Objetivo: Analisar através de metodologia molecular a microbiota fecal de recém-nascidos (RN) saudáveis, em aleitamento materno exclusivo. Materiais e métodos: Amostras fecais de dez RN foram avaliadas no 2º, 7º e 30º dias de vida (DV), através de sequenciamento do 16S rDNA bacteriano. Real-time PCR para bifidobacterias foi empregado nas amostras de 30 dias. Resultados: A diversidade bacteriana fecal aumentou do 2º para o 30º DV. E. coli predominou no 2º e 7º DV, e Clostridium no 30º DV. Usando real-time PCR, bifidobacterias foram identificadas em todas as amostras de 30 dias. Conclusão: Enterobacterias predominaram na primeira semana de vida. Aos 30 DV observou-se uma maior diversidade bacteriana, com predomínio de Clostridium.. A técnica inicial não permitiu identificar bifidobacterias. / Purpose: To evaluate by molecular methodology the fecal microbiota of healthy newborns, exclusively breastfed. Materials and methods: Fecal samples from ten neonates were analyzed on 2nd, 7th and 30th day of life, using 16S rDNA sequencing and real-time PCR for bifidobacteria. Results: The fecal bacteria diversity increased from the second to the 30th day of life. E. coli was predominant in the fecal samples from the 2nd and 7th day of life, and Clostridium.in the samples of the 30th day. Using real-time PCR bifidobacteria were identified in all 30th day samples. Conclusion: Enterobacteria were predominant in the first week of life. On 30th day of life a greater bacterial diversity was observed with predominance of Clostridium. The initial technique didnt allow the identification of bifidobacteria.

O presente projeto teve como proposta estudar a utilização do colostro bovino liofilizado como manejo alternativo para caprinos recém-nascidos. Estudos relacionados com a aquisição de proteção passiva e o desenvolvimento do epitélio intestinal, como aspectos citológicos e histológicos, atividade celular e expressão do receptor específico para o IGF-I (IGF-IR), foram realizados. Às 0, 7 e 14 horas de vida, 15 machos recém-nascidos receberam 5% do peso inicial de colostro bovino liofilizado (CBL) e 14 colostro caprino (CC), ambas as refeições com 55 mg/mL de IgG. Amostras de sangue foram coletadas às 0, 7, 14, 18, 24, 36, 48, 72 e 96 horas de vida para a quantificação da imunoglobulina G (IgG), proteína total (PT) e do fator de crescimento semelhante à insulina tipo I (IGF-I). Amostras do duodeno, jejuno e íleo foram coletadas às 18, 36 e 96 horas de vida para análises utilizando microscopia óptica e microscopia eletrônica de varredura e transmissão. A atividade de enzimas extracelulares, quantificação da proteína, DNA e RNA total e expressão do IGF-IR também foram determinadas. Amostras de um grupo adicional (0 h), que não ingeriu colostro, foram coletadas. No grupo CBL, as concentrações séricas de IgG às 14, 18, 24 e 48 horas foram maiores que às 0 e 7 horas, enquanto no grupo CC, apenas às 18 horas a concentração sérica foi maior que às 0 e 7 horas (P<0,05). A capacidade de absorção de IgG diminuiu entre 7 e 14 horas em CC (P<0,05), enquanto em CBL, manteve-se sem alteração nestes horários (P>0,05). As variáveis PT e IGF-I não foram influenciadas pela ingestão de colostro bovino liofilizado (P>0.05). Os indicativos de atividade celular, concentração de proteína, DNA e RNA total, proteína/DNA, proteína/RNA e RNA/DNA, e a atividade das enzimas aminopeptidase N, dipeptidil peptidase IV, aminopeptidase A, lactase, maltase e sacarase diferiram nos horários experimentais e em relação ao grupo adicional (P<0,05). Apenas as razões proteína/DNA, proteína/RNA no jejuno e a atividade da aminopeptidase A no íleo foram maiores no grupo CBL (P<0,05). A atividade da fosfatase ácida foi observada nas primeiras horas de vida, especialmente no duodeno. Com relação à morfologia do epitélio intestinal