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Biomedical subjects

M Tai

Publications and source records attributed to M Tai.

At least 19 recordsLinked to original sources
PubMed2005

Induction of mononuclear cell infiltration into liver by Japanese herbal medicine.

Juzen-Taiho-To (JTT) is a Japanese herbal medicine that has been administered mainly to patients weakened by long illness. Currently, it has also been used for cancer patients and showed antitumor effects that have been reported as phagocytosis enhancement, cytokine induction and antibody production. In this study, we examined the effect of oral administration of JTT in mice on the immunological restoration of the liver, especially focused on natural killer (NK) T-cell induction. Mice were grouped to receive JTT or placebo orally for a period of 1, 3 and 7 days. After sacrifice, the liver tissue was fixed, embedded and stained with hematoxylineosin and some antibodies by common staining methods. Transmission electron microscope (TEM) observation was also carried out. Although the JTT-treated mice had the same appearance as the non-JTT-treated mice, their livers were infiltrated by massive mononuclear cells, some of which were aggregated in clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of interleukin (IL)-12 and massive infiltration of mononuclear cells with large granules in the liver of JTT-treated mice. Oral administration of JTT may induce the expression of IL-12 and be followed by immunological restoration such as NK T-cell induction in liver

Animals↗
PubMed2001

Effects of olfactory bulbectomy on NMDA receptor density in the rat brain:.

Olfactory bulbectomy (OBX) transects the glutamatergic efferents from the olfactory bulbs, and the changes of glutamatergic N-methyl-D-aspartate (NMDA) receptor-mediated function are though to be involved in the behavioral deficits seen in OBX rats. In the present study, irritability scores in OBX male Wistar rats were correlated with discrete regional effects on NMDA receptor function measured using a [3H] MK-801 binding assay. Irritability scores, measured before and for 2 weeks after OBX, showed a gradual increase in irritability after OBX. A reduction of the NMDA receptor density was observed in the cerebral cortex and amygdala 16 days after OBX, but not in the striatum, olfactory tubercle, entorhinal cortex, and hippocampus. These results demonstrate that OBX causes changes in the NMDA receptor system in certain brain regions and suggest that these changes may be responsible for the behavioral deficits of OBX rats.

Animals↗
PubMed2000

Studies directed at the use of a parallel synthesis matrix to increase throughput in an in vivo assay.

Heparin is the anticoagulant of choice for hospitalized patients, but it is dosed only by injection because it is not absorbed following oral administration. We have discovered and prepared compounds (delivery agents) that facilitate the gastrointestinal absorption of heparin in rats, monkeys, and humans when given orally. We are currently developing a parallel synthesis approach to increase our delivery agent screening throughput in vivo. This approach has been used to produce micromolar quantities of compounds for testing in rats in a 5 x 5 parallel synthesis array. Using an amine benzoylation reaction sequence, 10 mixtures were prepared. These mixtures contained equal weight quantities of five N-substituted, non-alpha, amino acid delivery agents. Each of these mixtures was orally administered to rats in combination with heparin, and plasma clotting times (APTT) were measured to determine activity. Deconvolution of the data accurately identified the most active individual components. Independent synthesis of these compounds verified their activity. This parallel synthesis approach is an effective tool for the screening of oral heparin delivery agents and has increased screening throughput significantly.

Amino Acids↗
PubMed2000

Cronkhite-Canada syndrome: report of two cases.

Two cases of Cronkhite-Canada syndrome are reported. In the first case, a 56-year-old woman had an adenoma of the colon, arising within the Cronkhite-Canada polyps, which was removed by endoscopic polypectomy. This suggests possible neoplastic transformation of polyps in this syndrome. She achieved remission with corticosteroids, but the polyposis recurred (only in the stomach) 7 months after the remission. In the recurrent polyposis, corticosteroid therapy resulted again in complete remission, which has lasted for 5 years. In the second case, a 69-year-old man developed typical manifestations of the syndrome while under emotional stress. He had a past history of chronic pityriasis lichenoides, and serum antinuclear antibody was positive. These findings suggested a possible role of autoimmune response in the pathogenesis of the syndrome. Corticosteroids were also effective in this patient.

Adenoma↗
PubMed1998

Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin.

