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Biomedical subjects

M Maruno

Publications and source records attributed to M Maruno.

At least 73 records · Page 4Linked to original sources
PubMed1996

Cellular targets of exogenous tumour necrosis factor-alpha (TNF alpha) in human gliomas.

To identify the cellular targets of TNF alpha in human gliomas, a total of 30 surgical specimens (12 glioblastomas, 4 anaplastic astrocytomas, 3 astrocytomas, 7 brains adjacent to tumour (BAT), 4 histologically normal-appearing brains) were examined by in vitro binding technique using biotinylated TNF alpha. The TNF-binding sites (TNF-BS) were recognized in the tumour cells in 8 of the 12 glioblastomas, 3 of the 4 anaplastic astrocytomas and in all the 3 astrocytomas. The TNF-BS were also recognized in the vascular endothelial cells in all these cases. The presence of TNF-BS in blood vessels ranged from 7.7 to 74.4% of the background vessels. This wide range of variation in the presence of TNF-BS within the tumour cells and tumour blood vessels may be relevant to the variable response of individual tumours to TNF alpha therapy. Since the tissue of normal brain, which lacks TNF-BS, might hardly be affected by this cytokine, administration of TNF alpha may be considered as an adjuvant therapy in selected groups of patients.

Binding Sites↗
PubMed1996

Saponins from the root of Bupleurum falcatum.

Three new saponins and nine known saponins were isolated from the dried roots of Bupleurum falcatum. On the basis of chemical and spectral analyses, the structures of new compounds, named 4''-O-acetylsaikosaponin d and hydroxysaikosaponins a and c, were established. In aqueous acidic conditions, saikosaponins a and d were converted into not only known compounds, saikosaponins b1 and b2, but also hydroxysaikosaponins a and d, respectively. Furthermore, quantitative analysis of the decoction of Bupleuri Radix itself by HPLC exhibited that it contained saikosaponins a, c and d, and hydroxysaikosaponins a, c and d.

Carbohydrate Sequence↗
PubMed1996

Bioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysis.

To clarify the metabolic fate of glycyrrhizin when orally ingested, we investigated the bioavailability of glycyrrhetic acid, the aglycone of glycyrrhizin, after intravenous or oral administration of glycyrrhetic acid (5.7 mg kg-1, equimolar to glycyrrhizin) or glycyrrhizin (10 mg kg-1) at a therapeutic dose in rat. Plasma concentration of glycyrrhetic acid rapidly decreased after its intravenous administration, with AUC of 9200 +/- 1050 ng h mL-1 and MRT of 1.1 +/- 0.2 h. The AUC and MRT values after oral administration were 10600 +/- 1090 ng h mL-1 and 9.3 +/- 0.6 h, respectively. After oral administration of glycyrrhizin, the parent compound was not detectable in plasma at any time, but glycyrrhetic acid was detected at a considerable concentration with AUC of 11700 +/- 1580 ng h mL-1 and MRT of 19.9 +/- 1.3 h, while glycyrrhetic acid was not detected in plasma of germ-free rats at 12 h after oral administration of glycyrrhizin. The AUC value of glycyrrhetic acid after oral administration of glycyrrhizin was comparable with those after intravenous and oral administration of glycyrrhetic acid, indicating a complete biotransformation of glycyrrhizin to glycyrrhetic acid by intestinal bacteria and a complete absorption of the resulting glycyrrhetic acid from intestine. Plasma glycyrrhizin rapidly decreased and disappeared in 2 h after intravenous administration. AUC and MRT values were 2410 +/- 125 micrograms min mL-1 and 29.8 +/- 0.5 min, respectively. Plasma concentration of glycyrrhetic acid showed two peaks a small peak at 30 min and a large peak at 11.4 h, after intravenous administration of glycyrrhizin, with an AUC of 15400 +/- 2620 ng h L-1 and an MRT of 18.8 +/- 1.0 h. The plasma concentration profile of the latter large peak was similar to that of glycyrrhetic acid after oral administration of glycyrrhizin, which slowly appeared and declined. The difference of MRT values (19.9 and 9.3 h) for plasma glycyrrhetic acid after oral administration of glycyrrhizin and glycyrrhetic acid suggests the slow conversion of glycyrrhizin into glycyrrhetic acid in the intestine.

Administration, Oral↗
PubMed1996

Accumulation of allelic losses on chromosome 10 in human gliomas at recurrence.

