Paloma Bermejo

Differences of peripheral inflammatory markers between mild cognitive impairment and Alzheimer's disease.

Multiple pathogenic factors may contribute to the pathophysiology of Alzheimers disease (AD). Peripheral markers have been used to assess biochemical alterations associated with AD and mild cognitive impairment (MCI) involved in its pathophysiology. The present study was conducted to evaluate inflammatory peripheral markers in elderly patients with MCI, patients with AD and normal elderly subjects. We measured plasma levels of different cytokines (IL-6, TNF-alpha and IFN-alpha) and platelet levels of cyclooxigenase-2 (COX-2) from 34 patients with MCI, 45 patients with AD and 28 age-matched control subjects. MCI and AD patients showed similarities in TNF-alpha and COX-2 levels, and differences in IL-6 and INF-alpha. Whereas augmented IL-6 levels have been found in AD patients, a significant increase in INF-alpha has been detected only in patients with MCI possibly associated with the depression stage frequently found in cognitive impairment. In conclusion, inflammatory response may be an early factor in AD development and these changes in circulating markers are possibly related to the progression of MCI to AD.

Antiinflammatory and antioxidant activity of plants used in traditional medicine in Ecuador

Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.

Iron-chelating ability and antioxidant properties of phycocyanin isolated from a protean extract of Spirulinaplatensis.

The invitro scavenger activities of different reactive oxygen species (superoxide radical, hydroxyl radical, hydrogen peroxide, hypochlorous acid and peroxyl radical), the effects on lipid peroxidation and the iron-chelating ability of a Spirulinaplatensis protean extract and the biliprotein, phycocyanin, isolated from this microalga were studied. S. platensis protean extract inhibited the generation of hydroxyl radical (IC50=537μg/ml for the system with EDTA and 1500μg/ml without EDTA), the production of peroxyl radical (IC50=230μg/ml), and the lipid peroxidation process (IC50=2320μg/ml for the enzymatic system and 2180μg/ml for the non-enzymatic system). Besides, phycocyanin inhibited hydroxyl and peroxyl radicals and the lipid peroxidation process. The iron ions decreased the maximum fluorescence emission spectra of S. platensis protean extract and phycocyanin and it was an indicator of the metal-chelating activity. The antioxidant properties of S. platensis and phycocyanin may arise from both radical-scavenging and metal chelation. Our results suggest that S. platensis could be used as a dietary supplement to prevent some diseases where free radicals are involved.

Peripheral levels of glutathione and protein oxidation as markers in the development of Alzheimer's disease from Mild Cognitive Impairment.

There is a great interest in the relationship between Mild Cognitive Impairment (MCI) and the progression to Alzheimers disease (AD). Several studies show the importance of oxidative stress in the pathogenesis of AD. The purpose of this study was the link between oxidative damage, MCI and AD. It analysed protein carbonyls and erythrocyte glutathione system plasma levels of 34 subjects with MCI, 45 subjects with AD and 28 age-matched control subjects. The results showed an increase in protein modification, a decrease in GSH levels and GSH/GSSG ratio in AD and MCI patients compared to age-matched control subjects (p<0.05). The present study shows that some peripheral markers of oxidative stress appear in MCI with a similar pattern to that observed in AD, which suggests that oxidative stress might represent a signal of the AD pathology. AD and MCI are biochemically equivalent. MCI does not necessarily need to progress to AD on a biochemical level.

Inhibition of NOS‐2 expression in macrophages through the inactivation of NF‐κB by andalusol

Andalusol, ent‐6α,8α,18‐trihydroxy‐13(16),14‐labdadiene, is a naturally occurring diterpene, isolated from Sideritis foetens (Lamiaceae). This compound exhibited therapeutic activity when evaluated in in vivo models of paw and ear inflammation (Navarro et al., 1997: Z. Naturforsch., 52, 844‐849). The pharmacological effects of this diterpene have been analysed on the activation of the macrophage cell line J774 with lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ). Incubation of J774 macrophages with andalusol (0.1–100 μM) inhibited the synthesis of nitrite caused by LPS (1 μg ml−1) in concentration and time‐dependent manners. The maximal inhibition was observed when andalusol was added 30 min before LPS stimulation and decreased progressively as the interval between andalusol and LPS challenge increased up to 14 h. Incubation of J774 cells with LPS resulted in the expression of NOS‐2 protein (130 kDa) as identified by Western blot analysis. The levels of this enzyme decreased significantly in the presence of andalusol (IC50=10.5 μM), suggesting that this diterpene inhibited NOS‐2 expression. Andalusol inhibited nuclear factor κB activation, a transcription factor necessary for NOS‐2 expression in response to LPS and IFN‐γ. This compound also inhibited the degradation of IκBα favouring the retention of the inactive NF‐κB complexes in the cytosol. Related compounds to andalusol but lacking the polyol groups were less effective inhibiting NOS‐2 expression in LPS‐activated macrophages. The present findings provide a mechanism by which the anti‐inflammatory properties of this diterpene could be mediated.

Kaurane diterpenes protect against apoptosis and inhibition of phagocytosis in activated macrophages

The kaurane diterpenes foliol and linearol are inhibitors of the activation of nuclear factor κB, a transcription factor involved in the inflammatory response. Effects of these diterpenes on apoptosis and phagocytosis have been analysed in cultured peritoneal macrophages and in the mouse macrophage cell line, RAW 264.7.

Controlled release of cyclosporine from VP-HEMA copolymer systems of adjustable resorption monitorized by MEKC

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of drugs, taking cyclosporine as a model system. The copolymerization parameters described as reactivity ratios, rVP = 0.08 and rHEMA = 7.97, indicate that the copolymer systems prepared at high conversion have two main components with a microstructural arrangement which depends on the average composition, i.e., an initial HEMA-rich copolymer and a final PVP homopolymer or VP-rich copolymer. This microstructural distribution controls the resorption rate of the polymeric support and therefore the release process of cyclosporine which is demonstrated experimentally by the application of a modern technique known as micellar electrokinetic capillary chromatography (MEKC).

Modulated release of cyclosporine from soluble vinyl pyrrolidone--hydroxyethyl methacrylate copolymer hydrogels. A correlation of 'in vitro' and 'in vivo' experiments.

Soluble, uncrosslinked and high molecular weight copolymers of vinylpyrrolidone, VP, with 2-hydroxyethyl methacrylate, HEMA, prepared by free radical copolymerization, are proposed as supports for the modulated release of the immunosuppressor cyclosporine. Two copolymeric systems with copolymer compositions f(VP)=0.52 (namely VP--HEMA 60--40) and 0.42 (VP--HEMA 40--60) have been prepared and tested in vitro and in vivo using rats as animal model. Micellar electrokinetic capillary chromatography, MEKC, has been used for the simultaneous detection of the polymer reabsorption and the drug release for the in vitro experiments. The composition and microstructural distribution of the copolymer system controls the solubilization rate which modulates the in vitro release of the drug (with time profiles from a few days to several weeks for the VP--HEMA 60--40 and 40--60, respectively) and the in vivo response that correlates with the previous in vitro results: the more hydrophobic implant (VP--HEMA 40--60) reverts the immune response more slowly (2--4 weeks) compared to the more hydrophilic one (VP--HEMA 60--40, 1--2 weeks).