Influence of high ambient temperature on reproductive performance and physiology of rabbit does in a commercial rabbitry in Greece

Αντικείμενο της παρούσας εργασίας υπήρξε η μελέτη των αναπαραγωγικών και φυσιολογικών παραμέτρων των κονικλομητέρων υπό τις φυσικές συνθήκες εκτροφής τους στηνΕλλάδα, κατά τη θερινή (Ιούλιος 2000-Οκτώβριος 2000 και Μάϊος 2001-Ιούνιος 2001) και χειμερινή (Νοέμβριος-Απρίλιος 2001) περίοδο (μέση θερμοκρασία θαλάμων εκτροφής 19,5°C και 12,4°C αντίστοιχα). Για τους σκοπούς της μελέτης χρησιμοποιήθηκαν 809 ενήλικα θηλυκά και 20 ενήλικα αρσενικά κουνέλια διασταυρωμένα Νέας Ζηλανδίας χ Καλιφόρνιας. Οι φυσιολογικές παράμετροι που μελετήθηκαν ήταν: το σύνολο των γεννηθέντων κονικλιδίων (ζωντανών,νεκρών, θνησιγενών) ανά κονικλομητέρα, το βάρος της το-κετοομάδας, το μέσο ατομικό βάρος γέννησης και ο αριθμός απογαλακτισθέντων και το ποσοστό θνησιμότητας των θηλαζόντων κονικλιδίων με βάση τον αριθμό των ζωντανών γεννηθέντων και των υιοθετημένων ανά τοκετοομάδα. Ελήφθη η θερμοκρασία απευθυσμένου και ο ρυθμός αναπνοών των κονικλομητέρων. Η δυσμενής επίδραση των υψηλών θερινών θερμοκρασιών ήταν σημαντική στο μέγεθος της τοκετοομάδας κατά τη γέννηση (7,38 συνολικά γεννηθέντα τη θερινή περίοδο έναντι 8,05 τη χειμερινή Ρ0,05, και 68g έναντι 65g το χειμώνα, Ρ>0,05, αντίστοιχα).(Στις κονικλομητέρες κατά τη θερινή περίοδο παρατηρήθηκε στατιστικά μη σημαντική αύξηση της θερμοκρασίας απευθυσμένου (39,09°C έναντι 38,93°C χο χειμώνα), καθώς και στατιστικά σημαντική αύξηση του αριθμού των αναπνοών/λεπτό (128,08 αναπνοές/λεπτό έναντι 115,37 αναπνοές/ λεπτό το χειμώνα, Ρ<0,001). Πέρα από την επίδραση της θερμοκρασίας του περιβάλλοντος μελετήθηκε τόσο η επίδραση του αριθμού τοκετών ανά κονικλομητέρα όσο και η ατομικότητα της κάθε κονικλομητέρας στις αναπαραγωγικές παραμέτρους. Σημαντική ήταν η επίδραση του αριθμού τοκετών ανά κονικλομητέρα στο σύνολο των γεννηθέντων κονικλιδίων, στα ζωντανά, νεκρά και απογαλακτισθέντα κονικλίδια, στο βάροςτης τοκετοομάδας κατά τη γέννηση, στο μέσο ατομικό βάρος γέννησης των κονικλιδίων και τέλος στον αριθμό αναπνοών/λεπτό των κονικλομητέρων. Συμπερασματικά διαπιστώθηκε η αρνητική επίδραση των υψηλών θερμοκρασιών του περιβάλλοντος στις αναπαραγωγικές και φυσιολογικές παραμέτρους των κονικλομητέρων.The reproductive performance and physiological traits of intensively raised does were evaluated under farm conditions in Greece, during the hot (average farm temperature 19.5°C) and cold period (average farm temperature 12.4°C). The size of litter at birth (6.94 vs. 7.84 alive pups, P<0.001), the size of litter at weaning (5.95 vs. 7.06, P<0.001), the pre-weaning mortality rate (16.94% vs. 9.60%, P<0.001, the number of born dead (0.39 vs. 0.19, P<0.001) and the number of stillborn (0,05 vs 0,02 P<0.01) were significantly affected during the hot period, while litter weight and individual weight at birth did not seem to differ between hot and cold period (461 g vs. 466 g (P<0.05) and 68 vs. 65 g (P<0.05), respectively). Rectal temperature of does and respiration rate were higher in the hot period (39.09°C vs. 38.93°C (NS) and 128.08 respirations/min vs. 115.37 respirations/min; P<0.001). The effects of parity order and animals were also studied revealing that parity order influenced significantly total born, born alive, stillborn and weaned rabbits, litter weight and individual weight at birth, as well as the does' respiration rate. The interaction between parity and period was not significant for any of the recorded parameters. In conclusion, high ambient temperature impaired does' reproductive and physiological traits under those conditions, similar to most natural environmental conditions in Greece

Design, synthesis and antiparasitic evaluation of click phospholipids

A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure\u2013activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC50) against THP-1 macrophages ranged between 50 and 100 \ub5M. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases

Structure-activity relationships of antineoplastic ring-substituted ether phospholipid derivatives

