Baupain, a plant cysteine proteinase that hinders thrombin-induced human platelet aggregation.

Bauninia forficata is trivially known as cow paw, and popularly used in Brazil for treatment of diabetes mellitus. Denominated baupain a cysteine proteinase was purified from B. forficata leaves. In this study, we investigated the baupain effect on aggregation of isolated human platelets in vitro and the results show that baupain hinders thrombin - but not ADP- and collagen- induced platelet aggregation. With synthetic quenched-fluorescent peptides, the kinetics of the cleavage site of human proteinase-activated receptor 1 / 2 / 3 and 4 [PAR-1 / 2 / 3 and 4] by baupain was determined. In conclusion, similar to bromelain and papain, baupain hinders human platelets aggregation, probably through an unspecific cleavage in the Phe-Leu bond of PAR1.

Sunitinib, sorafenib, temsirolimus or bevacizumab in the treatment of metastatic renal cell carcinoma: a review of health economic evaluations.

Renal cell carcinoma (RCC) is the most prevalent kidney cancer and the 5-year overall survival figure in metastatic disease (mRCC) is about 10%. New targeted drugs (sunitinib, sorafenib, bevacizumab, temsirolimus) have shown activity in the treatment of mRCC, but they are all associated with a significant burden of cost. To support decision makers in their allocation of resources, costeffectiveness models are constructed to compare the costs and outcomes of anticancer therapy. This survey focuses on studies since 2003 exploring health economics in the treatment of metastatic and/or advanced RCC employing these new drugs. This paper summarizes the results, focuses on the level of evidence of these studies, compares the calculated cost-effectiveness ratios and makes suggestions for future studies. This review reveals costs per life years gained (LYG) or quality-adjusted life years (QALY) in the range of euro 22,648 to euro203,692, depending on whether the setting is first-line or second-line and drug used. When compared to the other agents, sunitinib has the best cost-effectiveness figure. Second-line therapy does not offer valid incremental cost-effectiveness ratios.

The Kadota Fund International Forum 2004--clinical group consensus.

The results from experimental studies indicate that hyperthermia is both an effective complementary treatment to, and a strong sensitiser of, radiotherapy and many cytotoxic drugs. Since the first international hyperthermia conference in 1975, Washington DC, techniques to increase tumour temperature have been developed and tested clinically. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, perfusion hyperthermia of organs, limbs, or body cavities, and whole body hyperthermia. The clinical value of hyperthermia in combination with other treatment modalities has been shown by randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, for melanoma and sarcoma. The addition of hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects, and/or better overall survival rates. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. In spite of these good clinical results, hyperthermia has received little attention. Problems with acceptance concern the limited availability of equipment, the lack of awareness concerning clinical results, and the lack of financial resources. In this paper the most relevant literature describing the clinical effects of hyperthermia is reviewed and discussed, and means to overcome the lack of awareness and use of this modality is described.

Identification and characterization of two distinct GnRH receptor subtypes in a teleost, the medaka Oryzias latipes.

We report the identification and characterization of two distinct GnRH receptor (GnRH-R) subtypes, designated GnRH-R1 and GnRH-R2, in a model teleost, the medaka Oryzias latipes. These seven-transmembrane receptors of the medaka contain a cytoplasmic C-terminal tail, which has been found in all other nonmammalian GnRH-Rs cloned to date. The GnRH-R1 gene is composed of three exons separated by two introns, whereas the GnRH-R2 gene has an additional intron and therefore consists of four exons and three introns. The GnRH-R1 and GnRH-R2 genes, both of which exist as single-copy genes in the medaka genome, were mapped to linkage groups 3 and 16, respectively. Inositol phosphate assays using COS-7 cells transfected with GnRH-R1 and GnRH-R2 demonstrated that they had remarkably different ligand sensitivities, although both receptors showed highest preference for chicken-II-type GnRH. Phylogenetic analysis showed the presence of three paralogous lineages for vertebrate GnRH-Rs and indicated that neither GnRH-R1 nor GnRH-R2 is the medaka ortholog to mammalian GnRH-Rs that lack a cytoplasmic tail. This, together with an observation that medaka-type GnRH had low affinity for GnRH-R1 and GnRH-R2, suggests that a third GnRH-R may exist in the medaka.

