Validation of a Portable Blood Gas Analyzer for Use in Challenging Field Conditions at High Altitude

BackgroundNovel, portable blood gas analyzers (BGAs) may serve as essential point-of-care tools in remote regions, during air travel or in ambulance services but they have not been extensively validated.Research QuestionWe compared accuracy of a portable BGA to a validated stationary device.MethodsIn healthy individuals and patients with chronic obstructive pulmonary disease participating in clinical field studies at different altitudes, arterial blood samples were obtained at rest and during exercise in a hospital at 760 m and in a high altitude clinic at 3100 m. Paired measurements by a portable BGA (EPOC, Siemens Healthcare) and a stationary BGA (Rapidpoint500, Siemens Healthcare) were performed to compute bias (mean difference) and limits of agreement (95% CI of bias).ResultsOf 105 individuals, 248 arterial blood samples were analyzed, 108 at 760 m, 140 at 3100 m. Ranges of values measured by portable BGA were: pH 7.241−7.473, PaCO2 21.5−52.5 mmHg, and PaO2 45.5−107.1 mmHg. Bias (95% CI) between devices were: pH 0.007 (−0.029 to 0.044), PaCO2 −0.3 mmHg (−4.8 to 4.2), and PaO2 −0.2 mmHg (−9.1 to 4.7). For pH, agreement between devices was improved by the equation to correct pH by portable BGA = −1.37 + pHmeasured × 1.19; bias after correction −0.007 (−0.023 to 0.009). The portable BGA was easily handled and worked reliably.InterpretationAccuracy of blood gas analysis by the portable BGA in comparison to the reference BGA was adequate for clinical use. Because of portability and ease of handling, portable BGA are valuable diagnostic tools for use in everyday practice as well as under challenging field conditions.

Assay Interference By Emicizumab in Aptt and Chromogenic Based FVIII:C and Inhibitor Assays

Background:Emicizumab, a humanized bispecific antibody, has been approved for the prophylactic treatment of hemophilia A in patients with and without inhibitors. Both activated partial thromboplastin time (APTT) based FVIII:C and inhibitor assays, as well as select chromogenic FVIII:C assays have been reported to be affected in the presence of emicizumab. Aims:To assess the effect of emicizumab spiked at 0, 25, 50, and 100 ug/mL into congenital FVIII deficient plasma, containing FVIII inhibitor at 0, 1 and 5 BU, in seven commonly used APTT and chromogenic based FVIII:C assays. Samples were also tested in an APTT and chromogenic based FVIII Nijmegen inhibitor assay. Methods:Four IVD approved, APTT based FVIII:C assays and three chromogenic FVIII:C assays were evaluated (Table 1). In addition, FVIII inhibitor levels were measured by Nijmegen Bethesda assay using either APTT (Actin®FSL, Siemens Healthcare) or chromogenic based (FVIII Chromogenic Assay, Siemens Healthcare) FVIII:C assays. Results:Reagent and dose-dependent increases in FVIII:C were observed for all APTT reagents tested as well as for the BIOPHEN FVIII:C chromogenic assay. The presence of low or high titer inhibitors did not impact APTT based FVIII:C measured. Neither of the two chromogenic FVIII:C assays, using bovine based FX and FIXa (i.e. FVIII Chromogenic Assay and Coatest®SP4) demonstrated measurable FVIII levels at any of the emicizumab concentrations tested. FVIII Nijmegen Bethesda inhibitor results using APTT based FVIII:C, when tested in the presence of emicizumab, consistently produced false negative results (Table 1) whereas results determined using the FVIII Chromogenic Assay measured inhibitor titers at expected concentrations. Conclusion:Confirming previously published results, emicizumab interferes in the APTT based FVIII:C and Nijmegen Bethesda inhibitor assays. Even at low emicizumab concentrations, false negative inhibitor titers are measured in APTT based inhibitor assays. Using a bovine based chromogenic FVIII:C assay is imperative when measuring both FVIII:C and FVIII inhibitors in samples containing emicizumab. Disclosures Tiefenbacher: Laboratory Corporation of America Holdings:Current Employment, Current equity holder in private company;Novo Nordisk:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Shire:Honoraria;Octapharma:Honoraria;Siemens Healthcare:Membership on an entity's Board of Directors or advisory committees;BioMarin:Membership on an entity's Board of Directors or advisory committees.

