SNPs and Type 2 Diabetes

Type 2 diabetes is considered a multifactorial trait in which multiple genetic and environmental factors interact in complex, non-linear ways to produce the common phenotype of hyperglycemia. Until recently, research efforts to identify the genetic variants that contribute to individual differences in predisposition to T2D were met with slow progress and limited success. Over the past three years, the advent of genome-wide association (GWA) scan has ushered in a new era regarding the capacity of identifying common genetic variants that contribute to predisposition to complex multifactorial phenotypes such as type 2 diabetes. The identification of the variants, genes and pathways implicated in T2D pathogenesis might facilitate its diagnosis and prevention and offer a route to new therapies. The aim of this paper is to review the literature regarding SNPs that have been associated with T2D predisposition

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

Introduction: Venlafaxine is a prescription drug approved for the treatment of major depressive disorder, generalized anxiety disorder, panic disorder and social anxiety disorder.  It is a serotonin and norepinephrine reuptake inhibitor and a weak dopamine reuptake inhibitor. The aim of the present study is to investigate the in vitro effect of venlafaxine on human genetic material, by estimating sensitive cytogenetic indices.Methods: Five venlafaxine solutions (A=15μg/ml, B=30μg/ml, C=45μg/ml, D=60μg/ml, E=75μg/ml) were added to cultures of peripheral blood lymphocytes of six healthy donors. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides, stained with the Fluorescence plus Giemsa method and Sister Chromatid Exchanges (SCEs), a sensitive marker of genotoxicity, Proliferation Rate Index (PRI), a reliable marker of cytostatic activity and Mitotic Index (MI), a marker which shows precisely the ability of a cell to proliferate were measured with the optical microscope.Results: Result analysis revealed t: a) a statistically significant (p=0.001) dose-dependent increase of SCEs and b) a statistically significant (p=0.001) reduction of PRI and MI in all concentrations. Furthermore, a correlation was observed between a) SCE and PRI index variations, b) MI and SCE index variations and c) PRI and MI index variations. Conclusions: Venlafaxine exhibited dose-dependent cytogenetic activity in vitro, increasing SCE frequencies and diminishing PRI and MI levels in healthy human cultured lymphocytes. Venlafaxine as other antidepressants seems to affect human T lymphocytes by modifying epigenetic and DNA replication procedures. This may provide additional information about the mechanism of action of the drug. Considering that the use of venlafaxine has rapidly increased with many off label indications, further studies in other cell lines and in vivo experimental settings are needed in order to evaluate its potential effects on human genetic material

Detection of IgG autoantibodies against desmocollin–3 in Greek patients with pemphigus

Pemphigus is an autoimmune bullous disorder caused by autoantibodies against desmosomal cadherins. The most common clinical forms are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Among the numerous proteins that are considered responsible for the cohesion of keratinocytes in epidermis, desmocollin-3 (Dsc-3) has been initially reported to participate in epidermal blistering in mice. There have been reports in which autoantibodies against Dsc-3 have been detected. In PV, a limited number of studies found no presence of IgG or IgA autoantibodies against Dsc-3. In this study we examined sera from Greek patients with PV and PF for the presence of IgG autoantibodies against Dsc-3. Immunoblotting for the detection of autoantibodies against Dsc-3 was performed in sera from all cases. Dsc-3 autoantibodies were not detected in either group (PV and PF). Our results confirm the hypothesis that the pathogenic role of Dsc-3 in epidermal blistering in PV and PF remains controversial. </p

Influence of conception and delivery mode on stress response marker Oct4B1 and imprinted gene expression related to embryo development: A cohort study

