Orientador: Madileine Francely Américo / Resumo: A contratilidade do músculo liso e o trânsito gastrintestinal (GI) são importantes parâmetros da motilidade, cujas alterações podem comprometer a absorção de nutrientes e a biodisponibilidade de fármacos. Diversos fármacos apresentam efeitos adversos associados ao trato GI e, mesmo aqueles utilizados para controlar esses efeitos, podem provocar alterações importantes na motilidade ainda pouco conhecidas. Camundongos das linhagens C57BL/6 e BALB/c são amplamente utilizados nas pesquisas biomédicas, entretanto poucos estudos consideram os parâmetros motores GI. Diante de métodos escassos para avaliar a motilidade in vivo e da importância de conhecer a fisiologia básica dos camundongos, bem como o efeito de fármacos sobre o trato GI, objetivou-se: 1) desenvolver protocolo para avaliação da contratilidade duodenal e trânsito gastrintestinal por meio da Biosusceptometria de Corrente Alternada (BAC), e avaliar comparativamente a morfologia e função gastrintestinal de camundongos das linhagens BALB/c e C57BL/6J e, 2) avaliar o efeito GI do tratamento com cisplatina e a influência da dexametasona como antiemético. A partir deste trabalho foi possível implementar um protocolo experimental inédito, por meio da BAC, para avaliar a contratilidade duodenal e o trânsito gastrintestinal em camundongos. Após prévia implantação de marcador magnético no duodeno de camundongos, observou-se uma alta e uma baixa frequência de contração, expressas em ciclos por minuto (cpm). BALB/c e C57BL/6J apre... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The smooth muscle contractility and gastrointestinal (GI) transit are important parameters of motility, whose alterations may compromise nutrient absorption and bioavailability of drugs. Several drugs have side effects associated with the GI tract and, even those used to control these effects may cause significant changes in motility that are still poorly understood. Mice C57BL/6 and BALB/c strains are widely used in biomedical research, but a few studies consider the GI motor parameters. In front of scarce methods to evaluate the in vivo motility and the importance of knowing the basic physiology of the mice, as well as the effect of drugs on the GI tract. Then, the objectives of this study were 1) to develop protocol for the evaluation of duodenal contractility and gastrointestinal transit through Alternating Current Biosusceptometry (ACB), and comparing the morphology and gastrointestinal function of BALB/c and C57BL/6J mice, and 2) to evaluate the GI effect of cisplatin treatment and the influence of dexamethasone as an antiemetic. From this work, it was possible to implement an original experimental protocol, through the BAC, to evaluate the duodenal contractility and the gastrointestinal transit in mice. After the previous implantation of a magnetic marker in the duodenum of mice, a high and low frequency of contraction, expressed in cycles per minute (cpm), was observed. BALB/c and C57BL/6J presented a high frequency of 40 cpm, while the low frequency in BALB/c was 29 ... (Complete abstract click electronic access below) / Doutor

This thesis presents studies relating to effects of different macronutrients, predominantly fat and carbohydrate, on gastrointestinal motility, hormone release/suppression, appetite and energy intake in healthy subjects, and on symptom generation in patients with functional dyspepsia. The three broad areas that have been investigated in these studies are: (i) the effect of load, and duration, of small intestinal nutrient exposure on gastric motility, gastrointestinal hormone release/suppression, appetite and energy intake in healthy subjects, (ii) the dietary factors that may contribute to symptom generation in patients with functional dyspepsia, through analysis of diet diaries and acute nutrient challenges, and (iii) the effects of the herbal medication, Iberogast®, on gastric motility in healthy subjects. The ingestion of nutrients, triggers a number of gastrointestinal responses, including the modulation of antropyloroduodenal motility, gastrointestinal hormone release/suppression, and the suppression of appetite and energy intake, resulting in a slowing of gastric emptying to an average rate of 1 - 3 kcal/min, which is required for efficient nutrient digestion and absorption. Additionally, the rate at which glucose enters the small intestine influences postprandial glycaemia and incretin responses. These responses have been demonstrated in animals to be dependent on the length, and region, of the small intestine exposed to fat and glucose, however, this has not