化学药物对家兔离体小肠平滑肌电生理特性的影响

观察各种化学药物对家兔离体小肠各段平滑肌的作用,采用常规离体灌流的十二指肠、空肠及回肠平滑肌标本作舒缩运动实验,记录用药前后各段小肠平滑肌的收缩活动特征及变化规律.结果显示：不同浓度的乙酰胆碱和磷酸组织胺能增强小肠各段平滑肌的收缩频率与幅度,其幅值变化与用药前有显著性差异（P＜0.01） ,并呈剂量依赖性;而不同浓度的肾上腺素和阿托品则抑制小肠各段平滑肌（P＜0.01） .不同肠段对各种化学药物的作用存在着差异,一般十二指肠作用最强,空肠次之,回肠最差.     

Application of drug receptor theories to the analysis of the myotropic effects of bradykinin.

Cat jejunum and terminal ileum, and rat stomach strip and rat uterus contract to bradykinin, while rat duodenum relaxes. Dose-response curves of classical hyperbolic shape are obtained in the first three preparations, but not in the others. The negative logs of the drug concentrations which give 50% of the maximal response. (pD2) Values were, respectively, 7.68 and 7.77 in the cat jejunum and terminal ileum, 6.78 in the rat stomach strip and 8.64 in the rat uterus in estrus. Theoretical dose-response curves, constructed by using experimental pD2 values in the equation of Clark, (General pharmacology. Verlag Van J. Springer, Berlin, 1937), are superimposed to experimental curves, obtained in the cat jejunum and terminal ileum, but not in the rat stomach strip. This comparison was not made in the rat uterus and duodenum. The myotropic effect of bradykinin appears to be a direct one in the cat jejunum, the terminal ileum and the rat stomach strip, because it is not affected by anticholinergics, antiadrenergics, antihistaminics and indomethacin. pD2 values and the slope of the dose-response curves of the rat uterus were reduced by indomethacin. The results indicate that cat jejunum and terminal ileum are sensitive and specific for bradykinin and appear to be the most reliable preparations for studies on the structure-activity relationships of this peptide.     

Contractile activity of duodenum, jejunum, and ileum at psychogenic stress in rabbits before and after muscarinic or nicotinic cholinoceptor blockade

In chronic experiments on rabbits, myoelectric activity (contractile activity index) in distal part of the duodenum, proximal and distal parts of the jejunum and proximal part of the ileum was studied under psychogenic stress caused by rigid fastening rabbit to a table in supine position. In duodenum, the stressor impact rendered stimulating, and in an ileum--inhibitory influence on their motility. In a jejunum the inhibition with the subsequent stimulation was observed, the latter being more expressed in a proximal part of the intestine. The proximo-distal gradient of exitatory and inhibitory influences of the psychogenic stress on contractile activity of the small bowel was revealed: in distal direction, inhibitory influences strengthen and stimulatory ones weaken. The muscarinic receptor blockade abolished increase of the duodenal and jejunal contractile activity obsereved in the control. The nicotinic cholinoceptor blockade abolished increase of the duodenal contractile activity in the 1-st phase of the stressor response and did not exclude an increase of the duodenal contractile activity in the 2-nd phase of the response. Muscarinic or nicotinic blockade did not influence the manifestation of the inhibitory reaction of proximal part of the ileum. In the period after release of the animal, the duodenal and jejunal contractile activity exeeded its initial level. This exeeding did not preserve after muscarinic cholinoceptor blockade but did preserve after nicotinic one in duodenum and proximal jejunum. The received data allow to conclude, that produced by the stress increase of the contractile activity of the distal part of duodenum, proximal and distal parts of jejunum produced by the stress, as well as exceeding the initial contractile activity level in the period after release of an animal, are mediated by cholinergic effector neurones of the enteric nervous system.     

In vitro drug permeation from chitosan pellets

The purpose of this study was to prepare and characterize coated pellets for controlled drug delivery. The influence of chitosan (CS) in pellets was evaluated by swelling, in vitro drug release and intestinal permeation assays. Pellets were coated with an enteric polymer, Kollicoat^® MAE 30 DP, in a fluidized-bed apparatus and the coating formulations were based on a factorial design. Metronidazole (MT) released from coated and uncoated pellets were assessed by dissolution method using Apparatus I. Intestinal permeation was evaluated by everted intestinal sac model in rats, used to study the absorption of MT from coated pellets containing CS or not through the intestinal tissue. Although the film coating avoided drug dissolution in gastric medium, the overall drug release and intestinal permeation were dependent on the presence of CS. Thus, pellets containing CS show potential as a system for controlled drug delivery.     