Background: Recent scientific data support that the mode of conception and delivery may influence epigenetic regulation and therefore embryo development. Octamer-binding transcription factor 4-B1 (OCT4B1), a novel variant of OCT4 with yet unknown biological function, is suggested to have a potential role in mediating cellular stress response. Furthermore, Insulinlike Growth Factor 2 (IGF2), Mesoderm-specific Transcript (MEST) and paternally expressed gene 10 (PEG10) are genes known as imprinted and are regulated via means of epigenetic regulation. The influence of delivery mode and conception on epigenetic regulation is an active research field. Objective: Our aim was to correlate the expression level of Oct4B1 and the expression and methylation level of IGF2, MEST, and PEG10 imprinted genes with the mode of delivery and conception in the umbilical cord blood of newborns. Materials and Methods: Samples of umbilical cord blood from infants born after vaginal delivery, caesarean section (CS) with the infant in cephalic position and CS due to breech position were examined. Furthermore, the investigation included infants conceived through means of assisted reproductive technology. Results: No statistically significant differences were found in mRNA expression levels between different modes of conception and delivery (p = 0.96). Oct4B1, IGF2, MEST, and PEG10 expression levels do not seem to be significantly affected by different modes of conception and delivery. Conclusion: These results indicate that the expression and methylation patterns of Oct4B1, IGF2, MEST and PEG10 in umbilical cord blood are not affected by the conception and delivery mode. Key words: Conception, Fertilization in vitro, Genomic imprinting, Fetal blood

MMP9 but Not EGFR, MET, ERCC1, P16, and P-53 Is Associated with Response to Concomitant Radiotherapy, Cetuximab, and Weekly Cisplatin in Patients with Locally Advanced Head and Neck Cancer

Concomitant administration of radiotherapy with cisplatin or radiotherapy with cetuximab appear to be the treatment of choice for patients with locally advanced head and neck cancer. In the present retrospective analysis, we investigated the predictive role of several biomarkers in an unselected cohort of patients treated with concomitant radiotherapy, weekly cisplatin, and cetuximab (CCRT). We identified 37 patients treated with this approach, of which 13 (35%) achieved a complete response and 10 (27%) achieved a partial response. Severe side effects were mainly leucopenia, dysphagia, rash, and anemia. Tumor EGFR, MET, ERCC1, and p-53 protein and/or gene expression were not associated with treatment response. In contrast, high MMP9 mRNA expression was found to be significantly associated with objective response. In conclusion, CCRT is feasible and active. MMP9 was the only biomarker tested that appears to be of predictive value in cetuximab treated patients. However, this is a hypothesis generating study and the results should not be viewed as definitive evidence until they are validated in a larger cohort

SOME STUDIES ON THE ANTIVIRAL AND ANTICELLULAR PROPERTIES OF INTERFEERONS.

