Increased 24-hour endothelin-1 urinary excretion in patients with chronic obstructive pulmonary disease

Abnormalities in endothelin-1 (ET-1) pulmonary metabolism have been reported in patients with pulmonary hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this study we have evaluated the 24-hour urinary excretion of ET-1 in COPD patients both during acute exacerbation and stable phase of the disease. ET-1 plasma and urinary levels were measured in 13 COPD patients on admission to the hospital for an acute exacerbation and at the recovery period. Ten healthy volunteers were also studied. Determination of plasma and 24-Hour urinary ET-1 levels were carried out with a radioimmunoassay test. Plasma ET-1 levels in COPD patients were similar during exacerbation and recovery and were not significantly different from those in the healthy subjects. 24-hour urinary excretion of ET-1 was increased in COPD patients during acute exacerbation; it decreased during recovery, but remained elevated when compared to normal subjects. A negative correlation was found between arterial oxygen pressure and ET-1 excretion; no correlation was found between plasma and urinary ET-1 values. In conclusion, COPD patients excrete higher amounts of ET-1 compared to healthy subjects. Urinary ET-1 values are further increased during acute exacerbation of the disease.     

Alteration of Hepatic microsomal enzyme systems and the lethal action of non-steroidal anti-arthritic drugs in acute and chronic models of inflammation

Depression of the hepatic microsomal enzyme system(s) in adjuvant-induced polyarthritis (AIP), a chronic inflammation model, has been confirmed indirectly by the enhancement of hexobarbital Na-induced sleeping time and extended for the first time to zoxazolamine-induced paralysis. In addition, barbital Na-induced anesthesia was increased during the course of AIP development, indicating that the CNS of these rats appears to be more sensitive to drug effects, since this barbiturate is excreted virtually unmetabolized. Most likely because of these effects, LD50 values for acetylsalicylic acid, phenylbutazone and indomethacin in AIP rats decreased in terms of mg/kg (increased toxicity) as the disease became more severe (Day 21) since they are known ultimately to be metabolized by the liver. On the other hand, the toxicity of a new non-steroidal anti-inflammatory agent, meseclazone, was not altered significantly in AIP. This is most likely due to the fact that its near total conversion to 5-chlorosalicylic acid has been shown to occur by hydrolytic cleavage as it pases through the intestinal wall with litter hepatic involvement. Finally, carrageenan edema, a model of acute inflammation, did not affect barbiturate sleeping times of zoxazolamine paralysis, nor were any of these drugs studied more lethal in this disease state.     

Impact of diet supplemented with microencapsulated condensed tannins on cow milk nutritional profile

Feed production systems should consider more sustainable solutions to reduce the pressure on earth's finite resources. In this work, we investigated the effect of microencapsulated condensed tannins (MCTs)-enhanced diet on the cow milk characteristics. The diet reduced the urea content, while preserved and the n-3 and n-6 portion of fatty acids. Aside from the rising of vitamin C level, MCTs had a negative effect on the amount of B group vitamins. MCTs may be considered a promising feed supplement that offers a good trade-off in terms of milk chemical quality while increasing the environmental sustainability of cattle livestock.     

Control of Morphological and Rheological Properties of Carrot Cell Wall Particle Dispersions through Processing

A range of thermal and mechanical processes were used to create dispersions with different particle morphologies, i.e., systems that contain primarily plant cell wall clusters with an average particle size (d(0.5)) of ～200 µm, single cells ((d(0.5)?=?～70 µm) or cell fragments (d(0.5)?=?～40 µm). The small and large deformation rheology (viscoelastic properties and flow properties) of these dispersions, with a range of total solid contents covering textures varying from a fluid to a paste, were determined. The particle dispersions showed weak gel-like behaviour. Their elastic modulus (G′) as a function of total solid content exhibited three regions of different rheological behaviours. The particles formed particulate colloidal networks at relatively low solid content. The interaction of particles contributed to the sharp increase in the elastic modulus of the dispersion in the concentrated region. Further packing of particles beyond the critical packing volume fraction, caused the G′ for the ‘cluster-cell’ and the ‘single-cell’ dispersions to reach a plateau value. This is due to particle deformation resulting in changes in their microstructure and their ability to pack closely. Plant particle dispersions displayed abrupt yielding at the critical stress with a 3–4 order decrease in viscosity and high yield stress at low solids due to the formation of particulate colloidal network.     