been directly investigated in humans. Functional dyspepsia is a clinical condition, characterised by chronic upper abdominal symptoms, such as nausea, bloating and early fullness, without a known cause, which affects approximately 11 - 29 % of the population. Many studies have reported that disturbed gastric motor activity may be the cause of these symptoms, but patients frequently experience symptoms following ingestion of food, and some patients report to eat smaller meals more frequently and avoid fatty and spicy foods. In addition, laboratory-based studies have indicated that functional dyspepsia patients may be hypersensitive to fat, but not carbohydrate. To date, the treatments used to reduce symptoms are frequently directed at the normalisation of gastroduodenal motility, using prokinetics. However, the beneficial effect of these drugs is relatively small and variable, and their adverse effects can be substantial. Herbal drug preparations have recently received considerable interest as an alternative treatment option in functional dyspepsia. A commercially available herbal preparation, Iberogast® which contains nine plant extracts, has been reported to improve upper abdominal symptoms in functional dyspepsia and to decrease fundic tone, increase antral contractility and decrease afferent nerve sensitivity in experimental animals. The effects of Iberogast® in the human gastrointestinal tract have not been investigated. The first three studies presented in this thesis have focused on the effects of delivering fat and glucose into the small intestine at different loads (Chapter 5, 6 and 7), lower, comparable to, and higher than gastric emptying normally occurs, and at different durations of infusion (but still at similar caloric loads - Chapter 5, fat only), on gastrointestinal motility, plasma hormone release/suppression, glycaemia, and energy intake in healthy male subjects. The study in Chapter 5 demonstrated that antral pressure waves and pressure wave sequences were suppressed, and basal pyloric pressure, isolated pyloric pressure waves, and plasma cholecystokinin and peptide YY stimulated, during both the low (1.33 kcal/min for 50 min: 67 kcal/min), and high (4 kcal/min for 50 min: 200 kcal), loads of lipid. The effect of the 4 kcal/min load was sustained so that the suppression of antral pressure waves and pressure wave sequences and increase in peptide YY remained evident after cessation of the infusion. The prolonged lipid infusion (1.33 kcal/min for 150 min: 200 kcal) suppressed antral pressure waves, stimulated cholecystokinin and peptide YY and basal pyloric pressure and tended to stimulate isolated pyloric pressure waves when compared with saline throughout the entire infusion period. These results indicate that both the load, and duration, of small intestinal lipid have an influence on antropyloroduodenal motility and patterns of cholecystokinin and peptide YY release. Chapter 6 demonstrated that lipid loads lower than gastric emptying normally occurs (0.25 kcal/min for 50 min: 12.5 kcal) transiently stimulated isolated pyloric pressure waves and cholecystokinin release and suppressed pressure wave sequences and hunger scores. Loads comparable to (1.5 kcal/min for 50 min: 75 kcal) and higher (4 kcal/min for 50 min: 200 kcal), than the normal rate of gastric emptying, were required to stimulate basal pyloric tone and peptide YY release and suppress antral and duodenal pressure waves. Only the 4 kcal/min load suppressed energy intake. The effects of lipid on all parameters, with the exception of hunger, were load-dependent. In addition, there were relationships between antropyloroduodenal motility and cholecystokinin and peptide YY concentrations with energy/food intake. The study in Chapter 7 demonstrated that loads of glucose lower than (1 kcal/min for 120 min: 120 kcal), comparable to (2 kcal/min for 120 min: 240 kcal) and higher than (4 kcal/min for 120 min: 480 kcal) the rate gastric emptying normally occurs, stimulated blood glucose, plasma insulin, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and cholecystokinin concentrations and suppressed the number of antral pressure waves, 2 and 4 kcal/min loads were required for the suppression of duodenal pressure waves and pressure wave sequences and the stimulation of basal pyloric pressure and suppression of energy intake only after the 4 kcal/min loads. There were also relationships between glucagon-like peptide-1 and glucose-dependent insulinotropic peptide with basal pyloric tone, and food/energy intake with pyloric pressures. The studies presented in the subsequent three chapters investigated