Zafiroula Iakovidou-Kritsi

Cytogenetic activity of diazepam in normal human lymphocyte cultures.

INTRODUCTION Diazepam (DZ) belongs to benzodiazepines, a group of drugs used for sedation, for the relief of anxiety, and in the treatment of epilepsy. It has been found that DZ influences cytotoxic activity and diminishes antiviral and antitumor reactions in human natural killer cells in vitro. It has also been demonstrated that DZ causes a significant increase in the frequency of chromosomal aberrations in human lymphocytes in vitro. MATERIALS AND METHODS In the present research the cytogenetic effects of DZ have been studied in normal human lymphocyte cultures of peripheral blood at 17.6-211.2 microM (final concentrations). Sister chromatid exchanges (SCEs), one of the most sensitive methods reflecting instability in DNA or a deficiency in DNA repair mechanisms, and proliferation rate index (PRI), a valuable indicator for cytostatic activity, have been evaluated. RESULTS After 72-h incubation, DZ was found to cause a dose-dependent, statistically significant increase of SCE frequency (p < 0.001), followed by an equally significant decrease of PRI (p < 0.001). CONCLUSION Our results suggest that DZs administration presents cytogenetic effects in normal human lymphocyte cultures.

Investigation of the genotoxic effect of pesticides on greenhouse workers' lymphocytes.

In the present study, the genotoxic effects of commonly applied pesticides were evaluated using the alkaline comet assay (pH > 13). The amount of DNA damage (% DNA in tail) in peripheral lymphocytes of 49 male agricultural workers from Southern Poland were measured and compared to 50 men from the same area who had no previous occupational exposure to pesticides. No statistically significant differences in basal DNA damage were found between the study groups. In addition, exposure of peripheral blood lymphocytes to hydrogen peroxide (100 and 150 μM) or γ‐irradiation (2.5 or 4.2 Gy) led to a similar degree of additional DNA damage and subsequent repair (for 2 hr) for all studied populations. In conclusion, our results indicate that the greenhouse workers who participated in this study had no detectable increased DNA damage or alteration in their cellular response to DNA damage in comparison to our control population. Environ. Mol. Mutagen., 2009.

Cytogenetic Effects of Valproic Acid and Ziprasidone in Human Lymphocyte Cultures

Background/Aims: Valproic acid or valproate (VA) is an anticonvulsant and mood-stabilizing drug primarily used in the treatment of epilepsy and bipolar disorder. Ziprasidone (ZPN) is an atypical antipsychotic drug used mainly for the treatment of schizophrenia. Methods: This study is a part of our investigation on the cytogenetic effects of psychotropic drugs. Lymphocytes of peripheral blood cultures from 3 healthy donors treated with VA, ZPN and combinations of these (at concentrations equivalent to the oral doses) were used for the estimation of sister chromatid exchanges (SCEs) and the proliferation rate index (PRI). As a biomarker of genotoxicity, we used SCEs, one of the most sensitive methods reflecting DNA damage and/or subsequent DNA repair, and as a marker of cytostaticity we estimated the PRI. Results: All treated lymphocyte cultures showed a statistically significant increase in SCE frequency and a significant decrease in PRI values (p < 0.001). The combined effect of the drugs induced similar or more intense results, without reaching levels indicating synergistic action. Conclusion: This in vitro study investigated the cytogenetic activity of monotherapy vs. combined chronic drug exposure, and could form a catalyst for further investigations aiming to develop more efficacious therapy with decreased cytogenetic damage.

A Comparative Study on the Cytogenetic Activity of Three Benzodiazepines In Vitro

Even though benzodiazepines (BDZs) possess a leading place among drugs used as anxiolytics, sedatives, muscle relaxants, and anticonvulsants, their cytogenetic effects have not been widely studied in humans. Alprazolam (AZ), bromazepam (BZ), diazepam, and lorazepam (LZ) are some of the most commonly prescribed BDZs. Previous positive findings on diazepams cytogenetic effects in human lymphocytes suggested additional investigation. In the present research, we explored the cytogenetic potential of AZ, BZ, and LZ in human lymphocyte cultures, using an expanded sample set, administering the under-investigation medications at final concentrations equivalent to oral dosage. As a biomarker of genotoxicity we used sister chromatid exchanges, one of the most sensitive methods reflecting DNA damage and/or subsequent DNA repair, and as a marker of cytostaticity we estimated the proliferation rate index. After 72 h of incubation in the cultures, all three BDZs caused a concentration-dependent, statistically significant increase of sister chromatid exchange frequency (p < 0.001) followed by a statistically significant decrease of proliferation rate index (p < 0.001) of lymphocytes. Our conclusive results suggest that AZ, BZ, and LZ, at concentrations equivalent to oral doses, exhibit statistically significant genotoxicity in human lymphocyte cultures.

Sudden infant death syndrome due to long QT syndrome: a brief review of the genetic substrate and prevalence

The pathophysiological mechanisms which lead to sudden infant death syndrome (SIDS) are not completely understood. Cardiac channelopathies are a well-established causative factor with long QT syndrome (LQTS) being the most frequent one, accounting for approximately 12% of SIDS cases. The genetic substrate of the above arrhythmogenic syndrome has been thoroughly described but only specific gene mutations or polymorphisms have been identified as SIDS causative. The review will focus on the prevalence of LQTS-induced SIDS or near-SIDS cases and the mutations held responsible. A literature search was performed in PubMed and Scopus electronic databases. Search terms used were: long QT syndrome, channelopathies, QT prolongation, cardiac ion channels. The above-mentioned search terms were always combined with the term: sudden infant death syndrome. Study types considered eligible were: case–control, family pedigree analysis, case reports. The prevalence of LQTS-induced SIDS according to six broad genetic studies ranges from 3.9 to 20.6%, with an average of 12%. Since LQTS can be effectively managed, LQTS-related SIDS cases could be prevented, provided that a screening method is efficient enough to detect all the affected infants.

Changes in activities of caspase-8 and caspase-9 in human cervical malignancy.

Introduction The apoptotic process of programmed cell death and its dysfunctions in a variety of human diseases, including cervical cancer, has become the focus of extensive scientific research. Caspases are considered key factors in the execution of apoptosis, although there are many aspects of their role to be elucidated. It has been found that disturbance of initiator caspase-8 and caspase-9 expression or function may contribute to cancer formation/progression, and inactivation of them could promote resistance to current treatment approaches. In our research, the activities of caspase-8 and caspase-9 have been estimated during the progression of human cervical malignancy. Materials and Methods The experimental material includes human cervical tissue samples (normal and pathological), in which enzyme activities have been measured colorimetrically. Results Activities of caspase-8 and caspase-9 presented the highest increase, compared to the controls, in the low-grade squamous intraepithelial lesion samples (statistically significant, P < 0.01 by t test). The activities diminished in the high-grade squamous intraepithelial lesion and even more in the cancer samples but remained higher than the controls. Conclusion The observed changes in the activities of caspase-8 and caspase-9 could be attributed to their involvement in the cervical tissues effort to resist malignancy progression.