72 research outputs found
Transepithelial Corneal Cross-Linking With Vitamin E-Enhanced Riboflavin Solution and Abbreviated, Low-Dose UV-A: 24-Month Clinical Outcomes
Purpose: To report the clinical outcomes with 24-month follow-up of transepithelial cross-linking using a combination of a D-alpha-tocopheryl polyethylene-glycol 1000 succinate (vitamin E-TPGS)-enhanced riboflavin solution and abbreviated low fluence UV-A treatment.
Methods: In a nonrandomized clinical trial, 25 corneas of 19 patients with topographically proven, progressive, mild to moderate keratoconus over the previous 6 months were cross-linked, and all patients were examined at 1, 3, 6, 12, and 24 months. The treatments were performed using a patented solution of riboflavin and vitamin E-TPGS, topically applied for 15 minutes, followed by two 5-minute UV-A treatments with separate doses both at fluence below 3 mW/cm2 that were based on preoperative central pachymetry.
Results: During the 6-month pretreatment observation, the average Kmax increased by +1.99 +/- 0.29 D (diopter). Postoperatively, the average Kmax decreased, changing by -0.55 +/- 0.94 D, by -0.88 +/- 1.02 D and by -1.01 +/- 1.22 D at 6, 12, and 24 months. Postoperatively, Kmax decreased in 19, 20, and 20 of the 25 eyes at 6 months, 12 months, and 24 months, respectively. Refractive cylinder was decreased by 3 months postoperatively and afterward, changing by -1.35 +/- 0.69 D at 24 months. Best spectacle-corrected visual acuity (BSCVA) improved at 6, 12, and 24 months, including an improvement of -0.19 +/- 0.13 logarithm of the minimum angle of resolution units at 24 months. There was no reduction in endothelial cell count. No corneal abrasions occurred, and no bandage contact lenses or prescription analgesics were used during postoperative recovery.
Conclusions: Transepithelial cross-linking using the riboflavin-vitamin E solution and brief, low-dose, pachymetry-dependent UV-A treatment safely stopped keratoconus progression
Chemistry meets Industry and Society A creative showcase conference
Buffalo milk contributes to 13% of the world milk production and is abundantly produced in Southern Italy regions. Buffalo milk is appreciated for its nutritive properties and is highly suitable for the manufacturing of wide range of dairy products. Several studies showed many bioactive peptides in different dairy species such as bovine, ovine and caprine milk, but few studies have been conducted on the buffalo dairy products (1). The present work is focused on the identification of bioactive peptides released after in vitro simulated gastrointestinal digestion of protein fraction isolated from buffalo-milk dairy products by ultra- and nanofiltration pilot plant.
The gastrointestinal digests of protein fractions were monitored by RP-UHPLC-DAD, while, the peptide identification was carried out by UHPLC-Orbitrap-based tandem mass spectrometry. 165 peptides were identified in Yoghurt, 152 in Scamorza, 146 in Mozzarella, 136 in Grana and Ricotta and 120 in Ice Cream samples (1). The peptides belong to both buffalo caseins (αs1-, β-, k-CN) and whey proteins (α-LA, β-LG).
Six G.I. digests of dairy products were tested in a model of oxidative stress using IEC-6 cells. Among them, buffalo ricotta cheese was the most active. UHPLC-PDA-MS/MS analysis revealed the presence of two abundant β-lactoglobulin peptides (BRP: YVEELKPTPEGDL, f:60-72 and BRP2: SFNPTQL, f:168-174). To confirm the hypothesized chemical structures and study their specific biological activity, the peptides were synthesized by conventional solid-phase peptide synthesis methods. The antioxidant potential of the identified peptides was then evaluated in a model of hydrogen peroxide induced oxidative stress in IEC-6 cell line. The peptides reduce ROS release and increase nuclear factor (erythroid-derived 2)-like 2 activation and the expression of antioxidant cytoprotective factors such as heme oxygenase 1, NAD(P)H: quinone oxidoreductase 1 and superoxide dismutase (2). The bioavailability of β-lactoglobulin peptides was evaluated in intestinal transport studies through Caco-2 cell monolayer. Only BRP2 showed equal bi-directional transport and linear permeability, suggesting that it was mainly absorbed through passive diffusion. In addition to its local effects, administration of BPR2 on mice mesenteric arteries counteracts the Angiotensin II-induced vasoconstriction by Nrf2 nuclear translocation, reduction of active form of Ras-related C3 botulinum toxin substrate 1 (Rac1) and NADPH oxidase activity. The analysis at molecular level of treated vessels showed an induction of Nrf2 translocation to nucleus associated with increased expression of MnSOD and Rac1 deactivation.
The data indicate how protein fraction of buffalo ricotta cheese could be an important source of antioxidant compounds, as well as YVEELKPTPEGDL and SFNPTQL peptides could be considered as an “ingredient” for nutraceuticals formulations and functional and personalized foods, in order to prevent the onset of some gastrointestinal pathologies and cardiovascular diseases
Characterization of New TRPM8 Modulators in Pain Perception
Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain.
Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration.
Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation.
Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain
Bioavailable Citrus sinensis extract: Polyphenolic composition and biological activity
Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrus sinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value
Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography
Purpose: This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XCT) in conjunction with conventional characterization methods. Method: Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results: The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XCT. Conclusion: TASC and XÎĽCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure
Nobiletin and xanthohumol sensitize colorectal cancer stem cells to standard chemotherapy
Colorectal cancer (CRC) mortality is mainly caused by patient refractoriness to common anti-cancer therapies and consequent metastasis formation. Besides, the notorious toxic side effects of chemotherapy are a concurrent obstacle to be tackled. Thus, new treatment approaches are needed to effectively improve patient outcomes. Compelling evidence demonstrated that cancer stem cells (CSCs) are responsible for treatment failure and relapse. New natural treatment approaches showed capabilities to selectively target the CSC subpopulation by rendering them targetable by standard cytotoxic compounds. Herein we show the anti-cancer properties of the polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively. The natural biofunctional fractions, singularly and in combination, reduced the cell viability of CRC stem cells (CR-CSCs) and synergized with 5-fluorouracil and oxaliplatin (FOX) chemotherapy. These phenomena were accompanied by a reduced S and G2/M phase of the cell cycle and upregulation of cell death-related genes. Notably, both phytoextracts in combination with FOX thwarted stemness features in CR-CSCs as demonstrated by the impaired clonogenic potential and decreased Wnt pathway activation. Extracts lowered the expression of CD44v6 and affected the expansion of metastatic CR-CSCs in patients refractory to chemotherapy. Together, this study highlights the importance of polymethoxyflavones and prenylflavonoids as natural remedies to aid oncological therapies
Biodistribution of biodegradable polymeric nano-carriers loaded with busulphan and designed for multimodal imaging
Application of hydrophilic-lipophilic deviation (HLD) formulation concept to multiple emulsion.
In-vitro and in-vivo evaluation of oligoethylene esters as dermal prodrugs of 18-b-glycirrethic acid.
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