Topiramate-Induced Modulation of Hepatic Molecular Mechanisms: An Aspect for Its Anti-Insulin Resistant Effect

Topiramate is an antiepileptic drug known to ameliorate insulin resistance besides reducing body weight. Albeit liver plays a fundamental role in regulation of overall insulin resistance, yet the effect of topiramate on this organ is controversial and is not fully investigated. The current work aimed to study the potential hepatic molecular mechanistic cassette of the anti-insulin resistance effect of topiramate. To this end, male Wistar rats were fed high fat/high fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant, hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular level, has opposed the high fat/high fructose diet effect, where it significantly increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while decreased insulin receptor isoforms. Besides, it improved the altered glucose homeostasis and lipid profile, lowered the ALT level, caused subtle, yet significant decrease in TNF-α, and boosted adiponectin in a dose dependent manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and epididymal fat weight/body weight ratios. The study proved that insulin-resistance has an effect on hepatic molecular level and that the topiramate-mediated insulin sensitivity is ensued partly by modulation of hepatic insulin receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and elevation of adiponectin receptors, as well as their ligand, adiponectin, besides its known improving effect on glucose tolerance and lipid homeostasis

Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast

BACKGROUND: Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. METHODS: Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. RESULTS: Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. CONCLUSIONS: The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance

B-type natriuretic peptide-induced delayed modulation of TRPV1 and P2X3 receptors of mouse trigeminal sensory neurons

Important pain transducers of noxious stimuli are small- and medium-diameter sensory neurons that express transient receptor vanilloid-1 (TRPV1) channels and/or adenosine triphosphate (ATP)-gated P2X3 receptors whose activity is upregulated by endogenous neuropeptides in acute and chronic pain models. Little is known about the role of endogenous modulators in restraining the expression and function of TRPV1 and P2X3 receptors. In dorsal root ganglia, evidence supports the involvement of the natriuretic peptide system in the modulation of nociceptive transmission especially via the B-type natriuretic peptide (BNP) that activates the natriuretic peptide receptor-A (NPR-A) to downregulate sensory neuron excitability. Since the role of BNP in trigeminal ganglia (TG) is unclear, we investigated the expression of BNP in mouse TG in situ or in primary cultures and its effect on P2X3 and TRPV1 receptors of patch-clamped cultured neurons. Against scant expression of BNP, almost all neurons expressed NPRA at membrane level. While BNP rapidly increased cGMP production and Akt kinase phosphorylation, there was no early change in passive neuronal properties or responses to capsaicin, \u3b1,\u3b2-meATP or GABA. Nonetheless, 24 h application of BNP depressed TRPV1 mediated currents (an effect blocked by the NPR-A antagonist anantin) without changing responses to \u3b1,\u3b2-meATP or GABA. Anantin alone decreased basal cGMP production and enhanced control \u3b1,\u3b2-meATP-evoked responses, implying constitutive regulation of P2X3 receptors by ambient BNP. These data suggest a slow modulatory action by BNP on TRPV1 and P2X3 receptors outlining the role of this peptide as a negative regulator of trigeminal sensory neuron excitability to nociceptive stimuli. \ua9 2013 Vilotti et al

Disorders of sex development: effect of molecular diagnostics

Disorders of sex development (DSDs) are a diverse group of conditions that can be challenging to diagnose accurately using standard phenotypic and biochemical approaches. Obtaining a specific diagnosis can be important for identifying potentially life-threatening associated disorders, as well as providing information to guide parents in deciding on the most appropriate management for their child. Within the past 5 years, advances in molecular methodologies have helped to identify several novel causes of DSDs; molecular tests to aid diagnosis and genetic counselling have now been adopted into clinical practice. Occasionally, genetic profiling of embryos prior to implantation as an adjunct to assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory testing of positive results found during newborn biochemical screening are performed. Of the available genetic tests, the candidate gene approach is the most popular. New high-throughput DNA analysis could enable a genetic diagnosis to be made when the aetiology is unknown or many differential diagnoses are possible. Nonetheless, concerns exist about the use of genetic tests. For instance, a diagnosis is not always possible even using new molecular approaches (which can be worrying for the parents) and incidental information obtained during the test might cause anxiety. Careful selection of the genetic test indicated for each condition remains important for good clinical practice. The purpose of this Review is to describe advances in molecular biological techniques for diagnosing DSDs

