A despeito das evidências de que a redução do repouso no leito após cateterismo cardíaco diagnóstico sob abordagem transfemoral não aumenta as complicações decorrentes da punção arterial, esta prática ainda não está incoporada em muitos laboratórios de hemodinâmica (LH), principalmente em centros latino-americanos. Buscando preencher esta lacuna do conhecimento testou-se neste estudo se a redução do tempo de repouso no leito para três horas (GI), comparada a repouso de cinco horas (GC), não aumenta as complicações decorrentes da punção arterial após cateterismo cardíaco diagnóstico eletivo com introdutor 6 French e abordagem transfemoral. Foi conduzido um Ensaio clínico randomizado (ECR) no LH de um hospital público e universitário, região metropolitana, do Rio Grande do Sul no período de janeiro de 2011 a setembro de 2013. Foram incluídos pacientes adultos ambulatoriais. O GI deambulou três horas após a retirada do introdutor, e o GC após cinco horas. Todos pacientes permaneceram cinco horas na sala de observação onde foram observados a cada hora, pela equipe de enfermagem, e contatados por telefone em 24, 48 e 72 horas após a alta hospitalar. Foram avaliados os seguintes desfechos: hematoma, sangramento, hematoma retroperitoneal, pseudoaneurisma, formação de fístula arteriovenosa e reação vaso vagal Incluíram-se 730 pacientes: GI (n=367) e GC (n=363), média de idade de 62+11 anos. Durante a permanência dos pacientes na sala de observação do LH o hematoma foi a complicação mais observada em ambos os grupos, 12(3%) no GI e 13(4%) no GC (P=0,87); no GI 11(3%) pacientes apresentaram hematoma classificado como pequeno e 1(0,3%) apresentou hematoma classificado como grande; enquanto que no GC 11(3%) pacientes apresentaram hematoma classificado como pequeno e 2(0,6%) apresentaram hematoma classificado como grande; o sangramento ocorreu em 4(1%) dos pacientes no GI e 6(2%) no GC (P=0,51), tanto no GI como no GC a ocorrência de sangramento foi considerada menor. A reação vaso vagal ocorreu em 5(1,4%) pacientes no GI e 4(1,1%) pacientes no GC (P=0,75). Nos contatos em 24, 48 e 72 horas a equimose foi a complicação mais prevalente nos três períodos, para ambos os grupos, seguida pelo relato de dor no local da punção, para nenhuma das comparações foi observado significância estatistica. Apenas 1(0,3%) paciente do GC apresentou pseudoaneurisma no contato em 48 horas, necessitando retornar ao hospital para tratamento. Não foi observada nenhuma outra complicação durante todo o período do estudo. Os resultados deste estudo permitem concluir que a intervenção na redução do tempo de repouso para três horas após cateterismo cardíaco diagnóstico eletivo mostrou-se segura, sem aumento de complicações quando comparada aos pacientes que permaneceram em repouso de cinco horas. / Despite evidence that point out that reduction of rest in bed time after diagnostic cardiac catheterization using transfemoral approach does not contribute to complications of arterial puncture, such practice was still not incorporated into several hemodynamic laboratories (HL), especially in Latin American centers. In order to fill this knowledge gap, this study presents a test for the reduction of rest in bed time of three hours (IG) compared to rest in bed time of five hours (CG), aiming at verifying if the time does not increase complications of arterial puncture after diagnostic cardiac catheterization using 6 French introducer and the transfemoral approach. A randomized clinical trial (RCT) was conducted at a HL in a public university hospital located in the metropolitan area of Rio Grande do Sul/Brazil, between January 2011 and September 2013. Adult outpatients were included in this trial. The IG remained three hours after the withdrawal of the 6 French introducer and the CG remained five hours in the ambulatory. All patients remained five hours in the observation room, being checked every one hour by the nursing staff and being contacted by telephone at 24, 48 and 72 hours after the discharge. The outcomes hematoma, bleeding, retroperitoneal hemorrhage, pseudoaneurysm, arteriovenous fistula and vasovagal response were assessed. For the study, 