Aims-To elucidate the implications of allelic loss on chromosome 10 in the malignant progression of human gliomas.Methods-Eight microsatellite loci (D10S249, D10S191, D10S210, D10S219, D10S246, D10S222, D10S221, and D10S212) were analysed for chromosomal deletions in histologically benign and malignant, including recurrent, gliomas. Of the 16 original tumours studied (two astrocytomas, nine anaplastic astrocytomas and five glioblastomas), the histological diagnosis at recurrence was anaplastic astrocytoma in six cases and glioblastoma in 10. Genomic DNA was extracted from formalin fixed, paraffin wax embedded sections. Samples of original and recurrent tumours were paired and amplified using PCR. Samples of histologically normal brain served as controls.Results-Of the original tumours, all five glioblastomas, five (56%) of nine anaplastic astrocytomas and none of the astrocytomas demonstrated loss of heterozygosity (LOH) on chromosome 10. Additional LOH was detected in the five cases of anaplastic astrocytoma that progressed to glioblastoma at recurrence. Additional LOH was not detected in the two cases of astrocytoma that progressed to anaplastic astrocytoma at recurrence. With the exception of one case, additional LOH was observed in the recurrent glioblastomas.Conclusion-LOH was observed at the loci of two adjacent microsatellite markers, D10S222 and D10S221 (10q23-q25), suggesting that this region on chromosome 10 is closely related to progression from anaplastic astrocytoma to glioblastoma.

Journal Article↗
PubMed1996

Effects of Hoelen on the efferent activity of the gastric vagus nerve in the rat.

Hoelen is used to treat gastric disease in Eastern traditional medicine. The efferent activity on the gastric vagus nerve was studied in the rat, and the activity was found to increase after administration of Hoelen into the duodenum. In addition, we examined the effect of Hoelen fractions. Both the fraction containing polysaccharide and the triterpenoid-rich fraction increased activity significantly. Hoelen would thus appear useful for treating gastric disease by activating efferent activity of the gastric vagus nerve through the action of triterpenoid and polysaccharide.

Analysis of Variance↗
PubMed1996

Morphological effects of tumor necrosis factor-alpha on the blood vessels in rat experimental brain tumors.

The morphological changes in the vascular endothelium caused by the administration of tumor necrosis factor-alpha (TNF-alpha) were studied in an experimental model of rat brain tumors. Wistar rats bearing implanted C6 glioma received human natural-type TNF-alpha (1.7 x 10(5) U/m2) through the carotid artery and were sacrificed 3 or 24 hours later. The endothelial cells of the tumor blood vessels, demonstrated by the immunoreaction to factor VIII-related antigen, were enlarged after TNF-alpha administration. Morphometry demonstrated that the nuclei of these endothelial cells were also increased in size. The endothelial cells in the brain remote to the tumor were not affected. An in vitro binding study demonstrated that TNF-alpha binding sites were distributed in the vascular endothelial cells within the tumor but not in the brain remote to the tumor. The selective effect of TNF-alpha on the tumor blood vessels in experimental brain tumors may be related to the selective distribution of the TNF-alpha binding site.

Animals↗
PubMed1995

Determination of schizandrin in human plasma by gas chromatography-mass spectrometry.

Schizandrin (SZ) is one of the lignan components from Schisandra fruits. A highly sensitive and precise method for the determination of SZ in human plasma was developed involving selected-ion monitoring with gas chromatography-mass spectrometry using a fused-silica capillary column. A 0.1-ml plasma sample was used for solid-phase extraction. A good linear relationship was obtained in the concentration range studied (2.0-500 ng/ml) and the method was sufficiently accurate and precise to support clinical pharmacokinetic studies. After oral administration of SZ at a dose of 15 mg to healthy male subjects, the average value of the maximum plasma concentration of SZ was 96.1 +/- 14.1 ng/ml. The plasma concentration of this substance could be monitored for 8 h after administration.

Cyclooctanes↗
PubMed1995

Reaction of microglial cells and macrophages after cortical incision in rats: effect of a synthesized free radical scavenger, (+/-)-N,N'-propylenedinicotinamide (AVS)

Reactive microglial cells and macrophages appear after trauma to the brain. To investigate the accumulation patterns of reactive microglial cells and macrophages after cortical incision, these cells were stained immunohistochemically with anti-ED1 antibody in the brain sections before and 1, 3, 5, and 7 days after incision. And to ascertain the participation of oxygen free radicals in these cellular reactions, a synthesized free radical scavenger, (+/-)-N,N'-propylenedinicotinamide (AVS) was administered in this model. Rats were administered AVS (300 mg/kg, i.p.) 30 min before, 2.5 h and every 24 h after incision (AVS group), while only saline was administered in the same manner as a control (saline group). In the saline group, both reactive microglial cells and macrophages had already appeared on day 1 post-incision. The former continued to increase in number during the following days, whereas the latter increased in number up to day 3 and thereafter decreased. Both the numbers of reactive microglial cells and macrophages were significantly decreased (P < 0.05) in the AVS group on days 5 and 7. The results suggest the participation of oxygen free radicals in the reaction of microglial cells and macrophages in traumatic brain injury.