Relationships between serum (ZZ)-bilirubin, its subfractions and biliverdin concentrations in infants at 1-month check-ups.

In 150 infants, including those with breast milk jaundice, who were brought to our hospital for their 1-month check-ups, the serum concentrations of (ZZ)-bilirubin, its subfractions and biliverdin were measured by high-performance liquid chromatography and the relationships among them investigated. (ZZ)-Bilirubin was found to have the highest serum concentration, followed by (ZE)-bilirubin, accounting for 14.0 (geometric mean) % of (ZZ)-bilirubin. Biliverdin had a serum concentration of 0.95% of (ZZ)-bilirubin. There was only a small amount of total (di- and mono-) glucuronosyl bilirubin, 0.42% of (ZZ)-bilirubin. (ZE)-Bilirubin, (EZ)-bilirubin, (EZ)-cyclobilirubin. biliverdin, diglucuronosyl bilirubin and monoglucuronosyl bilirubin (C-8 and C-12) showed positive logarithmic correlations with (ZZ)-bilirubin (R2=0.16 or above, P<0.05). (ZE)-Bilirubin showed a significant positive logarithmic correlation with (ZZ)-bilirubin (R2=0.863, P<0.0001). Furthermore, (EZ)-cyclobilirubin, the most important photoisomer in phototherapy for neonatal hyperbilirubinaemia, was detected in very small amounts in approximately half of the neonates (84 of 150) when they were in conditions of only weak ambient light. The relationship between total glucuronosyl bilirubin and (ZZ)-bilirubin concentrations fitted a model of saturation kinetics of bilirubin UDP-glucuronosyltransferase.

Growth of nisin-producing lactococci in cooked rice supplemented with soybean extract and its application to inhibition of Bacillus subtilis in rice miso.

Lactic acid fermentation of cooked rice and rice koji by supplementation with soybean extract (SBE) and its application to rice miso fermentation were investigated. By supplementing the cooked rice with SBE, lactic acid bacteria (LAB) grew well without any unfavorable effects on the rice such as off-flavor or coloration. Lactococcus lactis subsp. lactis IFO12007 (Lc. lactis, a producer of the bacteriocin nisin) proliferated at 10(8 to approximately 9) cells/g after 24 h of incubation and produced high activity of nisin. The fermented rice with Lc. lactis strongly inhibited not only Bacillus subtilis ATCC19659 but also the other Bacillus strains. While some strains of LAB markedly inhibited the growth of Asp. oryzae, resulting in failure of koji fermentation, Lc. lactis did not affect the growth of these molds. When Lc. lactis was used for rice miso fermentation as a lactic acid starter culture, Lc. lactis rapidly proliferated and produced high nisin activity of 6,400 IU/g, in the steamed rice, resulting in complete growth inhibition of B. subtilis, which had been inoculated at the beginning of the koji fermentation. The rice miso after 12 weeks of aging had a suitable pH, and favorable taste and color. Furthermore, hyposalting of rice miso could be done without difficulty by lactic acid fermentation of both rice and soybeans.

Recombinant human erythropoietin therapy for autologous blood donation in rheumatoid arthritis patients undergoing total hip or knee arthroplasty.

The effect of recombinant human erythropoietin on autologous blood donation was investigated in 73 rheumatoid arthritis patients who underwent hip or knee arthroplasty. Autologous blood donation of 400 mL was successful with recombinant human erythropoietin (12,000 U per week), and no homologous blood was required. The mean period of blood collection was 33.8 days. Mean hemoglobin levels were 9.7 g/dL before treatment, 10.7 g/dL before surgery, and 10.2 g/dL after surgery. This study confirmed recombinant human erythropoietin is effective for enabling preoperative blood donation in rheumatoid arthritis patients.

Pumpkin peroxisomal ascorbate peroxidase is localized on peroxisomal membranes and unknown membranous structures.