730 patients were included and separated into GI (n=367) and GC (n=363), mean age of 62 ± 11. While patients remained in the observation room in the HL, the hematoma was the most common complication observed in both groups, 12(3%) in IG and 13(4%) in CG (P=0.87); in IG, 11(3%) patients presented small hematoma and 1(0.3%) presented large hematoma; in CG, 11(3%) patients presented small hematoma and 2(0.6%) presented large hematoma; bleeding occurred in 4(1%) patients in IG and 6(2%) in CG (P=0.51); both IG and CG presented minor bleeding occurrences. The vasovagal response occurred in 5(1.4%) patients in IG and 4(1.1%) patients in CG (P=0.75). During telephone contacts at 24, 48 and 72 hours, ecchymosis was the most prevalent complication for the three periods in both groups, followed by pain at the puncture site. Statistical significance was not observed in any of the comparisons. Only 1(0.3%) patient in the CG had pseudoaneurysm within 48 hours after discharge and had to return to the hospital for treatment. No other complications were observed during the study period. The results of this study demonstrate that reducing the time of rest in bed for three hours after diagnostic cardiac catheterization proved to be a safe procedure, with no increase in complications when compared to patients who remained resting in bed for five hours. / Con relación a las evidencias de que la reducción del reposo en el lecho tras cateterismo cardíaco diagnóstico bajo abordaje transfemoral no aumenta las complicaciones decurrentes de la punción arterial, esta práctica aún no está incorporada en muchos laboratorios de hemodinámica (LH), principalmente en centros latinoamericanos. En la tentativa de rellenar este hueco del conocimiento se hizo un test en este estudio para saber si la reducción del tiempo de reposo en el leco para tres horas (GI), comparada a cinco horas (GC), no aumenta las complicaciones decurrentes de la punción arterial tras cateterismo cardíaco diagnóstico con introductor 6 French y vía transfemoral. Fue dirigido un Ensayo clínico randomizado (ECR) en LH de un hospital público y universitario, región metropolitana, de Río Grande del Sur en el periodo de enero de 2011 a septiembre de 2013. Fueron incluidos pacientes adultos ambulatoriales. GI deambuló tres horas luego de la retirada del introductor, y GC tras cinco horas. Todos los pacientes permanecieron cinco horas en la sala de observación donde fueron observados a cada hora, por el equipo de enfermería, y contactados por teléfono en 24, 48 y 72 horas tras el alta hospitalario. Fueron evaluados los siguientes resultados: hematoma, hemorragia, hematoma retroperitoneal, pseudoaneurisma, formación de fístula arteriovenosa, reacción vaso y vagal. Se incluyeron 730 pacientes en la sala de observación de LH, el hematoma fue la complicación más observada en ambos grupos, 12 (3%) GI y 13 (4%) GC (P=0,87); en GI 11(3%) pacientes presentaron hematoma clasificado como pequeño y 1(0,3%) presentó hematoma clasificado como grande; mientras que en GC 11(3%) pacientes presentaron hematoma clasificado como pequeño y 2 (0,6%) presentaron hematoma clasificado como grande; la hemorragia ocurrió en 4 (1%) de los pacientes en GI y 6 (2%) en GC (P=0,51), tanto en GI como en GC la ocurrencia de hemorragia fue considerada menor. La reacción vaso vagal ocurrió en 5 (1,4%) pacientes en GI y 4 (1,1%) pacientes en GC (P=0,75). En los contactos en 24, 48 y 72 horas la equimosis fue la complicación que más prevaleció en los tres periodos, para ambos grupos, seguida por el relato de dolor en el local de la punción, para ninguna de las comparaciones fue observada significancia estadística. 1 (0,3%) paciente de GC presentó pseudoaneurisma en el contacto en 48 horas, necesitando volver al hospital para tratamiento. No se observó ninguna otra complicación durante todo el periodo del estudio. Los resultados de este estudio permiten concluir que la intervención en la reducción del tiempo de reposo para tres horas luego de cateterismo cardíaco diagnóstico electivo es posible y segura, sin aumento de complicaciones cuando comparada a los pacientes que permanecieron en reposo de cinco horas.

