The influence of chronic administration of calcium carbonate on the bioavailability of oral ciprofloxacin

Six healthy male volunteers participated in a two-period, two-treatment study to determine the effect of chronic calcium carbonate administration on ciprofloxacin bioavailability. There was a mean reduction of 40% in Cmax and 43% in AUC when calcium carbonate was administered with ciprofloxacin, compared with ciprofloxacin alone (P < 0.05). There were no changes in either half-life or tmax. It is therefore recommended that patients being treated with ciprofloxacin for serious infections refrain from ingesting calcium supplements. If this is not possible, administration of ciprofloxacin 2 h before ingestion of the supplement is suggested.     

The laboratory study on biofragmentable anastomosis rings (BAR) in gastrointestinal tract reconstruction

To study and investigate the feasibility of biofragmentable anastomosis ring (BAR) for gastrointestinal (GI) tract reconstruction, we performed gastroenterostomy in 34 dogs. BAR anastomoses were performed with proper outer diameter and gape size in small bowel in 8 cases, in large bowel in 11 cases, in esophagus in 12 cases, in esophago-intestinal in 2 cases, in gastrojejunum in 1 cases. The postoperative serial X-ray examinations showed that BAR maintained good integration two weeks postoperation. The ring disintegrated into several small fragments that passed out of the body in feces from the 14th postoperative day after surgery. All of the dogs were killed on the 28th operative day and autopsied. The anastomosis site had smooth serosa and scar membrane in gross and were substituted by regenerative fibrous tissue. The specimen barim-air double contrast X-ray revealed that GI tract was coherent without leakage and stenosis. Therefor, the authors recognized that BAR can be recommended as a safe technique in GI operation.     

Endoscopic electromyographic study on upper gastrointestinal tract (author's transl)

Recently we made the electromyographic study on human gastrointestinal tract using the endoscopic method is useful for the clinical studies of the patho-physiological aspects on human gastrointestinal tract. The silver bipolar needle electrode which was 0.2 mm in diameter, 10 mm in length and 1.0 mm in interpolar distance and the electroencephalography recorder provided with pen-writer were used for this research. The endoscopy was done to the volunteer anesthetized his pharynx with xylocaine spray. 20 cases of gastro-electromyograms, 35 cases of duodeno-electromyograms and 5 cases of the electromyograms of duodenal papilla were recorded. On these endoscopic electromygorams, the typical rhythms and patterns of electrical activities were disturbed by various kinds of factors; that is, on the endoscopic manipulation, the sticking of needle electrode into the shallow layer of gastrointestinal wall and automatical pouring of water into canal through the endoscope. On volunteers' condition, his deep breathing, electrocardiogram and vasotonic condition were important factors. Typical duodeno-electromyograms showed the grouped spikes synchronizing with the duodenal peristalsis observed endoscopically. The electromyograms of the duodenal papilla showed the similar patterns and rhythms to those of duodeno-electromyograms on active phase. In the clinical study on the correlation and propagation between gastric and duodenal motility, the rhythms of electrical activities on duodeno-electromyograms were not similar to the rhythms of gastric peristalsis at the prepyloric region. The propagation of gastric movement to duodenal bulb were not able to be clarified. We assumed that the gastric and duodenal motility occurred each other on the different rhythms.     

The effects of vasculitis on the gastrointestinal tract and liver

Vasculitis can affect every organ of the digestive system. In many cases, it may first present with gastrointestinal symptoms. In several forms of vasculitis, including Churg Strauss syndrome, Henoch-Sch?nlein purpura, and lupus, the majority of patients have gastrointestinal involvement. The astute gastroenterologist should consider vasculitic causes of the symptoms seen in many patients. Making the correct diagnosis requires a thorough understanding of the potential role of vasculitis in causing these symptoms and the appropriate path to making a diagnosis. This article reviews the variety of manifestations of vasculitis on the digestive system, and emphasizes diagnosis and clinical manifestations.     

