厚朴叶和皮不同提取部位的药理作用比较研究

通过小鼠最大耐受量测定法进行厚朴叶的急性毒性研究,采用小鼠浓氨水引咳法、炭末推进法对厚朴叶和皮不同溶剂部位提取物的镇咳和胃肠推进作用进行了比较研究。结果显示厚朴叶小鼠最大耐受量为112g/kg,为厚朴成人每日用量的747倍,且7日内均未出现中毒和死亡现象。厚朴叶石油醚提取部位低剂量组、厚朴皮乙醚提取部位低剂量组和石油醚提取部位能明显延长氨水致小鼠咳嗽潜伏期或减少咳嗽的频率。同时,厚朴叶乙醚提取部位低剂量组能明显提高炭末在小肠中的推进率,厚朴皮乙醚提取部位低剂量组能显著减少炭末在胃中的残留率。以上结果表明:在实验剂量范围内,厚朴叶几无毒性;其低剂量的石油醚和乙醚提取部位有较强的镇咳和胃肠推进效果。提示其药用价值有深入研究的必要。     

Metabolism of orally administered rac-1-O-[1'-14C]dodecylglycerol and nutritional effects of dietary rac-1-O-dodecylglycerol in mice

The metabolism of orally administered rac-1-O-[1'-14C]dodecylglycerol was investigated in mice. The substrate was rapidly absorbed in the intestine and then incorporated into ether glycerolipids of various organs and tissues in high proportions. In intestine and liver, however, large amounts of rac-1-O-[1'-14C]dodecylglycerol were catabolized by oxidative cleavage of the ether bond followed by degradation of the radioactive cleavage product, i.e., lauric acid, to water-soluble metabolites that were excreted in the urine at a fast rate. The feeding of a rac-1-O-dodecylglycerol-containing diet (1 g rac-1-O-dodecylglycerol/kg body weight X day) given over a period of 4 weeks did not significantly alter body weights or organ weights of mice. Analysis of total lipids revealed that high proportions of the substrate were incorporated into ether lipids of all organs and tissues during the feeding period, generally accompanied by a remarkable increase in saturated acyl moieties and a concomitant decrease of linoleoyl moieties of total lipids. Yet, 4 weeks after removal of the rac-1-O-dodecylglycerol-containing diet, the lipids of murine organs and tissues showed a close resemblance to those of the control group.     

Widespread occurrence of glyceryl ether monooxygenase activity in rat tissues detected by a novel assay

An assay was set up for glyceryl ether monooxygenase activity in tissue samples using the novel substrate 1-O-pyrenedecyl-sn-glycerol and high-performance liquid chromatographic analysis of reaction mixtures with fluorescence detection, allowing robust detection of enzymatic activity in microgram amounts of tissue homogenates. The activity partially purified from rat liver strictly depended on the presence of a tetrahydropteridine. Tetrahydrobiopterin-dependent glyceryl ether monooxygenase activity was observed in all rat tissues tested except female heart, with highest activities in liver, intestine, and cerebellum. Activity was not uniformly distributed in brain: it was higher in cerebellum than in striatum or cortex. These data demonstrate that tetrahydrobiopterin-dependent glyceryl ether monooxygenase is found not only in liver and the gastrointestinal tract but also in brain and other organs of the rat and provide an additional goal for tetrahydrobiopterin biosynthesis in these organs.     

High incorporation of dietary 1-O-heptadecyl glycerol into tissue plasmalogens of young rats

When 1-O-heptadecyl-rac-glycerol was fed (20 mg/g of food) to 19-day-old rats for 10 days, a high incorporation of the heptadecyl group into the 1-O-alk-1'-enyl group of ethanolamine plasmalogens of all tissues was observed. For example, 62% of the alkenyl groups from liver plasmalogen was of the 17:0 variety. The analogous values for other tissues were 62% in kidney, 57% in lung, 57% in heart, 50% in intestine, 43% in erythrocytes, 25% in testis and 8% in brain. The corresponding figures in the control rats (fed normal rat chow) were only 2-3% of 17:0 for all tissues. Available evidence indicates that dietary 1-O-heptadecyl-sn-glycerol is utilized to form tissue plasmalogens without the cleavage of the ether bond. The relevance of these results to the possible dietary ether lipid therapy of patients suffering from congenital ether lipid deficiency is discussed.     