e densidade das vilosidades, o fornecimento de colostro bovino liofilizado não determinou alterações. As variações na ultraestrutura dos enterócitos revelaram a presença, no segmento jejuno, de material absorvido e do complexo endocítico apical às 0, 18 e 36 horas. No duodeno, a expressão gênica do IGF-IR ao nascimento foi maior que às 18 e 36 horas nos grupos CC e CBL (P<0,05). Enquanto, a expressão do receptor deste peptídeo bioativo no jejuno do grupo CBL foi maior às 18 e 36 horas em relação a 0 h (P<0,05). Os resultados obtidos do presente trabalho contribuem para que a fonte alternativa de imunoglobulinas, colostro bovino liofilizado, seja utilizada como um substituto para o colostro caprino sem alterações significativas na aquisição de proteção passiva e nas características histofisiológicas do tecido epitelial do intestino delgado de cabritos. / This project was proposed to study the use of lyophilized colostrum as an alternative management for newborn goat kids. Studies related to the acquisition of passive protection and development of the intestinal epithelium, as cytological and histological aspects, cellular activity and expression of the receptor specific for IGF-I (IGF-IR), were performed. At 0, 7 and 14 hours of life, 15 newborn males received 5% of initial weight of lyophilized bovine colostrum (LBC) and 14 goat colostrum (GC), both meals with 55 mg/mL of IgG. Blood samples were collected at 0, 7, 14, 18, 24, 36, 48, 72 and 96 hours of life to quantification of immunoglobulin G (IgG), total protein (TP) and insulin like growth factor type I (IGF-I). Samples of the duodenum, jejunum and ileum were collected at 18, 36 and 96 hours of life for analysis using optical microscopy and scanning and transmission electron microscopy. The activity of extracellular enzymes, quantification of total protein, DNA and RNA and expression of the IGF-IR were also determined. Samples from an additional group (0 h), not suckling, were collected. In LBC group, serum IgG concentrations at 14, 18, 24 and 48 hours were higher than at 0 and 7 hours, while in the GC group, only at 18 hours serum concentration was higher than at 0 and 7 hours (P<0.05). The capacity of IgG absorption decreased between 7 and 14 hours in GC (P<0.05), while in LBC, remained unchanged at these times (P>0.05). The variables TP and IGF-I were not influenced by ingestion of lyophilized bovine colostrum (P>0.05). The indicators of cellular activity, total protein, DNA and RNA concentration, protein/DNA, protein/RNA and RNA/DNA, and the enzyme activity of aminopeptidase N, dipeptidyl peptidase IV, aminopeptidase A, lactase, maltase and sucrase differed in sampling times and in relation to the additional group (P<0.05). Only the rations protein/DNA, protein/RNA in the jejunum and aminopeptidase A activity in the ileum were higher in the LBC group (P<0.05). The acid phosphatase activity was observed in the first hours of life, especially in the duodenum. Regarding the intestinal epithelium morphology and villi density, the supply of lyophilized bovine colostrum did not determine alterations. Changes in enterocytes ultrastructure revealed the presence in the jejunum segment of absorbed material and apical endocytic complex at 0, 18 and 36 hours. In the duodenum, IGF-IR gene expression at birth was higher than at 18 and 36 hours in the GC and LBC (P<0.05). While the expression of this bioactive peptide receptor in the jejunum of the LBC group was higher at 18 and 36 hours relative to 0 h (P<0.05). The results of this work indicate that the alternative source of immunoglobulins, lyophilized bovine colostrum, can be used as a substitute for goat colostrum without significant changes in the acquisition of passive protection and histophysiology characteristics of the small intestine epithelium of goat kids.

