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The scale-up of an antisolvent particle micronization process was investigated. The atomized rapid injection solvent extraction (ARISE) system utilizes high pressure carbon dioxide as the antisolvent for the precipitation of solutes from organic solutions. The process typically enables the production of dry powders with beneficial morphologies and enhanced properties such as flow-ability and dissolution rates. Para-coumaric acid (PCA) was selected as the model compound to be processed from acetone based solutions using carbon dioxide at 298 K and 9.5 MPa as the antisolvent. Three scales of operation were tested corresponding to 6- and 15-fold increments in processing capacity. Process outcomes were assessed in terms of product characteristics and product recovery. Upon processing by ARISE, the particle size of PCA was reduced up to 23 times consistently across the different operation scales with process recoveries up to 96%. [ABSTRACT FROM AUTHOR]

Economic theory indicates some ambiguity in the relationship between intellectual property rights (IPRs) and trade. Here, we extend the empirical literature that attempts to resolve this ambiguity by examining how IPRs affect trade along both the intensive – increasing volume of existing goods – and extensive – increasing variety of goods – margins oftrade. Our main results suggest that IPRs have a positive impact on imports, which is driven by a positive effect on the extensive margin and a negative impact on the intensive margin. Splitting countries according to their level of development, market size and imitative ability, we find that the positive impact of IPRs is strongest in less-developed countries, as well as larger countries and those with a higher degree of imitative ability. [ABSTRACT FROM AUTHOR]

Steady state migrating rat lymph dendritic cells (LDC) are semimature, expressing high levels of surface MHC class II, but low levels of surface costimulatory molecules. In this study, we show that surface CD40 is not detectable, but LDC contain intracellular CD40. Multiple isoforms of CD40 were detected, including the type 1 isoform required for signal transduction. Culture of LDC with syngeneic T cells does not induce redistribution of cytoplasmic CD40. When LDC were cultured with naive allogeneic CD4+ T lymphocytes, polarization of CD40 to the immune synapse occurred between 3 and 6 h postculture. By 24 h, although large numbers of T cells were engaged with LDC, CD40 could not be detected in LDC or at the synapses. We conclude that migrating LDC contain stores of CD40 that can be mobilized rapidly to the sites of interaction with Ag-specific T cells. The disappearance of CD40 by 24 h may help in the regulation of T cell activation [ABSTRACT FROM AUTHOR]

Summary: Many economic reforms are undertaken during an economic crisis, but is a crisis a good time to undertake trade reform? We investigate whether an economic crisis at the time of trade liberalization affects a country’s subsequent growth performance. We employ threshold regression techniques on five crisis indicators to identify the “crisis values” and to estimate the differential growth effects in the crisis and non-crisis regimes. Although trade liberalization in both crisis and non-crisis periods raises subsequent growth, we find that an internal crisis implies a lower acceleration and an external crisis a higher acceleration relative to the non-crisis regime. [ABSTRACT FROM AUTHOR]

Despite the increasing knowledge of the immunobiology and epidemiology of parasitic helminths of the gastrointestinal system and the cardiorespiratory system, complications arising from infections of animals and humans with these parasites are a major clinical and economic problem. This has been attributed to the high incidence of these parasites, the widespread emergence of multi-drug resistant parasite strains and the lack of effective vaccines. Efforts to develop and produce vaccines against virtually all helminths (with the exception of Dictyocaulus viviparus and some cestode species) have been hindered by the complexity of the host-parasite relationship, and incomplete understanding of the molecular and immune regulatory pathways associated with the development of protective immunity against helminths. Novel genomic and proteomic technologies have provided opportunities for the discovery and characterisation of effector mechanisms and molecules that govern the host-parasite interactions in these two body systems. Such knowledge provided clues on how appropriate and protective responses are elicited against helminths and, thus, may lead to the development of effective therapeutic strategies. Here, we review advances in the immune response to selected helminths of animal health significance, and subsequent vaccine potential. The topics addressed are important for understanding how helminths interact with host immune defences and also are relevant for understanding the pathogenesis of diseases caused by helminths. [ABSTRACT FROM AUTHOR]

We show that following oral inoculation, prions bind to ileal Peyer patch and cecal patch microfold cells (M cells) in vivo. Furthermore, we show evidence that the cecum acts a biological sump holding large concentrations of prions for relatively long periods, thus increasing the exposure time of cecal patch M cells. Our results show a critical initial step in the translocation of prions from the intestinal lumen of mammals in vivo, which is a precursor to infection. [ABSTRACT FROM AUTHOR]

The article discusses several courts cases regarding the civil liability that originated from the explosion involving the Buncefield Oil Storage Depot in Hertfordshire, England. It states that the High Court's decisions cover a massive area of legal territory and the series of events that led to the explosion. Furthermore, it mentions that the proceedings regarding the explosion has not yet reached its finality due to the civil proceedings on the damages caused by the explosion.

