Panic Attack during Elective Gastrointestinal Endoscopy

Background. Esophagogastroduodenoscopy (EGD) and colonoscopy (CS) can evoke anxiety, embarrassment, and discomfort. These concerns can culminate in panic attacks, which may traumatize patients and significantly decrease their compliance to the procedure. The objective of this study was to evaluate the relationship between preendoscopic anxiety and the possibility of a panic attack during an elective gastrointestinal endoscopy (EGE). Methods. The study population comprised of 79 Greek outpatients. The examination was carried out without the use of conscious sedation. Patients' anxiety levels were assessed before the procedure using the Greek version of the Spielberger State-Trait Anxiety Inventory (STAI-Y). Results. Seventy-nine patients were enrolled: 45 EGD and 34 CS. Females had higher state and trait anxiety levels than males (48.14 ± 7.94 versus 44.17 ± 7.43, P < 0.05; and 43.68 ± 6.95 versus 39.86 ± 7.46, P < 0.05). Patients who experienced panic attack had significantly higher levels of both trait and state anxiety, compared to those who were panic-free. There was no significant relationship between panic attacks and sex or type of procedure. Conclusions. Patients who experience panic attacks during endoscopic procedures appear to have significantly higher anxiety levels before the procedure. Administering the STAI questionnaire prior to the endoscopy seems to be a useful screening method for vulnerable patients

Synthetic flavonoid derivatives targeting the glycogen phosphorylase inhibitor site: QM/MM-PBSA motivated synthesis of substituted 5,7-dihydroxyflavones, crystallography, in vitro kinetics and ex-vivo cellular experiments reveal novel potent inhibitors

Glycogen phosphorylase (GP) is an important target for the development of new anti-hyperglycaemic agents. Flavonoids are novel inhibitors of GP, but their mode of action is unspecific in terms of the GP binding sites involved. Towards design of synthetic flavonoid analogues acting specifically at the inhibitor site and to exploit the site’s hydrophobic pocket, chrysin has been employed as a lead compound for the in silico screening of 1169 new analogues with different B ring substitutions. QM/MM-PBSA binding free energy calculations guided the final selection of eight compounds, subsequently synthesised using a Baker-Venkataraman rearrangement-cyclisation approach. Kinetics experiments against rabbit muscle GPa and GPb together with human liver GPa, revealed three of these compounds (11, 20 and 43) among the most potent that bind at the site (Ki s < 4 µM for all three isoforms), and more potent than previously reported natural flavonoid inhibitors. Multiple inhibition studies revealed binding exclusively at the inhibitor site. The binding is synergistic with glucose suggesting that inhibition could be regulated by blood glucose levels and would decrease as normoglycaemia is achieved. Compound 43 was an effective inhibitor of glycogenolysis in hepatocytes (IC50 = 70 µM), further promoting these compounds for optimization of their drug-like potential. X-ray crystallography studies revealed the B-ring interactions responsible for the observed potencies

Design, synthesis and evaluation of biological activity of new indole derivatives, analogs of natural products as potential inhibitors of protein kinases

