Long-term administration of butoctamide hydrogen succinate on nocturnal sleep of mentally retarded subjects: a polygraphic study versus placebo

Butoctamide hydrogen succinate (BAHS) has been proved to increase REM sleep in patients with reduced REM sleep. Following previous experiments on the effects of BAHS on nocturnal sleep of mentally retarded (MR) subjects, a polygraphic study was conducted on 20 MR subjects (age 8-14 years) to verify the effects of BAHS, 1) after long-term administration and 2) in different etiologies of MR. Subjects were divided into two balanced groups receiving placebo or 400 mg BAHS before sleep for a 6-month period. Basal sleep did not differ substantially in the two groups, both presenting reduced REM sleep. Low amounts of REM sleep were partially reversed by BAHS administration, which caused a significant increase in the REM sleep stage. Post-treatment sleep modifications found in the experimental group were not observed in the control group. BAHS produced its effects on REM sleep immediately after the first administration of the drug, but they became more apparent after long-term treatment. Our findings indicate that long-term administration of BAHS at low dosage maintains its effects on REM sleep of mentally retarded children, causing modifications similar to those previously obtained with single administration at higher dosages in cats, in healthy young and elderly volunteers and in Down's syndrome children. In addition, our observations demonstrate the effectiveness of BAHS on REM sleep, when utilized in mental retardation of etiologies other than Down's syndrome

The acetonation of methyl 5-C-methoxy-beta-D-galactopyranoside with 2,2-dimethoxypropane

The acetonation of methyl 5-C-methoxy-beta-beta-d-galactopyranoside (1a), masked bis-glycoside form of L-arabino-hexos-5-ulose, with a large excess of 2,2-dimethoxypropane and catalytic amounts of p-toluenesulfonic acid gives a mixture of five acetonides. The most abundant isolated product was the mixed acetal methyl 6-O-(1-methoxy-1-methylethyl)-3,4-O-isopropylidene-5-C-methoxy-beta-d- galactopyranoside (44% yield)

Simultaneous analysis of artemisinin and flavonoids of several extracts of Artemisia annua L. obtained from a commercial sample and a selected cultivar

Arteirtisia annua L. (Qinghao) is a promising and potent antimalarial herbal drug. This activity has been ascribed to its component artemisinin, a sesquiterpene lactone that is very effective against drug-resistant Plasmodium species with a low toxicity. Our studies indicate that several flavonoids of A. annua can promote and enhance the reaction of artemisinin with hemin. These data are in good agreement with previous investigations on the in vitro potentiation of antimalarial activity of artemisinin by such flavonoids. As a consequence, in view of a possible use of the phytocomplex rather than pure artemisinin, an HPLC/DAD/MS method is proposed for the simultaneous detection and quantification of both flavonoids and artemisinin. Different extracts, obtained from two different herbal drugs, a commercial sample and a selected cultivar, were analyzed in order to determine which solvents provide the best yields of both artemisinin and flavonoids. Qualitative and quantitative results obtained using an HPLC method are described, which will be useful for developing highly effective herbal drug preparations. (c) 2006 Elsevier GmbH. All rights reserved.13748749

Evaluation of different methods to determine total serum lipids for normalization of circulating organochlorine compounds

Objectives Serum levels of persistent organochlorine compounds may be predictive of their body burden, if adjusted by total serum lipids. Their value may be predicted by three diVerent formulae, requiring only values of serum cholesterol and triglycerides. The study was aimed at: (i) evaluating the validity of these formulae; (ii) evaluating the inXuence of diVerent estimates on serum levels of lipid adjusted persistent organochlorine compounds. Methods We determined the levels of cholesterol, triglycerides and phospholipids by enzymatic assays on serum samples from 121 subjects living in a polluted area of Northern Italy. On the same samples and on an additional set from 69 pregnant women of the same area, we determined also polychlorinated biphenyls, hexachlorobenzene and p,p-dichlorodiphenyldichloroethylene. In women, analytes were determined also on adipose tissue samples. Results Formulae provided results comparable to those obtained as sum of cholesterol, triglycerides and phospholipids. In women, we found highly signiWcant relationships among lipid adjusted pollutant levels in serum and adipose tissue, independently from the used formula. Conclusions Formulae allow a valid adjustment of organochlorine compounds in serum. The algorithm proposed by Phillips et al. provides some slight advantage over the others, in terms of simplicity of use

Cyclodextrins as carriers for kavalactones in aqueous media: Spectroscopic characterization of (S)-7,8-dihydrokavain and ß-cyclodextrin inclusion complex

