The mode of action of bradykinin

The action of bradykinin on transepithelial transfer of sodium and water in isolated rat jejunum and on smooth muscle contraction of rat terminal ileum has been investigated. (1) Bradykinin was shown to stimulate transfer at low control transfer, inhibit transfer at high control transfer and have no effect at intermediate transfer in rat jejunal sacs. Stimulation of transfer occurred only when bradykinin was in the serosal solutiun while inhibition of transfer occurred whether bradykinin was in the aerosal or mucosal solution. Bradykinin-induced stimulation of transfer was not affected by adrenalectomy, nephrectomy, combined adrenalectomy-nephrectomy,  nor maintenance on 1% saline drinking solution or low sodium diet pretreatment. Meclofenamic acid abolished the bradykinin-induced inhibition of water transfer while prostaglandins A1, E1 aud F2α all potentiated this action. Theophylline inhibited water transfer and potentiated the bradykinin-induced inhibition of water transfer. Cyclic AMP and dibutyryl cyclic AMP both inhibited water transfer and the bradykinin-induced inhibition of water transfer was potentiated by the latter. ( 2 ) Bradykinin-induced contractions of rat terminal ileum were little affected by hyoscine while those of acetylcholine were abolished. Anoxia reduced markedly responses tv bradykinin while those of acetylcholine were little affected . Theophylline reduced the responses of rat terminal ileum to bradykinin significantly more than those to acetylcholine. Aspirin and indomethacin reduced markedly the responses to bradykinin while not affecting those to acetylcholine and PGT2. Meslofenamic acid at a concentration of 3.4 µM blocked bradykinin-induced contractions but had no effect on those to acctylcholine, PGE2 or PGF2 and at a concentration of 17. 0 µM drastically reduced bradykinin responses but also reduced those to acetylcholine, PGE2 and PGF2α• Flufenamic acid drastically reduced responses to bradykinin while not affecting those to acetylcholine and PGE2 and slightly affecting those to PGF2α. Polyphloretin phosphate reduced responses to bradykinin, PGF2α and PGE2 but not acetylcholine . Diphloretin phosphate reduced responses to bradykinin, PGF2 and PGE2 in a dose dependent manner but not those to acetylcholine. SC 19220 , in a dose dependent manner, inhibited responses to bradykinin and PGE2 but not to acetylcholine and PGF2. 7 oxa - 13 -prostynoic acid non specifically reduced responses to acetylcholine, bradykinin and PGE2. Bradykinin, in the presence of SQ 20881 , increased the release of prostaglandin-like activity from rat terminal ileum and this was reduced or abolished in the presence of indomethacin, aspirin, meclofenamic acid or flufenamio acid. The extract of PG-like activity did not appear as PGE, PGA or PGFon TLC, but included a substance with similar mobility as 15-Keto-prosta-glandin E2.

Adrenoceptors and intestinal fluid and electrolyte transport in the rat

Noradrenaline was found to significantly stimulate fluid and Na absorption across everted sacs of rat jejunum. Of a number of a1, and 2-adrenoceptor antagonists tested only prazosin significantly inhibited the stimulant effect of noradrenaline and further experiments revealed an antiabsorptive effect of prazosin alone. Theophylline reduced jejunal fluid and Na absorption and this effect was not reversed by 2-adrenoceptor stimulation in contrast to previous findings in vivo. Evidence suggests the everted sac preparation is not appropriate to the study of intestinal fluid and electrolyte transport. The investigation of Jejunal ion transport in vitro was continued using an Ussing chamber preparation. Selective 2-adrenoceptor stimulation was found to depress electrogenic anion secretion, as neurotoxin tetrodotoxin indicated that this was a direct epithelial effect. 2-adrenoceptor agonists have considerable therapeutic value as antisecretory agents and the model of rat jejunum in vitro represents a convenient experimental model for research in this area. The selective 2-adrenoceptor antagonist ICI 118551 decreased basal SCC and inhibited increases in SCC in response to isoprenaline or salbutamol indicating the presence of a 2-adrenoceptor mechanism mediating both secretory tone and increases in secretory processes. Many intestinal secretagogues elicit electrolyte secretion via the stimulation of intramural secretory nervous pathways. If these pathways involve the activation of 2-adrenoceptorsthe 2-adrenoceptor antagonists may be useful in the treatment of diarrhoeal diseases. A single pass lumen perfusion technique was used to investigate possible sympathetic tone over colonic fluid and electrolyte absorption in the rat colon in vivo. The technique employed appeared to lack the necessary resolution for this study and alternative approaches are discussed