Hemorragia subaracnoidea aneurismática (HSAa) é considerada causa importante de morte e de sequelas neurológicas. A taxa de mortalidade desta doença pode alcançar 50% nos primeiros dois meses após sangramento de aneurisma encefálico. Apesar dos avanços científicos da modernidade, o resultado do tratamento da HSAa não mudou nos últimos anos. O presente estudo avaliou o papel de 14 biomarcadores genéticos, incluindo o polimorfismo (SNP) do gene eNOS, em pacientes da Amazônia com HSAa, para verificar as alterações alélicas associadas ao risco de vasoespasmo encefálico e déficit neurológico tardio. Avaliou-se a ancestralidade desta amostra de pacientes em que se utilizou 48 marcadores para identificar possível etnia associada à predisposição ao VE. Investigou-se 14 biomarcadores genéticos no tocante à resposta inflamatória encefálica na HSAa. Foram avaliados 265 doentes que foram divididos em dois grupos: grupo I (pacientes com vasoespasmo encefálico) e grupo 2 (pacientes sem vasoespasmo). A média das idades foi 51 anos, havia 224 mulheres (84%) e 124 pacientes (46,79%) apresentaram vasoespasmo encefálico (VE). A maior incidência de VE ocorreu na idade entre 50 e 59 anos. Tabagismo e hipertensão arterial sistêmica foram os fatores de risco mais associados à VE. Aneurismas encefálicos de tamanho pequeno e médio predominaram nesta casuística. As escalas amarela e vermelha do VASOGRADE associaram-se ao risco de VE (p < 0,001). Não houve variação na distribuição ancestral entre os grupos estudados e o que ocorre na população brasileira saudável na região Amazônica. O gene da eNOS com seus respectivos polimorfismos T-786C e 27VNTR4 correlacionaram-se com VE. Outros marcadores observados foram TP53, CASP8, ACE2, IL4 e XRCC1. O gene TP53 (modelo recessivo alelo 1) mostrou-se ser um fator protetor de VE, enquanto que genes com mutações INDEL CASP8 (modelo recessivo alelo 2) e o XRCC1 (modelo recessivo alelo 1) mostraram tendência ao desenvolvimento de VE com risco 2 vezes maior e 1,4 vezes maior que o grupo II (p < 0,001). Conclui-se que SNPs da eNOS se correlacionam com desenvolvimento de VE sintomático pós-HSAa. Este estudo também mostrou o papel dos marcadores inflamatórios na HSAa, o que auxiliaria na condução da terapia clínica. / Aneurysmal subarachnoid hemorrhage (aSAH) is a leading cause of premature death and neurological disability. It is considered as a devastating condition that accounts to 50% of mortality during the first two months after a hemorrhagic event. Despite foremost advances in the clinical management of post-aSAH patients, the rates of mortality and morbidity have not changed in recent years. This study appraised the role of 14 genetic biomarkers, including the eNOS polymorphism (SNP) between Amazon\'s patients with aSAH, as means to document how variant alleles are related to a higher disposition to cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). 265 patients were evaluated and then divided into two clusters: Group I (with symptomatic CV) and group II (presenting no symptomatic CV). The median ages of patients were 51.61 years of age, 224 (84.52%) were women and 124 patients (46.97%) had symptoms of cerebral vasospasm (CV). Tobacco smoking and systemic arterial hypertension are the risk factors most associated to CV. In the course of this research, most aneurysms found were small and medium-sized. The score VASOGRADE yellow and VASOGRADE red presented a high risk of CV (p < 0.001). We established a panel of 48 ancestry informative markers for estimating which ethnicity could present a predisposition to CV. There was no variation in the ancestral distribution between study groups and healthy brazilian folk over the Amazon region. The eNOS gene with its polymorphisms T-786C and 27 VNTR4 were correlated to CV. Other markers were accomplished: TP53, CASP8, ACE2, IL4, and XRCC1. The TP53 gene (recessive genetic model allele 1) supporting evidence of the protective role to CV. Whilst other genes with INDEL mutation like as CASP8 (recessive model allele 2) and the XRCC1 (recessive model allele 1) indicated a propensity to spread out CV with odds 2-fold higher, and 1.414 times greater than group II (p < 0.001). It follows that eNOS SNPs correlate to a positive association with a syntomatic CV post-aSAH. Also, this study showed up the role of inflammatory markers at aSAH to a further educated therapeutic choice for a better clinical response

