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Biomedical subjects

T Namba

Publications and source records attributed to T Namba.

At least 109 records · Page 6Linked to original sources
PubMed1996

Protective effect of celosian, an acidic polysaccharide, on chemically and immunologically induced liver injuries.

Hepatoprotective effect of celosian, an acidic polysaccharide isolated from the water extract of the seed of Celosia argentea, was investigated using chemical and immunological liver injury models. Celosian inhibited the elevation of serum enzyme (GPT, GOT, LDH) and bilirubin levels on carbon tetrachloride (CC1(4))-induced liver injuries in rat. In addition, the hepatoprotective effect of celosian was also observed in this model of liver injury by histopathological findings. Moreover, celosian suppressed rises in GPT or mortality on fulminant hepatitis induced by D-galactosamine/lipopolysaccharide (D-Ga1N/LPS) or Propionibacterium acnes/LPS in mice. These findings suggested that celosian is an active component in protection against chemical and immunological hepatitis and the activity was found to be a dose dependent. Celosian showed a concentration dependent inhibitory effect on lipid peroxide (LPO) generation in vitro. Though celosian did not reduce the release of tumor necrosis factor-alpha (TNF-alpha), it protected against recombinant human TNF-alpha (rhTNF-alpha)-induced liver injury in D-galactosamine sensitized mice.

Animals↗
PubMed1996

Potent antihepatotoxic activity of dicaffeoyl quinic acids from propolis.

Hepatoprotective activity guided chemical analyses led to the isolation of two dicaffeoyl quinic acid derivatives, methyl 3,4-di-O-caffeoyl quinate (1) and 3,4-di-O-caffeoyl quinic acid (2) from water extract of propolis, and their structures were determined by the use of 2D NMR. These compounds were stronger antihepatotoxic agents than glycyrrhizin.

Alanine Transaminase↗
PubMed1996

Assay for antiviral activity of herbal extracts using their absorbed sera.

We evaluated an antiviral assay procedure using serum obtained from guinea pigs administered 32 herbal extracts. In this assay, 21 of the 32 showed anti-herpes simplex virus type 1 (HSV-1) activity in serum. Ten of the 21 exhibited therapeutic anti-HSV-1 activity, and this was consistent with our previous results that 12 of the 32 were effective in murine infection models. Therefore, the serum pharmacological assay procedure was suitable for the selection of possible herbal extracts with biological activity in vivo as a pre-screening method before animal experiments.

Animals↗
PubMed1996

[Botanical origin of commercial samples of traditional Chinese drug xixin (Herba Aasari)].

It has been found out that amony the 158 samples of commercial drug. Xixin (Herba Asari) collected from 28 provinces/cities of China, only three guarters are derived from the species specified in the Chinese Pharmacopoeia and the rest are not. One hundred and eleven samples are derived from Asarum heterotropoides var. mandshuricum and are presently used in 26 provinces/cities, 25 samples are derived from A. himalaicum and used in 10 provinces, the other 22 samples are derived from 9 species such as A. sieboldii, A. forbesii, etc.

China↗
PubMed1995

Selective coupling of prostaglandin E receptor EP3D to Gi and Gs through interaction of alpha-carboxylic acid of agonist and arginine residue of seventh transmembrane domain.

