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Biomedical subjects

T Nishihata

Publications and source records attributed to T Nishihata.

At least 73 records · Page 4Linked to original sources
PubMed1984

Possible mechanism of uptake for several compounds in ionized form through human erythrocyte membrane.

The mechanism underlying uptake of certain compounds in ionized form across human red blood cell membrane was examined. The ionized forms of salicylate, 5-methoxy-salicylate and phenylalanylphenylalanine were significantly taken up into the interior space of human red blood cells instead of remaining in the membrane. Inhibition of the uptake of these compounds by 4,4'-diisothiocyano-2,2'-disulfonate stilbene and phlorizin indicates that their permeation of the erythrocyte membrane may involve the membrane protein fraction. Chelation at the protein site does not appear to occur. Instead, an amino group in the protein structure may mediate the transport of these ionized compounds.

Absorption↗
PubMed1984

Salicylate-promoted permeation of cefoxitin, insulin and phenylalanine across red cell membrane. Possible mechanism.

Uptake of sodium cefoxitin, D-phenylalanine and insulin into human red blood cells was significantly enhanced by the presence of salicylate and 5-methoxysalicylate in the medium. The mechanism of adjuvant action appeared to depend on an affinity between the adjuvant and the protein fraction in the erythrocyte membrane. The inhibitory effect of DIDS and phlorizin on the salicylate-enhanced uptake of these compounds strongly suggests that the ability of salicylate to permeate the membrane may be essential for it to act as an adjuvant.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Enhanced rectal absorption of cefmetazole and cefoxitin in the presence of epinephrine metabolites in rats and a high-performance liquid chromatographic assay for cephamycin antibiotics.

4-Hydroxy-3-methoxymandelic acid and 3,4-dihydroxymandelic acid were found to be potent adjuvants for the rectal absorption of water-soluble compounds in rats. Both adjuvants enhanced the absorption of two cephamycin antibiotics, cefmetazole and cefoxitin. Maximum plasma levels of the antibiotics were obtained within 30 min after rectal administration. The bioavailability of both antibiotics appeared to depend on the concentration of the adjuvant in the microenema, the dosage form used in these experiments. Instead of a microbial assay, a new chemical method involving high-performance liquid chromatography with an ion-pairing technique was developed for analyzing the cephamycin antibiotic plasma levels.

Adjuvants, Pharmaceutic↗
PubMed1984

The effects of salicylate on the rectal absorption of phenylalanine and some peptides, and the effects of these peptides on the rectal absorption of cefoxitin and cefmetazole.

The disappearance of phenylalanine and phenylalanylglycine from a perfusate circulated across rat rectal tissue was enhanced significantly in the presence of salicylate or 5-methoxysalicylate at pH 4.5, 7.4, and 8.5. The disappearance of di-, tri-, and tetraphenylalanine from a perfusate at pH 7.4, although facilitated by the presence of salicylate and 5-methoxysalicylate, was also fairly substantial when no adjuvant was present. These peptide analogues of phenylalanine also enhanced the rectal absorption of cefoxitin and cefmetazole, two highly water soluble antibiotics. Phenylalanine and phenylalanylglycine, both poorly absorbed across the rectal membrane when administered alone, did not enhance the rectal absorption of either antibiotic.

Animals↗
PubMed1984

Possible mechanism behind the adjuvant action of phosphate derivatives on rectal absorption of cefoxitin in rats and dogs.

The mechanism underlying the ability of phosphate derivatives to act as adjuvants and coadjuvants was examined in in vivo and in situ preparations in rats and dogs. The adjuvant effect of DL-alpha-glycerophosphate on the rectal absorption of sodium cefoxitin was greatly augmented by the presence of either sodium phytate or sodium tripolyphosphate. These coadjuvants only slightly enhanced cefoxitin rectal absorption when administered alone. Therefore, enhancement of the permeation of tripolyphosphate and phytate by alpha-glycerophosphate may be necessary before the coadjuvants can significantly affect cefoxitin absorption. The inhibitory effect of disodium 4,4'-diisothiocyano-2,2'-disulfonate stilbene, which is known to interact with the amino group in the protein fraction, on enhanced cefoxitin absorption suggests the involvement of the protein fraction in transport of cefoxitin across the rectal membrane.

Adjuvants, Pharmaceutic↗
PubMed1984

Enhanced intestinal absorption of amino acids and amino acid-like drug by possible formation of enamine in administered solution by the presence of ethylacetoacetate.

Ethylacetoacetate promoted the colonic and the jejunal absorption of amino acids such as L-phenylalanine and D-phenylalanine when administered in aqueous solution. Enhanced absorption of these isomers of amino acid might occur via a formation of enamine, which was observed in aqueous solution by monitoring ultraviolet absorbance at 288 nm. Since mixture of L- or D-phenylalanine and ethylacetoacetate in aqueous solution enhanced colonic absorption of cefmetazole while the solution did not affect so much on the jejunal absorption of cefmetazole compared to the colonic absorption of it, enhancing action of enamine probably produced in aqueous solution may be more effective at the colonic compartment.

Acetoacetates↗
PubMed1984

Effect of adjuvants on the rectal absorption and lymphatic uptake of pepleomycin in rats.

