Inhibitory effects of Sanguisorba officinalis root extract on HYBID (KIAA1199)-mediated hyaluronan degradation and skin wrinkling.

OBJECTIVES: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation. METHODS: Inhibition of Sanguisorba officinalis root extract and ziyuglycoside I, one of the components of Sanguisorba officinalis root extract, to the HYBID-mediated HA degradation was assessed by size-exclusion chromatography of HA depolymerized by stable transfectants of HYBID in HEK293 cells (HYBID/HEK293 cells) or normal human skin fibroblasts (Detroit 551 cells and NHDF-Ad cells). The HYBID mRNA and protein expression was examined by quantitative real-time PCR and immunoblotting in the skin fibroblasts treated with Sanguisorba officinalis root extract, and size distribution of newly produced HA was evaluated by preparing metabolically radiolabelled HA. A double-blind, randomized and placebo-controlled study was carried out in the 21 healthy Japanese women, who were topically treated with the formulation containing Sanguisorba officinalis root extract or the placebo on each side of the face including crow's foot area. RESULTS: Sanguisorba officinalis root extract, but not ziyuglycoside I, abolished HYBID-mediated HA degradation by HYBID/HEK293 cells. Sanguisorba officinalis root extract also inhibited HYBID-mediated HA degradation in skin fibroblasts by down-regulating HYBID mRNA and protein expression. Although control untreated skin fibroblasts produced polydispersed HA, the cells treated with Sanguisorba officinalis root extract produced only high-molecular-weight HA. Treatment with Sanguisorba officinalis root extract-formulated lotion significantly improved skin elasticity, and reduced skin wrinkling scores at the outer eye corner compared with the placebo formulation. CONCLUSION: Sanguisorba officinalis root extract showed an anti-HYBID-mediated HA degradation activity and anti-wrinkle activity on human facial skin, which is accompanied by the improvement in elasticity. Our study provides the possibility of a new strategy to inhibit HYBID-mediated HA degradation for anti-wrinkle care.

OBJECTIFS: l'acide hyaluronique (AH), un composant important de la matrice extracellulaire de la peau, assure de nombreuses activités biologiques, telles que l'hydratation qui contribue à la fermeté et l'élasticité de la peau. Nous avons rapporté que la réduction d'AH dans le derme papillaire et une surexpression de la protéine de liaison de l'AH impliquée dans la dépolymérisation de l'AH (HYBID, alias KIAA1199 ou CEMIP), une molécule clé de la dégradation de l'AH des fibroblastes cutanés, sont impliquées dans la formation des rides au niveau de la peau du visage chez les femmes d'origine japonaise et caucasienne. Cependant, peu ou aucune information n'est disponible concernant les substances qui inhibent la dégradation de l'AH provoquée par la protéine HYBID. MÉTHODES: l'inhibition de l'extrait de racine de la pimprenelle (Sanguisorba officinalis) et du ziyuglycoside I, l'un des composants de l'extrait de racine de Sanguisorba officinalis, sur la dégradation de l'AH provoquée par la protéine HYBID a été évaluée à l'aide d'une chromatographie par exclusion stérique de l'AH dépolymérisé par des transfectants stables de la protéine HYBID dans les cellules HEK293 (cellules HYBID/HEK293) ou les fibroblastes cutanés humains normaux (lignée cellulaire Detroit 551 et cellules des fibroblastes du derme humain chez l'adulte). L'expression de l'ARNm et de la protéine HYBID a été examinée par PCR quantitative en temps réel et par immuno-empreinte des fibroblastes cutanés traités avec de l'extrait de racine de Sanguisorba officinalis, et l'attribution des tailles des nouveaux échantillons produits de l'AH a été évaluée par préparation d'AH radiomarqué métaboliquement. Une étude en double aveugle, randomisée et contrôlée par placebo a été menée auprès des 21 femmes japonaises en bonne santé, qui ont été traitées localement avec la formulation élaborée à partir d'extraits de racine de Sanguisorba officinalis ou un placebo, sur chaque côté du visage, notamment sur la zone à pattes d'oie. RÉSULTATS: l'extrait de racine de Sanguisorba officinalis a permis d'arrêter la dégradation de l'AH provoquée par la protéine HYBID par les cellules HYBID/HEK293, mais ce n'était pas le cas du ziyuglycoside I. L'extrait de racine de Sanguisorba officinalis a également inhibé la dégradation de l'AH provoquée par la protéine HYBID des fibroblastes cutanés en diminuant l'expression de l'ARNm et des protéines HYBID. Bien que les fibroblastes cutanés témoins non traités aient produit de l'AH polydispersé, les cellules traitées aux extraits de racine de Sanguisorba officinalis ont produit uniquement de l'AH de haut poids moléculaire. Le traitement par lotion formulée à partir d'extraits de racine de Sanguisorba officinalis a amélioré de manière significative l'élasticité de la peau et réduit les scores de vieillissement du coin extérieur de la peau autour des yeux, par rapport à la formulation placebo. CONCLUSION: l'extrait de racine de Sanguisorba officinalis a démontré une action anti-dégradation de l'AH provoquée par la protéine HYBID et une activité antirides au niveau de la peau du visage humain, s'accompagnant d'une amélioration de l'élasticité. Notre étude fournit la possibilité d'une nouvelle stratégie pour inhiber la dégradation de l'AH provoquée par la protéine HYBID dans le cadre des soins antirides.