Synthesis and anaerobic biodegradation of indomethacin-conjugated cellulose ethers used for colon-specific drug delivery

Water soluble cellulose ethers, including methylcellulose and two hydroxyethylcelluloses with different molecular weights, were conjugate with indomethacin at room temperature. The chemical structures of the conjugates were characterized by FTIR, ¹H NMR and UV–vis spectroscopy. The results confirmed that different amounts of IND residues were covalently bonded to cellulose ether backbones through ester linkages. Their anaerobic biodegradation in colonic fermentation was investigated by gel permeation chromatography, gas chromatography and UV–vis spectroscopy. These conjugates were found to have different biodegradabilities, depending on the cellulose ether used and the amount of conjugated indomethacin residues. In vitro release experiments showed that hydroxyethylcellulose-based conjugates with low IND residues content could exhibit a sustained drug release behavior in colonic fermentation and were stable in the simulated media of the stomach and small intestine. Therefore, they are promising candidates for future applications in colon-specific drug delivery.     

A Virus from Epidemic Vomiting Disease

An illness consisting of vomiting, fever, and mild diarrhoea after a short incubation period was observed in a boarding school and reproduced in volunteers who received filtered extracts of faeces from a typical case. The main discriminatory diagnostic feature of the illness in volunteers was vomiting. The faeces contained no pathogenic bacteria nor any virus that could be detected in tissue cultures and there was no evidence that an infective agent could be grown in organ cultures of human intestine. The agent was shown to be ether stable and passed a 50-nm filter. Laboratory studies on another agent of uncertain significance and obtained in other epidemics are briefly described.     

Release of peptide YY by fat in the proximal but not distal gut depends on an atropine-sensitive cholinergic pathway

Peptide YY (PYY) is released when PYY cells in short term culture are exposed to fat suggesting that this peptide may be released by fat in the distal gut without neural stimulation. PYY is also released by fat in the proximal 1/2 of small intestine. To test the hypothesis that the release of PYY by fat in the proximal but not distal intestine may depend on an atropine-sensitive, cholinergic pathway, PYY levels were compared in four dogs equipped with duodenal and mid-intestinal fistulas when 60 mM oleate was perfused into either the proximal (between fistulas) or distal (beyond mid-intestinal fistula) 1/2 of gut at 2 ml/min for 120 min with intravenous administration of saline or atropine. We found that, when fat was confined to the proximal 1/2 of the intestine, PYY release was reduced following intravenous atropine when compared with saline (p<0.01). However, when fat was confined to the distal 1/2 of the intestine, PYY release was not affected by the intravenous atropine. We conclude that PYY release by fat in the proximal but not distal intestine depends on an atropine-sensitive, cholinergic pathway.     

Polyaza crown ether as non-nucleosidic building blocks in DNA-conjugates

The synthesis of amphiphilic polyaza crown ether monomers X (palmityl-substituted), Y (cholesteryl-substituted) and Z (dipalmityl-subtituted) and their incorporation into oligonucleotides are described. Their effects on thermal duplex stability were investigated by UV melting curve analysis. Thermal denaturation experiments showed remarkable stabilization of dsDNA by polyaza crown ether monomers when incorporated in opposite positions. The series of polyaza crown ether monomers (X, Y, and Z) with different lipophilicity showed a trend of increased stability of the corresponding dsDNA with increasing lipophilicity of the polyaza crown ether monomer.     

