L’estuaire de la Gironde est le plus grand estuaire macrotidal d’Europe formé par la confluence de la Garonne (où se situe l’agglomération de Bordeaux) et de la Dordogne. L’une de ses principales caractéristiques est la présence d’une zone à forte turbidité (bouchon vaseux) où les processus hétérotrophes (dégradation de la matière organique) sont favorisés et où au contraire les processus autotrophes (production primaire) sont limités par le manque de lumière. Ainsi, des déficits en oxygène pouvant être préjudiciables à la vie aquatique se développent systématiquement dans la zone du bouchon vaseux de la Garonne estuarienne. Ces préoccupations environnementales ont donc conduit à étudier en détail dans le cadre de ce travail de doctorat, les facteurs environnementaux qui provoquent ces hypoxies estuariennes. Dans un premier temps, j’ai réalisé un suivi sur le réseau d’eaux urbaines partiellement séparatif et unitaire de la Communauté Urbaine de Bordeaux, de ses stations d’épurations et déversoirs d’orage afin d’appréhender les apports urbains de matières organique et azotées et de les comparer à ceux en provenance du bassin versant amont. Bien que les deux stations d’épuration réalisent des abattements très significatifs sur la matière organique et l’ammonium, il s’avère que les flux vers le milieu naturel restent importants, notamment durant les périodes estivales, pendant lesquelles des orages peuvent engendrer des déversements d’effluents non traités. Ensuite, des expériences d’incubations ont permis de mettre en évidence le caractère fortement labile de cette matière organique urbaine. Le carbone organique dissous et l’ammonium, contenus dans les eaux usées, sont des composés fortement consommateurs en oxygène. Des expériences de respirométrie ont également permis d’estimer les taux de consommation en oxygène nettement plus importants dans les effluents urbains que dans les eaux de la Gironde. Enfin, l’analyse des données du réseau de mesures en continu de la qualité physico-chimique des eaux MAGEST (MArel Gironde ESTuaire) a démontré que l’estuaire subit dans sa section garonnaise des périodes d’hypoxie lors d’étiages prononcés, la masse d’eau la plus affectée par ces désoxygénations étant celle qui oscille aux alentours de l’agglomération de Bordeaux. Si ces résultats démontrent l’impact significatif de l’agglomération Bordelaise, le traitement statistique des données MAGEST pour la période 2005-2011 montre que les phénomènes de désoxygénation sont accrus en période d’étiage prononcé, en présence du bouchon vaseux et lorsque la température de l’eau est élevée. Dans ces conditions, l’oxygène dissous, déjà présent en faible quantité, peut être rapidement consommé lors d’apports supplémentaires d’eaux urbaines non traitées qui ont lieu pendant de fortes précipitations orageuses. Ce travail démontre également que le type de traitement biologique des eaux usées employé par les stations d’épuration et les capacités de stockage temporaire d’eaux d’orages ont un rôle critique sur les bilans de ces composés rejetés dans le milieu naturel. Enfin, ce travail permet de proposer aux gestionnaires des stratégies de rejets des effluents à court et moyen terme, en fonction des conditions hydrologiques et physico-chimiques du milieu, dans le but de limiter leur impact sur l’oxygénation des eaux estuariennes de la Garonne. / The Gironde Estuary is the largest macrotidal estuary in Western Europa, formed by the Garonne River (where the urban area of Bordeaux is located) and the Dordogne River. One of its main characteristics is the presence of a Turbidity Maximum Zone (TMZ) where heterotrophic processes (organic matter decomposition) are favored and where low penetration of light limits autotrophic processes (photosynthetic activity). Low dissolved oxygen (DO) that could impact aquatic biota occurred exclusively in the fluvial, low salinity and high turbidity sections of the estuary. These environmental concerns have led to study in detail in this work factors that cause estuarine hypoxia. First, I have estimated organic matter and ammonium fluxes from urban inputs in separate and combined sewer network of the Urban Community of Bordeaux, its wastewater treatment plants (WWTP) and combined sewer overflow, to compare them to the upstream watershed inputs. Even if the two WWTPs succeed in significant reduction in organic matter and ammonium contents of effluents, discharges into estuarine waters are important especially during summer, periods while storm events can generate untreated effluent inputs. This work demonstrates the high lability of this urban organic matter through incubation experiments. The dissolved organic carbon and ammonium contents in wastewater consume oxygen. Respirometry experiments allowed us to estimate higher oxygen uptake rates in wastewater than in the waters of the Gironde Estuary. Finally, the analysis of 7-yr data series from the continuous monitoring of the physico-chemical water quality (MAGEST network: MArel Gironde ESTuary) highlights periods of hypoxia in the upstream section of the estuary during pronounced low water around the Bordeaux conurbation. Statistical treatments of the 7-yr time series of DO concentration demonstrate the significant impact of the Bordeaux metropolitan area as it appears that the under-oxygenations increase during marked low water, in the presence of the TMZ, when the water temperature is high, and where the dissolved oxygen content is already low and can be quickly consumed after untreated storm water discharges. This study also shows that the nature of biological treatment used by the WWTPs and the temporary storage capacity of storm water have a critical role in the release of such compounds into the environment. This work finally provides strategies for effluent discharges to water managers, to short and medium terms, based on hydrological and physico-chemical conditions of the environment in order to limit their impact on the water oxygenation of the Garonne River.

La production de radicaux libres oxygénés (ROS), la surcharge calcique cytosolique et l’ouverture des pores de transition membranaires mitochondriales (mPTP) consécutives à l’ischémie myocardique (IM) sont aggravées lors de la reperfusion. Dans cette thèse, nous nous sommes intéressés : 1) à l’évaluation des effets de la trimétazidine sur le seuil électrique de fibrillation ventriculaire (VFT) et sur les lésions structurales et fonctionnelles des mitochondries lors de l’IM (étude 1, N=26 porcs); 2) à la détermination de la cinétique d’évolution des lésions d’ischémie/reperfusion (I/R) (étude 2a, N=30 porcs) ;3) à l’étude de l’impact de la ranolazine, du propranolol et de leur association dans la préventions des lésions d’I/R (étude 2b, N=30 porcs). Ces études qui ont été réalisées sur le cœur de porcs anesthésiés, ont permis de suivre l’évolution des paramètres électrophysiologiques et hémodynamiques cardiaques et, à l’échelle cellulaire, l’évolution de la structure et de la fonction des mitochondries. Les résultats montrent : 1) dans l’étude 1 : que la TMZ prévient la chute du VFT et l’ensemble des altérations structurales et fonctionnelles mitochondriales observées lors de l’IM ; 2) dans l’étude 2a : que les lésions observées durant l’IM sont significativement aggravées dans les premières dizaines de secondes de la reperfusion alors qu’une certaine amélioration est observée après 10 et surtout 45 min de reperfusion; 3) dans l’étude 2b : qu’un prétraitement par de la ranolazine, du propranolol et par leur association réduit la sévérité de ces lésions d’I/R. Les mécanismes moléculaires et cellulaires d’action des produits utilisés dans cette étude seraient en rapport avec l’amélioration des lésions de l’I/R / The generation of reactive oxygen species (ROS), the cytosolic calcium overload and the opening of mitochondrial permeability transition pores (mPTP) resulting from myocardial ischemia (MI) are aggravated during reperfusion. In the present work, the following points have been addressed: 1) the evaluation of trimetazidine effects on the electrical threshold of ventricular fibrillation (VFT) and both structural and functional alterations of mitochondria during MI (study 1, N=26 pigs); 2) the determination of the kinetics of ischemia/reperfusion (I/R) lesions (study 2a, N=30 pigs); 3) the protective effects of ranolazine and propranolol, alone or combined on I/R lesions (study 2b, N=30 pigs). All studies were performed in anesthetized pigs. They allowed to follow changes in cardiac electrophysiological and hemodynamic parameters and, at the cellular level, changes in the structure and function of mitochondria. The obtained results show: 1) in study 1, that TMZ can prevent the drop in VFT and all structural and functional alterations of mitochondria noticed during MI; 2) in study 2a, that the lesions seen during MI are significantly aggravated within the first seconds of reperfusion whereas some improvement is observed after 10 minutes and more markedly after 45 minutes of reperfusion; 3) in study 2b, that pretreatment with ranolazine or propranolol, alone or combined can reduce the severity of I/R lesions. The molecular and cellular mechanisms of action of both agents are thought to be involved in this improvement of I/R lesions