Neste estudo investigamos o papel dos hormônios sexuais femininos na inflamação pulmonar, sistêmica e no intestino de ratas ovariectomizadas (OVx) após a isquemia/reperfusão intestinal (I/R-i). Para tanto, ratas OVx Wistar (60 dias, 160 g) foram submetidas a I/R-i ocluindo-se a artéria mesentérica superior (45min), seguida por 2h de reperfusão intestinal. As ratas OVx receberam dose única de estradiol (280mg/kg, s.c.) ou progesterona (200mg/kg, s.c.) 24 h antes da indução da I/R-i. Como controle foram usadas ratas Não-OVx submetidas à I/R-i, ratas OVx falsamente submetidas à I/R-i (Sham) e ratas não manipuladas (Basal). Os dados obtidos revelaram que o pulmão de ratas OVx em relação ao grupo Não OVx aumentou a geração de IL-1b e VEGF, o recrutamento de neutrófilos e a permeabilidade vascular. Ainda, reduziu os níveis de IL-10, nitritos e expressão de PECAM-1 e P2X7. As ratas OVx apresentaram maior recrutamento celular no pulmão e aumento da expressão de ICAM-1 e redução na de PECAM-1. Nossos dados mostraram que o estradiol e a progesterona alteram a síntese de mediadores inflamatórios no pulmão e também exercem influência na expressão de moléculas de adesão endoteliais, do P2X7 e na concentração de fosfatase alcalina. Ainda, o tratamento hormonal reduziu a permeabilidade intestinal mas não a atividade de MPO. Portanto, os HSF exercem efeitos protetores no pulmão, reduzindo as repercussões inflamatórias geradas pela I/R i. / In this study we investigated the role of female sex hormones (FSH) in lung, systemic and intestine inflammation of ovariectomized (OVx) rats after intestinal ischemia/reperfusion (I/R-i). Therefore, OVx Wistar rats (60 days, 160 g) were subjected to I/R-i occluding the superior mesenteric artery (45min), followed by 2 hours of reperfusion. The OVx rats received a single dose of estradiol (280mg/kg, s.c.) or progesterone (200mg/kg, s.c.) 24 hours before induction of I/R-i. We used as control Non-OVx rats subjected to I/R-i, OVx rats falsely subjected to I/R-i (Sham) and non-manipulated rats (Naïve). The data revealed that the lungs of rats in OVx group increased the generation of IL-1b and VEGF, neutrophil recruitment and vascular permeability. Furthermore, reduced levels of IL-10, nitrites and expression of PECAM-1 and P2X7. The OVx rats showed higher lung cell recruitment and increased expression of ICAM-1 and reduced of PECAM-1. Our data showed that estradiol and progesterone affect the synthesis of inflammatory mediators in the lung and also influence the expression of endothelial adhesion molecules, P2X7 and concentration of alkaline phosphatase. Moreover, hormone therapy reduced intestinal permeability but not MPO activity. In conclusion, FSH exert protective effects in the lung, reducing the inflammatory effects generated by I/R-i.

