L’iode est un composant essentiel aux hormones thyroïdiennes. Les cellules thyroïdiennes captent l’iode circulant et le concentrent vers le colloïde. Il est alors incorporé à la thyroglobuline, protéine précurseur des hormones, par un mécanisme d’organification. La capacité de captation de l’iode par la thyroïde est finement régulée notamment par la « Thyroid Stimulating Hormone » (TSH) mais aussi l’iode circulant. En effet, en cas d’une élévation de l’iode circulant, la thyroïde déclenche un mécanisme d’autorégulation appelée l’effet Wolff-Chaikoff. Ce phénomène se traduit par une limitation transitoire de production des hormones thyroïdiennes qui s’accompagne notamment d’une diminution de l’expression du NIS (Natrium Iodide Symporter), la protéine responsable du transport actif de l’iode dans la thyroïde. Dans cette étude, des approches omiques globales ont été mises à profit pour étudier cette régulation dans le contexte de l’administration d’un produit iodé et de souris invalidées pour un gène codant pour un transporteur de monocarboxylate exprimé dans la thyroïde. Dans la première partie, l’effet des agents de contraste iodés (ICA), couramment utilisés en imagerie médicale, a été étudié. L’administration de ces agents entraine une réduction de la captation de l’iode souvent expliquée par un effet Wolff-Chaikoff associé à un potentiel relargage d’iode. Par une approche de protéomique quantitative global, le protéome de thyroïde de souris, après administration d’ICA, a été comparé au protéome en conditions d’excès d’iode. Après un traitement des données et une analyse bioinformatique, nos résultats mettent en évidence l’existence de peu de mécanismes en commun induits par l’iode et les ICA mais cependant de plus importantes variations d’expression de protéines sont déclenchées uniquement par les ICA. Cette étude est en accord avec une durée plus importante de l’inhibition de la fonction après une administration d’ICA comparée à celle de l’iode stable. Dans la deuxième partie, le rôle de SLC5A8 dans la fonction thyroïdienne et les mécanismes sous-jacents à l’effet Wolff-Chaikoff ont été étudiés chez des souris invalidées pour le gène Slc5a8 (Solute carrier family 5 number 8) et des souris non mutées. SLC5A8 est une protéine membranaire identifiée au laboratoire et exprimée dans la membrane apicale du thyrocyte. Cette protéine catalyse un transport de monocarboxylate dans différents organes mais son rôle dans la thyroïde demeure non élucidé. L’invalidation n’entraine pas d’effet majeur sur la fonction thyroïdienne. En mettant à profit une approche multiomique comparative, combinant la transcriptomique, la protéomique et la métabolomique, les effets de cette invalidation et/ou de la régulation par l’iode de la thyroïde ont été explorés. Le traitement des data révèle de nombreuses voies activées dans les différentes conditions avec des mécanismes de compensation de l’effet de l’invalidation par l’administration d’iode. Les résultats indiquent que la perte de fonction de SLC5A8 affecte l’organification et/ou maturation de la thyroglobuline, le contrôle du stress oxydatif et de l’iode libre dans la thyroïde. / Iodine is an essential component of thyroid hormones. Thyroid cells capture the circulating iodine and concentrate it in the colloid. Then, it is incorporated into the thyroglobulin, the hormone precursor protein, by an organification mechanism. The iodine uptake capacity by the thyroid is finely regulated, not only by the Thyroid Stimulating Hormone (TSH) but also by circulating iodine. Indeed, in case of high circulating iodine, the thyroid actives a self-regulating mechanism called the Wolff-Chaikoff effect. This phenomenon results in a transient limitation of thyroid hormone production which is accompanied by a decrease in the expression of NIS (Natrium Iodide Symporter), the protein that is responsible for the active transport of iodine in the thyroid. In this study, global omics approaches were used to study this regulation in the context of the administration of an iodized product and mice invalidated for a gene coding a monocarboxylate transporter expressed in the thyroid. In the first part, the effect of iodinated contrast media (ICM), commonly used in medical imaging, has been studied. The administration of these agents leads to a reduction in the uptake of iodine often explained by a Wolff-Chaikoff effect associated with an iodine release potential. Through an overall quantitative proteomic approach, the mouse thyroid proteome, after administration of ICM, was compared to the proteome under conditions of excess iodine. In the second part, the role of SLC5A8 in thyroid function and the mechanisms underlying the Wolff-Chaikoff effect were studied in mice invalidated for the Slc5a8 gene (Solute carrier family 5 number 8) and wild type mice. SLC5A8 is a membrane protein identified in the laboratory and expressed in the thyrocyte apical membrane. This protein catalyzes the monocarboxylates transport in different organs but its role in the thyroid remains unsolved. Invalidation does not have a major effect on thyroid function. By using a comparative multiomic approach which combines transcriptomics, proteomics and metabolomics, the effects of this invalidation and / or regulation by iodine in the thyroid have been explored. Data processing reveals many pathways activated under different conditions with mechanisms to compensate for the effect of invalidation by the administration of iodine. The results indicate that the loss of SLC5A8 function affects the organization and / or maturation of thyroglobulin, the control of oxidative stress and of free iodine in the thyroid.

