L’acidose lactique du Saguenay-Lac-St-Jean, ou syndrome de Leigh de forme canadienne-française (LSFC), est une maladie mitochondriale neurodégénérative causée par des mutations du gène LRPPRC et caractérisée par des crises d’acidose menant au décès en bas âge. On ne comprend pas encore les causes exactes de ces crises, et aucun traitement n’est actuellement disponible. L’objectif de cette étude a été de comparer le profil des métabolites sanguins et urinaires chez des sujets LSFC et des témoins, avant et après un repas, par une approche métabolomique ciblée. Le projet s’inscrit dans une démarche à long terme visant l’identification de biomarqueurs prédictifs des crises, permettant d'intervenir plus rapidement afin d’éviter le décès. Les échantillons biologiques ont été prélevés chez 9 sujets atteints du LSFC et 9 témoins appariés, à jeun et 90 minutes après un repas standardisé. Les analyses incluent un bilan biochimique et hormonal, un profil des acides aminés, des acides gras, des acides organiques et des acylcarnitines. Les métabolites significativement modifiés chez les patients peuvent être classés en deux catégories : (i) le reflet d’une dysfonction mitochondriale, et plus particulièrement de l’accumulation d’équivalents réduits en amont de la chaîne respiratoire, et (ii) des indices de risque cardiométabolique, qui s’observent davantage chez les patients adultes malgré leur jeune âge. Ainsi, il serait intéressant d’inclure au traitement des stratégies visant la diminution des facteurs de risque cardiométabolique, notamment par une modification des habitudes de vie. Notre étude démontre la pertinence d’avoir recours à la métabolomique dans l’étude des désordres de la phosphorylation oxydative. / L’acidose lactique du Saguenay-Lac-St-Jean, ou syndrome de Leigh de forme canadienne-française (LSFC), est une maladie mitochondriale neurodégénérative causée par des mutations du gène LRPPRC et caractérisée par des crises d’acidose menant au décès en bas âge. On ne comprend pas encore les causes exactes de ces crises, et aucun traitement n’est actuellement disponible. L’objectif de cette étude a été de comparer le profil des métabolites sanguins et urinaires chez des sujets LSFC et des témoins, avant et après un repas, par une approche métabolomique ciblée. Le projet s’inscrit dans une démarche à long terme visant l’identification de biomarqueurs prédictifs des crises, permettant d'intervenir plus rapidement afin d’éviter le décès. Les échantillons biologiques ont été prélevés chez 9 sujets atteints du LSFC et 9 témoins appariés, à jeun et 90 minutes après un repas standardisé. Les analyses incluent un bilan biochimique et hormonal, un profil des acides aminés, des acides gras, des acides organiques et des acylcarnitines. Les métabolites significativement modifiés chez les patients peuvent être classés en deux catégories : (i) le reflet d’une dysfonction mitochondriale, et plus particulièrement de l’accumulation d’équivalents réduits en amont de la chaîne respiratoire, et (ii) des indices de risque cardiométabolique, qui s’observent davantage chez les patients adultes malgré leur jeune âge. Ainsi, il serait intéressant d’inclure au traitement des stratégies visant la diminution des facteurs de risque cardiométabolique, notamment par une modification des habitudes de vie. Notre étude démontre la pertinence d’avoir recours à la métabolomique dans l’étude des désordres de la phosphorylation oxydative.

La glycogénose de type 1a (GSD1a) est une maladie métabolique rare liée à une absence d’activité glucose‐6 phosphatase (G6Pase). La G6Pase est une enzyme clé de la production endogène de glucose (PEG) catalysant l’hydrolyse du G6P en glucose avant sa libération dans le sang. Cette fonction est restreinte au foie, aux reins et à l’intestin. La GSD1a est caractérisée par des hypoglycémies chroniques, une hépatomégalie associée à une stéatose hépatique et une néphromégalie. A plus longterme, la plupart des patients développent des adénomes. Un modèle murin de GSD 1a existe mais les souris ne survivent pas après le sevrage. Nous avons donc généré un modèle original de GSD1a, en invalidant le gène de la sous‐unité catalytique de la G6Pase spécifiquement dans le foie, grâce à une stratégie CRE‐LOX inductible (souris L‐G6pc‐/‐). Dans ce travail, nous avons montré que les souris L‐G6pc‐/‐ sont viables et reproduisent parfaitement la pathologie hépatique de la GSD1a, y compris le développement d’adénomes hépatiques après 9 mois d’invalidation. La viabilité des souris nous a permis de débuter des traitements par thérapie génique ciblant le foie à l’aide de vecteurs lentiviraux et AAV. La survie de ces souris, qui ne peuvent pas produire du glucose par le foie, repose la question du rôle relatif de la production hépatique de glucose dans la régulation de la glycémie Nous avons montré que les souris L‐G6pc‐/‐ sont capables de réguler leur glycémie, même au cours d’un jeûne prolongé. Ce maintien de l’homéostasie glucidique est due à une induction rapide de la néoglucogenèse rénale et intestinale, principalement par un mécanisme dépendant du glucagon / Glycogen storage disease type 1a (GSD1a) is a rare metabolic disorder due to an absence of glucose‐6 phosphatase (G6Pase) activity. G6Pase is the key enzyme of endogenous glucose production (EGP) and catalyzes the last step before the glucose release into the bloodstream. This function to produce glucose is restricted to the liver, the kidneys and the intestine. GSD1a is characterized by chronic hypoglycemia, hepatomegaly associated with hepatic steatosis and nephromegaly. The longterm complications of G6Pase deficiency include hepatocellular adenomas. The available animal model of GSD1a rarely survive over three months of age and the study of mechanisms of hepatocellular adenomas development cannot be investigated. So, we generated an original mouse model of GSD1a with a liver‐specific invalidation of catalytic subunit of G6Pase gene by an inducible CRE‐LOX strategy (L‐G6pc‐/‐ mice). In this work, we demonstrated that L‐G6pc‐/‐ were viable and totally reproduced the liver pathology of GSD1a, including the late development of hepatocellular adenomas. Then, we have begun liver gene therapy treatment using lentiviral and AAV vectors to correct the hepatic pathology. Finally, concerning glucose homeostasis, we have demonstrated that L‐G6pc‐/‐ were able to regulate blood glucose, during prolonged fast, even in the absence of hepatic glucose production. Rapidly, L‐G6pc‐/‐ mice were able to induce renal and intestinal gluconeogenesis thanks to a key role of glucagon and the development of a metabolic acidosis. These results provide evidence that the major role of the liver for EGP during fasting requires re‐examination

A obstrução uretral é uma condição clínica comum em gatos, caracterizada por alterações metabólicas e do equilíbrio hidroeletrolítico e ácido-básico que são potencialmente fatais. Dentre as causas de obstrução uretral, a cistite idiopática é a mais frequentemente observada em diversos estudos. Outras causas incluem urolitíase, tampões uretrais e infecção do trato urinário. Em muitos casos, os gatos encontram-se em estado crítico e a morte pode ocorrer em decorrência de alterações metabólicas, como estado urêmico avançado e hipercalemia. As principais alterações eletrolíticas e do equilíbrio ácido-básico relatadas são hipercalemia, acidose metabólica, hiponatremia e hipocalcemia ionizada. Embora a obstrução uretral seja muito frequente na rotina clínica, estudos para caracterizar a população de gatos acometida ainda são escassos no Brasil. Características relacionadas ao manejo, dieta e perfil dos tutores podem influenciar na manifestação da doença. Os objetivos do presente estudo foram avaliar os parâmetros clínicos e as alterações hematológicas, bioquímicas, urinárias, eletrolíticas e ácido-básicas presentes em gatos com obstrução uretral e a associação entre estas variáveis. Além disso, objetivou-se conhecer as principais causas de obstrução uretral nos gatos atendidos no Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul. Para isso, foram incluídos no estudo 28 gatos com diagnóstico de obstrução uretral no período de dezembro de 2015 a dezembro de 2016. Foram obtidos dados referentes ao histórico, exame físico, coletados sangue e urina, além da realização de exames de imagem (radiografia e ultrassonografia abdominal). Em todos os gatos foram realizados hemograma, bioquímica sérica, análise de pH, gases e eletrólitos sanguíneos, urinálise e urocultura. Após, todos os pacientes foram tratados de acordo com um protocolo pré-estabelecido. A causa mais comum de obstrução uretral neste estudo foi a cistite idiopática, que ocorreu em mais de 60% dos casos, seguida de tampões uretrais e infecção do trato urinário. Nenhum caso de urolitíase foi diagnosticado, o que pode ser explicado por fatores como idade, ambiente e estilo de vida dos animais. A maioria dos gatos obstruídos apresentou múltiplos sinais sistêmicos, assim como alterações metabólicas, eletrolíticas e do equilíbrio ácido-básico, principalmente azotemia, hiperlactatemia, acidose metabólica, hipercalemia e hipocalcemia ionizada. Hipotermia, depressão do estado mental, bradicardia e desidratação foram os parâmetros clínicos que tiveram maior quantidade de associação com as alterações metabólicas e podem ser considerados bons preditores clínicos destas desordens. Por outro lado, o lactato não foi considerado um bom preditor de alterações clínicas e laboratoriais neste estudo. / Urethral obstruction is a common and potentially life-threatening condition, characterized by severe metabolic, electrolyte and acid-base disturbances. Among the causes of urethral obstruction, idiopathic cystitis is the most frequent in several studies. Other causes include urolithiasis, urethral plugs and urinary tract infection. In many cases, cats are critically ill and death may occur due to metabolic alterations, such as advanced uremic status and hyperkalemia. The main electrolyte and acid-base balance disorders reported are hyperkalemia, metabolic acidosis, hyponatremia and ionized hypocalcemia. Although urethral obstruction is a very common condition, there are few studies characterizing the population affected by the disease in Brazil. Characteristics related to management, diet and owner’s profile can influence the manifestation of the disease. The aim of the present study was to evaluate the association of clinical, haematological, biochemical, urinary, hydroelectrolyte and acid-base parameters in male cats with urethral obstruction. In addition, the objective was to determine the causes of urethral obstruction in male cats admitted to the Veterinary Teaching Hospital of Federal University of Rio Grande do Sul. Twenty-eight cats diagnosed with urethral obstruction were included in the study between December 2015 and December 2016. Data regarding medical history and physical examination were obtained. Blood and urine were collected, and imaging tests were performed (abdominal radiography and ultrasonography). Complete blood count, serum chemistry, blood pH, gas and electrolyte, urinalysis and urine culture were performed. All patients were treated accordingly to a previous established protocol. The most common cause of urethral obstruction in this study was idiopathic cystitis, which occurred in more than 60% of cases, followed by urethral plugs and urinary tract infection. No diagnosis of urolithiasis was achieved which could be explained by factors like age, environment and life style of cats. Most of obstructed cats presented with multiple systemic clinical signs, as well as, metabolic, electrolyte and acid-base alterations. The main disorders found were azotemia, hyperlactatemia, metabolic acidosis, hyperkalemia and ionized hypocalcemia. Hypothermia, depressed mental status, bradycardia and dehydration were the clinical parameters with the greatest amount of associations with the metabolic alterations and can be considered as good predictors of metabolic disorders. On the other hand, lactate was not considered a good predictor of clinical and laboratory abnormalities in this study.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2014-10-09T13:45:17Z No. of bitstreams: 2 Dissertação - Douglas de Almeida Lima - 2011.pdf: 787713 bytes, checksum: 9d4fa1fdcf2f6c61556740302d7ed8c4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2014-10-09T14:42:11Z (GMT) No. of bitstreams: 2 Dissertação - Douglas de Almeida Lima - 2011.pdf: 787713 bytes, checksum: 9d4fa1fdcf2f6c61556740302d7ed8c4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-10-09T14:42:11Z (GMT). No. of bitstreams: 2 Dissertação - Douglas de Almeida Lima - 2011.pdf: 787713 bytes, checksum: 9d4fa1fdcf2f6c61556740302d7ed8c4 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2011-08-26 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / This trial was realized in the veterinary and animal science school at Universidade Federal de Goias. The objective was to evaluate five diets, four of these diets was composed by ground corn with different fiber sources for each ration and one control treatment with whole corn (MI) without fiber source. The fiber sources used was sugar cane bagass (BIN), industrial corn residue silage (RM), soybean hulls (CS), cotton seed (CA). Five castrated Nellore steers with an average of 195 kg of body weight and with rumen fistulae, were used in this trial. The animals were distributed in individual pen provided of individual covered feeder and water tank for each two animals. Each period spent 19 days, with 10 days for food adaptation and nine days for collect of data. During the interval of collects were evaluated: feed behavior, ruminal pH, ammoniacal nitrogen, short chain of fatty acids, total counting of protozoa, fecal pH, total digestibility and dry mater, crude protein (PB), ether extract (EE), neutral detergent fiber (FDN) and acid detergent fiber (FDA) intakes. Latin square and Duncan test for 5% of probability were used for statistical analysis. The treatment BIN had the highest dry matter intake, although CA had the lowest value. The ether extract intake was highest for MI treatment, followed by CA and the CS had the lowest value. The highest values for FDN and FDA intakes were in treatment BIN. It was observed some rejection of cotton seed by the animals. The values for total digestibility for CA, RM, BIN, CS and MI treatments were 68.50; 66.19; 65.87; 64.20 e 56.15. The treatment CA showed greater DMD than CS (P<0.05). The treatments RM and BIN spent more time for ruminating and chewing activity. The value of ruminal pH in treatment BIN was greater than RM and CS (P<0.05). The treatments MI and CA weren´t different from RM and CS (P>0.05). In protozoa counting the highest numbers were observed for CS and BIN treatments. Although the lowest numbers for protozoa counting was founded for CA. Animal differences were noted in protozoa counting. The highest values for total short chain fatty acids were founded for CS, that was the same of RM (P>0.05), although BIN, MI and CA had the lowest value. Highest xiv values for propionate and acetate were found in CS treatment. The acetate:propionate ratios were higher in BIN, but for the others treatments the value didn´t differed between them (P>0.05). Butyrate, ammonia nitrogen and fecal pH any differences were found (P>0.05). It was concluded that sugar cane bagasse was the fiber source that keep a good result for ruminal pH, protozoa counting, dry matter intake and the total digestibility wasn´t different from the others. According to that we can conclude that sugar cane bagasse showed more efficient than the others fiber sources in the tested levels. / O objetivo deste ensaio foi avaliar cinco dietas, sendo quatro delas compostas por milho moído fino e com fontes distintas de fibra para cada ração e um tratamento com milho inteiro (MI). As fontes de fibras utilizadas foram: 1) bagaço de cana in natura (BIN); 2) resíduo de milho verde (RM); 3) casca de soja (CS) e 4) caroço de algodão (CA). Foram utilizados cinco animais castrados da raça Nelore, com peso médio de 195 kg e com fístula ruminal. Os animais foram distribuídos em baias individuais cobertas dotadas de comedouros individuais e bebedouros para cada duas baias. O período experimental teve duração de dezenove dias com dez dias de adaptação e nove dias de coletas. Durante o intervalo de coletas foram avaliados o comportamento ingestivo, o pH ruminal, o nitrogênio amoniacal, os ácidos graxos de cadeia curta, a contagem total de protozoários ruminais, o pH fecal, a digestibilidade no trato total, bem como o consumo de MS, PB, EE, FDN e FDA. O delineamento experimental utilizado foi o quadrado latino 5x5 e para comparações de médias foi utilizados o teste Duncan a 5% de probabilidade. O tratamento BIN teve maior CMS que RM, CS e CA (P<0,05). O consumo de EE do tratamento MI foi maior que CS e RM (P<0,05), porém não diferiu de CA (P>0,05). O maior consumo de FDN foi para o tratamento BIN. O consumo de FDA foram maiores para BIN e RM. Observou-se certa rejeição do caroço de algodão pelos animais, comprovado pelo menor consumo de FDN e FDA no tratamento CA (P<0,05) se igualando ao controle MI (P>0,05). O tratamento CA apresentou uma maior DMS que CS (P<0,05), enquanto que os demais tratamentos não diferiram entre si (P>0,05). Quanto ao comportamento ingestivo, os tratamentos RM e BIN foram os que obtiveram os maiores tempos de atividade mastigatória (p<0,05). O tratamento BIN teve um maior tempo de ruminação que os tratamentos CS e CA (P<0,05). Os valores de pH ruminal para BIN foi maior que RM e CS (P<0,05), porém, não diferiu de MI e CA (P>0,05). Os tratamentos MI e CA não diferiram de RM e CS (P>0,05), quanto ao pH ruminal. Na contagem de protozoários os maiores números foram observados pelos tratamentos CS (P<0,05). Enquanto que o menor número de protozoários foi encontrado no tratamento CA (P<0,05). Houve influência do xii animal nos resultados de contagem de protozoários. Os maiores valores para os ácidos graxos de cadeia curta totais foram encontrados para o tratamento CS, que não diferiu de RM, enquanto que BIN, MI e Ca tiveram as menores produções de ácidos graxos de cadeia curta totais. Foi em CS que encontrou maiores valores de propionato e acetato. Quanto à relação acetato: propionato foi maior para BIN, enquanto que para os demais tratamentos não houve diferença entre si (P>0,05). Quanto ao butirato, ao nitrogênio amoniacal e ao pH fecal não foram encontradas diferenças significativas entre os tratamentos (P>0,05). Conclui-se que o bagaço de cana foi a fonte de fibra que conseguiu manter um bom valor de pH, de contagem de protozoários, além de maior consumo de matéria seca e digestibilidade semelhante aos demais tratamentos. Portanto nos níveis testados o tratamento BIN se mostrou igual ao controle MI, no entanto foi mais eficiente quando comparado das demais fontes de fibras.