WITH THE PRESEND WORK WE INVESHGATEDΜΕ ΤΗΝ ΕΡΓΑΣΙΑ ΜΑΣ ΑΥΤΗ ΜΕΛΕΤΗΣΑΜΕ ΜΕΡΙΚΕΣ ΙΔΙΟΤΗΤΕΣ ΤΗΣ ΙΝΤΕΡΦΕΡΟΝΗΣ (IFN). ΔΕΙΞΑΜΕ ΟΤΙ ΕΑΝ Η IFN ΕΠΑΓΕΙ ΤΗΝ 2',5'ΟΛΙΓΟ Α ΣΥΝΘΕΤΑΣΗ ΟΙ ΕΠΑΓΩΓΕΣ ΤΗΣ IFN ΠΟΥ ΧΡΗΣΙΜΟΠΟΙΗΘΗΚΑΝ (POLY I-POLY C ΚΑΙ SV40) ΔΕΝ ΕΠΗΓΑΓΑΝ ΤΟ ΕΝΖΥΜΟ ΑΥΤΟ. Η ΜΕΤΑΓΡΑΦΗ ΤΗΣ 2',5'ΟΛΙΓΟ Α ΣΥΝΘΕΤΑΣΗΣ ΗΤΑΝ ΜΕΓΙΣΤΗ ΜΕΤΑ ΑΠΟ 12 ΩΡΩΝ ΚΑΤΕΡΓΑΣΙΑ ΤΩΝ ΚΥΤΤΑΡΩΝ ΜΕ IFN. Η ΑΝΑΝΕΩΣΗ ΤΗΣ IFN ΣΤΟ ΘΡΕΠΤΙΚΟ ΥΓΡΟ ΤΩΝ ΚΥΤΑΡΟΚΑΛΛΙΕΡΓΕΙΩΝΠΑΙΖΕΙ ΣΠΟΥΔΑΙΟ ΡΟΛΟ ΣΤΗΝ ΔΙΑΤΗΡΗΣΗ ΜΕΓΙΣΤΩΝ ΕΠΙΠΕΔΩΝ ΤΗΣ 2',5' ΟΛΙΓΟ Α ΣΥΝΘΕΤΑΣΗΣ. ΟΙ IFN ΕΙΝΑΙ ΓΝΩΣΤΟ ΟΤΙ ΕΠΗΡΕΑΖΟΥΝ ΤΗΝ ΠΡΩΤΕΙΝΙΚΗ ΣΥΝΘΕΣΗ ΜΕ ΔΙΑΦΟΡΟΥΣ ΤΡΟΠΟΥΣ. ΜΕ ΤΗΝ ΕΡΓΑΣΙΑ ΜΑΣ ΑΥΤΗ ΕΞΕΤΑΣΑΜΕ ΚΑΤΑ ΠΟΣΟ Η IFN ΕΠΗΡΕΑΖΕΙ ΤΗΝ ΙΣΤΟΝΗ ΚΑΙ ΤΗΝ ΑΚΤΙΝΗ. ΤΑ ΑΠΟΤΕΛΕΣΜΑΤΑ ΔΕΙΧΝΟΥΝ ΟΤΙ Η IFN ΔΕΝ ΕΠΗΡΕΑΖΕΙ ΤΑ ΕΠΙΠΕΔΑ ΜΕΤΑΓΡΑΦΗΣ ΤΩΝ ΔΥΟ ΑΥΤΩΝ ΠΡΩΤΕΙΝΩΝ ΕΝΩ ΑΝΤΙΘΕΤΑ ΕΠΑΓΕΙ ΤΗΝ ΜΕΤΑΓΡΑΦΕΙ ΤΗΣ 2',5' ΟΛΙΓΟ Α ΣΥΝΘΕΤΑΣΗ. Η IFN ΕΠΙΣΗΣ ΕΛΑΤΩΝΕΙ ΤΗΝ ΜΕΤΑΓΡΑΦΗ ΤΟΥ ΜΕΓΑΛΟΥ SV40 T ΑΝΤΙΓΟΝΟΥ. ΑΝ Η ΕΠΕΞΑΡΓΑΣΙΑ ΤΩΝ ΚΥΤΤΑΡΩΝ ΜΕ ΙΝΤΕΡΦΕΡΟΝΗ ΓΙΝΕΙ ΠΡΙΝ ΑΠΟ ΤΗ ΜΟΛΥΝΣΗ ΤΟΥΣ ΜΕ ΤΟΝ ΙΟ SV40, Η ΑΝΑΣΤΟΛΗ ΤΗΣ ΣΥΝΘΕΣΗΣ ΤΟΥ Τ-ΑΝΤΙΓΟΝΟΥ ΑΠΟ ΤΗΝ IFN ΕΞΑΡΤΑΤΑΙ ΑΠΟ ΤΗΝ ΔΙΑΡΚΕΙΑ ΕΠΕΞΕΡΓΑΣΙΑΣ ΜΕ IFN. ΑΝ ΟΜΩΣ Η ΕΠΕΞΕΡΓΑΣΙΑ ΥΠΕΡΒΕΙ ΤΙΣ 16 ΩΡΕΣ ΤΟ ΦΑΙΝΟΜΕΝΟ ΤΗΣ ΑΝΑΣΤΟΛΗΣ ΑΝΤΙΣΤΡΕΦΕΤΑΙ ΕΚΤΟΣ ΑΝ ΓΙΝΕΙ ΑΝΑΝΕΩΣΗΣ ΤΗΣ IFN ΣΤΟ ΘΡΕΠΤΙΚΟ ΜΕΣΟ . ΕΠΕΙΔΗ ΤΕΛΟΣ Η ΑΝΑΣΤΟΛΗ ΜΕΤΑΓΡΑΦΗΣ ΤΟΥ RNA ΤΟΥ Τ-ΑΝΤΙΓΟΝΟΥ ΕΙΝΑΙ ΜΙΚΡΟΤΕΡΗ ΑΠΟ ΑΥΤΗ ΤΗΣ ΜΕΤΑΦΡΑΣΗΣ, ΠΡΟΤΕΙΝΟΥΜΕ ΟΤΙ Η IFN ΔΡΑ ΚΑΙΣΤΗ ΜΕΤΑΓΡΑΦΗ ΚΑΙ ΣΤΗ ΜΕΤΑΦΡΑΣΗ ΤΟΥ Τ-ΑΝΤΙΓΟΝΟΥ