the contribution of dietary factors on the generation of symptoms in patients with functional dyspepsia when compared with healthy subjects (Chapter 8 and 9) and the effect of Iberogast® on motility in the healthy gastrointestinal tract (Chapter 10). The effects of equi-caloric high-carbohydrate vs. high-fat yoghurt preloads on symptom generation, plasma hormone concentrations, antral area and energy intake were compared between functional dyspepsia patients and healthy subjects (Chapter 8). Nausea and pain were greater in patients after the high-fat, when compared with high-carbohydrate and control, preloads and with healthy subjects. Discomfort was greater after all preloads in patients when compared with healthy subjects. Fasting cholecystokinin and stimulation of cholecystokinin by the high-fat preload were greater in patients, while fasting and postprandial peptide YY were lower in patients than in healthy subjects, with no differences in fasting, or postprandial, plasma ghrelin between patients and healthy subjects. Fasting antral area was greater in patients, with no differences postprandially between patients and healthy subjects. There were no differences in energy intake between the two groups. The relationship between the effect of dietary intake and eating behaviour over a 7-day period on the occurrence and severity of abdominal symptoms was compared between patients and healthy subjects (Chapter 9). The symptoms experienced by the patients included nausea, fullness discomfort, bloating and upper abdominal, and epigastric, pain, of a modest severity, which occurred within 30 min of eating. The number of “meals” ingested was significantly less in functional dyspepsia patients and there was a trend for total energy and fat intake to be less. The occurrence of these symptoms was also statistically related to the ingestion of fat and energy intake. The results of these studies indicate that diet, particularly the ingestion of fat, influences the development of symptoms in a subgroup of patients with functional dyspepsia. The study in Chapter 10 evaluated the effect of the herbal drug Iberogast® on gastric motility in the gastrointestinal tract. Iberogast® increased proximal gastric volume, increased antral pressure waves without affecting pyloric or duodenal pressures, and slightly increased the retention of liquid in the total stomach, but had no effect on gastric emptying of solids or intragastric distribution. These results demonstrate that Iberogast® affects gastric motility in humans, and the stimulation of gastric relaxation and antral motility may contribute to the reported therapeutic efficacy of Iberogast® in functional dyspepsia. The studies reported in this thesis provide new information about the regulation of gastric motility, hormone release/suppression, appetite and energy intake, by varying the loads of lipid and glucose infused into the small intestine in healthy subjects, which may have implications in patients with altered gastric motor functions, such as obese, type-2 diabetes and functional dyspepsia patients. In addition, studies in functional dyspepsia patients revealed that diet, in particular the ingestion of fat, contribute to the cause of their symptoms, and these findings may have important implications for the development of diet-based therapies for the treatment of functional dyspepsia. Furthermore, functional dyspepsia patients with impaired gastric relaxation and antral dysmotility may benefit from the effects of Iberogast® as demonstrated in the healthy gastrointestinal tract. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1331606 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, 2008

Efter operation och anestesi får patienter ofta en negativ påverkan på magsäck och tarmar. Illamående och kräkningar är ett stort problem och många har svårt att komma igång med intag av föda och normal tarmfunktion då magsäcken och tarmarna ”står stilla”. Flera faktorer bidrar- bl.a. smärtan, det kirurgiska traumat och de läkemedel vi ger i samband med anestesin. Av de senare är opioider, d.v.s morfin och morfinliknande läkemedel, starkt bidragande. I detta avhandlings- arbete har opioiders effekter på magsäckens motilitet studerats. Med ett absorptionstest (paracetamolmetoden) studerades hos frivilliga hur opioiden remifentanil påverkar magsäckstömning och om kroppspositionen har betydelse för tömningshastigheten ut i tarmen. Remifentanil fördröjde magsäcks-tömningen och under pågående opioid behandling hade kroppspositionen ingen större betydelse, vilket det däremot hade under kontrollförsöken. Med samma metod jämförde vi hos patienter två