Studies on the mechanism of inhibition of the mitochondrial electron transport by antimycin. III. Binding of antimycin to sub-mitochondrial particles and to complex III

1. Extraction by ether removes only about one-half of antimycin added to sub-mitochondrial particles, independently of the amount of antimycin added up to that necessary for 100% inhibition.

2. The amount of antimycin extractable with ether remains the same even when the antimycin is redistributed between an antimycin-inhibited preparation and an untreated. The antimycin remaining after ether extraction is redistributed between ether-accessible and ether-inaccessible sites when the preparation is incubated on its own or with an untreated preparation.

3. Low concentrations of cholate increase the extractability of the antimycin by ether.

4. Complex III binds antimycin more firmly than sub-mitochondrial particles. However, antimycin is readily extracted by ether, leading to restoration of enzymic activity and cleavage of the complex by bile salts.

5. The results are consistent with an explanation of the sigmoidal inhibition curve with antimycin and preparations of the intact respiratory chain in terms of an allosteric model.     

The diurnal migration of the fowl cestode, Raillietina cesticillus

R. cesticillus was found to undergo a diurnal migration in both multiple and single worm infections of the fowl. This migration involved movement of both scoleces and strobilae and occurred in an anterior direction when the intestine was empty of food, and in a posterior direction when the intestine contained food. The relevance of the migration to the histological picture of the worm in situ is discussed and some possible explanations for the migration are suggested.     

Isolation and characterization of brush-border membrane from trout intestine. Regional differences

The isolation of brush-border membranes from trout enterocytes is described for both middle and posterior intestine. Both procedures are based on differential centrifugations combined with calcium precipitation. Classical marker enzymes are quantified and indicate a valuable purification of the membranes (13-18-fold). No difference appears when comparing the relative amounts of phospholipids, cholesterol and proteins in microvillus membranes isolated from either middle or posterior intestine. In contrast, the membranes isolated from middle intestine are more unsaturated than those from the posterior one, and their sphingomyelin/phosphatidylcholine ratio is lower. These differences are reflected by fluorescence anisotropy studies with diphenylhexatriene as lipid fluorophore which indicate a higher fluidity of the microvillus membranes from the middle intestine as compared with those from the posterior intestine. These results point out the importance of the fatty acyl chains and that of the relative amounts of phosphatidylcholine and sphingomyelin in controlling the fluidity of biological membranes in relation with their transport properties.     

Myoelectric response of the small intestine to the orad presence of the tapeworm Hymenolepis diminuta.

During its 24-hr migratory cycle in the small intestine, Hymenolepis diminuta is located in the orad part of the small intestine during the early morning hours and then in the caudad part of the small intestine during the late afternoon and early evening. During the later period, tapeworm-induced alterations of interdigestive myoelectric activity, a correlate of smooth muscle contraction or intestinal motility, are most intense in the ileal region. The hypothesis tested was that the tapeworm-induced changes in intestinal motility are local responses of the intestine responding to the close proximity of the lumenally positioned tapeworm and to the nutritional state of the host. The small intestine was monitored before and for 20 days after infection using electrodes implanted on the serosa of the small intestine. Myoelectric recordings were analyzed for the frequency of the normal patterns of interdigestive myoelectric spiking patterns and the altered myoelectric spiking related to tapeworm infection. During the morning hours, when the tapeworms are situated in the orad small intestine, no changes were observed during the normal myoelectric pattern of the digestive phase in any region of the intestine. When examined after the conversion of the digestive to interdigestive phase of motility, only on day 10 postinfection was the interdigestive phase significantly altered. It was concluded that the presence of the tapeworm in the orad small intestine during the satiety stage of the rat causes no changes in the electric events of the small intestine, with the exception of day 10 postinfection. Because tapeworms in the orad small intestine do not induce the tapeworm-altered myoelectric activity observed in the afternoon and evening with caudally positioned tapeworms, tapeworm-altered motility is not simply a response of the small intestine to the local presence of the tapeworm.     