<p>UVOD: Anestezija je povezana sa promenama ventilacije, koje počinju sa prvim datim lekom, a mogu da traju i danima posle hirur&scaron;ke intervencije. Hipoksemija je najočiglednija posledica ove promene. U anesteziolo&scaron;koj praksi i perioperativnom tretmanu bolesnika kiseonička terapija zauzima značajno mesto. Jo&scaron; uvek ne postoje jasne, na dokazima zasnovane, smernice za upotrebu kiseoničke terapije u postoperativnom periodu. Razlog verovatno leži u činjenici da veliki broj faktora može da utiče na ishod lečenja hirur&scaron;kog bolesnika i zato je te&scaron;ko ispitati njihove pojedinačne uticaje. Kiseonička terapija tretira ili prevenira nastanak hipoksije obezbeđujući inspiratornu koncentraciju kiseonika veću od iste u vazduhu. Kod najvećeg broja pacijenata u postoperativnom periodu ne postoji potreba za strogom kontrolom inspiratorne koncentracije kiseonika, a administracija kiseoničke terapije sprovodi se primenom uređaja niskog protoka i varijabilne performanse, kao &scaron;to su nazalna kanila i kiseonička maska za lice. Brojna istraživanja poslednjih decenija poku&scaron;ala su da daju odgovor na pitanja da li postoji stvarna razlika u primeni ova dva uređaja, posebno u svetlu razvoja hipoksemije u postoperativnom periodu. Prednosti primene nazalne kanile su bolje prihvatanje od strane bolesnika u poređenju sa maskom, obično zbog manje izraženog osećaja klaustrofobije pri upotrebi nazalne kanile. Nazalna kanila, ne zahteva uklanjanje prilikom nege usne duplje ili per os unosa &scaron;to obezbeđuje kontinuitet u isporuci kiseonika. Nedostaci nazalne kanile vezani su za otežanu primenu kod bolesnika sa nazogastričnom sondom ili otežanim disanjem na nos. Pri protocima većim od 4 litre u mnuti može izazvati nelagodnost na nosnoj sluznici bolesnika. Literaturni podaci, ukazuju da se primenom kiseoničke maske ipak postižu veće inspiratorne koncentracije kiseonika, te da se epizode desaturacije i hipoksemije znatno ređe javljaju. Međutim, postoje i istraživanja koja ukazuju na mogućnost ponovnog udisanja vazduha iz mrtvog prostora maske, pri nižim protocima &scaron;to može uticati na parcijalni pritisak ugljen-dioksida u arterijskoj krvi. CILJEVI: Ciljevi istraživanja su da se ispitata učestalost javljanja hipoksemije unutar 48 sati od ekstubacije kod bolesnika u jedinici intezivne terapije, zatima da se ispita pojava desaturacije, da se utvrditi učestalost potrebe za primenom neinvazivne mehaničke ventilacije pozitivnim pritiskom kod bolesnika u jedinici intezivne terapije kod kojih se primenjuje kiseonička terapija putem nazalne kanile, odnosno kiseoničke maske. Takođe, cilj je i da se ispita da li postoji povezanost preoperativnih karakteristika bolesnika sa eventualnim izborom jednog od dva uređaja za primenu kiseoničke terapije u ranom postoperativnom periodu. METODOLOGIJA: Na Klinici za anesteziju i intenzivnu terapiju Kliničkog centra Vojvodine sprovedeno je prospektivno istraživanje kojim je obuhvaćeno 160 pacijenata nakon elektivnih hrur&scaron;kih procedura, koji su nakon operativnog zahvata praćeni u jedinici intenzivne terapije. Pacijenti su randomizovani u dve grupe (grupa M &ndash; kiseonička maska i grupa N &ndash; nazalna kanila) u odnosu na uređaj kojim je sprovođena postoperativna kiseonička terapija. Za sve pacijente uključene u studiju evidentirana je pol, starost, telesna masa, telesna visina, izračunat indeks telesne mase. Evidentiran je i ASA status, kao i NYHA status. U istraživanje nisu uključeni pacijenti sa plućnim komorbiditetima. Iz istraživanja su isključeni svi oni bolesnici kod kojih je do&scaron;lo do respiratornih komplikacija u perioperativnom periodu, kao i onih kod kojih je bila prisutna hemodinamska nestabilnost. Postoperativno svi pacijenti su sedirani, na mehaničkoj ventilaciji sme&scaron;teni u jedinicu intenzivne terapije. Nakon prevođenja na spontano disanje i ekstubacije započinjana je primena kiseonika putem kiseoničke maske za lice (6 l/min) odnosno nazalne kanile (4 l/min). Sprovođen je kontinuirani monitoring vitalnih parametara, saturacije hemoglobina kiseonikom, kao i novo ugljen-dioksida na kraju ekspirijuma. Kod svih pacijenata u četiri vremena rađene su gasne analize arterijske krvi. Svi praćeni parametri poređeni su između dve ispitivane grupe pacijenata. Za statističku obradu podataka kori&scaron;ćen je programski paket Statistical Package for Social Sciences - SPSS 21. Numerička obeležja su prikazana putem srednjih vrednosti (aritmetička sredina) i mera varijabiliteta (opseg vrednosti, standardna devijacija), a atributivna obeležja kori&scaron;ćenjem frekvencija i procenata. Komparacija vrednosti numeričkih obeležja između dve grupe vr&scaron;ena je primenom Studentovog t- testa, odnosno neparametrijskog Mann- Whitney testa. Testiranje razlike frekvencija atributivnih obeležja vr&scaron;eno je primenom &chi;2 testa. U cilju ispitivanja povezanosti dva ili vi&scaron;e obeležja, odnosno generisanja adekvatnih statističkih modela, kori&scaron;ćena je multivarijantna regresiona analiza. Statistički značajnim se smatraju vrednosti nivoa značajnosti p&lt;0.05. REZULTATI: U odnosu na preoperativne karakteristike ispitivanih pacijenata nije nađena statistički značajna razlika u distribuciji pacijenata u dve ispitivane grupe u odnosu na pol (2 test; 2=0,378;p=0,539), starost (T test; t=1,958; p=0,053), APACHE II skor na prijemu (Mann-Whitney test; U=1220,500; p=0,837), indeks telesne mase (T test; t=1,380; p=0,171), pu&scaron;ačkim navikama (2 test; 2=0,644;p=0,422), vrednostima preoperativnog hemoglobina (T test; t=0,442; p=0,660), saturacije hemoglobina kiseonikom (T test; t=0,883; p=0,380). Razlike nije bilo ni u pogledu trajanja mehaničke ventilacije (Mann-Whitney test; U=1114,500; p=0,345). Hipoksemija (parcijalni pritisak kiseonika u arterijskoj krvi manji od 65 mmHg) nije registrovana ni kod jednog od pacijenata u obe ispitivane grupe. Vrednsti SpO2 &lt; 92%, registrovane su kod ukupno 24 pacijenta u svim analiziranim vremenima (24%). Najveći broj pacijenata kod kojih je registrovana niska vrednost detektovan je u prvom satu nakon ekstubacije kada je vrednost manja od 92% registrovana kod 5 pacijenata (5%) i to kod 3 pacijenta u grupi M (6%) i 2 pacijenta u grupi N (4%). Između vizita 2. i 3. vrednosti satutracije manje od 92% registrovana je kod 19 pacijenata (19%), kod 8 pacijenata u grupi M (16%) i kod 11 pacijenata u grupi N (22%). U periodu između vizita 3. i 4. vrednosti saturacije niže od 92% registrovane su kod 19 (19%) pacijenata i to kod 10 pacijenata u grupi M (20%) i kod 9 pacijenata u grupi N (18%). Statistički značajna razlika zabeležena je u sve tri vizite (vizita 2, 3, 4) u vrednosti parcijalnog pritiska kiseonika u arterijskoj krvi. Tako su pacijenti u grupi kod kojih je primenjivana maska imali statistički značajno veće vrednosti parcijalnog pritiska kiseonika. Istovremeno pacijenti kod kojih je kiseonička terapija primenjivana putem maske imali su značajno veće vrednosti saturacije hemoglobina kiseonikom i ova razlika je bila statistički značajna u svim posmatranim vizitama. U prvih 48 sati nakon operacije neinvazivna mehanička ventilacija primenjena je kod 80 pacijenata. Kod svih pacijenata indikacija za primenu je bila pojava desaturacije. U odnosu na distribuciju pacijenata po ispitivanim grupama nije bilo statistički značajne razlike u broju pacijenata koji su zahtevali neinvazivnu mehaničku ventilaciju (2 test; 2=2,250; p=0,134). Pacijenti u grupi N proveli su vi&scaron;e minuta (srednja vrednost 56,85 +/- 19,80 minuta) na neinvazivnoj ventilaciji od pacijenata u grupi M (srednja vrednost 33,14 +/- 10,65 minuta), a ova razlika je statistički značajna (T test; t=2,923; p=0,009). Na osnovu multivarijantne regresione analize, pacijenti koji su kiseoničku terapiju primali putem nazalne kanile, sa porastom indeksa telesne mase imali su niže vrednosti parcijalnog pritiska kiseonika u arterijskoj krvi (r2=0,392). ZAKLJUČCI: Kiseonička maska za lice i nazalna kanila obezbeđuju adekvatnu primenu kiseoničke terapije u smislu prevencije nastanka hipoksemije u ranom postoperativnom periodu. Primenom kiseoničke maske za lice ostvaruju se vi&scaron;e vrednosti parcijalnog pritiska kiseonika u arterijskoj krvi. Epizode desaturacije če&scaron;će se javljaju kod pacijenata kod kojih se u ranom postoperativnom periodu primenjuje kiseonička terapija putem nazalne kanile. Pacijenti kod kojih se primenjuje kiseonička terapija putem maske ostvaruju veće vrednosti saturacije hemoglobina kiseonikom. Pacijenti kod kojih je kiseonička terapija u ranom postoperativnom periodu primenjivana putem nazalne kanile zahtevali su dužu primenu neinvazivne mehaničke ventilacije pluća. Kod pacijenata sa većim vrednostima indeksa telesne mase, za primenu kiseoničke terapije u ranom postoperativnom periodu, kiseonička maska za lice će obezbediti bolju oksigenaciju.