Purpose: Previous studies have shown that alkylphosphocholines (APCs) exhibit strong antineoplastic activity against various tumour cell lines in vitro and in several animal models. The current study was designed to investigate the influence of cycloalkane rings on the antiproliferative activity of APCs against a panel of eight human and animal cell lines (PC3, MCF7, A431, Hela, PC12, U937, K562, CHO). Specifically, we explored the effect of the presence of 4-alkylidenecyclohexyl and cycloalkylidene groups in alkoxyethyl and alkoxyphosphodiester ether lipids, respectively. In addition, the haemolytic activity of the new ring-substituted ether phospholipids (EP) was evaluated. Methods: Cells were exposed to various concentrations of the compounds for 72 h. The cytotoxicity was determined with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide] dye reduction assay. Similarly, red blood cells were distributed in 96-well microplates and treated with the test compounds at concentrations ranging from 100 to 6.25 μM for 1 h. After centrifugation, the absorbance of the supernatants was measured at 550 nm. Results: The majority of the compounds tested exhibited significant cytotoxic activity which depended on both the ring size and position with respect to the phosphate moiety, as well as the head group. Among the cycloalkylidene series the 11- adamantylideneundecyl-substituted N-methylmorpholino EP 13 was the most potent and exhibited broad-spectrum anticancer activity comparable to or superior to that of hexadecylphosphocholine (HePC). All the adamantylidene-substituted EPs were nonhaemolytic (concentration that exhibits 50% haemolytic activity, HC 50, &amp;gt;100 μM). Furthermore, the cyclohexylidene-substituted analogues were more potent against the cell lines tested, with the exception of U937 and K562, than the cyclodecapentylidene-substituted compounds. Hydrogenation of the double bond in the cycloalkylidene-substituted EPs (compounds 14 and 15) resulted in improvement of anticancer activity. Among the 2-(4-alkylidenecyclohexyloxy)ethyl EPs, 2-(4-hexadylidenecyclohexyloxy)ethyl phosphocholine (22) possessed the highest broad-spectrum cytotoxic activity than all the other analogues of this series and was nonhaemolytic (HC50 &amp;gt;100 μM). In general, the 2-(4-alkylidenecyclohexyloxy)ethyl-substituted EPs were more active against the more resistant cell lines U937, K562 and CHO than HePC. Conclusions: The presence of cycloalkane rings in the lipid portion of APCs reduces haemolytic effects compared to HePC and in several analogues results in improved antineoplastic activity. © Springer-Verlag 2005

Homeobox B9 integrates bone morphogenic protein 4 with inflammation at atheroprone sites

Aims Atherosclerosis develops near branches and bends of arteries that are exposed to disturbed blood flow which exerts low wall shear stress (WSS). These mechanical conditions alter endothelial cells (EC) by priming them for inflammation and by inducing turnover. Homeobox (Hox) genes are developmental genes involved in the patterning of embryos along their anterior–posterior and proximal–distal axes. Here we identified Hox genes that are regulated by WSS and investigated their functions in adult arteries. Methods and results EC were isolated from inner (low WSS) and outer (high WSS) regions of the porcine aorta and the expression of Hox genes was analysed by quantitative real-time PCR. Several Hox genes (HoxA10, HoxB4, HoxB7, HoxB9, HoxD8, HoxD9) were significantly enriched at the low WSS compared to the high WSS region. Similarly, studies of cultured human umbilical vein EC (HUVEC) or porcine aortic EC revealed that the expression of multiple Hox genes (HoxA10, HoxB9, HoxD8, HoxD9) was enhanced under low (4 dyn/cm2) compared to high (13 dyn/cm2) WSS conditions. Gene silencing studies identified Hox genes (HoxB9, HoxD8, HoxD9) that are positive regulators of inflammatory molecule expression in EC exposed to low WSS, and others (HoxB9, HoxB7, HoxB4) that regulated EC turnover. We subsequently focused on HoxB9 because it was strongly up-regulated by low WSS and, uniquely, was a driver of both inflammation and proliferation. At a mechanistic level, we demonstrate using cultured EC and murine models that bone morphogenic protein 4 (BMP4) is an upstream regulator of HoxB9 which elicits inflammation via induction of numerous inflammatory mediators including TNF and downstream NF-κB activation. Moreover, the BMP4-HoxB9-TNF pathway was potentiated by hypercholesterolaemic conditions. Conclusions Low WSS induces multiple Hox genes that control the activation state and turnover of EC. Notably, low WSS activates a BMP4-HoxB9-TNF signalling pathway to initiate focal arterial inflammation, thereby demonstrating integration of the BMP and Hox systems in vascular pathophysiology

Increased influenza vaccination rates in patients with autoimmune rheumatic diseases during the Covid-19 pandemic: a cross-sectional study

To assess non-compliance and potential changes in seasonal flu vaccination coverage before and during the Covid-19 pandemic in patients with autoimmune rheumatic diseases (ARDs). Consecutive patients with ARDs followed-up in 2 tertiary hospitals were telephone-interviewed (December 12–30, 2020) regarding seasonal flu vaccination during the 2019/20 and 2020/21 time periods. Self-reported disease flares that occurred after flu vaccination, as well as reasons for non-vaccination were recorded.One thousand fifteen patients were included. The rate of flu vaccination increased from 76% before to 83% during the COVID-19 pandemic (p = 0.0001). The rate of self-reported disease flares was &lt; 1% among vaccinated patients. Reasons for not vaccination in both periods, respectively, included: ‘was not recommended by their rheumatologists’ (35.0vs.12.2%, p &lt; 0.0001), ‘did not feel that they would have any benefit’ (36.9 vs. 32.6%), felt unsafe to do so (27.5 vs. 30.2%), or other reasons (18.9 vs. 23.8%). By multivariate analysis, age [OR = 1.03 (95% CI 1.02–1.04)] vs. [1.04 (95% CI 1.02–1.05)] and treatment with biologics [OR = 1.66 (95% CI 1.22–2.24) vs. [1.68 (95% CI 1.19–2.38)] were independent factors associated with vaccination in both periods. These findings, although are temporally encouraging, emphasize the need for continuous campaigns aiming at increasing patients’ and physicians’ awareness about the benefits of vaccination. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature