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Experimental studies on fluid pathophysiology in small intestinal obstruction in the rat. V. Effects of intraluminal hyperosmolality and simultaneous intravenous infusions on the experimentally obstructed and decompressed small intestine.

An influx of fluid into the lumen of the intestine similar to that seen in simple obstructional ileus may be provoked by introducing a hyperosmolal glucose solution into the bowel. In the otherwise intact small intestine the effect of this influx of fluid will be in accordance with a simple dilution curve. The intestinal mucosa thus functions in the manner of a semipermeable membrane permitting only hypo-osmolal fluids to enter the intestinal lumen and in amounts independent of parenteral fluid infusions, regardless of osmolality. This relationship persists even after the intestine has been totally obstructed for 3 days. The influx of fluid has the same principal characteristics, and the only limiting factor on the magnitude of this fluid shift to the intestine is the lack of fluids resulting from the marked dehydration of the organism due to ileus. Prerequisites for this are normal epithelial function and normal mucosal circulation. Thus it is clear that the organism in general and the small intestine in particular, even when exposed to prolonged obstruction, are still able to counteract intraluminal hyperosmolality by dilution with hypo-osmolal fluid.

Animals↗

[Intensive effect of traditional Chinese medicines activating blood to resolve stasis on medicines dredging intestines--influence on peristalsis of small intestine in guinea pigs].

OBJECTIVE: To observe the changes of peristalsis of small intestine in guinea pigs after administration of traditional Chinese medicines activating blood to resolve stasis (Compound Danshen Decoction, CDSD) or/and medicines dredging intestines (Dachengqi Decoction, DCQD), and to explore the synergetic or intensive effect of CDSD on DCQD. METHODS: By means of BL-420 Biological Experimental System, peristalsis of small intestine was recorded and analyzed following administration of DCQD, CDSD or Huoxue Chengqi Decoction (HXCQD, compound of CDSD and DCQD) respectively in different experimental periods. RESULTS: The amplitude and frequency of intestinal peristaltic wave obviously increased following administration of the three decoctions, but HXCQD appeared to be most dominantly. CONCLUSION: The effect of DCQD can be further enhanced by combining use of CDSD, suggesting that the traditional Chinese medicines activating blood to resolve stasis have an intensive effect on medicines dredging intestines.

Animals↗

Small intestinal submucosa as a small-diameter arterial graft in the dog.

Autogenous saphenous vein, human umbilical vein, modified bovine collagen, Dacron, and PTFE have been used as small-diameter arterial grafts with moderate success. We tested autogenous small intestine submucosa as a small-diameter arterial graft in both a carotid and femoral artery (mean ID 4.3 mm) of 18 dogs (total of 36 grafts). All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by Doppler ultrasound techniques and angiography. Two grafts ruptured and 5 grafts occluded by 21 days after surgery. One graft became occluded at 14 weeks. Fifteen dogs were sacrificed at periodic intervals until 48 weeks after surgery. Patent grafts had no evidence of infection, propagating thrombus, or intimal hyperplasia. Graft aneurysmal dilation occurred in 4 grafts (11%). The grafts were composed of a dense organized collagenous connective tissue with no evidence of endothelial cell growth on the smooth luminal surface. Three dogs are alive at 76 to 82 weeks after surgery. Overall, graft patency was 75%. Graft patency after cessation of anticoagulation therapy was 92.3% (12 of 13 grafts). We conclude that autogenous small intestinal submucosa can be used as a small-diameter arterial graft in the dog and is worthy of further investigation.

Animals↗

Receptors for vasoactive intestinal peptide and secretin on small intestinal epithelial cells.

