Mineralogy and textures of riebeckitic asbestos (crocidolite): The role of single versus agglomerated fibres in toxicological experiments.

Asbestos may cause adverse effects, but relationship between mineralogy and texture of fibres versus toxicity is still lacking. Toxicological studies can be interpreted and compared only if quantitative features of fibres are determined. Here, riebeckitic ("crocidolite") amphibole fibres were analysed by XRPD, FTIR, SEM-EDS and EMP-WDS; only crystals with stochiometry A□BNa2C(Fe2+2.5Mg0.5)CFe3+2TSi8O22W(OH)2 are present in the starting material used for the experiments. Fibres deposited from solutions of 0.1, 1, 10, 25, 50, 75 and 100mg/L were counted by image analysis using SEM images. At 0.1 and 1mg/L the fibres are well separated, whereas between 1 and 10mg/L they start to agglomerate. In-vitro tests performed on fibres deposited at the same mg/L concentrations show that the toxic potential follows a curvilinear increasing trend with a decreasing rate. Since the range of sizes of single fibres and their mineralogy are constant, this decreasing rate can be only attributed to the increasing amount of agglomerated fibres. Hence, single versus agglomerated fibre population is a factor that cannot be neglected in defining the final adverse effects of asbestos. The analytical protocol proposed here is valuable for any aero-dispersed dust, in polluted environments, as well as in the interpretation of experimental studies.

Active principles of Grindelia robusta exert antiinflammatory properties in a macrophage model.

Plant extracts and/or secondary metabolites are receiving considerable attention as therapeutic agents for treating inflammatory diseases such as periodontitis, which affects the tooth supporting tissues. The aim of this study was to investigate the effect of a Grindelia robusta extract enriched in saponins and polyphenols on Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS)-induced inflammatory mediator (IL-6, TNF-a, RANTES, MCP-1, PGE(2) ) and matrix metalloproteinase (MMP-1, -3, -7, -8, -9, -13) secretion by macrophages. LPS induced a marked increase in the secretion of all inflammatory mediators and MMPs tested by macrophages, as determined by enzyme-linked immunosorbent assays. At non-cytotoxic concentrations, the G. robusta extract inhibited dose-dependently the secretion of IL-6, RANTES, MCP-1 and, to a lesser extent, PGE(2) and TNF-a. Such inhibition was also observed for MMP-1, -3, -7, -8, -9 and -13 secretion. This ability of G. robusta extract to reduce the LPS-induced secretion of inflammatory mediators and MMPs was associated with a reduction of nuclear factor-kappa B (NF-kB) p65 activation. The results suggest that G. robusta extract possesses an antiinflammatory therapeutic potential through its capacity to reduce the accumulation of inflammatory mediators and MMPs.

Antioxidant effects of garlic in young and aged rat brain in vitro.

Oxidative stress plays a key role in the pathogenesis of age-related neurodegeneration, and the nonenzymatic production of 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) may represent a reliable index of cellular oxidative damage. Garlic (Allium sativum) has been associated with peripheral antioxidant activities and therefore might prevent or reverse 8-iso-PGF(2alpha) production, but scant data are available on its possible neuroprotective effects. Therefore, we have studied the possible antioxidant effects of a garlic extract in rat brain synaptosomes obtained from young (3-month-old) and aged (14-month-old) male Wistar rats that were perfused, in vitro, with graded concentrations of a garlic extract (10-500 microg/mL). Release in the effluent was evaluated, both in the basal state and after hydrogen peroxide-induced oxidative stress. In young rats, we observed a concentration-dependent inhibitory effect of the garlic extract on brain 8-iso-PGF(2alpha) production, both basally and after hydrogen peroxide-induced oxidative stimulus. In aged rats, 8-iso-PGF(2alpha) production was not affected by the garlic extract in the basal state, whereas, after hydrogen peroxide-induced oxidative stimulus, an antioxidant effect of the garlic extract appeared only at the higher concentration tested. In conclusion, garlic supplementation could be effective in preventing brain oxidative damage in young animals, whereas the aging brain seems to be resistant to the antioxidant effects of garlic, in vitro.

Glucagon-like peptide 1 (7-36) amide (GLP-1) and exendin-4 stimulate serotonin release in rat hypothalamus.

Glucagon-like peptide 1 (7-36) amide (GLP-1) and exendin-4 are gastrointestinal hormones as well as neuropeptides involved in glucose homeostasis and feeding regulation, both peripherally and at the central nervous system (CNS), acting through the same GLP-1 receptor. Aminergic neurotransmitters play a role in the modulation of feeding in the hypothalamus and we have previously found that peripheral hormones and neuropeptides, which are known to modulate feeding in the central nervous system, are able to modify catecholamine and serotonin release in the hypothalamus. In the present paper we have evaluated the effects of GLP-1 and exendin-4 on dopamine, norepinephrine, and serotonin release from rat hypothalamic synaptosomes, in vitro. We found that glucagon-like peptide 1 (7-36) amide and exendin-4 did not modify either basal or depolarization-induced dopamine and norepinephrine release; on the other hand glucagon-like peptide 1 (7-36) amide and exendin-4 stimulated serotonin release, in a dose dependent manner. We can conclude that the central anorectic effects of GLP-1 agonists could be partially mediated by increased serotonin release in the hypothalamus, leaving the catecholamine release unaffected.