Abstract: The experimental viscosities of the saturated gas expanded liquid system of acetone and carbon dioxide were determined under pressure using a falling-weight viscometer. System pressures and temperatures were manipulated as independent variables to simultaneously influence system properties of liquid phase compositions, densities, volume expansions and viscosities. Liquid viscosities were measured and presented as a function of other system properties. Viscosity measurements were conducted at constant system temperatures of 25, 30, 35 and 40°C, and at system pressures corresponding to liquid compositions between 0 and 0.90 carbon dioxide mole fractions along all four isotherms. Viscosity reduction was observed to be a function of increasing carbon dioxide concentration in the liquid phase, liquid volume expansion, liquid density and system pressure. A high degree of linear correlation was observed throughout the entire experimental envelope when viscosity reduction was presented as a function of liquid phase composition. Analysis of data obtained in this study in conjunction with results of previous research [R. Sih, F. Dehghani, N.R. Foster, Viscosity measurements on gas expanded liquid systems. Methanol and carbon dioxide, Journal of Supercritical Fluids 41 (2007) 148–157; R. Sih, M. Armenti, R. Mammucari, F. Dehghani, N.R. Foster, Viscosity measurements on saturated gas-expanded liquid systems. Ethanol and carbon dioxide, Journal of Supercritical Fluids 43 (2008) 460–468] shows that the viscosity behavior of independent gas expanded liquid systems consisting of carbon dioxide and either methanol, ethanol or acetone were universally related to system composition, organic solvent species and system temperature. [Copyright &y& Elsevier]

Individual country experience with trade liberalisation has been mixed. This paper examines the relationship between liberalisation and growth for a sample of 75 liberalising countries. To consider the importance of heterogeneity in the growth response to liberalisation this paper employs quantile regression methods which allow the coefficient on liberalisation to vary across the conditional growth distribution. The results suggest that countries experiencing the lowest rates of growth benefit most from liberalisation. The results also suggest that while such countries benefit most in the long-run they are the most likely to suffer from short-run negative effects of liberalisation. [ABSTRACT FROM AUTHOR]

El artículo considera la función de citocinas y ciertas moléculas inmunorreguladoras en la susceptibilidad cruzada entre la diabetes tipo 2 y la enfermedad periodontal. Nota que aunque varias moléculas como la interleucina 6 (IL-6) y el factor de necrosis tumoral α (TNF-α) se hayan asociado con la diabetes mellitus tipo 2 y la enfermedad periodontal (entre ellas las adipocinas derivadas de los adipocitos), la función de otras adipocinas relativo a la periodontitis no se ha establecido.

The article describes the immunobiological perspective of periodontal disease and type 2 diabetes mellitus. It tends to discover the roles of cytokines and novel immunoregulatory molecules including adipokines in relation between such diseases. It also discusses the result of the study involving the importance of adipocytes as immune-competent cells which is capable of secreting large amount of immunologically active molecules.

The relationship between openness and growth remains a controversial issue in development economics with many studies focusing on the export–growth relationship. This paper examines whether the relationship between exports and growth found in large cross-section studies also holds in the context of African economies. The paper employs threshold regression techniques to examine whether African countries benefit more from exports when they reach a certain level of development or openness. Our results suggest that there is indeed a positive relationship between exports and growth in Africa. The threshold regression analysis also suggests that it is not necessary for a country to reach a certain level of development or to have an existing export base for this relationship to hold, though it is found that the relationship is stronger for countries that experience higher rates of export growth. [ABSTRACT FROM AUTHOR]

Topographic positional regulation of nitrogen (N) dynamics in soil within Canadian Shield headwaters, located in calibrated catchments containing mature, tolerant hardwood forest, was examined to determine how N pools, mineralization, nitrification, and leaching in soil relate to N export in drainage waters. A uniformly high net N mineralization and nitrification potential for surficial soil layers rich in organic N was demonstrated for ridge, upper-middle slope, and lower slope – footslope topographic positions. Results from plot-scale studies revealed that NO3– concentrations in soil water from well-drained soils were very highly variable throughout the catchments, ranging from 25 to 175 µmol·L–1, with a median of 80 µmol·L–1. The isotopic effects of denitrification were not detected in soil water collected from lower slope – footslopes, and in situ rates of N2O production from soils on lower slope – footslopes and valley bottoms were very low and highly variable. Higher N exports from soils than from streams were not explained by differences in soil water N with topographic position or denitrification in lower landscape topographic positions. Using an average soil water N value, based on the replicated plots within catchments, did not reduce the calculated substantial differences in N export between soils and streams. [ABSTRACT FROM AUTHOR]

Abstract: The effective delivery of antigens via the oral route is an extremely desirable goal. Mucosal delivery of antigens stimulates mucosal and systemic immunity without affecting maternal antibodies and reduces the need for sterile needles or trained personnel. To date, there are very few commercially available oral vaccines and despite numerous reports in the scientific literature to show the success of biodegradable antigen carriers, none of these have achieved commercial status. Nevertheless, many studies have shown the great potential of biodegradable antigen carriers for oral vaccination in preclinical studies, but a more rational approach may be to specifically target antigen-loaded biodegradable microspheres to cells in the mucosal immune system which transport and process antigens for T cell recognition. Modern cell and molecular biology techniques have unearthed a wealth of information regarding important receptors involved in the capture of luminal antigens by microfold or membranous (M) cells and receptors on dendritic cells (DCs) which may allow future targeting of antigens to specific DC phenotypes, thus directing the immune response appropriately. In this review, we consider the use of currently available biodegradable antigen carriers and speculate on how these may be improved to more efficiently target mucosal effector sites. [Copyright &y& Elsevier]

Within the group of dense gas micronization processes, batch processes are attractive for the relative ease and cost-effectiveness of their scale-up. However, process parameters and product characteristics can differ significantly between processes. In this study, a comparison of the micronization of the polyphenolic compound curcumin by two batch-dense gas antisolvent methods was conducted. The effects of solvent selection and operating temperature on process performance, product morphology and crystallinity were investigated. Particles were precipitated from acetone, ethanol, methanol and acetone-ethanol feed solutions with the use of the gas antisolvent (GAS) and the atomized rapid injection of solvent extraction (ARISE) processes. Processing was operated at 9.5–10 MPa and 298–313 K. Both processes allowed the production of polymorphic curcumin with interesting implications for the preparation of therapeutic formulations. The GAS process generated recoveries up to 36%, while process recoveries for ARISE were up to 60%. [ABSTRACT FROM AUTHOR]