L’analyse visuelle du rythme cardiaque fœtal (RCF) est une excellente méthode de dépistage de l’hypoxie fœtale. Cette analyse visuelle est d’autre part sujette à une variabilité inter- et intra-individuelle importante. L’hypoxie fœtale au cours du travail s’exprime par des anomalies du RCF. La sous-évaluation de la gravité d’un RCF entraine une prise de risque indue pour le fœtus avec une augmentation de sa morbi-mortalité et sa surévaluation entraine un interventionnisme obstétrical inutile avec une augmentation du taux de césariennes. Ce dernier point pose par ailleurs en France un problème de santé publique.L’analyse automatisée du signal RCF permet de diminuer la variabilité inter- et intra-individuelle et d’accéder à d’autres paramètres calculés visant à augmenter la valeur diagnostique. Les critères d’analyse morphologiques du RCF (ligne de base, nombre d’accélérations, nombre et typage des ralentissements, variabilité à long terme (VLT)) ont été décrits ainsi que d’autres tels que les surfaces des ralentissements, les indices de variabilité à court terme (VCT) et les analyses fréquentielles. Il n’en demeure pas moins que la définition de la ligne de base, à partir de laquelle sont repérés les accélérations et les ralentissements reste, dans certains cas, difficile à établir.L’objectif principal de la thèse est d’établir un modèle prédictif de l’acidose fœtale à partir d’une analyse automatisée du RCF. L’objectif secondaire est de déterminer la pertinence des différents paramètres élémentaires classiques (CNGOF 2007) (fréquence de base, variabilité, accélérations, ralentissements) et celle d’autres paramètres inaccessible à l’œil (indices de variabilité à court terme, surfaces des ralentissements, analyse fréquentielle…). Par la suite, nous voulons identifier des critères de décision qui aideront à la prise en charge obstétricale.Nous proposons d’aborder l’analyse automatisée du RCF pendant le travail par l’intermédiaire d’une étude cas-témoins ; les cas étant des tracés RCF de nouveau-nés en acidose néonatale (pH artériel au cordon inférieur ou égal à 7,15) et les témoins, des tracés RCF de nouveau-nés sans acidose (pH artériel au cordon supérieur ou égal à 7,25). Il s’agit d’une étude monocentrique à la maternité de l’hôpital Saint Vincent de Paul, GHICL – Lille, sur notre base de données « Bien Naitre » (archivage numérique des tracés RCF depuis 2011), comptant un un nombre suffisant de cas sur ce seul centre. La maternité Saint Vincent de Paul (GHICL) présente depuis 2011 environ 70 cas par an d’acidose néonatale (pHa ≤ 7,10) (3,41%). Le logiciel R sera utilisé pour l’analyse statistique / Visual analysis of the fetal heart rate FHR is a good method for screening for fetal hypoxia but is not sufficiently specific. The visual morphological analysis of the FHR during labor is subject to inter- and intra-observer variability – particularly when the FHR is abnormal. Underestimating the severity of an FHR leads to undue risk-taking for the fetus with an increase in morbidity and mortality and overvaluation leads to unnecessary obstetric intervention with an increased rate of caesarean section. This last point also induces a French public health problem.FHR automated analysis reduces inter and intra-individual variability and accesses other calculated parameters aimed at increasing the diagnostic value. The FHR morphological analysis parameters (baseline, number of accelerations, number and typing of decelerations, long-term variability (LTV)) were described as well as others such as the decelerations surfaces, short-term variability (STV) and frequency analyzes. Nevertheless, when attempting to analyze the FHR automatically, the main problem is computation of the baseline against which all the other parameters are determined.Automatic analysis provides information on parameters that cannot be derived in a visual analysis and that are likely to improve screening for fetal acidosis during labor.The main objective of the thesis is to establish a predictive model of fetal acidosis from a FHR automated analysis. The secondary objective is to determine the relevance of the classical basic parameters (CNGOF 2007) (baseline, variability, accelerations, decelerations) and that of other parameters inaccessible to the eye (indices of short-term variability, surfaces of decelerations, frequency analysis ...). Later, we want to identify decision criteria that will help in the obstetric care management.We propose to validate FHR automated analysis during labor through a case-control study; cases were FHR recordings of neonatal acidosis (arterial cord pH less than or equal to 7.15) and controls, FHR recordings of neonatal without acidosis (arterial cord pH upper than or equal to 7.25). This is a monocentric study at the maternity hospital of Saint Vincent de Paul Hospital, GHICL - Lille, on our « Well Born » database (digital archiving of RCF plots since 2011), with a sufficient number of cases on this only center. Since 2011, the Saint Vincent de Paul hospital (GHICL) has had about 70 cases per year of neonatal acidosis (pHa less than or equal to 7.10) (3.41%). The R software will be used for statistical analysis.