Evaluation of azo food dyes for mutagenicity and inhibition of mutagenicity by methods using Salmonella typhimurium

The mutagenicity of 4 azo dyes (FD&C Yellow No. 5, FD&C Yellow No. 6, FD&C Red No. 40 and amaranth) that are widely used to color food has been evaluated. 4 different methods were used: (1) the standard Ames plate-incorporation assay performed directly on the dyes in the absence of S9 and in the presence of rat- or hamster-liver S9; (2) application of the standard plate assay to ether extracts of aqueous solutions of the dyes; (3) a variant of the standard assay, using hamster liver S9, preincubation, flavin mononucleotide (FMN) and other modifications designed to facilitate azo reduction; and (4) reduction of the dyes with sodium dithionite, followed by ether extraction and the standard plate assay. Assays that include chemical reduction (methods 3 and 4) were included because azo compounds ingested orally are reduced in the intestine with the release of free aromatic amines. No mutagenic activity was seen for any of the azo dyes tested by using the standard Ames plate assay (method 1). Ether extracts of some samples of FD&C Yellow No. 6, FD&C Red No. 40 and amaranth were active (method 2), but only at high doses, generally 250 mg-equivalents or more per plate. These results indicate the presence of low levels of ether-extractable mutagenic impurities. The FMN preincubation assay (method 3) gave negative results for all dye samples tested. Most batches of FD&C Red No. 40 tested had mutagenic activity that was detectable when the ether extract of less than 1 mg of dithionite-reduced dye was plated in the presence of S9 (method 4). This finding implies that an impurity in these samples of FD&C Red No. 40 can be reduced to yield an ether-extractable mutagen. Dithionite-reduced samples of FD&C Yellow No. 6 and amaranth showed ether-extractable mutagenic activity only at much higher doses than those at which activity was seen with most dithionite-reduced samples of FD&C Red No. 40 (method 4). FD&C Yellow No. 5 showed no mutagenic activity with this method. Mutagenic activity was not detected when FD&C Red No. 40 was tested by using the azo reduction preincubation assay with FMN (method 3).(ABSTRACT TRUNCATED AT 400 WORDS)     

The selective uptake and transmission of proteins to the circulation from the small intestine of the sucling rat

The relative concentration of various immunoglobulins attained in the sera of 14-day-old rats have been compared 4 h after their oral and intraluminal administration.The circulatory concentration of these proteins attained higher values when they were administered into the isolated proximal small intestine than when they were administered into the distal small intestine. Selective uptake of proteins was shown to predominate in the proximal small intestine.     

Non-desensitizing in vitro anaphylactic reaction of chicken visceral muscle

1. The contractions elicited in pieces of small intestine of actively immunized young chickens upon exposure to the specific antigen (Ag), or Schultz-Dale reaction, have been compared to similar responses of sensitized guinea-pig intestine. 2. Guinea-pig intestine responds, typically, with a large contraction to the first application of Ag. This is followed by a spontaneous relaxation of the preparation, while still in the presence of the Ag, and a rapid desensitization; i.e. further exposures to Ag fail to evoke new contractions. 3. In marked contrast, chicken intestine responds to the Ag with a contraction that remains at its maximal initial value for ca 5 min and then declines only slowly. 4. Exposure to the Ag does not desensitize chicken intestine, which relaxes upon washing out the antigenic protein but contracts again when this is re-introduced in the bath. 5. In addition, consecutive Schultz-Dale reactions of chicken intestine showed a consistent potentiation. They reached a maximal amplitude when the tissue was exposed to the Ag 5-7 times. Such a potentiation is abolished by storing the preparations for 24 hr at 4 degrees C. 6. These observations are discussed in terms of the known properties of avian antibodies.     