Quantification of circulating peptides and assessment of peptide uptake across the gastrointestinal tract of sheep

Gastrointestinal absorption of peptides was examined in sheep fed a forage-based diet. Peptide concentrations were determined in arterial, portal, and mesenteric blood and plasma by quantification of amino acid concentrations before and after acid hydrolysis of samples that had been first deproteinized then subjected to Sephadex G-15 gel-filtration to remove residual protein. In contrast to other studies of ruminants, peptide concentrations for individual amino acids were lower than for the corresponding free amino acids with peptide (expressed as a proportion of total nonprotein amino acid) representing not more than .25 to .3 of total amino acid. Peptide concentrations in arterial, mesenteric, and portal blood and plasma were similar, indicating that on this diet there was no net uptake of peptides from the small intestine (mesenteric-drained viscera, MDV) or the whole tract (portal-drained viscera, PDV). Increasing the intake of alfalfa pellets from 800 to 1,200 g/d, while increasing the absorption and net flux across the MDV and PDV of free amino acids, had no effect on peptide absorption. Preparation of blood and plasma samples for peptide analysis with methods used in studies in which substantial peptide absorption has been reported indicated no net MDV or PDV flux of peptide. Such conflicting data on the extent of gastrointestinal peptide flux are discussed in the context of methodological differences and the importance of diet and physiological state of the animal.     

Coexistence of proguanylin (1-15) and somatostatin in the gastrointestinal tract

In order to identify proguanylin-secreting cells, we have raised an antiserum against the synthetic fragment of human proguanylin (1-15) and have examined the proguanylin-positive cells in the human and rat gastrointestinal tract by immunohistochemical methods. Numerous proguanylin (1-15)-immunoreactive cells were found in the gastrointestinal tract. They were either pyramidal or spindle shaped in the stomach. Spindle-shaped cells, frequently possessing long slender processes, were located at the base of the pyloric epithelium and did not extend to the lumen. In the duodenum and jejunum, these cells were mostly pyramidal in shape and often had a slender process towards the lumen. The immunostaining was completely blocked by the human proguanylin (1-15) fragment. Paneth and goblet cells were negative against this antiserum. The number of serotonin-positive cells was much larger than that of proguanylin-positive cells in all the segments tested. The number of proguanylin-positive cells decreased from the jejunum to the ileum and very few cells were observed in the colon. In contrast to serotonin-positive cells, most somatostatin-positive cells were also positive for proguanylin. Thus, proguanylin (1-15) or its related protein appears to coexist with somatostatin in intestinal endocrine D cells which may be a source of circulating proguanylin. Proguanylin, like somatostatin, may also regulate intestinal function as a local regulator.     

The effect of Val'kofen tablets for children on the function of the gastrointestinal tract and liver in an experiment

It was prepared new child's medicinal form, the tablets "Valcophene" for making a wider variety of pediatric preparation's. It is studied the influence of "Valcophene" on the functional state of alimentary canal in experiment on rat's. Results investigation's are testified to absence of ulcerative action in new child's preparations. Studying influence in liver functional state is provided for new children's preparation "Valcophene" too. The chronic experiment is showed that "Valcophene" didn't influence on liver in experimental animals.     

Effects of piroxicam-beta-cyclodextrin on the gastrointestinal tract

Piroxicam-beta-cyclodextrin (PBC), a complex of piroxicam with beta-cyclodextrin, was developed with the aim of improving the hydrosolubility and bioavailability of piroxicam. The complex is more rapidly absorbed, with a consequent reduction in the time of contact of piroxicam with the gastric and duodenal mucosa. It is hoped that the shorter contact time might reduce the local toxicity of piroxicam, but it is also possible that transiently higher local concentrations of the drug might worsen the injury to the gastro-duodenal mucosa. Four studies have been conducted in healthy volunteers in order to investigate the effects of PBC on the gastro-intestinal tract. In 3 of these trials, all of similar design, PBC (containing 20 mg of piroxicam) was compared with piroxicam 20mg and placebo given once daily with assessment of faecal blood loss using the 51Cr-labelled red-cell technique, and endoscopic appearance of gastroduodenal mucosa before and after 28 consecutive days of treatment. One study showed a significant difference in respect of faecal blood loss towards the end of the 4-week study period favouring PBC over piroxicam, while the 2 others showed comparable but non-significant trends in favour of PBC. In a fourth study, 32 non-patient volunteers received either piroxicam 20mg once daily; PBC 20mg equivalence; indomethacin 50mg twice daily; or placebo. The treatment was given double blind for 14 days. Endoscopy was performed and gastric potential differences were measured by neutral observers before and at the end of treatment. There were no significant differences in the endoscopic scores between the active treatment groups. The gastric potential difference showed greater changes with indomethacin and piroxicam than with placebo and PBC.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of an antacid on the bioavailability of indomethacin

The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significantly only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.     