Background: Iosimenol 340 injection is a new, dimeric, iso-osmolar, iodinated contrast medium for X-ray angiography. Purpose: To compare the safety and efficacy of iosimenol injection to iodixanol injection in two randomized, controlled phase 2 trials. Material and Methods: One hundred and forty-four adult patients were enrolled in the two trials, one for evaluation during arteriography and the other for evaluation during computed tomography. Safety was compared by assessing adverse events, vital signs, ECGs, and laboratory parameters. Efficacy was assessed as X-ray attenuation in the computed tomography (CT) trial and as the quality of contrast enhancement in the arteriography trial. Results: There were no statistically significant differences in terms of safety or efficacy between the two contrast media. Both were well tolerated upon intravenous as well as intra-arterial injection. The most common adverse event was a feeling of warmth (observed in 35.1% of the patients with Iosimenol injection and 44.3% with iodixanol injection). Conclusion: Iosimenol upon intravenous as well as upon intra-arterial injection exhibits a safety profile and shows an efficacy similar to that of iodixanol.

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd3+)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd3+, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of introducing high CA doses in practice in order to afford sufficient contrast. Lanthanide (Ln3+) chelates based on 1,4,7,10–tetraazacyclododecane–1,4,7,10–tetraacetate (DOTA) have been shown to be particularly stable and effective. Chelates of DOTA exist in two interconverting coordination geometries which have varying water exchange rates. Researchers have envisioned a way to increase the per-dose efficacy both by control of the Gd3+–inner–sphere water exchange rate and via binding specificity (i.e. to tumors). The efficacy gains using these approaches have thus far been modest. A thorough structural characterization of europium (Eu3+) chelates of a DOTA-derivative which cannot undergo conformational exchange was carried out. These studies show that a single enantiomer of the ligand (S)–2–(4-nitrobenzyl)–1,4,7,10–tetraazacyclododecane–1,4,7,10–tetra(α–methyl)acetate (NB–DOTMA) can yield chelates which are both diastereoisomeric (previously reported) and regioisomeric (not previously speculated). Molecular mechanics simulations generated from the characterization data indicate that the nitrobenzyl (NB) substituent is oriented in different directions for the two possible regioisomers. The NB group can be chemically converted to confer macromolecular binding capability, and the orientation of the NB substituent may have a significant impact on the binding and/or relaxation behavior of a prototypical CA. The nuclear magnetic resonance (NMR) spectra of Eu–NB–DOTMA at various temperatures were compared. Unexpectedly, the chelates showed time-averaged structures which differ with a change in water exchange rate — the faster the rate, the greater the deviation from the expected structure. Consideration of the structures of Ln3+ chelates without accounting for their dynamic behavior does not yield an accurate value for the time-averaged hydration state. These observations suggest the "optimal" water exchange rate calculated using Solomon-Bloembergen-Morgan (SBM) theory may not lead to the highest-efficacy CAs. Binding and relaxometric studies of macromolecule-targeting derivatives of Gd–NB–DOTMA both by the author and in another lab showed that the coordination isomer with the slower water exchange rate should lead to more effective contrast, in direct opposition to the prevailing view of water exchange in the MRI community. Preliminary data do not indicate that regioisomeric chelates have significantly different relaxivity or macromolecular binding behavior. The ratios between regioisomeric Ln–NB–DOTMA chelates formed were shown to be dependent on the concentration and pH of the chelation reaction, but conditions were not found which led to the production of a single regioisomer. Attempts to carry out an efficient synthesis of a Ln3+ chelate with no potential for regioisomerism were unsuccessful.