</p> / <p>INTRODUCTION: Anesthesiology is associated with vicissitudes in ventilation, which start with application of first medicine and last for days following surgical intervention. Hypoxemia is a most common side effect of vicissitudes in ventilation. Oxygen therapy is important in anesthesiology and post-operative treatment of a patient. There are no clear evidence-based guidelines for application of oxygen therapy in post-operative period. Numerous factors influence patient&rsquo;s treatment outcome and it is difficult to examine each factor&rsquo;s independent impact. Oxygen therapy treats or prevents occurrence of hypoxemia by providing inspiratory concentration of oxygen greater than the amount found in air. Most patients in post-operative period don&rsquo;t require vigilant control of inspiratory concentration of oxygen, and administration of oxygen therapy is implemented with a low flow device with variable performances such as nasal cannula and oxygen face mask. Various research attempts where made in the last decades to discover an evident difference between these two devices, especially in cases where hypoxemia occurred in post-operative period. One advantage to using nasal cannula over oxygen face mask is that its better perceived by a patient as it reduces feeling of claustrophobia. Nasal cannula doesn&rsquo;t need to be removed during oral cavity care or &ldquo;per os&rdquo; intake which ensures continuous oxygen delivery. The drawback to using nasal cannula is that its challenging to insert it in a patient with nasogastric tube or difficult nasal breathing. Also, patient can experience nasal discomfort if the oxygen flow is bigger than four litters per minute. Literature data shows that application of oxygen trough the face mask achieves greater inspiratory concentrations of oxygen, and reduces the occurrence of desaturation and hypoxemia. Still, there is research which points out to the possibility of breathing in from dead space in the mask, in lower flows, which can partially affect pressure of carbon dioxide in artery blood. AIM: Aim of the research is to examine frequency of hypoxemia and non-invasive mechanical ventilation in patients treated with oxygen therapy via nasal cannula or oxygen face mask during the first 48 hours following patient extubating in intensive care unit. Also, aim is to examine correlation between patients&rsquo; pre-operative characteristics and the choice of one of the two devices for oxygen therapy in early postoperative period. METHODOLOGY: Clinic for Anesthesiology and Intensive Therapy at the Clinical Center of Vojvodina conducted this research on 160 patients who underwent elective surgical procedures and received post-operative care in Intensive Care Unit. Patients were randomly assigned to two groups (Group M with oxygen face mask and Group N with nasal cannula) relative to device which was used for post-operative oxygen therapy. Information recorded for all the patients included in the study constituted their gender, age, weight, hight, and body max index. ASA status, as well as NYHA status were also recorded. Research excluded any patient who experienced respiratory complications in post-operative period as well as those who experienced hemodynamic instability. Postoperatively all patients were sedated and on mechanical ventilation therapy in intensive care unit. After transition to spontaneous breathing and extubating, oxygen therapy was applied using oxygen mask (6 l/min) or nasal cannula (4 l/min). Vital parameters were continuously monitored as well as hemoglobin oxygen saturation, and carbon dioxide at the end of the expirium. Gas analysis of artery blood was carried out four times for all participants in the study. All parameters were compared between two examined patient groups. Statistical analysis was carried out using Statistical Package for Social Sciences - SPSS 21. Numerical features are depicted using arithmetic mean and variability rate, and attributive features are depicted with frequency and percentages. Comparison of the values of numerical characteristics between the two groups was performed using Student&#39;s t-test, that is, a non-parametric Mann-Whitney test. The frequency difference in attributive characteristics was tested using &chi;2 test. To generate adequate statistical model, multivariate regression analysis was applied to examine the link between two or more of features. Significant values are determined if level of significance is p&lt;0.05. RESULTS: Preoperative characteristics of the patient showed no significant differences between the two study groups. Characteristics were recorded with respect to gender (2 test; 2 = 0.378; p = 0.539), age (t-test; t = 1,958, p = 0,053 ), APACHE II score on admission (Mann-Whitney test; U = 1220.500; p = 0.837), body mass index (t-test; t = 1.380, p = 0.171), smoking habits (2 test; 2 = 0.644; p = 0.422), the values of the preoperative hemoglobin (t-test; t = 0.442, p = 0.660), and hemoglobin oxygen saturation (t-test; t = 0.883, p = 0.380). Difference was discovered in regards to duration of mechanical ventilation (Mann-Whitney test; U = 1114.500; p = 0.345). Hypoxemia (partial oxygen pressure in the arterial blood of less than 65 mmHg) was not registered in any of the patients in both study groups. Value SpO2&lt; 92%, was registered in 24 patients during every round (24%). Patients who registered value lower than 92% experienced it in the first hour post extubation. This was observed in 5 patients in total (5%) where 3 patients from group M (6%) and 2 from group N (4%). Between 2nd and 3rd rounds, saturation values lower than 92% were recorded in 19 patients (19%): 8 from group M (16%) and 11 from group N (22%). In the period between the 3rd and 4th rounds the value of saturation lower than 92% was detected in 19 (19%) patients: 10 from group M (20%) and 9 from group N (18%). Statistically significant difference was noted in all three rounds (rounds 2, 3, 4) in the values of the partial oxygen pressure in arterial blood. Thus, patients from the group treated with an oxygen face mask had significantly higher values of partial oxygen pressure. In addition patients treated by oxygen face mask had significantly higher levels of oxygen saturated hemoglobin, and this difference was statistically significant in all observed rounds. In the first 48 hours after surgery noninvasive mechanical ventilation was performed in 80 patients. Common indication for oxygen therapy in all patients was desaturation. There were no statistically significant differences in the number of patients who required non-invasive mechanical ventilation in either of the groups (2 test; 2 = 2.250; p = 0.134). Patients in group N received several minutes more (mean value of 56.85 +/- 19.80 minutes) of the non-invasive ventilation than patients in the group M (mean value of 33.14 +/- 10.65 minutes), and this difference was statistically significant (t-test; t = 2,923, p = 0,009). Based on the multivariate regression analysis, the patients who received oxygen therapy via nasal cannula, with the increase in body mass index had lower values of partial oxygen pressure in arterial blood (r2 = 0.392). CONCLUSION: Both face mask and nasal cannula ensure adequate application of oxygen therapy to prevent hypoxemia in the early postoperative period. Oxygen face mask achieves higher value of partial oxygen pressure in arterial blood. Episodes of desaturation more frequently occur in patients who receive oxygen therapy with nasal cannula in early postoperative period. Patients who receive oxygen therapy via oxygen face mask achieve higher hemoglobin oxygen saturation values. Patients who undergo oxygen therapy in the early postoperative period using nasal cannula require longer application of non-invasive mechanical ventilation. Patients with higher body mass index receive better oxygenation in the early postoperative period if facial mask is the device of choice.</p>

