Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats

Co-administration of piperine, an alkaloid isolated from Piper nigrum L. enhanced bioavailability of beta lactam antibiotics, amoxycillin trihydrate and cefotaxime sodium significantly in rats. The improved bioavailability is reflected in various pharmacokinetic parameters viz. tmax, Cmax, t(1/2) and AUC, of these antibiotics. The increased bioavailability could be attributed to the effect of piperine on microsomal metabolising enzymes or enzymes system.     

Effect of ethanol on the pharmacokinetics of 2-14C-methaqualone in the rat

Blood concentrations of radioactivity at 2, 3 and 4 hr and tissue concentrations at 4 hr following 2-¹⁴C-methaqualone (25 mg/kg po) administration, were statistically higher in rats simultaneously dosed with ethanol (3 gm/kg po) than in controls receiving only methaqualone. The major route of elimination was biliary excretion and ethanol inhibited the biliary clearance of carbon-14. An inhibition of metabolism by ethanol could not be demonstrated and reduced clearance was attributed to a depression of active secretory processes by ethanol. Consequently, an elevation of plasma concentrations of free drug and an increased uptake of methaqualone into lipoid tissues such as the brain occurred offering an explanation for reports of potentiation following administration of the ethanolmethaqualone combination.     

Clinical and experimental parallels in studying the effect of chymotrypsin on the pharmacokinetics of antibiotics]

The effect of intramuscular chimotripsin on the levels of methicillin and tetracycline administered respectively intramuscularly and orally was studied in patients with chronic pneumonia and in experimental rats. It was found that the dose of chimotripsin providing higher methicillin blood levels was many times lower than the enzyme doses providing analogous indices for the blood serum and organs of the rats. When the patients were treated with tetracycline and chimotripsin, increased blood levels of the antibiotic were observed. Administration of chimotripsin to the rats had no effect on tetracycline pharmacokinetics in the animals.     

Characterization of the pharmacokinetics of dioscin in rat

Dioscin (diosgenyl 2,4-di-O-alpha-l-rhamnopyranosyl-beta-d-glucopyranoside) is an important constituent of some traditional Chinese medicines with several bioactivities. We have investigated the pharmacokinetics of dioscin in rat after intravenous and oral administrations. Compartmental methods were used to perform pharmacokinetic data analysis. The dose-dependent pharmacokinetics of dioscin was characterized after intravenous administrations (0.064, 0.16, 0.4 and 1.0mg/kg) to rats. There was significant decrease in clearance with increasing dose (4.67+/-0.09 ml/min/kg (0.064 mg/kg) versus 3.49+/-0.23 ml/min/kg (1.0 mg/kg), P<0.05), and the plot of reciprocal clearance values versus the doses was linear (r=0.909, P<0.05). After an I.V. dose of 1mg/kg, simultaneous oral gavage of activated charcoal did not change the pharmacokinetic parameters indicating enterohepatic recycling of dioscin is not important in rat. The absolute oral bioavailability was very low (0.2%). In tissue distribution and bile excretion studies after I.V. and oral administrations, dioscin was shown to undergo a prolonged absorption from the intestinal tract and slow elimination from organs, and only a small amount of drug was recovered in bile. The cumulative amounts of dioscin in feces and urine indicated that the parent drug is mainly excreted in the feces.     

Stereoselective pharmacokinetics of 3,4-methylenedioxymethamphetamine in the rat

Studies to characterize the pharmacokinetics of the enantiomers of MDMA were conducted in rats using the iliac arterial cannulation. Two routes of administration, intravenous and subcutaneous, were evaluated at two dose levels for each route [20 and 40 mg/kg (+/-)-MDMA for subcutaneous, 10 and 20 mg/kg (+/-)-MDMA for intravenous administrations]. The average half-life (+/- SD) for all dosing groups was 2.5 +/- 0.8 h for (-)-(R)-MDMA and 2.2 +/- 0.8 h for (+)-(S)-MDMA. The more rapid clearance of (+)-(S)-MDMA compared with (-)-(R)-MDMA is consistent with the area under the curve (AUC) data of the parent drug and its primary metabolite MDA. The mean (+/- SD) AUC S/R ratios of MDMA and MDA were 0.70 +/- 0.05 and 3.1 +/- 0.8, respectively. Following a 20 mg/kg dose of racemic MDMA iv the mean (+/- SD) of the percent dose excreted as (-)-(R)-MDMA, (+)-(S)-MDMA, (-)-(R)-MDA, and (+)-(S)-MDA were 20 +/- 10, 12 +/- 6, 3 +/- 1, and 6 +/- 2, respectively.     