Low concentrations (1-10mg/mL) of double antibiotic paste (DAP) have demonstrated antibacterial properties in regenerative endodontics. The aim of this study was to evaluate if DAP made radiopaque (RoDAP) with barium sulfate has antibacterial effects against bacterial isolates from a mature and immature tooth with necrotic pulp. Clinical bacterial isolates were obtained from the canals of mature and immature teeth with necrotic pulps during root canal therapy or a regenerative procedure, respectively. Bacterial isolates were grown anaerobically for three weeks on 4x4mm dentin specimens prepared from extracted human teeth (n=48 per biofilm type). The dentin specimens were allocated into six groups and treated as follows: 1mg/mL RoDAP, 10mg/mL RoDAP, calcium hydroxide (UltraCal), placebo (barium sulfate in methylcellulose), no treatment, and no bacteria or treatment (sterile control). After one week of treatment the biofilm was detached and biofilm disruption assays were conducted to determine the bacterial numbers (CFUs/mL). The data was analyzed using Wilcoxon Rank Sum tests followed by pairwise comparisons. 1 and 10 mg/mL RoDAP as well as calcium hydroxide demonstrated significant antibacterial effects against the tested bacterial isolates. The placebo paste did not demonstrate any significant antibacterial effects. No significant difference in antibacterial effects was found against isolates from both mature and immature teeth regardless of the type of treatment. Both 1 and 10 mg/mL RoDAP demonstrated significant antibacterial effects against bacterial isolates from mature and immature teeth with necrotic pulps. RoDAP can be beneficial clinically since its adequate placement within the canal system can be confirmed radiographically.

Background: Computed tomography (CT), is commonly used imaging technique in cancer patients. In CT performed for tumour staging to detect the spread of tumours, the liver is a common place for metastases. There are two types of metastases in the liver, hypo- and hyper vascularised, which generally are best seen in the venous phase and the late arterial phase. Therefore, CT of the liver often includes a triple phase contrast-enhancement protocol.   Purpose: The aim of this study was to qualitatively and quantitatively examine, through image review and attenuation measurements, respectively, the overall image quality of CT examinations performed in conjunction with positron emission tomography, (PET)/CT and as separate, stand-alone CT-studies, at the Department of Nuclear Medicine and PET centre, Uppsala University Hospital.   Method: A retrospective cross-sectional patient records review was undertaken with a descriptive approach of the qualitatively and quantitative data. 286 examinations were included in the study.     Result: The examinations were of high-quality in terms of contrast-enhancement technique, 183/190 (96,3%) of late arterial phases and 211/286 (74%) of venous phases. Some characteristic differences in the contrast-enhancement of the liver and the metastases were found in the different CT phases, allowing for division into four separate categories based on their respective characteristics.   