[Experience of postoperative adjuvant chemotherapy of lung cancer at outpatient department].

In late years the cancer adjuvant chemotherapy shifts from an inpatient care to an outpatient treatment. For operated lung cancer patients, outpatient chemotherapy center has been working since October 2005 in our hospital. Chemotherapy regimens were carboplatin (CBDCA) + paclitaxel (PTX), CBDCA + gemcitabine (GEM), docetaxel (DTX) + tegaful-gimeracil-oteracil potassium (S-1), and GEM + vinorel bine (VRE). CBDCA was chosen instead of cisplatin (CDDP) and non-platinum doublets are also used because of less toxicity and more time saving. Adjuvant chemotherapy has been performed for a total of 25 outpatients. Twenty-two out of 25 completed chemotherapy. Neutrophilopenia was the most common toxicity and grade 3 or 4 neutrophilopenia was seen in 6 patients. Adjuvant chemotherapy of outpatients can be completed safely by the choice of a safe regimen, supportive therapy for the toxicity, and cooperation with the community medicine organization. Our chemotherapy regimen are thought to be feasible for postoperative lung cancer outpatients.

Omega-3 polyunsaturated fatty acids ameliorate the severity of ileitis in the senescence accelerated mice (SAM)P1/Yit mice model.

Clinical studies using omega-3 polyunsaturated fatty acids (omega3-PUFA) to Crohn's disease (CD) are conflicting. Beneficial effects of dietary omega3-PUFA intake in various experimental inflammatory bowel disease (IBD) models have been reported. However, animal models of large intestinal inflammation have been used in all previous studies, and the effect of omega3 fat in an animal model of small intestinal inflammation has not been reported. We hypothesized that the effects of omega3 fat are different between large and small intestine. The aim of this study was to determine whether the direct effect of omega3 fat is beneficial for small intestinal inflammation. Senescence accelerated mice (SAM)P1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. The numbers of F4/80-positive monocyte-macrophage cells as well as beta7-integrin-positive lymphocytes in the intestinal mucosa were increased significantly compared with those in the control mice (AKR-J mice). The area of mucosal addressin cell adhesion molecule-1 (MAdCAM-1)-positive vessels was also increased. The degree of expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and interferon (IFN)-gamma mRNA were increased significantly compared with those in the control mice. The feeding of two different kinds of omega3 fat (fish-oil-rich and perilla-oil-rich diets) for 16 weeks to SAMP1/Yit mice ameliorated inflammation of the terminal ileum significantly. In both the omega3-fat-rich diet groups, enhanced infiltration of F4/80-positive monocytes/macrophages in intestinal mucosa of SAMP1/Yit mice cells and the increased levels of MCP-1, IL-6 and IFN-gamma mRNA expression were ameliorated significantly compared with those in the control diet group. The results suggest that omega3 fat is beneficial for small intestinal inflammation by inhibition of monocyte recruitment to inflamed intestinal mucosa.

Autonomous catheter insertion system using magnetic motion capture sensor for endovascular surgery.