Adrenoceptor influences on fluid and electrolyte transport in the rat intestine

An investigation of rat jejunal and distal colonic electrolyte transport in-vitro was undertaken using an Ussing chamber prepartion. Selective α2-adrenoceptor stimualtion in the jejunum was found to depress theo-phylline elevated anion secretion, as evidenced by decreases in short- circuit current (SCC). or α1 -Adrenoceptor stimulation, after α2 -adrenoceptor antagonism in the jejunum, evoked transient increases in basal anion secretion, as reflected by transient increases in basal SCC. The use of the neurotoxin tetrodotoxin indicated that this was a direct epithelial secretory effect. 5-hydroxytryptamine (5-HT) on the jejunum elicited transient increases in basal anion secretion, as demonstrated by transient increases in basal SCC. The use of tetrodotoxin, reserpine and α1 -adrenoceptor antagonists, indicated that a major component of this epithelial secretory effect by 5-HT, was associated with activation of intramural nervous pathways of the sympathetic nervous system, ultimately stimulating α1-adrenoceptors. This might represent an important secretory mechanism by 5-HT in the jejunum. β2-Adrenoceptor stimulation in the distal colon was found to decrease basal SCC, as evidenced by the metoprolol resistant effect of the selective β2- adrenoceptor agonist salbutamol, and lack of effect of the selective β1-adrenoceptor agonist prenalterol. An investigation of rat distal colonic fluid and electrolyte transport in-vivo was undertaken using an colonic loop technique. Although a basal colonic absorption of Na+ and Cl-, and a secretion of K+ were observed, these processes were not under tonic α-adrenergic regulation, as evidenced by the lack of effect of selective α-adrenoceptor antagonism. The secretory effects of prostaglandin-E2 were inhibited by α-adrenoceptor activation, whereas such stimulation did not evoke pro-absorptive responses upon basal transport, unlike noradrenaline.

Efeito da Olmesartana na resposta inflamatória em modelo de mucosite intestinal em ratos

Intestinal Mucositis is inflammation and/or ulceration of mucosa of the gastrointestinal tract caused by anticancer therapies. Histologically, villous atrophy, damage to enterocytes and infiltration of inflammatory cells. Methotrexate (MTX) is a compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. The aim of this study was to evaluate the effect of Olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i.p.) administration of MTX (7 mg/kg) for three consecutive days. The animals were pretreated with oral OLM at 0.5, 1 or 5 mg/kg or with vehicle 30 min prior to exposure to MTX, for three days. Small intestinal (duodenum, jejunum and ileum) homogenates were assayed for levels of the IL-1β, IL-10 and TNF-α cytokines, malondialdehyde and myeloperoxidase activity. Additionally, immunohistochemical analyses of MMP-2, MMP-9, COX-2, RANK/RANKL and SOCS-1 and confocal microscopy analysis of SOCS-1 expression were performed. Treatment with MTX+OLM (5 mg/kg) resulted in a reduction of mucosal inflammatory infiltration, ulcerations, vasodilatation and hemorrhagic areas (p<0.05) as well as reduced concentrations of MPO (p<0.001) and the pro-inflammatory cytokines IL-1β and TNF-α (p<0.01), and increase antiinflammatory cytosine IL-10 (p,0.05). Additionally, the combined treatment reduced expression of MMP-2, MMP-9, COX-2, RANK and RANKL (p<0.05) and increased cytoplasmic expression of SOCS-1 (p<0.05). Our findings confirm the involvement of OLM in reducing the inflammatory response through increased immunosuppressive signaling in an IMM. We also suggest that the beneficial effect of Olmesartan treatment is specifically exerted during the damage through blocking inflammatory cytosines.

Biodistribution of the radiophamarceutical sodium pertechnetate (Na99mTcO4) after massive small bowel resection in rats

To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. Methods: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI-g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as signifi cant. Results: There were no signifi cant differences in %ATI-g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was signifi cantly greater than that of C and sham rats (p<0.05). Conclusion: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated

Small bowel adenocarcinoma. Two case reports

Introduction. Small bowel adenocarcinoma is a rare tumor, with a still not well studied tumorigenesis process, and non-specific symptoms that cause a delay in the diagnosis and consequently a worst outcome for the patient. Videocapsule endoscopy (VCE) and double-balloon enteroscopy (DBE) have revolutionized the diagnosis and management of patients with small bowel diseases. Surgery is the treatment of choice when feasible, while the chemotherapeutic approach is still not well standardized. Case reports. Two cases in 2 months (two women 52 and 72-yr-old) of primary bowel adenocarcinoma is reported. The site of the tumor was in jejunum, instead of the most common site in duodenum. The patients underwent DBE with biopsy and ink mark. Laparoscopic-assisted bowel segmental resection was performed. The pathologic diagnosis was primary jejunum adenocarcinoma. No post-operative mortality or significant morbidities were noted. Conclusion. The combination of DBE and laparocopic-assisted bowel surgery represents an ideal diagnostic and therapeutic method.

