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J Anastassopoulou

Publications and source records attributed to J Anastassopoulou.

8 recordsLinked to original sources
PubMed2002

Magnesium-DNA interactions and the possible relation of magnesium to carcinogenesis. Irradiation and free radicals.

Magnesium deficiency causes renal complications. The appearance of several diseases is related to its depletion in the human body. In radiotherapy, as well as in chemotherapy, especially in treatment of cancers with cis-platinum, hypomagnesaemia is observed. The site effects of chemotherapy that are due to hypomagnesaemia are decreased using Mg supplements. The role of magnesium in DNA stabilization is concentration dependent. At high concentrations there is an accumulation of Mg binding, which induces conformational changes leading to Z-DNA, while at low concentration there is deficiency and destabilization of DNA. The biological and clinical consequences of abnormal concentrations are DNA cleavage leading to diseases and cancer. Carcinogenesis and cell growth are also magnesium-ion concentration dependent. Several reports point out that the interaction of magnesium in the presence of other metal ions showed that there is synergism with Li and Mn, but there is magnesium antagonism in DNA binding with the essential metal ions in the order: Zn>Mg>Ca. In the case of toxic metals such as Cd, Ga and Ni there is also antagonism for DNA binding. It was found from radiolysis of deaerated aqueous solutions of the nucleoside 5'-guanosine monophosphate (5'-GMP) in the presence as well as in the absence of magnesium ions that, although the addition of hydroxyl radicals (*OH) has been increased by 2-fold, the opening of the imidazole ring of the guanine base was prevented. This effect was due to the binding of Mg2+ ions to N7 site of the molecule by stabilizing the five-member ring imitating cis-platinum. It was also observed using Fourier Transform Infrared spectroscopy, Raman spectroscopy and Fast Atom Bombardment mass spectrometry that *OH radicals subtract H atoms from the C1', C4' and C5' sites of the nucleotide. Irradiation of 5'-GMP in the presence of oxygen (2.5 x 10(-4) M) shows that magnesium is released from the complex. There is spectroscopic evidence that superoxide anions (O2-*) react with magnesium ions leading to magnesium release from the complex. From radiolysis data it was suggested that magnesium ions can act as radiosensitizers in the absence of oxygen, while in the presence of oxygen they act as protectors and stabilizers of DNA.

Animals↗
PubMed2002

Copper and carcinogenesis.

Metal ions play an important role in biological systems, and without their catalytic presence in trace or ultratrace amounts many essential co-factors for many biochemical reactions would not take place. However, they become toxic to cells when their concentrations surpass certain optimal (natural) levels. Copper is an essential metal. Catalytic copper, because of its mobilization and redox activity, is believed to play a central role in the formation of reactive oxygen species (ROS), such as O2-* and *OH radicals, that bind very fast to DNA, and produce damage by breaking the DNA strands or modifying the bases and/or deoxyribose leading to carcinogenesis. The chemistry and biochemistry of copper is briefly accounted together with its involvement in cancer and other diseases.

Animals↗
PubMed2000

The role of free radical reactions with haemoglobin and thalassaemia.

It is well known that all living systems depend on iron to transport (haemoglobin), store (myoglobin) and utilize (cytochromes, cytochrome oxide) oxygen for respiration. Iron is an essential component in the active sites of the enzyme that protects against oxidation, such as the iron superoxide dismutase, in bacteria and plants. In normal human plasma almost all iron loading of transferrin is 20-30% maximum. In this presentation we review and summarize recent developments in our understanding of iron transport and storage in living systems.

Free Radicals↗
PubMed1996

Molecular modeling of azole antifungal agents active against Candida albicans. 1. A comparative molecular field analysis study.