Protein kinases are key components of many cellular signaling pathways and play a crucial role in vital cellular processes. Deregulation of protein kinase activity results in a wide range of pathological disorders among which cancer plays a prominent role. Over the past decades, a great deal of research has been directed towards the discovery of new protein kinase inhibitors. As a result, a number of small molecules have been licensed for the treatment of various types of cancer, while many others are under clinical trials.The majority of protein kinase inhibitors reported in the literature are small heterocycles targeting the ATP-binding site of the enzymes. Despite their structural diversity, recent data indicate that their structures cover a limited part of chemical space. Moreover, many bioactive protein kinase inhibitors contain an azepinone motif as part of their structure, which is involved in important binding interactions with the ATP-binding site and contributes to their selectivity.Based on these observations, we have focused on the generation of new azepinone containing scaffolds, aiming at the discovery of new chemotypes with potential protein kinase inhibitory activities. Particularly, the design and synthesis of small tetracyclic heterocycles, which bear two new regioisomeric 2-carboxyethyl-1H-pyrrole-annulated indoloazepinone scaffolds was studied.Concise access to the new regioisomeric tetracyclic derivatives was accomplished through amide coupling of appropriate pyrrole and indole precursors followed by an intramolecular Heck coupling reaction of the intermediate amide conjugates.Preliminary evaluation of four newly synthesized tetracyclic molecules against a panel of fifty protein kinases at a single concentration of 10 μΜ indicated their inhibitory activities and revealed promising selectivity profiles. The obtained data revealed that a limited number of kinase targets were inhibited more than 70% by the tested derivatives. The new compounds displayed no significant antiproliferative activity against MCF-7 cancer cells. Importantly, derivative 49b exhibited selective TAK1 kinase inhibitory activity and figures as a promising hit compound for the discovery of new TAK1 inhibitors.Οι πρωτεϊνικές κινάσες εμπλέκονται σε πλήθος σηματοδοτικών μονοπατιών και διαδραματίζουν κρίσιμο ρόλο σε ζωτικές κυτταρικές λειτουργίες. Η απορρύθμιση της λειτουργίας τους έχει ως επακόλουθο την εμφάνιση παθολογικών καταστάσεων, μεταξύ των οποίων ο καρκίνος έχει εξέχοντα ρόλο. Κατά τις τελευταίες δεκαετίες, έχει αναπτυχθεί έντονο ερευνητικό ενδιαφέρον για την ανακάλυψη νέων αναστολέων, με εκλεκτική ανασταλτική δράση έναντι συγκεκριμένων κινασών. Ως αποτέλεσμα αυτών των προσπαθειών, ένας σημαντικός αριθμός μικρών μορίων έχουν λάβει έγκριση για τη θεραπεία διαφόρων μορφών καρκίνου, ενώ πολλοί άλλοι βρίσκονται υπό μελέτη σε κλινικές δοκιμές.Η πλειονότητα των αναστολέων πρωτεϊνικών κινασών, που περιγράφονται στη βιβλιογραφία, είναι μικρά ετεροκυκλικά μόρια, που στοχεύουν τη θέση πρόσδεσης του ATP των ενζύμων. Παρόλη την χημική ετερογένεια τους, πρόσφατα δεδομένα αποδεικνύουν ότι αυτή κινείται εντός ορίων. Επιπλέον, αρκετοί βιοδραστικοί αναστολείς περιέχουν στη δομή τους ένα δακτύλιο αζεπινόνης, ο οποίος εμπλέκεται σε κρίσιμες αλληλεπιδράσεις με τη θέση δέσμευσης του ATP και συνεισφέρει στην εκλεκτικότητά τους.Με βάση τις προηγούμενες παρατηρήσεις, η παρούσα μελέτη εστίασε στον σχεδιασμό νέων ετεροκυκλικών μορίων που ενσωματώνουν δακτύλιο αζεπινόνης, με απώτερο σκοπό την ανακάλυψη νέων χημειοτύπων με ανασταλτική δράση έναντι πρωτεϊνικών κινασών. Ειδικότερα, σχεδιάσθηκαν νέα τετρακυκλικά ετεροκυκλικά μόρια, ανάλογα δύο τοποϊσομερών σκελετών, οι οποίοι έφεραν ένα τρικυκλικό ινδολοαζεπινονικό σύστημα, συμπυκνωμένο κατάλληλα με έναν 2-καρβοξυαιθυλο-1Η-πυρρολικό δακτύλιο.Η σύνθεση των νέων τετρακυκλικών ενώσεων περιελάμβανε την αμιδική σύζευξη κατάλληλων πρόδρομων πυρρολικών και ινδολικών παραγώγων και την ενδομοριακή Pd-καταλυόμενη σύζευξη Heck των προκυπτόντων αμιδικών συζευγμάτων.Τέσσερα νέα τετρακυκλικά παράγωγα που συντέθηκαν στα πλαίσια της μελέτης αυτής προωθήθηκαν σε βιολογικές δοκιμασίες για την προκαταρκτική αποτίμηση της βιολογικής δραστικότητάς τους. Οι ενώσεις παρουσίασαν ενδιαφέρουσες ανασταλτικές δράσεις και ικανοποιητικό προφίλ εκλεκτικότητας έναντι μίας αντιπροσωπευτικής ομάδας πενήντα πρωτεϊνικών κινασών, καθώς ανέστειλαν έναν περιορισμένο αριθμό ενζύμων σε ποσοστό άνω του 70%, όταν ελέχθησαν σε τελική συγκέντρωση 10 μM. Ωστόσο, δεν εμφάνισαν ικανότητα αναστολής του πολλαπλασιασμού καρκινικών κυττάρων MCF-7. Αξίζει να σημειωθεί, το παράγωγο 49b, εμφάνισε εκλεκτική ανασταλτική δράση έναντι της TAK1 κινάσης και αναδείχθηκε ως μία ενδιαφέρουσα πρόδρομη ένωση για την ανακάλυψη νέων ΤΑΚ1 αναστολέων, με πιθανές θεραπευτικές εφαρμογές

Increased plasma levels of 8-iso-PGF2α and IL-6 in an elderly population with depression