Introdução: a revisão de literatura aponta que os recém-nascidos submetidos ao banho de imersão produzem menor variação térmica pós-banho comparado aos submetidos ao banho com esponja. No Brasil, o Ministério da Saúde vem capacitando profissionais que atuam em unidades de internação neonatal para implementar o Método Mãe Canguru e, entre outras práticas, recomenda que o recém-nascido pré-termo (RNPT) e com baixo peso seja submetido ao banho de imersão envolto em cueiro ou lençol, sugerindo mudança da prática hegemônica do banho com esponja ou banho de imersão convencional. No entanto, a técnica de banho de imersão recomendada carece de evidências científicas quanto a sua segurança em relação às repercussões na estabilidade da temperatura corporal (T), frequência cardíaca (FC), cortisol salivar (CS) e comportamental em RNPT. Hipótese: os RNPT submetidos ao banho de imersão envoltos em lençol (BIE) apresentam respostas fisiológicas e comportamentais similares aos submetidos à técnica de banho de imersão convencional (BIC), nos primeiros 20 minutos pós-banho. Objetivo: avaliar os parâmetros fisiológicos e comportamentais de RNPT submetidos ao banho de imersão envolto em lençol (BIE) e banho de imersão convencional (BIC). Método: ensaio clínico randomizado cruzado com amostra composta por 43 RNPT, internados na Unidade Neonatal de um hospital escola da cidade de São Paulo. Os RNPT foram alocados no grupo A ou B, seguindo uma lista de randomização gerada pelo software R que foi envelopada e mantida com os auxiliares da pesquisa responsáveis pelos banhos dos RNPT. A randomização definiu a técnica do primeiro banho que o RN seria submetido. Somente após análise dos dados foi aberto o envelope da randomização sendo identificado que no grupo A, o primeiro banho foi o BIC (intervenção controle) e no grupo B, o BIE (intervenção experimental). A técnica do BIE seguiu a técnica recomendada no Manual Atenção Humanizada ao Recém-Nascido de Baixo Peso: Método Mãe-Canguru, publicada pelo Ministério da Saúde. Foram utilizadas filmadoras para obter os valores da FC e da SatO2 registradas pelo monitor cardíaco instalado nos RNPT e para captar imagens das reações comportamentais antes e após os banhos. As temperaturas axilares foram aferidas com termômetro digital e amostras de saliva foram coletadas com esponja oftálmica (Merocel)®, refrigeradas e processada pelo teste Elisa. As filmagens do estado comportamental 10 minutos pré e 10 e 20 minutos pós-banho foram analisadas utilizando o instrumento de avaliação do sono-vigília validado por Brandon e Holditch-Davis. Os dados foram registrados em formulário próprio e armazenados em planilha Microsoft Excel. A análise estatística foi realizada com os programas Minitab, versão 16.1 e SPSS, versão 20. Além da análise descritiva das variáveis numéricas para obtenção de medidas de tendência central e dispersão e frequências absoluta e relativa, foram utilizados os testes Qui-quadrado e Exato de Fisher; o teste T pareado, ANOVA e Modelos Generalizados Lineares na análise dos dados. Resultados: As temperaturas axilares médias dos RNPT pré-BIC e pré-BIE foram, respectivamente, 36,695°C e 36,667°C, p = 0,329. No 10° minuto pós-BIC e BIE, as médias das temperaturas axilares foram, respectivamente, 36,533°C e 36,535°C, p = 0,944. No 20° minuto pós-BIC e BIE, as médias da temperatura axilar foram 36,626°C e 36,628°C, p = 0,663. Houve queda na temperatura axilar no 10° minuto pós-banho, independente do tipo de banho realizado (p <0,001). A hipótese de que o BIE é equivalente ao BIC em relação à variação da temperatura axilar foi confirmada. Houve redução significante nos valores das FC no 10° e 20° minutos pós-BIC e BIE comparados aos valores pré-banho, independente do tipo de banho (p<0,001). Ocorreu aumento gradativo dos valores médios de SatO2 no 10º e 20° minutos após os banhos sem diferenças significantes nos valores pré-banhos, p = 0,969. A concentração do cortisol salivar aumentou após o banho em ambos os grupos, p = 0,001, entretanto não ocorreram diferenças entre os grupos, ou seja, os níveis de cortisol salivar aumentaram após o banho, independente do tipo de banho, p = 0,797. O percentual de tempo em estado sono ativo aumentou após o banho, independente do tipo de banho, p<0,001, ou seja, houve mudança significativa no comportamento do recém-nascido, sem diferenças entre os banhos, p = 0,425. Conclusão: Tanto os RNPT que receberam BIC quanto os que receberam BIE apresentaram queda na temperatura corporal no 10° minuto pós-banho com aumento da temperatura corporal no 20° minuto pós-banho. Comparado aos achados da literatura, a redução da temperatura corporal foi menor que no banho com esponja. O BIE é equivalente ao BIC, portanto ambos são indicados aos RNPT. Convêm salientar o aumento dos custos do BIE em razão do consumo de lençol e da capacitação necessária da equipe de enfermagem nesta técnica de banho, sem prolongar o tempo médio dispendido no banho, visto que poderá reduzir a temperatura da água do banho e consequentemente causar queda na temperatura corporal do RN. / Introduction: the literature review shows that newborns underwent to immersion baths produce less post-bath thermal variation compared to those underwent to the sponge bath. In Brazil, the Ministry of Health has been qualifying working professionals in neonatal hospitalization units to implement the Kangaroo Mother Care and, among other practices, recommends that the preterm newborn infants (PNI) and underweight are underwent to the swaddle immersion bath wrapped in clothes or sheet, suggesting change of the hegemonic practice of sponge bath or conventional immersion bath. However, the immersion bath technique recommended requires more scientific evidence about its safety in relation to impact on the stability of body temperature (T), heart rate (HR), salivary cortisol (SC) and behavioral in PNI. Hypothesis: PNI underwent to swaddle immersion bath wrapped in sheet (SIB) have physiological and behavioral responses similar to those underwent to the conventional immersion bath technique (CIB), in the first 20 minutes post-bath. Objective: To evaluate the physiological and behavioral parameters of preterm newborn infants underwent to swaddle immersion bath in sheet (SIB) and conventional immersion bath (CIB). Method: Randomized crossover clinical trial with a sample of 43 preterm newborn infants in the neonatal unit of a university hospital in the city of Sao Paulo. PNI were allocated in the A or B groups, following a randomization list which was generated by the software R, which was enveloped and maintained with research assistants who were responsible for the baths of PNI. Randomization list defined the first bath technique that the newborn was underwent. The randomization envelope was only opened after data analysis being identified that in group A, the first bath was the CIB (control intervention) and group B, the SIB (experimental intervention). The SIB technique followed the technique recommended in the Humane Care Infant, Low Birth Weight: Kangaroo Mother Care Manual, published by the Ministry of Health of Brazil. Video cameras were used for the HR and SpO2 values recorded at heart monitor installed in the PNI and to capture images of behavioral responses before and after baths. Axillary temperatures were measured with a digital thermometer and saliva samples were collected with ophthalmic sponge (Merocel) ®, refrigerated and processed by the Elisa test. The video recorded of behavioral states of 10 minutes pre-baths and 10 and 20 minutes post-baths were analyzed using the sleep-wake assessment tool validated by Brandon and Holditch-Davis. Data were recorded and stored in the proper form in Microsoft Excel spreadsheet. Statistical analysis was performed using Minitab software, version 16.1 and SPSS, version 20. In addition to the descriptive analysis of numerical variables to obtain measures of central tendency, dispersion, absolute and relative frequencies, Chi-square tests were used and Fisher Exact, the paired T-test, ANOVA and Generalized Linear Models in the data analysis. Results: The mean axillary temperatures of PNI pre-CIB and SIB were respectively 36.695 °C and 36.667 °C, p = 0.329. At 10 minutes post-CIB and SIB, the mean axillary temperatures were, respectively, 36.533 ° C to 36.535 ° C, p = 0.944. At 20 minutes post- CIB and SIB, the average of axillary temperature were 36.626°C and 36.628 ° C, p = 0.663. There was a decrease in the axillary temperature at 10 minutes post-bath, regardless of the type performed bath (p < 0.001). The hypothesis that the SIB is equivalent to the CIB related to the variation in the axillary temperature was confirmed. There was a significant reduction in the HR values at the 10th and 20 th minutes after CIB and SIB compared to pre-bath values, regardless type of the bath (p< 0.001). There was a progressive rise on SpO2 mean values on the 10th and 20 th minutes after baths with no significant differences in pre-baths values, p = 0.969. The salivary cortisol concentrations increased after bathing in both groups, p = 0.001, however there were no differences between the groups, in other words, salivary cortisol levels increased after bathing, regardless of the type of bath, p = 0.797. The percentage of time in active sleep state increased after bathing, regardless of bath type, p <0.001, that is meaning there was significant change in newborn behavior, without differences between baths, p = 0.425. Conclusion: Both the PNI who received CIB, as those receiving SIB, had a decrease in body temperature in the 10th minute post bath followed by an increased body temperature at 20 minutes post-bath. Compared to previous studies, reduction of body temperature was lower than in the sponge bath. The SIB is equivalent to the CIB therefore both are recommended for preterm infants. It should be emphasized the increased in the SIB costs due to the bed sheet consumption and the required nursing staff training in this bath technique, without extending the average time spent in the bath, as it may reduce the temperature of the bath water, consequently causing body temperature drop on the newborn