Prostaglandin (PG) E receptor EP3D is coupled to both Gi and Gs. To examine the roles of the interaction of alpha-carboxylic acid of PGE2 and its putative binding site, the arginine residue in the seventh transmembrane domain of EP3D, in receptor-G protein coupling, we have mutated the arginine residue to the noncharged glutamine. PGE2 with a negatively charged alpha-carboxylic acid and sulprostone, an EP3 agonist with a noncharged modified alpha-carboxylic acid, inhibited the forskolin-stimulated adenylate cyclase activity via Gi activation in the EP3D receptor in the same concentration-dependent manner. In contrast, the adenylate cyclase stimulation via Gs activation by sulprostone was much lower than that by PGE2. On the other hand, both PGE2 and sulprostone showed potent Gi activity but failed to show Gs activity in the mutant receptor. EP3D receptor showed a high affinity binding for PGE2 in the form coupled to either Gi or Gs. Although the mutant receptor showed high affinity binding when coupled to Gi, it lost high affinity binding in the condition of Gs coupling. Furthermore, sulprostone bound to the Gi-coupled EP3D receptor with higher affinity than the Gs-coupled receptor. Among various EP3 agonists, alpha-carboxylic acid-unmodified agonists showed both Gi and Gs activities, but the modified agonists showed only Gi activity. These findings suggest that the interaction between the alpha-carboxylic acid of PGE2 and the arginine residue of the receptor regulates the selectivity of the G protein coupling.

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Identification of prostaglandin E receptor 'EP2' cloned from mastocytoma cells EP4 subtype.

We previously cloned a cDNA for a mouse PGE receptor positively coupled to adenylate cyclase from mouse mastocytoma cells, and reported it as EP2 subtype of PGE receptor [Honda, A., Sugimoto, Y., Namba, T., Watabe, A., Irie, A., Negishi, M., Narumiya, S. and Ichikawa, A. (1993) J. Biol. Chem. 268, 7759-7762]. However, it is not sensitive to one of the EP2 agonists, butaprost. Recently another subtype of PGE receptor coupled to adenylate cyclase has been identified pharmacologically and named EP4. These findings have led us to examine whether the cloned receptor is the EP4 subtype. AH23848B, a selective EP4 antagonist, not only displaced the [3H]PGE2 binding to the cloned receptor but antagonized the PGE2-stimulated cAMP formation in the receptor. In contrast, EP2 specific agonist, butaprost and 19(R)OH-PGE2 neither bound to the receptor nor stimulated the cAMP formation. These results suggest that this receptor previously reported as 'EP2' subtype is identical to the pharmacologically defined EP4 subtype and not of EP2 subtype.

Adenylyl Cyclases↗
PubMed1995

Quantitation of IL-1 beta mRNA by a combined method of RT-PCR and an ELISA based on ion-sensitive field effect transistor.

A method for quantitative RT-PCR using ELISA detection was developed and applied to the quantitation of IL-1 beta mRNA in clinical samples. To compensate for the 'tube effect' of RT-PCR, a synthetic RNA, pRSET RNA, was added to sample solutions as an internal standard and co-amplified with IL-1 beta mRNA. Sense primers for IL-1 beta and pRSET were labeled with digoxigenin and FITC, respectively, while anti-sense primers for both were labeled with biotin. Double-stranded PCR products were captured by two solid-phase pipettetips. One was coated with an anti-digoxigenin antibody and another with an anti-FITC antibody, and sandwiched by avidin-urease, and their activities were measured by coupling them with a pH-FET in a pH-measuring cell containing urea solution. The ratio of the signal intensity for IL-1 beta to that for pRSET was used to quantify the concentration of IL-1 beta mRNA. A calibration curve was obtained by using a known amount of AW 109 RNA as an external standard of IL-1 beta RNA. It was found that 10(2)-10(6) copies of IL-1 beta mRNA were measurable by the present method. Expression levels of IL-1 beta mRNA in clinical samples, such as monocytes of peripheral blood or synovial cells from patients with RA or OA, were determined.

Base Sequence↗
PubMed1995

Efficacy of traditional herbal medicines in combination with acyclovir against herpes simplex virus type 1 infection in vitro and in vivo.