Animals↗
PubMed1995

A case of trichorrhexis nodosa developed in winter.

A young Japanese man developed localized trichorrhexis nodosa (LTN) of the scalp hair in the winter season. To investigate the roles of shampoo, severe sunlight exposure and/or mechanical injuries, we performed the following studies. Hair was collected from the patient and from a control. The study was performed in two steps. In the first step, hair was put into shampoo, rinsed with saline water, and then exposed to ultraviolet B (UVB) radiation once a day for one week. In the second step, the hair was similarly treated, but each shaft was bent gently with forceps before UVB exposure. Scanning electron microscopic studies revealed cuticular changes when the hair was treated only with shampoo and UVB. When it was treated with shampoo, UVB, and mechanical bending, the patient's hair developed longitudinal and transverse fractures of the hair shafts, while the control hair showed only partial damage to the hair shaft. On the basis on the above findings, we conclude that mechanical bending may damage the hair shaft.

Adolescent↗
PubMed1995

Absorption and excretion of paeoniflorin in rats.

The absorption and excretion of paeoniflorin after intravenous and oral administration was studied in rats to evaluate the significance of paeoniflorin in the pharmacological action of Paeony root. The plasma concentration of paeoniflorin after intravenous administration at the doses of 0.5, 2.0 and 5.0 mg kg-1 rapidly decreased, simulated by a biexponential curve, with mean terminal half-lives of 11.0, 9.9 and 12.6 min, respectively. The Vdss values were 0.332, 0. 384 and 0.423 L kg-1 and the CLtot values were 26.1, 31.2 and 30.3 mL min-1 kg-1 at each dose. When given orally at the same doses, the absolute bioavailability values (F) determined by the AUC were 0.032, 0.033 and 0.038, respectively. The cumulative urinary and faecal excretions of paeoniflorin at the dose of 5 mg kg-1 after intravenous administration were 50.5 and 0.22% of the dose within 72 h, and 1.0 and 0.08% of the dose after oral administration within 48 h, respectively. Cumulative biliary excretion after intravenous or oral administration at a dose of 0.5 mg kg-1 was 6.9 and 1.3% of the dose within 24 h, respectively. The total CLR and CLB value after intravenous dosing was less than the CLtot value. These findings suggest that paeoniflorin is metabolized in other organs as well as in the liver. We conclude that paeoniflorin absorbed is excreted mainly in urine, it has a low bioavailability and the metabolites may be involved in the pharmacological action of Paeony root.

Absorption↗
PubMed1995

Structure determination of biliary metabolites of schizandrin in rat and dog.

After oral administration of schizandrin (1) to rat, the bile was collected and treated with beta-glucuronidase and arylsulfatase. Eleven metabolites, SZ-M0 (3), SZ-M1 (4), SZ-M2 (5), SZ-M3 (6), SZ-M4 (7), SZ-M5 (8), SZ-M6 (9), SZ-M7 (10), SZ-M8 (11), SZ-M9 (12) and SZ-M10 (13) were isolated from the bile treated with the enzymes. The bile after oral administration of 1 to dog was collected and treated with enzymes in the same way, and eight metabolites, 3-8, 10 and SZ-MD2 (14) were isolated from the bile treated with enzymes. The structures of these metabolites were determined on the basis of chemical and spectral studies. The major metabolite in the bile of rat was 7 and the major metabolites in the bile of dog were 7 and 14.

Animals↗
PubMed1995

[Effects of Onpi-to (TJ-8117) on mesangial injury induced by anti Thy-1 antibody].

We investigated the effect of Onpi-to (TJ-8117) on the mesangial injury induced by anti-Thy-1 antibody. TJ-8117 (400 mg/kg/day, p.o.) given from the 1st day (from the day of injection of the anti-thymocyte serum) or 4th day (after mesangial proliferation), markedly inhibited the mesangial proliferation and hypercellularity in glomeruli. TJ-8117 prevented the increase in the number of PCNA or ED-1 positive cells in glomeruli. These results suggest that TJ-8117 is effective against glomerular disease with mesangial injury.

Animals↗
PubMed1995

[Porphyria in dermatology].