INTRODUÇÃO: A lesão do ligamento cruzado anterior (LCA) é considerada uma lesão grave e pode afetar a carreira de um jogador de futebol profissional. O tratamento cirúrgico é frequentemente necessário para o tratamento da instabilidade. Embora a reconstrução do LCA seja considerada um procedimento eficaz em restaurar a estabilidade articular, a literatura mostra que apenas 55% dos atletas retornam à prática de esportes competitivos após a cirurgia. Jogadores de futebol profissional dependem de habilidades técnicas, táticas e físicas, como boa função do joelho e capacidade aeróbia. O objetivo deste trabalho é avaliar a capacidade aeróbia em jogadores profissionais de futebol de campo com lesão do LCA e após seis meses de reabilitação pós-operatória. MÉTODOS: Vinte jogadores profissionais de futebol de campo com lesão do LCA foram submetidos a reconstrução do LCA com tendões flexores autólogos e foram comparados com 20 jogadores profissionais de futebol de campo em atividade, sem histórico de lesão no joelho. Avaliamos a capacidade aeróbia máxima pelo consumo máximo de oxigênio (VO2max) e submáxima pelos limiares ventilatórios (LV1 e LV2), avaliados por ergoespirometria em esteira utilizando o protocolo de Heck modificado. Os testes foram realizados no pré-operatório e aos seis meses de pós-operatório e os resultados comparados ao grupo controle de jogadores profissionais em plena atividade. Também realizamos questionários de função subjetiva do joelho (Lysholm e IKDC), dinamometria isocinética computadorizada e avaliação da composição corporal por bioimpedância. RESULTADOS: No grupo com lesão do LCA a média da idade foi de 21,7 anos, enquanto no grupo controle foi de 22,1 anos (p=0,99). O intervalo de tempo a lesão e a cirurgia foi, em média, cinco meses. No pré-operatório, o VO2max, em mL/kg/min, foi em média ? desvio padrão de 45,2 +- 4,3, aos seis meses de pós-operatório 48,9 +- 3,8 (p < 0,001) e no grupo controle 56,9 +- 4,2 (p < 0,001 comparado ao pré-operatório e pós-operatório). A porcentagem de gordura corporal, em média +- desvio padrão, no pré-operatório foi de 14,7+- 3,7, no pós-operatório 14,9 +- 5,4 e no grupo controle 12,8 +- 4, sem diferença estatisticamente significativa entre os grupos. Os resultados do questionário Lysholm no pré-operatório, pós-operatório e no grupo controle foram, em média, 77,25, 94,12 e 97,5 (p < 0,05 em todas as comparações) e do questionário IKDC subjetivo foram 59,46, 87,75 e 97,28 (p < 0,001 em todas as comparações). O déficit de pico de torque de extensão do joelho a 60 O/s, foi de 21,5% no pré-operatório, 15,7% no pós-operatório (p=0,63) e 3,1% no grupo controle (p < 0,001 com relação ao pré-operatório e pós-operatório). CONCLUSÃO: Os jogadores profissionais de futebol de campo avaliados seis meses após a reconstrução do LCA apresentaram VO2max significativamente inferior aos resultados do grupo controle, embora os resultados pós-operatórios tenham sido significativamente superiores aos observados no pré-operatório. Houve uma melhora significativa nos scores de função do joelho no pós-operatório com relação ao pré-operatório e a composição corporal dos indivíduos não apresentou diferenças estatisticamente significativas / INTRODUCTION: Anterior cruciate ligament (ACL) injury is a severe injury and may impact a professional football player\'s career. Surgical treatment is often indicated due to knee instability. Although ACL reconstruction (ACLR) is considered a successful procedure in restoring knee stability in athletes, it has been shown that only 55% return to competitive sports after surgery. Professional football players need technical, tactical and physical skills to succeed, including adequate knee function and aerobic capacity. Our purpose is to evaluate aerobic capacity in professional football players with ACL injury and six months after ACL reconstruction. METHODS: Twenty professional football players underwent ACL reconstruction with autologous hamstring grafts and were compared to 20 active, uninjured professional football players. We assessed maximal aerobic capacity with maximal oxygen consumption (VO2max) and submaximal with ventilatory thresholds, measured by ergoespirometric test performed in a treadmill with a modified Heck protocol. The tests were performed pre-operatively and six months after ACLR, and compared to the control group. We also performed knee function questionnaires (Lysholm and IKDC), isokinetic strength test and body composition evaluation with electric bioimpedance. RESULTS: ACL group average age was 21.7 y.o., and control group 22.1 y.o.(p=.99). Time span between injury and surgery was 5 months, in average. Pre-operative VO2max was 45.2 +- 4.3 mL/kg/min, post-operative was 48.9 +- 3.8 (p > .001) and control group was 56.9 +- 4.2 (p < 001 in both comparisons). Pre-op body fat percentage was 14.7+-3.7, post-op was 14.9 +- 5.4 and control 12.8 +- 4 (n.s.). Lysholm questionnaire results were 77.25, 94.12, and 97.5 (pre-op, post-op and control, respectively, p <. 05 in all comparisons). IKDC results were 59.46, 87.75 and 97.28 (pre-op, post-op and control, respectively, p < .001 in all comparisons). Preop peak torque isokinetic knee extension deficit at 60°/s was 21.5%, postop 15.7% (p=.63) and control 3.1% (p <. 001). CONCLUSION: Professional football players had significantly lower VO2max six months after ACLR compared to controls, although their results were significantly higher than observed pre-operatively. There was a significant improvement in knee function scores after ACLR. Body composition evaluation was not significant different among the groups evaluated

Algumas atividades antrópicas podem provocar alterações nos recursos naturais, seja ela no rio, no solo ou no mar. Os efeitos destas alterações podem ser observados na biota, na qualidade das águas, na disponibilidade de nutrientes, interferindo em todos os elementos que compõem o ecossistema, influenciando-o em maior ou menor grau. O presente estudo procurou determinar o efeito dos poluentes sulfato de zinco, cloreto de amônia, dodecilsulfato de sódio e benzeno, numa espécie bioindicadora marinha, el larvas de mexilhão (Perna perna), além de acrescentar dados sobre a biologia e analisar quimicamente a presença de hidrocarbonetos nos tecidos dos animais adultos e das larvas. Para tanto foram utilizados testes de toxicidade, estudos sobre a bioenergética (consumo de oxigênio e excreção de amônia), enzimas biomarcadoras e excreção de fósforo e nitrogênio. Com relação à biologia, foram encontrados indivíduos sexualmente maduros a partir de 26,1 e 27 mm de comprimento para fêmeas e machos, respectivamente, e há diferença, ainda que esta não seja estatisticamente significativa, entre ovócitos e larvas submetidos a ação de poluentes. A análise de hidrocarbonetos indicou que existe uma contribuição biogênica e petrogênica no litoral norte do Estado de São Paulo. Para as demais análises verificou-se que, quando comparados aos grupos controles, as larvas foram sensíveis e responderam aos diferentes poluentes, geralmente com inibição da atividade. / Some antropic activities may be the cause fo alterations in natural resources, being it river, soil or sea. These alteration effects may be observed in the biota, water quality, nutrients disponibility, interfering with all elements that are part of a ecosystem, with greater or lesser influence degree. The present study was directed to determine the effect of pollutants, such as zinc sulphate, ammonia chlorate, sodium dodecilsulphate and benzene, acting over larvae of a marine bioindicator, the mussel (Perna perna), besides adding data on biology and chemically analysing hidrocarbon presence in larvae and adult animal tissues. In order to obtain these results, toxicity tests were used and bioenergetic (oxygen consumption and ammonia excretion), biomarkers, phosphorus and nitrogen excretion, were studied. As for biology, individuals sexually mature were found starting with 26,1 and 27 mm length females and males, respectively, and there is difference between larvae and ovocites, although statistically not significant, submitted to pollutants action. The hydrocarbon analysis indicates a biogenic and petrogenic contribution to north coast of São Paulo State. For the other analyses the observed results, when compared to control groups, showed that larvae are sensitive, and responded to different pollutants, generally with activity inhibition.

Introdução: A reabilitação cardiopulmonar e metabólica (RCPM) é uma importante estratégia no tratamento da insuficiência cardíaca isquêmica. Entretanto, os seus principais mecanismos de melhora e as correlações com aumento na capacidade de exercício e menos sintomas ainda não estão totalmente esclarecidos. Objetivos: Investigar os efeitos de um programa multidisciplinar de RCPM sobre o tempo de tolerância ao esforço (TLim) e a resposta da fase rápida (fase II) da cinética do consumo de oxigênio (variável relacionada ao desempenho oxidativo muscular) em cardiopatas isquêmicos. Adicionalmente, avaliar as variáveis cardiovasculares, ventilatórias e metabólicas nos TCPE máximo (TRIM) e de endurance (TSCC), além da composição corporal pela bioimpedância elétrica, fração de ejeção (FE) e qualidade de vida. Métodos: Cento e seis pacientes com cardiopatia isquêmica encaminhados ao PRCPM foram submetidos ao TRIM em esteira rolante e, após intervalo de 1 a 7 dias, ao TSCC, com 80% da carga atingida no TRIM. Trinta e sete (37) pacientes foram excluídos, 31 por adesão < 50% às sessões de treinamento, 3 com IMC> 35kg.m-2 e 3 com FE<35%. Após 12 semanas de RCPM, 69 pacientes foram ressubmetidos aos mesmos testes e analisados os efeitos sobre o TLim, fase II da cinética do V\'O2 e a qualidade de vida. Resultados: Os pacientes tiveram evidente redução da sua limitação funcional e 95,6% tornaram-se classe I (pré-RCPM era 62,3%), 4,3% classe II (31,8% antes intervenção) e nenhum mais na classe III da NYHA (5,8% anteriormente), após a intervenção da RCPM. Apresentaram melhora significativa no desempenho ao esforço em ambos protocolos TRIM e TSCC, no entanto, o aumento no tempo de tolerância ao esforço foi quase 3 vezes superior no TSCC. Dentre os diversos sistemas avaliados pelo TCPE, o componente periférico foi o que apresentou melhora mais significativa, principalmente pelo incremento na fase II da cinética do V\'O2, com redução da constante de tempo (tau) ? (p<0,001) e de modo paralelo o mean response time (p <0,001), que engloba também a fase III. Houve redução dos índices isquêmicos ao esforço, bem como da densidade arritmogênica significativa em 37%. Houve melhora significativa em todos os domínios do questionário de vida (p<0,001) e modesta, mas com significância estatística na composição corporal pela BIE com incremento da massa magra e redução da massa gorda após treinamento e, também, da FE. A qualidade de vida se correlacionou com a fase II da cinética do V\'O2 (tau), tanto no sumário físico quanto mental. Na análise de regressão múltipla, o sumário físico pós-RCPM teve como variáveis preditoras a fase II da cinética do V\'O2 e a FE. Conclusões: A RCPM resultou em importantes benefícios fisiológicos e de qualidade de vida aos pacientes com cardiopatia isquêmica com CF predominante I e II. A qualidade de vida esteve associada à obtenção da resposta mais rápida da cinética do V\'O2, que reflete a melhora no metabolismo oxidativo muscular. O treinamento físico regular promoveu retardamento do limiar de isquemia miocárdica e redução da densidade arritmogênica. O TSCC, em relação ao TRIM, detectou ganhos de maior magnitude após o programa de RCPM, como o TLim, e proporcionou a mensuração de novos índices na avaliação das respostas à intervenção do treinamento físico como a cinética do V\'O2 / Introduction: Cardiopulmonary and Metabolic Rehabilitation (CPMR) is an important strategy in the treatment of ischemic heart failure. However, their main mechanisms of improvement and correlations with increased exercise capacity and fewer symptoms are still not fully understood. Objectives: To investigate the effects of a multidisciplinary CPMR program on exercise tolerance time (TLim) and the response of the fast phase (phase II) of the kinetics of oxygen consumption (variable related to muscle oxidative performance) in ischemic cardiomyopathy. Additionally, to evaluate cardiovascular, ventilatory and metabolic variables in maximal (Max) and endurance (End) cardiopulmonary tests, and body composition by bioelectrical impedance analysis, ejection fraction (EF) and quality of life. Methods: One hundred and six patients with ischemic cardiomyopathy referred to CPMR underwent Max on a treadmill and, after an interval of 1 to 7 days, the End with 80% load achieved in Max. Thirty-seven (37) patients were excluded, 31 with participation of <50% in the training sessions, 3 with BMI> 35kg.m-2 and 3 with EF <35%. After 12 weeks of CPMR, 69 patients underwent the same tests and analyzed the effects on TLim. Results: The patients had an evident reduction in functional limitation and 95.6% became Class I (pre-CPMR was 62.3%), 4.3% class II (31.8% before intervention) and no longer in class III (5.8% previously), after the intervention of the CPMR. They had significant improvement in performance when effort on both Max and End protocols, however, the increase in exercise tolerance time was nearly 3 times higher in End. Among the various systems assessed by CPET, peripheral component showed the most significant improvement, especially the increase in the phase II kinetics V\'O2, reducing the time constant (tau) ? (p <0.001) and so parallel the mean response time (p <0.001), which also includes the phase III. There was a reduction of ischemic effort indices as well as the significant arrhythmogenic density by 37%. There was significant improvement in all domains of quality of life (p <0.001) and modest, but with statistical significance, in body composition by bioelectrical impedance with increasing lean mass and decreasing fat mass after training and also the EF. The quality of life was correlated with the phase II kinetics V\'O2 (tau), both physical and mental domains. In multiple regression analysis, the physical summary post CPMR had as predictors phase II kinetics V\'O2 and EF. Conclusions: The CPMR has resulted in important physiological benefits and quality of life for patients with ischemic heart disease with predominant NYHA I and II. The quality of life was associated with obtaining more rapid response kinetics V\'O2, reflecting the improvement in muscle oxidative metabolism. Regular physical training promoted retardation in the threshold of myocardial ischemia and reduced arrhythmogenic density. The End, when compared to Max, detected gains of greater magnitude after CPMR as Tlim, and provided the measurement of new indices in the evaluation of responses to the intervention of physical training as the kinetics of V\'O2

