Ethanol-mediated neutrophil extravasation in feline pancreas

Ethanol is a common cause of both acute and chronic pancreatitis. Studies in other organs suggest that polymorphonuclear neutrophils activated by ethanol may cause tissue injury in a variety of conditions. The aim of this study was to investigate the effects of ethanol on neutrophil extravasation in the feline pancreas. Pancreata were isolated and perfused at different flow rates with varying concentrations of ethanol in either a physiological or neutrophil depleted perfusate. Neutrophil extravasation was assessed by measuring pancreatic tissue myeloperoxidase (MPO) activity. Ethanol at 2.5% (54.25 mmol/liter) was the lowest concentration that still caused significant neutrophil extravasation (3.1+/-0.8 vs 1.9+/-0.2 units, P<0.05) and was accompanied by an increase in vascular resistance of 15%. Reduction of pancreatic perfusion by 15% did not significantly increase neutrophil extravasation. (1.1+/-0.3 vs 1.6+/-0.2 units, NS) Perfusion of the pancreas with neutrophil-depleted blood containing either ethanol or saline, followed by perfusion with an ethanol-free perfusate, showed an increase in neutrophil extravasation in the ethanol group compared to the control group (3.2+/-0.9 vs 1.9+/-0.2 units, P<0.05). In conclusion, ethanol causes neutrophil extravasation in the feline pancreas independent of blood flow changes and occurs despite the absence of direct neutrophil exposure to ethanol.     

The control of protein release from poly(DL-lactide co-glycolide) microparticles by variation of the external aqueous phase surfactant in the water-in oil-in water method

A unique feature of p21 that distinguishes it from the other cyclin-dependent kinase (CDK) inhibitors is its ability to associate with the proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerases delta and epsilon. While it is now well established that inhibition of cyclin/CDK complexes by p21 can result in G1 cell cycle arrest, the consequences of p21/PCNA interaction on cell cycle progression have not yet been determined. Here, we show, using a tetracycline-regulated system, that expression of wild-type p21 in p53-deficient DLD1 human colon cancer cells inhibits DNA synthesis and causes G1 and G2 cell cycle arrest. Similar effects are observed in cells expressing p21CDK-, a mutant impaired in the interaction with CDKs, but not in cells expressing p21PCNA-, a mutant deficient for the interaction with PCNA. Analysis of cells treated with a p21-derived PCNA-binding peptide provides additional evidence that the growth inhibitory effects of p21 and p21CDK result from their ability to bind to PCNA. Our results suggest that p21 might inhibit cell cycle progression by two independent mechanisms, inhibition of cyclin/CDK complexes, and inhibition of PCNA function resulting in both G1 and G2 arrest.     

The role of prostaglandin E2 and nitric oxide in cell death in J774 murine macrophages

We investigated the role of prostaglandin E2 (PGE2) and its interactions with nitric oxide (NO) on cell death and NO-mediated cytotoxicity in the murine macrophage cell line J774. Stimulation of the J774 cells with lipopolysaccharide together with interferon-gamma resulted in a dose-dependent cytotoxicity and production of PGE2 and NO, measured as nitrite. Our results showed a linear correlation between PGE2 release and cytotoxicity. The cyclooxygenase (COX) inhibitor indomethacin completely inhibited PGE2 biosynthesis, without affecting NO production or cell death. This supports previous reports suggesting that overproduction of endogenous PGE2 is mainly the consequence of cell death and does not cause it. In contrast, the NO synthase inhibitor N(omega)-monomethyl-L-arginine (L-NMMA) gave a significant, though incomplete suppression of NO release and cell death. This points to the presence of other cytotoxic factors besides NO. To evaluate the toxic effect solely due to NO, macrophages were exposed to the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Incubation with SNAP also resulted in a concentration-dependent cell injury and PGE2 production. When exogenously added, PGE2 protected against SNAP-mediated cytotoxicity and simultaneously increased PGE2 release into the medium, without inducing COX-2. The cytoprotection and the stimulation of PGE2 release were both reversed by indomethacin. In conclusion, PGE2 biosynthesis may represent a mechanism by which inflammatory macrophages protect themselves against the cytotoxic effects of NO.     

Congenital cystic diseases of liver and extrahepatic bile ducts

The paper presents 30-year experience in treating 158 patients with congenital cystic diseases of the liver and bile ducts. Depending on the pattern of hepatobiliary lesions, the diagnostic value of techniques, such as ultrasound, computerized tomography, scintigraphy of the liver duodenoscopy with THCG was defined. Analyzing the late outcomes provided recommendations for the most optimal surgical management: cystic fenestration and tunneling in hepatic polycystosis, pericystectomy in solitary cysts of the liver, different varieties of bile draining operations in choledochal cysts and Caroli's disease.     

Cycling stability of a hybrid activated carbon//poly(3-methylthiophene) supercapacitor with N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide ionic liquid as electrolyte

A long cycle-life, high-voltage supercapacitor featuring an activated carbon//poly(3-methylthiophene) hybrid configuration with N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide ionic liquid, a solvent-free green electrolyte, was developed. The cyclability of a laboratory scale cell with electrode mass loading sized for practical uses was tested at 60 °C over 16,000 galvanostatic charge-discharge cycles at 10 mA cm⁻² in the 1.5 and 3.6 V voltage range. The reported average and maximum specific energy and power, specific capacitance and capacity, equivalent series resistance and coulombic efficiency over cycling demonstrate the long-term viability of this ionic liquid as green electrolyte for high-voltage hybrid supercapacitors.     