The influence of polyethylene glycol conjugation on bovine hemoglobin's intrinsic effect on the gastrointestinal system of the rat

The purpose of this study was to determine the impact of polyethylene glycol (PEG) conjugation on bovine hemoglobin's effect on gastrointestinal (GI) blood flow and motility in the Sprague Dawley rat. This study was divided into two parts: part one assessed blood flow, while the other evaluated bolus transit time through the GI. To examine blood flow, thirty-two rats were divided into four experimental groups (PEG-hemoglobin, bovine hemoglobin, Ringer's Lactate and autologous blood sham). Blood flow within the superior mesenteric artery was monitored during graduated isovolemic hemodilution. In the second part of the study, GI motility was estimated by bolus transit time. Thirty-six rats were assigned to four groups (PEG-hemoglobin, bovine hemoglobin, Ringer's Lactate and no treatment sham) and following an overnight fast, the rats were given a bolus injection (25 mL/kg) of test article. Three hours following injection, they received an oral 0.3 mL gavage of a charcoal/arabic gum mixture and were later sacrificed and their GI tract evaluated. Results indicated that the infusion of bovine hemoglobin reduced both baseline blood flow through the mesenteric artery and gastrointestinal transit time. In contrast, PEG-hemoglobin maintained baseline blood flow through the mesenteric artery and had no effect on GI transit time or morphology. Therefore, PEG conjugation of bovine hemoglobin significantly attenuated its intrinsic effect on the GI system of the rat.     

A special closure system of the gastrointestinal tract of the rat (author''s transl)

Serial determinations of FSH, LH, estradiol-17 beta and progesterone in plasma and of total gonadotropins, total estrogens and pregnanediol in urine were performed in 10 adolescent girls between 15 and 19 years of age. Two types of menstrual cycles could be distinguished. The first type is characterized by a nearly normal pattern of FSH, while a preovulatory rise of estradiol-17 beta and an LH-peak is still missing. Only few days prior to menstrual bleeding a small rise of estradiol and progesterone in plasma as well as of estrogens and pregnanediol in urine can be seen, being equivalent to a short luteinization of the follicle without ovulation taking place. The second type already shows all criteria of a regular ovulatory cycle. However the plasma level of LH, estradiol and progesterone and the excretion of estrogens and pregnanediol are still below the average values of control cycles of adult women. On the basis of the hormonal pattern and a shortened luteal phase, a relative insufficiency of this type of cycles is still evident. These studies demonstrate, that the cyclic ovarian function postmenarchial develops gradually and that the onset of ovulation is a marked step in this development. This process of maturition, which is due to the gradual development of the positive feedback of estrogens on the release of LH by the pituitary gland, allows to distinguish in adolescence between cycles before and after maturition of the feed-back mechanism in the ANS.     

Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine

In mice, the mdr1a and mdr1b genes encode drug-transporting proteins that can cause multidrug resistance in tumor cells by lowering intracellular drug levels. These P-glycoproteins are also found in various normal tissues such as the intestine. Because mdr1b P-glycoprotein is not detectable in the intestine, mice with a homozygously disrupted mdr1a gene [mdr1a(-/-) mice] do not contain functional P-glycoprotein in this organ. We have used these mdr1a(-/-) mice to study the effect of gut P-glycoprotein on the pharmacokinetics of paclitaxel. The area under the plasma concentration-time curves was 2- and 6-fold higher in mdr1a(-/-) mice than in wild-type (wt) mice after i.v. and oral drug administration, respectively. Consequently, the oral bioavailability in mice receiving 10 mg paclitaxel per kg body weight increased from only 11% in wt mice to 35% in mdr1a(-/-) mice. The cumulative fecal excretion (0-96 hr) was markedly reduced from 40% (after i.v. administration) and 87% (after oral administration) of the administered dose in wt mice to below 3% in mdr1a(-/-) mice. Biliary excretion was not significantly different in wt and mdr1a(-/-) mice. Interestingly, after i.v. drug administration of paclitaxel (10 mg/kg) to mice with a cannulated gall bladder, 11% of the dose was recovered within 90 min in the intestinal contents of wt mice vs. <3% in mdr1a(-/-) mice. We conclude that P-glycoprotein limits the oral uptake of paclitaxel and mediates direct excretion of the drug from the systemic circulation into the intestinal lumen.     

