Evidence of involvement of leptin and IL-6 peptides in the action of interferon-beta in secondary progressive multiple sclerosis

Leptin is a peptide hormone which acts on cells of immune system by influencing the production of cytokines. Serum leptin levels and cytokine production by peripheral blood mononuclear cells (PBMC) were measured in 18 secondary progressive multiple sclerosis (SPMS) patients under IFN-beta-1b treatment. There were no overall effects on leptin, interleukin-6 (IL-6), IL-10 and IL-12 p40 after 2, 6 and 12 months of treatment. However, leptin and IL-6 decreased after 6 and 12 months of treatment in 12 patients who did not show progression of disability. Thus, our pilot data show that the beneficial effect of IFN-beta on some SPMS patients might be associated with the reduced levels of leptin and reduced IL-6 production by PBMC.     

The intercalation to DNA of bipyridyl complexes of platinum(II) with thioureas

The non-covalent interaction of the complexes [Pt(bpy)(R,R'NCSNR',R')(2)]Cl(2) (bpy=2,2'-bipyridine; R=R'=R'=R'=H; R=Me, R'=R'=R'=H; R=n-Bu, R'=R'=R'=H; R=p-tolyl, R'=R'=R'=H; R=Et, R'=H, R'=Et, R'=H) with calf thymus DNA has been studied at pH 7 and 25 degrees C. The processes give rise to: (i) reversible bathochromic shifts and strong hypochromicity of the absorption bands of the complexes, (ii) induced circular dichroism and (iii) an increase both in the melting temperature and viscosity of the DNA comparable to that observed for other well known metallointercalators. The binding constants, K(B), have been determined spectrophotometrically using the McGhee von Hippel equation. Plot of logK(B) vs -log[Na(+)] for the complex with unsubstituted thiourea gives a straight line with a slope value close to that expected for a dicationic intercalator. The binding affinity of the various complexes for DNA is independent of the thiourea nature; this suggests that the intercalation occurs through stacking of the bpy moiety while the ancillary ligands lie outside the nucleobases far away from the sugar phosphate backbone. The data show also that the electronic effects of the ligand substituents are not transmitted to the intercalating unit.     

Structural characterization of phytotoxic terpenoids from Cestrum parqui

Isolation, chemical characterization and phytotoxicity of nine polyhydroxylated terpenes (five C13nor-isoprenoids, two sesquiterpenes, a spirostane and a pseudosapogenin) from Cestrum parqui L'Herr are reported. In this work we completed the phytochemical investigation of the terpenic fraction of the plant and described the structural elucidation of polar isoprenoids using NMR methods. All the configurations of the compounds have been assigned by NOESY experiments. Four new structures have been identified as (3S,5R,6R,7E,9R)-5,6,9-trihydroxy-3-isopropyloxy-7-megastigmene, 5alpha-spirostan-3beta,12beta,15alpha-triol, and 26-O-(3'-isopentanoyl)-beta-d-glucopyranosyl-5alpha-furost-20(22)-ene-3beta,26-diol, and as an unusual tricyclic sesquiterpene. The compounds have been assayed for their phytotoxicity on lettuce at the concentrations ranging between 10(-4) and 10(-7)M. The activities of some compounds were similar to that of the herbicide pendimethalin.     

Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease

BACKGROUND: Intra-peritoneal adipose tissue is recognized as a predictor of metabolic syndrome and may contribute to the risk for cardiovascular disease by the production of adipocytokines, including adiponectin. Nevertheless, there is no knowledge on whether other visceral depots of adipose tissue, including the epicardial fat, have any metabolically active role, including production of adiponectin. AIM OF THE STUDY: We sought to evaluate adiponectin protein expression in epicardial adipose tissue in vivo both in patients with severe coronary artery disease (CAD) and in subjects without CAD. METHODS: Twenty-two patients were enrolled for the study. We selected 16 patients who underwent elective coronary artery bypass graft surgery for critical CAD, 5 who underwent surgery for valve replacement and 1 for correction of an interatrial defect. Epicardial adipose tissue biopsy samples were obtained before the initiation of cardiopulmonary bypass. Adiponectin protein level in epicardial adipose tissue was evaluated by Western blotting. RESULTS: Adiponectin protein value, expressed as adiponectin/actin ratio, in epicardial adipose tissue was significantly lower in patients with severe CAD than in those without CAD (1.42 +/- 0.77 vs 2.36 +/- 0.84 p = 0.02, 95% CI 0.64-1.74). CONCLUSIONS: This study showed for the first time that human epicardial adipose tissue expresses adiponectin. Adiponectin expression is significantly lower in epicardial fat isolated from patients with CAD.     