O presente projeto teve como proposta estudar a utilização do colostro bovino liofilizado como manejo alternativo para caprinos recém-nascidos. Estudos relacionados com a aquisição de proteção passiva e o desenvolvimento do epitélio intestinal, como aspectos citológicos e histológicos, atividade celular e expressão do receptor específico para o IGF-I (IGF-IR), foram realizados. Às 0, 7 e 14 horas de vida, 15 machos recém-nascidos receberam 5% do peso inicial de colostro bovino liofilizado (CBL) e 14 colostro caprino (CC), ambas as refeições com 55 mg/mL de IgG. Amostras de sangue foram coletadas às 0, 7, 14, 18, 24, 36, 48, 72 e 96 horas de vida para a quantificação da imunoglobulina G (IgG), proteína total (PT) e do fator de crescimento semelhante à insulina tipo I (IGF-I). Amostras do duodeno, jejuno e íleo foram coletadas às 18, 36 e 96 horas de vida para análises utilizando microscopia óptica e microscopia eletrônica de varredura e transmissão. A atividade de enzimas extracelulares, quantificação da proteína, DNA e RNA total e expressão do IGF-IR também foram determinadas. Amostras de um grupo adicional (0 h), que não ingeriu colostro, foram coletadas. No grupo CBL, as concentrações séricas de IgG às 14, 18, 24 e 48 horas foram maiores que às 0 e 7 horas, enquanto no grupo CC, apenas às 18 horas a concentração sérica foi maior que às 0 e 7 horas (P<0,05). A capacidade de absorção de IgG diminuiu entre 7 e 14 horas em CC (P<0,05), enquanto em CBL, manteve-se sem alteração nestes horários (P>0,05). As variáveis PT e IGF-I não foram influenciadas pela ingestão de colostro bovino liofilizado (P>0.05). Os indicativos de atividade celular, concentração de proteína, DNA e RNA total, proteína/DNA, proteína/RNA e RNA/DNA, e a atividade das enzimas aminopeptidase N, dipeptidil peptidase IV, aminopeptidase A, lactase, maltase e sacarase diferiram nos horários experimentais e em relação ao grupo adicional (P<0,05). Apenas as razões proteína/DNA, proteína/RNA no jejuno e a atividade da aminopeptidase A no íleo foram maiores no grupo CBL (P<0,05). A atividade da fosfatase ácida foi observada nas primeiras horas de vida, especialmente no duodeno. Com relação à morfologia do epitélio intestinal e densidade das vilosidades, o fornecimento de colostro bovino liofilizado não determinou alterações. As variações na ultraestrutura dos enterócitos revelaram a presença, no segmento jejuno, de material absorvido e do complexo endocítico apical às 0, 18 e 36 horas. No duodeno, a expressão gênica do IGF-IR ao nascimento foi maior que às 18 e 36 horas nos grupos CC e CBL (P<0,05). Enquanto, a expressão do receptor deste peptídeo bioativo no jejuno do grupo CBL foi maior às 18 e 36 horas em relação a 0 h (P<0,05). Os resultados obtidos do presente trabalho contribuem para que a fonte alternativa de imunoglobulinas, colostro bovino liofilizado, seja utilizada como um substituto para o colostro caprino sem alterações significativas na aquisição de proteção passiva e nas características histofisiológicas do tecido epitelial do intestino delgado de cabritos. / This project was proposed to study the use of lyophilized colostrum as an alternative management for newborn goat kids. Studies related to the acquisition of passive protection and development of the intestinal epithelium, as cytological and histological aspects, cellular activity and expression of the receptor specific for IGF-I (IGF-IR), were performed. At 0, 7 and 14 hours of life, 15 newborn males received 5% of initial weight of lyophilized bovine colostrum (LBC) and 14 goat colostrum (GC), both meals with 55 mg/mL of IgG. Blood samples were collected at 0, 7, 14, 18, 24, 36, 48, 72 and 96 hours of life to quantification of immunoglobulin G (IgG), total protein (TP) and insulin like growth factor type I (IGF-I). Samples of the duodenum, jejunum and ileum were collected at 18, 36 and 96 hours of life for analysis using optical microscopy and scanning and transmission electron microscopy. The activity of extracellular enzymes, quantification of total protein, DNA and RNA and expression of the IGF-IR were also determined. Samples from an additional group (0 h), not suckling, were collected. In LBC group, serum IgG concentrations at 14, 18, 24 and 48 hours were higher than at 0 and 7 hours, while in the GC group, only at 18 hours serum concentration was higher than at 0 and 7 hours (P<0.05). The capacity of IgG absorption decreased between 7 and 14 hours in GC (P<0.05), while in LBC, remained unchanged at these times (P>0.05). The variables TP and IGF-I were not influenced by ingestion of lyophilized bovine colostrum (P>0.05). The indicators of cellular activity, total protein, DNA and RNA concentration, protein/DNA, protein/RNA and RNA/DNA, and the enzyme activity of aminopeptidase N, dipeptidyl peptidase IV, aminopeptidase