[Absorption studies following roentgen irradiation of the abdomen in malignant lymphogranulomatosis using the D-xylose absorption test and the I-131 triolein test].
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Abdomen↗
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Results for “Rectal Absorption”
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Effect of carbohydrate ingestion on glucose kinetics during exercise in the heat.
Six endurance-trained men [peak oxygen uptake (V(O(2))) = 4.58 +/- 0.50 (SE) l/min] completed 60 min of exercise at a workload requiring 68 +/- 2% peak V(O(2)) in an environmental chamber maintained at 35 degrees C (<50% relative humidity) on two occasions, separated by at least 1 wk. Subjects ingested either a 6% glucose solution containing 1 microCi [3-(3)H]glucose/g glucose (CHO trial) or a sweet placebo (Con trial) during the trials. Rates of hepatic glucose production [HGP = glucose rate of appearance (R(a)) in Con trial] and glucose disappearance (R(d)), were measured using a primed, continuous infusion of [6,6-(2)H]glucose, corrected for gut-derived glucose (gut R(a)) in the CHO trial. No differences in heart rate, V(O(2)), respiratory exchange ratio, or rectal temperature were observed between trials. Plasma glucose concentrations were similar at rest but increased (P < 0.05) to a greater extent in the CHO trial compared with the Con trial. This was due to the absorption of ingested glucose in the CHO trial, because gut R(a) after 30 and 50 min (16 +/- 5 micromol. kg(-1). min(-1)) was higher (P < 0.05) compared with rest, whereas HGP during exercise was not different between trials. Glucose R(d) was higher (P < 0.05) in the CHO trial after 30 and 50 min (48.0 +/- 6.3 vs 34.6 +/- 3.8 micromol. kg(-1). min(-1), CHO vs. Con, respectively). These results indicate that ingestion of carbohydrate, at a rate of approximately 1.0 g/min, increases glucose R(d) but does not blunt the rise in HGP during exercise in the heat.
Adult↗
Development of a thermo-reversible insulin liquid suppository with bioavailability enhancement.
The purpose of this work is to develop a thermo-reversible insulin liquid suppository, which undergoes a phase transition to bioadhesive gels at body temperature and enhances the bioavailability of insulin. The effects of insulin and sodium salicylate on the physicochemical properties of a liquid suppository composed of poloxamer P 407, P 188 and polycarbophil were investigated. The pharmacodynamic study and quantitative histological assessment of the rectal mucosa of rats were carried out after the dose of insulin-loaded liquid suppositories with different amounts of sodium salicylate into streptozotocin-treated rats. Only thermo-reversible insulin liquid suppository [insulin/P407/P188/polycarbophil/sodium salicylate (100 (IU/g)/15/20/0.2/10%)] showed the optimal physicochemical properties and good safety in rats. It gave significantly lower plasma glucose levels, AUC(0-->4h) (the area below basal glucose level) and C(nadir) (the plasma glucose levels at the nadir) than did the solid and liquid suppositories without sodium salicylate in rats, indicating that the insulin from liquid suppository with sodium salicylate could be well absorbed in rats due to the absorption enhancing effect of sodium salicylate. It is concluded that thermo-reversible insulin liquid suppository [insulin/P 407/P 188/polycarbophil/sodium salicylate (100 (IU/g)/15/20/0.2/10%)], which was easy to administer without any pain during insertion and remained at the administered sites, could have a potential to be developed as a more convenient, safe and effective rectal delivery system of insulin.
Administration, Rectal↗
Molecular and topological characterization of the rat parotid Na+-K+-2Cl- cotransporter1.
Na+-K+-2Cl- cotransporters play a central role in driving salt and water movements across secretory and absorptive epithelia. We report the cloning of the rat parotid secretory Na+-K+-2Cl- cotransporter, rtNKCC1. The predicted amino acid sequence of this protein is highly homologous to a previously cloned NKCC1 from the shark rectal gland and to mammalian NKCC1s cloned from several cultured cell lines, confirming the presence of the NKCC1 isoform in a naturally occurring mammalian secretory epithelium. In contrast to previously published NKCC1 clones, our sequence also includes an apparently complete 2680 bp 3'-UTR. Hydropathy analyses of rtNKCC1 predicts that this protein consists of large hydrophilic N and C termini (approx. 30 kDa and 50 kDa, respectively) flanking a central hydrophobic transmembrane region consisting of ten to 12 membrane spanning domains. In addition, we report the results of confocal immunofluorescent microscopic studies using rat parotid acini and antibodies directed against specific regions of the predicted N- and C-terminal portions of rtNKCC1. These studies demonstrate that the epitopes recognized by these antibodies are exposed in permeabilized but not in unpermeabilized cells, indicating that the predicted N and C termini of rtNKCC1 are intracellular.