anestesimetoder och studerade magsäcks-tömning direkt efter en operation. Ingen skillnad kunde påvisas mellan en opioidbaserad och en opioidfri anestesi, men inom respektive grupp var det en stor variation i magsäckstömning mellan individerna. Med en barostat studerades tonus i övre delen av magsäcken. Hos hälften av de frivilliga orsakade remifentanil en ökning av tonus och hos den andra hälften en minskning av tonus. Vidare undersöktes hos en grupp patienter opioiden fentanyls påverkan på den elektriska aktiviteten i magsäcken. Med en elekroga-strograf (EGG) registrerades de långsamma elektriska vågor som koordinerar muskelrörelserna i magsäcken. Hos hälften av de undersökta påverkades aktiviteten av fentanyl med en sänkt vågfrekvens eller upphörande av vågor, medan aktiviteten var opåverkad hos den övriga hälften. För att finna en förklaring till variationen gjordes genetiska analyser av genen för opioidreceptorn hos de undersökta i barostat och EGG studierna. Variationer i genomet, s.k. polymorfism, var inte associerad till utfallen i studierna. Studierna har visat på att opioider har en uttalad effekt på magsäckens motilitet och att den varierar kraftigt mellan individer. Polymorfism i genen för opioid- receptorn förklarade inte skillnaden mellan individer. Direkt efter operation bidrar sannolikt andra faktorer än anestesimetod till det variabla utfallet i magsäckstömning. / After anesthesia and/or surgical procedures, gastrointestinal motility is commonly impaired. The causes are multifactorial, with surgical trauma, pain and perioperative drugs playing a major role. This thesis explores opioid effects on gastric motility in healthy volunteers and patients undergoing surgery. Gastric emptying was studied by an absorption test (paracetamol method), and in healthy volunteers a remifentanil infusion delayed gastric emptying. Body position altered emptying during the control situations, but not during the remifentanil infusion. Further, two anesthetic methods were compared and no differences were found in immediate postoperative gastric emptying between a remifentanil/propofol based intravenous anesthesia and an opioid free inhalational anesthesia, although the interindividual variability was high. Proximal gastric tone was studied using a gastric barostat. An infusion of remifentanil caused two patterns of reaction regarding gastric tone, with half of the subjects increasing and half decreasing in gastric tone. Gastric myoelectrical activity was evaluated with electrogastrography (EGG), and a bolus dose of fentanyl caused a decrease in frequency of the gastric slow waves or disrupted this activity. However, the activity was unaffected in half of the investigated subjects. Analysis of polymorphisms (A118G and G691C) in the µ-opioid receptor gene was performed to find an explanation for the great interindividual variations seen in the barostat and EGG studies, but no association could be found. These studies have shown that opioids have pronounced effects on gastric motility with variable individual responses that are difficult to predict. Polymorphisms in the µ-opioid receptor gene could not explain the variations. Postoperatively, other factors might contribute more than opioids to the impairment in gastric motility. / ISSN 1652-4063

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / In humans, intracranial hypertension (ICH) disturbs cardiovascular function and also modifies gastrointestinal physiology as clinically manifested by nausea and vomiting symptoms. Since gastric compliance drives the gastric emptying of liquid which is inhibited by ICH, it was studied the ICH effect on gastric compliance behavior in anesthetized rats and the neuropathways possibly serving this phenomenon. Anesthetized male Wistar rats (N=65, 280-320g) received a carotid cannula to monitor arterial pressure (AP) and heart rate (HR). Under stereotactic guidance a cannula was positioned into each lateral ventricule: one for cerebrospinal fluid simile infusion and the other to record intracranial pressure (ICP in mmHg). All animals received a catheter balloon that was positioned in the proximal stomach and connected to a U shaped barostat filled with standard ionic solution set 4cm above the animals xyphoid appendix. Gastric volume changes transmitted to this communicant vessel system were sensed and recorded by a plethysmometer for 80min After a basal period of 20min the animals were randomly allocated to either experimental protocols: control or ICH. In controls the animals remained untouched while in ICH the ICP was increased from basal to 10, 20, 40, or 60 mmHg, for 30min. In crescent