A, lactase, maltase and sucrase differed in sampling times and in relation to the additional group (P<0.05). Only the rations protein/DNA, protein/RNA in the jejunum and aminopeptidase A activity in the ileum were higher in the LBC group (P<0.05). The acid phosphatase activity was observed in the first hours of life, especially in the duodenum. Regarding the intestinal epithelium morphology and villi density, the supply of lyophilized bovine colostrum did not determine alterations. Changes in enterocytes ultrastructure revealed the presence in the jejunum segment of absorbed material and apical endocytic complex at 0, 18 and 36 hours. In the duodenum, IGF-IR gene expression at birth was higher than at 18 and 36 hours in the GC and LBC (P<0.05). While the expression of this bioactive peptide receptor in the jejunum of the LBC group was higher at 18 and 36 hours relative to 0 h (P<0.05). The results of this work indicate that the alternative source of immunoglobulins, lyophilized bovine colostrum, can be used as a substitute for goat colostrum without significant changes in the acquisition of passive protection and histophysiology characteristics of the small intestine epithelium of goat kids.

Vascular Endothelial Growth Factor (VEGF) is a highly conserved ligand that is involved in the regulation of angiogenesis and vasculogenesis, however, alternative roles of the ligand have been emerging. Organisms such as jellyfish and Drosophila contain VEGF homologs, yet they do not possess endothelial cells or a vascular system indicating that VEGF might have other primitive roles. In this current study we investigated how VEGF affects the post-natal development of the intestinal epithelial by either overexpressing VEGF or by reducing the bioavailability of VEGF with the overexpression of soluble VEGF receptor (sFLT-1) within the gastrointestinal tract. After three weeks of VEGF overexpression, mutant mice displayed an increase in villus height and proliferation in the transit-amplifying zone with the decrease of crypts per measured length and Lgr5 expression. On the other hand, sFLT-1 overexpressing mice had an increase in crypt depth with a decrease in villus height, proliferation in the transit-amplifying zone, crypts per measured length and reduced expression of Dll1 and Bmp4. Overall the availability of VEGF has the ability to alter the proliferation of progenitor cells in the crypt by either a direct or indirect signals. These studies reveal that by some means VEGF is altering the developing post-natal intestinal epithelium and proliferation. Largely, elucidating the interaction between VEGF and intestinal stem cells in intestinal development and differentiation may help to advance intestinal stem cell therapies in intestinal dysfunction or disease

Lors d’une infection microbienne, la défense de l’hôte comprend deux facettes complémentaires. Premièrement, le système immunitaire cible les pathogènes dans le but de les éliminer, une attaque correspondant à la résistance. Dans un second temps, l’organisme doit réparer les dégâts causés par le pathogène ou par la réponse immunitaire de l’hôte, un mécanisme appelé résilience. J’ai étudié les effets d’une infection intestinale par la bactérie Serratia marcescens chez la drosophile. Nous avons mis en évidence un processus de purge dans l’intestin, lors duquel les enterocytes -les cellules principales de l’intestin- se vident partiellement de leur contenu. L’épithélium intestinal devient alors très fin mais se régénère rapidement, protégeant ainsi la mouche des effets délétères de l’infection. J’ai identifié un transporteur d’acides aminés, CG1139, qui est nécessaire à la régénération de l’intestin. CG1139 est requis pour la mobilisation de certaines réserves métaboliques de la drosophile et pour le transport rétrograde de ces dernières vers l’intestin. / Upon microbial infections, host defenses comprise two complementary facets. First, immune effectors target and kill the invading pathogen, an attack referred to as resistance. Second, the infected host must repair the damages inflicted by microbes or by the immune response itself, a mechanism called resilience. I have studied the effects of an intestinal infection with the bacterium Serratia marcescens in Drosophila. We have discovered a purge mechanism in the intestine, where enterocytes -the main cell type in the gut- extrude some of their internal contents. The intestinal epithelium thus becomes very thin but rapidly recovers its shape, thereby protecting the fly against the deleterious effects of infection. I have identified an amino acid transporter, CG1139, which is required for the intestinal recovery. CG1139 is necessary to mobilize the fly’s internal metabolic reserves and to transport some these metabolic stores back to the gut, in a retrograde manner.