The rectal absorption of pepleomycin sulfate (PEPS) in rats was increased significantly by the coadministration with each of diclofenac (DC), sodium 5-methoxysalicylate (5-MSA) and phenylalanine enamine of ethylacetoacetate (Enamine). 5-MSA increased the lymphatic uptake of PEPS after rectal administration while DC and Enamine did not. The mechanism behind the enhancing action of 5-MSA on the lymphatic uptake of PEPS may be due to the suppressing action of 5-MSA on the vascular permeability to PEPS. DC increased the vascular permeability to PEPS but Enamine did not affect it. Findings obtained in this study may indicate that adjuvant used acts independently at the rectal mucosal membrane and at the vascular membrane for membrane for membrane permeability to PEPS.

Adjuvants, Pharmaceutic↗
PubMed1984

Study of the mechanism behind adjuvant action of diethylethoxymethylene malonate enhancing the rectal absorption of cefmetazole and lysozyme.

Diethylethoxymethylene malonate (DEEMM) and diethyl maleate (DEM) enhanced the rectal absorption of cefmetazole in rats when studies were carried out using in vivo, in situ rectal loop and in vitro rectal everted sac method. Since an increase of cefmetazole transport was found when concentration of nonprotein sulfhydryls in rectal tissue was decreased by the presence of either DEEMM or DEM in the study using in vitro everted sac method and the enhancement of cefmetazole absorption by the coadministration of either DEEMM or DEM was suppressed by the treatment with dimercaprol, membrane permeability of rectal tissue seems to be regulated by the concentration of nonprotein sulfhydryls in rectal tissue. On the other hand, it was also found that there were differences between the action of DEEMM and the action of DEM from the following two results: 1) enhancing action of DEEMM was suppressed by the presence of calcium ion in microenema while action of DEM was not so much influenced, and 2) DEEMM enhanced the rectal absorption of lysozyme in rabbits but DEM did not.

Adjuvants, Pharmaceutic↗
PubMed1983

Effects of sodium salicylate on epithelial cells of the rectal mucosa of the rat: a light and electron microscopic study.

Using a ligation method, rat rectal epithelium was exposed to 2% sodium salicylate, and light and electron microscopic methods were used to assay for: 1) permeability of the epithelium to a marker dye, trypan blue, and 2) damage expressed in terms of disruption of the epithelial surface. Rectal mucosa was exposed to salicylate at pH 4.8, 7.0, and 9.0, and the effects of pretreatment with phlorizin were also studied. Results indicated that 2% sodium salicylate does very little damage to rectal epithelial cells at pH 7.0 while enhancing their permeability to trypan blue, an effect that is reversed upon washing out the sodium salicylate. The major cellular change induced by salicylate was a reduction in the length or distribution of glycocalyx filaments on microvilli of epithelial cells. It was also noted that pretreatment with phlorizin counteracted some of the effects of salicylate treatment.

Animals↗
PubMed1983

Simultaneous analysis of 1-beta-D-arabinofuranosylcytosine, 1-beta-D-arabinofuranosyluracil and sodium salicylate in biological samples by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic column switching system is described for the rapid and complete separation of 1-beta-D-arabinofuranosylcytosine (Ara-C), 1-beta-D-arabinofuranosyluracil (Ara-U) and sodium salicylate using an internal standard of sodium cefmetazole. The system is highly selective and separates these compounds from interfering compounds commonly in biological matrices. The system was tested by following the pharmacokinetics of Ara-C after rectal administration in the presence of sodium salicylate which is an aid to drug absorption. The chromatographic system is also suitable for monitoring levels of Ara-C and its metabolite Ara-U after intravenous administration of Ara-C.

Animals↗
PubMed1983

Adjuvant effects of glyceryl esters of acetoacetic acid on rectal absorption of insulin and inulin in rabbits.

The promoting effect of glyceryl esters of acetoacetic acid on the rectal absorption of insulin and inulin was studied. A decrease in the serum glucose level was observed in rabbits following the administration of an insulin suppository containing glyceryl-1,3-diacetoacetate (adjuvant II) or 1,2-isopropylideneglycerine-3-acetoacetate (adjuvant IV). The promoting effects of adjuvants II and IV on the rectal absorption of insulin and inulin were suppressed by the addition of calcium and magnesium to the suppository. This indicates that adjuvant interaction with the calcium and magnesium ion located in the rectal membrane is involved in the enhanced absorption of insulin and inulin. Adjuvant release from the suppository formulation in addition to adjuvant lipid solubility were found to be other important factors for enhanced absorption of insulin and inulin.

Acetoacetates↗
PubMed1983

Effect of enamine derivatives on the rectal absorption of insulin in dogs and rabbits.

Enamine derivatives resulting from the reaction between ethyl acetoacetate and amino acids were found to promote rectal absorption of insulin in normal rabbits, with the enamine of sodium DL-phenylalanate being the most effective adjuvant tested. Results of glucose tolerance tests in fasted alloxan diabetic rabbits showed that after oral administration of glucose, insulin suppositories containing enamines derived from either sodium phenylalanine or leucine were able to lower the serum glucose level to within the normal range for more than 2.5 h. The absorption-promoting effect of the sodium DL-phenylalanate enamine on rectal absorption of insulin in dogs was studied in two different formulations, gelatin microenema and suppository. The gelatin microenema containing the insulin solution caused a greater increase in the plasma insulin level than that obtained after administration of an insulin suppository.

Adjuvants, Pharmaceutic↗
PubMed1983

Enhancement of rectal absorption of insulin using salicylates in dogs.

Sodium salicylate and 5-methoxysalicylate both increased the rectal absorption of insulin in dogs when co-administered with insulin in various formulations. Microenema formulations containing 4% gelatin showed the highest insulin bioavailability of the formulations studied whereas microenemas (without gelatin) and suppository formulations were not as effective in enhancing the rectal absorption of insulin.

Animals↗