Microparticulate polyelectrolyte complexes for gentamicin transport across intestinal epithelial

Polysaccharide microparticles for the oral administration of gentamicin were designed in order to obtainan increased drug absorption by means of microparticle transport across the intestinal epithelia. Alginate/chitosan microparticles with a size of ∼ 2 μm were developed by spray-drying a water solution containingthe drug complexed with the polyanionic alginate and subsequent alginate cross-linking process bycalcium ions and chitosan. The pre-formulation study, performed by changing the concentration of bothcross-linkers, led to the selection of the most suitable formulation which was assayed for its capacity to be translocated across intestinal epithelia, via both M cells contained in Follicle Associated Epithelium (FAE) ofPeyer’s patches and enterocytes of the mucosal epithelium. An ex vivo perfusion technique of rabbit andrat intestinal tissues containing Peyer’s patches combined with an in vitro method by using Caco-2 cellmonolayers demonstrated the microparticulate carrier ability to be taken up by both M cells and enterocytes.However, only the endocytosis by M cells appeared to provide the microparticle transport from theepithelium toward deeper sub-epithelial regions

Zingiber officinale Roscoe rhizome extract alleviates neuropathic pain by inhibiting neuroinflammation in mice

Background: Current therapies for neuropathic pain are generally symptomatic and possess several side effects, limiting their prolonged usage. Hypothesis/Purpose: Thus, it is urgent to develop novel and safe candidates for the management of this chronical condition. For this purpose, we investigated the analgesic effect of a standardized extract from Zingiber officinale Roscoe rhizomes (ZOE) obtained by CO2 supercritical extraction, in a mice model of peripheral neuropathy. We also explored the mechanism of action of ZOE and its main constituents using an in vitro model of neuroinflammation. Methods: Peripheral mono-neuropathy was induced in mice, by spared nerve injury (SNI). The analgesic effect of ZOE after oral administration was assessed by measuring mechanical and thermal allodynia in SNI mice. The mechanism of action of ZOE and its main constituents were investigated using spinal cords samples and in an in vitro model of neuroinflammation by ELISA, western blotting and immunofluorescence techniques. Results: Oral administration of ZOE 200 mg kg 121 ameliorated mechanical and thermal allodynia in SNI mice, with a rapid and a long-lasting effect. ZOE did not alter locomotor activity. In BV2 cells and spinal cord samples, ZOE, 6-gingerol and 6-shogaol reduced pERK levels, whereas ZOE and terpene fraction reduced HDAC1 protein levels, inhibited NF-\u3baB signalling activation and decreased IL-1\u3b2, TNF-\u3b1 and IL-6 release. ZOE and each tested constituent had a positive effect on inflammation-impaired SH-SY5Y cell viability. Conclusions: The oral administration of ZOE attenuated SNI-induced neuropathic pain symptoms by reducing spinal neuroinflammation, suggesting ZOE as a novel and interesting candidate for the management of neuropathic pain

Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as \u3949-Tetrahydrocannabinol (\u3949-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-Type C. sativa plants, but, unlike \u3949-THC, it is completely nonpsychoactive. Fibre-Type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of \u3949-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and \u3949-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of \u3949-THC deprived hemp

The effect of desflurane on neuronal communication at a central synapse

Although general anesthetics are thought to modify critical neuronal functions, their impact on neuronal communication has been poorly examined. We have investigated the effect induced by desflurane, a clinically used general anesthetic, on information transfer at the synapse between mossy fibers and granule cells of cerebellum, where this analysis can be carried out extensively. Mutual information values were assessed by measuring the variability of postsynaptic output in relationship to the variability of a given set of presynaptic inputs. Desflurane synchronized granule cell firing and reduced mutual information in response to physiologically relevant mossy fibers patterns. The decrease in spike variability was due to an increased postsynaptic membrane excitability, which made granule cells more prone to elicit action potentials, and to a strengthened synaptic inhibition, which markedly hampered membrane depolarization. These concomitant actions on granule cells firing indicate that desflurane re-shapes the transfer of information between neurons by providing a less informative neurotransmission rather than completely silencing neuronal activity

Use of a Zwitterionic Surfactant to Improve the Biofunctional Properties of Wool Dyed with an Onion (Allium cepa L.) Skin Extract

