A Low Cost Face Mask for Inhalation Anaesthesia in Rats

Inhalation anaesthesia in small laboratory rodents has become very popular in Biomedical Research. A  common method to deliver volatile anesthetic agents is through a face mask. The main disadvantage of this  method is the exposure of personnel to anaesthetic agents. The authors describe a low-cost face mask, made  with materials commonly accessible in the operating room that can be connected to an anaesthetic machine  eliminating personnel exposure to hazardous levels of anaesthetic agents and allowing for effective adjustments  to the anaesthetic depth.

Fatal venous air embolism in swine during surgical procedure

Η εμβολή με αέρα της φλεβικής κυκλοφορίας είναι ένα σχετικά σπάνιο γεγονός που μπορεί να συμβεί τόσο κατάτην εκτέλεση απλών χειρουργικών χειρισμών όσο και κατά τη διάρκεια μεγάλων χειρουργικών επεμβάσεων. Αν και υπάρχειπληθώρα βιβλιογραφικών αναφορών για τον άνθρωπο, η αναφορά περιστατικών σε ζώα είναι περιορισμένη. Περιγράφεται περιστατικόφλεβικής εμβολής με αέρα, που παρατηρήθηκε κατά τη διάρκεια χειρουργικής επέμβασης, για την τοποθέτηση μοσχεύματοςαπό πολυτετραφλουοροαιθυλένιο μεταξύ κοινής καρωτίδας και έξω σφαγιτιδας φλέβας σε χοίρο. Πριν και μετά τηντοποθέτηση του μοσχεύματος πραγματοποιήθηκε λήψη μετρήσεων της ενδοαγγειακής πίεσης και των μεταβολών της διαμέτρουτης έξω σφαγιτιδας φλέβας, κεντρικά και περιφερικά της αναστόμωσης του μοσχεύματος, καθώς και μετρήσεις των μεταβολώντης ροής τόσο στην κοινή καρωτίδα όσο και στην έξω σφαγιτιδα φλέβα, κεντρικά και περιφερικά των αντίστοιχων αναστομώσεων.Το ζώο παρέμενε σταθερό αιμοδυναμικά για δυο ώρες και σαράντα λεπτά, οπότε αιφνιδίως παρατηρήθηκε ραγδαία πτώσητου κορεσμού του αίματος σε οξυγόνομε ταυτόχρονη μείωση της καρδιακής συχνότητας. Παρά τους χειρισμούς που έγιναν από τη χειρουργική ομάδα, μετά από δέκα λεπτά το ζώο κατέληξε. Κατά τη νεκροτομική εξέταση παρατηρήθηκε συγκέντρωση μεγάλης ποσότητας αέρα στη δεξιά καρδιά, στην πρόσθια και την οπίσθια κοίλη φλέβα, στην πνευμονική αρτηρία, καθώς και στις στεφανιαίες αρτηρίες. Παρόλο που πιθανολογείται ότι η είσοδος του αέρα έγινε από την αναισθητική μηχανή ή το σημείο της αναστόμωσης, ο τρόπος εισόδου παραμένει άγνωστος.Air embolism can occur after minor invasive procedures, as well as during major surgical operations. Reports of air embolism cases in veterinary literature are not very often, although it is considered that it happens more often than it is recognized. During a surgical procedure in swine, for the creation of a fistula of PTFE graft between the right common carotid artery and the right jugular vein under general anaesthesia, the animal died due to massive venous air embolism. Although it is supposed that the air was possibly inserted through the anaesthetic machine or through the anastomosis, the exact mechanism of the air insertion remains unknown

Evaluation of a stable Gonadotropin-Releasing Hormone analog in mice for the treatment of endocrine disorders and prostate cancer