Η CT αγγειογραφία εγκεφάλου (CTA) είναι μέθοδος καθιερωμένη για την διερεύνηση και την θεραπεία των ενδοκρανιακών ανευρυσμάτων. Σκοπός της μελέτης μας ήταν η σύγκριση των ευρημάτων της ψηφιακής αγγειογραφίας (DSA) με αυτά της CTA και με τα χειρουργικά ευρήματα σε ασθενείς με οξεία υπαραχνοειδή αιμορραγία, καθώς επίσης και η αξιολόγηση της κλινικής χρησιμότητας της μεθόδου. Κατά την διάρκεια τριών ετών, 82 ασθενείς προσήλθαν με κλινική εικόνα και σημειολογία συμβατή με υπαραχνοειδή αιμορραγία. Η CTA έγινε αμέσως μετά την απλή CT, ενώ η DSA εντός των πρώτων 48 ωρών από την εισαγωγή. Όλα τα ανευρύσματα που ευρέθησαν με τις δύο μεθόδους υπεβλήθησαν σε χειρουργική αποκατάσταση ή ενδαγγειακό εμβολισμό. Σε όσους ασθενείς βρέθηκε αρνητικό αποτέλεσμα και με τις δύο μεθόδους, έγινε επαναληπτική DSA 15 ημέρες μετά το επεισόδιο με σκοπό την επιβεβαίωση της απουσίας ανευρύσματος. Οι CTA εξετάσεις καθώς και οι κλασσικές αγγειογραφίες μελετήθηκαν από μια ομάδα δύο ακτινολόγων για κάθε τεχνική, οι οποίοι έπρεπε να καταγράψουν την ύπαρξη ή μη ανευρύσματος, να περιγράψουν τα χαρακτηριστικά του και να αξιολογήσουν την μέθοδο. Χειρουργική ή και ενδαγγειακή θεραπεία έγινε σε 45 ασθενείς και ανευρέθησαν 53 ανευρύσματα. Χρησιμοποιώντας την CTA, ευρέθησαν 47 ανευρύσματα σε 42 ασθενείς. Η DSA ανίχνευσε 43 ανευρύσματα σε 39 ασθενείς. Η ευαισθησία της CTA για τον εντοπισμό όλων των ανευρυσμάτων με βάση το χειρουργικό/θεραπευτικό αποτέλεσμα ήταν 88,7%, η ειδικότητα 100%, η θετική προβλεπτική αξία (PPV) 100%, η αρνητική προβλεπτική αξία (NPV) 80,7% και η ακρίβεια 92,3%. Αντίστοιχα, η ευαισθησία της DSA ήταν 87,8%, η ειδικότητα 98%, η PPV 97,7%, η NPV 89,1% και η ακρίβεια 92,9%. Όσον αφορά στα ανευρύσματα ≥3 mm, η CTA είχε ευαισθησία που κυμαινόταν μεταξύ 93,3 έως 100%, ίση με αυτή της DSA. Η CTA εμφάνισε τα ίδια ποσοστά ευαισθησίας με αυτά της DSA σε ανευρύσματα ≥3 mm. Εμφάνισε επίσης 100% ποσοστό ανίχνευσης σε ανευρύσματα της πρόσθιας αναστομωτικής και του διχασμού της μέσης εγκεφαλικής αρτηρίας, ενώ μερικές εντοπίσεις όπως η οπίσθια αναστομωτική αρτηρία παραμένουν προβληματικές. 80 Κατά την διάρκεια της παρούσας μελέτης προσπαθήσαμε να δημιουργήσουμε μια τεχνική προσομοίωσης της διεγχειρητικής εικόνας των ραγέντων ενδοκρανιακών ανευρυσμάτων, με τη χρήση volume rendering techniques σε εικόνες που προκύπτουν από CT αγγειογραφία. Η τρισδιάστατη κατασκευή των εικόνων προέκυψε από την συνεργασία μιας ομάδας αποτελούμενης από τέσσερις ακτινολόγους, έναν νευροχειρουργό και έναν ιατρικό φυσικό. Το αποτέλεσμα αυτής της συνεργασίας ήταν η παραγωγή μιας εικόνας οριοθετημένης στο χώρο, με οδηγά σημεία που εύκολα μπορούσαν να αναπαραχθούν κατά την διάρκεια του χειρουργείου. Οι εικόνες χειρουργικής προσομοίωσης ενός ανευρύσματος είναι πιθανώς χρήσιμο εργαλείο για τον προεγχειρητικό σχεδιασμό των ενδοκρανιακών ανευρυσμάτων. / Cerebral CT angiography is an established method applied to both the detection and treatment planning of intracranial aneurysms. The aim of our study was to compare DSA to CTA findings and with the surgical results mainly in patients with acute SAH and to evaluate the clinical usefulness of CTA. During the last three years, 82 consecutive patients were admitted under clinical symptoms and signs suggestive of harbouring an intracranial aneurysm. CT angiography performed immediately afterwards the plain CT, while DSA was performed within the first 48 hours of admission. All aneurysms detected, were confirmed during surgery or endovascular embolization. Repeat DSA was performed in all patients having both the initial CTA and the DSA 15 days after the onset of symptoms negative. CT angiograms and conventional angiographies were studied by a consensus of two radiologists for each technique, who performed aneurysm detection, morphological features characterization and evaluation of the technique. Surgical or/and endovascular