BACKGROUND: In order to reduce fluoroscope usage in endovascular surgery, there is a need to develop autonomous catheter insertion systems. METHODS: We propose a system for tracking the position and speed of a catheter using a magnetic motion capture sensor to provide feedback to a catheter-driving mechanism, to perform autonomous catheter insertion in major vasculature. Catheter insertion speed control and path reconstruction experiments were performed with the system inside a silicone model of major vasculature to simulate surgery. RESULTS: The system controlled the catheter for speeds of 6.14 mm/s and reproduced a two-dimensional path inside the silicone blood vessel phantom with less than 7 mm of error. CONCLUSIONS: We found that error in speed control rises as a result of friction between the catheter and the model wall. Path reconstruction error depends on the model's cross-sectional diameter, the properties of the catheter insertion mechanism, the magnetic sensor and the system guidance technique.

Antioxidant activity of thiosulfinates derived from garlic.

Garlic extract significantly inhibited the oxidation of methyl linoleate in homogeneous acetonitrile solution, whereas the antioxidant effect of allicin-free garlic extract, prepared by removing allicin by prepared by removing allicin by preparative HPLC, was much lower than that of the garlic extract. These results suggest that the antioxidant properties are mostly attributed to the presence of allicin in the garlic extract. Allicin a major component of the thiosulfinates in garlic extract, was found to be effective for inhibiting methyl linoleate oxidation, but its efficiency was less than that of alpha-tocopherol. Next, the reactivity of allicin toward the peroxyl radical, which is a chain-propagating species, was investigated by direct ESR detection. The addition allicin to 2,2'-azobis(2,4-dimethylvaleronitrile)-peroxyl radical solution caused the signal intensity of the peroxyl radical to dose-dependently decrease, indicating that allicin is capable of scavenging the the peroxyl radical and acting as an antioxidant. Finally, we studied the structure-anioxidant activity relationship for thiosulfinates and suggested that the combination of the allyl group (-CH2CH=CH2) and the -S(O)S- group is necessary for the antioxidant action of thiosulfinates in the garlic extract. In addition, one of the two possible combinations, -S(O)S-CH2CH=CH2, was found to make a much larger contribution to the antioxidant activity of the thiosulfinates than the other, CH2=CH-CH2-S(O)S-.

Auditory evoked magnetic fields to speech stimuli in newborns--effect of sleep stages.

The aim of the study was to examine whether a newborn can detect changes in a speech stimulus consisting of a fricative followed by a vowel /su/. In addition, we studied possible effect of the two sleep stages (active and quiet sleep) on the evoked magnetic responses. In young children (6 years), the same stimulus evokes a prominent deflection, consisting of two peaks. The first one (P1m) is evoked by the beginning of the fricative consonant and has a latency of about 145 ms. The second peak (P2m) with a latency of 340 ms, is evoked by the switch to the vowel. In newborns (n = 10), the waveform resembled that of the older children but latencies of the corresponding peaks were longer, 190 and 435 ms, correspondingly. The results suggest that already the newborn brain detects the change inside the auditory speech stimulus, namely the fricative sound changing into a vowel. However, the immaturity of the brain is reflected in the prolonged latencies. In addition, the responses were higher in amplitude in quiet sleep than in active sleep (F (1.9) = 36.5; p < 0.0002). This is in line with the enhanced somatosensory magnetic fields to tactile stimulation in quiet compared to active sleep in newborns.

The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice.

The flavonoid nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), found in Citrus depressa Rutaceae, a popular citrus fruit in Okinawa, Japan, reportedly inhibits the production of pro-matrix metalloproteinase (proMMP)-1, 3, and 9 in rabbit synovial fibroblasts in vitro. In the present study, we demonstrated the inhibitory effects of nobiletin on the proliferation of the cancer cell line, TMK- 1, and its production of MMPs. In the SCID mouse model, we found that nobiletin inhibited the formation of peritoneal dissemination nodules from TMK-1. The enzymatic activity of MMP-9 expressed in culture medium obtained from a co-culture of TMK-1 and mouse fibroblastic cells was inhibited by nobiletin in a concentration-dependent manner. In the SCID mouse model, total weight of dissemination nodules was significantly lower in the treated group compared with the vehicle control group (0.07 g vs. 0.78 g, P = 0.0059). The total number of dissemination nodules was also significantly lower than in the vehicle control group (7.5 vs. 69.3 / body, P = 0.0001). These results suggest that nobiletin may be a candidate anti-metastatic drug for prevention of peritoneal dissemination of gastric cancer.

Cancer chemoprevention by ginseng in mouse liver and other organs.

Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p<0.05). Incidence of liver tumor development was also lower in red ginseng extracts-treated group, although the difference from control group was not statistically significant. Anti-carcinogenic activity of white ginseng extracts, besides red ginseng extracts, was also investigated. In the present study, the administration of white ginseng extracts was proven to suppress tumor promoter-induced phenomena in vitro and in vivo. It is of interest that oral administration of the extracts of Ren-Shen-Yang- Rong-Tang, a white ginseng-containing Chinese medicinal prescription, resulted in the suppression of skin tumor promotion by 12-o-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice. These results suggest the usefulness of ginseng in the field of cancer prevention.

Effects of apatite and wollastonite containing glass-ceramic powder and two types of alumina powder in composites on osteoblastic differentiation of bone marrow cells.

Previously we developed a composite consisting of apatite and wollastonite containing glass-ceramic (AW-GC) powder and bisphenol-a-glycidyldimethacrylate (Bis-GMA)-based resin (designated AWC), and demonstrated that AWC showed direct contact with living bone. Another new composite consisting of mainly the delta-crystal phase of alumina bead powder and Bis-GMA-based resin (designated ABC) was developed. Although alumina ceramics are bioinert and a composite filled with the pure alpha-crystal phase of alumina powder (designated alphaALC) did not allow direct bone formation in vivo, ABC was shown to have excellent osteoconductivity. One purpose of this study was to investigate whether AW-GC powder in a composite promotes osteoblastic differentiation of rat bone marrow cells as AW-GC bulk did. Another purpose was to evaluate the effects of the delta-crystal phase of alumina powder in a composite on osteoblastic differentiation. In a cell culture with dexamethasone, alkaline phosphatase (AP) activity at both days 7 and 14, and the levels of osteocalcin mRNA and alpha1(I) collagen mRNA at day 14 and osteopontin mRNA at day 7, were highest on AWC, followed by ABC, and finally alphaALC. Scanning electron microscopy showed more abundant mineralized globules and a fibrous collagen matrix on AWC at day 14, followed by ABC. In a cell culture without dexamethasone, AP activity at both days 7 and 14, and the level of osteopontin mRNA at day 7, were higher on ABC than on any other composite, whereas osteocalcin mRNA could not be detected. These results indicate that AW-GC powder in a composite promotes osteoblastic differentiation of bone marrow cells intensively when supplemented with dexamethasone. The delta-crystal phase of alumina powder in a composite promotes greater osteoblastic differentiation than the alpha-crystal phase of alumina powder.

Hematological studies on black cumin oil from the seeds of Nigella sativa L.

The methanol soluble portion of black cumin oil, which is prepared by compression of seeds of Nigella sativa L., showed inhibitory effects on arachidonic acid (AA)-induced platelet aggregation and blood coagulation. By bioactive assay of AA-induced platelet aggregation, the methanol soluble part was purified to isolate a new compound 2-(2-methoxypropyl)-5-methyl-1,4-benzenediol (1) and two known compounds, thymol (2), carvacrol (3), having very strong inhibitory activity. Further, we then examined the isolated compounds (1-3) and eight related compounds by the screening test for AA-induced platelet aggregation. Compounds possessing aromatic hydroxyl and acetoxyl group had more potent activity than aspirin, which is well known as a remedy for thrombosis.

Hydrophobic extracts of a Chinese herb (CMX-13) exhibit potent immunosuppressive properties and prevent acute rejection in a highly histoincompatible model of rat lung transplantation.

