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Biomedical subjects

T Higuchi

Publications and source records attributed to T Higuchi.

At least 595 records · Page 33Linked to original sources
PubMed1984

Positive and negative ion fast atom bombardment mass spectrometry of glycosphingolipids. Discrimination of the positional isomers of gangliosides with sialic acids.

High molecular weight gangliosides (GD1a, GD1b, GT1a, and GT1b) and neutral glycosphingolipids (Forssman antigen, globoside, and CTH) containing various fatty acids were analyzed by positive and negative ion fast atom bombardment mass spectrometry (POS-FAB-MS and NEG-FAB-MS) without any derivatization. NEG-FAB-MS of the molecules gave intense peaks of the molecular ion species, (M-H)-, and many fragment ions useful for the elucidation of carbohydrate structure were also detected with significant intensity. The fragment ions were assessed to be cleaved at the glycosidic linkages sequentially from the non-reducing end with or without the ceramide portion and it was possible to distinguish structural isomers having different binding positions of sialic acid. All molecular ion species of neutral glycosphingolipids with various fatty acids were detected at intensities that were in accordance with the relative abundance of the fatty acids.

Animals↗
PubMed1984

Spinal pathway of the milk-ejection reflex in the rat.

The effects of lesions of the spinal cord on the milk-ejection reflex evoked by suckling were studied in urethane-anesthetized lactating rats. All lesions were made between C6 and C7 vertebrae and milk ejection was monitored by recording intramammary pressure. In the first experiment on the rats with bilateral lesions, a 3-h suckling test with 5 pups on each side was performed. Eleven (84.6%) of 13 rats with the section of the dorsal funiculus (Group 2), and 12 (85.7%) of 14 rats with the combined section of the dorsal and ventral funiculi (Group 4) displayed regular milk ejection. The incidence of milk ejection in both groups was not significantly different from 81.8% (9 rats) of the 11 sham-operated rats (Group 1). In contrast, none of the 12 rats with bilateral section of the lateral funiculus (Group 3) displayed milk ejection and the incidence of milk ejection was significantly lower than that in Group 1. In the second experiment on the rats with unilateral section of the lateral funiculus, bilateral suckling with 10 pups (5 pups on each side) and unilateral suckling (both ipsilateral and contralateral to the lesion) with 5 pups were consecutively performed in the 10 rats. Milk ejection was induced in 50% by contralateral suckling and in 100% by bilateral suckling, and the incidence was significantly higher than that (0%) observed during ipsilateral suckling. A significant difference in the incidence of milk ejection was also observed between contralateral and bilateral sucklings.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1984

A study of somatostatin receptors in amygdaloid-kindled rat brain.

Kindling is an animal model of epilepsy. Previously somatostatin (SRIF) was implicated in seizure activity in the brain. Recently we reported a significant increase in brain SRIF content in the temporal cortices and cortices of kindled rats. Since the interaction between the neurotransmitter and the receptor eventually is responsible for the biological response, the present study was undertaken to examine evidence for the participation of SRIF receptor in the kindled state. In this study we present a procedure for detection of SRIF receptors using radiolabeled (D-Tyr8)-SRIF as a tracer. The present study indicates that in kindled rats there are no differences in the total number or affinity of the binding sites in the temporal cortex and a slight increase in the total number of binding sites in the cortex when compared with controls. These results, in view of our other observations, suggest that in kindled rat brain there may be an increased release of SRIF but no down-regulation of SRIF receptors in temporal cortex and cortex. There appears to be a significant decrease in the number of SRIF receptors in kindled hippocampus. The mechanism by which this occurs remains unclear.

Amygdala↗
PubMed1983

Profound suppression of kindled seizures by cysteamine: possible role of somatostatin to kindled seizures.

Recently we reported significant increase in immunoreactive somatostatin content in various brain regions of amygdaloid-kindled rats. We report here that acute intraperitoneal administration of cysteamine, an agent reported to deplete brain and gastrointestinal immunoreactive somatostatin content in kindled rats, led to profound suppression of kindled seizures. Purified anti-somatostatin antibody injected intracerebroventricularly also blocked the kindled seizures. The results show that endogenous immunoreactive somatostatin has a role in the development of seizures in amygdaloid kindled rats.

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

Changes of immunoreactive somatostatin and beta-endorphin content in rat brain after amygdaloid kindling.

A possible contribution of brain beta-endorphin and somatostatin to the epileptogenicity established by amygdaloid kindling was investigated in rats. Fourteen male rats were chronically implanted with electrodes placed bilaterally into the amygdala. The rats received 1 sec of electrical stimulation to the left amygdala each day. Generalized seizures were observed on average 10 days after initiation of kindling and the electrical stimulation was continued up to twenty-one days. Two months after the completion of the kindling procedure, each kindled and control rat was killed by microwave irradiation and the brains were dissected on ice into thirteen subregions. Each region was homogenized and centrifuged twice in 0.1 N acetic acid. The supernatant extracts were decanted and stored at - 20 degrees C until assay. Immunoreactive beta-endorphin and somatostatin were measured by radioimmunoassays. There were no significant differences in brain beta-endorphin contents between the two groups. In kindled rats, immunoreactive somatostatin was increased significantly in amygdala, sensorimotor, piriform, and entorhinal cortex. The results suggest that changes in somatostatin may be associated with epileptic susceptibility induced by the electrical kindling procedure.

