The genetic basis of cleft lip and cleft palate

Η χειλεοσχιστία και η υπερωιοσχιστία μαζί ή σαν μεμονωμένες περιπτώσεις αποτελούν ένα μεγάλο τμήμα των σχιστιών του προσώπου, που παρατηρούνται κατά τη γέννηση. Πρόκειται για μια ιατρική κατάσταση, που έχει τύχει εκτεταμένης έρευνας από την επιστημονική κοινότητα λόγω των επιπτώσεων στην υγεία καθώς και των κοινωνικών επιπτώσεων στην καθημερινή ζωή των ασθενών. Υπάρχουν πολλές υποθέσεις και πολλά επιστημονικά δεδομένα για τα γονίδια που εμπλέκονται στη γένεσή τους. Η χειλεοσχιστία και η υπερωιοσχιστία μπορούν να αποτελούν κλινικές εκφράσεις σε πολλά σύνδρομα, αλλά μπορούν επίσης να εμφανιστούν και σαν μεμονωμένες περιπτώσεις και σε αυτή την περίπτωση θεωρούνται μη συνδρομικές. Ειδικά στις μη συνδρομικές μορφές η γενετική ετερογένεια και οι διαφορές ανάμεσα στους μελετώμενους πληθυσμούς μας παρέχουν πολλές φορές αντικρουόμενα αποτελέσματα για τα εμπλεκόμενα γονίδια. Είναι επίσης ευρέως αποδεκτό ότι η χειλεοσχιστία και η υπερωιοσχιστία είναι μια πολυπαραγοντική ιατρική κατάσταση, στην παθογένεση της οποίας και οι περιβαλλοντικοί παράγοντες παίζουν σπουδαίο ρόλο.Cleft lip and cleft palate (CLP) together or as isolated incidents constitute a large proportion of orofacial deformities which are observed during birth. It is a medical condition widely researched in the scientific community primarily because of health effects but also social effects on the everyday life of the affected children. There is wide speculation and much scientific data about the genes which are implicated on its genesis. CLP can be a clinical feature in many syndromes, but they can also be observed as isolated incidents in cases considered as non syndromic. Especially in non syndromic forms genetic heterogeneity and the differences among studied populations provide us with sometimes conflicting results about the implicated genes. It is also widely accepted that CLP is a multifactorial medical condition and in its pathogenesis, environmental factors also play a crucial role

Cathepsins H and L in colorectal cancer

Cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biologi­cal processes while they also play an essential role in cancer progression, invasion and metastasis. The purpose of our study was: first to compare the expression levels of cathepsins H and L in the supernatants of colon cancer tissues from 74 patients versus the same enzymic expressions of the supernatants of the adjacent normal colorectal tissues and second to correlate our findings to the grade of the malignancy by using an enzyme-linked immunosorbent assay (ELISA). The results indicated that the cathepsins H and L of all malignant tissues presented significant higher expression’s values than the corresponding control. Specifically the concentration of cathepsin H that has been found increased significantly as malignancy proceeded, was higher than the corresponding control as following: 155% in B1 stage and 204,44% in D stage. Between the two inves­tigated proteases cathepsin L has showed the greatest increase, which in D stage was 261,03% higher than the corresponding control. According to these results, the expression of cysteine proteases H and L could be of critical value in the diagnosis and progression of colon cance

Pregabalin’s effect on human genetic material: in vitro study

Purpose of the study: Pregabalin is a prescription drug approved for the treatment of generalized anxiety disor­der; partial epilepsy; neuropathic pain and fibromyalgia. It is an alpha-2-delta ligand, structurally related to the neurotransmitter GABA that inhibits calcium currents via high-voltage-activated channels containing the a2d-1 subunit.Aim of the present study was to investigate the in vitro effect of pregabalin on healthy human cultured lymphocytes, by esti­mating three sensitive cytogenetic indices: Sister Chromatid Exchanges (SCEs), Proliferation Rate Index (PRI) and Mitotic Index (MI).Methods: SCEs are considered as one of the most sensitive markers of genotoxicity, whereas PRI is one of the most reli­able markers of cytostatic activity and MI shows precisely the ability of the cell to proliferate. We prepared eight pregabalin solutions commonly used in clinical practice. The solutions were added to cultures of peripheral blood lymphocytes taken from two young healthy donors. After 72 hours of incubation with the appropriate technique the cultured lymphocytes were plated on glass slides, stained with the Fluorescence plus Giemsa method and the above indices were estimated with the optical microscope.Results and Conclusions: Pregabalin at therapeutic doses exhibited dose-dependent cytogenetic activity in vitro, increasing SCE frequencies and diminishing PRI levels in normal human lymphocyte cultures. Interestingly, the variation of the magni­tude of MI reduction seems to be directly related to the decrease of PRI values as well as to the increase of SCE frequencies. Considering that the use of pregabalin is rapidly increased, further studies in other cell lines and in in vivo experimental settings are needed in order to evaluate its effect on genetic material