treatment was performed in 45 patients and 53 aneurysms were confirmed. Using 3D-CT angiography we detected 47 aneurysms in 42 patients. Conventional angiography depicted 43 aneurysms in 39 patients. The sensitivity of CTA for the detection of all aneurysms versus surgery was 88.7%, the specificity 100%, the positive predictive value (PPV) 100%, the negative predictive value (NPV) 80.7% and the accuracy 92.3%. Consequently, the sensitivity of DSA was 87.8%, the specificity 98%, the PPV 97.7%, the NPV 89.1% and the accuracy 92.9%. Considering the aneurysms ≥ 3 mm, CTA showed a sensitivity ranging from 93.3% to 100%, equal to that of DSA. Cerebral CT angiography has an equal sensitivity to DSA in the detection of intracranial aneurysms greater than 3 mm. It has also 100% detection rate in AcoA and MCA bifurcation aneurysms, while some locations like posterior communicating artery aneurysms remain problematic. The delineating features of each aneurysm are better depicted with CTA due to 3D visualization. The use of Digital Subtraction Angiography as a diagnostic tool can be limited in equivocal cases. A supplement to the above work is our effort to describe a technique for simulating the surgical view of ruptured intracranial aneurysms, using volume 82 rendering techniques in spiral CT angiography data. The 3D rendered images were assessed by a team consisted of four radiologists, one neurosurgeon and one medical physicist. The resultant ‘surgical view’ image was standardized in space using a three-dimensional coordinate system, which allowed for its reproduction in the operating theatre. The surgical views are easily reproducible and αποτελούν a useful tool for the surgical planning of intracranial aneurysms.

No description available.

No description available.

Outcome after traumatic brain injury (TBI) depends on the extent of primary cell death and on the development of secondary brain injury. The general aim of this thesis was to find strategies and quality systems to minimize the extent of secondary insults in neurointensive care (NIC). An established standardized management protocol system, multimodality monitoring and computerized data collection, and analysis systems were used. The Uppsala TBI register was established for regular monitoring of NIC quality indexes. For 2008-2010 the proportion of patients improving during NIC was 60-80%, whereas 10% deteriorated. The percentage of ‘talk and die’ cases was &lt; 1%. The occurrences of secondary insults were less than 5% of good monitoring time (GMT) for intracranial pressure (ICP) &gt; 25 mmHg, cerebral perfusion pressure (CPP) &lt; 50 mmHg and systolic blood pressure &lt; 100 mmHg. Favorable outcome was achieved by 64% of adults. Nurse checklists of secondary insult occurrence were introduced. Evaluation of the use of nursing checklists showed that the nurses documented their assessments in 84-85% of the shifts and duration of monitoring time at insult level was significantly longer when secondary insults were reported regarding ICP, CPP and temperature. The use of nurse checklist was found to be feasible and accurate.  A clinical tool to avoid secondary insults related to nursing interventions was developed. Secondary brain insults occurred in about 10% of nursing interventions. There were substantial variations between patients. The risk ratios of developing an ICP insult were 4.7 when baseline ICP ≥ 15 mmHg, 2.9 when ICP amplitude ≥ 6 mmHg and 1.7 when pressure autoregulation ≥ 0.3. Hyperthermia, which is a known frequent secondary insult, was studied. Hyperthermia was most common on Day 7 after admission and 90% of the TBI patients had hyperthermia during the first 10 days at the NIC unit. The effects of hyperthermia on intracranial dynamics (ICP, brain energy metabolism and BtipO2) were small but individual differences were observed. Hyperthermia increased ICP slightly more when temperature increased in the groups with low compliance and impaired pressure autoregulation. Ischemic pattern was never observed in the microdialysis samples. The treatment of hyperthermia may be individualized and guided by multimodality monitoring.

