Orientador: Luiz Claudio Di Stasi / Banca: Leonardo Noboru Seito / Banca: Silvio Luis De Oliveira / Resumo: Pfaffia glomerata (Spreng.) Pedersen ("ginseng brasileiro") é uma planta medicinal que apresenta um amplo espectro de usos como tônico, antiestresse e afrodisíaco. Esta espécie pertence ao complexo grupo de plantas medicinais conhecidas como "ginseng" e compõe um grupo específico de plantas denominadas adaptógenas, definidas como produtos capazes de aumentar a resistência não específica do organismo frente a diferentes estímulos estressores; considerando-se tal definição, é previsível que os compostos fitoquímicos presentes na P. glomerata sejam úteis no controle e prevenção de doenças na qual o estresse é fator etiológico, como é o caso da Doença Inflamatória Intestinal (DII). Dessa forma, o presente trabalho possui como objetivo avaliar a atividade anti-inflamatória intestinal da fração butanólica de P. glomerata (rica em saponinas), sobre o modelo de doença inflamatória intestinal induzida por ácido 2, 4, 6-trinitrobenzenosulfônico (TNBS) em ratos. Para tal, foram estudados parâmetros macroscópicos (escore da lesão, extensão da lesão, relação peso/comprimento do cólon, diarreia e aderência) e bioquímicos (atividade da mieloperoxidase e da fosfatase alcalina e quantificação da glutationa total) do processo inflamatório intestinal. Análises fitoquímicas mostraram principalmente a presença de triterpenos e saponinas, incluindo a ecdisterona, e indícios de compostos fenólicos. Os tratamentos com a fração butanólica de P. glomerata não foram capazes de impedir a formação lesões induzidas pelo TNBS e nem de auxiliar na resolução de um quadro inflamatório intestinal pré-existente, que também foi causado pelo TNBS. Com base nestes dados, a hipótese inicial de que um produto adaptógeno modularia o sistema imune por meio de sua ação antiestresse foi rejeitada nas condições experimentais utilizadas / Abstract: Pfaffia glomerata (Spreng.) Perdersen, also called Brazilian ginseng, is a medicinal plant which has a broad use as tonic, anti-stress, and aphrodisiac. This specie belongs to the medicinal plants complex known as ginseng and it is part of a specific group of plants called adaptogens, which are defined as products that are capable of increasing non-specific body resistance against different stressors; considering the definition of adaptogens it is possible to assume that phytochemical compounds present in P. glomerata are also useful in controlling and preventing diseases in which stress is an etiological factor, such as Inflammatory Bowel Disease (IBD). Thereby, this present work aims to study the intestinal anti-inflammatory activity from the butanolic extract of P. glomerata (enriched in saponins) in the TNBS-induced inflammatory bowel disease in rats. To this, macroscopic (score, lesion extension, weight/length ratio, diarrhea and adherence) and biochemical (myeloperoxidase and alkaline phosphatase activities and total glutathione content) parameters of the inflammatory bowel disease were studied. Phytochemical analysis showed the presence of triterpens and saponins, including ecdysterone, and signs of phenolic compounds. Treatments with butanolic extract from P. glomerata were not able to prevent TNBS-induced lesions nor were able to ameliorate in the resolution of the pre-existing intestinal inflammatory process also caused by TNBS. According to these data, the initial hypothesis that an adaptogen product would modulate the immune system by its anti-stress action was rejected in the experimental conditions utilized / Mestre