Conclusion: In summary, the performed CT examinations were in majority performed in the right phase. The image quality of Contrast-to-noise, (CNR) and Signal-to-noise (SNR) were satisfactory even if the CNR could be higher for a better distinguish and detected small structures in the images. / Bakgrund: Datortomografi (DT), är den vanligaste avbildningstekniken för cancerpatienter. Vid DT för utredning av tumörspridning är levern en vanlig plats för metastaser. Det finns två typer av metastaser i levern, hypo- och hypervaskulära, som vanligen ses bäst i venfas respektive i sen artärfas. DT-undersökningarna av levern inkluderar därför ofta ett trippelfas-undersöknings-protokoll. Syfte: Syftet med denna studie var att kvalitativt och kvantitativt undersöka, genom bildgranskning respektive attenueringsmätningar, den totala bildkvaliteten för DT-undersökningar utförda i samband med positronemissionstomografi (PET) / DT och som separata, fristående CT-studier, vid Institutionen för nuklearmedicin och PET-center, Uppsala universitetssjukhus.   Metod: En retrospektiv tvärsnittsstudie med patientjournaler där en beskrivande metod användes för att beskriva den kvalitativt och kvantitativt datan. 286 DT-undersökningar granskades och inkluderades i studien. Resultat: Undersökningarna utfördes med DT i samband med PET/ DT, och även som separata DT undersökningar, var av hög kvalité vad gäller kontrastförstärkningsteknik varav 183/190 (96,3%) av sena artärfasundersökningarna och 211/286 (74%) av venfasundersökningarna erhöll maximal kvalitetspoäng. Vissa karakteristiska skillnader i kontrastförstärkningen av levern gentemot metastaserna hittades för de mycket och dåligt vaskulariserade metastaserna i de olika CT-faserna, vilket möjliggjorde uppdelning i fyra separata kategorier baserat på deras respektive egenskaper.   Slutsats: Sammanfattningsvis utfördes de utförda DT-undersökningarna i majoritet i rätt fas. Bildkvaliteten på Kontrast-till-brus, (CNR) och Signal-till-brus (SNR) var tillfredsställande även om CNR kunde vara högre för att bättre skilja och upptäcka små strukturer i bilderna.

No description available.

No description available.

Yes / Acute kidney injury (AKI) can occur rarely in patients exposed to iodinated contrast and result in contrast-induced AKI (CI-AKI). A key risk factor is the presence of pre-existing chronic kidney disease (CKD), therefore it is important to assess patient risk and obtain kidney function measurement prior to administration. Point of care (PoC) testing provides an alternative strategy but there remains uncertainty, with respect to diagnostic accuracy and clinical utility. A device study compared three PoC analysers (Nova StatSensor, Abbott i-STAT, Radiometer ABL800 FLEX) with a reference laboratory standard (Roche Cobas 8000 series, enzymatic creatinine). Three hundred adult patients attending a UK hospital phlebotomy department were recruited to have additional blood samples for analysis on the PoC devices. The ABL800 FLEX had the