Nitric oxide-related toxicity in cultured astrocytes: effect of Bacopa monniera

There is growing evidence that high concentrations of nitric oxide (NO), generated by activated astrocytes, might be involved in a variety of neurodegenerative diseases, such as Alzheimer's disease, ischemia and epilepsy. It has recently been suggested that glial cells may produce NO under superoxide radical stimulation by enzyme-independent mechanism. This suggests that also natural antioxidants may have therapeutical relevance in neurodegenerative diseases. Studies of Bhattacharya et al. have evidenced that Bacopa monniera (BM) (family Scrophulariaceae), an Ayurvedic medicinal plant clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative, is able to reduce the memory-dysfunction in rat models of Alzheimer's disease, but the molecular mechanisms of this action are yet to be determined. In the present study, we examined the effect of a methanolic extract of BM on toxicity induced by the nitric oxide donor, S-nitroso-N-acetyl-penicillamine (SNAP), in culture of purified rat astrocytes. Our results indicate that, after 18 h of treatment, SNAP induced an increase in the production of reactive species, but did not induce the rupture of cellular membrane. Conversely, this NO donor induced a fragmentation of genomic DNA compared to control astrocytes. The extract of BM inhibited the formation of reactive species and DNA damage in a dose dependent manner. This data supports the traditional use of BM and indicates that this medicinal plant has a therapeutic potential in treatment or prevention of neurological diseases.     

Expression of univin, a TGF-beta growth factor, requires ectoderm-ECM interaction and promotes skeletal growth in the sea urchin embryo

Pl-nectin is an ECM protein located on the apical surface of ectoderm cells of Paracentrotus lividus sea urchin embryo. Inhibition of ECM-ectoderm cell interaction by the addition of McAb to Pl-nectin to the culture causes a dramatic impairment of skeletogenesis, offering a good model for the study of factor(s) involved in skeleton elongation and patterning. We showed that skeleton deficiency was not due to a reduction in the number of PMCs ingressing the blastocoel, but it was correlated with a reduction in the number of Pl-SM30-expressing PMCs. Here, we provide evidence on the involvement of growth factor(s) in skeleton morphogenesis. Skeleton-defective embryos showed a strong reduction in the levels of expression of Pl-univin, a growth factor of the TGF-beta superfamily, which was correlated with an equivalent strong reduction in the levels of Pl-SM30. In contrast, expression levels of Pl-BMP5-7 remained low and constant in both skeleton-defective and normal embryos. Microinjection of horse serum in the blastocoelic cavity of embryos cultured in the presence of the antibody rescued skeleton development. Finally, we found that misexpression of univin is also sufficient to rescue defects in skeleton elongation and SM30 expression caused by McAb to Pl-nectin, suggesting a key role for univin or closely related factor in sea urchin skeleton morphogenesis.     

Resistance to multiple steroids in two sisters

A 14-year-old Native American girl from the Iroquois Nation was referred as a potential patient with the syndrome of Apparent Mineralocorticoid Excess. Instead, her evaluation revealed resistance to glucocorticoids, mineralocorticoids, and androgens. She lacked Cushingoid features in spite of significantly high cortisol levels. Menstruation was regular and there was no clinical evidence of masculinization despite high serum androgen levels in the male range. The patient's sister had similar clinical features. Partial resistance to exogenous glucocorticoid and mineralocorticoid administration was well demonstrated in both patients. It is proposed that these patients represent the first cases of partial resistance to multiple steroids, possibly owing to a coactivator defect.     

Human milk oligosaccharides: an enzymatic protection step simplifies the synthesis of 3'- and 6'-O-sialyllactose and their analogues

We describe a chemo-enzymatic synthesis of 3'- and 6'-O-sialyllactose, two trisaccharides occurring in the 'acidic fraction' of the human milk oligosaccharides and endowed with potential antiadhesive activity. The key step is the highly regioselective 6'-O-acylation of benzyllactoside, which gave access to suitably protected lactose building blocks to be used as acceptors in the sialylation reaction. Moreover, the synthesis of the carboxymethyl and sulfo analogues of the title compounds is reported.     

Cytogenetic mapping of five YAC clones to human chromosome region 2q31 --> q32.1 in relation to the FRA2G common fragile site

In this work, five YAC clones have been mapped by fluorescent in situ hybridization (FISH) to human chromosome region 2q31 q32.1 and ordered in relation to each other and to the FRA2G common fragile site. YAC clones that span the fragile site have been identified. Moreover a deleted HOXD 13 gene has been identified on the 942D2 YAC.     