Biocompatibility of polyglycidol with human peripheral blood mononuclear cells

Polyglycidol (PGly), a hyperbranched water‐soluble polyether with numerous terminal hydroxyl groups, has structural similarities with polyethylene glycol. Our laboratory is exploring drug delivery using hyperbranched PGly‐cytokines conjugates. Using human peripheral blood mononuclear cells and a tumor derived human B cell line, HBL‐1; various PGly concentrations were tested for cytotoxicity. Our data indicated that hyperbranched PGly was similar in toxicity to PEG 8000, a commercial polymer. It was concluded that hyperbranched PGly did not exhibit significant cytotoxicity and showed promise for use as a biocompatible polymer. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

The Effect of the Ionizing Radiation on Hydroxyapatite–Polydimethylsiloxane Layers

The bio hydroxyapatite (HAp) was used from a long time in different medical and environmental applications. The HAp layers with a uniform surface were used for various medical applications such as orthopedic and dental metal implants. In this work, we reported on the influence of X‐ray radiation on the structural and morphological properties of composite layers based on HAp and polydimethylsiloxane (PDMS) deposited on titanium substrates. The HAp:PDMS layers were investigated by different complementary methods such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and glow discharge optical emission spectrometry (GDOES). FTIR spectral analysis showed that the molecular structure of the coatings was not changed after their irradiation even though, the depth profile analysis performed by GDOES indicated a depletion of Ca and P elements from the HAp:PDMS irradiated samples. By SEM, we showed that the morphological features of the coatings were also changed, as the irradiated layers are delaminated. The biological assays confirmed that the antibacterial activity of HAp:PDMS composite layers increased after irradiation. The results obtained in this study highlighted that the biological properties of HAp:PDMS layers could be influenced by irradiation. POLYM. ENG. SCI., 59:2406–2412, 2019. © 2019 Society of Plastics Engineers     

TAS-116, a Well-Tolerated Hsp90 Inhibitor,Prevents the Activation of the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells

Chronic inflammation has been associated with several chronic diseases, such as age-related macular degeneration (AMD). The NLRP3 inflammasome is a central proinflammatory signaling complex that triggers caspase-1 activation leading to the maturation of IL-1β. We have previously shown that the inhibition of the chaperone protein, Hsp90, prevents NLRP3 activation in human retinal pigment epithelial (RPE) cells; these are cells which play a central role in the pathogenesis of AMD. In that study, we used a well-known Hsp90 inhibitor geldanamycin, but it cannot be used as a therapy due to its adverse effects, including ocular toxicity. Here, we have tested the effects of a novel Hsp90 inhibitor, TAS-116, on NLRP3 activation using geldanamycin as a reference compound. Using our existing protocol, inflammasome activation was induced in IL-1α-primed ARPE-19 cells with the proteasome and autophagy inhibitors MG-132 and bafilomycin A1, respectively. Intracellular caspase-1 activity was determined using a commercial caspase-1 activity kit and the FLICA assay. The levels of IL-1β were measured from cell culture medium samples by ELISA. Cell viability was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase (LDH) measurements. Our findings show that TAS-116 could prevent the activation of caspase-1, subsequently reducing the release of mature IL-1β. TAS-116 has a better in vitro therapeutic index than geldanamycin. In summary, TAS-116 appears to be a well-tolerated Hsp90 inhibitor, with the capability to prevent the activation of the NLRP3 inflammasome in human RPE cells.     

Digestive protection of probiotic Lacticaseibacillus rhamnosus in Ricotta cheese by monoglyceride structured emulsions

This research aimed at studying the potential use of monoglyceride (MG) structured emulsions (MSEs) as delivery and protective systems for probiotic bacteria in Ricotta cheese. To this purpose, a low-fat commercial Ricotta cheese was added with MSEs formulated with milk, as water phase, and sunflower oil (MSE-SO) or anhydrous milk fat (MSE-AMF), as lipid phase. A commercial whole milk Ricotta cheese (W-RC) was considered as reference. A probiotic Lacticaseibacillus rhamnosus strain was inoculated as free cells in W-RC or embedded into the MSEs and added to the low-fat Ricotta at the same reference fat content. After physico-chemical characterisation, L. rhamnosus viability and sample destructuring behaviour upon in vitro digestion were evaluated. At the end of in vitro digestion, both W-RC and sample containing MSE-SO were unable to protect cells. By contrast, sample with AMF ensured a sufficient probiotic viability, even after 14 days of storage at 4 °C. This result was attributed to system composition and structure. During the gastric phase, the presence of caseins and MG-AMF mixed structures induced the formation of clots, entrapping and protecting cells against the acidic pH of the stomach, as confirmed by confocal micrographs and particle size. During the intestinal phase, cell viability was guaranteed by the formation of mixed micelles promoted by MG. It was demonstrated that microbial cells located near MG structures where they found protection.     

Strategies to Modulate Specialized Metabolism in Mediterranean Crops: From Molecular Aspects to Field

Plant specialized metabolites (SMs) play an important role in the interaction with the environment and are part of the plant defense response. These natural products are volatile, semi-volatile and non-volatile compounds produced from common building blocks deriving from primary metabolic pathways and rapidly evolved to allow a better adaptation of plants to environmental cues. Specialized metabolites include terpenes, flavonoids, alkaloids, glucosinolates, tannins, resins, etc. that can be used as phytochemicals, food additives, flavoring agents and pharmaceutical compounds. This review will be focused on Mediterranean crop plants as a source of SMs, with a special attention on the strategies that can be used to modulate their production, including abiotic stresses, interaction with beneficial soil microorganisms and novel genetic approaches.     

Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.