抗生素和高脂饮食对大鼠肠道乳杆菌多样性的影响

【目的】对正常、高脂、抗生素处理大鼠肠道内乳杆菌进行定性和定量分析,比较不同处理组大鼠肠道乳杆菌的多样性。【方法】应用纯培养和非培养技术(16S r RNA基因序列分析、变性梯度凝胶电泳、实时荧光定量PCR)对大鼠肠道乳杆菌进行分离鉴定和多样性分析。【结果】16S r RNA基因序列同源性分析结果显示,正常组大鼠肠道内分离出的乳杆菌包括约氏乳杆菌(Lactobacillus johnsonii)、鼠乳杆菌(Lactobacillus murinus)、嗜酸乳杆菌(Lactobacillus acidophilus)、罗伊氏乳杆菌(Lactobacillus reuteri)、植物乳杆菌(Lactobacillus plantarum)、肠道乳杆菌(Lactobacillus intestinals)、动物乳杆菌(Lactobacillus animalis)和阴道乳杆菌(Lactobacillus vaginalis);但L.animalis在高脂处理组大鼠肠道内未分离到,L.intestinals和L.vaginalis在抗生素处理组大鼠中未分离到。DGGE结果显示3个组别大鼠肠道中乳杆菌构成差异明显,同一组内样品间相似性较高;相较于正常组和高脂组,抗生素组的丰度较差;且正常组大鼠肠道内乳杆菌的多样性高于高脂组和抗生素组。q-PCR结果显示正常组大鼠肠道乳杆菌的数量明显高于高脂组和抗生素组,高脂组的数量也明显高于抗生素组,且3个组别之间存在显著差异(P0.01)。【结论】高脂饮食及抗生素的使用会减少肠道内乳杆菌多样性。     

Influence of short-chain fatty acids and osmolality on mucin release in the rat colon

Summary The influence of short-chain fatty acids (SCFA) and osmolality on mucin release in the rat colon was studied histochemically by determining number of stained mucin-containing cells. SCFA did not significantly influence the number of cells staining for mucin. Hypertonic solutions (360 mosm/l) did not affect mucin release in the proximal colon, but stimulated mucin release in the distal colon. Solutions of lower osmolality (300 or 250 mosm/l) caused a considerable release of mucin from goblet cells as well as vacuolated cells in both the proximal and the distal colon; the lower the osmolality, the more mucin was released. The mucosa of the distal colon was conspicuously affected by solutions of lower osmolality. The influence of osmolality on mucin release was entirely local.Supported by a grant from the Deutsche Forschungsgemeinschaft (En 65/9)The authors wish to thank Prof. H. Höller and G. Rechkemmer for critical advice and Miss G. Becker for technical assistanceA preliminary portion of this study was presented at the 3rd Meeting of the European Intestinal Transport Group, Southampton, 21.–23. April, 1980     

Effect of antibiotics in the environment on microbial populations

Antibiotics act as an ecological factor in the environment that could potentially affect microbial communities. The effects include phylogenetic structure alteration, resistance expansion, and ecological function disturbance in the micro-ecosystem. Numerous studies have detected changes of microbial community structure upon addition of antibiotics in soil and water environment. However, the causal relationship between antibiotic input and resistance expansion is still under debate, with evidence either supporting or declining the contribution of antibiotics on alteration of antibiotic resistance. Effects of antibiotics on ecological functions have also been discovered, including nitrogen transformation, methanogenesis, and sulfate reduction. In the latter part, this review discusses in detail on factors that influence antibiotic effects on microbial communities in soil and aquatic environment, including concentration of antibiotics, exposure time, added substrates, as well as combined effects of multiple antibiotics. In all, recent research progress offer an outline of effects of antibiotics in the natural environment. However, questions raised in this review need further investigation in order to provide a comprehensive risk assessment on the consequence of anthropogenic antibiotic input.     