Review: of supercritical fluids; 88 refs. [ABSTRACT FROM AUTHOR]

Inhalable dry formulations for pulmonary delivery of curcumin have been produced by supercritical antisolvent micronization. The antioxidant curcumin was co-processed with hydroxypropyl-beta-cyclodextrin (HP-β-CD) and polyvinylpyrrolidone (PVP) to form binary and ternary composites with enhanced flow-ability for pulmonary delivery. The micronization process adopted was the atomized rapid injection solvent extraction (ARISE) system, and was operated at 95 bar and at temperatures of 25 °C and 40 °C. The products were evaluated in terms of morphology, composition, crystallinity and aerodynamic particle size distributions. A synergistic effect of the excipients on the aerodynamic properties of micronized curcumin formulations has been found. The fine particle fraction (FPF) of curcumin in ARISE-processed powders was as high as 61% in ternary systems, whilst untreated curcumin had a FPF of 10% and micronized binary systems had FPF below 40%. The process produced yields of about 80%, demonstrating significant potential for further development of curcumin formulations for pulmonary administration. [ABSTRACT FROM AUTHOR]

Nanocarriersystems, such as liposomes, polymersomes, and micelles,find applications in the delivery of a wide range of compounds, includingtargeted delivery of pharmaceuticals. Nanocarrier systems have theability to increase the bioavailability, reduce toxicity, and avoidundesirable interactions of active pharmaceutical ingredients. Inthis work, a novel dense gas technique known as depressurization ofan expanded solution into aqueous media (DESAM) was used to producedifferent types of nanocarrier systems. The effects of using differenttypes of dense gases and different operating temperatures were investigated.Encapsulation of hydrophilic compounds in the vesicles (liposomesand polymersomes) was also studied. The highest encapsulation efficienciesin liposomes and polymersomes achieved were 10.2 and 9.7%, respectively.The DESAM process was also able to reduce the residual solvent contentin the product to 2.2% (v/v), which is significantly lower than thesolvent residual levels reported for conventional processing. [ABSTRACT FROM AUTHOR]

Silybin (SLB), akind of antihepatotoxic polyphenolic substance,is currently available for a variety of acute and chronic liver diseases.However, its poor solubility and low bioavailability have stronglylimited its therapeutic applications. In this work, we demonstratea simple solution to address these issues by designing SLB/poly(vinylpyrrolidone)(PVP) nanodrugs via the aerosol solvent extraction system (ASES).In the ASES process, SLB and PVP are prepared via coprecipitationby using the dimethylformamide/dense gas CO2solvent/antisolventstrategy. The size of the as-obtained SLB/PVP nanodrugs (denoted asNanoSLB) can be tuned from 100 to 300 nm. Compared with raw SLB, NanoSLBis of low crystallinity and hence shows drug solubility greatly enhancedby more than 8-fold. This work will broaden the applications of water-insolubledrugs in pharmaceutical treatments. [ABSTRACT FROM AUTHOR]

Abstract: The solubility and solubility trends of organometallic complexes in supercritical carbon dioxide are reviewed. The influence of intermolecular forces, physical properties and the metal chelates on solubility is explored. A number of thermodynamic models used to predict the solubility behavior of organometallic complexes in supercritical carbon dioxide, and the advantages and limitations to these thermodynamic models are also discussed. [Copyright &y& Elsevier]

Abstract: The use of lipids in drug delivery dates from the 1970s . In this paper, an overview of lipid-based carrier systems encapsulating Active Pharmaceutical Ingredients (API), and their preparation by dense gas technology, is given. Lipid-based products at different stages of development (marketed commercialized products, clinical trial products, and current projects under research) and the production techniques utilizing dense gases are discussed. [Copyright &y& Elsevier]

Background. There are no reported data to explain how Salmonella suppress nitrite ion production in macrophages or whether this phenomenon is unique to typhoidal or non-typhoidal serovars. The aims of this study were, therefore, to investigate these phenomena. Methods. We measured survival of S. typhimurium 14028 and its phoP mutant in murine J774 macrophages, cultured with or without interferon gamma. We compared expression of inducible nitric oxide synthase (iNOS) mRNA and protein, and nitrite ion production and also examined binding of nuclear factor κB (NFκB) and activator protein 1 (AP-1) tomacrophage DNA. Results. S. typhimurium 14028 inhibited binding of NFκB and AP-1 to DNA in murine J774. A macrophages via an intact phoP regulon. This correlated with increased survival and reduced iNOS expression. Suppression of NFκB activity was ameliorated in macrophages cultured with IFN-γ and this correlated with increased expression of iNOS mRNA and nitrite ion production, although IFN-γ had no effect on AP-1/DNA interaction. We show, that with one exception, suppression of iNOS is unique to typhoidal serovars. Conclusion. S. typhimurium inhibit NFκB and AP-1 interaction with macrophage DNA via the PhoP regulon, this reduces nitrite ion production and is principally associated with typhoidal serovars. [ABSTRACT FROM AUTHOR]

Abstract: Recently, subcritical water (SBCW: water that has been heated to a temperature between 100°C and 200°C at pressures of up to 70bar) has been used to dissolve several hydrophobic pharmaceutical compounds (). Furthermore, a number of active pharmaceutical ingredients (APIs) have been rapidly precipitated from SBCW solutions (). It is possible to alter the precipitate morphology by altering the processing variables; including the SBCW-API solution injection temperature and adding impurities (such as pharmaceutical excipients, e.g. lactose) to the precipitation chamber. The work presented in this article demonstrates that the morphology of pharmaceutical particles can be tuned by adding organic solvents (ethanol and methanol) to the SBCW-API solutions. Particle morphology has also been tuned by adding different pharmaceutical excipients (polyethylene glycol 400 and lactose) to the precipitation chamber. Different morphologies of pharmaceutical particles were produced, ranging from nanospheres of 60nm diameter to 5μm plate particles. Budesonide was used as the model API in this study. Two experimental products were spray dried to form dry powder products. The aerodynamic particle size of the powder was established by running the powder through an Andersen Cascade Impactor. It has been shown that the drug particles produced from the SBCW micronization process, when coupled with a spray drying process, are suitable for delivery to the lungs. [ABSTRACT FROM AUTHOR]