Doenças inflamatórias intestinais (DII) em humanos são reações crônicas de etiologia complexa. Trata-se de uma reação imunológica exacerbada e depende da microbiota. O sistema nervoso interage com a imunidade do intestino de um modo bidirecional. Relatos clínicos e poucos achados experimentais apontam para uma ligação entre transtornos depressivos e doenças inflamatórias intestinais, sugerindo interação neuroimunológica na patogenia deste processo. Ainda, o tratamento de Doenças inflamatórias intestinais (DIIDoença de Crohn e Colite Ulcerativa) com antidepressivos em modelos murino de colite têm sugerido bons resultados na redução da inflamação. O mecanismo da inflamação na DII e a participação do sistema nervoso ou da modulação de tal processo pelo emprego de antidepressivos ainda não está totalmente elucidado. Este estudo teve como objetivo estudar o efeito do antidepressivo amitriptilina em um modelo murino de colite. A colite foi induzida em camundongos C57BL/6 por Dextrano Sulfato de Sódio (DSS) e a amitriptilina (AMT) foi administrada por via oral, em regime profilático ou terapêutico. Avaliamos a dose de AMT no teste de suspensão da cauda (TSC), o acúmulo de neutrófilos pela atividade de mieloperoxidase (MPO), burst oxidativo, curva de sobrevida, histopatologia do intestino, atividade da doença por sintomas clínicos, a depleção de muco intestinal, citocinas inflamatórias no cólon e no soro, fenotipagem de linfócitos T CD4+, T CD8+, e monócitos CD14+,. Resultados: A dose de AMT (200 μg/ml) e os regimes de tratamento utilizados aqui foram capazes de impedir ou diminuir a histopatologia da colite, os sinais clínicos (ganho de peso (%), comprimento e peso do cólon) e a mortalidade dos animais no modelo terapêutico do grupo inflamado e tratado com AMT. A atividade de MPO, níveis circulantes de IL- 1 β, IL- 6 e TNF- α foram reduzidas nos dois protocolos experimentais (profilático e terapêutico). Conclusões: Este estudo incluiu um período de tratamento prolongado, visto que os antidepressivos são conhecidos por serem eficazes em seres humanos depois de várias semanas a meses de prescrição, e confirmou a eficiência da via de administração oral, uma vez que os antidepressivos são geralmente administrados por via oral a seres humanos. Este regime de tratamento melhorou o potencial anti-inflamatório de AMT na redução DSS-colite em camundongos, com base nos parâmetros estudados / Inflammatory bowel disease (IBD) in humans is a complex etiology of chronic reactions. It is an exacerbated immune reaction and depends on the microflora. The nervous system interacts with the intestinal immunity of a bidirectional fashion. Clinical reports and few experimental findings point to a link between depressive disorders and inflammatory bowel disease, suggesting neuroimmunological interaction in the pathogenesis of this process. Also, treatment of inflammatory bowel diseases (Crohn\'s disease DII- and Ulcerative Colitis) with antidepressants in murine models of colitis have pointed to positive results in reducing inflammation. The mechanism of inflammation in IBD and the involvement of the nervous system or modulation of this process by the use of antidepressants is not yet fully elucidated. This study aimed to study the effect of amitriptyline in a murine model of colitis. Colitis was induced in C57BL / 6 mice by Dextran Sodium Sulfate (DSS) and amitriptyline (AMT) were orally administered in a prophylactic or therapeutic regimen. We evaluated the AMT dose in the tail suspension test (TST), the accumulation of neutrophils by myeloperoxidase activity (MPO), oxidative burst, survival curve, bowel histopathology, disease activity by clinical symptoms, depletion of intestinal mucus, colon and inflammatory cytokines in the serum phenotype of CD4+ T lymphocytes, CD8+ and CD14+ monocytes. Results: The dose of AMT (200 μg / ml) and treatment regimens used herein are able to prevent or decrease the pathology of colitis, clinical signs (weight gain (%), colon weight and length) and mortality animals in the therapeutic model inflamed group and treated with AMT. MPO activity, circulating levels of IL- 1 β, IL- 6 and TNF- α were reduced in both experimental protocols (prophylactic and therapeutic). Conclusions: This study included a prolonged period of treatment, as antidepressants are known to be effective in humans after several weeks or months of limitation, and confirmed the effectiveness of oral administration route, since antidepressants are generally administered orally to humans. This treatment scheme has improved potential anti-inflammatory AMT in reducing DSS colitis in mice based on the study parameters

Youth with inflammatory bowel disease (IBD) have higher rates of depression than healthy youth. A cognitive-behavioral treatment, primary and secondary control enhancement training-physical illness (PASCET-PI), for depressed adolescents with IBD was associated with reductions in depressive symptoms. The purpose of this study was to examine the salience of nonspecific processes (factors inherent in any human relationship) and specific processes (factors related to therapy content) during PASCET-PI sessions and their association with improvements in psychological functioning. Participants included 10 adolescent patients with IBD with mean illness duration of 31.9 months. At intake, eight participants qualified for a diagnosis of major depressive disorder and two for a diagnosis of minor depression. Participants completed measures of depressive symptomatology and clinicians completed the Children's Global Assessment Scale (CGAS). Measures were completed at posttreatment, 6 months posttreatment, and 1 year posttreatment. Independent judges used the Psychotherapy Process Q-sort (PQS) to rate the salience of therapeutic processes for PASCET-PI sessions #2 and #8 for each subject. PQS ratings of PASCET-PI sessions were con-elated with ideal prototypes of cognitive-behavioral treatment (CBT), inteqnrsonal therapy (IPT), and psychodynamic (PD) orientations that were previously developed based on PQS ratings of an ideal session, according to expert therapists. Findings indicate that PASCET-PI sessions most closely resembled the CBT prototype (r = .51, p < .05). Change scores on outcome measures were correlated with PQS-prototype correlates to determine which processes were associated with improved psychological functioning. Findings suggest that reductions in depressive symptomatology were associated with processes characteristic of various orientations. Thus, CBT processes were not exclusive in promoting change. There were strong positive relationships between change scores of the PCS and prototypes of all orientations (CBT, IPT, and PD) at posttreatment and between the CDI and ASQ and all orientations at 6-months follow-up (r = .62 -.72, p < .05). Comparisons of specific process-outcome correlates and nonspecific process-outcome correlates did not reveal significant differences.