ICP, the pressure was increased in the same animal, at every 20min, from basal to 20, 40 and then 60 mmHg. Separate groups of animals also underwent neurotomy or respective sham operation: subdiafragmatic vagotomy, splancnotomy plus bilateral ganglionectomy and after the basal period were submitted to 10 mmHg of ICP. Brains from other animals (control ICP 10 and ICP 60 mmHg) were removed for histological studies. Data (mean  SEM) were compared to respective basal values after ANOVA and Bonferroniâs test. In controls, hemodynamic parameters and GV remained within stable levels. In ICP 10 mmHg, GV decreased (P<0.05) from basal levels (2.70Â0.12ml) to 2.30Â0.14ml at 30min to remain decreased afterwards, while at ICP 20, 40 and 60mmHg decreased early at 20min of ICH (2.36Â0.18 vs 2.03Â0.19, 2.69Â0.27 vs 2.03Â0.25 e 2.83Â0.12 vs 1.95Â0.11ml, respectively), remaining as such up to the end (P<0.05). In crescent ICP, GV decreased from basal levels (2.94Â0.04ml) at ICP 40mmHg to 2.70Â0.07ml as well as at ICP 60 mmHg to 2.67Â0.06ml (P<0.05). In all groups were observed arterial hypertension and bradycardia, typical findings of Cushingâs reflex. In animals without vagal connection, GV despite beginning from lower basal values (1.82Â0.18ml) decreased (P<0.05) at 30min to 1.69Â0.18ml. After sympathectomy, GV remained stable (P>0.05) throughout the experiment (2.29Â0.21ml vs 2.11Â0.23ml). Moderate meningeal edema-coroid plexus- was observed moreover at brains from ICP 60mmHg subset. In conclusion, experimental ICH besides inducing Cushingâs reflex (arterial hypertension and bradycardia) also decreases gastric compliance in anesthetized rats in an ICP dependent manner. Vagotomy had no effect and this phenomenon is likely to be mediated by sympathetic neuropathways. / Em humanos, a hipertensÃo intracraniana (HIC) alÃm de promover distÃrbios hemodinÃmicos, tambÃm provoca alteraÃÃes na funÃÃo gastrintestinal, apresentadas clinicamente com nÃuseas e vÃmitos. Como a HIC em ratos acordados inibe o esvaziamento gÃstrico de lÃquido e este à influenciado pela complacÃncia gÃstrica (CG), estudou-se o efeito da HIC sobre a CG e os mecanismos neurais envolvidos no fenÃmeno. Ratos Wistar (N=65, 280-320g) anestesiados com uretana tiveram a artÃria carÃtida canulada para registro hemodinÃmico. Mediante estereotaxia, cÃnulas-guias foram implantadas bilateralmente nos ventrÃculos laterais, para registro simultÃneo da PIC e compressÃo do sistema ventricular por infusÃo de lÃquido cefalorraquidiano-sÃmile (LCR-sÃmile). Um catÃter com um balÃo na extremidade foi posicionado no estÃmago proximal e conectado a um sistema de vasos comunicantes com barostato. VariaÃÃes do volume do balÃo gÃstrico (VG) transmitidas ao barostato foram detectadas por um sensor eletrÃnico de volume e registradas continuamente por 80min num pletismÃmetro. ApÃs um perÃodo basal de 20min, os ratos foram aleatoriamente submetidos Ãs seguintes condiÃÃes: Controle (PIC espontÃnea), PIC 10mmHg, PIC 20mmHg, PIC 40mmHg, PIC 60mmHg e PIC Crescente. ApÃs a compressÃo ventricular, os animais foram monitorados por mais 30min. Para o estudo dos mecanismos neurais, grupos de ratos, previamente submetidos a laparotomia seguida ou nÃo (falsa cirurgia) de vagotomia subdiafragmÃtica ou esplancnicectomia+gangliectomia celÃaca bilaterais, foram estudados sob PIC de 10mmHg. Um grupo à parte de animais (n=9) PIC controle, PIC 10mmHg e PIC 60mmHg tiveram seus encÃfalos retirados para avaliaÃÃo histolÃgica. Os dados foram expressos em mÃdiaÂEPM e analisados pela ANOVA seguido pelo teste de Bonferroni. No grupo controle, os parÃmetros hemodinÃmicos e de VG se mantiveram constantes. No grupo PIC 10mmHg, em relaÃÃo ao perÃodo basal (2.70Â0.12ml), o VG diminuiu para 2.30Â0.14ml aos 30min de HIC, assim permanecendo por todo o experimento (P<0.05). Jà nos grupos PIC 20mmHg, PIC 40mmHg e PIC 60mmHg, o VG diminuiu em relaÃÃo ao perÃodo basal aos 20min de HIC (2.36Â0.18 vs 2.03Â0.19, 2.69Â0.27 vs 2.03Â0.25 e 2.83Â0.12 vs 1.95Â0.11ml, respectivamente), assim permanecendo atà o final (P<0.05). No grupo PIC crescente, em relaÃÃo ao perÃodo basal (2.94Â0.04ml), o VG diminuiu para 2.70Â0.07ml com PIC 40 mmHg e para 2.67Â0.06ml com PIC 60mmHg (P<0.05). Em todos os grupos observou-se hipertensÃo arterial e bradicardia, efeitos tÃpicos do reflexo de Cushing. Nos animais sem conexÃo vagal, o VG embora partindo de nÃveis basais menores (1.82Â0.18ml) diminuiu (P<0.05) aos 30min para 1.69Â0.18ml. Nos animais submetidos a esplacnicectomia, em relaÃÃo ao perÃodo basal (2.29Â0.21ml), o VG permaneceu inalterado (P>0.05) durante (2.11Â0.23ml) e apÃs a compressÃo ventricular. Nas lÃminas analisadas identificou-se edema parenquimatoso e congestÃes menÃngea, do plexo corÃide e parenquimatosa de graus leve a moderado, principalmente nos animais submetidos a PIC de 60 mmHg. A HIC diminui a CG de ratos anestesiados, sendo o fenÃmeno PIC dependente e possivelmente mediado por via esplÃncnica

