Bisphosphonate’s effect in hepatic rat cells: An electron microscopy study

Σκοπός: Τα διφωσφονικά αποτελούν εκλεκτικούς αναστολείς της οστικής απορρόφησης και η μακροχρόνια χρήση τους έχει συσχετισθεί με ανεπιθύμητες επιδράσεις στο γαστρεντερικό σύστημα. Σκοπός της εργασίας είναι η διερεύνηση των πιθανών επιδράσεων των διφωσφονικών στη δομή των ηπατικών κυττάρων. Υλικά και μέθοδος: Ελήφθησαν δείγματα ηπατικού ιστού από δέκα θηλυκά ποντίκια Wistar ηλικίας δώδεκα μηνών που έλαβαν Αλενδρονάτη από του στόματος για 13 εβδομάδες και από δέκα θηλυκά ποντίκια Wistar ηλικίας δώδεκα μηνών που δεν έλαβαν το φάρμακο και χρησιμοποιήθηκαν ως μάρτυρες. Τα δείγματα μελετήθηκαν με το ηλεκτρονικό μικροσκόπιο. Αποτελέσματα: Στα ηπατικά κύτταρα των ποντικιών που έλαβαν Αλενδρονάτη βρέθηκαν εκτεταμένη απώλεια γλυκογόνου, διαφόρου μεγέθους κενοτόπια, διευρυμένα κολπώδη τριχοειδή, καθώς και απουσία των μικρολαχνών σε πολλά σημεία του χώρου του Disse. Συμπέρασμα: Πρόκειται για την πρώτη μελέτη με ηλεκτρονικό μικροσκόπιο ηπατικών δειγμάτων μετά τη χορήγηση διφωσφονικών, η οποία υποδεικνύει ήπια ηπατική βλάβη. Μια πιθανή συσχέτιση μεταξύ της χρήσης της Αλενδρονάτης και της ηπατικής λειτουργίας καθίσταται εμφανής. Ωστόσο, εξαιτίας του μικρού αριθμού δειγμάτων περισσότερες μελέτες είναι απαραίτητες ώστε να διαλευκανθεί αυτή η συσχέτιση.Purpose: Bisphosphonates (BPs) are selective inhibitors of osteoclast mediated bone resorption, used for the treatment of bone disorders as well as for tumors, whereas long-term bisphosphonate use is associated with adverse gastrointestinal effects. The objective of the study is to investigate the possible effects of BPs in hepatic structure. Materials and methods: Specimens from the liver of ten female 12-month old Wistar rats were used as control group and of ten female 12-month old Wistar rats to which Alendronate (Fosamax, Merck) was administered per os for 13 weeks, were used as experimental group. Samples were observed under a Transmission Electron Microscope. Results: In the experimental group, extensive depletion of the glycogen, different sized vacuoles and enlarged sinusoids were found in hepatic cells. Furthermore, there was lack of microvilli of hepatocytes in the Disse’s space. The same findings were reported in all sections of the experimental group. Conclusion: This is the first study of liver structure after the administration of bisphosphonates, with electron microscopy. This report, indicate the presence of mild hepatic damage in liver tissues studied. Our study demonstrates a possible correlation between alendronate administration and hepatic cell function, nevertheless due to the small specimen further research is needed

Zyklisches subakutes Abdomen und primäre Sterilität

Zuweisung der 31-jährigen Patientin (Nulligravida) durch die sie betreuende Reproduktionsmedizinerin zur weiteren Abklärung einer primären Sterilität und Dysmenorrhö in die gynäkologische Poliklinik. Beschrieben wird eine seit der Menarche progrediente Dysmenorrhö mit mittlerweile invalidisierendem Schmerzmaximum im linken Unterbauch am 5. Zyklustag. Während eines vorgängigen Therapieversuchs mit Ethinylestradiol und Levonorgestrel oral im Langzeitzyklus sei die Patientin vollkommen schmerzfrei gewesen

Homenaje al señor Jean Pictet

El señor Jean Pictet, al limite de la edad laboral y tras cuarenta y dos años de actividad al servicio del CICR, se jubilará el 30 dejunio de 1979. La can era del señor Pictet es de plenitud. Comenzó el año 1937 en el CICR, a la vez como pensador, jurista, escritor, profesor y hombre de actión, participando en todas las grandes empresas de la Cruz Roja, de las que ha sido inspirador y guí

Extrinsic intestinal denervation modulates tumor development in the small intestine of ApcMin/+ mice