Dense CO2 can be used as an environmentally-benign polymer processing medium because of its liquid-like densities and gas-like mass transfer properties. In this work, polymer bio-blends of polycarbonate (PC), a biocompatible polymer, and polycaprolactone (PCL), a biodegradable polymer were prepared. Dense CO2 was used as a reaction medium for the melt-phase PC polymerization in the presence of dense CO2-swollen PCL particles and this method was used to prepare porous PC/PCL blends. To extend the applicability of dense CO2 to the biomedical industry and polymer blend processing, the impregnation of ibuprofen into the blend was conducted and subsequent dissolution characteristics were observed. [ABSTRACT FROM AUTHOR]

Abstract: The viscosities of the gas expanded liquid system of methanol with carbon dioxide were experimentally determined with a recently developed method of falling-weight viscometry. Carbon dioxide concentrations within the gas expanded liquid system were systematically increased by the addition of carbon dioxide into an isochoric system containing metered amounts of methanol. New experimental viscosity data for the expanded liquid phase of methanol with carbon dioxide are presented at 25, 30, 35 and 40°C and at mole fractions of carbon dioxide in the liquid phase between 0.10 and 0.85 in 0.05 increments along all four isotherms. The apparent correlating factor for deducing the viscosity of carbon dioxide expanded methanol appears to be the composition of the liquid phase and the degree of volume expansion of the liquid phase, as opposed to liquid density and system pressure values. Viscosity reduction is almost linear up to about 0.5 mole fraction carbon dioxide before the rate of viscosity reduction upon carbon dioxide enrichment decreases. An increase in the degree of volume expansion of the liquid phase brings about a dramatic initial reduction in liquid phase viscosity. Viscosity reduction appears to be linear in excess of 300% liquid phase volume expansion. [Copyright &y& Elsevier]

Abstract: Most pharmaceutical compounds are administered to the human body as tablets or by injection. If the dissolution of a drug is low, high dosage is needed and hence may cause some side effects to the human body. One method of enhancing the dissolution rate of a drug into the biological environment is to reduce the particle size. Cyclosporine A, one of the immunosuppressant drugs that have been commonly used for the treatment of respiratory tract infections, was chosen as the drug of interest since it has low solubility and high permeability (Class 2) in water. The phase behaviour of the cyclosporine–carbon dioxide (CO2) system was investigated prior to the micronization process. The melting point of cyclosporine substantially decreased from 150°C at 1bar to 25°C at 55bar when exposed to CO2 at high pressure. Micron-sized cyclosporine was successfully produced by both rapid expansion of supercritical solution (RESS) and particles from gas-saturated solution (PGSS) techniques. After micronization, the average particle size of cyclosporine precipitated by both techniques was found to be less than 1μm, which is related to a 97% reduction compared with the unprocessed cyclosporine. No significant change in the morphology and particle size was observed with respect to the extraction temperature and pre-expansion pressure, whilst an increase in nozzle diameter resulted in a slight increase in particle size and decrease in degree of aggregation. The fine particle mass (FPM) of micronized cyclosporine produced by RESS and PGSS was found to be 48 and 59%, respectively. [Copyright &y& Elsevier]

We examined fifth-year seedling response to soil disturbance and vegetation control at 42 experimental locations representing 25 replicated studies within the North American Long-Term Soil Productivity (LTSP) program. These studies share a common experimental design while encompassing a wide range of climate, site conditions, and forest types. Whole-tree harvest had limited effects on planted seedling performance compared with the effects of stem-only harvest (the control); slight increases in survival were usually offset by decreases in growth. Forest-floor removal improved seedling survival and increased growth in Mediterranean climates, but reduced growth on productive, nutrient-limited, warm–humid sites. Soil compaction with intact forest floors usually benefited conifer survival and growth, regardless of climate or species. Compaction combined with forest-floor removal generally increased survival, had limited effects on individual tree growth, and increased stand growth in Mediterranean climates. Vegetation control benefited seedling growth in all treatments, particularly on more productive sites, but did not affect survival or alter the relative impact of organic matter removal and compaction on growth. Organic matter removal increased aspen coppice densities and, as with compaction, reduced aspen growth. [ABSTRACT FROM AUTHOR]

Solubility data of drugs in supercritical fluids (SCF) are crucial for designing pharmaceutical processes, such as micronization of drug powders or extraction using SCF. A new empirical equation is proposed to correlate solute solubility in supercritical carbon dioxide (SC CO2) with temperature, pressure and density of pure SC CO2. The proposed equation is ln y2=M0+M1P+M2P2+M3PT+(M4T)/P+M5 ln ρ, where y2 is the mole fraction solubility of the solute in the supercritical phase, M0–M5 are the model constants calculated by least squares method, P (bar) is the applied pressure, T is temperature (K) and ρ is the density of pure SC CO2. The accuracy of the proposed model and four other empirical equations employing P, T and ρ variables, was evaluated using 106 published solubility data sets by calculating the average of absolute relative deviation (AARD). The mean AARD for the proposed model is 21.4 (±15.9)%, which is an acceptable error when compared with the experimental uncertainty. The AARD values for other equations were 33.7 (±24.5), 36.2 (±27.2), 48.3 (±77.2) and 27.1 (±21.2). The mean AARD of the new equation is significantly lower than those obtained from previous empirical models (paired t-test, P<0.0005). The proposed model presented more accurate correlation for solubility data in SC CO2. It can be employed to speed up the process of SCF applications in the pharmaceutical industry. [Copyright &y& Elsevier]