Azidotische Belastungen des Pansens gelten bei Milchkühen besonders in der Frühlaktation als weit verbreitet. Sie werden als subakute Pansenazidosen (SARA) für die häufigen Produktionskrankheiten verantwortlich gemacht. Ziele : dieser Untersuchungen waren a) die Kontrolle des Säure-Basen-Haushalt (SBH) bei HF- Hochleistungskühen im peripartalen Zeitraum zum Vorkommen von SARA, b) die Prüfung bewährter sowie neuer Methoden zur Pansensaftanalyse, c) die Analyse von SBH-Harnparametern sowie d) die Prüfung möglicher Beziehungen von Stoffwechselparametern im Blut zu SBH-Parametern im Pansensaft. Versuchsanordnung : In 10 Betrieben Niedersachsens wurden an je 10 Kühen Verlaufsuntersuchungen mit vier Proben/Tier durchgeführt: 1. Trockenstehperiode/Färsen -30 Tage ante partum (d a.p.) bis zur Kalbung; 2. 2 bis 7 Tage post partum (d p.p.); 3. in der Frühlaktation 8 bis 30 d p.p. und 4. in der Mittellaktation 80 bis 150 d p.p. Pansensaft vormittags mit Geishauser- Sonde gewonnen, Blut aus der V. jugularis externa sowie Harn per Blasenkathederisierung. Analysiert wurden im Pansensaft der pH-Wert, die Pufferkapazität als Titrationsbilanz über die Titrationsazidität und - alkalität, die Methylenblauprobe sowie die Sedimentaktivitätszeit (SAT), im Harn der pH-Wert, die Netto-Säure-Basen-Ausscheidung (NSBA) sowie der Basen-Säure-Quotient (BSQ) und im Blutserum Glukose, freie Fettsäuren (FFS), Betahydroxybutyrat (BHB), L-Laktat, Cholesterol, Protein, Albumin, Bilirubin, Harnstoff, Kreatinin, Na, K, Cl, Ca, P, Mg, ALP, ASAT, GLDH sowie die CK. Ergebnisse: Zwischen Kühen und Färsen wurden bei den gemessenen Parametern keine gesicherten Unterschiede festgestellt. Es gab auch keine Unterschiede zwischen den Betrieben. Die Pansen-pH-Werte bewegten sich von x= 6,8 (6,43/7,0;1./3. Quartil) zu Beginn des Trockenstehens über minimal x = 6,3 (5,9/6,7) 30 bis 60 d p.p. bis x = 6,6 (6,2/6,8) in der Mittellaktation. Sie lagen alle im physiologischen Bereich. 20 Kühe hatten Pansen-pH-Werte von < 5,8, 6 Kühe von < 5,5 und 21 Kühe von > 7,2. Damit kamen die Kühe der SARA-Definition, bezogen auf das einmalige Auftreten von pH-Werten < 5,8 bei einer Kuh, nahe; bezogen auf alle gemessenen Pansen-pH-Werte betrug der Anteil < 5,8 aber nur 9,8 %. Die Titrationsbilanz war in der Trockensteherperiode ausgeglichen; bei allen drei Kontrollen p.p. bestand ein Basendefizit. Die Pufferkapazität war in der 1. Woche p.p. und in der Frühlaktation vermindert. Panse-pH-Werte und Titrationsbilanz korrelierten sehr eng (r=0,98,p<0,001). Die Methylenblauprobe war a.p. mit x = 3:37 (2:22/4:59) Minuten am längsten, in der Mittellaktation mit 3:01 (2:25/4:30) Minuten am kürzesten und ingesamt physiologisch. Es gab keine signifikanten Unterschiede zwischen den einzelnen Kontollzeiträumen. Die SAT war physiologisch und schwankte zwischen zwei und fünf Minuten ohne signifikante Unterschiede zwischen den Entnahmezeiträumen. Im Harn lagen die NSBA mit x = 70 mmol/l (20/122 = 1./3.Quartil) und der BSQ mit x = 2,2 (1,6/2,8) nur bei den Frischmelkern unter den unteren Grenzwerten und deuteten die Gefahr von SARA an. Der Harn-pH-Wert war mit x = 7,98 (7,7/8,2) physiologisch. Von der Gesamtheit alle NSBA-Werte waren 37% < 83 mmol/l sowie 28,9% < 25 mmol/l; beim BSQ waren es 52,6% < 2,5 sowie 27,4% < 1,5. Die für die NSBA, den BSQ und den Harn-pH-Wert berechneten Sensivitäten und Spezifitäten für einen Pansen-pH-Wert < 5,8 liegen mit 44,8% und 64,5% (NSBA), 55,8% und 47,9% (BSQ) sowie 2,3% und 97% (Harn-pH-Wert) unter den diagnostischen Erfordernissen.Sie können somit keine sicheren Rückschlüsse auf den Pansenzustand geben. Bei den Blutbefunden wurden Kühe mit Pansen-pH-Werten < 5,8 (SARA) und >5,8 gegenüber gestellt. Die Korrelationskoeffizienten, die Sensitivität und die mittels Receiver-Operating-Characteristics Analysen ermittelten Flächen unter der Kurve zwischen Pansen-pH-Wert und den Blutparametern waren niedrig ( p> 0,05). Schlussfolgerung: Hochleistende HF-Kühe haben peripartal nicht zwangsläufig eine SARA. Die Titrationsbilanz ergänzt den Pansensaft-pH-Wert, ist routinemäßig aber nicht nötig. Im Harn liegen die NSBA und BSQ häufiger unter den Grenzwerten und korrelieren nicht gesichert mit dem Pansen-pH-Wert. Auch Blutparameter erlauben keine sichere Aussage über den Pansenzustand. Die Diagnose von SARA muss mit direkter Messung des Pansen-pH-Wertes gestellt werden.