Gonadotropin-releasing hormone (GnRH) receptor agonists have wide clinical applications including the treatment of prostate cancer and endocrine disorders. However, such agonists are characterized by poor pharmacokinetic properties, often requiring repeated administration or special formulations. Therefore, the development of novel peptide analogs with enhanced in vivo stability could potentially provide therapeutic alternatives. The pharmacological evaluation of a bioactive peptide [Des-Gly10,Tyr5(OMe),D-Leu 6,Aze-NHEt9]GnRH, analog 1, is presented herein and compared with leuprolide. Peptide stability was evaluated using mouse kidney membrane preparations, followed by a liquid chromatography-tandem mass spectrometry-based approach that afforded identification and quantification of its major metabolites. The analog was significantly more stable in vitro in comparison with leuprolide. In vitro and in vivo stability results correlated well, encouraging us to develop a clinically relevant pharmacokinetic mouse model, which facilitated efficacy measurements using testosterone as a biomarker. Analog 1, an agonist of the GnRH receptor with a binding affinity in the nanomolar range, caused testosterone release in mice that was acutely dose-dependent, an effect blocked by the GnRH receptor antagonist cetrorelix. Repeated dosing studies in mice demonstrated that analog 1 was well tolerated and had potency similar to that of leuprolide, based on plasma and testis testosterone reduction and histopathological findings. Analog 1 also shared with leuprolide similar significant antiproliferative activity on androgen-dependent prostate cancer (LNCaP) cells. On the basis of pharmacokinetic advantages, we expect that analog 1 or analogs based on this new design will be therapeutically advantageous for the treatment of cancer and endocrine disorders. Copyrigh

Multifractal Scaling, Geometrical Diversity, and Hierarchical Structure in the Cool Interstellar Medium

Multifractal scaling (MFS) refers to structures that can be described as a collection of interwoven fractal subsets which exhibit power-law spatial scaling behavior with a range of scaling exponents (concentration, or singularity, strengths) and dimensions. The existence of MFS implies an underlying multiplicative (or hierarchical, or cascade) process. Panoramic column density images of several nearby star- forming cloud complexes, constructed from IRAS data and justified in an appendix, are shown to exhibit such multifractal scaling, which we interpret as indirect but quantitative evidence for nested hierarchical structure. The relation between the dimensions of the subsets and their concentration strengths (the "multifractal spectrum'') appears to satisfactorily order the observed regions in terms of the mixture of geometries present: strong point-like concentrations, line- like filaments or fronts, and space-filling diffuse structures. This multifractal spectrum is a global property of the regions studied, and does not rely on any operational definition of "clouds.'' The range of forms of the multifractal spectrum among the regions studied implies that the column density structures do not form a universality class, in contrast to indications for velocity and passive scalar fields in incompressible turbulence, providing another indication that the physics of highly compressible interstellar gas dynamics differs fundamentally from incompressible turbulence. (Abstract truncated)Comment: 27 pages, (LaTeX), 13 figures, 1 table, submitted to Astrophysical Journa

Nose-to-Brain delivery of donepezil hydrochloride following administration of an HPMC-Me-β-CD-PEG400 nasal film in mice

Nasal administration has been demonstrated as an effective alternative for drug delivery to central nervous system (CNS), especially for use in neurodegenerative diseases. Donepezil Hydrochloride (DH) is a widely used acetylcholinesterase inhibitor for the management of Alzheimer's disease, able to cross the blood brain barrier after oral administration. However, DH undergoes extensive first-pass metabolism, a fact that limits the amount of drug reaching the CNS. The purpose of the present study was the nose-to-brain delivery in vivo of DH, formulated in the recently developed HPMC-Me-β-CD-PEG400 based polymeric nasal film. In particular, a pharmacokinetic study was carried out in comparison with oral (per os) administration of DH solution. Sparse sampling non-compartmental analysis was applied of all in vivo data to determine the pharmacokinetic parameters. The pharmacokinetic profiles after intranasal and per os administration revealed the pre-eminence of the nasal film in DH delivery, either to the CNS or bloodstream resulting in Cmax values 5.7 and 3.9 times as higher, respectively at each site. The effectiveness of nasal film is also witnessed by AUC values, as well as Drug Targeting Efficiency Percentage and nose-to-brain Direct Transport Percentage, respectively found equal to 212% and 53%. © 2023 Elsevier B.V