Coccidiosis in broiler chickens, caused by infection with Eimeria spp. remains one of the most economically important production diseases. Development of a genetic biomarker panel of sub-clinical infection would be an important biological tool for the management of broiler flocks. We analysed expression of MicroRNAs (miRNAs) to determine the potential for these in diagnosing coccidiosis in broiler flocks. miRNA expression, in the ilea of Ross 308 broilers, was compared between chickens naturally clinically or sub-clinically infected with Eimeria maxima and Eimeria acervulina using NextSeq 500 sequencing. 50 miRNAs with greatest coefficient of variance were determined and principal component analysis showed that these miRNAs clustered within the clinical and sub-clinical groups much more closely than uninfected controls. Following false detection rate analysis and quantitative PCR we validated 3 miRNAs; Gallus gallus (gga)-miR-122-5p, gga-miR-205b and gga-miR-144-3p, which may be used to diagnose sub-clinical coccidiosis. • Our data adds to the current data elucidating microRNA (miRNA) profiles in broilers • We report unique miRNA profiles for broilers with clinical and sub-clinical coccidiosis • We then validated a small miRNA gene panel using qPCR which could be used in early diagnosis of sub-clinical coccidiosis [ABSTRACT FROM AUTHOR]

Summary: Immune evasion is a critical survival mechanism for bacterial colonization of deeper tissues and may lead to life‐threatening conditions such as endotoxaemia and sepsis. Understanding these immune evasion pathways would be an important step for the development of novel anti‐microbial therapeutics. Here, we report a hitherto unknown mechanism by which Salmonella exploits an anti‐inflammatory pathway in human immune cells to obtain survival advantage. We show that Salmonella enterica serovar Typhimurium strain 4/74 significantly (P < 0·05) increased expression of mRNA and surface protein of the type 1 receptor (VPAC1) for anti‐inflammatory vasoactive intestinal peptide (VIP) in human monocytes. However, we also show that S. Typhimurium induced retrograde recycling of VPAC1 from early endosomes to Rab11a‐containing sorting endosomes, associated with the Golgi apparatus, and anterograde trafficking via Rab3a and calmodulin 1. Expression of Rab3a and calmodulin 1 were significantly increased by S. Typhimurium infection and W‐7 (calmodulin antagonist) decreased VPAC1 expression on the cell membrane while CALP‐1 (calmodulin agonist) increased VPAC1 expression (P < 0·05). When infected monocytes were co‐cultured with VIP, a significantly higher number of S. Typhimurium were recovered from these monocytes, compared with S. Typhimurium recovered from monocytes cultured only in cell media. We conclude that S. Typhimurium infection exploits host VPAC1/VIP to gain survival advantage in human monocytes. [ABSTRACT FROM AUTHOR]

• Subcritical water is used as the solvent for processing of drug nanoparticles. • The use of organic solvents is eliminated by using cold water as anti-solvent. • The nanopharmaceuticals exhibit high dissolution rate. Nanonization of poorly water-soluble drugs offers an efficient approach for enhancing the bioavailability of drugs where the solubility and dissolution rate are the main limitations. The solvent anti-solvent precipitation methods have been the most straightforward technique for producing ultrasmall drug nanoparticles with narrow size distributions. By using subcritical water (SBCW) as the solvent, the use of organic solvents could be eliminated, providing a green route to nanopharmaceuticals. In this review, we aim to give a comprehensive overview and latest progress on SBCW processing for nanoparticles of poorly water-soluble drug compounds. The effects of processing parameters and stabilizers on the properties of the nanoparticles are summarized. Perspectives on existing challenges and opportunities for scale-up and commercialization of the SBCW technology are discussed. [ABSTRACT FROM AUTHOR]

• Different formulation strategies for drug delivery using dense CO 2 are discussed. • Dense CO 2 -based processes for drug formulation development are reviewed. • Drug micronization, coprecipitation, encapsulation and coating are critically compared. • Examples of drug formulations recently developed are presented. Dense carbon dioxide technology is promising for the processing of drug compounds and development of varied pharmaceutical formulations through micronization, coprecipitation, encapsulation and coating techniques. The main advantages of this technology are the possibility to process thermo-sensitive compounds at low temperatures and using no/low amounts of organic solvents. Many processes have been developed and modified throughout the years to allow the production of composite materials with the desired characteristics. In this review, various processing methods using dense CO 2 and recent process modifications are classified, and their differences and similarities are discussed. Formulation strategies to improve dissolution and flow properties of active compounds are also presented, giving insights into the selection of the most suitable formulation strategy and processing method. [ABSTRACT FROM AUTHOR]

