Balanced Caloric Restriction Minimizes Changes Caused by Aging on the Colonic Myenteric Plexus.

Aging can promote significant morphofunctional changes in the gastrointestinal tract (GIT). Regulation of GIT motility is mainly controlled by the myenteric neurons of the enteric nervous system. Actions that aim at decreasing the aging effects in the GIT include those related to diet, with caloric restriction (CR). The CR is achieved by controlling the amount of food or by manipulating the components of the diet. Therefore, the objective of this study was to evaluate different levels of CR on the plasticity of nicotinamide adenine dinucleotide phosphate- (NADPH-) reactive myenteric neurons in the colon of Wistar rats during the aging process using ultrastructural (transmission electron microscopy) and morphoquantitative analysis. Wistar male rats (Rattus norvegicus) were distributed into 4 groups (n = 10/group): C, 6-month-old animals; SR, 18-month-old animals fed a normal diet; CRI, 18-month-old animals fed a 12% CR diet; CRII, 18-month-old animals fed a 31% CR diet. At 6 months of age, animals were transferred to the laboratory animal facility, where they remained until 18 months of age. Animals of the CRI and CRII groups were submitted to CR for 6 months. In the ultrastructural analysis, a disorganization of the periganglionar matrix with the aging was observed, and this characteristic was not observed in the animals that received hypocaloric diet. It was observed that the restriction of 12.5% and 31% of calories in the diet minimized the increase in density and cell profile of the reactive NADPH neurons, increased with age. This type of diet may be adapted against gastrointestinal disturbances that commonly affect aging individuals.

Histological study of the left colon of rats after extra-mucosal seromyotomy (continent valves). Evaluation of colonic emptying.

PURPOSE: To elaborate an animal model with the objective of studying the continence of the biological valves surgically performed in the left colon of rats. METHODS: Thirty four rats were operated on and divided into three groups (G). G1 (sham) animals which underwent laparotomy only; G2 (perineal amputation without valves): animals which underwent amputation of the anal sphincter complex combined with a perineal colostomy; G3 (abdominoperineal amputation combined with valves): animals which underwent abdominoperineal amputation combined with three, equidistant and circumferential (360 degrees), extra-mucosal seromyotomies, of the descending colon, which were sutured to create biological valves combined with perineal colostomy. Animals were euthanized in the late postoperative period and surgical valves were saved for histopathological study. RESULTS: Surgical procedure provoked intestinal dilation, as well as segmented chambers along the descending colon. Retained fecalomas between the valves and proximal to them were also noted. Six rats died of intestinal obstruction due to fecal impaction at the surgical site. The sequence of events was: stasis, obstruction, distention, perforation, peritonitis and death. Histopathology showed inflammation due to foreign body type reaction around the sutured colon causing partial concentric stenosis, capable of interfering normal mechanical activity of the distal colon. This process resulted in retardation of the intestinal transit. CONCLUSION: Extra-mucosal seromyotomies, with seromuscular suture, can be used as an operative procedure capable of causing retardation in the intestinal transit of rats.

Histological study of the left colon of rats after extra-mucosal seromyotomy (continent valves): evaluation of colonic emptying / Estudo histológico do cólon esquerdo de ratos após a confecção de seromiotomias extra-mucosas (válvulas continentes): avaliação do grau de esvaziamento do conteúdo colônico

PURPOSE: To elaborate an animal model with the objective of studying the continence of the biological valves surgically performed in the left colon of rats. METHODS: Thirty four rats were operated on and divided into three groups (G). G1 (sham) animals which underwent laparotomy only; G2 (perineal amputation without valves): animals which underwent amputation of the anal sphincter complex combined with a perineal colostomy; G3 (abdominoperineal amputation combined with valves): animals which underwent abdominoperineal amputation combined with three, equidistant and circumferential (360(0)), extra-mucosal seromyotomies, of the descending colon, which were sutured to create biological valves combined with perineal colostomy. Animals were euthanized in the late postoperative period and surgical valves were saved for histopathological study. RESULTS: Surgical procedure provoked intestinal dilation, as well as segmented chambers along the descending colon. Retained fecalomas between the valves and proximal to them were also noted. Six rats died of intestinal obstruction due to fecal impaction at the surgical site. The sequence of events was: stasis, obstruction, distention, perforation, peritonitis and death. Histopathology showed inflammation due to foreign body type reaction around the sutured colon causing partial concentric stenosis, capable of interfering normal mechanical activity of the distal colon. This process resulted in retardation of the intestinal transit. CONCLUSION: Extra-mucosal seromyotomies, with seromuscular suture, can be used as an operative procedure capable of causing retardation in the intestinal transit of rats.

