Targeted lipidomics distinguishes patient subgroups in mild cognitive impairment (MCI) and late onset Alzheimer's disease (LOAD)

AbstractBackgroundDiverse research approaches support the concept that a clinical diagnosis of Late-Onset Alzheimer's Disease (LOAD) does not distinguish between subpopulations with differing neuropathologies, including dementia patients with amyloid deposition and dementia patients without amyloid deposition but with cortical thinning. Mild cognitive impairment (MCI) is generally considered the prodromal phase for LOAD, however, while a number of studies have attempted to define plasma biomarkers for the conversion of MCI to LOAD, these studies have not taken into account the heterogeneity of patient cohorts within a clinical phenotype.MethodsStudies of MCI and LOAD in several laboratories have demonstrated decrements in ethanolamine plasmalogen levels in plasma and brain and increased levels of diacylglycerols in plasma and brain. To further extend these studies and to address the issue of heterogeneity in MCI and LOAD patient groups we investigated the levels of diacylglycerols and ethanolamine plasmalogens in larger cohorts of patients utilizing, high-resolution (0.2 to 2ppm mass error) mass spectrometry.ResultsFor the first time, our lipidomics data clearly stratify both MCI and LOAD subjects into 3 different patient cohorts within each clinical diagnosis. These include i) patients with lower circulating ethanolamine plasmalogen levels; ii) patients with augmented plasma diacylglycerol levels; and iii) patients with neither of these lipid alterations.ConclusionsThese represent the first serum biochemical data to stratify MCI and LOAD patients, advancing efforts to biochemically define patient heterogeneity in cognitive disorders.General significanceLipidomics offers a new approach for identifying biomarkers and biological targets in cognitive disorders

Surgical treatment of scoliosis in a rare disease: arthrogryposis

<p>Abstract</p> <p>Background</p> <p>The reported incidence of scoliosis in arthrogryposis varies from 30% to 67% and, in most cases, the curves progress rapidly and become stiff from early age.</p> <p>The authors report six cases of scoliosis in arthrogryposis to assess the role of surgical treatment.</p> <p>Methods</p> <p>Six cases (3 males, 3 females; mean age at surgery 13.2 years) with arthrogryposis multiplex congenita associated with the characteristic amyoplasia were reviewed: they were operated on for scoliosis at the authors' Spine Surgery Department between 1987 and 2008.</p> <p>Surgery was performed using the Harrington-Luque instrumentation (2 cases), the Luque system (1), a hybrid segmental technique with hooks and screws (1) and spinal anchoring with pedicle screws (2).</p> <p>Results</p> <p>The patients were clinically and radiologically reviewed at a mean follow-up of 4.2 years, ± 2.7 (range, 1 to 9 years). Three minor postoperative complications were encountered; a long-term pulmonary complication was seen in one case after reintervention and was successfully resolved after 10 days. Surgery was successful in the other 5 cases, where solid arthrodesis was achieved and no significant curve progression was observed at follow-up.</p> <p>Conclusions</p> <p>The experience acquired with the present case series leads the authors to assert that prompt action should be taken when treating such aggressive forms of scoliosis. In case of mild spinal deformities in arthrogryposis, brace treatment should be attempted, the evolution of the curves being unpredictable; however, when the curve exceeds 40° and presents with marked hyperkyphosis, hyperlordosis or pelvic obliquity, surgery should not be delayed.</p

ES2 as a novel verbascoside-derived compound in the treatment of cutaneous wound healing

Several pathologies are characterized by chronic wounds and often resistant to many of the common therapies, leading to chronic infections that can become even life-threatening for patients. For this reason, the identification of new products able to ameliorate the healing process is still an on-going research. Natural compounds have been used to improve skin conditions due to their dermo-cosmetic and therapeutic activities including anti-inflammatory, antioxidant and cell-migratory properties. Among these compounds, it has been recently demonstrated that Verbascoside, a phenyl propanoid glycoside widely used in the cosmetic field, can improve keratinocytes proliferation. Because of its high hydrophilic character, Verbascoside has a limited range of possible topical applications and the synthesis of ES2, a semi-synthetic derivative of Verbascoside was performed to bypass some of the drawback aspects of this molecule. In the present study, the wound healing properties of Verbascoside and ES2 were compared in both keratinocytes "in vitro" wound scratch and in wounded SKH1 mice. The results showed that both compounds were not cytotoxic and ES2 showed an efficient ability to promote the proliferation of human keratinocytes compared to Verbascoside. The findings were also confirmed in vivo but only at early time points (2/3 days). Taken together, these data suggest that the Verbascoside-derivative ES2 could be considered a novel and promising candidate for the topical treatment of wounds

Evaluation of in vitro antioxidant properties of some traditional Sardinian medicinal plants: Investigation of the high antioxidant capacity of Rubus ulmifolius

The antioxidant capacities of 11 botanical species used in the tradition of Sardinia as teas beverages or as decoction for medicinal purposes were evaluated using different in vitro methods (BR, TEAC, DPPH and FC). Among the various species, Rubus ulmifolius, resulted the more active with all the used methods. Phytochemical investigation on the extract yields in the isolation of several phenolic compounds namely caffeic acid, ferulic acid, quercetin-3-O-glucuronide, kaempferol-3-O-glucuronide, kaempferol-3-O-(600-p-coumaroyl)- b-D-glucopyranoside, kaempferol-3-O-(600-caffeoyl)-b-D-glucopyranoside, chlorogenic acid, 4-caffeoylquinic acid and 5-caffeoylquinic acid. The antioxidant activity of isolated compounds was also evaluated