strongest concordance with laboratory measured serum creatinine (mean bias=-0.86, 95% limits of agreement = -9.6 to 7.9) followed by the i-STAT (average bias=3.88, 95% limits of agreement = -8.8 to 16.6) and StatSensor (average bias=3.56, 95% limits of agreement = -27.7 to 34.8). In risk classification, the ABL800 FLEX and i-STAT identified all patients with an eGFR≤30, whereas the StatSensor resulted in a small number of missed high-risk cases (n=4/13) and also operated outside of the established performance goals. The screening of patients at risk of CI-AKI may be feasible with PoC technology. However in this study it was identified that the analyser concordance with the laboratory reference varies. It is proposed that further research exploring PoC implementation in imaging department pathways is needed. / Yorkshire and Humber Academic Health Science Network (Grant Number: YHP0318)

Εισαγωγή: Τα ιωδιούχα σκιαγραφικά μέσα (ΣΜ) σήμερα χρησιμοποιούνται ευρέως τόσο για διαγνωστικούς λόγους όσο και κατά τη διάρκεια επεμβατικών πράξεων στην Επεμβατική Ακτινολογία ή/και την καρδιολογία. Δυστυχώς, η χρήση τους δεν στερείται επιπλοκών με την νεφροτοξικότητα (Νεφροτοξικότητα οφειλόμενη στα ΣΜ - ΝΣΜ) να είναι μία από τις πιο σοβαρές συνέπειες. Παρά το γεγονός ότι πολλές στρατηγικές με σκοπό τόσο την πρόληψη όσο και την θεραπεία έχουν προταθεί και δοκιμαστεί ευρέως τα τελευταία χρόνια στη μάχη κατά της ΝΣΜ, καμία δεν έχει καταφέρει να δείξει ισχυρά αξιόπιστα αποτελέσματα. Η Παρστατίνη είναι το αμινο τελικό 41-αμινοξέων πεπτίδιο που διασπάται και αποσπάται από τον υποδοχέα PAR1 όταν αυτός ενεργοποιείται από τη θρομβίνη. Οι χαμηλές δόσεις Παρστατίνης είναι γνωστό ότι εμφανίζουν προστατευτική δράση στο μυοκάρδιο αρουραίου μετά από βλάβη του τύπου της ισχαιμίας / επαναιμάτωσης. Η κύρια υπόθεση της μελέτης μας ήταν ότι η συγκεκριμένη ουσία μπορεί να ασκήσει προστατευτική δράση στους νεφρούς έναντι της ΝΣΜ. Για να ελεγχθεί αυτή η υπόθεση, χρησιμοποιήσαμε ένα πειραματικό μοντέλο ΝΣΜ σε θηλαστικά (Κόνικλους Νέας Ζηλανδίας). Υλικά και Μέθοδοι: Το πρώτο στάδιο της μελέτης αφορούσε στην ανάπτυξη ενός αξιόπιστου πειραματικού μοντέλου νεφροτοξικότητας μετά τη χορήγηση ιωδιούχων σκιαγραφικών μέσων. Το μοντέλο αναπτύχθηκε και αξιολογήθηκε εκτενώς σε μία σειρά από λευκούς κονίκλους Νέας Ζηλανδίας. Εν συνεχεία ακολούθησε η συστηματική δοκιμή της προστατευτικής δράσης της Παρστατίνης. Στο μέρος αυτό τα πειραματόζωα χωρίστηκαν σε τρεις υπό-ομάδες. Μια υπό-ομάδα έλαβε την υπό δοκιμή ουσία (Παρστατίνη) σε δόση 10μg/kg ακριβώς 15 λεπτά πριν από την έναρξη της ενδοφλέβιας έγχυσης του ΙΣΜ αντίθεσης. Σε αυτή τη φάση όλα τα πειραματόζωα της ομάδας ελέγχου προήλθαν από τα προκαταρκτικά πειράματα τα οποία είχαν λάβει ίσο όγκο φυσιολογικού ορού (NaCl 0,9%). Στις λοιπές δύο υπό-ομάδες χορηγήθηκε Παρστατίνη σε δόση είτε υποδεκαπλάσια (1μg/kg) είτε δεκαπλάσια (100μg/kg) της αρχικής. Ως κατώφλι για την αναγνώριση ανάπτυξης ΝΣΜ τέθηκε η τιμή της κρεατινίνης του ορού ίση ή άνω του 1,5mg/dl 48 ώρες μετά την έγχυση του ΣΜ. Ένα αντιπροσωπευτικό δείγμα πειραματόζωων υποβλήθηκε σε ευθανασία 48 ώρες μετά τη