Effect of first-pass metabolism on enantioselective pharmacokinetics after oral administration of (+)-, (-)- and racemic homochlorcyclizine to rats

The enantioselective relationship between the pharmacokinetics and hepatic metabolism of homochlorcyclizine hydrochloride (HCZ) was investigated using rats. There were no significant differences in blood concentrations between the three forms after intravenous administration (5 mg/kg) of (+)-, (-)- and racemic HCZ. On the other hand, there were significant differences in the pharmacokinetics between (-)- and (+)-HCZ and between (-)- and racemic HCZ after oral administration (50 mg/kg) of these three forms. The Cmax and AUC0-infinity of (-)-HCZ were lower than those of (+)-isomer and racemate, and its CLo was clearly higher than the others. The (+)-isomer and racemate showed no significant differences in their pharmacokinetic parameters. At a lower dose (10 mg/kg), however, no enantiomeric differences were found in the pharmacokinetic parameters of (+)- and (-)-HCZ. Also examined was the cytochrome p-450-dependent-oxidative metabolism of (+)-, (-)- and racemic HCZ in vitro using rat liver 9000 x g supernatant fraction. The in vitro metabolism of (-)-HCZ was extremely fast, compared with those of the (+)-isomer and the racemate. The Vmax in vitro showed a good correlation with the CLo in vivo after oral administration (50 mg/kg) of all three forms of HCZ. In vitro study of enantiomeric inhibition of the metabolism showed that (+)-HCZ was a competitive inhibitor of (-)-HCZ metabolism, with a Ki of 6.96 microM. (-)-HCZ was also a competitive inhibitor of (+)-HCZ metabolism, with a Ki of 20.4 microM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Zinc uptake in five sectors of the rat gastrointestinal tract: kinetic study in the whole colon

PURPOSE: The uptake of zinc as acexamic acid salt in the rat gastrointestinal tract, using an in situ static technique, was studied. Our aim was to investigate an absorption window for zinc and the uptake kinetics in the colon. METHODS: To detect selectivity phenomena in zinc absorption, buffered saline solutions of zinc (50 micrograms/ ml) were perfused in stomach, whole colon and three 33-cm fractions of the small intestine (proximal, middle and distal segments). To characterize zinc uptake kinetics in whole colon, five different zinc concentrations (5, 25, 50, 150 y 250 micrograms/ml) were assayed. Zinc secreted into the gastrointestinal tract during the experiments was deducted from the uptake. RESULTS: Zinc secretion was characterized as an apparent zero-order process for all the studied segments (mean secretion rate = 0.10 +/- 0.03 microgram/(ml x min)). The stomach exhibited little ability to absorb zinc (apparent first order rate constant = 0.17 +/- 0.07 h-1), whereas the highest transport rates were found in the last two thirds of the small intestine and colon (first order constants: 0.66 +/- 0.13 h-1, 1.00 +/- 0.06 h-1, 0.97 +/- 0.14 h-1, 0.96 +/- 0.19 h-1 for proximal, middle, distal and colon segments, respectively). Zinc uptake in the colon was characterized by means of a Michaelis-Menten and first-order combined kinetics, with the following parameters: Vm = 0.36 +/- 0.02 microgram/(ml x min), Km = 18.01 +/- 0.40 microgram /ml and Ka = 0.40 +/- 0.01 h-1. CONCLUSIONS: Zinc is preferably absorbed in the middle and distal parts of the rat gastrointestinal tract. In the colon a saturable mechanism may be involved in apparent absorption.