Amino Acid Sequence↗
Immunolocalisation of aquaporin 3 in the gill and the gastrointestinal tract of the European eel Anguilla anguilla (L.).
The expression of a putative water channel protein, aquaporin 3 (AQP-3), has been localised within branchial and intestinal tissues from the 'silver' life stage of the European eel Anguilla anguilla, using a specific polyclonal antibody directed against the C-terminal of the amino acid sequence. Western blots using the AQP-3 antiserum identified the presence of a major immunoreactive protein of 24 kDa in extracts of gills from both freshwater (FW) and 3 week seawater (SW)-acclimated eels. SW acclimation induced a 65 % reduction in AQP-3 protein abundance in the gill extracts. AQP-3 immunoreactivity was apparent throughout the branchial epithelium from both FW and SW-acclimated fish, but especially so within the chloride cells, which also stained heavily with specific antisera for the beta-subunit of the Na, K-ATPase. AQP-3 immunoreactivity not only colocalised with Na, K-ATPase within the basolateral tubular network but also stained the apical regions of the chloride cell where Na, K-ATPase was absent. Although there were no obvious differences in expression between the chloride cells of FW and SW-acclimated fish, considerably higher intensities of immunoreactivity were apparent near the periphery of the non-chloride cells of FW fish, especially within cells forming the base of the primary filaments and the branchial arch. AQP-3 immunoreactivity was also detected in intra-epithelial macrophage-like cells within the intestine of FW and SW-acclimated eels and in the mucous cells of the rectal epithelium of SW-acclimated fish. These results suggest that AQP-3 may play an important functional role in osmoregulation the teleostean gill but is unlikely to be responsible for the increases in intestinal water absorption that occur following SW acclimation.
Acclimatization↗
Effect of pharmaceutical adjuvants on the rectal permeability of drugs. II. Effect of Tween-type surfactants on the permeability of drugs in the rat rectum.
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Adjuvants, Pharmaceutic↗
Multiple-dose charcoal and whole-bowel irrigation do not increase clearance of absorbed salicylate.
BACKGROUND: This study assesses whether oral multiple-dose charcoal therapy (MDC) or whole-bowel irrigation (WBI) enhances the excretion of previously absorbed salicylate. METHODS: A controlled, randomized, three-limbed crossover protocol was used in nine humans who ingested aspirin. Salicylate levels were measured in serial serum specimens and 32-hour urine collections and kinetic parameters were calculated. RESULTS: There were no differences among the control (CTL), MDC, or WBI groups for area under the serum concentration vs time curve (CTL, 2320 +/- 501 mg/L.h MDC, 2040 +/- 454 mg/L.h; WBI, 2093 +/- 418 mg/L.h) or for urinary salicylates (CTL, 54.9% +/- 9.4%; MDC, 50.9% +/- 8.0%, WBI, 52.4% +/- 13.7% of ingested dose). CONCLUSIONS: Our data do not support the use of either MDC or WBI to enhance the excretion of previously absorbed salicylate in poisoned patients. In patients with drug overdoses, a clear rectal effluent remains as the endpoint for WBI.
Administration, Oral↗
[Biopharmaceutical study of aminophenazone-containing suppositories. 2. Results of in vitro drug release and in vivo drug absorption].
Ten kinds of surface active ingredients of Th. Goldschmidt AG. (Essen-FRG) in concentrations of 5% were mixed with Witepsol W 35 and Massa Estarinum 299 suppository masses of Hüls-Troisdorf AG. Werk (Witten-FRG) which are official in Hungary. According to the authors the above tensides, which have been used advantageously first of all in ointments, creams and cosmetic preparations, can also be applied in rectal preparations. In the publication of two parts it has been established that these ingredients influence physical parameters of suppositories beneficially. They always increase significantly in vitro diffusion values and in some cases with order of magnitude. Massa Estarinum 299 containing 5% of Emulgator BTO proved to be the best in case of chosen suppositories containing aminophenazone. Correlation between in vitro and in vivo investigations has shown the importance of correct selection of base and ingredient materials in biopharmaceutical work.