λήψη του ΣΜ με σκοπό την ιστολογική εξέταση/ανάλυση. Αποτελέσματα: Το πρώτο μέρος της μελέτης συμπεριέλαβε συνολικά 32 πειραματόζωα. Σε 7 εξ’ αυτών πραγματοποιήθηκε μόνο πείραμα προσομοίωσης (ομάδα sham) έτσι ώστε να οριστούν οι τιμές βάσης. Η μέση τιμή της κρεατινίνης ορού σε αυτή την ομάδα ήταν 0,90 mg/dl (Cl:0,80-1,10). Τα υπόλοιπα πειράματα έδειξαν ότι η μεγαλύτερη αναπαραγωγιμότητα του μοντέλου επιτυγχάνεται με ρυθμό έγχυσης του σκιαγραφικού μέσου αντίθεσης μεταξύ 2,5 έως 3,0 ml/min. Έτσι το σύνολο της σκιαγραφικής ουσίας χορηγείτο μεταξύ 28-35 λεπτών. Σε συνολικά 15 πειραματόζωα τα οποία αποτέλεσαν και την ομάδα ελέγχου και για τα λοιπά πειράματα (control group) η μέση τιμή της κρεατινίνης ορού ήταν 3,09 mg/dl (CI:2,40-4,00), ενώ το 86,7% αυτών ανέπτυξε κλινικά σημαντική ΝΣΜ. Όσον αφορά τα αποτελέσματα του δεύτερου μέρους αναγνωρίστηκε η θεραπευτική δράση της Παρστατίνης σε δόση ίση με 10μg/Kg. Ποίο συγκεκριμένα στην ομάδα πειραματόζωων (n=18) που έλαβε την ανωτέρο δόση η μέση τιμή της κρεατινίνης 48 ώρες μετά τη χορήγηση του ΙΣM ήταν 1,01mg/dl (CI:0,93-2,34) (Στατιστικά σημαντική διαφορά συγκριτικά με την ομάδα ελέγχου, p=0,012). Το αποτέλεσμα αυτό εξαλείφεται με τον δεκαπλασιασμό και με τον υπό-δεκαπλασιασμό της ανωτέρο δόσης. Στατιστικά σημαντικά μικρότερος ήταν και ο αριθμός των πειραματόζωων που ανέπτυξαν ΝΣΜ στην ομάδα της Παρστατίνης συγκριτικά με την ομάδα ελέγχου (27,8% έναντι 86,7%, p<0,001). Τα ιστολογικά αποτελέσματα έδειξαν σημαντικά μικρότερη σωληναριακή νέκρωση στην ομάδα των πειραματόζωων που έλαβαν θεραπεία με Παρστατίνη συγκριτικά με την ομάδα ελέγχου (13,13 Vs 26.60 στην ομάδα ελέγχου, ρ = 0.0007). Συμπέρασμα: Η υπό δοκιμή ουσία Παρστατίνη (Parstatin) αναστέλλει επιτυχώς την ανάπτυξη νεφροτοξικότητας μετά την χορήγηση σκιαγραφικών μέσων σε ένα πειραματικό in-vivo μοντέλο. Το παραπάνω αποτέλεσμα αποδείχτηκε τόσο με εργαστηριακές μετρήσεις της κρεατινίνης ορού όσο και μετά από ιστολογική μελέτη νεφρών. Το παραπάνω αποτελεί ένα πολύ αισιόδοξο μήνυμα. Παρόλα αυτά περαιτέρω μελέτες είναι αναγκαίες για την επικύρωση του προστατευτικού αυτού ρόλου. / Introduction: Iodinated Contrast Media (CM) are today widely used in routine non-invasive or percutaneous invasive imaging examinations and therapeutic interventions. Unfortunately, use of CM is not free of complications with nephrotoxicity (Contrast-Induced nephropathy – CIN) being one of the most severe. Although numerous preventing and/or therapeutic strategies have been proposed and widely tested during recent years in the battle against CIN, none of them manage to show strong reliable evidence that can prevent CIN development. Parstatin is the N-terminal-41-amino-acid peptide cleaved by thrombin from the protease-activated receptor-1. Low doses of Parstatin are known to have a protective effect in the rat myocardium after ischemia/reperfusion injury. The primary hypothesis of our study was that Parstatin may exert a nephroprotective role against the development of CIN. To test this hypothesis we used a mammalian experimental CIN model. Materials and Methods: The first stage of the