Adrenal gland insufficiency – the clinical manifestation of deficient production or action of adrenal steroids – is a life-threatening disorder. Among many factors which can predispose to primary adrenal failure, an autoimmune adrenalitis and infectious agents play a major role. The initial host defense against bacterial infections is executed primarily by the pattern recognition receptors, e.g. Toll-like receptors (TLRs), expressed in cells from the innate immune system. Upon activation, TLRs have been found to regulate various levels of innate and adaptive immunity as well as control tissue inflammation. TLRs are implicated in adrenal cell turnover and steroidogenesis during inflammation. Therefore, TLRs play a crucial role in the activation of adrenal inflammation mediating adrenal gland dysfunction during septicemia. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Το σύνδρομο αναπνευστικής δυσχέρειας (ΣΑΔ) είναι ένα από τα συνηθέστερα προβλήματα και η κύρια αιτία θανάτου σε πρόωρα νεογνά. Παρά τη μείωση της νοσηρότητας και θνητότητας μετά την εισαγωγή της χρήσης εξωγενούς επιφανειοδραστικού παράγοντα στη θεραπεία του ΣΑΔ, υπάρχουν περιπτώσεις νεογνών που όχι μόνο δεν παρατηρείται βελτίωση, αλλά εμφανίζεται αυξημένος κίνδυνος εμφάνισης πνευμονικής αιμορραγίας. Η φλεγμονή, όχι μόνο τοπική αλλά και συστηματική, παίζει σημαντικό ρόλο στην παθογένεια του ΣΑΔ. Για να καθορίσουμε το ανοσολογικό προφίλ και την κατεύθυνση της πόλωσης της ανοσολογικής απόκρισης, μετρήσαμε με Cytometric Bead Array τις κυτταροκίνες type 1 (IL-2, TNF-α, IFN-γ) και type 2 (IL-4, IL-5, IL-10) 47 πρόωρων νεογνών με ΣΑΔ, και μιας ομάδας ελέγχου 30 υγειών, κατάλληλων για την ηλικία κύησης, τελειόμηνων νεογνών. Τα επίπεδα IL-6 και TGF-β1 ορού μετρήθηκαν με ELISA. Τα δείγματα αίματος συλλέχθηκαν κατά τη γέννηση (αίμα ομφάλιου λώρου) τόσο από τα πρόωρα νεογνά όσο κι από την ομάδα ελέγχου, και από νεογνά που έλαβαν επιφανειδραστικό παράγοντα και από εκείνα που εμφάνισαν πνευμονική αιμορραγία. Αξιοσημείωτη αύξηση στα επίπεδα όλων των κυτταροκινών παρατηρήθηκε τη στιγμή της γέννησης (p <0.05, εκτός των IL-5 και TNF-α). Η type 1 αυτή ‘’πόλωση’’ του ανοσοποιητικού συστήματος δεν επηρεάστηκε από την ηλικία κύησης, και παρέμεινε η ίδια ακόμη και μετά τη χορήγηση επιφανειοδραστικού παράγοντα (ανεξαρτήτως προέλευσης). Ωστόσο, τα νεογνά που εμφάνισαν πνευμονική αιμορραγία και είχαν χειρότερη πρόγνωση, εμφάνισαν διαφορετικό ανοσολογικό προφίλ στο οποίο κυριαρχούν οι προφλεγμονώδεις κυτταροκίνες. Η type 1 ‘’πόλωση’’ διατηρήθηκε, αλλά εμφανίζεται πιο έντονη. Τα επίπεδα των IL-10 και TGF-β1 στον ορό αυτών των νεογνών είναι μειωμένα. Ο ρόλος της φλεγμονής στην εξέλιξη του ΣΑΔ είναι φανερός. Τα πρόωρα νεογνά με ΣΑΔ εμφανίζουν μια έντονη type 1 ‘’πόλωση’’ του ανοσοποιητικού συστήματος, η οποία παραμένει ανεξαρτήτως της θεραπευτικής αγωγής που χορηγείται και ενισχύεται όταν οι πιθανές επιπλοκές εμφανιστούν. / Respiratory distress syndrome (RDS) is one of the most common problems and the leading cause of death in premature infants. Although the introduction of surfactant treatment for RDS management was beneficial lowering mortality and morbidity, some neonates do not improve, while others are at increased risk for pulmonary hemorrhage. Inflammation, not only local but also systemic, plays an important role in the pathogenesis of RDS. In order to determine the immunological profile and direction of polarization of immune response, we used Cytometric Bead Array to measure type 1 (IL-2, TNF-α, IFN-γ) and type 2 (IL-4, IL-5, IL-10) cytokines of forty-seven premature infants with established RDS, and a control group of 30 healthy, appropriate for gestational age, full-term neonates. Serum IL-6 and TGF-β1 levels were measured by ELISA. Blood samples were obtained at time of delivery (cord blood) for both premature and control group, and from neonates who received surfactant treatment and those who developed pulmonary hemorrhage. A remarkable increase to all cytokine levels was noted at time of delivery (p <0.05, except for IL-5 and TNF-α). This type 1-polarized immunological pattern was not affected by gestational age, and remained the same even after surfactant administration (irrespective of extract’s origin). However, neonates who developed pulmonary hemorrhage and had worse final outcome, presented different cytokine profile in which pro-inflammatory cytokines prevail. Type 1 polarization was maintained, though more intense; serum IL-10 and TGF-β1 levels appeared suppressed in these newborns. Overall, the role of inflammation in the progress of neonatal RDS is evident. Premature infants with established disease present a strong type 1 polarization, which persists irrespective of treatment provided, and is amplified when possible complications appear.