To investigate the roles of peroxisomal membrane proteins in the reversible conversion of glyoxysomes to leaf peroxisomes, we characterized several membrane proteins of glyoxysomes. One of them was identified as an ascorbate peroxidase (pAPX) that is localized on glyoxysomal membranes. Its cDNA was isolated by immunoscreening. The deduced amino acid sequence encoded by the cDNA insert does not have a peroxisomal targeting signal (PTS), suggesting that pAPX is imported by one or more PTS-independent pathways. Subcellular fractionation of 3- and 5-d-old cotyledons of pumpkin revealed that pAPX was localized not only in the glyoxysomal fraction, but also in the ER fraction. A magnesium shift experiment showed that the density of pAPX in the ER fraction did not increase in the presence of Mg(2+), indicating that pAPX is not localized in the rough ER. Immunocytochemical analysis using a transgenic Arabidopsis which expressed pumpkin pAPX showed that pAPX was localized on peroxisomal membranes, and also on a unknown membranous structure in green cotyledons. The overall results suggested that pAPX is transported to glyoxysomal membranes via this unknown membranous structure.

Inhibition of the visual cycle in vivo by 13-cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy.

Isotretinoin (13-cis retinoic acid) is frequently prescribed for severe acne [Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M., Butkus, D. & Arnaud-Battandier, J. (1979) N. Engl. J. Med. 300, 329-333] but can impair night vision [Fraunfelder, F. T., LaBraico, J. M. & Meyer, S. M. (1985) Am. J. Ophthalmol. 100, 534-537] shortly after the beginning of therapy [Shulman, S. R. (1989) Am. J. Public Health 79, 1565-1568]. As rod photoreceptors are responsible for night vision, we administered isotretinoin to rats to learn whether night blindness resulted from rod cell death or from rod functional impairment. High-dose isotretinoin was given daily for 2 months and produced systemic toxicity, but this caused no histological loss of rod photoreceptors, and rod-driven electroretinogram amplitudes were normal after prolonged dark adaptation. Additional studies showed, however, that even a single dose of isotretinoin slowed the recovery of rod signaling after exposure to an intense bleaching light, and that rhodopsin regeneration was markedly slowed. When only a single dose was given, rod function recovered to normal within several days. Rods and cones both showed slow recovery from bleach after isotretinoin in rats and in mice. HPLC analysis of ocular retinoids after isotretinoin and an intense bleach showed decreased levels of rhodopsin chromophore, 11-cis retinal, and the accumulation of the biosynthetic intermediates, 11-cis and all-trans retinyl esters. Isotretinoin was also found to protect rat photoreceptors from light-induced damage, suggesting that strategies of altering retinoid cycling may have therapeutic implications for some forms of retinal and macular degeneration.

Formation of propentdyopents and biliverdin, oxidized metabolites of bilirubin, in infants receiving oxygen therapy.

BACKGROUND: Bilirubin has antioxidative effects. When bilirubin reacts with reactive oxygen species, oxidized metabolites of bilirubin are formed, such as biliverdin and propentdyopents. A decrease in serum bilirubin concentration and an increase in serum and urinary oxidized metabolites of bilirubin may indicate the protective action of bilirubin against reactive oxygen species. METHODS: In the in vitro study, we measured the oxidative products of bilirubin formed through the action of O2- by the xanthine-xanthine oxidase system, either as free bilirubin or bilirubin-human serum albumin complex. In the clinical investigation, serum concentrations of (ZZ)-bilirubin (4Z, 15Z-bilirubin), the subfraction and biliverdin, and urinary propentdyopent absorption, were measured in blood and urine samples, respectively, collected from 30 5-day-old neonates with birth weights of 1500-3624 g who had been hospitalized at the Ehime Prefectural Hospital and who had not undergone phototherapy. RESULTS: In the in vitro study, a significant formation of propentdyopents was observed in aqueous solution. A statistically significant correlation was found between serum (ZZ)-bilirubin concentration and serum biliverdin concentration (r = 0.82, P < 0.0001), but not between serum (ZZ)-bilirubin concentration and urinary propentdyopent absorption. Serum (ZZ)- and serum (ZE)-bilirubin and biliverdin concentrations, and urinary propentdyopent absorption were compared between the groups with and without oxygen therapy. No significant differences were found in serum (ZZ)-bilirubin, serum (ZE)-bilirubin and biliverdin concentration, urinary propentdyopent absorption, serum biliverdin/serum (ZZ)-bilirubin, or urinary propentdyopent absorption/serum (ZZ)-bilirubin. Neither a decrease in serum bilirubin concentration nor an increase in serum biliverdin concentration and urinary propentdyopent absorption after oxygen therapy were demonstrated in the present study. CONCLUSIONS: In the in vitro study, we demonstrated for the first time that propentdyopents were produced from (ZZ)-bilirubin by the xanthine-xanthine oxidase system but biliverdin was not. In the in vivo study, serum biliverdin concentration and urinary propentdyopent absorption seem to have a different relationship to serum (ZZ)-bilirubin concentration in sick and early neonates.