study involved the development of a reliable experimental model of nephrotoxicity after administration of iodinated contrast media. The model was developed and extensively evaluated in a series of New Zealand white rabbits. The next stage involved the systematic testing of the protective effect of Parstatin. In this part the animals were divided into three sub-groups. A sub-group received the test substance (Parstatin) at a dose of 10mg/kg just 15 minutes before intravenous infusion of iodinated contrast medium. In the other two sub-groups Parstatin was administered at a dose of either subdivided by ten times (1mg/kg) or multiplied by ten times (100mg/kg) of the original. In this phase the control group was derived from the preliminary experiments of the first stage. As a threshold for the recognition of CIN development was the value of serum Creatinine equal to or more than 1,5 mg/dl 48 hours after injection of the CM. A representative sample of experimental animals was euthanized 48 hours after receiving the CM in order to perform histological examination and analysis. Results: The first part of the study included a total of 32 animals. In 7 of them only a simulation experiment was performed (group sham) to define baseline values of sCr. The mean serum Creatinine in this group was 0,90mg/dl (Cl:0,80-1,10). Following experiments showed that greater reproducibility of the model is achieved with injection rate of the contrast medium contrast between 2.5 έως 3,0 ml/min. Based on that the total contrast agent was administered between 28-35 minutes. In a total of 15 rabbits which were and the control group for the following experiments (control group) the mean sCr was 3,09 mg/dl (CI:2,40-4,00), while 86.7% of them developed clinically significant CIN. Regarding the results of the second part recognized that the maximum therapeutic effect of Parstatin is accomplished with a dose of 10mg/Kg. More specifically in the group of animals (Group P10, n=18) who received the abovementioned dose the mean sCr values 48 hours after administration of the CM was 1,01 mg/dl (CI:0,93-2,34) (Statistically significant difference compared with the control group, p=0,012). This therapeutic effect was eliminated when the dose was either multiplied or divided by 10. A significantly lower number of animals developed the CIN in the treatment group (Group P10) compared with the control group (27.8% vs. 86.7%, p<0.001). The histological results showed significantly less tubular necrosis in the group of animals treated with Parstatin compared to controls (13,13 Vs 26.60 in the control group, p = 0.0007). Conclusion: The test substance Parstatin successfully inhibits the development of contrast-induced nephrotoxicity in an in-vivo experimental model. The above result was verified both by laboratory measurements of serum Creatinine and after histological examination of kidney specimens. The above is a very optimistic message. Nevertheless, further studies are necessary to validate the protective role of Parstatin against contrast nephrotoxicity in both experimental and clinical settings.