To improve the loadability and antioxidant properties of wool impregnated with onion skin extract, the introduction of SB3-14 surfactant in the dyeing process was evaluated. A preliminary investigation on the surfactant–quercetin interaction indicated that the optimal conditions for dye solubility, stability, and surfactant affinity require double-distilled water (pH = 5.5) as a medium and SB3-14 in a concentration above the c.m.c. (2.5 × 10−3 M). The absorption profile of textiles showed the flavonoid absorption band (390 nm) and a bathochromic feature (510 nm), suggesting flavonoid aggregates. The higher absorbance for the sample dyed with SB3-14 indicated greater dye uptake, which was further confirmed by HPLC analysis. The Folin–Ciocalteu method was applied to evaluate the total phenol content (TPC) released from the treated wool, while the assays FRAP, DPPH, ABTS, and ORAC were applied to evaluate the corresponding total antioxidant activity (TAC). Higher TPCs (about 20%) and TACs (5–55%) were measured with SB3-14, highlighting textiles with improved biofunctional properties. Spectrophotometric analyses were also performed with an artificial sweat. The potential cytotoxic effect of SB3-14 in both monomeric and aggregated forms, cell viability, and induction of apoptosis were evaluated in RAW 264.7 cells. These analyses revealed that SB3-14 is safe at concentrations below the c.m.c

Hippocampal synaptic and membrane function in the DBA/2J-mdx mouse model of Duchenne muscular dystrophy

Dystrophin deficiency is associated with alterations in cell physiology. The functional consequences of dystrophin deficiency are particularly severe for muscle physiology, as observed in Duchenne muscle dystrophy (DMD). DMD is caused by the absence of a 427 kDa isoform of dystrophin. However, in addition to muscular dystrophy symptoms, DMD is frequently associated with memory and attention deficits and epilepsy. While this may be associated with a role for dystrophin in neuronal physiology, it is not clear what neuronal alterations are linked with DMD. Our work shows that CA1 pyramidal neurons from DBA/2J-mdx mice have increased afterhyperpolarization compared to WT controls. All the other electrotonic and electrogenic membrane properties were unaffected by this genotype. Finally, basal synaptic transmission, short-term and long-term synaptic plasticity at Schaffer collateral to CA1 glutamatergic synapses were unchanged between mdx and WT controls. These data show that the excitatory component of hippocampal activity is largely preserved in DBA/2J-mdx mice. Further studies, extending the investigation to the inhibitory GABAergic function, may provide a more complete picture of the functional, network alterations underlying impaired cognition in DMD. In addition, the investigation of changes in neuronal single conductance biophysical properties associated with this genotype, is required to identify the functional alterations associated with dystrophin deficiency and clarify its role in neuronal function

Electromagnetic fields counteract IL-1β during chondrogenesis in synovial bovine mesenchymal progenitor cells

Objective. Mesenchymal stem cells (MSCs) isolated from synovium and from synovial fluid, have shown a chondrogenesis potential suggesting that synovium is an excellent source of MSCs for cartilage regeneration. Electromagnetic fields (EMFs) display several effects on cartilage: increase the synthesis of proteoglycans (PGs), prevents the catabolic effect of the pro-inflammatory cytokine interleukin-1β (IL-1β), appear useful for the treatment of osteoarthritis. Our goal was to evaluate if the chondrogenic differentiation of synovial bovine mesenchymal progenitor cells, may be influenced by EMFs. Further, as chondrogenic differentiation of MSCs could be altered in an inflammatory environment and EMFs can counteract IL-1β activity, we also evaluated the role of EMFs during chondrogenic differentiation in the presence of IL-1β. Design. Synovial fluid was aspirated from the metacarpophalangeal joints of bovine. Synovial cells at the 3rd passage were centrifuged to obtain pellet cultures. Pellets were cultured in chondrogenic medium alone (control) or supplemented with 10 ng/ml TGF-β3 and/or 50 ng/ml IL-1β. The pellets were unexposed or exposed to EMF (75 Hz, 1.5 mT) (Igea, Carpi, Italy), during the whole period in culture (34 days). Alcian blue for sulphated glycosaminoglycans and immunostaining for type II collagen, were performed. PG synthesis was measured by radioactive 35S-sulphate incorporation. Results. Pellets cultured in the presence of TGF-β3 exhibited positive staining for type II collagen and Alcian blue, compared to control, indicating chondrogenic differentiation of synovial bovine mesenchymal progenitor cells. In the presence of IL-1β, type II collagen and Alcian blue staining dramatically decreased compared to TGF-β3 treatment alone. When pellets treated with both TGF-β3 and IL-1β were exposed to EMF, the histochemical staining for type II collagen and Alcian blue increased compared to EMF-unexposed pellets, suggesting that EMF might counteract the IL-1β effect. Biochemical analysis on PG synthesis confirmed histochemical data. Conclusions. The presence of inflammatory cytokines, such as IL-1β in human joints, may explain why existing methods of cartilage engineering repair strategies, that rely on the in situ differentiation of MSCs, fail to provide a reliably successful. Results of this study support the hypothesis that EMF treatment may favour chondrogenic differentiation in inflammatory conditions, suggesting a possible strategy for improving the clinical outcome of cartilage repair procedures