Porphyrins are fluorescent chemicals excited by visual light. Skin changes in patients with porphyrias develop when the skin is exposed to sunlight and porphyrins have precipitated. This reaction is phototoxic. Since the phototoxic reaction varies with each porphyria, each porphyria demonstrates different skin changes. Conversely, skin changes do not develop if skins are completely protected from exposure to the sun in patients with porphyrias with show severe abnormalities in the metabolism of porphyrin pathways. In Japan, relatively popular porphyrias in dermatology clinic are porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP) and congenital erythropoietic porphyria (CEP). Histopathologically, one of the most important findings in porphyria is a deposition of PAS positive materials at the dermo-epidermal junction and around the small blood vessels in the dermis.

Humans↗
PubMed1994

Altered expression of antithrombotic molecules in human glioma vessels.

A total of 14 surgical specimens, including 7 glioblastomas, 3 anaplastic astrocytomas, 2 brains adjacent to glioblastoma and 2 grossly normal brains, were investigated immunohistochemically for the expression of antithrombin III (AT-III), heparan sulfate proteoglycan (HSPG) and thrombomodulin (TM) in the endothelium of microvessels. The immunoreaction to AT-III was of moderate intensity in grossly normal brains, brains adjacent to glioblastoma, and anaplastic astrocytomas, but was only weak in glioblastomas, especially in the capillaries. The immunoreaction to HSPG was constantly intense in the microvessels in all the specimens. Although the immunoreaction to TM was negative or only faint in the microvessels in grossly normal brains, it was moderately to strongly intense in anaplastic astrocytomas and brains adjacent to glioblastoma. The intensity of immunoreaction to TM was variable, from faint to strong in the capillaries, and moderate to strong in larger microvessels in glioblastomas. The present study suggested that the alterations in the expression of those antithrombotic molecules could explain, at least in part, the tendencies for intratumoral hemorrhage as well as intravascular thrombosis in the different areas of malignant gliomas.

Antithrombin III↗
PubMed1994

Expression of thrombomodulin in astrocytomas of various malignancy and in gliotic and normal brains.

A total of 22 surgical specimens, 16 astrocytomas with various malignancy, 3 brains adjacent to tumor and 3 brains with non-neoplastic lesion, was investigated immunohistochemically for the expression of thrombomodulin (TM). This membrane protein is localized on the vascular endothelium of nearly every human tissue and plays a crucial role in the maintenance of antithrombotic property of the endothelial cells. Although the normal cerebral vessels were negative for TM, the tumor vessels were positive for TM. The increased expression of TM was, however, demonstrated not only in glioblastomas but also in low-grade astrocytomas. Furthermore, the vessels in the brains adjacent to tumor and gliotic brains were also positive for TM. Those observations suggested that the tendency of intratumoral bleeding, which is rather characteristic of glioblastomas, is not simply explained by the altered expression of vascular endothelial TM. In two cases of glioblastoma, not only the blood vessels but also the tumor cells were positive. Considering the mitogenic activity of thrombin, a ligand for TM, the increased expression of TM might be related to the tumor neovascularization and also the tumor growth.

Astrocytoma↗
PubMed1994

Complete regression of anaplastic astrocytoma by intravenous tumor necrosis factor-alpha (TNF alpha) after recurrence: a case report.

A 61-year-old male patient had a recurrence of anaplastic astrocytoma after initial chemoradiotherapy. After histologic confirmation of the recurrent tumor, he was treated with intravenous administration of human natural tumor necrosis factor-alpha (TNF alpha). Morphometric analysis of the tumor volumes demonstrated that the tumor continued to regress for 8 months during the course of intravenous TNF alpha therapy, and finally disappeared (total dose of intravenous TNF alpha, 785,000 JRU). The regression of tumor paralleled the neurologic improvement. He has had no signs of recurrence for 2 years. The present experience indicates that at least a certain population of malignant gliomas can be successfully treated by a systemic administration of TNF alpha without a major adverse effect.

Brain↗
PubMed1994

Studies on anti-allergic components in the roots of Asiasarum sieboldi.

The methanolic extract of the roots of Asiasarum sieboldi has been evaluated for anti-allergic effects on various experimental models in vitro and in vivo. Bioassay-guided fractionation of the methanolic extract resulted in isolation of suppressive compounds in the PCA test: methyleugenol (1), elemicin (2), gamma-asarone (3), (-)-asarinin (4), and (-)-sesamin (5). Furthermore, elemicin (2) and (2E,4E,8Z,10E)-N-isobutyl-2,4,8,10-dodecatetraenami de (6) were found to exhibit an inhibitory action on 5-lipoxygenase (5-LOX) from RBL-1 cells. 3',4'-Dimethoxycinnamaldehyde (7) and xanthoxylol (8) potently reduced the contractile response of guinea pig ileal strips to LTD4.

Animals↗