BACKGROUND: The potential of higher plants as sources for new immunosuppressive medications is well recognized. In our experiments we investigated the immunosuppressive effect of a highly refined and potent extract of a Chinese herbal preparation, CMX-13, on inhibiting acute allograft rejection (AR) in a highly histoincompatible rat lung transplant model, BN-->LEW, and on lymphocyte activation and cytokine gene expression in vitro. METHODS: Left lung transplants: the control group (group 1) received only dimethylsulfoxide (DMSO) which is the solvent for CMX-13. Group 2 received intramuscular cyclosporin A (CsA, 25 mg/kg) on day 2 posttransplant. Group 3 and 4 received i.p. CMX-13 (0.5 mg/day, low dose and 5 mg/day, high dose, respectively) on day 1, 2, and 3 posttransplant. All animals were killed on day 6 posttransplant. Several pathological categories of inflammation were examined. In vitro experiments: rat spleen cells were incubated with Con A or irradiated stimulator cells with/without serial dilutions of CMX-13 or CsA. Cell proliferation was measured by 3H-thymidine incorporation. mRNA expression of interleukin-2 and interferon-gamma was examined by reverse transcriptase-polymerase chain reaction. RESULTS: The severity of AR in animals receiving high dose CMX-13 was significantly reduced (stage II, P<0.05) compared with controls (stage IV). Significant differences were also seen when more specific parameters of inflammation were examined (necrosis, 0 vs. 1.7+/-1.0, P<0.05; interalveolar hemorrhage, 0 vs. 3.0+/-0.9, P<0.05). The responses seen in the animals treated with high dose CMX-13 were similar to those in the CsA group. CMX-13 inhibited T cell proliferative responses induced by Con A and alloantigen stimulation in a dose-dependent manner that were similar to CsA. Interleukin-2, and interferon-gamma mRNA expression in Con A-stimulated spleen cells was not inhibited by CMX-13 although CsA showed significant inhibition. CONCLUSIONS: 1) CMX-13 significantly reduces the stage of AR and parameters of inflammation in a highly histoincompatible rat lung transplant model. 2) CMX-13 has equal potency to CsA in the inhibition of Con A and alloantigen stimulated rat spleen cell proliferation. 3) CMX-13 showed no inhibitory effects on IL-2 and gamma-IFN mRNA expression, suggesting that its mechanism of action is different from CsA. 4) CMX-13 or derivatives may have potential utility as an immunosuppressive agent(s) in modulation of AR and management of other inflammatory and immunological disorders.

Effect of a radical scavenger "water soluble protein" from broad beans (Vicia faba) on antioxidative enzyme activity in cellular aging.

We isolated a free-radical scavenger "water soluble protein (WSP)" from broad beans. Hydrocortisone (HC) is known to inhibit superoxide generation and was used as the reference scavenger. WSP was examined for its effect on antioxidation in young (PDL 20, 25% of the maximum life span) and old (PDL 50, 62.5% of the maximum life span) human fibroblasts (TIG-1). Cells were treated with WSP or HC for 4 and 6 wk in young cells, and for 3 and 6 wk in old cells. The cytosolic superoxide dismutase activity in the cells treated with WSP or HC tended to decrease as compared with that in the non-treated cells (control) with the exception of WSP-treated young cells 4 wk after culturing. Young cells were equal in glutathione peroxidase activity to the control, but the activity level in WSP- or HC-treated young cells 6 wk after culturing was 10-50% lower than that in the control. Young and old cells treated with WSP or HC were superior to the control in catalase activity with the exception of HC-treated old cells. WSP- or HC-treated cells were higher in glutathione (GSH) concentration than the control with the exception of WSP-treated young cells 4 wk after culturing and HC-treated old cells 6 wk after culturing. Such increases in catalase activity and GSH concentration by WSP treatment may be related to the delay of cellular aging-dependent degeneration.

[Anesthetic management for a patient with autoimmune hemolytic anemia].

A 69-year-old woman with autoimmune hemolytic anemia (AIHA) received gastric resection and splenectomy under general anesthesia combined with epidural anesthesia. Her blood type had been determined as type A, Rh type CCDee, with anti-e-antibody and anti-pdl-antibody positive as autoantibodies. We applied the technique of hemodilutional autologous transfusion to supplement the blood loss during the operation to prevent hemolysis or occurrence of new antibody after homologous transfusion. We should pay much attention to a patient with AIHA to find signs of peri-operative hemolysis and to give the treatment for hemolysis in early stage. We consider that the hemodilutional autologous transfusion is a useful technique for the anesthetic management of the patient having a rare blood type.

Clinical application of argatroban as an alternative anticoagulant for extracorporeal circulation.

The authors attempted experimental and clinical use of argatroban as an alternative anticoagulant in left heart bypass with the centrifugal pump, percutaneous cardiopulmonary support (PCPS), and extracorporeal membrane oxygenation (ECMO) to determine if it has complementary effects in preventing thrombus formation without aggravating bleeding tendency. Its reversible binding to thrombin and its short half-life contributed to reduce the risk of excessive blood loss without clot formation within the extracorporeal circulation circuit during thoracic aortic surgery using left heart bypass. PCPS and ECMO were safely performed at doses ranging from 0.5 to 10 micrograms/kg/min to maintain activated clotting time at approximately 200 seconds. Although experimental studies showed argatroban to be advantageous in preserving platelet and fibrinogen, further clinical investigations are necessary.

Saponins isolated from Allium chinense G. Don and antitumor-promoting activities of isoliquiritigenin and laxogenin from the same drug.