INTRODUÇÃO: Durante procedimentos endovasculares, estão presentes os riscos relacionados ao uso dos contrastes iodados, tais como a nefropatia por contraste, uma vez que é fundamental o emprego de um meio de contraste para a obtenção das imagens radiológicas vasculares. A injeção intravascular de gás CO2 purificado é reconhecidamente uma alternativa relativamente mais segura ao contraste iodado, contudo, seu manuseio artesanal pode também trazer dificuldades técnicas e riscos aos pacientes. Para contemplar estas questões, foi desenvolvido o protótipo de um injetor intravascular de CO2 medicinal, microprocessado, dedicado à obtenção de imagens angiográficas. OBJETIVOS: Realizar os testes de viabilidade técnica inicial do protótipo em modelo in vivo. MÉTODOS: Realizar a angioplastia da artéria renal esquerda de 10 porcos, divididos em 2 grupos: Grupo 1 (n=5) injeção de contraste iodado, Grupo 2 (n=5) injeção de CO2 através do protótipo. Monitorização clínica e laboratorial dos animais no pré, intra e pós-operatório, com exames de função renal na véspera e 48h após os procedimentos e 3 gasometrias arteriais seriadas no intra-operatório. Observação clínica foi mantida por 48h no pós- operatório. RESULTADOS: Os procedimentos de angioplastia com CO2 foram realizados com sucesso técnico de 100%, sem necessidade de complementação com injeção de contraste iodado no Grupo 2. Não foram identificadas falhas no protótipo em funcionamento. Não foram identificadas alterações clínicas ou radiológicas sugestivas de contaminação por ar ambiente do sistema de CO2 e nem alterações laboratoriais nos animais. As imagens angiográficas obtidas no Grupo 2 foram consideradas, numa avaliação subjetiva, relativamente inferiores às imagens obtidas no Grupo 1. DISCUSSÃO: A qualidade inferior de imagem no Grupo 2 pode ser atribuída ao equipamento de fluoroscopia utilizado, com software desatualizado em relação aos equipamentos atuais, que incluem pré-configurações para angiografia com CO2; no entanto, ainda assim todos os procedimentos propostos no Grupo 2 foram realizados com sucesso técnico, o que nos leva a classificar as imagens deste grupo 2 como satisfatórias. O manuseio do aparelho mostrou-se ágil e eficiente, com a programação dos parâmetros sendo realizada com facilidade através do visor \"touch screen\", comparativamente superior ao método artesanal de injeção de CO2 com seringas em selo d\'água. CONCLUSÕES: O protótipo do aparelho injetor intravascular de CO2 funcionou de forma adequada durante os testes e as imagens obtidas permitiram a compleição com sucesso dos procedimentos. Portanto, os resultados positivos obtidos sugerem que o equipamento é tecnicamente viável / INTRODUCTION: During endovascular procedures, several risks related to iodinated contrast media are taken, such as Contrast Induced Nephropathy, since these are fundamental to obtain radiological vascular images under fluoroscopy. Intravascular medical grade CO2 injection is a widely accepted and relatively safer alternative to iodinated contrast, but its handling and manual delivery system could as well bring risks to patients, such as room air injection. To address these problems, we developed a prototype for a micro processed intravascular medicinal CO2 injector, dedicated to help obtain angiographic images. OBJECTIVES: To perform the in vivo Early Feasibility Clinical Studies of the prototype. METHODS: Perform a left renal artery angioplasty of 10 pigs, divided in 2 groups: Group 1 (n=5) injection of iodinated contrast and Group 2 (n=5) injection of CO2 with the prototype. Clinical and laboratorial data were measured pre, peri and post-operatively, by pre-operative and 48h post- operative creatinine tests and 3 peri-operative serial arterial blood gas analysis. Animais were kept under clinical observation for 48h after procedures. RESUL TS: Angioplasty procedures had 100% technical success in both groups, without the need of extra imaging with iodinated contrast in Group 2. There were no technical failures with the prototype. There were no identifiable clinical or radiological signs of room air intravascular injections. Ali laboratorial measurements were under normal value ranges. Angiography images obtained in Group 2 were subjectively considered inferior to images from Group 1. DISCUSSION: The inferior image quality in Group 2 could be attributed to the employed fluoroscopy equipment, since its software is not up to date to current equipment, which includes a dedicated CO2 angiography preset. Nevertheless, ali procedures in Group 2 were successful, and images in this group were therefore considered satisfactory. Handling of the prototype proved to be user friendly, since ali injection parameters are performed through a touch screen panel, much superior from previous authors experience with manual saline submerged syringe filling before intravascular injection. CONCLUSIONS: The intravascular CO2 injector prototype worked properly during the tests and the obtained images allowed successful procedures without unexpected complications, in consonance with previous positive in vitro results. Therefore, the study results suggest the positive early technical feasibility of the device