Structure elucidation of phenolic compounds from red/white wine with antiatherogenic properties

The oxidative modification of low-density lipoproteins (LDL) is supposed to play a critical role in atherogenesis. During this oxidation a potent inflammatory phospholipid mediator named platelet activating factor (PAF) is produced, and it is believed to be the key for the initiation of the inflammation and therefore for the process of atherogenesis. From many studies, it is established that wine has beneficial effects on health, including protection against cardiovascular diseases. According to our point of view, the cardioprotective effect of wine may be attributed partly to the existence of PAF antagonists in red or white wine and partly to the existence of antioxidants that reduce the oxidation of LDL and therefore the production of PAF. In this study, wine compounds that antagonize PAF were isolated and purified via chromatographic procedures, and determined structurally using chemical, enzymatic and spectroscopic methods.     

Fatty acid lithium salts from Cunninghamella echinulata have cytotoxic and genotoxic effects on HL‐60 human leukemia cells

Polyunsaturated fatty acids, especially gamma linolenic acid (GLA), are potentially useful agents in the treatment of cancer. Cunninghamella echinulata, a fungus species that is able to synthesize GLA, when cultivated under nitrogen‐limited conditions in a medium having glucose as carbon and energy source, accumulated 32–35% of lipids containing 11–18% GLA. The conversion yield of glucose to lipid was around 0.11 g per gram of glucose consumed while the lipid production was 5 g/L. Fatty acid lithium salts (FALS) were prepared from the total Cunninghamella lipids and studied for their effects on HL‐60 human leukemic cells. Cytotoxicity of FALS on HL‐60 leukemic cells was linearly related to the FALS concentration. High FALS concentration (i.e. 15 and 20 μg/mL) induced DNA fragmentation, while concurrent treatment of cells with H₂O₂ (at 100 μM) and FALS resulted in enhanced cytotoxicity of H₂O₂. However, when FALS were employed at low concentrations (i.e. 5 and 10 μg/mL), they demonstrated a protective effect on HL‐60 cells against H₂O₂ genotoxicity, whereas at 20 μg/mL FALS enhanced the ability of H₂O₂ to induce DNA fragmentation. It is concluded that FALS derived from C. echinulata lipids could be an effective preparation against HL‐60 human leukemic cells.     

Inhibitory activity of the novel Zn[(OPPh2)(SePPh2)N]2 complex towards the Platelet Activating Factor (PAF) and thrombin: Comparison with its isomorphous Co(II) and Ni(II) analogues

The Zn[(OPPh₂)(SePPh₂)N]₂ complex was prepared by a metathetical reaction between a Zn(II) salt and the deprotonated form of the dichalcogenoimidodiphosphinato ligand [(OPPh₂)(SePPh₂)N]⁻. X-ray crystallography revealed a pseudo-tetrahedral MO₂Se₂ coordination sphere, owed to the asymmetric (O,Se) nature of the chelating ligand. A comparison between the structural features of the M[(OPPh₂)(SePPh₂)N]₂ complexes, M = Co, Ni, Zn, shows that the three complexes are isomorphous. The IR and ³¹P NMR properties of Zn[(OPPh₂)(SePPh₂)N]₂ are analyzed in the framework of its crystallographic structure, and are compared with data on similar systems. The above three complexes, along with the (OPPh₂)(SePPh₂)NH ligand and SeO₂, are investigated as inhibitors of the Platelet Activating Factor (PAF) and thrombin activities. The paramagnetic M[(OPPh₂)(SePPh₂)N]₂ complexes, M = Co, Ni, exhibit an approximately 65-fold increased activity, compared to diamagnetic Zn[(OPPh₂)(SePPh₂)N]₂, in both the PAF- and the thrombin-induced aggregation of washed rabbit platelets (WRP). The above three complexes show a comparable significant inhibitory activity in the PAF-induced aggregation of rabbit platelet rich plasma (RPR). Remarkably, SeO₂, a form of Se present in blood, exhibits a very strong and selective inhibitory activity towards the PAF-induced aggregation of WPR. Our studies extend the dataset of metal complexes investigated as inhibitors of PAF and thrombin.     

Abnormal platelet response to PAF and ADP in beta-thalassaemia

1. AGEPC (2 microM) caused a noticeable increment in platelet aggregation, in increasing order, in 9 heterozygous beta-thalassaemic subjects, 18 homozygous beta-thalassaemics and 12 splenectomized homozygous beta-thalassaemics. 2. Recombination experiments with "patient" platelets and "normal" plasma or the reverse, as well as hydrolysis of labelled AGEPC from "normal" and "patient" serum, suggested that the observed abnormalities were due to platelets rather than to the plasma PAF hydrolase. 3. A normal splenectomized subject showed also hyperaggregability and PAF serum levels in a splenectomized patient were found twice as high in a non-splenectomized patient. 4. ADP (5 microM) caused decreased or normal platelet aggregation in the homozygous patients, approximately normal in the heterozygous subjects and increased in the splenectomized patients.     

Phosphono-platelet activating factor I. synthesis of 1-O-hexadecyl-2-O-acetyl-glyceryl-3-(2-trimethyl ammonium-methyl) phosphonate and its platelet activating potency

The total synthesis of 1-O-alkyl-2-acetyl-3-glyceryl-(2-trimethyl ammoniummethyl) phosphonate, the phosphono analogue of 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, is described. The phosphonolipid shows much lower activity than the phospholipid stimulating serotonin release from rabbit platelets.     

Induction of somatic and male crossing-over by bleomycin in Drosophila melanogaster

Bleomycin (BLM) is well known as an antibiotic as well as for its antineoplastic activity. A clinical preparation of BLM was tested for its recombinogenicity in a higher eukaryotic organism, Drosophila melanogaster. Feeding of the F1 larvae on a medium with BLM increased somatic crossing-over spots on female tergites and induced recombination in male germ cells. However, nonlinear dose-response curves were obtained. Malformed tergites were also observed in females treated with BLM.     

Recombinogenic and mutagenic effects of the antitumor antibiotic bleomycin in Aspergillus nidulans

Bleomycin, an antibiotic and antineoplastic drug that inhibits DNA synthesis and causes several types of chromosomal aberration, was found to increase mitotic recombination in Aspergillus nidulans. Heterozygous prototrophic diploid strains grown on media containing bleomycin produced significant increases of yellow and white sectors compared with controls. Further, the increased colour segregants were due to mitotic crossing-over, whereas the non-dis junctional segregants remained at the control level. Bleomycin also induced point mutations in the methionine-suppressor system of the methGl biAl strain of Aspergillus nidulans. Conidia treated in suspension with various concentrations of bleomycin increased the methionine-independent mutants 30-fold and more.     

Immunohistochemical profile of ovarian inclusion cysts in patients with and without ovarian carcinoma

Summary The expression of cytokeratin, epithelial membrane antigen, Leu-M1, B72.3, carcinoembryonic antigen, human placental lactogen, proliferating cell nuclear antigen, p53, and ovarian carcinoma-associated antigen OC-125 was evaluated in inclusion cysts in contralateral ovaries of patients with unilateral ovarian carcinoma. The findings were compared with the findings in inclusion cysts in ovaries of patients without ovarian carcinoma. Although there was more frequent expression of tumour markers B72.3 and CEA in patients with ovarian carcinoma, these differences did not reach statistical significance.