Biodistribution of the radiophamarceutical sodium pertechnetate (Na99mTcO4) after massive small bowel resection in rats

To evaluate the biodistribution of sodium pertecnetate (Na99mTcO4) in organs and tissues, the morphometry of remnant intestinal mucosa and ponderal evolution in rats subjected to massive resection of the small intestine. Methods: Twenty-one Wistar rats were randomly divided into three groups of 7 animals each. The short bowel (SB) group was subjected to massive resection of the small intestine; the control group (C) rats were not operated on, and soft intestinal handling was performed in sham rats. The animals were weighed weekly. On the 30th postoperative day, 0.l mL of Na99mTcO4, with mean activity of 0.66 MBq was injected intravenously into the orbital plexus. After 30 minutes, the rats were killed with an overdose of anesthetic, and fragments of the liver, spleen, pancreas, stomach, duodenum, small intestine, thyroid, lung, heart, kidney, bladder, muscle, femur and brain were harvested. The biopsies were washed with 0.9% NaCl.,The radioactivity was counted using Gama Counter WizardTM 1470, PerkinElmer. The percentage of radioactivity per gram of tissue (%ATI-g) was calculated. Biopsies of the remaining jejunum were analysed by HE staining to obtain mucosal thickness. Analysis of variance (ANOVA) and the Tukey test for multiple comparisons were used, considering p<0.05 as signifi cant. Results: There were no signifi cant differences in %ATI-g of the Na99mTcO4 in the organs of the groups studied (p>0.05). An increase in the weight of the SB rats was observed after the second postoperative week. The jejunal mucosal thickness of the SB rats was signifi cantly greater than that of C and sham rats (p<0.05). Conclusion: In rats with experimentally-produced short bowel syndrome, an adaptive response by the intestinal mucosa reduced weight loss. The biodistribution of Na99mTcO4 was not affected by massive intestinal resection, suggesting that short bowel syndrome is not the cause of misleading interpretation, if an examination using this radiopharmaceutical is indicated

Modulation de l’homéostasie lipidique intestinale suite à une intervention en médecine traditionnelle Cri chez un modèle animal d’obésité et de pré-diabète

Introduction : Les taux d’obésité et de diabète de type 2 et leurs complications sont plus élevés chez les populations autochtones que chez la population générale. Une des raisons pour ces taux très élevés de complications est la résistance culturelle des autochtones envers les soins de santé contemporains souvent dus aux traitements culturellement inadéquats pour ces affections. Afin d’adresser cette problématique, l’équipe sur les médecines autochtones antidiabétiques des Instituts de recherche en santé du Canada (ÉMAAD-IRSC) a étudié 17 plantes de la pharmacopée traditionnelle des Cris de la Nation de la Baie James, dont le peuplier baumier Populus balsamifera. Objectifs : Le but de cette présente étude est d’examiner les effets de P. balsamifera sur les contenus lipidiques de l’intestin ainsi que la composition des protéines clés impliquées dans le métabolisme des lipides. Matériel et méthodes : Les souris étaient assignées à huit semaines de diètes, soit la diète standard (CHOW), une diète à forte teneur lipidique (HFD) ou une HFD avec ajout de 125 mg/kg de Populus balsamifera. Résultats : Les résultats ont montré que les teneurs totales de l’intestin en cholestérol, en phospholipides et en triglycérides ne sont pas influencées par l’absence ou la présence de l’extrait de P. balsamifera. La teneur en acides gras a significativement augmenté dans le traitement HFD comparé au groupe contrôle CHOW. Le traitement avec P. balsamifera a significativement réduit le contenu d’acides gras dans le jéjunum vers des valeurs observées pour la diète contrôle. Une modification non significative a été notée dans l’expression des protéines FAS, CPT-1, ACC-P. Conclusion : Ces résultats renforcent davantage le potentiel d’utilisation de l’extrait de peuplier baumier dans le contexte de forte prévalence d’obésité dans les populations autochtones.