• Gene response to coccidiosis is different in fast (Ross 308) and slow (Ranger Classic) broilers. • Fast growing broilers may repair tissue damage quicker than slow growing broilers. • Slow growing broilers may show a degree of immunosuppression early in coccidiosis. • The study reports a potential genetic biomarker of coccidiosis in broilers. We analysed intestinal tissues from groups of fast growing (Ross 308) broilers with natural or experimental coccidiosis, by genomic microarray. We identified genes that were differentially expressed (DE) in all groups and analysed expression of a panel of these, by qPCR, in Ross 308 and slow growing (Ranger classic) broilers, infected with 2500 or 7000 oocysts of Eimeria maxima for 6 or 13 days post-infection (dpi). Four genes (ADD3, MLLT10, NAV2 and PLXNA2) were upregulated (P <0.05) in Ross 308 but were not DE in Ranger Classic at 6 dpi with 2500 oocysts. Six genes (PTPRF, NCOR1, CSF3, SGK1, CROR and CD1B) were upregulated (P <0.05) in both Ross 308 and Ranger Classic infected with 2500 oocysts at 6 dpi but were not DE at 6 dpi with 7000 oocysts. At 13 dpi with 7000 oocysts, NAV2 and NCOR1 were upregulated in Ross 308 (P <0.05) and PTPRF was upregulated in both genotypes (P <0.05). DE of immune genes within the biomarker panel also occurred, with CSF3 upregulated in both genotypes infected with 2500 oocysts at 6 dpi and in Ranger Classic infected with 7000 oocysts, at 6 and 13 dpi (P <0.05). IL-22 was down-regulated in Ranger Classic infected with 2500 or 7000 oocysts at 6 dpi (P <0.05) but upregulated in both genotypes at 13 dpi (P <0.05). CD72 was down-regulated in Ranger Classic infected with 2500 oocysts at 6 dpi and with 7000 oocysts at 6 and 13 dpi (P <0.05). CD72 was upregulated in Ross 308 infected with 2500 oocysts at 6 dpi but was down-regulated following infection with 7000 oocysts at 13 dpi (P <0.05). In conclusion, differential gene expression occurs in fast and slow growing broiler genotypes with coccidiosis. In addition, we highlight a potential genetic biomarker panel for early diagnosis of coccidiosis. [ABSTRACT FROM AUTHOR]

Abstract Rare-earth doped NaYF 4 upconversion nanomaterials have found many applications from biosensing through photoelectric conversion to luminescent anti-counterfeiting. However, the scalable synthesis methods of ultrasmall NaYF 4 nanoparticles are still challenging. Herein, We demonstrated that the intensified mixing of the precursor by a high-gravity rotating packed bed (RPB) reactor before the hydrothermal synthesis process enabled the preparation of ultrasmall NaYF 4 :Yb3+/Er3+ upconversion nanoparticles, with much smaller size, more uniform distributions and higher Er3+-doping level than those obtained in the stirred tank reactor (STR) route. In stark contrast to conventional synthetic techniques that require stringent control over several experimental variables for controlling morphologies and sizes, the process intensification approach presented here requires modification of only a single variable while enabling tremendous improvements to control the formation of NaYF 4 based UCNPs with small feature size. The UCNPs dispersed well in various organic solvents (e.g. ethanol, acetone, toluene, cyclohexane, etc.), forming transparent nanodispersions with upconversion luminescence under 980 nm NIR light irradiation. The preliminary applications of NaYF 4 :Yb3+/Er3+ nanodispersions for upconversion luminescent transparent hybrid films and anti-counterfeiting were also demonstrated. Graphical abstract Unlabelled Image Highlights • Process intensification for synthesis of NaYF 4 :Yb3+/Er3+ nanophosphors was realized. • Effects of high gravity level on nanoparticle size are analyzed. • The obtained NaYF 4 :Yb3+/Er3+ nanophosphors exhibited uniform size distribution. • Transparent nanodispersions with upconversion luminescence were prepared. • NaYF 4 :Yb3+/Er3+ nanodispersions are promising for anti-counterfeiting. [ABSTRACT FROM AUTHOR]

In this work, we reported the preparation of 3D graphene/iron oxides aerogels (IO/GA) by in situ growth of iron oxide nanoparticles (IO) on the graphene oxides in high gravity rotating packed bed (RPB) followed by freeze drying treatments. The RPB was used to intensify the mass transfer and mixing during the adsorption and nucleation process of IO, guaranteeing highly homogeneous reaction conditions to the reactants. Thereafter, the IO nanoparticles obtained in the RPB route (IO/GA-RPB) exhibited an average size of 6 nm with uniform size distribution. By contrast, the IO nanoparticles prepared from traditional stirred tank reactor (IO/GA-STR) showed much larger particle size (33 nm). The 3D structured IO/GA-RPB nanocomposites were demonstrated to be efficient heterogeneous photo-Fenton catalysts for the degradation of methyl-blue. The kinetic studies of the catalytic reaction systems in the temperature range of 293 K–323 K and pH value of 1–7 were performed. The reaction rate constants and apparent activation energy were determined. The related catalytic mechanism of the photo-Fenton reaction was investigated. The excellent catalytic efficiency of the 3D-foam-structured heterogeneous IO/GA-RPB catalyst, along with the knowledge of the kinetics data, make them promising for in scale-up applications of photo-Fenton reaction. [ABSTRACT FROM AUTHOR]

Murine/LPS models of Gram negative sepsis indicate that vasoactive intestinal peptide (VIP) has therapeutic potential. We investigated the unknown effect of VIP on JAK/STAT proteins and genes in human monocytes infected with Salmonella Typhimurium 14028. S . Typhimurium 14028 increased expression of both IL-6 receptor (IL-6R) and interferon gamma receptor 1 (IFNγR1) on monocytes but co-culture of infected monocytes with VIP (10 −7  M) only decreased expression of IFNγR1 ( P  < 0.05). In contrast, S . Typhimurium 14028 infection or co-culture with VIP had no effect on IL-10 receptor expression on the monocyte surface. However, S . Typhimurium 14028 down regulated IFNGR1 gene expression and this was not altered by co-culture with VIP, suggesting that changes in IFNγR1 protein may be due to an effect on cytoplasmic transport. 15 JAK/STAT genes, out of 84 studied, were up-regulated by S . Typhimurium 14028 infection and five were down-regulated. Co-culture with VIP significantly decreased expression of two genes (IFNG and IL-20) and increased expression of three genes (SOCS1, SOCS3 and STAT4) (P < 0.05). S . Typhimurium 14028 also increased expression of PTPN1, which dephosphorylates JAK2 and TYK2. This was unaltered by co-culture with VIP but S . Typhimurium 14028-induced expression of ISG15, associated with susceptibility to Gram negative infection, was further increased by VIP. We conclude that the effect of VIP on JAK/STAT genes may preclude its therapeutic use in human Gram negative sepsis. [ABSTRACT FROM AUTHOR]

