND METHODS: The study included male Wistar Kyoto rats (age: 6 weeks). The rats were randomly divided into the following 5 groups (n = 6 per group): control group, ISO group, isosorbide mononitrate (ISMN) group (5 mg/kg), KXA-L group (0.1 mL/kg), and KXA-H group (0.3 mL/kg). The rats in the last three groups were given intragastric administration for 14 days, and rats in control group and ISO group were given the same amount of normal saline daily. ISO (120 mg/kg) was used to induce MI on the 13th and 14th days. We assessed electrocardiograms (ECGs), myocardial specific enzymes, histopathological changes, and apoptosis. RESULTS: We found that KXA reduced the increase in the ST-segment amplitude (elevation or depression) and the levels of myocardial marker enzymes induced by ISO in MI rats, improved the pathological changes in myocardial tissue, and reduced cardiomyocyte apoptosis. At the same time, KXA significantly inhibited the up-regulation of caspase-3 and Bax expression and down-regulation of Bcl-2 expression induced by ISO. RNA sequencing showed that 90 up-regulated genes induced by ISO were down-regulated after KXA treatment, whereas 27 down-regulated genes induced by ISO were up-regulated after KXA treatment. In addition, KEGG pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathway may be an important target of KXA in the treatment of ISO-induced MI in rats. The results of RNA sequencing verified by Western blot analysis showed that KXA significantly inhibited the activation of the ISO-induced MAPK pathway. CONCLUSIONS: KXA improves cardiac function in MI rats by inhibiting apoptosis mediated by the MAPK signaling pathway.

Manufacturing parameter analysis for alumina coating on steel substrate by automated image processing of isolated splats samples.

Thermal spray technology, which involves the Atmospheric Plasma Spraying (APS), encompasses a category of coating processes that supply surface properties to protect or improve the performance of a substrate or component. The coating produced by this technology is built by overlapped splats, whose morphology determines the coating properties. In the same way, the splats obtained in a separated distribution by interposing a perforated mask but using the same thermal spray parameters, has a relationship with the overlapped splats inside the coating. The samples with isolated splats have the advantage of being faster and cheaper to generate and analyse. This article analyses alumina plasma-sprayed splats on steel substrates by image processing techniques, which recognize individual splats and their corresponding morphology (doughnut and pancake) parameters. These parameters allow the user to efficiently classify the splats. After that classification, a quality control can be implemented by comparison between the original and checked sample of isolated splats and a new sample obtained during a small interruption in the normal operation. Additionally, these parameters obtained in an automated way can be used to evaluate the effect of different selections of spraying process parameters.

Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases.

Forest trees are a major source of biogenic volatile organic compounds (BVOCs). Terpenes and terpenoids are known as the main BVOCs of forest aerosols. These compounds have been shown to display a broad range of biological activities in various human disease models, thus implying that forest aerosols containing these compounds may be related to beneficial effects of forest bathing. In this review, we surveyed studies analyzing BVOCs and selected the most abundant 23 terpenes and terpenoids emitted in forested areas of the Northern Hemisphere, which were reported to display anti-inflammatory activities. We categorized anti-inflammatory processes related to the functions of these compounds into six groups and summarized their molecular mechanisms of action. Finally, among the major 23 compounds, we examined the therapeutic potentials of 12 compounds known to be effective against respiratory inflammation, atopic dermatitis, arthritis, and neuroinflammation among various inflammatory diseases. In conclusion, the updated studies support the beneficial effects of forest aerosols and propose their potential use as chemopreventive and therapeutic agents for treating various inflammatory diseases.

A novel and sensitive HILIC-CAD method for glucosamine quantification in plasma and its application to a human pharmacokinetic study.