Infections of implantable cardiac devices by biofilm forming bacteria in western Algeria hospitals

Background: The significant increase in the use of implantable cardiac devices (ICDs) has been accompanied by biofilm formation and increase rate of infection on the devices. The purpose of our study is to describe the clinical and microbiological findings of infection of ICDs in the cardiology units of western Algeria hospitals. Methodology: All patients with clinical diagnosis of ICD infections or infective endocarditis upon removal of their ICDs from December 2012 to August 2014 in cardiology units of 4 Algerian hospitals were included in the study. Each element of the ICD pocket and lead was separately sonicated in sterile saline, inoculated onto Chapman and MacConkey agar plates and incubated aerobically at 37oC for colony count after 24 hours. Biochemical identification of the bacteria isolates was made by API 20E, API 20 NE and API Staph, and confirmed by Siemens Healthcare Diagnostics WalkAway® 96 Plus System. Antibiotic susceptibility testing on each isolate was performed by the disk diffusion method on Mueller Hinton agar. Biofilm formation was detected by Congo Red Agar (CRA) and Tissue Culture Plate (TCP) methods, and hydrophobicity of the bacterial cell was determined by the MATH protocol. Results: Over a period of twenty-one months, 17 ICDs were removed from patients with post-operative infections; 6 (35.3%) had early infection of ICD and 11 (64.7%) had late ICD infection. Fifty-four bacterial strains were isolated and identified, with coagulase-negative staphylococci being the predominant bacteria with 46.3% (25/54). There was no significant association between hydrophobicity and antimicrobial resistance in the 54 isolates but there is positive correlation between biofilm production and antimicrobial resistance, with the strongest biofilm producers resistant to more than one antibiotic. Four independent predictors of infection of resynchronization devices were reported; reoperation, multi-morbidity, long procedure, and ICD implantation. Conclusion: Our study is the first in Algeria to describe microbiological characteristics of ICD infection. The bacteria in the biofilm were protected, more resistant and tolerated high concentrations of antibiotics and thus played a major role in the development of ICD infections. Despite the improvements in ICD design and implantation techniques, ICD infection remains a serious challenge. Keywords: implantable cardiac devices, staphylococci, resistance, biofilm, hydrophobicity French title: Infections des dispositifs cardiaques implantables par des bactéries formant un biofilm dans les hôpitaux de l'ouest Algérien Contexte: L'augmentation significative de l'utilisation des dispositifs cardiaques implantables est un risque majeur d'augmentation du taux d'infection et donc du risque de formation d'un biofilm sur ce genre de dispositifs. L'objectif de notre étude est de décrire les résultats cliniques et microbiologiques de l'infection sur les dispositifs cardiaques implantables (DCI) dans les unités de cardiologie des hôpitaux de l'ouest Algérien. Méthodologie: Tous les patients cliniquement diagnostiqués avec une infection sur DCI, ou une endocardite infectieuse et ayant subit un retrait de leur dispositif cardiaque sont inclus dans cette étude et cela sur une période entre décembre 2012 et aout 2014 dans 4 unités de cardiologie. Chaque élément du DCI (boitier et sonde) est trempé séparément dans une solution saline stérile, ensemencé sur deux milieux de culture, un milieu de Chapman et un milieu MacConkey et incubé en aérobiose à 37°C pour la numération des colonies après 24 heures. L'identification biochimique des isolats de bactéries est effectuée par le API 20E, API 20 NE et API Staph, et confirmée par le système WalkAway® 96 Plus de Siemens Healthcare Diagnostics. Les tests de sensibilité aux antibiotiques de chaque isolat sont effectués par la méthode de diffusion des disques sur gélose de Mueller Hinton. La formation d'un biofilm est détectée par les méthodes de la gélose rouge du Congo (CRA) et de la plaque de culture tissulaire (TCP), et l'hydrophobicité de la cellule bactérienne est déterminée par le protocole MATH. Résultats: Sur une période de 21 mois, 17 DCI sont retirés de patients atteints d'infections postopératoires; 6 patients (35,3%) sont identifiés comme ayant une infection précoce sur leurs DCI et 11 patients (64,7%) ayant une infection tardive. Cinquante-quatre souches bactériennes sont isolées et identifiées, les staphylocoques à coagulase négative étant les bactéries prédominantes avec 46,3% (25/54). Il n'y a pas d'association significative entre l'hydrophobicité et la résistance aux antimicrobiens dans les 54 isolats, mais il existe une corrélation positive entre la production de biofilm et la résistance aux antimicrobiens, les plus puissants en biofilm sont résistant à plus d'un antibiotique. Quatre facteurs prédictifs indépendants d’infection des dispositifs cardiaques implantable sont retrouvés dans ce travail: ré-intervention, longue procédure, sujets multi-tarés, et implantation d’un DCI Conclusion: Notre étude est la première en Algérie à décrire les caractéristiques microbiologiques de l'infection des DCI. Les bactéries présentes dans le biofilm sont protégées, plus résistantes et tolèrent de fortes concentrations d'antibiotiques et jouent ainsi un rôle majeur dans le développement des infections par DCI. Malgré des améliorations dans les techniques de conception et d'implantation de DCI, l'infection des dispositifs cardiaques implantables reste un problème grave et très couteux. Mots-clés: dispositifs cardiaques implantables; staphylocoque; résistance; biofilm; hydrophobicité