Ciprofloxacin (CIP) has been widely used to treat many types of bacterial infections. Herein, we reported a green approach for preparation of CIP nanoparticles via solvent anti-solvent precipitation by using subcritical water-ethanol mixture as the solvent. The solubility of CIP in subcritical water-ethanol mixture (with various ethanol ratio of 0, 5, and 20 wt%) at the temperature range from 100 °C to 170 °C and constant pressure of 4 MPa were measured. The chemical structure of CIP was stable after processed in subcritical water-ethanol mixture at up to 170 °C, confirmed by Fourier transformed infrared analysis. The obtained solubility data of CIP were correlated using a modified Apelblat model and the results of the predicted solubility show good agreement with the experimental value. The nanonization of CIP via solvent anti-solvent precipitation process that used the tunable solvent power of subcritical water-ethanol mixture was conducted. Two kinds of no-ionic, hydrophilic polymer, including polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), were introduced as stabilizers in the precipitation process to obtain CIP nanoparticle with improved dissolution rate. These results show that as-synthesized CIP nanoparticles are promising for oral administration of CIP drugs. [ABSTRACT FROM AUTHOR]

The Atomized Rapid Injection Solvent Extraction (ARISE) process is a new technique for the production of micron-size particles using a supercritical antisolvent. Scale-up of the process can be achieved simply by maintaining the antisolvent/solvent ratios and pressure differentials while increasing batch volumes. In this work, two model compounds, para -coumaric acid (PCA) and hydroxypropyl-β-cyclodextrin (HPβCD), were processed using ARISE at different operating scales. The batch size for PCA varied between 0.2 g/batch and 1.6 g/batch, while the batch size of HPβCD varied from 0.8 g/batch to 13.9 g/batch. The economic evaluation of the process was based on production rates between 2 and 10 t/a, which are typical for high-specialty grade chemicals. Capital investment and production costs were estimated using the scaling–exponential method. Investment costs were estimated between 190 and 950 US$/kg of product while production costs were calculated between 52 and 255 US$/kg of product (year 2015). The figures indicate that ARISE can be economically viable for the manufacturing of specialty chemicals as pharmaceuticals. [ABSTRACT FROM AUTHOR]

The dissolution properties of curcumin are notoriously poor and hinder its bioavailability. To improve its dissolution properties, curcumin has been formulated with methyl-β-cyclodextrin and polyvinylpyrrolidone by the atomized rapid injection solvent extraction (ARISE) system. The compounds were co-precipitated from organic solutions using carbon dioxide at 30 °C and 95 bar as the antisolvent. Curcumin formulations were also produced by physical mixing and freeze drying for comparative purposes. The morphology, crystallinity, solid state molecular interactions, apparent solubility and dissolution profiles of samples were observed. The results indicate that the ARISE process is effective in the preparation of curcumin micro-composites with enhanced dissolution profiles compared to unprocessed material and products from physical mixing and freeze drying. [ABSTRACT FROM AUTHOR]

The solubility of bicalutamide, megestrol acetate, prednisolone, beclomethasone dipropionate, and clarithromycin in subcritical water (SBCW) at the temperature range from 383.15 to 443.15 K and constant pressure of 5.5 MPa were measured using a modified solvent-antisolvent method combined with SBCW technology. The chemical structures of these five kinds of solutes were stable after processed in SBCW at up to 443.15 K, which was demonstrated by Fourier transformed infrared analysis. The solubility of selected solutes increased exponentially as the temperature of the SBCW increased from 383.15 to 443.15 K. The obtained solubility data were correlated using a modified Apelblat model and the results of the predicted solubility show good agreement with the experimental value. [ABSTRACT FROM AUTHOR]

Oral beclomethasone dipropionate (BDP) has been extensively studied in the management of ulcerative colitis in clinical practice in recently years. However, the effective bioavailability and absorption of BDP are limited by its poor water solubility when administered orally. Herein, we report a green process for the synthesis of BDP nanoparticles via solvent anti-solvent precipitation, in which the subcritical water (SBCW) and cold water were used as the solvent and anti-solvent respectively. Polyethylene glycol (PEG), a non-ionic, hydrophilic polymer was introduced as stabilizers in the SBCW process to obtain sub-50 nm BDP nanoparticles with improved dissolution rate. Scanning electronic microscopy (SEM), Fourier transform infrared (FTIR) spectrophotometry, powder X-ray diffraction (XRD) and dissolution tests were performed to investigate the corresponding particle morphology, structure and dissolution rate properties of the BDP nanoparticles. The obtained BDP nanoparticles are < 50 nm in diameters with uniform distribution, exhibiting similar chemical structures, lower crystallinity and much higher dissolution rate than the raw BDP drug. These results show that as-synthesized BDP nanoparticles are promising for oral administration of BDP towards the management of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Clarithromycin (CLA) is an important drug used to treat various bacterial infections, while its effective bioavailability is limited by the poor water-solubility of the CLA molecule. Subcritical water (SBCW) processes have been demonstrated to be a new promising alternative for the preparation of drug nanoparticles with enhanced dissolution rate. In this work, we reported ultrafine CLA nanoparticles via anti-solvent precipitation in subcritical water, with detailed studies on the effects of operating parameters. The corresponding particle morphology, and dissolution rate properties of the CLA nanoparticles were characterized through scanning electronic microscopy (SEM), Fourier transform infrared spectrophotometry (FT-IR), powder X-ray diffraction (XRD) and dissolution tests. Under optimized experimental conditions, which was using 1.5 mL of SBCW at 150 °C as the solvent and 15 of aqueous PVP solution (0.4 wt%) as the anti-solvent, uniform sub-50 nm sized CLA nanoparticles are obtained. According to the dissolution testing, the ultrafine CLA nanoparticles exhibit very high dissolution rate (over 85% at 60 min) compared with that of raw CLA (10% at 60 min). Our results suggest that as-synthesized ultrafine CLA nanoparticles via anti-solvent precipitation in subcritical water are promising for efficient therapy. [ABSTRACT FROM AUTHOR]