Amygdala↗
PubMed1983

Diffusion of phenol in the presence of a complexing agent, tetrahydrofuran.

The effect of a complexing agent, tetrahydrofuran, on the diffusion of phenol across a stagnant fluid layer has been studied. At a given activity of free phenol, the steady-state flux of phenol appearing in an acceptor phase was greatly enhanced. However, as the fraction of phenol associated with the complexing agent increased, the flux of phenol decreased, since the transport was then controlled by the diffusion of the complex, a larger structure. A mathematical model of simultaneous association and diffusion was derived to determine whether the diffusional behavior of two associating species could be accounted for in terms of the association equilibrium constant and Fick's second law. Experimental results supported the model. It was concluded that the presence of a complexing agent tends to reduce the rate of diffusion, the effect being more pronounced at high concentrations of complexing agent.

Chelating Agents↗
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

Prodrugs of 6-thiopurines: enhanced delivery through the skin.

Soft-alkylated derivatives of 6-mercaptopurine, its riboside, and 2-amino-6-mercaptopurine riboside have been prepared and evaluated to improve the delivery of the thiopurines through the skin. The soft-alkylated derivatives were prepared by the alkylation of the thiopurines with acylheteroalkyl halides under neutral or basic conditions. The penetration of the derivatives through hairless mouse skin was measured using diffusion cells. All of the derivatives underwent extensive degradation during their diffusion through skin so that the parent thiopurine, even in the case of the ribosides, was the major product observed in the receptor phase. The pivaloyloxymethyl derivatives showed the greatest potential for enhancing the penetration of the thiopurines through the skin. Among the 6-mercaptopurine derivatives, VII and XI were the most effective; they delivered 5 and 13 times, respectively, more 6-mercaptopurine than 6-mercaptopurine itself.

Animals↗
PubMed1983

Long-acting contraceptive agents: design of the WHO Chemical Synthesis Programme.

The great demand for improved long-acting injectable steroid contraceptives, particularly in developing countries, and the relative lack of interest from the pharmaceutical industry to develop such products stimulated WHO to launch a synthetic and screening programme to find improved, safe and acceptable injectable preparations. More than 210 esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) and levonorgestrel (D-(-)-13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one) have been prepared in university-based research laboratories situated mainly in developing countries, and then screened by NICHHD in animal models. The following three compounds, levonorgestrel butanoate, cyclopropylcarboxylate and cyclobutylcarboxylate, proved to be particularly long-acting when administered as microcrystalline suspensions. The overall strategy of this research and development programme is described.

Animals↗
PubMed1983

1,1,3,3-Tetramethylurea and triethanolamine as a new useful matrix for fast atom bombardment mass spectrometry of gangliosides and neutral glycosphingolipids.

Analysis of gangliosides from bovine brain was successfully performed by a newly developed method of fast atom bombardment mass spectrometry (FAB-MS). The use of triethanolamine with a few drops of 1,1,3,3-tetramethylurea as the matrix solution gave intense molecular ions of intact gangliosides tested, namely, GM1 and GD1a, corresponding to (M + Na)+ and (M + 2Na-H)+. Glycerol, that is usually used as a matrix solution for FAB-mass spectrometry, was not suitable for the analysis of gangliosides. Along with the molecular ion species, the ions pertaining to the carbohydrate sequence also appeared on the spectrum. The method was found to be useful for structural analysis using intact molecules of gangliosides and neutral glycosphingolipids.

Animals↗
PubMed1983

Negative ion fast atom bombardment mass spectrometry of gangliosides and asialo gangliosides: a useful method for the structural elucidation of gangliosides and related neutral glycosphingolipids.

Structural elucidation, including molecular weight, carbohydrate sequence and molecular species of the ceramide portion, of gangliosides and asialo gangliosides from bovine brain, was successfully performed by negative ion fast atom bombardment mass spectrometry (NEG-FAB-MS). Ceramide monohexoside, ceramide dihexoside, asialo GM2 (GA2) and asialo GM1 (GA1), all of which were prepared from bovine brain gangliosides by treatment with 1 M formic acid and monosialogangliosides, GM3, GM2, and GM1, were analyzed without any derivatization by NEG-FAB-MS. They clearly gave the intensive molecular ion species, (M-H)-, and the fragment ions cleaved at glycosidic linkage sequentially from the non-reducing end with or without the ceramide portion. The spectra were quite simple, easily obtained without expansion of ion intensity, and extremely useful for the structural elucidation of underivatized glycosphingolipids.

Animals↗
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↗