Assesment of health related quality of life in elderly nursing home residents in Heraklion

Καθώς το προσδόκιμο επιβίωσης επεκτείνεται, παράλληλα αυξάνεται και ο πληθυσμός των ηλικιωμένων. Σήμερα το 10% των Ευρωπαίων ηλικιωμένων ζει σε ιδρύματα κλειστής περίθαλψης και έχει αυξημένες ανάγκες φροντίδας. Η διερεύνηση λοιπόν της Σχετιζόμενης με την Υγεία Ποιότητα Ζωής (Σ.Υ.Π.Ζ.) των ηλικιωμένων που ζουν σε ιδρύματα, παρουσιάζει ιδιαίτερο ενδιαφέρον για τη δημόσια Υγεία.. Σκοπός της μελέτης αυτής είναι η αξιολόγηση της Σ.Υ.Π.Ζ. των τροφίμων του γηροκομείου-πτωχοκομείου, Ηρακλείου Κρήτης, ως προς τους τομείς: κινητικότητας, πόνου, ύπνου, ενεργητικότητας, συναισθηματικών αντιδράσεων και κοινωνικής απομόνωσης, ώστε να γίνει κατανοητό σε ποιους από τους παραπάνω τομείς της Σ.Υ.Π.Ζ., θα ήταν ωφέλιμο για τους ηλικιωμένους να γίνουν παρεμβάσεις βελτίωσης. Η μελέτη έλαβε χώρα από 3/2013 έως 3/2014 και πραγματοποιήθηκε στο Πτωχοκομείο – Γηροκομείο Ηρακλείου Κρήτης. Οι ένοικοι του ιδρύματος είναι 116 άτομα, τα οποία προσεγγίστηκαν στο σύνολο τους για το σκοπό της μελέτης και τελικά συναίνεσαν να συμμετέχουν 92 άτομα. Αποτελεί μελέτη περίπτωσης στην οποία ακολουθείται μεθοδολογία συγχρονικής μελέτης. Για τη συλλογή δεδομένων χρησιμοποιήθηκε το N.H.P. (Nottingham Health Profile) ένα διεθνώς αποδεκτό, ερωτηματολόγιο το οποίο έχει κριθεί κατάλληλο για την χρήση του σε ιδρυματιζόμενους ηλικιωμένους. Δημόσια Υγεία & Διοίκηση Υπηρεσιών Υγείας Τμήμα Ιατρικής – Πανεπιστήμιο Κρήτης 2 Από τα αποτελέσματα της μελέτης τα προβλήματα υγείας έδειξαν να επιβαρύνουν τους επιμέρους τομείς. Συγκεκριμένα τα άτομα με καρδιαγγειακά προβλήματα έχουν στατιστικώς σημαντικά χειρότερη ποιότητα ζωής στους τομείς της ενέργειας και του πόνου. Τα άτομα με έκπτωση κινητικότητας έχουν επίσης στατιστικώς σημαντικά χειρότερη ποιότητα ζωής στους τομείς της ενέργειας, του πόνου, τις συναισθηματικές αντιδράσεις και βεβαίως της κινητικότητας. Τα άτομα με έκπτωση ακοής και όρασης έχουν στατιστικώς σημαντικά χειρότερη ποιότητα ζωής στους τομείς της κινητικότητας και της ενέργειας αντίστοιχα. Συνολικά τα άτομα με ένα ή περισσότερα προβλήματα υγείας έχουν στατιστικά σημαντικά χειρότερη ποιότητα ζωής στα πεδία της ενέργειας του πόνου και της κινητικότητας. Τέλος, στατιστικά σημαντική θετική συσχέτιση παρατηρήθηκε μεταξύ της ηλικίας και των πεδίων ενέργειας και κινητικότητας και μεταξύ των ετών διαμονής στο ίδρυμα και των πεδίων του πόνου και του ύπνου, των οποίων τα σκορ αυξανόμενα δείχνουν χαμηλότερο επίπεδο Σ.Υ.Π.Ζ. βάση του N.H.P., στους αντίστοιχους τομείς. Συμπερασματικά, τα αποτελέσματα έδειξαν ότι τα υψηλότερα επίπεδα δυσφορίας της Σ.Υ.Π.Ζ. αντιστοιχούν στον τομέα της ενέργειας, ενώ ακολουθούν η κινητικότητα και οι συναισθηματικές αντιδράσεις. Παρατηρείται ότι ο ύπνος, η κοινωνική απομόνωση και τέλος ο πόνος παρουσιάζουν τα χαμηλότερα επίπεδα δυσφορίας. Η μελέτη αυτή δίνει μια χρήσιμη εκτίμηση της Σ.Υ.Π.Ζ. των ηλικιωμένων ενοίκων του ιδρύματος, και των παραγόντων που την επηρεάζουν. Συμβάλει επίσης στην αποσαφήνιση των κατευθύνσεων στις οποίες ενδείκνυνται να γίνουν στοχευμένες παρεμβάσεις βελτίωσης της Σ.Υ.Π.