L’homéostasie énergétique ou ‘balance énergétique’ est l’équilibre qui s’établit chez l’Homme et l’animal adulte entre la prise quotidienne de nutriments sous la forme de glucides, de lipides ou de protéines et leur oxydation pour ne produire que la quantité énergétique strictement nécessaire. Pour maintenir cette balance l’organisme doit recueillir en permanence des signaux nerveux, métaboliques ou hormonaux de la part de cellules spécifiques. Ces senseurs des besoins énergétiques transmettent alors à des centres régulateurs leurs informations qui en retour, par voie hormonale ou nerveuse, informent les organes effecteurs des mesures à prendre pour stocker, produire ou consommer l’énergie. Les trois principaux centres de cette balance sont 1/ le cerveau, centre intégrateur de l’information ; 2/ un groupe d’organes effecteurs parmi lesquels le foie, le tissu adipeux, les muscles squelettiques, le pancréas et 3/ un centre senseur de la qualité et de la quantité des aliments, le tractus gastrointestinal (Migrenne 2006). En plus d’être la source d’énergie nécessaire à la vie des cellules, les nutriments tels que les acides gras, le cholestérol ou encore le glucose sont aussi des molécules de signalisation cellulaire à la fois par leur fixation à des récepteurs membranaires mais aussi via des récepteurs nucléaires. Un déséquilibre dans l’homéostasie énergétique dû à une alimentation déséquilibrée, à un manque d’exercice physique ou à des facteurs génétiques est une caractéristique de l’obésité et de complications telles que le diabète de type 2 et les maladies cardiovasculaires (Hill, 2006). Au cours de ma thèse je me suis intéressé à l’intestin pour son rôle de régulateur de l’homéostasie énergétique dans un contexte physiologique ou physiopathologique d’obésité via sa capacité à sécréter l’incrétine Glucagon-Like Peptide-1 (GLP-1) en réponse au glucose et aux acides biliaires. J’ai étudié plus particulièrement le rôle du récepteur nucléaire en tant que senseurs moléculaires des acides biliaires FXR dans les cellules sécrétrices de cette incrétine car à l’heure actuelle rien n’était connu quant à son rôle ni même quant à son expression dans la cellule L. Pour cela, j’ai utilisé des lignées cellulaires murines et humaines où j’ai mis au point les conditions expérimentales pour répondre aux questions posées. Grâce à des ARN d’intestins issus de différents modèles de souris la relevance chez le rongeur a été testée. La relevance de ces résultats sur des biopsies intestinales humaine a également été testée. Grâce à ces outils, j'ai pu montré que FXR dans les cellules L était fonctionnel et que son activation interférait avec la voie de la glycolyse entrainant moins de synthèse et de sécrétion de GLP-1. Cela nous a permis de proposer un nouveau mécanisme moléculaire par lequel les séquestrants des acides biliaires exercent leur effets bénéfiques chez des patients atteints de diabète de type 2. / Originally identified as dietary lipid detergents, bile acids (BA) are now recognized as signaling molecules which bind to the transmembrane receptor TGR5 and the nuclear receptor FXR (Farnesoid X Receptor). Upon binding to TGR5 at the surface of enteroendocrine L cells, bile acids (BA) promote the secretion of the incretin GLP-1 which potentiates the glucose-induced insulin secretion by pancreatic beta-cells. More than 50% of the insulin secretion in response to glucose is mediated by GLP-1 and the other incretin Glucose-dependent Insulinotropic Polypeptide (GIP). Once secreted, GLP-1 is rapidly (2-3 minutes) degraded by the endothelial enzyme Dipeptydil Peptidase 4 (DPP4). GLP-1 analogues and DPP4 inhibitors are successfully used for the treatment of T2D. FXR is a ligand-activated nuclear receptor highly expressed in the liver and in the distal intestine. FXR controls