A obstrução uretral é uma condição clínica comum em gatos, caracterizada por alterações metabólicas e do equilíbrio hidroeletrolítico e ácido-básico que são potencialmente fatais. Dentre as causas de obstrução uretral, a cistite idiopática é a mais frequentemente observada em diversos estudos. Outras causas incluem urolitíase, tampões uretrais e infecção do trato urinário. Em muitos casos, os gatos encontram-se em estado crítico e a morte pode ocorrer em decorrência de alterações metabólicas, como estado urêmico avançado e hipercalemia. As principais alterações eletrolíticas e do equilíbrio ácido-básico relatadas são hipercalemia, acidose metabólica, hiponatremia e hipocalcemia ionizada. Embora a obstrução uretral seja muito frequente na rotina clínica, estudos para caracterizar a população de gatos acometida ainda são escassos no Brasil. Características relacionadas ao manejo, dieta e perfil dos tutores podem influenciar na manifestação da doença. Os objetivos do presente estudo foram avaliar os parâmetros clínicos e as alterações hematológicas, bioquímicas, urinárias, eletrolíticas e ácido-básicas presentes em gatos com obstrução uretral e a associação entre estas variáveis. Além disso, objetivou-se conhecer as principais causas de obstrução uretral nos gatos atendidos no Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul. Para isso, foram incluídos no estudo 28 gatos com diagnóstico de obstrução uretral no período de dezembro de 2015 a dezembro de 2016. Foram obtidos dados referentes ao histórico, exame físico, coletados sangue e urina, além da realização de exames de imagem (radiografia e ultrassonografia abdominal). Em todos os gatos foram realizados hemograma, bioquímica sérica, análise de pH, gases e eletrólitos sanguíneos, urinálise e urocultura. Após, todos os pacientes foram tratados de acordo com um protocolo pré-estabelecido. A causa mais comum de obstrução uretral neste estudo foi a cistite idiopática, que ocorreu em mais de 60% dos casos, seguida de tampões uretrais e infecção do trato urinário. Nenhum caso de urolitíase foi diagnosticado, o que pode ser explicado por fatores como idade, ambiente e estilo de vida dos animais. A maioria dos gatos obstruídos apresentou múltiplos sinais sistêmicos, assim como alterações metabólicas, eletrolíticas e do equilíbrio ácido-básico, principalmente azotemia, hiperlactatemia, acidose metabólica, hipercalemia e hipocalcemia ionizada. Hipotermia, depressão do estado mental, bradicardia e desidratação foram os parâmetros clínicos que tiveram maior quantidade de associação com as alterações metabólicas e podem ser considerados bons preditores clínicos destas desordens. Por outro lado, o lactato não foi considerado um bom preditor de alterações clínicas e laboratoriais neste estudo. / Urethral obstruction is a common and potentially life-threatening condition, characterized by severe metabolic, electrolyte and acid-base disturbances. Among the causes of urethral obstruction, idiopathic cystitis is the most frequent in several studies. Other causes include urolithiasis, urethral plugs and urinary tract infection. In many cases, cats are critically ill and death may occur due to metabolic alterations, such as advanced uremic status and hyperkalemia. The main electrolyte and acid-base balance disorders reported are hyperkalemia, metabolic acidosis, hyponatremia and ionized hypocalcemia. Although urethral obstruction is a very common condition, there are few studies characterizing the population affected by the disease in Brazil. Characteristics related to management, diet and owner’s profile can influence the manifestation of the disease. The aim of the present study was to evaluate the association of clinical, haematological, biochemical, urinary, hydroelectrolyte and acid-base parameters in male cats with urethral obstruction. In addition, the objective was to determine the causes of urethral obstruction in male cats admitted to the Veterinary Teaching Hospital of Federal University of Rio Grande do Sul. Twenty-eight cats diagnosed with urethral obstruction were included in the study between December 2015 and December 2016. Data regarding medical history and physical examination were obtained. Blood and urine were collected, and imaging tests were performed (abdominal radiography and ultrasonography). Complete blood count, serum chemistry, blood pH, gas and electrolyte, urinalysis and urine culture were performed. All patients were treated accordingly to a previous established protocol. The most common cause of urethral obstruction in this study was idiopathic cystitis, which occurred in more than 60% of cases, followed by urethral plugs and urinary tract infection. No diagnosis of urolithiasis was achieved which could be explained by factors like age, environment and life style of cats. Most of obstructed cats presented with multiple systemic clinical signs, as well as, metabolic, electrolyte and acid-base alterations. The main disorders found were azotemia, hyperlactatemia, metabolic acidosis, hyperkalemia and ionized hypocalcemia. Hypothermia, depressed mental status, bradycardia and dehydration were the clinical parameters with the greatest amount of associations with the metabolic alterations and can be considered as good predictors of metabolic disorders. On the other hand, lactate was not considered a good predictor of clinical and laboratory abnormalities in this study.