A family of novel compounds (delivery agents) that promote the gastrointestinal absorption of USP heparin in rats and primates has been discovered. The delivery agents in combination with heparin were administered either orally or intracolonically in an aqueous propylene glycol solution and caused dramatic increases in both plasma heparin concentrations (anti-Factor Xa) and clotting times (APTT). Using one of the most effective delivery agents in this series, an estimated relative bioavailability of 8% can be achieved following oral administration to cynomolgus monkeys. To establish a correlation between the in vivo data and an in vitro parameter, immobilized artificial membrane (IAM) chromatography was performed. Log relative k' values were correlated to the efficiency of oral heparin delivery.

Amino Acids↗
PubMed1997

Haemodynamic comparison of sevoflurane and isoflurane anaesthesia in surgical patients.

PURPOSE: To compare the haemodynamic responses to surgical incision during sevoflurane and isoflurane anaesthesia and to compare the haemodynamic effects of each anaesthetic alone with those obtained using an equipotent mixture of each anaesthetic plus N2O during steady-state surgical stimulation. METHODS: Twenty-four patients undergoing gastrectomy were randomized to receive sevoflurane (n = 12) or isoflurane (n = 12). At 1.5 MAC, haemodynamic measurements were performed before and after surgical incision. During intestinal anastomosis, patients in each group were given (in random order) either 1.5 MAC of the designated anaesthetic or 0.85 MAC of the volatile plus 0.65 MAC N2O. Haemodynamic measurements were repeated under each condition. RESULTS: One patient in the sevoflurane group and two in the isoflurane group were excluded from the incision study because of hypotension. In both groups, incision increased the heart rate (HR), mean arterial pressure, mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), cardiac index, and systemic vascular resistance index (SVRI). There were no intergroup differences in the effects of incision. Inclusion of N2O resulted in an increase of MPAP (P < 0.05) in both groups, an increase of central venous pressure and PCWP in the sevoflurane group (P < 0.005), and a decrease of HR (P < 0.005) and an increase of SVRI (P < 0.05) in the isoflurane group. There were no intergroup differences in the effects of N2O. CONCLUSIONS: At 1.5 MAC, sevoflurane and isoflurane do not prevent the haemodynamic response to incision. The haemodynamic effects of each volatile anaesthetic with N2O are minimal compared with those of equi-MAC volatile alone.

Adult↗
PubMed1997

The devastating consequence of iodine deficiency.

Endemic cretinism is the most striking consequence of iodine deficiency. Although cretinism is a serious condition, it usually involves only about 5% of the population even in serious endemic areas. There is a spectrum between cretinism and normality, many are able to perform simple work and look apparently normal, but it is difficult for them to perform skilled labor. Studies in China using the IQ distribution curve revealed that every person in an endemic area lost about 10-15 IQ points, so that the socio-economic development of the community was severely affected.

Adolescent↗
PubMed1995

A sparse matrix screen to establish initial conditions for protein renaturation.

Protein renaturation is of particular interest not only for the basic mechanisms of protein folding but also as a practical problem for proteins overexpressed in microorganisms, since recombinant proteins may accumulate as misfolded aggregates in "inclusion bodies" that are inactive after purification. We have established a systematic screening method to identify conditions which promote protein renaturation. A matrix of 50 different buffers, which were originally developed for protein crystallization, were found to facilitate the renaturation for eight of nine different proteins examined. The proteins tested include the adhesive protein bindin, recombinant bindin, and a variety of enzymes, including bacterial alkaline phophatase, horseradish peroxidase, lysozyme, trypsin, beta-galactosidase, rabbit carboxylesterase, and acetylcholinesterase. The total amount of activity recovered varied from 9 to 333% depending on the protein. The conditions that were found to promote renaturation are very different from the optimal conditions for enzyme activity. The finding that most of the proteins tested renatured to a significant extent in one or more of the buffers in the matrix suggests that the sparse matrix screen may be of general utility for establishing initial renaturation conditions for a wide variety of proteins. One initial renaturation conditions have been identified, the conditions may be optimized by systematically altering other parameters of the renaturation process.

Acetylcholinesterase↗
PubMed1995

Studies on cognitive enhancing agents. I. Antiamnestic and antihypoxic activities of 2-dimethylaminoethyl ethers and related compounds.