BA, lipid and glucose metabolism. Whether FXR is expressed, functional in intestinal enteroendocrine L cells and in which extend its activation affects GLP-1 production are not yet reported. Encouraging data were obtained during my M2 training course. The aim of my thesis was thus to assess whether FXR in enteroendocrines cells could participate in the control of the deregulation of glucose homeostasis. Multiple in vitro, ex vivo and in vivo human and murine models allowed us to show that FXR is present and functional in L cells. FXR activation decreases GLP-1 production and secretion in L cells by inhibiting glycolysis pathway through an interference with the carbohydrate responsive transcription factor ChREBP. Finally, I identified an additional mechanism of action of the bile acid sequestrant Colesevelam, a molecule currently successfully used in USA for treating type 2 diabetic patients.

Includes bibliographical references (leaves 159-213) Shows that IGF-I peptides are effective in diminishing post-surgical catabolism and enhancing adaptive gut hyperplasia in rats recovering from massive small bowel resection.

xxiii, 222 leaves : ill., plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Shows that IGF-I peptides are effective in diminishing post-surgical catabolism and enhancing adaptive gut hyperplasia in rats recovering from massive small bowel resection. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Science, 1992

<p>This investigation focused on the mRNA expression of drug metabolising Cytochromes P-450 (CYP) and UDP-glucuronosyltransferases (UGT) and the transport protein P-glycoprotein (Pgp) in the small intestine of humans and rats.</p><p>The mRNA expression of the investigated genes in the human small intestine (duodenum) varies between individuals giving each one of us personal profile. In general, the most dominant forms are Pgp, CYPs 2C9, 2D6, 3A4, and UGTs 1A1, 1A10, 2B7. However, which of these is the highest expressed one varies between individuals.</p><p>The correlation in expression between some CYP forms and UGT forms respectively is relatively high, which indicates that they have some regulatory mechanisms in common. It was also shown that the mRNA expression of both CYPs and UGTs may be affected by endogenous and exogenous factors. Sex and ethnic background, affected the mRNA expression of CYP2A6 and 2E1 respectively. Commonly used drugs such as acetylsalicylicacid (ASA) and omeprazole (omep) affect CYP2A6, CYP2E1 (ASA) and CYP3A4, UGT1A4 (omep). The expression of UGT1A4 is also affected by smoking. All these factors are commonly used and can therefore lead to important drug-drug interactions.</p><p>It was also shown that the human small intestinal CYP mRNA expression pattern differs from that found in the rat. The rat CYP expression is rather constant between the different individuals, and the main rat intestinal forms are CYP1A1, CYP2C, CYP2D6 and CYP3A1. The expression is the same for females and males and no difference can be seen between the different segments of the rat small intestine. As metabolic studies have often been done with rat liver we compared the mRNA expression in the two organs. We found that the mRNA expression of 1A1 was absent in the liver and that the CYP2B1, CYP2Cs, CYP2D1 and Pgp all had a stronger mRNA expression in the small intestine compared to the liver. It is therefore important to realise that results from metabolic studies on liver may not be directly extrapolated to the small intestine.</p><p>Artemisinin is an orally used drug in multidrug treatment of malaria in Southeast Asia. It has been suggested that artemisinin can induce drug metabolism and therefore be involved in drug-drug interactions. This study shows that artemisinin induces mainly the CYP2B via nuclear receptor CAR.</p>