Changes in thymidine uptake in the gastrointestinal tract of the rat following treatment with 16,16-dimethyl prostaglandin E2

Thymidine uptake in the organs of the gastrointestinal tract of the rat was studied to determine if cell synthesis was involved in the increases in weight of the stomach, small intestine and colon which result from treatment with 16,16-dimethyl prostaglandin E₂ (16,16-dimethyl PGE₂). Animals were treated for 2 days with 16,16-dimethyl PGE₂. They were injected with the ³H-thymidine, sacrificed and the organs of interest were removed. The total amount of tritium in the stomach, duodenum, jejunum, ileum, and colon was determined.Thymidine uptake was significantly increased in the duodenum (1.50 times), jejunum (1.53 times), and colon (1.40 times) but not in the stomach and ileum. The increases were dose related in the duodenum and jejunum. The colon showed a similar dose response pattern but the changes with dose did not reach significance.These results confirm and extend a previous report that 16,16-dimethyl PGE₂ increased thymidine uptake in the duodenum but not the stomach (1). This is different from gastrin which has been shown by others to increase thymidine uptake in the stomach, duodenum, ileum and colon (2,3).     

Molecular cloning, distribution and ontogenetic expression of the oligopeptide transporter PepT1 mRNA in Tibetan suckling piglets

The gene encoding the oligopeptide transporter PepT1 (HGMW-approved gene symbol SLC15A1) from Tibetan porcine intestine was cloned. The open reading frame of this cDNA encodes 708 deduced amino acid residues that show high sequence similarity with its ovine and bovine counterparts. The putative protein has 12 putative transmembrane domains, including many structural features that are highly conserved among the vertebrate orthologs. PepT1 mRNA expression can be detected in duodenum, jejunum and ileum from Tibetan pigs at 28 days by RT-PCR. Real-time PCR analysis indicated that the jejunum had the highest expression of PepT1 when compared with the duodenum and ileum. PepT1 mRNA expression in the duodenum and proximal jejunum increases continuously from day 1 to day 14: expression was highest at day14 (P < 0.01) and then decreased gradually from day 21 to day 35. Our findings show that PepT1 mRNA expression in the distal jejunum increased gradually with age in suckling Tibetan piglet, and this may have important implications for amino acid and protein nutrition in young animals.     

Effects of chitosan oligosaccharides on intestinal oxidative stress and inflammation response in heat stressed rats

This study was to verify the effects of chitosan oligosaccharides (COS) on intestinal integrity, oxidative status, and inflammatory response in a heat-stressed rat model. A total of 24 male Sprague Dawley rats were randomly divided into 3 treatment: CON, the control group; HS, the heat stress group; HSC, the heat stress group with 200 mg/kg COS. Rats in the HS and HSC group exposed to a cyclical heat stress for 7 consecutive days. The CON and HS group provided basal diet, and the HSC group provided the same diet with 200 mg/kg COS. Compared with the HS group, rats in the HSC group had lower serum diamine oxidase and D-lactate acid level, higher villus height of jejunum and ileum, lower malondialdehyde (MDA) content in duodenum, jejunum, and ileum mucosa, higher glutathione peroxidase (GSH-Px), catalase (CAT) and total antioxidant capacity (T-AOC) activity in duodenum mucosa, higher T-AOC activity in jejunum mucosa, and higher glutathione (GSH) level in ileum mucosa. Compared with the HS group, rats in the HSC group had higher interleukin-10 (IL-10) level, but lower tumor necrosis factor-α (TNF-α) level in duodenum, jejunum, and ileum mucosa. These results indicated that COS may alleviate intestinal damage under heat stress condition, probably by modulating intestinal inflammatory response and oxidative status.     

In vivo changes in the intestinal reflexes and the response to CCK in the inflamed small intestine of the rat

Functional motor changes and morphological alterations have been associated with intestinal inflammation. The aim of our study was to evaluate functional alterations of intestinal reflexes and of the responses to CCK in the Trichinella spiralis model of intestinal inflammation. Rats were prepared with strain gauges and electrodes in the small intestine to evaluate spontaneous motor activity, the ascending contraction of the peristaltic reflex, and the motor responses to CCK-8 infusion. Infected animals showed increased motor activity at the duodenum and jejunum but not at the ileum. Ascending contraction was increased in both duodenum and ileum. Ascending excitation after N(omega)-nitro-L-arginine was still increased as well as the residual response after atropine. Response to CCK-8 during intestinal inflammation was changed in the jejunum, in which it turned from the inhibition shown in healthy animals to excitation. NADPH-diaphorase staining did not show any changes between distribution and density of positive neurons in either healthy or infected animals. In conclusion, intestinal inflammation induces functional changes in the motor activity that could explain the abnormal motor responses observed in inflammatory disorders.     

Profile of gastrointestinal damage induced by platelet-activating factor

The ulcerogenic actions of an intravenous infusion of platelet-activating factor (100 ng/kg/min) was studied in the rat. Damage to the stomach, duodenum, jejunum, ileum and colon were assessed histologically and using intraluminal acid phosphatase release as a marker of cellular damage. A 10-min infusion of platelet-activating factor caused extensive haemorrhagic damage to each of the regions examined, with the exception of the colon. Acid phosphatase release was significantly elevated in the stomach, jejunum, ileum (p less than 0.001) and duodenum (p less than 0.01), but not in the colon. These studies demonstrate that platelet-activating factor is a potent ulcerogen in the stomach and small intestine, and support a role for this endogenous phospholipid as a mediator of the ulceration associated with endotoxin-induced shock.     

Study of the physicochemical and biological stability of pediocin PA‐1 in the upper gastrointestinal tract conditions using a dynamic in vitro model

Aims: To evaluate the survival of Pediococcus acidilactici UL5 and its ability to produce pediocin PA‐1 during transit in an artificial gastrointestinal tract (GIT). To investigate the physicochemical and biological stability of purified pediocin PA‐1 under GIT conditions. Methods and Results: Skim milk culture of Ped. acidilactici UL5 was fed to a dynamic gastrointestinal (GI) model known as TIM‐1, comprising four compartments connected by computer‐controlled peristaltic valves and simulating the human stomach, duodenum, jejunum and ileum. This strain tolerated a pH of 2·7 in the gastric compartment, while lower pH reduced its viability. Bile salts in the duodenal compartment brought a further 4‐log reduction after 180 min of digestion, while high viable counts (up to 5 × 10⁷ CFU ml^?1 fermented milk) of Ped. acidilactici were found in both the jejunal and ileal compartments. Pediococcus acidilactici recovered from all four compartments was able to produce pediocin at the same level as unstressed cells. The activity of the purified pediocin in the gastric compartment was slightly reduced after 90 min of gastric digestion, while no detectable activity was found in the duodenal, jejunal and ileal compartments during 5 h of digestion. HPLC analysis showed partial degradation of the pediocin peptide in the duodenal compartment and massive breakdown in the jejunal and ileal compartments. Conclusions: Pediococcus acidilactici UL5 showed high resistance to GIT conditions, and its ability to produce pediocin was not affected, suggesting its potential as a probiotic candidate. The physicochemical and biological stability of pediocin was significantly poor under GIT conditions. Significance and Impact of the Study: Pediococcus acidilactici UL5 appears to be a potential probiotic candidate because its capacity to produce pediocin PA‐1 is not affected by the GI conditions as well as the strain shows an acceptable survival rate. Meanwhile, purified pediocin PA‐1 losses activity during GIT transit; microcapsules could be used to deliver it to the target site.     

Regional differences in the appearance of adult-type glycosphingolipids in the small intestine of inbred rats at weaning time

The small intestine of 15- to 33-day-old rats was cut into four segments: duodenum, proximal jejunum, distal jejunum, and ileum. Neutral glycosphingolipids and gangliosides were purified from each segment and analyzed by thin-layer chromatography in order to study the developmental appearance of adult-type glycolipids at each level of the small intestine. Type 1 A-6 glycolipid was first detected in the ileum at 15 days and subsequently in the jejunum and duodenum at 19 days of age. N-Glycolylneuraminic acid was expressed first in the ileum at 17 days, then in the proximal jejunum at 21 days, but only after 29 days in the duodenum. In each region, 6-8 days were required between first detection and full expression of N-glycolylneuraminic acid. The presence of 2-hydroxylated fatty acids in glucosylceramide was found first in the ileum at 19 days, 2-3 days before appearing in the duodenum and proximal jejunum. A period of 2-3 days was necessary to reach full adult-type level of 2-hydroxylated fatty acids in glucosylceramide. These results show that adult-type glycolipids appear earlier in the distal than in the proximal region of the rat small intestine, and that different glycolipids appear at different times and at different rates. The finding that the biochemical differentiation of the whole small intestine expands over a period of 3 days to 2 weeks, depending on the region and the glycolipid, before being fully completed indicates that, in addition to the time lag observed between the distal and the proximal region, the new cells arising from the crypt of Lieberkhün after 15 days of age are not at once fully differentiated.     