Aminopyrine↗
Pharmacokinetics of rectal paracetamol after repeated dosing in children.
Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P < 0.05) between saliva and serum concentrations. A one-compartment linear model with first-order elimination and absorption and lag-time was fitted to the data (ADAPT II). At steady state, the mean (SD) concentration was 15.2 (6.8) mg litre-1. Mean (SD) time to reach 90% of the steady state concentration was 11.4 (8.6) h. Body weight, age and body surface area were well correlated (P < 0.05) with clearance and apparent volume of distribution. There was no evidence of accumulation leading to supratherapeutic concentrations during this dosing schedule for a mean of approximately 2-3 days.
Acetaminophen↗
Assessment of the intestinal retention of beta-carotene in humans.
OBJECTIVE: Assessment of the intestinal absorption of beta-carotene (BC) in humans as well as plasma clearance of BC has been difficult. We have used the total gut washout method (TGWM) to assess BC retention during transit through the intestine, as well as the effect that different diets and age have on BC retention. METHODS: HPLC was used to quantitate fecal and serum BC concentrations from young and elderly subjects who had undergone the TGWM to remove all intestinal contents prior to ingesting BC or placebo with or without a meal. Meals contained different combinations of calories and fat. RESULTS: In subjects receiving no meal, 83% of ingested BC was recovered in rectal effluent collected within 24 hours post-BC administration. The quantity of BC in feces of individuals receiving meals was 49-71%. There was no significant change in serum concentrations of other carotenoids or retinoids following consumption of BC with any of the different meals. Interestingly, both diet and age influenced the efficiency of BC absorption. An increase in dietary fat content resulted in an higher serum BC concentration in young subjects within 8 and at 24 hours post BC administration, whereas a higher caloric content resulted in a decrease in serum BC concentration in older subjects within 8 hours of BC administration. CONCLUSION: Results indicate that the TGWM provides an accurate means for assessing the intestinal retention of BC in humans.
Adolescent↗
Metabolism of chenodeoxycholate by intestinal mucosa.
The metabolism of 14C-labeled bile salts was studied in vitro during their absorption from infused segments of rat intestine. The transported bile salts were recovered in transudates which were collected from the serosal surface of infused segments. In the jejunum, 36% of transported [14C]deoxycholate and 48% of transported [14C]chenodeoxycholate were recovered as metabolites which migrated as a seemingly single polar compound on thin layer chromatography; 52 to 72% of these metabolites could be deconjugated by cholylglycine hydrolase to yield original [14C]deoxycholate or [14C]chenodeoxycholate, respectively. The jejunum metabolized 9 times more [14C]chenodeoxycholate than the ileum (38.1 nmoles per hr per g compared with 4.2 nmoles per hr per g), despite the fact that both segments transferred the same amount of radioactivity. In contrast, [14C]cholate, [14C]glycocholate, and [14C]glycodeoxycholate were transferred intact by the jejunum, ileum, and colon. Human jejunal and rectal mucosa were able to metabolize [14C]chenodeoxycholate to polar metabolites in vitro. Polar metabolites were also found in the portal plasma and jejunal wall 20 min after the feeding of [14C]chenodeoxycholate to bile fistula rats. It is suggested that these results complicate the interpretation of in vitro experiments on absorption of dihydroxy bile salts, and that they indicate that the human small intestine may be able to metabolize chenodeoxycholate.
Animals↗
Novel drug delivery strategies for the treatment of inflammatory bowel disease.
Inflammatory bowel disease (IBD) encompasses two idiopathic inflammatory diseases of the intestinal tract: Crohn's disease and ulcerative colitis. Existing therapy for IBD consists mainly of orally or rectally administered small drug molecules, such as 5-aminosalicylates and corticosteroids, or potent systemic immune suppressants. IBD presents a challenging target for drug delivery, particularly by the oral route, as, contrary to most therapeutic regimens, minimal systemic absorption and maximal intestinal wall drug levels are desired. Several delivery strategies are employed to achieve this goal, including the chemical modification of the drug molecules, the use of controlled- and delayed-release formulations and the use of bioadhesive particles. The goal of this review is to summarise existing IBD therapy and examine novel approaches in intestinal drug delivery.
Drug Delivery Systems↗
Applications of microemulsion based drug delivery system.