Investigation of the Chinese crude drug "Xiebai," the bulbs of Allium chinense G. Don (Liliaceae), led to the isolation of 2 saponins, xiebai-saponin I (laxogenin 3-O-beta-xylopyranosyl (1-->4)-[alpha-arabinopyranosyl (1-->6)-beta-glucopyranoside) (1) and laxogenin 3-O-alpha-arabinopyranosyl (1-->6)-beta-glucopyranoside (2), and the aglycone, laxogenin (3), together with 2 chalcones, isoliquiritigenin (4) and isoliquiritigenin-4-O-glucoside (5), and beta-sitosterol glucoside (6). Compounds 1-5 were tested in vitro for their inhibitory effect on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32Pi-incorporation into phospholipids of HeLa cells. In addition to this, laxogenin (3) was proven to have an antitumor-promoting activity in a two-stage lung carcinogenesis experiment.

New megastigmane and tetraketide from the leaves of Euscaphis japonica.

New megastigmane (1) and tetraketide (2) were isolated from the leaves of Euscaphis japonica and the structures were elucidated by means of spectroscopic and chemical evidence.

[Toxicosis of high-dose methotrexate (HD-MTX) for osteosarcoma, cured with treatment by leucovorin (LV) rescue and hemoperfusion--a case report].

A 17-year-old boy suffered from osteosarcoma in his left distal femur. He was treated with 4 courses of HD-MTX preoperatively, then a wide resection and replacement with endprosthesis was performed. After surgery, 4 more courses of HD-MTX were administered. In the last course of HD-MTX, the serum level of MTX had not decreased to a safe level after 48 hours following MTX administration. Liver and renal dysfunction then occurred, so massive leucovorin rescue and hemoperfusion were done. Fortunately, all complications disappeared. The patient is alive and well, and has been disease free for six years since surgery.

Ultrastructure of the interface between alumina bead composite and bone.

We developed a composite (ABC) consisting of alumina bead powder as an inorganic filler and bisphenol-a-glycidyl dimethacrylate (Bis-GMA)-based resin as an organic matrix. Alumina bead powder was manufactured by fusing crushed alpha-alumina powder and quenching it. The beads took a spherical form 3 microm in average diameter. The proportion of filler in the composites was 70% w/w. The composite was implanted into rat tibiae and cured in situ. Specimens were prepared 1, 2, 4, and 8 weeks after the operation and observed by transmission electron microscopy. The results were compared with those of a bone composite made of alpha-alumina powder (alpha-ALC). In ABC-implanted tibiae, the uncured surface layer of Bis-GMA-based resin was completely filled with newly formed bonelike tissue 2 weeks after implantation. The alumina bead fillers were surrounded by and in contact with bonelike tissue. No intervening soft tissue was seen. In alpha-ALC-implanted tibiae, a gap was always observed between the alpha-ALC and the bonelike tissue. These results indicate that the ABC has osteoconductivity, although the precise mechanism is still unclear.

Increase of the cellular growth of old human diploid fibroblasts by radical scavenger: methanolic extract of broad beans.

The methanolic extract from broad beans (MEBB), which is comprised of phenolic compounds, has free-radical scavenging activity. The effects of MEBB on cytosolic antioxidant enzymes and cell proliferation were examined in cultures of old (78-84% life-span completed) WI-38 human diploid fibroblasts. Because catechin is polyphenol and has radical scavenging activity, it was used as the control in experiments. We observed that MEBB increased cellular growth when added to the cell culture. In MEBB at 40 and 120 micrograms/mL, the cell proliferation increased by 14 and 27%, respectively, as compared to the control. In catechin, cell proliferation increased as well. Regarding cytosolic glutathione peroxidase (GSH-Px) activity, treatment of old cells with MEBB at 40 and 120 micrograms/mL resulted in decreases as compared to the control. In contrast, catechin showed no similarities to the modification of GSH-Px activity. Cytosolic SOD activity was increased by treatment with 40 micrograms/mL MEBB, and the activity showed a gradual decrease with increased MEBB concentrations. A similar trend occurred in the cells treated with catechin (4-20 microM). These results suggest that cytosolic antioxidant enzyme activities in old cells may be modulated by MEBB treatment. We conclude that there may be a relation between the optimum MEBB concentration for the increase of cellular growth and the MEBB concentration required to exhibit a decrease in GSH-Px activity.