A doença do refluxo gastroesofágico (DRGE), apresenta significativa variedade de sintomas e sinais esofagianos ou extra-esofagianas. Entre suas complicações, embora pouco freqüentes, estão o esôfago de Barrett e o adenocarcinoma, sendo, portanto, fundamental reconhecer os fatores implicados na etiologia e agravamento da DRGE. Nos últimos anos, tem sido dada maior importância à influência da atividade física na DRGE. Investigações recentes, embora com resultados conflitantes, em sua maioria, apontam para a exacerbação do refluxo gastroesofágico (RGE) durante o exercício físico. OBJETIVOS: Avaliar a influência da atividade física na DRGE, por meio do teste ergométrico de esforço (TE), em pacientes portadores de doença erosiva, bem como a relevância do tônus do esfíncter inferior do esôfago (EIE) e do índice de massa corporal (IMC), comparando com um grupo de pacientes portadores da forma não erosiva da doença. MÉTODOS: Foram avaliados prospectivamente 29 pacientes portadores de DRGE erosiva e, como grupo controle, 10 pacientes com a doença não erosiva. Todos foram submetidos à avaliação clínica, realização de endoscopia digestiva alta, manometria e pHmetria esofágica. Também realizaram TE precedendo a retirada da sonda de pH-metria. As seguintes variáveis foram avaliadas: eficácia do TE, consumo máximo de oxigênio (VO2max), tempo de refluxo ácido (TRA) e sintomas de RGE durante o TE, influência do tônus do EIE e do IMC na ocorrência de RGE no TE. RESULTADOS: A VO2max demonstrou correlação significativa somente no grupo de pacientes com esofagite erosiva quando esta foi maior ou igual a 70% (p=0,032) durante a realização do TE. As demais variáveis analisadas não demonstraram influência significativa entre a ocorrência de RGE e atividade física (p>0,05). CONCLUSÕES: 1) Atividade física de alta intensidade pode predispor a ocorrência de episódios de refluxo gastroesofágico em portadores de DRGE erosiva; 2) Atividade física de baixa intensidade ou de curta duração não exercem influencia, independentemente do IMC; 3) O tônus do EIE não exerce influência na ocorrência de episódios de RGE durante realização de TE / Gastroesophageal Reflux Disease (GERD) is a worldwide prevalent condition that exhibits a large variety of signs and symptoms of esophageal or extraesophageal nature and can be related to the adenocarcinoma of the esophagus. Therefore, its of crucial importance to recognize the etiologic and aggravating factors of GERD. In the last few years, greater importance has been given to the influence of physical exercises on GERD. Some recent investigations, though showing conflicting results, point to an exacerbation of gastroesophageal reflux during physical exercises. Objectives: To evaluate the influence that physical activities can have on GERD patients presenting with erosive and non erosive disease by means of an ergometric stress test and evaluate the influence of the lower esophageal sphincter tonus and body mass index (BMI) during this situation. METHODS: Twenty-nine GERD patients with erosive disease (group I) and 10 patients with non-erosive disease (group II) were prospectively evaluated. All the subjects were submitted to clinical evaluation, followed by upper digestive endoscopy, manometry and 24h esophageal pH monitoring. A stress test was performed 1 hour before removing the esophageal pH probe. During the ergometric stress test, the following variables were analyzed: test efficacy, maximum oxygen uptake (VO2 max), duration of acid reflux and gastroesophaeal reflux symptoms and the influence of the lower esophageal sphincter tonus and influence of body mass index (BMI) in the occurrence of GER during these physical stress. RESULTS: VO2 max showed significant correlation when it was 70% or higher only in the group of erosive disease, evaluating the patients with or without acid reflux during the stress test (p = 0,032). The other variables considered didnt show significant correlations between gastroesophageal reflux and physical activity (p > 0,05). CONCLUSIONS: 1) Highly intensive physical activity can predispose the occurrence of gastroesophageal reflux episodes in GERD patients with erosive disease. 2) Light or short sessions of physical activity have no influence on reflux, regardless of BMI. 3) The tonus of the lower esophageal sphincter does not influence the occurrence of episodes of GER during exercise testing