A obstrução uretral é uma condição clínica comum em gatos, caracterizada por alterações metabólicas e do equilíbrio hidroeletrolítico e ácido-básico que são potencialmente fatais. Dentre as causas de obstrução uretral, a cistite idiopática é a mais frequentemente observada em diversos estudos. Outras causas incluem urolitíase, tampões uretrais e infecção do trato urinário. Em muitos casos, os gatos encontram-se em estado crítico e a morte pode ocorrer em decorrência de alterações metabólicas, como estado urêmico avançado e hipercalemia. As principais alterações eletrolíticas e do equilíbrio ácido-básico relatadas são hipercalemia, acidose metabólica, hiponatremia e hipocalcemia ionizada. Embora a obstrução uretral seja muito frequente na rotina clínica, estudos para caracterizar a população de gatos acometida ainda são escassos no Brasil. Características relacionadas ao manejo, dieta e perfil dos tutores podem influenciar na manifestação da doença. Os objetivos do presente estudo foram avaliar os parâmetros clínicos e as alterações hematológicas, bioquímicas, urinárias, eletrolíticas e ácido-básicas presentes em gatos com obstrução uretral e a associação entre estas variáveis. Além disso, objetivou-se conhecer as principais causas de obstrução uretral nos gatos atendidos no Hospital de Clínicas Veterinárias da Universidade Federal do Rio Grande do Sul. Para isso, foram incluídos no estudo 28 gatos com diagnóstico de obstrução uretral no período de dezembro de 2015 a dezembro de 2016. Foram obtidos dados referentes ao histórico, exame físico, coletados sangue e urina, além da realização de exames de imagem (radiografia e ultrassonografia abdominal). Em todos os gatos foram realizados hemograma, bioquímica sérica, análise de pH, gases e eletrólitos sanguíneos, urinálise e urocultura. Após, todos os pacientes foram tratados de acordo com um protocolo pré-estabelecido. A causa mais comum de obstrução uretral neste estudo foi a cistite idiopática, que ocorreu em mais de 60% dos casos, seguida de tampões uretrais e infecção do trato urinário. Nenhum caso de urolitíase foi diagnosticado, o que pode ser explicado por fatores como idade, ambiente e estilo de vida dos animais. A maioria dos gatos obstruídos apresentou múltiplos sinais sistêmicos, assim como alterações metabólicas, eletrolíticas e do equilíbrio ácido-básico, principalmente azotemia, hiperlactatemia, acidose metabólica, hipercalemia e hipocalcemia ionizada. Hipotermia, depressão do estado mental, bradicardia e desidratação foram os parâmetros clínicos que tiveram maior quantidade de associação com as alterações metabólicas e podem ser considerados bons preditores clínicos destas desordens. Por outro lado, o lactato não foi considerado um bom preditor de alterações clínicas e laboratoriais neste estudo. / Urethral obstruction is a common and potentially life-threatening condition, characterized by severe metabolic, electrolyte and acid-base disturbances. Among the causes of urethral obstruction, idiopathic cystitis is the most frequent in several studies. Other causes include urolithiasis, urethral plugs and urinary tract infection. In many cases, cats are critically ill and death may occur due to metabolic alterations, such as advanced uremic status and hyperkalemia. The main electrolyte and acid-base balance disorders reported are hyperkalemia, metabolic acidosis, hyponatremia and ionized hypocalcemia. Although urethral obstruction is a very common condition, there are few studies characterizing the population affected by the disease in Brazil. Characteristics related to management, diet and owner’s profile can influence the manifestation of the disease. The aim of the present study was to evaluate the association of clinical, haematological, biochemical, urinary, hydroelectrolyte and acid-base parameters in male cats with urethral obstruction. In addition, the objective was to determine the causes of urethral obstruction in male cats admitted to the Veterinary Teaching Hospital of Federal University of Rio Grande do Sul. Twenty-eight cats diagnosed with urethral obstruction were included in the study between December 2015 and December 2016. Data regarding medical history and physical examination were obtained. Blood and urine were collected, and imaging tests were performed (abdominal radiography and ultrasonography). Complete blood count, serum chemistry, blood pH, gas and electrolyte, urinalysis and urine culture were performed. All patients were treated accordingly to a previous established protocol. The most common cause of urethral obstruction in this study was idiopathic cystitis, which occurred in more than 60% of cases, followed by urethral plugs and urinary tract infection. No diagnosis of urolithiasis was achieved which could be explained by factors like age, environment and life style of cats. Most of obstructed cats presented with multiple systemic clinical signs, as well as, metabolic, electrolyte and acid-base alterations. The main disorders found were azotemia, hyperlactatemia, metabolic acidosis, hyperkalemia and ionized hypocalcemia. Hypothermia, depressed mental status, bradycardia and dehydration were the clinical parameters with the greatest amount of associations with the metabolic alterations and can be considered as good predictors of metabolic disorders. On the other hand, lactate was not considered a good predictor of clinical and laboratory abnormalities in this study.