Wulfenia carinthiaca Jacq., Antioxidant and Pharmacological Activities

Relative antioxidant activities of a methanolic extract of three phenylpropanoid glycosides and three iridoid glycosides from Wulfenia carinthiaca were evaluated using the Briggs- Rauscher (BR) reaction method. This method is based on the inhibitory effects by antioxidants on oscillations of the BR reaction. The total extract showed a certain antioxidant activity with respect to resorcinol chosen as standard. The three phenylpropanoid glycosides showed a very high relative antioxidant activity while iridoid glycosides had practically no activity. These experimental results were confirmed by empirical calculations based on the BDE (Bond Dissociation Enthalpy) theory. The total phenolic content was also measured for the phenylpropanoid glycosides using the Folin-Ciocalteu reagent. The obtained values as gallic acid equivalents were in perfect agreement with the relative antioxidant activities. From a pharmacological point of view the results obtained demonstrate that the methanolic extract of W. carinthiaca have antinociceptive and antiedematogenic effects in the different models adopted. The plant extract produced a significant inhibition, dose related, of the rat paw edema induced by carrageenin. The anti-inflammatory activity is probably due to the phenylpropanoid compounds present in the plant. The histological sections of paw tissue in animals treated with Wulfenia carinthiaca extract confirmed the anti-inflammatory effects. The results of the antinociceptive assay indicated a significant reduction on the number of abdominal writhes of mice, induced by acetic acid

Deoxypodophyllotoxin content and antioxidant activity of aerial parts of Anthriscus sylvestris Hoffm

Deoxypodophyllotoxin content of the aerial parts of Anthriscus sylvestris Hoffm. growing at different altitudes was evaluated in comparison to the roots. The lignan accumulation in ground parts was at least double compared to aerial ones. In addition antioxidant-guided fractionation of the crude methanol extract of aerial parts was performed with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Active fractions contained mainly luteolin-7-O-glucoside and chlorogenic acid. Antioxidant properties of both crude extract and isolated compounds were also investigated with the Briggs-Rauscher (BR) oscillating reaction. A satisfactory agreement between the results obtained with the two methods was observed

Polyphenols from Polygala spp. and their antioxidant activity

Members of Polygalaceae are known to contain a variety of different polyphenolic compounds such as xanthones, flavonoids and diphenylderivatives. Here, we report the isolation and structural characterization of two phenol derivatives, named Alpestrin (= 3,3\u2019,5\u2019-trimethoxy[1,1\u2019-biphenyl]-4-ol;10)) and Alpestriose A (=6-O-benzoyl-1-O-\uf07b6-O-acetyl-[4-hydroxy-3,5-dimethoxyphenyl)prop-2-enoyl] -\uf062-D-fructofuranosyl\uf07d-\uf061-D-glucopyranoside; 11), and of four known compounds (12-15) from the methanolic extract of Polygala alpestris. The relative in vitro antioxidant activities of these compounds, and in comparison with other phenolic substances from Polygala vulgaris, were evaluated by means of the Briggs-Rauscher (BR) oscillanting reaction, a method based on the inhibitory effects by antioxidant free-radical scavengers. The experimental antioxidant activity values (relative to resorcinol as a standard) were compared with those calculated on the basis of the bond-dissociation enthalpies. The structure/activity relationships for the compounds examined are also discussed

Phytochemical and Antioxidant-Related Investigations on Barkof Abies spectabilis (D. Don) Spach. from Nepal

The bark of several coniferous species, a waste product of the timber industry, contains significant amounts of natural antioxidants. In our ongoing studies of Nepalese medicinal plants, we examined the bark from Abies spectabilis as the starting material for extracting antioxidant compounds. In vitro antioxidant activity evaluated by means of three antioxidant methods, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH), Briggs-Rauscher oscillating reaction (BR) and Trolox Equivalent Antioxidant Capacity (TEAC) and total phenol contents with the Folin-Ciocalteau reagent; the ferrous iron chelating capacity was also assessed. The methanol extract of A. spectabilis showed significant antioxidant activity and polyphenol contents (IC50 4.13 \u3bcg/mL, 0.20 \u3bcg/mL eq. resorcinol, 4.22 mM eq. Trolox, 3.9 \u3bcg/g eq. gallic Acid in the DPPH, BR, TEAC and Folin-Ciocalteau tests, respectively) and weak Fe2+ chelating capacity. Phytochemical studies were also carried out with 1D- and 2D NMR experiments and DI-ESI-MS, HPLC-DAD and LC-MSn measurements. Oligomeric C-type proanthocyanidins, mainly trimeric gallocatechin derivatives, were the most abundant compounds (16% of extract expressed as procyanindin B1). Gallocatechin oligomers (up to six units) and prodelphynidin-gallocatechin polymers were also identified in the extract. Prodelphynidin B4, cyclograndisolide and trans-docosanil ferulate were also isolated and characterized by NMR and MS spectroscop

Gastroprotective Effect and Antioxidant Properties of Different Laurus nobilis L. Leaf Extracts

Laurus nobilis L. (Family Lauraceae) is an evergreen tree widely distributed in the Mediterranean area and Europe. It is used in folk medicine of different countries as a stomachic and carminative as well as in treatment of gastric diseases. Extracts obtained with different methods (methanol and chloroform) from laurel leaves were evaluated for their gastroprotective activities in the rat. The antioxidant capacity of the different extracts has been also measured in vitro. In order to confirm the activities investigated, histological observations were performed. The gastric damage was significantly reduced by all extracts administered. The more effective protection was produced by chloroformic and methanolic crude extracts. The results obtained after oral administration of L. nobilis leaf extracts are in good agreement with their antioxidant capacity, confirming the relationship between pharmacological efficacy and antiradical activity. Histological evidences confirm the results evaluated with the animal procedures