Traditional herbal medicines have been safely used for the treatment of various human diseases since ancient China. We selected 10 herbal extracts with therapeutic antiherpes simplex virus type 1 (HSV-1) activity. Among these, Geum japonicum Thunb., Rhus javanica L., Syzygium aromaticum (L.) Merr. et Perry, or Terminalia chebula Retzus showed a stronger anti-HSV-1 activity in combination with acyclovir than the other herbal extracts in vitro. When acyclovir and/or a herbal extract were orally administered at doses corresponding to human use, each of the 4 combinations significantly limited the development of skin lesions and/or prolonged the mean survival times of infected mice compared with both acyclovir and the herbal extract alone (P < 0.01 or 0.05). These combinations were not toxic to mice. They reduced virus yields in the brain and skin more strongly than acyclovir alone and exhibited stronger anti-HSV-1 activity in the brain than in the skin, in contrast to acyclovir treatment by itself. Combinations of acyclovir with historically used herbal medicines showed strong combined therapeutic anti-HSV-1 activity in mice, especially reduction of virus yield in the brain.

Acyclovir↗
PubMed1995

Bellidifolin stimulates glucose uptake in rat 1 fibroblasts and ameliorates hyperglycemia in streptozotocin (STZ)-induced diabetic rats.

Bellidifolin, isolated from Swertia japonica, was found to be a potent hypoglycemic agent in STZ-induced diabetic rats by both oral and intraperitoneal administration. Bellidifolin significantly lowered the loaded glucose level in normal as well as diabetic rats. Bellidifolin also lowered blood triglyceride levels significantly. It stimulated glucose uptake activity in Rat 1 fibroblasts expressing human insulin receptors.

Animals↗
PubMed1995

Potent inhibitors of tyrosinase activity and melanin biosynthesis from Rheum officinale.

Thirty-three crude drug extracts were screened for their tyrosinase inhibitory activity. Among them, the acetone extract of the rhizomes of Rheum officinale Baillon showed the strongest inhibitory activity. Tyrosinase inhibitory activity-guided fractionation and chemical analysis led to the isolation of two potent compounds, 3,4',5-trihydroxystilbene-4'-O-beta-D-(2"-O-galloyl)glucopyr anoside (1) and 3,4',5-trihydroxystilbene-4'-O-beta-D-(6"-O-galloyl)glucopyr anoside (2). These compounds showed a competitive inhibition against tyrosinase and also inhibited the melanin biosynthesis.

Enzyme Inhibitors↗
PubMed1995

In situ hybridization studies of prostacyclin receptor mRNA expression in various mouse organs.

1. Expression of prostacyclin receptor (IP receptor) mRNA was examined in various mouse organs, and the cells expressing IP receptor mRNA were identified by in situ hybridization studies. Co-localization of mRNA for the IP receptor with that for preprotachykinin A (PPTA), a precursor protein for substance P, with mRNA for the prostaglandin E receptor subtypes (EP1, EP3 and EP4), and with renin mRNA, was examined by double in situ hybridization studies in the dorsal root ganglion and kidney, respectively. 2. IP receptor mRNA was expressed in the thymus and spleen. Expression in the thymus was found exclusively in the medulla, where mature thymocytes expressed transcripts for the IP receptor. Expression in the spleen was found as scattered signals over the white pulp and as punctate signals in the red pulp. The former was found in splenic lymphocytes and the latter in megakaryocytes. 3. IP receptor mRNA was also expressed in the vascular tissues of various organs such as the aorta, coronary arteries, pulmonary arteries and the cerebral arteries, where its expression was confined to smooth muscle cells. No expression was found in veins. In the kidney, IP receptor mRNA was detected in the interlobular arteries and glomerular arterioles but not in the juxtaglomerular (JG) cells which were labelled with the renin mRNA probe. 4. IP receptor mRNA was expressed in about 40% of the neurones in the dorsal root ganglion. Both small- and large-sized neurones were labelled but no labelling was found in the glia. Expression of PPTA mRNA was found in about 30% of total neurones. About 70% of these neurones expressed IP receptor mRNA, and about half of the IP receptor-positive neurones expressed PPTA mRNA. In addition to IP mRNA, mRNAs for EP1, EP3 and EP4 receptors were expressed in about 30%, 50% and 20%, respectively, of the dorsal root ganglion neurones. About 25%, 41% and 24% of the IP receptor-positive neurons co-expressed the EP1, EP3 and EP4 receptor, respectively. 5. These results not only verified IP receptor expression in various cells and tissues known to be sensitive to prostacyclin, but also revealed its expression in other systems, which urges the study of the actions of prostacyclin in these tissues. They also indicated that the actions of prostacyclin on blood vessels and platelets are mediated by the same type of receptor. Absence of IP receptor mRNA in the JG cells suggests that the action of prostacyclin on renin release may be indirect.