An imbalance of the T cell immune response is observed in inflammatory bowel disease. Intestinal microbes have been linked to the disease and the disease process leads to severe mucosal injury and systemic translocation of bacterial products. Aminosalicylates, corticosteroids and immunomodulators reduce these aggressive activities but are associated with potentially serious adverse events. The aim of this work was to investigate the effects of administration of prebiotics and probiotics that modulate the gut microflora and modulate the immune response, in ameliorating severity of colitis. The prebiotic, high amylose maize resistant starch was used at two different concentrations. A number of Bifidobacterium and Lactobacillus strains were used as probiotics. BALB/c mice were administered the prebiotics and probiotics and intrarectally infused with 2.5 mg trinitrobenzene sulfonic acid (TNBS) in 45% ethanol, thereby generating colitis. Mucosal cytokine responses, colonic microbial profiles and disease activity indices were monitored. The 5% concentration of high amylose maize resistant starch delayed progression of TNBS colitis as evidenced by reduced weight loss, lesser tissue damage, abrogation of the expression and synthesis of IFN-?? and upregulation of IL-4 and IL-10. The 30% concentration of high amylose maize resistant starch exacerbated the inflammatory response with an increase in acetic acid, coliforms and endopores in the colonic contents. Three strains of bifidobacteria and 3 strains of lactobacilli were individually screened for their activity against TNBS colitis. Each strain had a distinctive effect on the course of colon inflammation. Lactobacillus fermentum VRI 003 was selected for further study as it provided most protection. The ratio of immunosuppressive cytokines to pro-inflammatory cytokines was restored closer to the normal T cell cytokine levels. It also reduced the incidence of translocation of enteric bacteria into the spleens. Dosing a minimum daily dose of 6x109 CFU L. fermentum VRI-003 to ulcerative colitis patients in remission and maintained on standard therapy for 6 months prevented the exacerbation of symptoms, including diarrhea and abdominal pain, and improved the patient general well being. It also suppressed production of IFN-?? and sustained IL-10 levels. Moreover, absence of endospores and lower numbers of coliforms were detected in the faeces of UC patients during L. fermentum VRI-003 treatment. In summary, 5% high amylose maize resistant starch and L. fermentum VRI 003 prevented colon inflammation by changing the nature of the T cell immune response and modifying the colonic microflora in the murine model. The clinical evidence supported these findings.

Thesis (Ph. D.)--University of California, Riverside, 2009. / Includes abstract. Available via ProQuest Digital Dissertations. Title from first page of PDF file (viewed March 20, 2010). Includes bibliographical references. Also issued in print.

Personer med IBS lider av en sjukdom som inte syns utåt vilket kan skapa påfrestningar i det dagliga livet och i mötet med vården. Därför är det väsentligt att sjuksköterskan har empati, kunskap och engagemang i mötet med dessa personer. Syftet med studien var att belysa det stöd som efterfrågas av personer med IBS i mötet med sjukvården och hur sjuksköterskan förhåller sig i mötet. Metoden som användes till studien var litteraturstudie. Resultatet visar att personer med IBS är i behov av stöd genom information, bekräftelse och ett professionellt förhållningssätt av vårdarna i mötet. Sjuksköterskans förhållningssätt i mötet med dessa personer visades vara oprofessionellt genom b1.a. ignorans, fördomar och även förlöjligande av deras symptom. I diskussionen framkom det att personer med IBS upplever välbefinnande när vårdare besitter ett professionellt förhållningssätt. Slutsatsen blev att personer med IBS gynnas av stöd i form av information och bekräftelse från sjukvården.