Kavalactones represent the active constituents of kava–kava (Piper methysticum G. Forster),endowed with sedative and anaesthetic properties. Kavalactones are polar constituents, but poorly soluble in water with a low bioavailability. In this study, the formation of inclusion complexes of one of the most representative avalactone isolated from kava–kava extract, (S)-7,8-dihydrokavain (DHK), with beta-cyclodextrin (beta-CyD) was investigated mainly by spectroscopic methods. NMR experiments were extensively used for the complete characterization of the complex and included 1H NMR complexation shifts analysis, 1H NMR diffusion measurements (DOSY), and ROESY experiments. In particular DOSY experiments demonstrated that in the presence of beta-CyD the translational diffusion of kavalactone is sizably slowed down (2.5×10−10m2/s) with respect to the free drug (4.4×10−10m2/s) according to the inclusion of DHK in the cavity of beta-CyD. ROESY experiments confirmed the inclusion of DHK in the hydrophobic pocket of beta-CyD through the primary hydroxyl rim, being the most relevant interactions between the H3' of beta-CyD and the ortho protons on the phenyl ring of the DHK, and between H5' of beta-CyD and the meta/para protons of DHK phenyl ring. The inclusion of the phenyl ring of DHK, leaving the lactone moiety outside of CyD was also confirmed by the induced CD effects. The binary solution DHK/beta-CyD shows a 50% intensity increase of the negative band of the pi–pi* transitions of the phenyl ring with respect to the absorption observed with DHK alone. Molecular dynamics simulations results corroborated and further clarify observed spectroscopic data. It was found that the phenylethyl substituent at C6 has a preferential equatorial position in the free state, and an axial one in the complex, justifying the large downfield shift experienced by H6 of DHK upon binding. Finally the influence of beta-CyD on water solubility of DHK was investigated by phase-solubility studies. In the range 2–4mM of host, solubility of DHK was increased only two-fold, but being beta-CyD also a penetration enhancer, in vivo studies will be performed to clarify a possible role of the complex on the bioavailability of DHK

Studies on the interactions between some flavonols and cyclodextrins

The interactions of some natural flavonols with alpha, beta- and gamma-Cds have been investigated. Guest molecules were galangin, kaempferol and quercetin. Inclusion complexes were prepared by kneading and freeze-drying. The complexes were characterized using different physico-chemical methods based on differential scanning calorimetry (DSC), infrared spectroscopy (IR) and NMR spectroscopy. In the proton and carbon spectra the effects of complexation on the chemical shifts of the internal and external protons of Us in the presence of each flavonoid were observed. Moreover, the water-solubility of the flavonols in the presence of Us was also evaluated. The increased solubility of quercetin and kaempferol in the presence beta-Cd was evidenced. For all three guests, multidimensional NMR experiments in DMSO and water are consistent with dynamic binding processes, dominated by insertion of the B ring into the wider rim of the Cd cavity

Induction of erythroid differentiation of human K562 cells by 3-O-acyl-1,2-O-isopropylidene-D-glucofuranose derivatives

In this paper we report the synthesis of twelve 3-O-acyl-l,2-O-isopropylidene-D-glucofuranose derivatives and the results obtained on their effects in inducing erythroid differentiation of human leukemic K562 cells. The data obtained demonstrate that two of the newly synthetized compounds are able to induce erythroid differentiation of K562 cells. In addition, these same compounds potentiate K562 erythroid differentiation induced by cytosine arabinoside, retinoic acid and mithramycin. Inducers of erythroid differentiation stimulating fetal v-globin synthesis could be considered for possible use in the experimental therapy of hematological diseases associated with a failure in the expression of adult gamma-globin genes

Variation in artemisinin and flavonoid content in different extracts of Artemisia annua L.

Artemisia annua L. is a promising and potent antimalarial drug. This activity has been ascribed to its content of artemisinin, a sesquiterpene lactone that is stage specific and very effective against drug-resistant Plasmodium species and which has low toxicity. The in vitro antiplasmodial activity of artemisinin is enhanced by the flavonoids of the extract, as recently proposed by the authors. Different extracts (tinctures, infusions and decoctions), obtained from a cultivar selected by the University of Campinas (0.52% artemisinin), were analyzed in order to prove the selectivity of the solvents to obtain high yields of both artemisinin and flavonoids. Tinctures 40 and 60% v/v showed a greater power of extraction in comparison with infusions and decoctions. The best performance was obtained using 60% v/v tincture. The extraction efficiency for artemisinin was 40% and for flavonoids was 29.5%. Among aqueous extracts, the best results were obtained by preparing an infusion with boiling water, left to cool for 15 minutes before filtration. The extraction efficiency for artemisinin was 57.5% and for flavonoids was 8.2%. If leaves are boiled for several minutes the artemisinin concentration is decreased, probably due to the heat instability of this constituent. Also microwave could represent a valid alternative method to extract the phytocomplex, the extraction efficiency for artemisinin was 4 1.0% and that for flavonoids was 7.7%.1121111111