OBJETIVO: Modelo de experimentação, com confecção de válvulas biológicas no cólon esquerdo de ratos com o objetivo de estudar o grau de continência dessas válvulas. MÉTODOS: Trinta e quatro ratos foram operados e distribuidos em três grupos: G1 (grupo simulado) submetido apenas à laparotomia, G2 (grupo amputado sem válvula) submetido à amputação do conjunto esfincteral mais colostomia perineal e G3 (grupo amputado com válvula) submetido à amputação do conjunto esfincteral, confecção de três seromiotomias extra-mucosas, eqüidistantes e circunferenciais (360(0) - válvulas biológicas), no colon descendente mais colostomia perineal. No pós-operatório tardio, os animais dos três grupos foram submetidos à eutanásia para coleta da peça cirúrgica e estudo histopatológico das válvulas. RESULTADOS: Os resultados mostraram que o procedimento culminou em dilatação intestinal, confirmada pela formação de verdadeiras câmaras de segmentação e pela presença de fecalomas retidos entre as válvulas e cranialmente a elas. Seis ratos morreram em decorrência de obstrução intestinal por impacção de fezes no local operado, na seqüência: obstrução, estase, distensão, perfuração, peritonite e morte. As alterações histopatológicas confirmaram o processo inflamatório com reação do tipo corpo estranho, no perímetro do cólon suturado, proporcionando uma estenose parcial concêntrica, levando à alteração da atividade mecânica do cólon distal, resultando no retardo do trânsito intestinal. CONCLUSÃO: As seromiotomia extramucosas, com sutura seromuscular, podem ser utilizadas como técnica operatória para se obter retardo do trânsito intestinal em ratos.

Membrane permeability and antipyrine absorption in a rat model of ischemic colitis.

The aim of this study was to determine whether the duration of ischemia affects antipyrine absorption in the large intestine. This was carried out in a rat model of ischemic colitis in which ischemia and associated inflammation was induced by marginal vessel ligation. Blood flow was disrupted by positioning an o-ring around the distal rectum and ligating the marginal vessel at two locations in the hind-gut ligament artery region. Ligation was performed for 1, 2, 3, and 5h. We assessed large intestine damage by measuring key indicators of inflammation, myeloperoxidase (MPO) activity and thiobarbituric acid reactant substrates (TBARS) in the mucosa and by histological staining with hematoxylin-eosin stain. Antipyrine membrane permeability was assessed in Ussing-type diffusion chambers, and related pharmacokinetics were calculated from antipyrine plasma concentration measurements following colon administration of the drug. Vessel ligation caused some sloughing of epithelial cells and elevated the MPO and TBARS levels. Prolonged ligation failed to affect the apparent permeability coefficient (P(app)) of antipyrine. Prolonged ligation, however, gradually increased plasma antipyrine concentrations to near control levels. This increase was paralleled by increases in the absorption rate constant AUC and antipyrine bioavailability. Taken together, these results suggest that the absorption kinetics of antipyrine may depend on blood flow changes in the large intestine that occur with inflammation.

A new flavonoid derivative, dosmalfate, attenuates the development of dextran sulphate sodium-induced colitis in mice.

In this study, we have evaluated the efficacy of dosmalfate, a new flavonoid derivative compound, for the prevention and treatment of experimental colitis. To induce colitis, BALB/c mice received 5% dextran sulphate sodium (DSS) in their drinking water continuously for 7 days. Colitis was quantified by a clinical damage score, colon length, weight loss, stool consistency and rectal bleeding. Inflammatory response was assessed by neutrophil infiltration, determined by histology and myeloperoxidase (MPO) activity. Interleukin (IL)-1 beta, prostaglandins (PG)E(2) and (PG)D(2) concentrations in colonic tissue, histological and histochemical analysis of the lesions were also measured. Dosmalfate (400-800 mg/kg body weight, p.o.) ameliorated severe colitis reduced the degree of inflammation through reduction of neutrophil infiltration and IL-1 beta levels. (PG)E(2) and (PG)D(2) synthesis were significantly reduced in colitis control group and treatment with dosmalfate abolished the decrease in PG synthesis in colon mucosa. We conclude that dosmalfate is protective in acute DSS-induced colitis. The beneficial effects seem to be related to a decrease of neutrophil infiltration, absence of up-regulation of IL-1 beta and increase of PG production in colon mucosa.