Characterization of mucin isolated from rat tracheal transplants

Subcutaneous rat tracheal grafts yield several milligrams of secretions from which a homogeneous mucin fraction was isolated and purified. Histological evidence demonstrated that a normal mucociliary epithelium and mucous secretion were maintained for the 4–6 weeks of the experiment. The collected secretions were initially characterized by column chromatography on Sepharose CL-6B which separated the excluded high molecular weight mucins (unpurified mucin fraction) from most of the serum-type glycoproteins and proteins, including albumin. A reductive alkylation treatment of the unpurified mucin fraction followed by Sepharose CL-4B chromatography removed contaminating protein and most of the mannose-containing material from the mucin fraction. The void volume material from this column produced a single high molecular weight band upon sodium dodecyl sulfate agarose/acrylamide gel electrophoresis. The purified mucin fraction contained 16.5% protein and primarily galactose, N-acetylglucosamine, N-acetylgalactosamine, and sialic acid. This fraction also underwent β-elimination in the presence of alkaline borohydride, demonstrating the presence of O-glycosidic linkages.     

Effect of the anthracycline antibiotics rubomycin and ruboxyl on the morphology and electric activity of the rat myocardium

It has been shown that 2 months after discontinuation of rubomycin administration to rats at a dose of 0.7 mg/kg there is a considerable damage of cardiomyocyte morphology manifested in myofibril disintegration and contractions, vacuolization, as well as chromatin coagulation indicative of the inhibition of nuclear synthesis. The experiments on the papillary muscles isolated from the same hearts have demonstrated a depression of Na-conductivity and reduction in the force of isometric contractions. Ruboxyl at a dose of 3 mg/kg caused no changes in the morphology and electrical activity. It is suggested that depression of Na-conductivity is mediated by a decrease in the number of sarcolemmal channels due to the inhibition of the channel-forming protein synthesis.     

Purification and immunofluorescent localization of rat submandibular mucin

Rat submandibular mucin (RSM) was purified by acid precipitation, then alcohol precipitation of the 30000g supernatant of gland homogenate, followed by column chromatography on Sephadex G-200. The mucin, which was eluted in the void volume, had an amino acid profile typical of a salivary mucus glycoprotein with high proportions of threonine, serine and proline (48.8% of total amino acids), and low proportions of aromatic and basic amino acids. It consisted of 63% (w/w) carbohydrate, which was shown by g.l.c. analysis to contain N-acetylglucosamine, N-acetylgalactosamine, galactose, sialic acid and fucose in the proportions 1.0:3.4:2.6:3.1:1.2. After staining of the mucin with periodic acid/Schiff reagent, analytical equilibrium ultracentrifugation in a CsCl density gradient produced a symmetrical peak of buoyant density 1.449g/ml, without evidence of protein contaminants. Sedimentation velocity centrifugation revealed a major periodate/Schiff-positive component (S⁰_20,w 5.06) with an associated shoulder of slower sedimenting material, suggesting polydispersity in the size of the mucin. Our findings suggest that the RSM purified in these studies has a molecular weight between 200000 and 1×10⁶. Antibody to RSM was prepared in a rabbit and produced a single precipitin line on immunoelectro-osmophoresis with the mucin. Immunofluorescence studies showed that the antibody localized only to submandibular acinar cells and confirmed that these cells were the source of RSM. The antibody was not directed towards the blood-group-A determinant (terminal N-acetylgalactosamine) present in the mucin.     

Effect of N-acetylcysteine on the pharmacokinetics of acetaminophen in rats

Oral administration of N-acetylcysteine (163 mg/kg at zero time and 82 mg/kg 30 minutes later) to adult male Sprague-Dawley rats given an intravenous injection of acetaminophen, 150 mg/kg at zero time, increased the formation of acetaminophen sulfate and thereby enhanced the elimination of acetaminophen. Apparently, N-acetylcysteine is an in vivo source of inorganic sulfate since availability of the latter is rate-limiting in the formation of acetaminophen sulfate. Increased metabolic conversion of acetaminophen to its sulfate conjugate results in decreased formation of other metabolites of acetaminophen, presumably including the reactive metabolite responsible for the hepatotoxic effect of the drug. This may account, at least in part, for the protective effect of N-acetylcysteine against acetaminophen-induced hepatotoxicity.