Effect of Season on Hematologic, Biochemical, and Hormonal Analytes in Rams of Two Breeds

Clinicopathological investigations are essential for the evaluation of the health status of ruminants. Apart from species-specific reference intervals, the effect of common biological factors should be considered for an accurate interpretation of laboratory data. The aim of this study was to evaluate the effect of season on hematologic and biochemical analytes, and serum total thyroxine and cortisol in adult rams of two breeds. Four blood samples (one every season) were collected from each ram. Complete blood count was performed on the Advia 120 (Siemens Healthcare Diagnostics, USA), while the differential leukocyte count was manually conducted. Biochemical and hormonal analyses were performed on Flexor E (Vital Scientific, The Netherlands), AVL 9180 (Roche Diagnostics, Belgium), and Immulite 1000 (Siemens Healthcare Diagnostics, USA), respectively. Linear mixed effects models (R language) were employed for statistical analyses. Forty-three (26 Chios, 17 Florina), adult, clinically healthy rams were included. Statistically significant (p<0.05), mostly breed-independent seasonal differences were observed in almost all of the analytes. However, when assessing these differences in view of the respective reference intervals, only a few of them were considered biologically important. Specifically, mild hyperglycemia and mild decrease in the concentration of total calcium and inorganic phosphorus were detected in winter, while a mild increase in thyroxine concentration (autumn) and creatine kinase activity (spring and summer) was also noted. In conclusion, seasonal effects should be considered when evaluating laboratory results in rams; however, season does not appear to have an essential effect on the clinicopathological profile of rams reared in the Mediterranean region.

P2673Challenging time limits: Using a single high-sensitive troponin I to rule-out acute myocardial infarction in early presenters

Introduction According to ESC guidelines, an acute myocardial infarction (MI) can be excluded without serial troponin measurements in patients presenting with a single high-sensitive troponin below the 99th percentile and chest pain starting >6 hours prior to admission. However, it is unclear if single-testing of high-sensitive troponin can rule-out MI in early presenters. Purpose To investigate the diagnostic performance of a single value of high-sensitive cardiac troponin I (hs-cTnI) at presentation for ruling-out MI in patients presenting with chest pain to the Emergency Department irrespective of chest pain onset. Methods We conducted a substudy of preliminary data from the RACING-MI trial. We included patients presenting with chest pain suggestive of MI to the Emergency Department of a Regional Hospital. We used the Siemens hs-cTnI (Siemens Healthcare, TNIH, Limit of detection: 2.21 ng/L) and a diagnostic cut-off value <3 ng/L to rule-out MI at presentation. Two physicians independently adjudicated the final diagnosis based on all clinical information. Patients were stratified based on time from chest pain onset to hospital admission as very early (0–3 hours), early (3–6 hours) and late presenters (>6 hours). Results We included 989 patients with available hs-cTnI results at admission. MI was confirmed in 82 (8.3%) patients. Using hs-cTnI <3 ng/L as diagnostic cut-off value at presentation, 302 (30.5%) patients without MI were classified as rule-out. Overall, the negative predictive value (NPV) for MI was 100% (95% CI 98.7–100). Based on chest pain onset, 33.8% of patients were classified as very early, 12.8% as early, and 42.7% as late presenters, with 10.7% patients with unreported/unknown onset. NPV was 100% (95% CI 96.5–100) for very early, 100% (95% CI 88.3–100) for early and 100% (95% CI 97.3–100) for late presenters. Conclusions Using a single hs-cTnI value <3ng/L as diagnostic cut-off to rule-out MI seems to be safe and to allow rapid rule-out of MI in patients presenting with chest pain to the emergency department, even in very early presenters. ClinicalTrials.gov Identifier: NCT03634384. Acknowledgement/Funding Randers Regional Hospital, A.P Møller Foundation, Boserup Foundation, Korning Foundation, Højmosegård Grant, Siemens Healthcare (TNIH assays), etc.