L'athérosclérose est une maladie cardiovasculaire complexe affectant la paroi artérielle où le développement et la progression de la plaque sont fortement favorisés par une inflammation chronique. L'instabilité de la plaque carotidienne peut conduire à de potentiels évènements ischémiques majeurs tels que l'accident vasculaire cérébral (AVC) dont le caractère imprévisible rend la prévention primaire très compliquée. Ainsi, il n'existe pas à l'heure actuelle de biomarqueurs prédictifs efficaces de la rupture de plaque. Néanmoins, il est maintenant clairement établi que l'hémorragie intraplaque (IPH), la néovascularisation et l'accumulation excessive de macrophages sont les principaux facteurs d'instabilité de la plaque. Sur la base de travaux précédents, l'objectif de cette thèse était d'évaluer de manière indépendante les effets de l'activité physique (AP) et de la sédentarité, premièrement sur les paramètres histologiques d'instabilité de plaque, et deuxièmement, sur les facteurs de risque secondaires de l'athérosclérose, que sont l'inflammation, le stress oxydant et le profil hémorhéologique de patients asymptomatiques à risque d'AVC traités chirurgicalement. La 1ère étude a montré que l'AP régulière était associée à une prévalence d'IPH diminuée, et était l'unique facteur protecteur de l'IPH. Cette étude a également suggéré un effet bénéfique de l'AP sur le stress oxydant, ainsi que sur l'accumulation de macrophages. Dans une 2ème étude, nous avons caractérisé l'état fonctionnel de protéines potentiellement impliquées dans les dysfonctions du système immunitaire, et l'implication des cellules inflammatoires dans ces mécanismes. Nous avons alors identifié une cytokine pro-inflammatoire jouant un rôle déterminant dans les processus inflammatoires de déstabilisation de plaque. L'étude 3 nous a permis de caractériser l'effet du niveau d'AP sur la réponse monocytaire chez des patients avec plaque d'athérosclérose, et d'identifier une chimiokine qui pourrait avoir un rôle dans la modulation de la réponse monocytaire par l'AP. Enfin, la 4ème étude démontre l'altération de paramètres hémorhéologiques chez des patients atteints de maladie carotidienne sévère, et comment l'AP permet de limiter cette altération via la diminution de l'agrégation érythrocytaire. Ce travail de thèse apporte des informations quant à la pratique de l'AP dans la prévention primaire de l'athérosclérose. Des études complémentaires seront toutefois nécessaires afin de confirmer ces résultats, en proposant notamment une approche interventionnelle en activité physique / Atherosclerosis is a complex cardiovascular disease that affects the arterial wall where plaque development and progression are severely promoted by chronic inflammation. Carotid plaque destabilization could lead to potential major ischemic events such stroke which is still unpredictable, making primary prevention very complex. Thus, there is still currently no suitable predictive biomarker of plaque rupture. Nevertheless, it is now clearly established that intraplaque hemorrhage (IPH), neovascularization and excessive macrophage accumulation are the three main risk factors of plaque instability. Based on previous studies, the aim of this work was to evaluate independently the impact of physical activity (PA) and sedentary behavior, first on histological parameters of plaque instability, and secondly on secondary risk factors of atherosclerosis, such as inflammation, oxidative stress and hemorheological profile of asymptomatic patients at high-risk of stroke who underwent endarterectomy surgery. The first study shows that regular PA was associated to a decreased occurrence of IPH, and was the only protective factor for IPH. This study also suggested a beneficial effect of PA on macrophage accumulation as well as on oxidative stress. Then, in the 2nd study, we have characterized the functional state of proteins potentially implicated in immune system dysfunctions, and the implication of inflammatory cells in these mechanisms. We have identified a pro-inflammatory cytokine as a key driver of disrupting inflammatory process of plaque. In the same way, we have characterized in the 3rd study, the effect of PA on the monocytic response in atherosclerosis patients, and identified a chemokine associated that could explain the modulation of this monocytic response by PA. Finally, the 4th study demonstrates the hemorheological parameters alteration in carotid artery disease patients, and how PA could limit this alteration via red blood cell aggregation. This PhD thesis provided information regarding regular PA in primary prevention of atherosclerosis. However, additional studies are required to confirm these results, using in particular PA interventional approach