Effect of Bladder Injection of OnabotulinumtoxinA on the Central Expression of Genes Associated with the Control of the Lower Urinary Tract: A Study in Normal Rats

To investigate a possible central mechanism of action of Botulinum toxin A (BoNT/A) following injection in the bladder, complementary to the acknowledged peripheral bladder effect, we studied changes in the expression of neuropeptides and receptors involved in lower urinary tract function in the spinal cord (SC) and dorsal root ganglia (DRG) of normal rats following BoNT/A bladder injection. Thirty-six Sprague-Dawley rats, divided into three groups of n = 12, received bladder injections of 2U or 5U OnabotulinumtoxinA (BOTOX&reg;), or saline. Six animals from each group were sacrificed on days 7 and 14. Expression of Tachykinin 1 (Tac1), capsaicin receptor (TRPV1), neuropeptide Y (NPY), proenkephalin (PENK) and muscarinic receptors M1, M2, M3, was evaluated in the bladder, L6-S1 DRG, and SC segments using real-time PCR and Western blotting. Real-time PCR revealed increased expression of NPY in all tissues except for SC, and increased TRPV1 and PENK expression in DRG and SC, whereas expression of Tac1, M1 and M2 was decreased. Less significant changes were noted in protein levels. These findings suggest that bladder injections of OnabotulinumtoxinA may be followed by changes in the expression of sensory, sympathetic and cholinergic bladder function regulators at the DRG/SC level

The effect of 3,4-methylenedioxymethamphetamine (MDMA) on human genetic material: an in vitro study

Background: 3,4-methylenedioxymethamphetamine (MDMA), is a synthetic illicit psychostimulant drug  that affects  mood and social interactions. The aim of the present study is to investigate the in vitro effect of MDMA on human genetic material, by estimating sensitive cytogenetic indices.Methods: MDMA solutions (A=15μg/ml, B=30μg/ml, C=45μg/ml, D=60μg/ml, E=75μg/ml) were added in cultures of peripheral blood lymphocytes of four healthy donors. After 72 hours of incubation, the cultured lymphocytes were collected, plated on glass slides, stained with the Fluorescence plus Giemsa method and SCEs, PRI and MI were measured with the optical microscope. Sister Chromatid Exchanges (SCEs) is a sensitive marker of genotoxicity, Proliferation Rate Index (PRI) is a reliable marker of cytostatic activity and Mitotic Index (MI) is a reliable indicator of cell ability to proliferate.Results: Result analysis revealed: a) a statistically significant (p=0.001) reduction of SCEs on lower MDMA concentration and a significant induction (p=0.001) of SCEs after the effect of higher MDMA concentrations, b) PRI and MI reduction (p=0.001) after the effect of MDMA concentrations 45, 60 and 75μg/ml. Correlation was observed between a) SCE and PRI index variations, b) MI and SCE index variations and c) PRI and MI index variations. Conclusions: MDMA exhibited an interesting cytogenetic activity in vitro. It seems to affect human T lymphocytes by epigenetic and DNA replication modifications. This may provide additional information about the mechanism of action of the drug. Further studies in other cell lines and in vivo experimental settings are needed in order to evaluate its potential effects on human genetic material

Screening for adeno-associated viruses and human papillomaviruses in greek women with no cervical lesion

In order to investigate the correlation between human papillomaviruses (HPV), causative agents of cervical cancer, and adeno-associated viruses (AAV), possible protective factor from this disease, we evaluated first the prevalence of cervical infection by these two viruses in asymptomatic Greek females (i.e. with normal cervices and no pathologic history). Our data indicates relatively low prevalence for both viruses (8.8% for HPV and 17.7% for AAV), compared to studies from other countries. This report is the first concerning prevalence of cervical AAV infection in Greece