Background Innervation interacts with enteric immune responses. Chronic intestinal inflammation is associated with increased risk of colorectal cancer. We aimed to study potential extrinsic neuronal modulation of intestinal tumor development in a mouse model. Methods Experiments were performed with male ApcMin/+ or wild type mice (4 weeks old, body weight approximately 20 g). Subgroups with subdiaphragmatic vagotomy (apcV/wtV), sympathetic denervation of the small intestine (apcS/wtS) or sham operated controls (apcC/wtC) were investigated (n = 6-14 per group). Three months after surgical manipulation, 10 cm of terminal ileum were excised, fixed for 48 h in 4% paraformaldehyde and all tumors were counted and their area determined in mm2 (mean ± standard error of the mean (SEM)). Whole mounts of the muscularis of terminal ileum and duodenum (internal positive control) were also stained for tyrosine hydroxylase to confirm successful sympathetic denervation. Results Tumor count in ApcMin/+ mice was 62 ± 8 (apcC), 46 ± 11 (apcV) and 54 ± 8 (apcS) which was increased compared to wildtype controls with 4 ± 0.5 (wtC), 5 ± 0.5 (wtV) and 5 ± 0.6 (wtS; all p < 0.05). For ApcMin/+ groups, vagotomized animals showed a trend towards decreased tumor counts compared to sham operated ApcMin/+ controls while sympathetic denervation was similar to sham ApcMin/+. Area covered by tumors in ApcMin/+ mice was 55 ± 10 (apcC), 31 ± 8 (apcV) and 42 ± 8 (apcS) mm2, which was generally increased compared to wildtype controls with 7 ± 0.6 (wtC), 7 ± 0.4 (wtV) and 7 ± 0.6 (wtS) mm2 (all p < 0.05). In ApcMin/+ groups, tumor area was decreased in vagotomized animals compared to sham operated controls (p < 0.05) while sympathetically denervated mice showed a minor trend to decreased tumor area compared to controls. Conclusions Extrinsic innervation of the small bowel is likely to modulate tumor development in ApcMin/+ mice. Interrupted vagal innervation, but not sympathetic denervation, seems to inhibit tumor growth

Pit picking vs. Limberg flap vs. primary open method to treat pilonidal sinus disease - A cohort of 327 consecutive patients.

Background Minimally invasive methods in pilonidal sinus disease (PSD) surgery are becoming standard. Although long-term results are available for some techniques, long-term outcome data of patients after pit picking is lacking. We aimed at investigating perioperative and long-term outcomes of patients undergoing pit picking, Limberg flap or primary open surgery to treat PSD. Methods In a single-centre observational study, we evaluated the outcomes of 327 consecutive patients undergoing PSD surgery between 2011 and 2020. Results PSD had recurred in 22% of Limberg flap patients and 62% of pit picking patients at 5 years (p=0.0078; log rank test). Previous pilonidal surgeries, smoking, body mass index, immunodeficiency, and diabetes did not significantly influence the long-term recurrence rate. Primary open treatment was performed for 72% of female patients presenting with primary disease. Conclusions Due to its especially dismal long-term results, pit picking should be abandoned, and Limberg flap should be promoted instead, even for primary disease and in females

Development and Characterization of a Monoclonal Antibody against Ochratoxin B and Its Application in ELISA

A monoclonal antibody specific to ochratoxin B (OTB) was employed for the development of an indirect competitive OTB-ELISA. The optimized OTB-ELISA resulted in a limit of detection (LOD) for OTB of 3 µg/L (8 nM), a limit of quantification (LOQ) of 3.7 µg/L (10 nM), and a 50% inhibitory concentration (IC50) of 150 nM. Due to very low cross-reactivity to OTA (2.7%) and structurally related molecules (0%), this OTB-ELISA was found to be suitable to detect OTB with excellent precision in different matrices, i.e., beer, coffee and wine. Therefore, this OTB-ELISA will allow screening of OTB in food and feed products

Functional network topology of the right insula affects emotion dysregulation in hyperactive-impulsive attention-deficit/hyperactivity disorder

Contains fulltext : 236832.pdf (Publisher’s version ) (Open Access

Conspiracy Beliefs and Knowledge About HIV Origins Among Adolescents in Soweto, South Africa

We examined adolescents\u27 knowledge regarding the origin of HIV/AIDS and correlates of beliefs surrounding conspiracy theories in Soweto, South Africa. Now, a decade post-AIDS denialism, South Africa has the largest antiretroviral therapy roll-out worldwide. However, conspiracy theories stemming from past AIDS denialism may impact HIV prevention and treatment efforts