Animals↗
PubMed1995

Effect of alcohol and electrical stimulation on leakage of creatine kinase from isolated fast and slow muscles of rat.

Binge drinking of alcohol may lead to acute alcoholic myopathy with rhabdomyolysis, which is characterized by skeletal muscle damage, elevated serum creatine kinase (CK), and myoglobinuria. This study was undertaken to test whether alcohol acts directly on the skeletal muscles to enhance the leakage of CK, and to assess the influence of fiber-type composition and repetitive contractions of the muscle on the effect of alcohol. After 4 hr of incubation in normal physiological solution at 37 degrees C, mean leakage of CK was 0.7 units/mg from isolated rat extensor digitorum longus (EDL), which has more fast-twitch glycolytic muscle fibers, and 1.2 units/mg from the soleus, which has more slow-twitch oxidative muscle fibers. Ethanol at 0.1, 0.2, and 0.5% concentrations caused significantly greater increase in leakage of CK from soleus than from EDL. In normal physiological solution, electrical stimulation at 1 Hz for 4 hr increased the leakage of CK by about the same degree in both EDL and soleus. In the presence of 0.1 and 0.2% ethanol, electrical stimulation markedly potentiated the alcohol-induced leakage of CK from both soleus and EDL. These results indicate that alcohol increases the leakage of CK by acting directly on skeletal muscle fibers, especially of the slow-twitch oxidative type, and that repeated muscle contractions potentiate the alcohol effect. These studies suggest that exercise may increase the chances of rhabdomyolysis in the alcoholics.

Animals↗
PubMed1995

Effect of ethanol on function of the rat heart and skeletal muscles.

The present study was undertaken to evaluate the acute effects of ethanol on responses of the rat heart and skeletal muscles both in vivo and in vitro. In the anesthetized rat, intravenous infusion of ethanol at 0.1-0.5 g/kg body weight (33-167 mM) decreased the breathing rate by 8-83%, heart rate by 4-52%, and QRS amplitude by 5-27%, and increased the P-R interval by 1-49%. In the anterior tibialis muscle subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, ethanol at 0.1 g/kg increased the amplitude of the muscle action potential (AP) by 7%, whereas at 0.5 g/kg it decreased the muscle AP by 32%. The nerve-evoked tetanic tension was reduced by 7-34% at 0.1-0.5 g/kg ethanol. In the isolated rat heart, perfusion of ethanol at 0.1-3.0% (22-651 mM) decreased the heart rate by 8-48% and QRS amplitude by 10-39%, and increased the P-R interval by 5-61%. Left ventricular pressure was increased by 10% at 0.1% ethanol, and decreased by 80% at 3.0% ethanol. In the isolated rat phrenic nerve-diaphragm muscle preparation subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the nerve AP by 5-89%, nerve-evoked muscle AP by 2-96%, and peak tetanic tension by 1-87%. On repetitive direct muscle stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the muscle-evoked muscle AP by 8-65%, and muscle-evoked tetanic tension by 2-65%. These studies indicate that ethanol causes smaller reduction in responses of the heart and skeletal muscles at clinical concentrations, but marked reduction in these responses at higher concentrations due to direct action on excitability of these tissues. At higher concentrations, ethanol causes greater reduction in excitability of the skeletal muscle than of the heart.

Animals↗
PubMed1995

Ca(2+)-free, high-Ca2+ coronary perfusion suppresses contractility and excitation-contraction coupling energy.