Ζ. των ενοίκων, ενώ παράλληλα αποτελεί ένα ακόμα οδηγό σημείο για συναφείς μελέτες στον Ελλαδικό χώρο και συγκρίσεις με δεδομένα του εξωτερικού.While the life expectancy is increased, the population of the elderly people is also increased. Nowadays, the 10% of the European elderly people have increased care requirements and institutional care is being provided to them. Thus, the investigation of the Health Related Quality of Life (H.R.Q.L.) of the institutionalized elderly is of great interest in terms of Social Care. The aim of the current study is the evaluation of the H.R.Q.L. of the institutionalized elderly people living in the almshouse of Heraklion. The study focused in the field of the mobility, pain, sleep, activity, emotional reactions and social isolation, in order to be better understood the potential improvement of the elderly’s life upon interventions of the referred circumstances of H.R.Q.L. The study was carried out in the almshouse-nursing home of Heraklion of Crete (March 2013-March 2014). For the purpose of the study all the residents (116) of the Institution, were asked to participate in the study and 92 of them gave their consent. A cross-sectional analysis was used for the purposes of the current case study. For the collection of the data, the Nottingham Health Profile (NHP) questionnaire was used. NHP questionnaire is an internationally recognized quality of life questionnaire for its appropriateness to be used to institutionalized elderly. According to the results of this study, health related problems affect negatively the issues studied that were mentioned above. In particular, people with cardiovascular diseases have statistically worse quality of life in terms of activity and feeling of pain, than people who do not have cardiovascular diseases. The individuals with mobility problems not only have decreased H.R.Q.L. in terms of mobility, activity and feeling of pain, but also in terms of emotional reactions. On the other hand, the individuals with hearing or vision problems have decreased quality of life in terms of mobility and activity, respectively. It was also concluded, that individuals with one or more health related problems have decreased H.R.Q.L in terms of activity, feeling of pain and mobility. Last but not least, it was also statistically implied a positive correlation between the age of the elderly and the fields of activity, feeling of pain, sleep and time of residence in the institution. When these parameters were increased, according to the results derived from the use of the NHP, a decreased level of H.R.Q.L. was observed. As a conclusion, it can be said, that the highest H.R.Q.L. levels were observed in the people with activity problems followed by individuals with mobility and emotional reaction problems. It was also observed, that sleep, social isolation and feeling of pain contribute to a lesser extent to the discomfort of the elderly. The current study is a useful tool for the evaluation of the H.R.Q.L. of the residents participated in the study and also of the factors influence the H.R.Q.L. This study also contributes to a better understanding of the fields of improvement that can have beneficial effects to the H.R.Q.L. of the elderly. In addition, the current study can be a useful tool for future relevant studies in Greece or abroad. Ke