Modulation de l’homéostasie lipidique intestinale suite à une intervention en médecine traditionnelle Cri chez un modèle animal d’obésité et de pré-diabète

Introduction : Les taux d’obésité et de diabète de type 2 et leurs complications sont plus élevés chez les populations autochtones que chez la population générale. Une des raisons pour ces taux très élevés de complications est la résistance culturelle des autochtones envers les soins de santé contemporains souvent dus aux traitements culturellement inadéquats pour ces affections. Afin d’adresser cette problématique, l’équipe sur les médecines autochtones antidiabétiques des Instituts de recherche en santé du Canada (ÉMAAD-IRSC) a étudié 17 plantes de la pharmacopée traditionnelle des Cris de la Nation de la Baie James, dont le peuplier baumier Populus balsamifera. Objectifs : Le but de cette présente étude est d’examiner les effets de P. balsamifera sur les contenus lipidiques de l’intestin ainsi que la composition des protéines clés impliquées dans le métabolisme des lipides. Matériel et méthodes : Les souris étaient assignées à huit semaines de diètes, soit la diète standard (CHOW), une diète à forte teneur lipidique (HFD) ou une HFD avec ajout de 125 mg/kg de Populus balsamifera. Résultats : Les résultats ont montré que les teneurs totales de l’intestin en cholestérol, en phospholipides et en triglycérides ne sont pas influencées par l’absence ou la présence de l’extrait de P. balsamifera. La teneur en acides gras a significativement augmenté dans le traitement HFD comparé au groupe contrôle CHOW. Le traitement avec P. balsamifera a significativement réduit le contenu d’acides gras dans le jéjunum vers des valeurs observées pour la diète contrôle. Une modification non significative a été notée dans l’expression des protéines FAS, CPT-1, ACC-P. Conclusion : Ces résultats renforcent davantage le potentiel d’utilisation de l’extrait de peuplier baumier dans le contexte de forte prévalence d’obésité dans les populations autochtones.

Phytate-phosphorus and phytase contents on the relative weight of organs, intestinal morphometry and performance of broilers.

ABSTRACT: In order to evaluate the efficiency of phytase in diets with low and high phytate phosphorus (PP) content, as a consequence of wheat bran inclusion, on the relative weight of organs, intestinal morphometry and performance, three hundred and eighty-four male Cobb500 broilers were housed in metabolic cages. Animals were assigned into four treatments in a 2x2 factorial scheme in a randomized block design with eight replicates of 12 birds each. From 11 days of age birds received experimental diets, which consisted of: Diet low in PP; Diet low in PP with phytase (500FTU kg-1); Diet with a high PP and Diet with a high PP with phytase (500FTU kg-1). At 22 and 32 days of age two birds were slaughtered in order to collect gizzard, heart, liver, cecum, cloacal bursa, and at 32 days, a portion of the duodenum, jejunum and ileum was collected for morphometric evaluation. From 22 to 32 days of age average feed intake, average weight gain, average body weight and feed conversion ratio were also evaluated. Data were subjected to analysis of variance, fixed effects of diet and phytase and interaction between factors as well as the random block effects were tested. There was no significant interaction for the variables studied, concluding that phytase in diets with low or high phytate phosphorus content did not change the relative weight of organs, intestinal morphometrics and performance; only isolated effects were observed. RESUMO: Para avaliar a eficiência da fitase em dietas com baixo e alto teor de fósforo fítico (PP), em função da inclusão ou não do farelo de trigo, sobre o peso relativo de órgãos, morfometria intestinal e desempenho, foram alojados 384 frangos de corte, machos da linhagem Cobb500, em gaiolas metabólicas. Os animais foram distribuídos em quatro tratamentos em um arranjo fatorial 2x2 em delineamento de blocos casualizados com oito repetições e 12 aves por unidade experimental (UE). A partir de 11 dias de idade as aves receberam as dietas experimentais, que consistiram em: Dieta com baixo teor de PP; Dieta com baixo teor de PP com fitase (500FTU kg-1); Dieta com alto teor de PP e Dieta com alto teor de PP com fitase (500FTU kg-1). Aos 22 e 32 dias de idade foram abatidas duas aves por UE para coletar a moela, coração, fígado, ceco, bolsa cloacal, e aos 32 dias foi coletada uma porção do duodeno, jejuno e íleo para avaliação da morfometria. No período de 22 a 32 dias de idade foram avaliados o consumo médio de ração, ganho de peso médio, peso médio corporal e a conversão alimentar. Os dados foram submetidos à análise de variância, onde foram testados os efeitos fixos de dieta e fitase e a interação entre os fatores, bem como o efeito aleatório de bloco. Não foi observada interação significativa para nenhuma das variáveis estudadas, concluindo-se que a fitase em dietas com baixo ou alto de PP não altera o peso relativo dos órgãos, a morfometria intestinal e o desempenho, apenas efeitos isolados foram observados.