Nitrogen budget for fescue pastures fertilized with broiler litter in Major Land Resource Areas of the southeastern US

The southeast US produces a tremendous number of broiler chickens (Gallus gallus), which in turn produce massive quantities of litter (manure and bedding materials). In the Southeast, litter is most often disposed of via land application to pastures, however, the ultimate fate of much of the applied nitrogen (N) is not known. We have constructed N budgets for three sites across the southeastern U.S. in an effort to determine how much of the applied N is useful for plant production and how much is left to be absorbed by the environment. Study sites were located in the Coastal Plain (Alabama), Piedmont (Georgia), and Cumberland Plateau (Tennessee) Major Land Resource Areas (MLRA) of the southeastern US. Litter was applied in the Spring of two consecutive years at a rate to supply 70 kg of available N ha^–1. The total amount of N applied ranged from 103 to 252 kg N ha^–1 depending on site and year. Nitrogen fluxes monitored in this study were broiler litter N, ammonia (NH₃) volatilization, denitrification, plant uptake, and leaching. Plant uptake represented the largest flux of applied N, averaging 43% of applied N. Losses due to NH₃ volatilization and denitrification combined were only 6% of applied N on average. Loss of N due to NO₃-N leaching appeared to be significant only at the Coastal Plain site where NO₃-N concentrations in the groundwater peaked at 38 mg N l^–1. We believe the majority of excess N shown in these budgets is likely accounted for by leaching losses and soil accumulation. Regardless of these assumptions and low gaseous losses, it is apparent that on average, 57% of applied N is destined for a fate other than plant uptake. The results of this study indicate that land-application of broiler litter at currently recommended rates has the potential for negative impacts on the environment of the southeastern U.S. in the long-term.     

A new thermoset for separation of polystyrene and naphthalene in preparative chromatography

Many research groups in recent years have demonstrated the importance of obtaining new materials and reducing environmental impact. In this context, the chemical modification of cellulose and its derivatives has received much attention. This study synthesized cellulose acetate gel (CAMDIH) obtained through the modification of cellulose acetate (CA) with a degree of substitution of 2.5, by crosslinking reactions using 4,4′‐diphenylmethane diisocyanate in homogeneous medium. The formation of crosslinks were observed by the presence of Fourier transform infrared spectroscopy absorption bands at 3046 and 864 cm^?1, which correspond to the absorption of aromatic groups associated with the incorporation of 4,4′‐diphenylmethane diisocyanate in the CA structure. The potential applications of the gel as a stationary phase were tested using column chromatography in the fractionation and separation of standard solutions of polystyrene and naphthalene. The findings showed the effectiveness of the gel as a stationary state in the separation of mixture compounds. Furthermore, the study found that CAMDHI is an innovative material when considering its simple synthesis and the low costs involved in the process. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46063.     

Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca²⁺ release from the sarcoplasmic reticulum (0 mM Ca²⁺), but it reduced the subsequent tonic phase characterised by Ca²⁺ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca²⁺ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K⁺ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.     

Shear-induced orientation in polymer/clay dispersions via in situ X-ray scattering

We report in situ X-ray scattering measurements of shear-induced orientation in polymer-clay dispersions. Two different organically modified clays, montmorillonite and fluorohectorite, are dispersed in a low molecular weight, viscous polymer melt, facilitating studies at room temperature. Orientation measurements are performed in the flow-gradient plane, allowing characterization of both the average degree and direction of particle orientation during shear. In all cases, the orientation angle is finite, indicating systematic misalignment of the particle long axes relative to the flow direction. In concentrated fluorohectorite and montmorillonite dispersions, anisotropy and orientation angle are roughly independent of shear rate, and negligible relaxation is observed upon flow cessation. Conversely, a lower concentration montmorillonite sample exhibits orientation that is more responsive to shear flow, and partially relaxes upon flow cessation. In this sample, the orientation behavior is interpreted in light of rotational diffusion of the clay particles. This same sample exhibits oscillatory structural dynamics upon shear flow reversal, attributed to tumbling rotations of the disk-like clay particles in shear. Large-amplitude oscillatory shear is similarly demonstrated to be capable of inducing significant particle orientation; the degree of orientation is principally determined by the applied strain amplitude. Complementary measurements of rheological properties exhibit many characteristics commonly reported in polymer-clay nanocomposites. Based on the structural measurements reported here, the rheological phenomena are interpreted to arise from a combination of flow-induced particle orientation and rate- and time-dependent destruction or reformation of particle networks.     

Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that exist on a disease spectrum due to pathological, clinical and genetic overlap. In up to 97% of ALS cases and ~50% of FTLD cases, the primary pathological protein observed in affected tissues is TDP-43, which is hyperphosphorylated, ubiquitinated and cleaved. The TDP-43 is observed in aggregates that are abnormally located in the cytoplasm. The pathogenicity of TDP-43 cytoplasmic aggregates may be linked with both a loss of nuclear function and a gain of toxic functions. The cellular processes involved in ALS and FTLD disease pathogenesis include changes to RNA splicing, abnormal stress granules, mitochondrial dysfunction, impairments to axonal transport and autophagy, abnormal neuromuscular junctions, endoplasmic reticulum stress and the subsequent induction of the unfolded protein response. Here, we review and discuss the evidence for alterations to these processes that have been reported in cellular and animal models of TDP-43 proteinopathy.