N-(2-Dimethylaminoethyl)carboxamide (1a-d), 2-dimethylaminoethyl alkyl ether (2a, b), and 2-dimethylaminoethyl 2-hydroxy-2-phenethyl ether (3a-c) and its amino and methylene analogues (3d, 4) have been screened for antiamnestic and antihypoxic activities in mice. A clear reversing effect on electroconvulsive shock-induced amnesia was found with 1a-d, 2a,b, and 2-dimethylaminoethyl 2-hydroxy-2-phenylethyl ether (3a). However, a protective effect against hypoxia was only observed with 3a. Compound 3a, which displayed the dual activity, was further investigated for ameliorating effect on CO2-induced memory impairment, and it was found to be more potent than indeloxazine and bifemelane. In addition, the acute toxicity of 3a in mice was significantly lower than that of tacrine, but its serum-to-brain penetration ability in rats was less than that of the reference drugs.

Amnesia↗
PubMed1995

Studies on cognitive enhancing agents. II. Antiamnestic and antihypoxic activities of 1-aryl-2-(2-aminoethoxy)ethanols.

A series of 2-(2-aminoethoxy)-1-phenylethanols having a variety of N- and phenyl-substitution patterns as well as 5- and 6-membered heteroaryl counterparts of our prototype compound 1 (2-(2-dimethylaminoethoxy)-1-phenylethanol) have been prepared and evaluated for antiamnestic and antihypoxic activities. Compound 3b, the 3-methylphenyl analogue of 1, proved to be significantly more potent than 1 in reversing electroconvulsive shock-induced amnesia as well as CO2-induced learning-impairment in mice. It exhibited low acute toxicity in mice and afforded a greater brain/serum concentration ratio than 1 after oral administration to rats.

Amnesia↗
PubMed1995

Studies on cognitive enhancing agents. III. Antiamnestic and antihypoxic activities of a series of 1-bicycloaryl-2-(omega-aminoalkoxy)ethanols.

2-(2-Aminoethoxy)-1-hydroxyethyl derivatives of bicyclic arenes (naphthalene, thianaphthene, benzofuran, and indole) were prepared and screened for antiamnestic (AA) and antihypoxic (AH) activities which were evaluated by measuring the reversing potency in electroconvulsion-induced amnesia and the protective effect against hypoxia, respectively, in mice. Compound 3o, 1-(benzo[b]thiophen-5-yl)-2- (2-diethylaminoethoxy)ethanol, showed the best AA and AH activity profile, being superior to our prototype compound, 2-(2-dimethylaminoethoxy)-1-phenylethanol (1). Elongation of the ethylene linkage in the side chain of 3o to 3- and 4-carbon moieties brought about a significant decrease in AH activity. Compound 3o was further investigated for its protective effect against CO2-induced memory impairment and for acute toxicity in mice. It is ten-fold more potent than tacrine in the amnesia-reversal assay and is considerably less toxic than tacrine.

Amnesia↗
PubMed1995

[Studies on structure of light degradation products of (-)-(S)-10-(1-aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dihyd ro-7H- pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (T-3761) in aqueous solution and solid state].

The structures of light degradation products of (-)-(S)-10-(1-aminocyclopropyl)-9-fluoro-3-methyl-7-oxo-2,3-dih ydr o-7H- pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (T-3761) in aqueous solution and in the solid state were investigated. In aqueous solution, ten products were detected using HPLC and in the solid state, one main product was detected. All these light degradation products were isolated and their structures were elucidated. It was revealed that in almost all light degradation products only the 1-aminocyclopropyl side chain at the 10-position of T-3761 is changed to various structures by light oxidation. Surprisingly we found a unique light degradation product, in which carboxylic acid at the 6-position of T-3761 is changed to the hydroxy moiety.

Anti-Infective Agents↗
PubMed1995

[Determination of T-3761 in body fluids by high-performance liquid chromatography].

A high-performance liquid chromatographic procedure was developed for determination of T-3761 in human serum and urine. The method was based on column switching for serum, and direct injection for urine. The peaks were monitored by ultraviolet detection. The calibration curve was linear and quantitative in the concentration range of 0.01-30 micrograms/ml for serum and 0.5-900 micrograms/ml for urine. The intra-assay coefficient of variation was less than 7%. The intra-day and inter-day coefficient of variation were less than 4%.

Anti-Infective Agents↗
PubMed1995

[Study of metabolism of T-3761 in animal].