In vitro genotoxicity of two widely used benzodiazepines: alprazolam and lorazepam

Alprazolam (AZ) and Lorazepam (LZ) belong to benzodiazepines, a multi-membered group of biologically active substances. Even though they are widely used as drugs for the relief of anxiety, sedation and in the treatment of epilepsy, knowledge about their cytogenetic activity is limited.Materials and Methods: In the present study the cytotoxic and cytostatic actions of AZ and LZ have been evaluated in normal human lymphocyte cultures of peripheral blood at final concentrations (0.16-3.84 μM for AZ and 0.62-3.72 μΜ for LZ) equivalent to oral dosage (for AZ 0.25-6 mg/day and for LZ 1-6 mg/day), employing Sister Chromatid Exchanges (SCEs), one of the most sensitive methods reflecting instability of DNA or a deficiency in DNA repair mechanisms, and Proliferation Rate Index (PRI), a valuable indicator of cytostatic activity.Results: After 72h incubation in the cultures, both AZ and LZ caused a dose-dependent, statistically significant increase of SCE frequency (p < 0.001) followed by a statistically significant decrease of PRI (p < 0.001) of lymphocytes.Conclusions: Our results suggest that AZ and LZ at oral doses exhibit statistically significant genotoxicity in normal human lymphocyte cultures

Agomelatine’s effect on human genetic material: in vitro study

Εισαγωγή: Η αγομελατίνη αποτελεί ένα εγκεκριμένο φάρμακο για τη θεραπεία της μείζονος καταθλιπτικής διαταραχής. Παρουσιάζει δράση μελατονινεργικού αγωνιστή και ανταγωνιστή των 5-HT2C υποδοχέων της σεροτονίνης. Σκοπός της παρούσας έρευνας είναι η μελέτη της επίδρασης της αγομελατίνης στο ανθρώπινο DNA in vitro με τον υπολογισμό ευαίσθητων κυτταρογενετικών δεικτών.Υλικό και Μέθοδος: Oι χρωματιδιακές ανταλλαγές (Sister Chromatid Exchanges, SCEs) θεωρούνται ένας από τους πιο ευαίσθητους δείκτες γονοτοξικότητας. O δείκτης ρυθμού πολλαπλασιασμού (Proliferation Rate Index, PRI) είναι ένας από τους πιο αξιόπιστους δείκτες κυτταροστατικότητας, ενώ ο μιτωτικός δείκτης (Mitotic Index, MI) δείχνει με ακρίβεια την ικανότητα του κυττάρου για πολλαπλασιασμό. Αρχικά παρασκευάστηκαν διαλύματα αγομελατίνης πέντε διαφορετικών συγκεντρώσεων (A=2.5μg/ml, B=5μg/ml, C=10μg/ml, D=15μg/ml και E=20μg/ml). Oι συγκεντρώσεις B και C είναι οι πιο συχνά χρησιμοποιούμενες στην κλινική πράξη. Τα διαλύματα προστέθηκαν σε καλλιέργειες λεμφοκυττάρων από περιφερικό αίμα τεσσάρων νεαρών υγειών αιμοδοτών. Μετά από 72 ώρες επώασης, με την κατάλληλη τεχνική τα καλλιεργημένα λεμφοκύτταρα επιστρώθηκαν σε αντικειμενοφόρους πλάκες, χρωματίστηκαν με την μέθοδο Fluorescence plus Giemsa και οι προαναφερθέντες δείκτες υπολογίστηκαν με οπτικό μικροσκόπιο.Αποτελέσματα: Η ανάλυση των αποτελεσμάτων αποκάλυψε στατιστικά σημαντική αύξηση των χρωματιδιακών ανταλλαγών και μείωση τόσο του δείκτη ρυθμού πολλαπλασιασμού όσο και του μιτωτικού δείκτη . Επιπρόσθετα, προέκυψε συσχέτιση μεταξύ α) της αύξησης των SCEs και των μεταβολών του ΜΙ και του PRI και β) των μεταβολών ΜΙ-PRI.Συμπεράσματα: Η αγομελατίνη σε θεραπευτικές δόσεις προκάλεσε δοσοεξαρτώμενες μεταβολές στους υπό μελέτη κυτταρογενετικούς δείκτες. Το παραπάνω ενδέχεται να καταδεικνύει στοιχεία για το μηχανισμό δράσης του φαρμάκου. Λαμβάνοντας υπόψη την αυξανόμενη χρήση της αγομελατίνης επιβάλλεται περεταίρω μελέτη της κυτταρογενετικής της δράσης σε περισσότερους αιμοδότες καθώς και σε άλλες κυτταρικές σειρές.Introduction: Agomelatine is a prescription drug approved for the treatment of major depressive disorder. It is a melatonergic agonist and a 5-HT2C antagonist. The cytogenetic behavior of agomelatine has not been studied. The aim of the present study is the investigation of the in vitro effect of agomelatine on human DNA, by estimating sensitive cytogenetic indices. Methods: SCEs (Sister Chromatid Exchanges) are considered as one of the most sensitive markers of genotoxicity, PRI (Proliferation Rate Index) is one of the most reliable markers of cytostatic activity, whereas MI (Mitotic Index) shows precisely the ability of the cell to proliferate. We have investigated the effect of five agomelatine solutions on SCEs, PRI and MI of human cultured lymphocytes stained with the Fluorescence plus Giemsa method and estimated with the optical microscope. Results: Analysis of the results has revealed statistically significant (p<0.001) dose-dependent increase of SCE frequencies and significant reduction of PRI and MI values on lymphocyte cultures treated with agomelatine. Furthermore, a correlation was observed between a) the magnitude of the SCE induction and the PRI alterations, b) the magnitude of the MI alterations and the SCE induction and c) the magnitude of PRI alterations and MI alterations. Conclusions:Agomelatine at therapeutic doses exhibited dose-dependent cytogenetic activity in vitro. This may provide additional information about the mechanism of action of the drug. Considering that the use of agomelatine has rapidly increased, further studies in other cell lines and in vivo experimental settings are needed in order to evaluate its effect on human genetic material