Eimeria dispersa, E. adenoeides, and E. meleagrimitis: intestinal mucosal disruption in turkeys as seen with scanning electron microscopy.

Tissues from the digestive tract of turkeys infected with Eimeria dispersa, E. adenoeides, or E. meleagrimitis were compared with tissues from uninfected controls as seen with light microscopy (LM) and scanning electron microscopy (SEM). Six regions were examined--duodenum, jejunum, ileum, cecal neck, cecal pouch, and large intestine. Although LM showed large numbers of E. dispersa in the epithelial cells, SEM usually showed little mucosal disruption. Occasionally the surface of duodenum and jejunum, as seen with SEM, was convoluted and disrupted. In one bird, some parasite-induced damage was found with either LM or SEM in the duodenum and jejunum of turkeys given E. adenoeides oocysts. Although LM showed parasites in the rest of the digestive tract of all E. adenoeides infected birds, SEM showed only a localized sloughing of the mucosa in the cecal pouch. The most extensive damage to the villar surface was caused by E. meleagrimitis. Infections often disrupted the villar tips, especially in the small intestine and cecal neck. Localized areas of pitting were often found on individual villi. All 3 species produced oocyst extrusion sites, especially in the ileum and the ceca.     

Electrical PD,short-circuit current and fluxes of Na and Cl across avian intestine

In vitro measurements were made of transmural potential difference (PD), short-circuit current (Isc), resistance and unidirectional fluxes of 22Na and 36Cl across the duodenum, jejunum, ileum and colon of normal sodium-replete domestic fowl (Gallus domesticus). The PD ranged from about 1 mV across the duodenum to 8 mV across the colon while the Isc was, respectively, 2.8 and 64 microA X cm-2. The jejunum and ileum exhibited values between these extremes. Unidirectional fluxes (under short-circuit conditions) of Na and Cl were lowest across the duodenum where there was no evidence of active transport of these ions. Unidirectional fluxes of Na and Cl were less across the jejunum than across the ileum or colon. A net active transport of Na (but not Cl) was observed in the ileum (= 106% of the Isc) and colon (= 50% of Isc). The possible physiological significance of these observations in the domestic fowl are discussed and are compared to that of a mammal, the rabbit.     

Expression,localization and possible functions of aquaporins 3 and 8 in rat digestive system

Although aquaporins (AQPs) play important roles in transcellular water movement, their precise quantification and localization remains controversial. We investigated expression levels and localizations of AQP3 and AQP8 and their possible functions in the rat digestive system using real-time polymerase chain reactions, western blot analysis and immunohistochemistry. We investigated the expression levels and localizations of AQP3 and AQP8 in esophagus, forestomach, glandular stomach, duodenum, jejunum, ileum, proximal and distal colon, and liver. AQP3 was expressed in the basolateral membranes of stratified epithelia (esophagus and forestomach) and simple columnar epithelia (glandular stomach, ileum, and proximal and distal colon). Expression was particularly abundant in the esophagus, and proximal and distal colon. AQP8 was found in the subapical compartment of columnar epithelial cells of the jejunum, ileum, proximal colon and liver; the most intense staining occurred in the jejunum. Our results suggest that AQP3 and AQP8 play significant roles in intestinal function and/or fluid homeostasis and may be an important subject for future investigation of disorders that involve disruption of intestinal fluid homeostasis, such as inflammatory bowel disease and irritable bowel syndrome.     

Profile of gastrointestinal damage induced by platelet-activating factor

The ulcerogenic actions of an intravenous infusion of platelet-activating factor (100 ng/kg/min) was studied in the rat. Damage to the stomach, duodenum, jejunum, ileum and colon were assessed histologically and using intraluminal acid phosphatase release as a marker of cellular damage. A 10-min infusion of platelet-activating factor caused extensive haemorrhagic damage to each of the regions examined, with the exception of the colon. Acid phosphatase release was significantly elevated in the stomach, jejunum, ileum (p<0.001) and duodenum (p<0.01), but not in the colon. These studies demonstrate that platelet-activating factor is a potent ulcerogen in the stomach and small intestine, and support a role for this endogenous phospholipid as a mediator of the ulceration associated with endotoxin-induced shock.     