The metabolism of T-3761 in mouse, rat, rabbit, dog and monkey was studied. Four metabolites, other than unchanged T-3761, were detected and identified as follows: T-3761 glucuronide; T-3761M1, adduct of glucose; T-3761M2 and T-3761M3, compounds metabolized at 1-aminocyclopropyl ring. In urine of mouse, T-3761 glucuronide was mainly detected, but in urine of other animals, T-3761 was mainly detected.

Administration, Oral↗
PubMed1991

Competitive binding radioassay for the determination of 5-fluorodeoxyuridine and 5-fluorodeoxyuridine-5'-monophosphate levels in plasma and tumor tissue.

A competitive binding radioassay was developed to measure 5-fluoro-2'-deoxyuridine (FUDR) as well as 5-fluoro-2'-deoxyuridine monophosphate (FdUMP), FdUMP has been measured by a competitive binding radioassay with thymidylate synthase as the binding enzyme (TS assay). FUDR was enzymatically converted to FdUMP by thymidine kinase, and then the converted FdUMP was measured by the competitive binding assay to determine the concentration of FUDR in plasma and tumor tissue. As little as 100 pg/ml of FUDR or 50 pg/ml of FdUMP can be detected quantitatively by this method. When TS assay and high-performance liquid chromatography were compared for the measurement of FUDR and FdUMP levels in plasma and tumor tissue of Ehrlich carcinoma (EC)-bearing mice following administration of FUDR, a close agreement was observed for FUDR levels, though low FdUMP levels were detectable only by the TS assay method. The examination of intracellular metabolism of FUDR in EC cells by this method showed that metabolic conversion of FUDR into FdUMP or 5-fluorouracil is rapid. Thus, we have established a highly sensitive method for measuring not only FdUMP but also FUDR with TS assay. This should be very useful for experimental and clinical studies on fluoropyrimidines.

Animals↗
PubMed1989

[Study on metabolism of pyridonecarboxylic acid. I. Isolation and identification of metabolites of (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1- (2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262) in urine].

Metabolism of (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dihydro-4- oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262) was studied. Metabolites were isolated from urine of mouse, rat, rabbit, dog and monkey following oral administration of T-3262, and identified using high performance liquid chromatography and mass spectrometry. Two metabolites, other than unchanged (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)-1,4- dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (T-3262 base), in which 3-aminopyrrolidinyl ring of T-3262 was metabolized, were identified as: (+-)-7-(3-acetyl-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro- 1,4- dihydro-4-oxo-1, 8-naphthyridine-3-carboxylic acid (T-3262A) in all animals: (+-)-1-(2,4-difluorophenyl)-6-fluoro-7-(3-hydroxy-1-pyrrolidinyl)-1,4- dihydro- 4-oxo-1,8-naphthyridine-3-carboxylic acid (T-3262B) in monkey. The glucuronide of T-3262 was detected in mouse, dog and monkey, the glucuronides of T-3262A and T-3262B were detected in monkey. M-I, unidentified metabolite, was detected only in mouse.

4-Quinolones↗
PubMed1989

[Study on metabolism of pyridonecarboxylic acid II. Determination of metabolites of (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl)- 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262) in blood, urine, bile, and feces].

The fate of (+-)-7-(3-amino-1-pyrrolidinyl)-6-fluoro-1-(2,4-difluorophenyl-1,4- dihyro-4-oxo-1,8-naphthyridine-3-carboxylic acid p-toluenesulfonate hydrate (T-3262) was studied using T-3262 and 14C-T-3262 in various animals. 1. Metabolites in serum and urine were assayed for mouse, rat, rabbit, dog and monkey following oral administration of T-3262. In serum, besides unchanged T-3262 base, T-3262A (N-acetylated) was detected in rat, rabbit and monkey; T-3262B (deamino-hydroxylated) was detected in monkey. In urine, unchanged T-3262 base was excreted mainly. But a few of metabolites (T-3262A, T-3262B, T-3262 glucuronide, T-3262A glucuronide, T-3262B glucuronide, and unknown compound M-1) were detected, and species difference existed in types of metabolites. 2. Metabolites in bile and feces were assayed for mouse and rat following oral administration of T-3262 and 14C-T-3262. Metabolites in bile were similar to the urine, but the volume of T-3262A and T-3262A glucuronide was larger than in urine. In feces, the excreted compounds mainly consisted of unchanged T-3262 base. 3. p-Toluenesulfonic acid, which is the counter acid for T-3262 base, was absorbed following the oral administration of T-3262, and excreted in urine in the unchanged form.

4-Quinolones↗