We show that IL-36R is expressed by T (CD4+ and CD8+) and B (CD19+) lymphocytes in human blood and also by CD4+ T lymphocytes in the intestinal lamina propria. IL-36R protein was mostly stored in the cytoplasm of CD4 lymphocytes and B cells, during steady state conditions and the greatest expression of IL-36R mRNA was measured in CD4+ (T helper) lymphocytes. IL-36 β, which functions via IL-36R induced rapid and significant (P < 0.05) proliferation of CD4+ lymphocytes, within 48 h. IL-36R expression was also maintained on the surface of circulating CD4+ lymphocytes which enter the intestinal lamina propria. In conclusion our study is the first to show that (1) all human blood lymphocytes express IL-36R; (2) IL-36R expression is maintained by circulating CD4+ lymphocytes which enter the intestinal lamina propria and (3) IL-36R/IL-36 β induces rapid CD4 lymphocyte proliferation. The possible significance of these results in the context of human disease is discussed. [ABSTRACT FROM AUTHOR]

Transparent dispersion of silver nanoparticles (Ag-NPs) is important for transparent conductive coatings to fabricate the printed electronic devices such as flexible displays and solar cells. However, it is still great challenge to produce the transparent dispersion of Ag-NPs in large scale. In this work, we synthesize the transparent dispersion of monodispersed Ag-NPs with excellent conductive performance by a high-gravity strategy using rotating packed bed (RPB) reactor, which is easy to realize the large scale production. Based on the nano-dispersion, the transparent conductive films are further fabricated. The as-synthesized Ag-NPs are monodispersed in liquid medium with the average diameter about 7 nm. Compared with stirred tank reactor (STR), the Ag-NPs in transparent dispersions prepared by RPB have a smaller average diameter, a narrower particle size distribution (PSD) and better stability. The transparent conductive films with continuous percolated network structure exhibit excellent transparency and conductive properties. The visible transmittance of the films with a sheet resistance of 98.1 Ω/□ and 12.7 Ω/□ can reach 91% and 85% respectively. It is expected that the high-gravity technology would provide a promising strategy for the large-scale preparation of transparent silver dispersion for fabricating transparent electric devices. [ABSTRACT FROM AUTHOR]

Inhalable formulations of curcumin with hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone have been produced by a newly developed anti-solvent micronization technique based on the supercritical fluid (SCF) technology. The micronization process used is the atomized rapid injection solvent extraction process (ARISE), which utilizes high pressure carbon dioxide as the anti-solvent. The composition, particle morphology and aerodynamic performance of the samples were observed. Curcumin formulations with aerodynamic performance suitable for inhalation delivery have been produced and tested in vitro using normal and lung cancer cells (MRC-5 cells and H1299 cells, respectively). The cytotoxicity study revealed that the encapsulation of curcumin improved its biodistribution and solubility for lung cancer cells. A rapid cell uptake was observed for all formulations by confocal microscopy and flow cytometry. Fluorescence life time imaging microscopy showed a rapid release of curcumin in the cells. Results show that co-processing by ARISE preserved the anticancer properties of curcumin and generated inhalable powders thus demonstrating potential in the localized treatment of lung cancer. [ABSTRACT FROM AUTHOR]

We compared the effect of VIP on human blood monocytes infected with Salmonella typhimurium 4/74 or stimulated with LPS. VIP (10 −7 M) increased monocyte viability by 24% and 9% when cultured for 24 h with 4/74 or Salmonella LPS (100 ng/ml), respectively. Significantly increased ( P < 0.05) numbers of 4/74 were also recovered from monocytes co-cultured with VIP after 6 h post-infection (pi) and this remained high after 24 h pi. Both 4/74 and LPS increased ( P < 0.05) the concentration of TNF-α, IL-1β and IL-6 measured in monocyte supernatants. However, LPS induced this effect more rapidly while, with the exception of IL-6, 4/74 induced higher concentrations ( P < 0.05). VIP significantly decreased ( P < 0.05) TNF-α and IL-1β production by 4/74-infected monocytes after 6 pi, but only after 24 h in LPS-cultured monocytes. This trend was reversed for IL-6 production. However, TNF-α and IL-1β production by 4/74-infected monocytes, cultured with VIP, still remained higher ( P < 0.05) than concentrations measured in supernatants cultured only with LPS. VIP also increased ( P < 0.05) production of anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24 h. We also show a differential effect of VIP on the expression of TNFα and IL-6 receptors, since VIP was only able to decreased expression in LPS-stimulated monocytes but not in 4/74-infected monocytes. In conclusion, we show a differential effect of VIP on human monocytes infected with virulent Salmonella or stimulated with LPS. Our study suggests that the use of VIP in bacteraemia and/or sepsis may be limited to an adjunctive therapy to antibiotic treatment. [ABSTRACT FROM AUTHOR]