As principais incapacidades funcionais que se observam após o Acidente Vascular Encefálico (AVE), sob o ponto de vista clínico, decorrem da hemiparesia, da incoordenação, da hipertonia espástica dos membros superior e inferior contralaterais à lesão e da fraqueza ipsilateral e contralateral ao hemisfério lesado. Evidências sugerem que o aprendizado e a realização de tarefas motoras de habilidade podem induzir mudanças comportamentais e neurofisiológicas, o que ocorre tanto em animais intactos quanto naqueles submetidos às lesões do SNC. Nesse sentido, alguns trabalhos evidenciam a participação da atividade dendrítica, observada pelo aumento da imunorreatividade a MAP2, induzida por experiências comportamentais. Sendo assim, o objetivo do presente estudo foi avaliar o desempenho motor e a expressão da MAP2 no córtex motor primário, em ratos sham ou submetidos à HIC e aos treinamentos de habilidade do alcance (TH) ou ao treinamento de não-habilidade (TNH). Para tanto, ratos Wistar adultos foram inicialmente adaptados às diferentes tarefas motoras empregadas ao longo de três semanas, sendo, posteriormente, submetidos à cirurgia de indução da hemorragia intracerebral (HIC) por meio da administração intra-estriatal de colagenase tipo IV ou de veículo (animais Sham) (S). Em seguida, os animais dos grupos S_TH e HIC_TH foram submetidos ao treinamento da tarefa de habilidade do alcance e preensão, os animais dos grupos S_TNH e HIC_TNH foram submetidos ao treinamento da tarefa de não-habilidade e os animais S_ST e HIC_ST não receberam nenhum tipo de treinamento durante 4 semanas. Ao longo desse período, os animais foram testados pelo teste do Staircase quanto ao desempenho motor ao final da 2° e 4° semana de treinamento. Encerrado o período de treinamento, os animais foram profundamente anestesiados, perfundidos e tiveram seus encéfalos processados para a análise imunoistoquímica. Os resultados mostram que a realização da tarefa de habilidade do alcance e preensão foi capaz de aumentar a imunorreatividade da MAP2 no córtex motor primário (M1) em ambos os hemisférios, tanto em animais lesados quanto em animais não-lesados. Além disso, os animais HIC e HIC_TNH apresentaram também aumento da imunorreatividade à MAP2 em ambos os hemisférios. Porém, apenas os animais HIC_TH apresentaram recuperação funcional dos movimentos do membro anterior afetado, avaliados pelo teste comportamental. Concluindo, o presente estudo demonstra que o treino de habilidade induz plasticidade dendrítica no M1 em condições normalidade e lesão e, como estratégia de reabilitação, mostra-se superior ao treino de não-habilidade, na recuperação funcional do membro anterior após a HIC experimental. / Under clinical view, the main functional impairment observed after stroke is resulting from the hemiparesis, incoordination, spastic hypertonia and from ipsilateral and contralateral weakness . Evidences suggest that learning and achievement of motor tasks ability may induce behavioral and neurophysiological changes, which occur in both intact and injured animals. Accordingly, some studies reveal the participation of dendritic activity, observed by increasing the immunoreactivity to MAP2, induced by behavioral experiences. Thus, the aim of this study was to evaluate the motor performance and the expression of MAP2 in primary motor cortex (M1), in rats submitted or not to the IHC and rehabilitation using skilled (SK) or unskilled (US) training. Animals were initially adapted to different motor tasks employed over three weeks, and, subsequently, submitted to surgery for the induction of intracerebral hemorrhage (IHC) by means of administration of bacterial collagenase type IV or vehicle (animals Sham) (S) into the striatum . Then, animals in groups S_SK and IHC_SK were submitted to the training skilled forelimb reaching, animals in groups S_US and IHC_US were submitted to the training unskilled and animals S and HIC received no type of training during 4 weeks. Throughout that period, the reaching ability was tested using the Staircase test at the end of 2nd and 4thweek of training. At the end of the rehabilitation period, animals were deeply anesthetized, perfused and the immunohistochemistry was processed. Results show that the achievement of the task skilled forelimb reaching was able to increase the MAP2 immunoreactivity in primary motor cortex (M1) in both hemispheres, both in injured animals as in intact animals. In addition, animals form IHC and IHC_US groups also presented increased immunoreactivity to MAP2 in both cerebral hemispheres. However, only IHC_SK animals presented functional recovery of movements of the forelimb, evaluated by test behavioral. In conclusion, this study shows that training of skills tasks can induce modifications in M1 under conditions of normality and lesion and, as a strategy of rehabilitation, induced higher plasticity than the unskilled training correlated with functional recovery of the forelimb after IHC experimental.