More than 1.2 million people are estimated to be currently living with the human immunodeficiency virus (HIV) in the United States of America. The gastrointestinal (GI) tract is both a major target and an important component of HIV pathogenesis. The GI processes that are dysregulated during HIV infection are controlled by the enteric nervous system (ENS). Indeed, both clinical and experimental studies have implicated the ENS in HIV and simian immunodeficiency virus (SIV) pathogenesis. In addition to direct viral effects, the HIV virus also indirectly affects the GI tract via cellular and/or viral toxins released by infected cells. Trans-activator of transcription (Tat) is a viral toxin that plays an important role in replication of the HIV virus. While, the HIV virus does not directly infect neurons, Tat has been shown to modulate neuronal function. HIV infection in the gut is accompanied by: translocation of bacteria and bacterial products from the gut lumen to peripheral blood, immune activation and inflammation. Lipopolysaccharide (LPS) is a major bacterial product that is used to determine the rate of bacterial translocation and to drive inflammation. Despite reports of enteric ganglionitis in SIV infected monkeys and autonomic denervation in the jejunum of HIV patients, little is known of the mechanism underlying enteric neuropathogenesis in HIV and the role of the ENS in HIV pathogenesis. In the present study, we assessed the effects of Tat on enteric neuronal excitability and how Tat and LPS interact in the ENS to bring about inflammation and GI motility problems observed in HIV patients. We show that Tat significantly increased enteric neuronal excitability by modulating sodium channels expressed on enteric neurons. Tat sensitized ENS cells to LPS-mediated increase in pro-inflammatory cytokines via a TLR4-mediated pathway involving MyD88. Mice expressing the tat transgene (Tat+) had faster GI transit rates and significantly higher frequencies of diameter changes in the proximal ileum than controls (Tat-). Tat+ mice were also more sensitive to LPS-mediated decreases in colonic transit rate. This study highlights the role of viral and bacterial proteins in HIV pathogenesis in the gastrointestinal tract and also demonstrates a critical role of the ENS in HIV pathogenesis.

Wang, Hui Chuan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 184-202). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

A isquemia aguda mesentérica é uma condição de grande emergência vascular, que é fatal na população mundial em 60% a 80% dos casos. O objetivo desse trabalho foi estudar, os efeitos da isquemia/reperfusão intestinal sobre o receptor P2X2 e diferentes classes neuronais no plexo mioentérico. Foram analisados o íleo de ratos: controle, Sham e isquemia/reperfusão intestinal (I/R-i) com de 24h e 1 semana de reperfusão. Foram realizadas colocalização do receptor P2X2 com a NOS, ChAT, Calb, Calr, S100 e anti-HuC/D. Os resultados mostraram diminuição de neurônios P2X2-ir colocalizados com a NOS, ChAT e Hu, e um aumento com S100 no grupo I/R-i 1 semana. A densidade apresentou um aumento de células P2X2-ir e S100 e diminuição de ChAT e Hu no grupo I/R-i de 1 semana. O perfil neuronal apresentou um aumento nos neurônios NOS-ir, ChAT, Calb (Dogiel Tipo II) e Calr. Conclui-se que a isquemia levou a alterações diferenciadas no receptor P2X2, células gliais e neurônios entéricos, que podem causar disfunções gastrintestinais, como por exemplo, problemas na motilidade intestinal. / The acute mesenteric ischemia is a vascular condition of extreme emergency, which is fatal in the world population by 60% to 80% of cases. The aim of this work was to study the effects of intestinal ischemia/reperfusion on the P2X2 receptor and different neuronal classes in the myenteric plexus. We analyzed the ileum of rats: control, Sham and ischemia/reperfusion (I/R-i) with 24 hours and 1 week of reperfusion. The colocalization were performed by P2X2 receptor with NOS, ChAT, Calb, Calr, S100 and anti-HUC/D. The results showed a decrease of P2X2-ir neurons colocalizated with ChAT and Hu, and an increase in the group with S100 in the I/R-i 1 week group. The density of cells showed an increase of P2X2-ir and S100 and a decrease of Hu and ChAT in I/R-i 1 week group. The profile area showed an increase in NOS-ir, ChAT-ir, Calb (Dogiel Type II) and Calr-ir neurons. We conclude that ischemia led to different changes in P2X2 receptor, enteric neurons and glial cells, which can cause gastrointestinal disorders, such as intestinal motility disorder.