Cellular Proliferation of Intestinal Epithelia in the Rat Two Months after Partial Resection of the Ileum

Sprague-Dawley rats subjected 2 months previously to partial resection (10 per cent) of the small intestine and their controls were injected with tritiated thymidine and sacrificed at 2 and 23 hours. Segments of the duodenum, jejunum, and ileum were autoradiographed, and the migration of the labelled cells during the period between 2 and 23 hours was measured with an eyepiece micrometer. The cells had migrated 35, 42, and 34 per cent of the total distance from the crypts to the tips of the villi in the control segments of duodenum, ileum, and jejunum respectively, and 43, 90, and 82 per cent, respectively, in similar segments from resected animals. The rate of migration in the portion of the intestine remaining after resection was approximately three times the normal rate in the ileum, twice the normal rate in the jejunum, and showed an increase of one-third in the duodenum. These results demonstrate that the rate of cell renewal is considerably greater in the remaining portion of the intestine of resected animals than in normal intestine. The increased rate of migration after resection, together with the increase in the height of the villi, resulted in an increase in the rate of cell renewal amounting to 141 per cent in the ileum, 114 per cent in the jejunum, and 23 per cent in the duodenum when compared with control segments.     

Effects of met-enkephalin on the mechanical activity and distribution of met-enkephalin-like immunoreactivity in the cat small intestine

Naloxone-dependent effects of Met-enkephalin (10(-8) M) on the spontaneous and electrically induced mechanical activities were studied in longitudinal and circular preparations isolated from the cat duodenum, jejunum and ileum. Met-Enkephalin changed the spontaneous activity of all preparations tested with the exception of the circular preparations from the ileum. Met-Enkephalin-induced responses of the longitudinal preparations from the ileum were abolished by treatment with tetrodotoxin (10(-7) M), while the responses of both longitudinal and circular preparations from the duodenum and jejunum were only partially depressed, being resistant to tetrodotoxin components. The latter were most pronounced in the duodenum. The neurogenic electrically induced (0.5 msec, 5 Hz, 150 pulses) responses of all the preparations consisted mainly of contractile components which were significantly and naloxone-dependently reduced by Met-enkephalin (10(-8) M). The contractile components of the responses, which were reduced by Met-enkephalin, were entirely abolished by atropine (3 x 10(-6) M). Both Met-enkephalin and atropine inhibitory effects on the neurogenic responses were more pronounced in the ileum. Met-Enkephalin was found in nerve fibers of the myenteric plexus distributed mainly among the circular muscle. Single immunoreactive nerve fibers were observed in the longitudinal muscle layer of the duodenum but not in the jejunum and ileum. The distribution of Met-enkephalin-like immunoreactivity along the small intestine did not show significant differences among the three intestinal regions tested. The results obtained suggest that Met-enkephalin can modulate the mechanical activity of the cat small intestine, inhibiting cholinergic transmission and/or activating smooth muscle opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Iron absorption by small intestine of chickens

Iron (Fe) absorption by three segments (duodenum, jejunum, and ileum) of the small intestine of chickens was studied by a perfusion technique in vivo in closed circuit using⁵⁹Fe Cl₃ and was related to the histological characteristics of each segment. The serosal transfers of Fe for the duodenum and jejunum were the same (14%/cm), but significantly different (p<0.05) from those of the ileum (9%/cm), which may be explained by the morphological and histological properties of the gut of chickens. However, the presence of Fe in blood and in liver was significantly lower after perfusion of the jejunum and ileum than after perfusion of the duodenum. It is concluded that chickens show an early adaptation of small intestine to Fe absorption in response to the considerable loss of Fe suffered during the laying process.     

Variance and covariances of the numbers of synonymous and nonsynonymous substitutions per site

Nei and Gojobori (1986) developed a simple method to estimate the numbers of synonymous (ds) and nonsynonymous (dN) substitutions per site. In the present paper, we have developed a method for computing variances and covariances of ds's and dN's and of the proportions of synonymous (ps) and nonsynonymous (pN) differences. We also have developed a method for computing the variances of mean dS, dN, pS, pN, without constructing a phylogenetic tree of the genes. We have conducted computer simulations based on simple evolutionary models and have shown that the new method gives good estimates of variances and covariances.