Activity of a FIX-Padua Transgene Product in Commonly Used FIX:C One-Stage and Chromogenic Assay Systems Following PF-06838435 (SPK-9001) Gene Delivery

Background PF-06838435 (SPK-9001), a gene therapy candidate containing a high specific-activity factor IX variant (R338L, FIX-Padua), is currently in phase 3 of clinical development for the treatment of Hemophilia B. Initial data with this vector is promising with significant reductions in bleeding episodes and FIX consumption (George LA et al, NEJM 2017; 377:2215-2217). To date, little is known about the activity of the expressed transgene product as measured in FIX:C one-stage and chromogenic assay systems commonly used to monitor FIX replacement therapy in patients with Hemophilia B. Aim The goal of the study was to assess the activity of the PF-06838435 expressed transgene product in plasma samples collected from participants in the Phase 1/2 trial using four commonly used FIX:C aPTT reagents. For comparison, the activity of the expressed FIX-Padua gene product was also assessed in the ROX FACTOR IX chromogenic assay. In addition, the activity of the Padua variant in congenital FIX deficient plasma spiked with increasing concentrations of purified recombinant human FIX Padua protein (rHFIXp - Samelson-Jones Lab, CHOP/UPenn), as well as recombinant human FIX (rHFIX, BeneFIX®, Pfizer Inc.), was assessed in the same FIX:C assay procedures. Methods FIX:C, in four samples collected from two different patients who received FIX gene therapy, was tested in four in vitro diagnostic (IVD) approved FIX:C one-stage assay systems, STA®-PTT Automate and STA®-C.K. Prest® on the STA-R Evolution® (Diagnostica Stago Inc.), Dade Actin® FSL on the BCS®XP (Siemens Healthcare), and HemosIL® SynthASil® on the ACL TOP® (Instrumentation Laboratory). In addition, samples were also tested in the ROX FACTOR IX (Rossix AB) chromogenic assay on the BCS®XP (Siemens Healthcare). The aPTT reagents selected for this study correspond to 90% of the FIX:C assay reagents currently used in CAP accredited laboratories in the US(2014 CAP Proficiency Survey) and represent the three main types of activator commonly used in the FIX one-stage clot assay: silica (STA®-PTT Automate, HemosIL® SynthASil®), ellagic acid (Dade Actin® FSL) and kaolin (STA®-C.K. Prest®). For comparison, FIX:C in each of the five FIX:C assay systems was also determined in samples spiked with purified rHFIXp (provided by Dr. Samelson-Jones) or rHFIX (provided by Spark Therapeutics Inc.) in 20X buffer solutions. On the day of testing rHFIXp, and rHFIX 20X buffer solutions were diluted 1:20 in congenital FIX deficient plasma to achieve approximate final FIX:C concentrations of 40, 30 and 20%, extrapolated from an estimated 8-fold specific activity to antigen ratio. Results A consistent pattern in the measured FIX:C for the PF-06838435 transgene product was observed in the five FIX:C assay systems (Fig. 1). For the aPTT based FIX:C assays, Actin FSL, gave the lowest FIX:C values, whereas PTT Automate measured the highest FIX:C levels. In all cases, the chromogenic FIX:C assay gave the lowest activity values for the transgene product. A similar FIX:C assay dependent pattern was observed for the purified rHFIXp spiked at 40, 30 and 20% FIX:C (Fig. 2). In all FIX:C assays tested, rHFIXp was under-recovered to a varying degree from target, with recoveries for the 20% FIX:C samples ranging between -26.5% (STA®-PTT Automate) and -73.5% (Dade Actin® FSL) in the aPTT based FIX:C assays and -85% in the ROX FIX chromogenic assay. In contrast, rHFIX (BeneFIX®) was recovered within ±25% of expected values in all aPTT based FIX:C assays and, consistent with previously reported data, modestly under-recovered in the ROX FIX chromogenic assay (Fig. 3). Conclusion This study found differences in the FIX:C results obtained for a Padua FIX variant transgene product and recombinant human FIX-Padua when tested in commonly used IVD approved FIX:C assays in North America. These results suggest that FIX:C assay selection is important for measuring FIX-Padua activity, which will be particularly relevant in hemophilia B gene therapy following FIX-Padua gene transfer. Disclosures George: University of Pennsylvania: Equity Ownership; Pfizer: Consultancy. High:Spark Therapeutics: Employment, Equity Ownership, Patents & Royalties. Carr:Sparks Therapeutics Inc.: Consultancy. Tiefenbacher:Laboratory Corporation of America: Employment, Equity Ownership; Siemens Healthcare: Consultancy.