A series of 56 azole antifungal agents belonging to chemically diverse families related to bifonazole, one of the antimycotic drugs of clinical use, were investigated using the comparative molecular field analysis (CoMFA) paradigm. The studied compounds, which have been already synthesized and reported to be active in vitro against Candida albicans, were divided into a training set and a test set. The training set consisted of 40 molecules from all the different structural classes. Due to the lack of experimental structural data on these derivatives, molecular mechanics techniques were used to obtain putative active conformations for all the compounds. the correctness of this molecular modeling work was confirmed a posteriori by comparison with structural data of the analog 2w obtained by X-ray crystallographic analysis (Massa, S.; et al. Eur. J. Med. Chem. 1992, 27, 495-502). Two different alignment rules of the training set molecules were used in this study and are based on the assumption that according to published results on azole antifungal agents, all the studied compounds exert their inhibitory activity through the coordination of their azole moiety to the protoporphyrin iron atom of the fungal lanosterol 14alpha-demethylase enzyme. The predictive ability of each resultant CoMFA model was evaluated using a test set consisting of 16 representative compounds that belong to all the different structural classes. The best 3D-quantitative structure-activity relationship model found yields significant cross-validated, conventional, and predictive r2 values equal to 0.57, 0.95, and 0.69, respectively. The average absolute error of predictions of this model is 0.30 log units, and the structural moieties of the studied antifungal agents which are thought to contribute to the biological activity were identified. The predictive capability of this model could be exploited in further synthetic studies on antifungal azoles. Furthermore, the results obtained by using two different alignments of the inhibitors suggest that the binding mode of these molecules involves both a coordination to the iron protoporphyrin atom and an additional, likewise relevant, hydrophobic interaction with the active site.

Antifungal Agents↗
PubMed1996

Fluctuations in serum magnesium levels during total intravenous anaesthesia with propofol.

Forty patients who underwent eye surgery under total intravenous anaesthesia with propofol where investigated in order to determine the fluctuations of serum magnesium levels during anaesthesia. Six blood samples were taken before anaesthesia, after induction, 1 hour later, 2 hours later, after recovery, and 24 hours after surgery. In the same time intervals, systolic and diastolic blood pressure, heart rate and temperature were recorded. The results showed a statistically significant decrease in serum magnesium levels during anaesthesia. No correlations between this decrease and the fluctuations of blood pressure, heart rate or temperature were found. These results indicate that there is a shift of magnesium into the tissue stores due to the state of anaesthesia, possibly by a direct effect of the anaesthetic agents on the cell membrane itself. Further investigation is needed with other techniques and agents employed in general anaesthesia.

Adult↗
PubMed1995

Prophylactic effects of intravenous magnesium on hypertensive emergencies after cataract surgery. A new contribution to the pharmacological use of magnesium in anaesthesiology.

The pharmacological effects of magnesium sulphate heptahydrate (MgSO4.7H2O) on hypertensive patients during the perioperative period were used, to control critical rises of blood pressure. This double-blind study included 40 hypertensive elderly patients, who underwent eye surgery under local anaesthesia; they were divided into two groups (A and B) of 20 patients each. An intravenous dose of 4g MgSO4.7H2O was given to group. A, while group B, which was used as a control group, was given to a placebo. All patients were premedicated with 10 mg oral diazepam 1.5 h before the operation. Systolic and diastolic blood pressure, heart rate and ECG were monitored for 1 h. None of the patients who received MgSO4.7H2O showed any ECG disturbances. Systolic and diastolic blood pressure, as well as heart rate, fluctuated outside the critical range, whereas in the control group an increase of blood pressure was noted which was treated with other anti hypertensive drugs. The results indicated that parenteral administration of MgSO4.7H2O in hypertensive patients before surgery stabilized blood pressure fluctuations outside the critical range, without causing the pressure to fall to a level that might risk undesirable side effects during eye surgery under local anaesthesia.

Aged↗
PubMed1990

Possible role of water structure in biological magnesium systems.

Magnesium chloride-water solutions have been studied by Fourier Transform Infrared Spectroscopy (FT-IR) in the near infrared region, 5000-10,000 cm-1. The effect of the concentration of magnesium chloride and temperature on the solutions has been studied from the spectra and it is concluded that magnesium chloride modifies the structure of the bulk water. The important absorption bands of water at 5200 and 7020 cm-1 may be assigned to combination vibrations and overtones. They are shifted either by increasing the magnesium chloride concentration or the temperature. The hydrated magnesium ions, [Mg(H2O)6]2+, will most probably break important hydrogen bonds in the clusters of water (H2O)n, where n = 2, 3, 4, 5, 6.../forming new hydrogen bonds in the presence of hexa-aquated magnesium cations. FAB mass spectra also suggest the formation of hydrated magnesium cations, Mg (H2O)6(2+).

Crystallization↗