Na+ transport in perfused intestine and in isolated enterocytes of freshwater trout deprived of essential fatty acid

1. Unidirectional Na+ fluxes obtained in perfused preparation of intestine and Na+ effluxes from enterocytes isolated by a specific method have been determined in the middle intestine of freshwater rainbow trout. 2. Fish were fed semi-purified diets containing 8% by wt of either cod liver oil as reference, grape seed oil or hydrogenated coconut oil which are both deficient in fatty acids (FA) of the (n-3) series essential for the trout. 3. Important modifications in the Na+ intestinal absorption were induced by these deficient diets when measured in perfused intestine. 4. Conversely, no changes were seen in the Na+ active or passive effluxed when measured in enterocytes isolated from trout fed the same diets. 5. Na+,K+-ATPase activities were also unmodified by any diet. 6. It is concluded that deprivation of essential fatty acids reduces Na+ absorption capabilities of trout intestine, an effect which is mainly located at the apical membrane of enterocytes. 7. These results strongly demonstrate that apical entry and active serosal transport are separately modified in trout intestine by EFA deficient diet. 8. Furthermore the FA of the (n-3) series are essential for the retention of functional properties of membranes and ionic permeabilities in particular.     

Dietary regulation of ornithine transcarbamylase mRNA in liver and small intestine

In the rat, changes in dietary protein intake give rise to changes in the levels of ornithine transcarbamylase (OTC) in liver and small intestine--an increase in liver and decrease in small intestine. The changes in enzyme level are accompanied by similar changes in levels of specific mRNA. Thus in liver, there is an increase in the level of specific mRNA when protein intake is increased, whereas in small intestine there is a small decrease. Comparison of changes in specific mRNA with total poly-A-containing RNA showed that the change in OTC mRNA in liver paralleled the change in total RNA levels. In contrast, in small intestine the small decrease in OTC mRNA levels when protein intake was increased was in the face of an increase in the level of total mRNA. Whereas the level of OTC is 20-fold higher in liver than in small intestine, the mRNA level for the enzyme differs by only 2.5-fold.     

A Successful Treatment for Toxic Symptoms resulting from Ether Anæsthesia,based on a Biochemical Investigation

(1) Blood-sugar rises and blood-pressure falls as ether an?sthesia progresses.-(2) Blood-sugar is high and blood-pressure low when symptoms of shock are present.-(3) There is some justification for thinking that the pancreatic hormone is deficient as the result of the ketosis produced in connection with ether an?sthesia.-(4) Insulin administration is a successful method of treatment for post-an?sthetic toxic symptoms, which are always associated with a high blood-sugar, and also prevents these from developing. It tends to increase a fallen blood-pressure and reduce a raised blood-sugar during ether an?sthesia.     

The effect of Myrtus communis L. ethanol extract on the small intestine and lungs in experimental thermal burn injury

Thermal trauma can damage organs away from the skin burn site and lead to multiple organ dysfunction. Following thermal injury, all tissues are exposed to ischemia, and as a result, resuscitation and reperfusion occur during the burning shock. Burn damage starts systemic inflammatory reactions that produce toxins and reactive oxygen radicals that lead to peroxidation. This study aimed to investigate, for the first time, the possible antioxidant effects of Myrtus communis ethanol extract on burn-induced oxidative distant organ injury orally. The thermal trauma was generated under ether anesthesia by exposing the dorsum of rats to 90 ^°C water bath for 10 s. 100 mg/kg/day Mrytus communis ethanol extract was applied orally for two days. Malondialdehyde (MDA) and glutathione (GSH) levels, glutatinone-S-transferase (GST), superoxidedismutase (SOD) and catalase (CAT) activities were determined to detect the possible antioxidant effects of myrtle on small intestine and lung tissues. Burn damage significantly increased MDA levels in lung and small intestine tissues, and significantly decreased GSH levels, CAT and GST activities in the small intestine and lung tissues compared to control group. Mrytus communis ethanol extract decreased MDA level and increased GSH level, SOD, CAT and GST activities significantly in either small intestine or lung tissues. Mrytus communis extract may be an ideal candidate to be used as an antioxidant adjunct to improve oxidative distant organ damage to limit the systemic inflammatory response and decreasing the recovery time after thermal injury.