Unique percutaneous direct puncture technique for occlusion of a hypoglossal canal dural arteriovenous fistula

PurposeTo report percutaneous transcranial puncture, embolization and occlusion of a very symptomatic hypoglossal canal/anterior condylar vein dural arteriovenous fistula (DAVF) using syngo iGuide navigational software in a patient in whom transarterial and transvenous embolization and surgery had failed.MethodsAfter unsuccessful arterial and venous embolization and surgical treatment of a symptomatic hypoglossal canal DAVF, a 47-year-old man was transferred for further management. With exquisite anatomic detail provided by C-arm cone-beam computed tomography (CBCT) equipment (Artis zee Biplane, Dyna CT VC21H, Siemens Healthcare GmbH, Germany) and syngo iGuide needle guidance navigational software (Siemens Healthcare GmbHy) for planning a safe direct approach, the hypoglossal/anterior condylar vein, the dominant outflow vein of the fistula, was needle punctured percutaneously at the hypoglossal foramen and occluded with ethylene vinyl alcohol copolymer liquid embolic agent (Onyx, Medtronic, Minneapolis, Minnesota, USA) after placing two anchoring platinum coils (Target detachable coils, Stryker Neurovascular, Fremont, California, USA).ResultsAfter a year of progressively severe left eye proptosis, chemosis and increased intraocular pressure, the symptoms quickly subsided after this embolization and the patient was symptom free at his 3-month and later checkups.ConclusionWith guidance and imaging provided by CBCT and syngo iGuide navigational software, an otherwise untreatable DAVF was successfully embolized and obliterated by an aggressive unique percutaneous trans-cranial needle puncture of the dominant outflow vein in the hypoglossal canal.

Mελέτη της επίδρασης της μυκοτοξίνης ζεαραλενόνης στις αιματολογικές, βιοχημικές και ορμονικές παραμέτρους, την οξειδοαναγωγική κατάσταση του αίματος, καθώς και σε παραμέτρους εκτίμησης του σπέρματος αρσενικών κονίκλων