Ziel: war die Untersuchung, ob sich die Aktivität entzündlich rheumatischer Erkrankungen in ausgewählten Parametern des Energiestoffwechsels von PBMC (periphere mononukleäre Zellen des Blutes) reflektiert. Methoden: Es wurden die PBMC von 30 gesunden Probanden und von 28 Patienten (16 inaktiv; 12 aktiv) mit einer Rheumatoiden Arthritis, einem Systemischen Lupus Erythematodes oder einer Vaskulititis präpariert. Aktive Patienten wurden vor und 4-5 Tage nach Beginn einer hochdosierten Glukokortikoidtherapie untersucht. Es wurde der Sauerstoffverbrauch, der Verbrauch an Sauerstoff auf einen definierten mitogenen Stimulus und einzelne Hauptenergieverbrauchende Prozesse mittels der Clark Elektrode bestimmt. Ergebnisse: Für den Sauerstoffverbrauch konnte ein geschlechtsunabhängiger Normalwert von 3.84 +/- 0.1 (alle Werte in nmol O2/min pro 10^7 Zellen) ermittelt werden. Bei inaktiven Patienten war der Sauerstoffverbrauch mit 4.18 +/- 0.28 leicht, bei aktiven Patienten mit 4.82 +/- 0.33 jedoch deutlich und signifikant (p0.05). Desweiteren wurde in stimulierten PBMC von aktiven Patienten eine signifikante Verminderung des Sauerstoffverbrauches für Kationentransportprozesse und Proteinsynthese nachgewiesen. Unter einer 4-5tägigen hochdosierten Glukokortikoidtherapie normalisierten sich die genannten Parameter wieder. Zusammenfassung: In dieser Studie konnte zum ersten Mal gezeigt werden, dass sich Parameter des zellulären Energiestoffwechsels von PBMC zur Einschätzung von Aktivität und Therapieerfolg entzündlich rheumatischer Erkrankungen eignen. / Objective: To investigate whether the activity of rheumatic diseases is reflected by selected parameters of cellular energy metabolism of peripheral blood mononuclear cells (PBMC). Methods: PBMC were prepared from 30 healthy volunteers and from 28 patients (16 inactive; 12 active) with rheumatoid arthritis, systemic lupus erythematosus or vasculitis. Active patients were examined prior to and 4-5 days after starting, restarting or increasing the dose of corticosteroids. Cellular oxygen consumption (as a measure of ATP production), bioenergetic cellular response to a defined stimulus and main ATP-consuming processes were measured using a Clark electrode. Results: A sex-independent normal value for oxygen consumption of 3.84 +/-0.1 (all data in nmol O2/min per 10^7 cells) was found. In inactive patients the respiration rate was slightly increased at 4.18 +/- 0.28, but was significantly increased in active patients to 4.82 +/- 0.33 (p

Der erste Teil der Arbeit beschäftigt sich mit dem Einfluss von Ionenströmen auf die Aktionspotentialgenerierung. Kapitel 1 zeigt den Einfluss der Chloridpermeabilität auf die Response und die Volumenregulation bei äußerer Erregung. In Kapitel 2 zeigen wir, dass passiven Leckströmen, für deren Kompensation neuronale Zellen einen enormen Energieaufwand betreiben, das Membranpotential gegen Fluktuationen in anderen funktionalen Ionenströmen stabilisieren und damit ein gesichertes Verarbeiten und Weiterleiten von Informationen in Form von Aktionspotentialen erst ermöglichen. Der zweite Teil beschäftigt sich mit dem Energiemetabolismus neuronaler Zellen. In Kapitel 3 bestimmen wir den Sauerstoffverbrauch in Hirnschnitten bei verschiedenen Aktivitätszuständen und zeigen, dass das Auftreten einer hämodynamische Response für hohe Aktivitätsformen notwendig ist. Wir schließen daraus, dass das vaskuläre System nur so weit angelegt ist, als es zur Vorsorgung bei hoher energetischer Belastung erforderlich ist. In Kapitel 4 verwenden wir ein von uns entwickeltes Modell des neuronalen Energiestoffwechsels um zu untersuchen, wie die Charakteristiken von NAD(P)H-Fluoreszenzkurven, auf die zelluläre glykolytische und respiratorische Aktivität zurückzuführen sind. Außerdem zeigen wir, wie die Fähigkeit neuronaler Zellen, Lactat alternativ zur Glukose als energielieferndes Substrat zu benutzen, von ihrer glykolytischen und oxidativen Kapazität abhängt. Da in viele neurodegenerativen Erkrankungen eine reduzierte Aktivität des Enzymkomplexes α-ketogluteratedehydrogenase (KGDHC) auftritt, haben wir in Kapitel 5 den Einfluss einer gestörten KGDHC Aktivität auf den neuronalen Energiestoffwechsel untersucht. Wir zeigen, wie eine reduzierte KGDHC Aktivität neuronale Leistungsfähigkeit kompromittiert. Außerdem identifizieren wir mögliche Bildungsstellen für reaktive Sauerstoffspezies (ROS) der Atmungskette und zeigen, dass eine Reduktion der KGDHC Aktivität die Bilddung von ROS vermindert. / The first part of this work deals with the influence of ion currents on the generation of action potentials (APs). Chapter 1 shows the influence of chloride on the fidelity of APs and cellular volume regulation. In chapter 2 we show that sufficiently large leak currents function as important stabilizers of the membrane potential and thus are required to allow robust AP firing. The second part deals with the energy metabolism of neuronal cells. In chapter 3 we determine the relative oxygen consumption rate of hippocampal brain slices under different activity states. We show that a hemodynamic response is necessary for sufficient oxygen supply during highly active states. We conclude that the effort spent on the structure of the vascular system is economized to just match the neuronal energy demand. In chapter 4 we use a model of the neuronal energy metabolism developed by us to show how the characteristics of NAD(P)H fluorescence curves relies on the cellular glycolytic and respirational activity. In addition we show how the ability of neuronal cells to use lactate instead of glucose as energy delivering substrate depends on their respective glycolytic and respiratory activity. Since a reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases, we examined the influence of a reduced KGDHC activity on the neuronal energy metabolism and show how it leads to a compromised neuronal functionality. In addition we developed a detailed kinetic model of the respiratory chain (RC) and identified the possible sites for production of reactive oxygen species (ROS) by the RC. We show that a reduced KGDHC activity should decrease ROS production by the RC.