Les reins jouent un rôle majeur dans la régulation de l'homéostasie acide-base. La production et l'excrétion rénale d'ammonium assurent environ deux tiers de l'excrétion nette d'acides dans les conditions normales et jusqu'à 90% en situation d'acidose métabolique. Bien que l'excrétion d'ammonium soit un processus finement régulé et capital au maintien de l'équilibre acido-basique, à ce jour aucun transporteur spécifique d'ammonium n'a été décrit chez les mammifères. Les protéines Rhésus Rhcg et Rhbg, membres distants de la famille des transporteurs d'ammonium Mep/Amt, semblaient de bons candidats à cette fonction. L'invalidation du gène Rhcg puis celle de Rhbg ont donc été entreprises chez la souris afin d'estimer leur rôle potentiel dans le transport de l'ammonium. / Doctorat en sciences, Spécialisation biologie moléculaire / info:eu-repo/semantics/nonPublished

Azidotische Belastungen des Pansens gelten bei Milchkühen besonders in der Frühlaktation als weit verbreitet. Sie werden als subakute Pansenazidosen (SARA) für die häufigen Produktionskrankheiten verantwortlich gemacht. Ziele : dieser Untersuchungen waren a) die Kontrolle des Säure-Basen-Haushalt (SBH) bei HF- Hochleistungskühen im peripartalen Zeitraum zum Vorkommen von SARA, b) die Prüfung bewährter sowie neuer Methoden zur Pansensaftanalyse, c) die Analyse von SBH-Harnparametern sowie d) die Prüfung möglicher Beziehungen von Stoffwechselparametern im Blut zu SBH-Parametern im Pansensaft. Versuchsanordnung : In 10 Betrieben Niedersachsens wurden an je 10 Kühen Verlaufsuntersuchungen mit vier Proben/Tier durchgeführt: 1. Trockenstehperiode/Färsen -30 Tage ante partum (d a.p.) bis zur Kalbung; 2. 2 bis 7 Tage post partum (d p.p.); 3. in der Frühlaktation 8 bis 30 d p.p. und 4. in der Mittellaktation 80 bis 150 d p.p. Pansensaft vormittags mit Geishauser- Sonde gewonnen, Blut aus der V. jugularis externa sowie Harn per Blasenkathederisierung. Analysiert wurden im Pansensaft der pH-Wert, die Pufferkapazität als Titrationsbilanz über die Titrationsazidität und - alkalität, die Methylenblauprobe sowie die Sedimentaktivitätszeit (SAT), im Harn der pH-Wert, die Netto-Säure-Basen-Ausscheidung (NSBA) sowie der Basen-Säure-Quotient (BSQ) und im Blutserum Glukose, freie Fettsäuren (FFS), Betahydroxybutyrat (BHB), L-Laktat, Cholesterol, Protein, Albumin, Bilirubin, Harnstoff, Kreatinin, Na, K, Cl, Ca, P, Mg, ALP, ASAT, GLDH sowie die CK. Ergebnisse: Zwischen Kühen und Färsen wurden bei den gemessenen Parametern keine gesicherten Unterschiede festgestellt. Es gab auch keine Unterschiede zwischen den Betrieben. Die Pansen-pH-Werte bewegten sich von x= 6,8 (6,43/7,0;1./3. Quartil) zu Beginn des Trockenstehens über minimal x = 6,3 (5,9/6,7) 30 bis 60 d p.p. bis x = 6,6 (6,2/6,8) in der Mittellaktation. Sie lagen alle im physiologischen Bereich. 20 Kühe hatten Pansen-pH-Werte von < 5,8, 6 Kühe von < 5,5 und 21 Kühe von > 7,2. Damit kamen die Kühe der SARA-Definition, bezogen auf das einmalige Auftreten von pH-Werten < 5,8 bei einer Kuh, nahe; bezogen auf alle gemessenen Pansen-pH-Werte betrug der Anteil < 5,8 aber nur 9,8 %. Die Titrationsbilanz war in der Trockensteherperiode ausgeglichen; bei allen drei Kontrollen p.p. bestand ein Basendefizit. Die Pufferkapazität war in der 1. Woche p.p. und in der Frühlaktation vermindert. Panse-pH-Werte und Titrationsbilanz korrelierten sehr eng (r=0,98,p<0,001). Die Methylenblauprobe war a.p. mit x = 3:37 (2:22/4:59) Minuten am längsten, in der Mittellaktation mit 3:01 (2:25/4:30) Minuten am kürzesten und ingesamt physiologisch. Es gab keine signifikanten Unterschiede zwischen den einzelnen Kontollzeiträumen. Die SAT war physiologisch und schwankte zwischen zwei und fünf Minuten ohne signifikante Unterschiede zwischen den Entnahmezeiträumen. Im Harn lagen die NSBA mit x = 70 mmol/l (20/122 = 1./3.Quartil) und der BSQ mit x = 2,2 (1,6/2,8) nur bei den Frischmelkern unter den unteren Grenzwerten und deuteten die Gefahr von SARA an. Der Harn-pH-Wert war mit x = 7,98 (7,7/8,2) physiologisch. Von der Gesamtheit alle NSBA-Werte waren 37% < 83 mmol/l sowie 28,9% < 25 mmol/l; beim BSQ waren es 52,6% < 2,5 sowie 27,4% < 1,5. Die für die NSBA, den BSQ und den Harn-pH-Wert berechneten Sensivitäten und Spezifitäten für einen Pansen-pH-Wert < 5,8 liegen mit 44,8% und 64,5% (NSBA), 55,8% und 47,9% (BSQ) sowie 2,3% und 97% (Harn-pH-Wert) unter den diagnostischen Erfordernissen.Sie können somit keine sicheren Rückschlüsse auf den Pansenzustand geben. Bei den Blutbefunden wurden Kühe mit Pansen-pH-Werten < 5,8 (SARA) und >5,8 gegenüber gestellt. Die Korrelationskoeffizienten, die Sensitivität und die mittels Receiver-Operating-Characteristics Analysen ermittelten Flächen unter der Kurve zwischen Pansen-pH-Wert und den Blutparametern waren niedrig ( p> 0,05). Schlussfolgerung: Hochleistende HF-Kühe haben peripartal nicht zwangsläufig eine SARA. Die Titrationsbilanz ergänzt den Pansensaft-pH-Wert, ist routinemäßig aber nicht nötig. Im Harn liegen die NSBA und BSQ häufiger unter den Grenzwerten und korrelieren nicht gesichert mit dem Pansen-pH-Wert. Auch Blutparameter erlauben keine sichere Aussage über den Pansenzustand. Die Diagnose von SARA muss mit direkter Messung des Pansen-pH-Wertes gestellt werden.