Η ΖΕN είναι μια μη στεροειδής, οιστρογόνος μυκοτοξίνη, η οποία έχει καταγεγραμμένη τοξική δράση στο αναπαραγωγικό σύστημα, καθώς και αιματοτοξική, ηπατοτοξική, νεφροτοξική, ανοσοτοξική και προοξειδωτική δράση. Σκοπός της παρούσας έρευνας ήταν η μελέτη της επίδρασης μιας χαμηλής δόσης ΖΕN (50μg/kg) χορηγούμενης μακροχρονίως στις αιματολογικές και βιοχημικές παραμέτρους, την οξειδοαναγωγική κατάσταση του αίματος, καθώς και το αναπαραγωγικό σύστημα αρσενικών κονίκλων. Δέκα αρσενικοί, κλινικά υγιείς ενήλικες κόνικλοι εντάχθηκαν στον πειραματικό πληθυσμό της μελέτης. Η παρασκευή του διαλύματος ΖΕΝ πραγματοποιήθηκε με τη διασπορά κονιορτοποιημένης μυκοτοξίνης σε διαλύτη διμεθυλο σουλφοξείδιο. Ο πειραματικός σχεδιασμός περιελάμβανε 7 εβδομάδες ελέγχου και 7 εβδομάδες χορήγησης τοξίνης. Κατά την περίοδο ελέγχου, οι κόνικλοι λάμβαναν καθημερινά per os 0,5 ml νερού, ενώ πραγματοποιούνταν λήψεις δειγμάτων αίματος και σπέρματος ανά εβδομάδα. Κατά την περίοδο χορήγησης, οι κόνικλοι λάμβαναν καθημερινά 0,5 ml διαλύματος τοξίνης, ενώ τα δείγματα αίματος και σπέρματος λαμβάνονταν κατά τον ίδιο τρόπο. Στα δείγματα ολικού αίματος πραγματοποιήθηκε γενική εξέταση (ADVIA 120, Siemens Healthcare Diagnostics, Η.Π.Α.) και κυτταρολογική εξέταση των επιχρισμάτων. Στα δείγματα ορών προσδιορίστηκε η συγκέντρωση των παρακάτω βιοχημικών παραμέτρων (Flexor E, Vital Scientific N.V., Ολλανδία· AVL 9180 Electrolyte Analyser, Roche Diagnostics, Βέλγιο): ολικές πρωτεΐνες, λευκωματίνη, σφαιρίνες, χολοστερόλη, τριγλυκερίδια, γλυκόζη, ολικό ασβέστιο, ανόργανος φωσφόρος, νάτριο, κάλιο, ουρία, κρεατινίνη, ALP, ALT, AST, γ-GT, και ολική χολερυθρίνη. Δείγματα ορών εξετάστηκαν για τη συγκέντρωση των δραστικών μεταβολιτών οξυγόνου (ROMs) (Diacron Labs S.r.l., Ιταλία) και τη συγκέντρωση βασικών επιπέδων τεστοστερόνης (Immulite 1000, Siemens Healthcare Diagnostics, Η.Π.Α.). Τα δείγματα σπέρματος εξετάστηκαν ως προς: i) τις κινητικές παραμέτρους των σπερματοζωαρίων με τη χρήση του Sperm Class Analyzer (Microptic S.L., Automatic Diagnostic Systems, Ισπανία), ii) τη ζωτικότητα των σπερματοζωαρίων με την εφαρμογή διπλής φθορίζουσας χρώσης καλσεΐνης-ιωδιούχου προπιδίου, iii) τη μορφολογία των σπερματοζωαρίων με τη χρήση της χρωστικής Spermblue® και iv) την ακεραιότητα της πυρηνικής χρωματίνης με τη χρήση της φθορίζουσας χρωστικής πορτοκαλόχρωμης ακριδίνης. Με το πέρας του πειραματισμού, ελήφθησαν δείγματα ήπατος, νεφρών, επινεφριδίων, όρχεων και επιδιδυμίδων, προκειμένου να εξεταστούν ιστολογικά. Η στατιστική επεξεργασία των αποτελεσμάτων πραγματοποιήθηκε με την εφαρμογή ενός μικτού γραμμικού μοντέλου επαναλαμβανόμενων μετρήσεων. Κατά την περίοδο έκθεσης στη ΖΕΝ παρατηρήθηκε στατιστικώς σημαντική αύξηση των τιμών των παραμέτρων RDW, MPV, WBC, AST, της ολικής χολερυθρίνης, καθώς και των απόλυτων αριθμών των μονοκυττάρων και των εωσινοφίλων, ενώ αντιθέτως, οι συγκεντρώσεις της ουρίας, της κρεατινίνης, της γλυκόζης, του ολικού ασβεστίου, του καλίου και του νατρίου μειώθηκαν σημαντικά. Κατά την περίοδο έκθεσης στη ΖΕΝ, η παράμετρος BCF αυξήθηκε σημαντικά, καθώς και το ποσοστό των σπερματοζωαρίων με μορφολογικές ανωμαλίες κεφαλής και μέσου τμήματος, και το ποσοστό των σπερματοζωαρίων με διαταραχές ακεραιότητας της πυρηνικής χρωματίνης. Η ιστοπαθολογική εξέταση κατέδειξε την παρουσία κυτταροπλασματικής κενοτοπίωσης στα ηπατικά κύτταρα και τα επιθηλιακά κύτταρα των εγγύς νεφρικών ουροφόρων σωληναρίων. Συμπερασματικά, υπό τις παρούσες πειραματικές συνθήκες, η χορήγηση ΖΕΝ σχετίστηκε με την παρουσία φλεγμονώδους απόκρισης ή/και αντίδρασης υπερευαισθησίας, ήπιας ηπατοκυτταρικής βλάβης και ηπατικής δυσλειτουργίας, πιθανής νεφρικής βλάβης και/ή διαταραχής στην εντερική απορρόφηση. Αντιθέτως, οι περισσότερες παρατηρούμενες σημαντικές μεταβολές στις ποιοτικές παραμέτρους του σπέρματος θεωρούνται περιορισμένης βιολογικής σημασίας, καθώς με τα μέχρι σήμερα βιβλιογραφικά δεδομένα δεν αναμένεται να επηρεάσουν τη γονιμότητα των κονίκλων.

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