We studied the mechanoenergetic effects of a short-term Ca(2+)-free, high-Ca2+ Tyrode solution coronary perfusion in eight excised, cross-circulated canine hearts. The perfusion protocol consisted of coronary perfusion with Ca(2+)-free Tyrode solution for 10 min followed by high-Ca2+ (16 mM) Tyrode solution for 5 min. This new protocol successfully induced acute contractile failure in seven hearts, without myocardial ultrastructural changes. We studied the end-systolic pressure-volume relation (slope = Emax, a contractility index) and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA) in these failing hearts. These hearts had no increase in end-diastolic pressure at a given volume, a 40% decrease in Emax and a proportional decrease in the PVA-independent VO2 for 1-4 h, but no decrease in the oxygen cost of PVA, defined as the slope of the VO2-PVA relation. The oxygen cost of Emax for Ca2+ handling, defined as the slope of the relation between PVA-independent VO2 and Emax, was unchanged in the failing hearts. We conclude that the present protocol induced left ventricular contractile failure, primarily involving the suppression of Ca2+ handling energy for excitation-contraction coupling.

Animals↗
PubMed1995

Five new C-methyl flavonoids, the potent aldose reductase inhibitors from Matteuccia orientalis Trev.

Five new compounds, matteuorien, matteuorienin, and matteuorienate A (7), B (8), and C (9) were isolated together with five known compounds from the MeOH extract of the rhizome of Matteuccia orientalis Trev. The structures of these compounds were determined by the use of spectroscopic methods including two dimensional (2D)-NMR experiments and chemical methods, except for the configuration at the C-3"' of matteuorienate A (7), B (8), and C (9). Among them, matteuorienate A, B, and C showed very strong aldose reductase inhibitory activity. A structure-activity relationship study showed that a carboxyl group played an important part in aldose reductase inhibitory activity in these three compounds.

Aldehyde Reductase↗
PubMed1995

Inhibitory effects of Egyptian folk medicines on human immunodeficiency virus (HIV) reverse transcriptase.

Extracts of 41 medicinal plants used in Egyptian folk medicine were screened for their inhibitory effects on human immunodeficiency virus-1 reverse transcriptase. The extracts of fruits of Phyllanthus emblica, Quercus pedunculata, Rumex cyprius, Terminalia bellerica, Terminalia chebula and Terminalia horrida showed significant inhibitory activity with IC50 < or = 50 micrograms/ml. Through a bioassay guided-fractionation of the methanol extract of the fruit of P. emblica, putranjivain A (1) was isolated as a potent inhibitory substance with IC50 = 3.9 microM, together with 1,6-di-O-galloyl-beta-D-glucose (2), 1-O-galloyl-beta-D-glucose (3), kaempferol-3-O-beta-D-glucoside (4), quercetin-3-O-beta-D-glucoside (5) and digallic acid (6). The inhibitory mode of action by 1, 2 and 6 was non-competitive with respect to the substrate but competitive with respect to a template-primer. Furthermore, the stereochemistry of 1 was established in this paper by nuclear magnetic resonance spectroscopy.

Carbohydrate Conformation↗
PubMed1995

[Study on baths with crude drug. II.: the effects of coptidis rhizoma extracts as skin permeation enhancer].

Skin permeation and its enhancing activity of Coptidis Rhizoma (Coptis japonica Makino) were studied in regard to its application as a bath agent. As a result, methanol extracts and three alkaloids (berberine, coptisine, and palmatine isolated from Coptidis Rhizoma) enhanced effectively the skin permeation of 5-fluorouracil, which is taken as a hydrophilic permeant. Furthermore, it was observed that diffusion coefficient is almost constant on the skin permeation of 5-fluorouracil and was also observed that these three kinds of alkaloids did not penetrate through the skin, but adsorbed into the skin. These results suggest that these three protoberberine type alkaloids increase the concentration of polar drugs in the skin and enhance the skin permeation similarly to surfactants.

Animals↗