In vitro and in silico cloning of Xenopus laevis SOD2 cDNA and its phylogenetic analysis

By using the methodology of both wet and dry biology (i.e., RT-PCR and cycle sequencing, and biocomputational technology, respectively) and the data obtained through the Genome Projects, we have cloned Xenopus laevis SOD2 (MnSOD) cDNA and determined its nucleotide sequence. These data and the deduced protein primary structure were compared with all the other SOD2 nucleotide and amino acid sequences from eukaryotes and prokaryotes, published in public databases. The analysis was performed by using both Clustal W, a well known and widely used program for sequence analysis, and AntiClustAl, a new algorithm recently created and implemented by our group. Our results demonstrate a very high conservation of the enzyme amino acid sequence during evolution, which proves a close structure-function relationship. This is to be expected for very ancient molecules endowed with critical biological functions, performed through a specific structural organization. The nucleotide sequence conservation is less pronounced: this too was foreseeable, due to neutral mutations and to the species-specific codon usage. The data obtained by using AntiClustAl are comparable with those produced with Clustal W, which validates this algorithm as an important new tool for biocomputational analysis. Finally, it is noteworthy that evolutionary trees, drawn by using all the available data on SOD2 nucleotide sequences and amino acid and either Clustal W or AntiClustAl, are comparable to those obtained through phylogenetic analysis based on fossil records.     

Testicular germ cell tumours: the paradigm of chemo-sensitive solid tumours

Testicular germ cell tumours (TGCTs) are the most frequent solid malignant tumour in men 20–40 years of age and the most frequent cause of death from solid tumours in this age group. Up to 50% of the patients suffer from metastatic disease at diagnosis. The majority of metastatic testicular cancer patients, in contrast to most other metastatic solid tumours, can be cured with highly effective cisplatin-based chemotherapy. From a genetic point of view, almost all TGCTs in contrast to solid tumours are characterised by the presence of wild type p53. High p53 expression levels are associated with elevated Mdm2 levels and a loss of p21^Waf1/Cip1 expression suggesting a changed functionality of p53. Expression levels of other proteins involved in the regulation of cell cycle progression indicate a deregulated G1–S phase checkpoint in TGCTs. After cisplatin-induced DNA damage, the increasing levels of p53 lead to the trans-activation of a number of genes but not of p21^Waf1/Cip1, preferentially directing TGCT cells into apoptosis or programmed cell death, both via the mitochondrial and the death receptor apoptosis pathways. The sensitivity of TGCTs to chemotherapeutic drugs may lay in the susceptibility of germ cells to apoptosis. Taken together, this provides TGCT as a tumour type model to investigate and understand the molecular determinants of chemotherapy sensitivity of solid tumours. This review aims to summarise the current knowledge on the biological basis of cisplatin-induced apoptosis and response to chemotherapy in TGCTs.     

O-Methylglucogalloyl esters: synthesis and evaluation of their antimycotic activity

The two anomers of O-methyl gluco-2,3-digalloyl esters were synthesized and their antimycotic activity toward yeasts of biomedical importance was evaluated. When used at subinhibitory concentration and regardless of stereochemistry at the anomeric carbon, these compounds enhance the antimycotic activity of Amphotericin B.     

The cell biology of Hermansky-Pudlak syndrome: recent advances

Hermansky-Pudlak syndrome (HPS) defines a group of at least seven autosomal recessive disorders characterized by albinism and prolonged bleeding. These manifestations arise from defects in the biogenesis of lysosome-related organelles, including melanosomes and platelet dense granules. Most genes associated with HPS in humans and rodent models of the disease encode components of multisubunit protein complexes that are expressed ubiquitously and play roles in intracellular protein trafficking and/or organelle distribution. A small GTPase of the Rab family, Rab38, is also implicated in the pathogenesis of the disease. This article reviews recent progress toward elucidating the cellular functions of these proteins.     

Increased conformational rigidity of humic substances by oxidative biomimetic catalysis

A synthetic water-soluble meso-tetra(2,6-dichloro-3-sulfonatophenyl)porphyrinate of iron(III) chloride, Fe(TDCPPS)Cl, was employed as a biomimetic catalyst in the oxidative coupling of terrestrial humic materials. High-performance size-exclusion chromatography (HPSEC), solid-state nuclear magnetic resonance (CPMAS-(13)C NMR), electron paramagnetic resonance (EPR), and diffuse reflectance infrared spectroscopy (DRIFT) were used to follow conformational and structural changes brought about in different humic materials by the oxidative coupling. Increase in apparent weight-average molecular weight (Mw(a)) occurred invariably for all humic substances with the oxidative polymerization catalyzed by Fe(TDCPPS)Cl. HPSEC further showed that the polymerization reaction turned the loosely bound humic supramolecular structures into more stable conformations which could no longer be disrupted by the disaggregating effect of acetic acid. DRIFT spectroscopy suggested the formation of new alkyl and aromatic ethers following the oxidative coupling with the biomimetic catalyst. CPMAS-(13)C NMR and EPR spectra suggested a reduced molecular mobility of humic components and enhanced stabilization of free radicals in larger oxidized fragments. All findings concur in indicating that the biomimetic catalysis by Fe(TDCPPS)Cl increased the molecular mass and chemical rigidity of humic materials by formation of intermolecular covalent bonds via a free-radical mechanism. The development of a technology based on oxidative polymerization by biomimetic catalysis may be of importance in controlling the properties and reactivity of humic matter for industrial and environmental applications.