Oxidative damage and immune-inflammatory activation have been suggested to play a role in depression. The purpose of the study was to investigate possible associations and interactions of these pathophysiological mechanisms in geriatric depression by determining the levels of plasma 8-iso-prostaglandin F2α (8-iso-PGF2α) and interleukin-6 (IL-6) in elderly depressed individuals. Subjects over 60 years of age with depression and controls were randomly selected from a population in the community after screening with the Geriatric Depression Scale. Plasma concentrations of 8-iso-PGF2α and IL-6 were measured in both groups. Depressed patients had significantly higher mean (± S.D.) 8-iso-PGF2α levels compared to healthy controls (245.01 ± 179.92 pg/ml vs 97.64 ± 42.72 pg/ml, respectively). Similarly, the same groups demonstrated significantly elevated IL-6 levels compared with controls (58.73 ± 39.90 pg/ml vs 15.41 ± 9.27 pg/ml). This study indicates an association between increased levels of plasma 8-iso-PGF2α and IL-6 with depressive symptomatology in elderly individuals and indicates the necessity for further investigation, possibly within the framework of an integrated involvement of oxidative damage and inflammation in the pathophysiology of depression in the elderly

Increased plasma levels of 8-iso-PGF(2 alpha) and IL-6 in an elderly population with depression

Oxidative damage and immune-inflammatory activation have been suggested to play a role in depression. The purpose of the study was to investigate possible associations and interactions of these pathophysiological mechanisms in geriatric depression by determining the levels of plasma 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)) and interleukin-6 (IL-6) in elderly depressed individuals. Subjects over 60 years of age with depression and controls were randomly selected from a population in the community after screening with the Geriatric Depression Scale. Plasma concentrations of 8-iso-PGF2 alpha and IL-6 were measured in both groups. Depressed patients had significantly higher mean (+/- S.D.) 8-iso-PGF2 alpha levels compared to healthy controls (245.01 +/- 179.92 pg/ml vs 97.64 +/- 42.72 pg/ml, respectively). Similarly, the same groups demonstrated significantly elevated IL-6 levels compared with controls (58.73 +/- 39.90 pg/mI vs 15.41 +/- 9.27 pg/ml). This study indicates an association between increased levels of plasma 8-iso-PGF2 alpha and IL-6 with depressive symptomatology in elderly individuals and indicates the necessity for further investigation, possibly within the framework of an integrated involvement of oxidative damage and inflammation in the pathophysiology of depression in the elderly. (c) 2007 Elsevier Ireland Ltd. All rights reserved

Factors associated with caregiver psychological distress in chronic schizophrenia

Caregivers of patients with schizophrenia experience increased levels of psychological distress. This study investigated the impact of caring for patients with chronic schizophrenia on the mental health status of the caregivers and described the relationship between various socio-demographic and clinical characteristics and caregiving psychological distress. The study was carried out at the Psychiatric Hospital of Athens. The Symptom Check List Revised (SCL-90-R) was administered to 87 caregivers of chronic schizophrenia patients and 90 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was administered to schizophrenia patients in order to assess illness severity. The group of caregivers scored higher on the majority of symptom dimensions of the SCL-90-R than the control group. Clinical features of schizophrenia, i.e. duration of illness and PANSS positive and negative symptoms significantly predicted caregiving psychological distress. Caregivers’ and patients’ socio-demographic characteristics were not associated with caregivers’ distress, with the exception of caregivers’ sex: female caregivers experienced significantly higher levels of psychological distress than males. The study suggests that clinical features of schizophrenia influence distress levels in caregivers of patients with chronic schizophrenia. The stronger predictors of distress appear to be female caregiver’s gender, duration of illness as well as positive and negative symptomatology

Characterization of the lipid profile in dementia and depression in the elderly

The purpose of the study was to examine the association of plasma lipid concentrations with changes in cognitive function and depressive states in elderly Greek individuals. The study population consisted of 3 groups: A) 37 subjects with dementia, B) 33 subjects with depression, and C) 33 controls. All individuals were screened with the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and an evaluation of their psychiatric state. Lipid profile was assessed in all subjects, and the results were statistically evaluated at P &lt;.05 level of significance. Groups A and B had significantly lower levels of total plasma cholesterol and HDL cholesterol than group C (P &lt;.01). Triglyceride levels did not differ significantly between groups A and C, although they were significantly higher in group B. The results of this study suggest that an association does exist between the plasma concentration of cholesterol and HDL-C and depression and/or cognitive impairment. Further studies are required to explore the significance of these observations and establish if lipid levels could serve as markers for diagnostic and therapeutic purposes