Πρόσφατα δεδομένα υποδεικνύουν ότι η έκφραση του p75NTR και των Trk υποδοχέων των νευροτροφινών (TrkA, TrkB, TrkC) είναι ιδιαίτερα σημαντική όχι μόνο στη νευρωνική επιβίωση κατά τη διάρκεια της ανάπτυξης και την ενήλικο ζωή αλλά και σε ποικίλες κυτταρικές διαδικασίες όπως η ανοσολογική απάντηση του οργανισμού σε φλεγμονές. Ο σκοπός αυτής της μελέτης ήταν να ερευνήσει την κυτταρική εντόπιση και κατανομή του p75NTR και των Trk υποδοχέων των νευροτροφινών στην ελκώδη κολίτιδα σε σύγκριση με το φυσιολογικό έντερο του ενήλικα ανθρώπου χρησιμοποιώντας την ανοσοϊστοχημική μέθοδο. Στη μελέτη συμπεριελήφθησαν 45 περιπτώσεις ελκώδους κολίτιδας και 5 δείγματα φυσιολογικού εντέρου. Παρατηρήθηκε αύξηση της έκφρασης όσον αφορά τους TrkA υποδοχείς τόσο στο επιθήλιο όσο και στα κύτταρα του εντερικού νευρικού συστήματος στο φλεγμονώδες σε σχέση με το φυσιολογικό έντερο. Έντονη έκφραση των TrkB υποδοχέων ταυτοποιήθηκε στο μυϊκό τοίχωμα των αγγείων και στα εντεροενδοκρινή κύτταρα του επιθηλίου στο φλεγμονώδες και στο φυσιολογικό έντερο. Μειωμένη έκφραση, τόσο στο επιθήλιο όσο και στο εντερικό νευρικό σύστημα, όσον αφορά την έκφραση των TrkB και TrkC υποδοχέων παρατηρήθηκε στις περιπτώσεις ελκώδους κολίτιδας σε σχέση με το φυσιολογικό έντερο. Ο p75NTR παρουσίασε έκφραση αποκλειστικά στα πλέγματα του νευρικού συστήματος, τόσο στο φυσιολογικό όσο και στο φλεγμονώδες έντερο. Τα παραπάνω αποτελέσματα υποδεικνύουν ότι οι νευροτροφίνες μέσω της δέσμευσής τους με τους Trk υποδοχείς και τον p75NTR πιθανόν εμπλέκονται στην παθογένεια των φλεγμονών όπως η ελκώδης κολίτιδα κατά την ενήλικο ζωή. / -

The gastro-intestinal (GI) tract represents the largest surface of the body and is continuously exposed to the microbial environment. In such anatomy, the survival of the host requires that the intestinal microbial flora be contained without excessive immune-reactivity to commensal bacteria while retaining the ability to respond to episodic pathogens. The discriminative recognition between beneficial commensal bacteria and potentially harmful pathogens demands an accurate interpretation by the GI mucosal immune system. Any defects in the processes of innate immune recognition and killing may lead to the development and perpetuation of chronic intestinal inflammation, namely inflammatory bowel disease (i.e. Crohn's disease (CD) and ulcerative colitis (UC)) and post-infectious irritable bowel syndrome (PI-IBS). The aim of ours studies was to evaluate the contribution of candidate genes, involved in the homeostasis and regulation of the intestinal innate immune response, to the susceptibility to CD, DC, and PI-IBS. In the first phase, we describe functional and genetic association results supporting NLRP3, encoding NALP3/cryopyrin, as a novel CD susceptibility gene. We subsequently report that the MEFV gene, encoding pyrin, known to interact with and be involved in the same pathway as NALP3/cryopyrin, does not contribute to CD and DC susceptibility. No CD or DC additional associations were observed upon NLRP3-MEFV gene-gene interaction analyses. In the third phase, we report the first association study evaluating genetic determinants for PI-IBS, using the well-characterized Walkerton population cohort. We uncovered variants in the TLR9, CDH1, and IL6 regions associated with PI-IBS susceptibility. These results are in keeping with the pathophysiologic changes observed in patients with PI-IBS, which include increased intestinal permeability and intestinal immune activation. / Overall, these results contribute to a better understanding of the genetic susceptibility to CD, DC and PI-IBS and shed light on new pathogenic signaling pathways in the development of these diseases.

Glucagon-like peptide-2 (GLP-2) augments intestinal adaptation in animal models of short bowel syndrome (SBS) and in adult patients with SBS. However, GLP-2 has not been used as a therapy for pediatric SBS. In this thesis, it is hypothesized that exogenous GLP-2 therapy will improve outcomes of intestinal adaptation in proximal intestinal resection (JI) and distal intestinal resection (JC) neonatal piglet models of SBS. Improvements in morphological parameters (increased small intestinal length) and histological parameters (increased jejunal villus length or jejunal crypt depth) of intestinal adaptation in JI and JC neonatal piglets treated with GLP-2 were observed. However, improved clinical outcomes (fewer days of diarrhea, fewer days on parenteral nutrition, more days on enteral nutrition alone) were only observed in GLP-2 treated JC animals. Since the JC anatomical subtype (no remnant ileum) represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.

No description available.