Binding of 125I-labeled vasoactive intestinal peptide (VIP) to dispersed enterocytes prepared from guinea pig small intestine was saturable, temperature dependent, and reversible, and reflected interaction of the labeled peptide with a single class of binding sites. Each enterocyte possessed approximately 60,000 binding sites and binding of the tracer to these sites could be inhibited by VIP [concentration for half-maximal effect (Kd), 12 nM] and by secretin (Kd greater than 1 micro M), but not by glucagon, gastrin, cholecystokinin, calcitonin, bombesin, litorin, physalaemin, substance P, eledoisin, serotonin, carbamylcholine, or histamine. With VIP and secretin, there was a close correlation between the relative potency for inhibition of binding of 125I-VIP and that for increasing cellular cAMP. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of cellular cAMP. In addition to inhibiting binding of 125I-VIP and increasing cellular cAMP in enterocytes, secretin caused an increase in short-circuit current across guinea pig small intestine in vitro. Prostaglandin E1 increased cellular cAMP, but did not alter binding of 125I-VIP and the increase in cAMP caused by prostaglandin E1 plus VIP or secretin was equal to the sum of the increase caused by each agent alone.

Animals↗

Immunocytochemical evidence for a paracrine interaction between GIP and GLP-1-producing cells in canine small intestine.

Glucagon-like-peptide 1 (GLP-1) released from the intestine is considered to be an important incretin. We have recently demonstrated that glucose-dependent insulinotropic peptide (GIP) stimulated GLP-1 secretion from canine ileal L cells in culture. To investigate further the interplay between GLP-1- and GIP-secreting cells, we set out to determine the exact location and abundance of both cell types throughout the canine intestine. Canine small intestine was subdivided into 15-20 segments and investigated by immunocytochemistry with computer-assisted imaging. The abundance of GIP-, GLP-1- and somatostatin-immunoreactive cells was determined. GIP-secreting K cells were equally distributed in duodenum and jejunum, with the GLP-1-secreting L cells concentrated in the jejunum (5% duodenum, 73% jejunum and 22% ileum). These results indicated that the middle section of the small intestine containing 69% of the K cells also contained 51% of the L cells. Double immunostaining confirmed this overlap and furthermore over 30% of the L cells in this region were found adjacent to K cells. These results suggest the existence of a paracrine interaction between the K and L cells and indicate the importance of the jejunum in the regulation of insulin release by enteric-derived incretins.

Animals↗

[Nitrogen and amino acid absorption in the small intestine of growing pigs. 2. Apparent and true crude protein digestibility and amino acid absorption to the end of the small intestine].

Studies of the apparent and true ileal digestibility of crude protein and the apparent and true amino acid (AA) absorption were carried out with 7 female pigs in the live weight range between 22 and 34 kg after ileorectostomy. Protein sources of varied quality with regard to the method of treatment (toasted) and untoasted soybean oilmeal) and to the AA composition (vital gluten or vital gluten + L-lysine X HCl) were used. Distinct differences regarding the apparent ileal digestibility of crude protein and the apparent absorption of amino acids were discovered between the protein sources, the cause of which is to be seen in the different amounts of endogenous N. The true ileal digestibility of crude protein and amino acid absorption were partly distinctly higher than the values of the apparent ileal digestibility of crude protein and AA absorption. On the whole one can say that the results of the investigation gained by means of ileorectostomy can be compared to the values gained from cannulated animals. Thus the experimental method used is suitable for studying the absorption process to the end of the small intestine of pigs.

Amino Acids↗

Effect of cimetidine on intestinal adaptation following massive resection of the small intestine.

Gastric acid hypersecretion follows massive resection of the small intestine. Steatorrhea as well as other metabolic imbalances is a challenging management problem associated with massive resection of the small intestine. In the literature, it has been suggested that the empiric use of cimetidine controls gastric acid hypersecretion following massive resection of the small intestine. In this study, an 80 per cent resection of the small intestine was performed upon 12 mongrel dogs. Ileal pH measurements, fecal fat content and serial intestinal biopsies were obtained for morphometric measurements. Steatorrhea was reduced by approximately 40 per cent in the cimetidine treated dogs. Ileal pH measurements declined immediately following intestinal resection. The cimetidine treated dogs demonstrated a return to normal levels within ten days following intestinal resection, p less than 0.05. Intestinal adaptation morphometric parameters revealed an accelerated adaptational response in the cimetidine treated dogs, p less than 0.05. Results of this study colaborates with the empiric and clinical indication for the use of cimetidine in the short gut syndrome clinical situation. In addition, the data suggest an intestinal adaptation accelerated response during the first phase of intestinal adaptation following massive resection of the small intestine in the dog.