Colon cancer: An epidemiological study in Northern Greece

Colorectal or colon cancer is the third most common form of cancer with 655,000 deaths worldwide per year and the second leading cause of cancer-related death in the Western world.  variety of risk factors have been linked to colon cancer including genetic factors (age, sex and hereditary mutations of repair enzymes genes), environmental exposures, daily life habits (diet, smoking, obesity and sedentary habits) and inflam­matory conditions of the digestive tract. The present research is a retrospective epidemiological study concerning 280 patients with colon cancer who were hospitalized at Theagenion Cancer Hospital of Thessaloniki during 2006, 2007 and 2008. They were classified according to their age, sex, place of residence, occupation and tobacco consumption. The results revealed that 58.57% were males and 41,43% females, 82,49% of the patients were older than 60 years of age, 38,93% were urban and 60% rural district inhabitants. Pensioners represented 47,50%, farmers 18,93%, housekeepers 13,57%, employers or free lancers 10,71%. For the rest 9,29% no in­formation has been recorded. Regarding the consumption of tobacco, 16,79% of them were smokers, 34,64% non smokers, whereas there was no information about the smoking habits of the remaining (48,57%). The results of this research with respect to age and sex of the patients are in agreement with bibliographical data, but conclu­sions can not be drawn about the connection between occupation and colon cancer onset. The fact that among the patients the non smokers were more than smokers, which is in contrast with the international data, could be attributed to the insufficiency of respective information for 48,57% of the patients. The unexpectedly higher frequency of colorectal cancer appearance among rural district inhabitants rather than among urban district inhabitants should be researched as soon as possible. The deficiency of information about fundamental risk factors of colon cancer, as genetic and environmental factors and life­style among Greek population requires the continuation and the extension of this epidemiological study, because prevention is the best cure and epidemiological studies have offered substantial contribution to prevention

Cytogenetic behaviour of crocin on cultured lymphocytes from leukemic patients

Crocin is isolated from saffron, an important spice rich in carotenoids obtained from the stigmas of Crocus sativus L, commonly consumed all around the world and used as a medical drug to treat numerous diseases. In the present work a comparative study of the cytogenetic behaviour of crocin between cultured lymphocytes from chronic lymphocytic leukemic patients as well as from healthy individuals was undertaken in order to test the hypothesis that the sister chromatid exchange assay in vitro can be used for the prediction of the in vivo tumor response to the potential chemotherapeutic action of crocin. Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in cultured lymphocytes from peripheral blood of all donors. Results showed that all tested crocin solutions didn’t cause remarkable changes to the PRI values of lymphocytes neither of the leukemic patients, nor of healthy individual. Contrariwise, after crocin affection a statistically significant decrease of the SCEs frequency of lymphocytes of leukemic patients had been observed (p<0,001, t-test) whereas the SCEs of the healthy donor’s cells presented slight, but not statistically significant increase. Our results indicate that crocin did not prove to be cytostatic in the tested concentrations, but it mainly reduced significantly the DNA damages along with being demonstrated as cytoprotectiv