Introdução: a revisão de literatura aponta que os recém-nascidos submetidos ao banho de imersão produzem menor variação térmica pós-banho comparado aos submetidos ao banho com esponja. No Brasil, o Ministério da Saúde vem capacitando profissionais que atuam em unidades de internação neonatal para implementar o Método Mãe Canguru e, entre outras práticas, recomenda que o recém-nascido pré-termo (RNPT) e com baixo peso seja submetido ao banho de imersão envolto em cueiro ou lençol, sugerindo mudança da prática hegemônica do banho com esponja ou banho de imersão convencional. No entanto, a técnica de banho de imersão recomendada carece de evidências científicas quanto a sua segurança em relação às repercussões na estabilidade da temperatura corporal (T), frequência cardíaca (FC), cortisol salivar (CS) e comportamental em RNPT. Hipótese: os RNPT submetidos ao banho de imersão envoltos em lençol (BIE) apresentam respostas fisiológicas e comportamentais similares aos submetidos à técnica de banho de imersão convencional (BIC), nos primeiros 20 minutos pós-banho. Objetivo: avaliar os parâmetros fisiológicos e comportamentais de RNPT submetidos ao banho de imersão envolto em lençol (BIE) e banho de imersão convencional (BIC). Método: ensaio clínico randomizado cruzado com amostra composta por 43 RNPT, internados na Unidade Neonatal de um hospital escola da cidade de São Paulo. Os RNPT foram alocados no grupo A ou B, seguindo uma lista de randomização gerada pelo software R que foi envelopada e mantida com os auxiliares da pesquisa responsáveis pelos banhos dos RNPT. A randomização definiu a técnica do primeiro banho que o RN seria submetido. Somente após análise dos dados foi aberto o envelope da randomização sendo identificado que no grupo A, o primeiro banho foi o BIC (intervenção controle) e no grupo B, o BIE (intervenção experimental). A técnica do BIE seguiu a técnica recomendada no Manual Atenção Humanizada ao Recém-Nascido de Baixo Peso: Método Mãe-Canguru, publicada pelo Ministério da Saúde. Foram utilizadas filmadoras para obter os valores da FC e da SatO2 registradas pelo monitor cardíaco instalado nos RNPT e para captar imagens das reações comportamentais antes e após os banhos. As temperaturas axilares foram aferidas com termômetro digital e amostras de saliva foram coletadas com esponja oftálmica (Merocel)®, refrigeradas e processada pelo teste Elisa. As filmagens do estado comportamental 10 minutos pré e 10 e 20 minutos pós-banho foram analisadas utilizando o instrumento de avaliação do sono-vigília validado por Brandon e Holditch-Davis. Os dados foram registrados em formulário próprio e armazenados em planilha Microsoft Excel. A análise estatística foi realizada com os programas Minitab, versão 16.1 e SPSS, versão 20. Além da análise descritiva das variáveis numéricas para obtenção de medidas de tendência central e dispersão e frequências absoluta e relativa, foram utilizados os testes Qui-quadrado e Exato de Fisher; o teste T pareado, ANOVA e Modelos Generalizados Lineares na análise dos dados. Resultados: As temperaturas axilares médias dos RNPT pré-BIC e pré-BIE foram, respectivamente, 36,695°C e 36,667°C, p = 0,329. No 10° minuto pós-BIC e BIE, as médias das temperaturas axilares foram, respectivamente, 36,533°C e 36,535°C, p = 0,944. No 20° minuto pós-BIC e BIE, as médias da temperatura axilar foram 36,626°C e 36,628°C, p = 0,663. Houve queda na temperatura axilar no 10° minuto pós-banho, independente do tipo de banho realizado (p <0,001). A hipótese de que o BIE é equivalente ao BIC em relação à variação da temperatura axilar foi confirmada. Houve redução significante nos valores das FC no 10° e 20° minutos pós-BIC e BIE comparados aos valores pré-banho, independente do tipo de banho (p<0,001). Ocorreu aumento gradativo dos valores médios de SatO2 no 10º e 20° minutos após os banhos sem diferenças significantes nos valores pré-banhos, p = 0,969. A concentração do cortisol salivar aumentou após o banho em ambos os grupos, p = 0,001, entretanto não ocorreram diferenças entre os grupos, ou seja, os níveis de cortisol salivar aumentaram após o banho, independente do tipo de banho, p = 0,797. O percentual de tempo em estado sono ativo aumentou após o banho, independente do tipo de banho, p<0,001, ou seja, houve mudança significativa no comportamento do recém-nascido, sem diferenças entre os banhos, p = 0,425. Conclusão: Tanto os RNPT que receberam BIC quanto os que receberam BIE apresentaram queda na temperatura corporal no 10° minuto pós-banho com aumento da temperatura corporal no 20° minuto pós-banho. Comparado aos achados da literatura, a redução da temperatura corporal foi menor que no banho com esponja. O BIE é equivalente ao BIC, portanto ambos são indicados aos RNPT. Convêm salientar o aumento dos custos do BIE em razão do consumo de lençol e da capacitação necessária da equipe de enfermagem nesta técnica de banho, sem prolongar o tempo médio dispendido no banho, visto que poderá reduzir a temperatura da água do banho e consequentemente causar queda na temperatura corporal do RN. / Introduction: the literature review shows that newborns underwent to immersion baths produce less post-bath thermal variation compared to those underwent to the sponge bath. In Brazil, the Ministry of Health has been qualifying working professionals in neonatal hospitalization units to implement the Kangaroo Mother Care and, among other practices, recommends that the preterm newborn infants (PNI) and underweight are underwent to the swaddle immersion bath wrapped in clothes or sheet, suggesting change of the hegemonic practice of sponge bath or conventional immersion bath. However, the immersion bath technique recommended requires more scientific evidence about its safety in relation to impact on the stability of body temperature (T), heart rate (HR), salivary cortisol (SC) and behavioral in PNI. Hypothesis: PNI underwent to swaddle immersion bath wrapped in sheet (SIB) have physiological and behavioral responses similar to those underwent to the conventional immersion bath technique (CIB), in the first 20 minutes post-bath. Objective: To evaluate the physiological and behavioral parameters of preterm newborn infants underwent to swaddle immersion bath in sheet (SIB) and conventional immersion bath (CIB). Method: Randomized crossover clinical trial with a sample of 43 preterm newborn infants in the neonatal unit of a university hospital in the city of Sao Paulo. PNI were allocated in the A or B groups, following a randomization list which was generated by the software R, which was enveloped and maintained with research assistants who were responsible for the baths of PNI. Randomization list defined the first bath technique that the newborn was underwent. The randomization envelope was only opened after data analysis being identified that in group A, the first bath was the CIB (control intervention) and group B, the SIB (experimental intervention). The SIB technique followed the technique recommended in the Humane Care Infant, Low Birth Weight: Kangaroo Mother Care Manual, published by the Ministry of Health of Brazil. Video cameras were used for the HR and SpO2 values recorded at heart monitor installed in the PNI and to capture images of behavioral responses before and after baths. Axillary temperatures were measured with a digital thermometer and saliva samples were collected with ophthalmic sponge (Merocel) ®, refrigerated and processed by the Elisa test. The video recorded of behavioral states of 10 minutes pre-baths and 10 and 20 minutes post-baths were analyzed using the sleep-wake assessment tool validated by Brandon and Holditch-Davis. Data were recorded and stored in the proper form in Microsoft Excel spreadsheet. Statistical analysis was performed using Minitab software, version 16.1 and SPSS, version 20. In addition to the descriptive analysis of numerical variables to obtain measures of central tendency, dispersion, absolute and relative frequencies, Chi-square tests were used and Fisher Exact, the paired T-test, ANOVA and Generalized Linear Models in the data analysis. Results: The mean axillary temperatures of PNI pre-CIB and SIB were respectively 36.695 °C and 36.667 °C, p = 0.329. At 10 minutes post-CIB and SIB, the mean axillary temperatures were, respectively, 36.533 ° C to 36.535 ° C, p = 0.944. At 20 minutes post- CIB and SIB, the average of axillary temperature were 36.626°C and 36.628 ° C, p = 0.663. There was a decrease in the axillary temperature at 10 minutes post-bath, regardless of the type performed bath (p < 0.001). The hypothesis that the SIB is equivalent to the CIB related to the variation in the axillary temperature was confirmed. There was a significant reduction in the HR values at the 10th and 20 th minutes after CIB and SIB compared to pre-bath values, regardless type of the bath (p< 0.001). There was a progressive rise on SpO2 mean values on the 10th and 20 th minutes after baths with no significant differences in pre-baths values, p = 0.969. The salivary cortisol concentrations increased after bathing in both groups, p = 0.001, however there were no differences between the groups, in other words, salivary cortisol levels increased after bathing, regardless of the type of bath, p = 0.797. The percentage of time in active sleep state increased after bathing, regardless of bath type, p <0.001, that is meaning there was significant change in newborn behavior, without differences between baths, p = 0.425. Conclusion: Both the PNI who received CIB, as those receiving SIB, had a decrease in body temperature in the 10th minute post bath followed by an increased body temperature at 20 minutes post-bath. Compared to previous studies, reduction of body temperature was lower than in the sponge bath. The SIB is equivalent to the CIB therefore both are recommended for preterm infants. It should be emphasized the increased in the SIB costs due to the bed sheet consumption and the required nursing staff training in this bath technique, without extending the average time spent in the bath, as it may reduce the temperature of the bath water, consequently causing body temperature drop on the newborn