Adaptation, Physiological↗

Concentration-dependent preferences of absorptive and excretive transport cause atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts as an interface between the body and ingested compounds.

Intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor of gliotoxin, was studied in isolated rat small intestine as a model cyclic dipeptide. Absorption clearance (CLabs) decreased in the presence of glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 degrees C. These indicate that cyclo(Phe-Ser) is in part transported by PEPT1. However, Eadie-Hofstee plot of absorption revealed an atypical profile at lower concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative experiments of absorptive and excretive transport showed that excretive transport from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the serosal side, and vise versa at a 1 mM cyclo(Phe-Ser). These results as well as the results of kinetic analysis indicate that intestinal absorption consists of passive transport, carrier-mediated absorptive transport by PEPT1 and carrier-mediated excretive transport, resulting in atypical absorption. Although cyclic dipeptides have potentials for drug, their intestinal absorption may be complex. The results of this study lead us conclude that absorptive and excretive transport by the small intestine acts as an interface between the body and ingested compounds.

Algorithms↗

Concentration-dependent atypical intestinal absorption of cyclic phenylalanylserine: small intestine acts as an interface between the body and ingested compounds.

Intestinal absorption of peptides in linear form has been studied extensively, but there is little knowledge of peptides in a cyclic form. In this report, intestinal absorption of cyclic phenylalanylserine (cyclo(Phe-Ser)), a precursor of gliotoxin, was studied in isolated rat small intestine as a model cyclic dipeptide. Absorption clearance (CLabs) decreased in the presence of glycylsarcosine, cephalexin or cephradine, substrates for H+/oligopeptide cotransporter (PEPT1). CLabs of cyclo(Phe-Ser) also decreased at 4 degrees C, thus indicating that cyclo(Phe-Ser) is in part transported by PEPT1. However, the Eadie-Hofstee plot of absorption revealed an atypical profile at lower concentrations of cyclo(Phe-Ser) (around 0.1 mM). Moreover, comparative experiments of absorptive and excretive transport showed that excretive transport from the serosal to mucosal side of isolated intestinal tissue at a 0.1 mM cyclo(Phe-Ser) was superior to absorptive transport from the mucosal side to the serosal side, and vice versa at a 1 mM cyclo(Phe-Ser). A kinetic model was constructed, in which cyclo(Phe-Ser) concentration for excretive transport was assumed to be at the binding site of excretive transporter, but not the unbound cytoplasmic concentration. These results as well as the results of kinetic analysis indicate that intestinal absorption consists of passive transport, carrier-mediated absorptive transport by PEPT1 and carrier-mediated excretive transport, resulting in atypical absorption. Although cyclic dipeptides have potentials as drugs, their intestinal absorption may be complex. The results of this study lead us to conclude that absorptive and excretive transport by the small intestine acts as an interface between the body and ingested compounds.

Animals↗

Evaluation of intestinal intramucosal pH, arterial and portal venous blood gas values, and intestinal blood flow during small intestinal ischemia and reperfusion in dogs.