Vegetation dynamics of south-western Italy in the last 28 kyr inferred from pollen analysis of a Tyrrhenian Sea core

A continuous pollen record covering the last 28 kyr was obtained from core C106 collected in the Bay of Salerno in the southern Tyrrhenian Basin, seven radiocarbon dates and the recognition of two tephra layers (Y3 and Pompeii Pumice) providing good chronological constraints. The clear climatic signal given by the pollen spectra integrated by isotopic data, combined with comparisons with other Mediterranean sites, allowed the Last Glacial, Late Glacial and Holocene periods to be distinguished in the core. In particular, the Last Glacial period is characterised by large quantities of herbaceous and steppe elements such as Artemisia. The beginning of the Late Glacial has been correlated with the first increase of deciduous Quercus and the reduction of steppe and herbaceous elements. The Younger Dryas event is recorded only by oxygen isotopes while the vegetation does not seem to change, as in other Mediterranean sites. The Holocene corresponds to rich deciduous and evergreen forests. The first features which could be interpreted as signs of human presence are represented by a few grains of Juglans, Castanea and cereal-type while intensive olive cultivation and deforestation seem to fall within the Middle Ages. Received October 10, 2001 / Accepted June 20, 2002 Correspondence to: Elda Russo Ermolli     

Determination of organophosphorus pesticide residues in human tissues by capillary gas chromatography-negative chemical ionization mass spectrometry analysis

We describe an analytical method that allows the determination of organophosphorus pesticides (OPs) in different human tissues. It involves an extraction procedure with ethanol-ethyl acetate, followed by gel permeation chromatography clean-up step and analysis by capillary gas chromatography-negative chemical ionization mass spectrometry in the selected ion monitoring mode. The method was tested for 37 OPs and the recoveries obtained vary between 60 and 106% with standard deviations ranging between +/-2 and +/-10. These values are independent of the analyzed tissue. Peak area repeatability as RSD for some OPs was < or =4.8% while a good linear relationship in the range 1.0-500 pg microl(-1) with r(2)> or =0.9878 was obtained. The limit of detection for the 37 OPs falls between 0.01 and 0.09 ng g(-1) with an RSD< or =9.5%. The analytical set up in this paper has been used to analyze different samples of human tissues (liver, healthy kidney, cancer kidney and adipose tissue) of 24 patients. The number of the identified OPs in the tissue samples is different (max. 20) according to the sample while their concentration ranges between the limit of detection and 28.0 ng g(-1). The highest concentrations have been determined in liver samples without any pathology (0.4-28.0 ng g(-1)) while the lowest concentrations have been determined in healthy kidney samples (0.01-1.50 ng g(-1)). In the cancer kidney samples OP concentrations vary between 0.03 and 4.6 ng g(-1): these concentrations are more elevated than those determined in healthy kidney samples. The comparison between the concentration of OPs determined in the healthy part, when possible, and those determined in the cancer part of the same kidney sample are very interesting: in fact, in the latter the OP concentration is generally 1-2-times higher than that in the former, an index of lower enzymatic activity in the cancer tissue.     

Noradrenergic regulation of inflammatory gene expression in brain

It is now well accepted that inflammatory events contribute to the pathogenesis of numerous neurological disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease, and AID's dementia. Whereas inflammation in the periphery is subject to rapid down regulation by increases in anti-inflammatory molecules and the presence of scavenging soluble cytokine receptors, the presence of an intact blood-brain barrier may limit a similar autoregulation from occurring in brain. Mechanisms intrinsic to the brain may provide additional immunomodulatory functions, and whose dysregulation could contribute to increased inflammation in disease. The findings that noradrenaline (NA) reduces cytokine expression in microglial, astroglial, and brain endothelial cells in vitro, and that modification of the noradrenergic signaling system occurs in some brain diseases having an inflammatory component, suggests that NA could act as an endogenous immunomodulator in brain. Furthermore, accumulating studies indicate that modification of the noradrenergic signaling system occurs in some neurodiseases. In this article, we will briefly review the evidence that NA can modulate inflammatory gene expression in vitro, summarize data supporting a similar immunomodulatory role in brain, and present recent data implicating a role for NA in attenuating the cortical inflammatory response to beta amyloid protein.