The clinical effect of glucosamine, the most widely used supplement in patients with osteoarthritis, on joint pain and function improvement, is reported to be inconsistent. Inter-patient variability in the pharmacokinetics of glucosamine, especially its oral absorption, could contribute to the inconsistent clinical outcomes. To test this hypothesis, a novel but simple Hydrophilic Interaction Liquid Chromatography coupled with Charged Aerosol Detector method was developed and validated. The sample was prepared by simple protein precipitation and analysed using an amino column and acetonitrile:100 mM ammonium formate with gradient elution. The developed method was linear (12.5-800 ng/mL, r2 = 0.999) and the relative standard deviations for intra- and inter-day accuracy, precision and repeatability were all less than 6%. The sensitivity of the method (lower limit of quantitation; 12.5 ng/mL) allowed the quantification of endogenous and exogenous glucosamine levels in 12 patients with osteoarthritis, taking 1500 mg glucosamine daily. The analysis showed 120-fold variation (81.7% variance) in exogenous glucosamine levels among the patients, indicating that substantial variability in the extent of absorption and/or rate of elimination could be a possible cause for the reported inconsistent clinical outcomes. The newly-developed method was sensitive and can be used to study the pharmacokinetics of glucosamine.

Chelation Treatment by Early Inhalation of Liquid Aerosol DTPA for Removing Plutonium after Rat Lung Contamination.

Occupational contamination is a potential health risk associated with plutonium inhalation. DTPA remains the chelating drug of choice to decorporate plutonium. In this study, plutonium was found to be more effectively removed from lungs by a single inhalation of nebulized DTPA solution at only 1.1 µmol.kg-1 than by a single intravenous (i.v.) dose of DTPA at 15 µmol.kg-1. When DTPA was inhaled promptly after contamination, it removed the transportable fraction of plutonium prior blood absorption, thereby preventing both liver and bone depositions. Conversely, DTPA injection was better than inhalation at reducing the extrapulmonary burden, probably due to the much greater circulating dose, favoring the mobilization of plutonium already translocated. Thus, prompt inhalation, concomitantly supplemented with i.v. injection, of DTPA induced an important decrease in extrapulmonary deposits. Repeated DTPA inhalations over several weeks were more efficient than a single inhalation in limiting both pulmonary and extrapulmonary plutonium retention, due at least in part to the chelation of the transportable fraction of lung plutonium. Furthermore, repeated DTPA injections remained better at reducing liver and bone plutonium retentions. Taken together, our results suggest that multiple DTPA inhalations may be considered an effective treatment after inhalation of plutonium, particularly given the ease of this needle-free delivery, for the two following conditions: 1. A treatment combining i.v. injection and inhalation should be given in an emergency scenario to efficiently chelate the activity already absorbed; 2. Inhalations should be administered daily to effectively trap the early transferable fraction.

African biomass burning is a substantial source of phosphorus deposition to the Amazon, Tropical Atlantic Ocean, and Southern Ocean.

The deposition of phosphorus (P) from African dust is believed to play an important role in bolstering primary productivity in the Amazon Basin and Tropical Atlantic Ocean (TAO), leading to sequestration of carbon dioxide. However, there are few measurements of African dust in South America that can robustly test this hypothesis and even fewer measurements of soluble P, which is readily available for stimulating primary production in the ocean. To test this hypothesis, we measured total and soluble P in long-range transported aerosols collected in Cayenne, French Guiana, a TAO coastal site located at the northeastern edge of the Amazon. Our measurements confirm that in boreal spring when African dust transport is greatest, dust supplies the majority of P, of which 5% is soluble. In boreal fall, when dust transport is at an annual minimum, we measured unexpectedly high concentrations of soluble P, which we show is associated with the transport of biomass burning (BB) from southern Africa. Integrating our results into a chemical transport model, we show that African BB supplies up to half of the P deposited annually to the Amazon from transported African aerosol. This observational study links P-rich BB aerosols from Africa to enhanced P deposition in the Amazon. Contrary to current thought, we also show that African BB is a more important source of soluble P than dust to the TAO and oceans in the Southern Hemisphere and may be more important for marine productivity, particularly in boreal summer and fall.

Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model.

More than 5% of any population suffers from asthma, and there are indications that these individuals are more sensitive to nanoparticle aerosols than the healthy population. We used an air-liquid interface model of inhalation exposure to investigate global transcriptomic responses in reconstituted three-dimensional airway epithelia of healthy and asthmatic subjects exposed to pristine (nCuO) and carboxylated (nCuOCOOH) copper oxide nanoparticle aerosols. A dose-dependent increase in cytotoxicity (highest in asthmatic donor cells) and pro-inflammatory signaling within 24 h confirmed the reliability and sensitivity of the system to detect acute inhalation toxicity. Gene expression changes between nanoparticle-exposed versus air-exposed cells were investigated. Hierarchical clustering based on the expression profiles of all differentially expressed genes (DEGs), cell-death-associated DEGs (567 genes), or a subset of 48 highly overlapping DEGs categorized all samples according to "exposure severity", wherein nanoparticle surface chemistry and asthma are incorporated into the dose-response axis. For example, asthmatics exposed to low and medium dose nCuO clustered with healthy donor cells exposed to medium and high dose nCuO, respectively. Of note, a set of genes with high relevance to mucociliary clearance were observed to distinctly differentiate asthmatic and healthy donor cells. These genes also responded differently to nCuO and nCuOCOOH nanoparticles. Additionally, because response to transition-metal nanoparticles was a highly enriched Gene Ontology term (FDR 8 × 10-13) from the subset of 48 highly overlapping DEGs, these genes may represent biomarkers to a potentially large variety of metal/metal oxide nanoparticles.

Carrier-free combination dry powder inhaler formulation of ethionamide and moxifloxacin for treating drug-resistant tuberculosis.

This study aimed to develop a combination dry powder formulation of ethionamide and moxifloxacin HCl as this combination is synergistic against drug-resistant Mycobacterium tuberculosis (Mtb). L-leucine (20% w/w) was added in the formulations to maximize the process yield. Moxifloxacin HCl and/or ethionamide powders with/without L-leucine were produced using a Buchi Mini Spray-dryer. A next generation impactor was used to determine the in vitro aerosolization efficiency. The powders were also characterized for other physicochemical properties and cytotoxicity. All the spray-dried powders were within the aerodynamic size range of <5.0 µm except ethionamide-only powder (6.0 µm). The combination powders with L-leucine aerosolized better (% fine particle fraction (FPF): 61.3 and 61.1 for ethionamide and moxifloxacin, respectively) than ethionamide-only (%FPF: 9.0) and moxifloxacin-only (%FPF: 30.8) powders. The combination powder particles were collapsed with wrinkled surfaces whereas moxifloxacin-only powders were spherical and smooth and ethionamide-only powders were angular-shaped flakes. The combination powders had low water content (<2.0%). All the powders were physically stable at 15% RH and 25 ± 2 °C during 1-month storage and tolerated by bronchial epithelial cell-lines up to 100 µg/ml. The improved aerosolization of the combination formulation may be helpful for the effective treatment of drug-resistant tuberculosis. Further studies are required to understand the mechanisms for improved aerosolization and test the synergistic activity of the combination powder.

Fast and non-derivative method based on high-performance liquid chromatography-charged aerosol detection for the determination of fatty acids from Agastache rugosa (Fisch. et Mey.) O. Ktze. seeds.

This study utilised response surface methodology to optimise the conditions for the extraction of A. rugosa seeds oil (ARO). Single-factor experiment and response surface methodology (RSM) were performed to identify the extraction time, liquid-solid ratio and extraction temperature that provided the highest yield of ARO. The optimal extraction time, liquid-solid ratio and extraction temperature were 8 h, 4:1 mL/g and 55 °C. The fatty acids (FAs) content and oil yield obtained through the optimised impregnation-extraction process were 19.67 mg/g and 32.1%. These values matched well with the predicted values. Linolenic acid was identified to be the main active ingredient of ARO. The high-performance liquid chromatography-charged aerosol detection method presented here is fast and does not require derivatisation. Therefore, it could be used to quantitatively analyse the FAs present in ARO and applied to detect compounds with low or no ultraviolet response.

Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary antioxidant therapy.

Coenzyme Q10 (CoQ10) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ10 nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ10 formulations. Preparations were identified as nanosuspensions (particle size in the range 35-60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ10 delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02µm). Stability tests showed that the most stable formulation, after 90days, was the one containing vitamin-E TPGS, followed by the CoQ10-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ10.

The impact of three recent coal-fired power plant closings on Pittsburgh air quality: A natural experiment.

Relative to the rest of the United States, the region of southwestern Pennsylvania, including metropolitan Pittsburgh, experiences high ambient concentrations of fine particulate matter (PM2.5), which is known to be associated with adverse respiratory and cardiovascular health impacts. This study evaluates whether the closing of three coal-fired power plants within the southwestern Pennsylvania region resulted in a significant decrease in PM2.5 concentration. Both PM2.5 data obtained from EPA ground stations in the study region and aerosol optical depth (AOD) data retrieved from the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments onboard the Terra and Aqua satellites were used to investigate regional air quality from January 2011 through December 2014. The impact of the plant closings on PM2.5 concentration and AOD was evaluated using a series of generalized additive models. The model results show that monthly fuel consumption of the Elrama plant, which closed in October of 2012, and monthly fuel consumption of both the Mitchell and Hatfield's Ferry plants, which closed in October of 2013, were significant predictors of both PM2.5 concentration and AOD at EPA ground stations in the study region, after controlling for multiple meteorological factors and long-term, region-wide air quality improvements. The model's power to predict PM2.5 concentration increased from an adjusted R2 of 0.61 to 0.68 after excluding data from ground stations with higher uncertainty due to recent increases in unconventional natural gas extraction activities. After preliminary analyses of mean PM2.5 concentration and AOD showed a downward trend following each power plant shutdown, results from a series of generalized additive models confirmed that the activity of the three plants that closed, measured by monthly fuel consumption, was highly significant in predicting both AOD and PM2.5 at 12 EPA ground stations; further research on PM2.5 emissions from unconventional natural gas extraction is needed. IMPLICATIONS: With many coal-fired power plants scheduled to close across the United States in the coming years, there is interest in the potential impact on regional PM2.5 concentrations. In southwestern Pennsylvania, recent coal-fired power plant closings were coupled with a boom in unconventional natural gas extraction. Natural gas is currently seen as an economically viable bridge fuel between coal and renewable energy. This study provides policymakers with more information on the potential ambient concentration changes associated with coal-fired power plant closings as the nation's energy reliance shifts toward natural gas.

Characterization of antioxidant polyphenols from Myrciaria jaboticaba peel and their effects on glucose metabolism and antioxidant status: A pilot clinical study.

Brazilian berries, such as Myrciaria jaboticaba (jaboticaba), are good sources of polyphenols with a recognized function in oxidative stress attenuation proved in non-clinical studies. In the present study, the polyphenols profile and their contribution to the antioxidant capacity of the jaboticaba peel were analyzed using high-performance liquid chromatography (HPLC) with photodiode array (DAD), electrochemical (ECD), charged aerosol (CAD), and mass spectrometry (MS) detections. Anthocyanins, ellagitannins and gallotannins, ellagic acid and derivatives, and flavonols were found in jaboticaba. Anthocyanins were the phenolics found in higher concentrations. However, ellagitannins were the main contributors to the total antioxidant capacity. Moreover, the effect of jaboticaba peel intake on antioxidant and glucose parameters in a single-blind placebo-controlled crossover study was investigated. The serum antioxidant capacity was significantly higher when the subjects had consumed the test meal containing jaboticaba. Serum insulin decreased subsequent to the second meal at 4h after jaboticaba peel consumption.