OBJECTIVES: To determine whether small intestinal ischemia and reperfusion affects intestinal intramucosal pH (pHi), arterial and portal venous blood gas values, and intestinal blood flow (IBF) and to investigate relationships between regional intestinal tissue oxygenation and systemic variables in dogs. ANIMALS: 15 healthy adult Beagles. PROCEDURE: Occlusion of superior mesenteric artery (SMA) for 0, 30, or 60 minutes, followed by reperfusion for 180 minutes, was performed; IBF, pHi, arterial and portal venous blood gas values, arterial pressure, and heart rate were measured at various time points; and intestinal mucosal injury was histologically graded. RESULTS: Occlusion of the SMA induced significant decreases in pHi and IBF. After the release of the occlusion, IBF returned rapidly to baseline values, but improvement in pHi was slow. Arterial and portal venous blood gas analyses were less sensitive than tonometric measurements of pHi, and there was no correlation between results of blood gas analyses and tonometric measurements. Histologic score for intestinal mucosal injury increased significantly, depending on duration of ischemia, and there was a correlation between tonometric results and the histologic score. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that it is difficult to accurately evaluate local oxygenation disorders by monitoring at the systemic level, whereas clinically pHi is the only reliable indicator of inadequate regional intestinal tissue oxygenation in dogs.

Animals↗

Endocytosis and processing of protein by isolated villus and crypt cells of the mouse small intestine.

A small but antigenically significant amount of intact food proteins is absorbed at the intestinal level. These proteins are transported by an endocytotic mechanism mostly in degraded form via the lysosomal pathway of the enterocytes, but those that escape lysosomal degradation appear to be a small fraction of potential food antigens that enter the body. To establish whether protein uptake and processing are similar between mature and immature enterocytes, villus and crypts cells were isolated from the small intestine of adult mice. In each fraction, we measured lysosomal cathepsin activities and cell binding, uptake, and degradation of horseradish peroxidase (HRP). The following results were observed: (a) mice exhibited an increasing villus-to-crypt gradient of cathepsins B and D; (b) binding, internalization and degradation of HRP were twice as high in crypt cells as in villus cells, indicating that the rate of endocytosis in crypt cells doubled; and (c) the percentage of intracellular intact and degraded HRP remained similar in both cell types, suggesting that lysosomal degradation was not the limiting step of endocytosis. Chloroquine and ammonia increased intracellular intact HRP, but monensin did not. These results suggest that intestinal villus and crypt cells do not transfer proteins at the same rate. This may have important biological consequences in physiopathological states in which the crypt/villus ratio is greatly increased.

Animals↗

Normal physiology of small intestinal motility.

The small intestine produces a number of different contractions in various spatial and temporal patterns that promote efficient digestion, absorption, and propulsion of ingested material. The small bowel also serves a protective role through the use of special situation contractions that rapidly propel enteric contents into the stomach or colon, from which they may be expelled. Contractile activity of the small intestine is coordinated by an interplay of myogenic, neural, and chemical controls.

Animals↗

Ultrastructural aspects of the small intestinal lead toxicology. Part I: Surface ultrastructure of the small intestine mucosa in rats with lead acetate poisoning.

The effects of low concentration of lead acetate on the apical surface of the jejunal enterocytes were studied. Young male rats were divided into 2 groups which received 0.01% lead acetate solution in drinking water during 30 and 60 d respectively. Blood lead concentrations of poisoned rats were elevated to 30.33 micrograms Pb/100 ml at d 30 of intoxication, then slightly depressed at the end of experiment. Weight gain was impaired only in the 60-d group in comparison with controls. Samples from jejunum were processed for scanning electron microscopy using a critical point drying method and gold evaporation. The fine structure of the surface enterocytes was always determined in the epithelial bands above the levels of crypts nearly half a distance from crypt to villous top. The shape of the jejunal villi in poisoned rats was similar to that in non-poisoned rats. A marked feature of the rats' jejunum exposed to heavy metal for 30 d was a rough appearance of the surface villi, probably associated with distortion of the glycocalyx layer. Extensive areas with degenerative lesions were observed on the surface of the most villi on the 60th d of intoxication. Microvilli of enterocytes distributed within these areas were deformed and sometimes could be completely absent. All enterocytes exhibited various degrees of glycocalyx disturbance. It was concluded that the pronounced toxic effects of lead were related to modification of biochemical properties of the surface coat of enterocytes. This abnormal function of the glycocalyx could result in damage and microvillous malformations.

Animals↗