The use of microemulsions as drug delivery vehicle has been an exciting and attractive area of research because of its many potential and extraordinary benefits. Microemulsions offer an interesting and potentially quite powerful alternative carrier system for drug delivery because of their high solubilization capacity, transparency, thermodynamic stability, ease of preparation, and high diffusion and absorption rates when compared to solvent without the surfactant system. The oral efficacy of microemulsion has already been proved by cyclosporine formulation (Neoral), but apart from oral route, microemulsions for other routes like dermal, transdermal, ocular, vaginal, rectal, buccal, periodontal, parenteral, and nasal delivery routes have also been developed. The present review focuses on various applications of microemulsions through different above mentioned routes and also gives idea about new application of micro emulsion as oral solid dosage form, as microreactors and as blood substitute.
Aerosols↗
Pharmacokinetics and tolerance of fluconazole suppositories in healthy volunteers.
Fluconazole (Diflucan, CAS 86386-73-4) suppositories offer a novel way to administer this systemically active antimycotic. The pharmacokinetics and toleration of this new formulation have now been examined in healthy adult volunteers. In crossover experiments the bioequivalence was demonstrated for 200 mg suppositories and 200 mg capsules, and for 25 mg suppositories and 25 mg fluconazole in an oral suspension. The mean bioavailability of the 200 mg suppository relative to the capsule was about 93%. The mean bioavailability of the 25 mg suppository relative to the oral suspension was 107%. Absorption of fluconazole after administration of the suppositories was, however, somewhat slower than after oral ingestion of the capsule or suspension. The pharmacokinetic parameters of the 200 mg and 25 mg suppositories suggest that the kinetics of rectally administered fluconazole are linear with dosage. Daily administration of the 200 mg suppository gives a continuous increase in the mean fluconazole plasma concentration, until steady-state is reached on about the 5th day. The systemic and local toleration of the fluconazole suppositories was good.
Adult↗
[An autopsy case of rectal cancer receiving cisplatin at total dose of 3.250 mg and platinum concentrations in autopsy tissue samples].
An autopsy case of a 57-year-old man who had received cisplatin, total dose of 3,250 mg (1,920 mg/m2) after proctectomy for advanced rectal cancer with hepatic metastasis is reported. Platinum concentrations in autopsy tissue samples are also reported. Cisplatin at a dose of 20-40 mg was administered intravenously once a week for 82 weeks, but renal failure did not occur. The patient died 529 days after his last cisplatin therapy, due to acute suppurative cholangitis. On autopsy, the hepatic hilar metastasis involved the bile duct, but the other metastasis of the liver became regeneration and necrosis, and the kidneys showed few findings but congestion and arteriosclerotic change. The spleen evidenced mild hemosiderosis. Tissue samples obtained at the time of autopsy were assayed for platinum using flameless atomic absorption spectrometry. The spleen had the highest concentration, about 2.7 times as high as that of the liver. The liver, the heart and the kidneys had high platinum concentrations (greater than 3.04 micrograms/g), but those of the jejunum and the ileum were low (less than 0.95 micrograms/g). Although cisplatin, FT 207 and krestin were effective for the rectal cancer, platinum was undetectable (less than 0.13 micrograms/g) in the ascending and the transverse colons.
Adenocarcinoma↗
Enhanced rectal absortion of insulin and heparin in rats in the presence of non-surfactant adjuvants.
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Adjuvants, Pharmaceutic↗
[Use of suppositories for rectal immunization].
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Animals↗
[Effect of exogenous factors on prececal nutrient and amino acid reabsorption, ascertained in swine with ileorectal anastomoses. 1. Effect of the degree of grinding up of grain].
Pigs fitted with ileo-rectal anastomoses (IRA) and in parallel experiments intact (INT) pigs were used to estimate the influence of the different grinding fineness of barley and wheat (coarse, medium, fine) on the apparent and true precaecal and total digestibility resp. absorption of various N free and N containing nutrients, among them crude protein and the indispensable and dispensable amino acids. Coarse grinding (25 ... 50% of the particles greater than 2 mm) resulted in significantly lower digestibility values than medium and fine grinding--with more striking differences in barley than in wheat. Precaecally most nutrients and amino acids are distinctly less digestible than at the end of the total tract. The precaecal lysine absorption determined with IRA pigs is remarkably low. The results are discussed. In order to attain a good utilization of the protein contained in cereals grains should be ground in hammermills with maximal sieve meshes of 3 mm. It is proposed to tabulate crude protein and amino acids in future on the basis of a standardized true precaecal digestibility resp. absorption.
Amino Acids↗