Enhancement of nitric oxide generation by low frequency electromagnetic field.

Oxidative stress is implicated in the intracellular signal transduction pathways for nitric oxide synthase (NOS) induction. The electromagnetic field (EMF) is believed to increase the free radical lifespan [S. Roy, Y. Noda, V. Eckert, M.G. Traber, A. Mori, R. Liburdy, L. Packer, The phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst in rat peritoneal neutrophils is increased by a 0.1 mT (60 Hz) magnetic field, FEBS Lett. 376 (1995) 164-6; F.S. Prato, M. Kavaliers, J.J. Carson, Behavioural evidence that magnetic field effects in the land snail, Cepaea nemoralis, might not depend on magnetite or induced electric currents, Bioelectromagnetics 17 (1996) 123-30; A.L. Hulbert, J. Metcalfe, R. Hesketh, Biological response to electromagnetic fields, FASEB 12 (1998) 395-420]. We tested the effects of EMF on endotoxin induced nitric oxide (NO) generation in vivo. Male BALB/C mice were injected with lipopolysaccharide (LPS) intraperitoneously (i.p.), followed by the exposure to EMF (0.1 mT, 60 Hz). Five hours and 30 min after the LPS administration, mice were administered with a NO spin trap, ferrous N-methyl-D-glucaminedithiocarbamate (MGD-Fe). Thirty minutes later, mice were sacrificed, and their livers were removed. The results were compared to three control groups: group A (LPS (-) EMF(-)); group B (LPS(-) EMF(+)); group C (LPS(+) EMF(-)). The ESR spectra of obtained livers were examined at room temperature. Three-line spectra of NO adducts were observed in the livers of all groups. In groups A and B very weak signals were observed, but in groups C and D strong spectra were observed. The signal intensity of the NO adducts in Group D was also significantly stronger than that in Group C. EMF itself did not induce NO generation, however, it enhanced LPS induced NO generation in vivo.

Effect of inhaled indomethacin in asthmatic patients taking high doses of inhaled corticosteroids.

BACKGROUND: Cyclooxygenase products of arachidonic acid may play a part in bronchoconstriction and airway inflammation in asthma. OBJECTIVE: We sought to determine the effect of inhaled indomethacin on asthma control and asthma exacerbations during reduction of inhaled corticosteroids in patients with moderate-to-severe steroid-dependent asthma. METHODS: We conducted a double-blind, randomized, parallel-group, multicenter study in 38 patients with asthma taking high doses (> or =1500 microg/d) of beclomethasone dipropionate (BDP). After a run-in period, patients were assigned inhaled indomethacin (50 mg/d) or placebo for 6 weeks, during which the daily doses of BDP were reduced to half at week 2 and then to one third of the baseline dose at week 4. RESULTS: Data were available from 34 patients. After the reduction of BDP doses, FEV(1), peak expiratory flow, asthma symptoms, and exhaled nitric oxide concentrations deteriorated in both treatment groups, but these effects were less pronounced in the indomethacin group compared with the placebo group. During the 6-week treatment period, 89% of the patients receiving placebo had relapse of asthma, whereas only 38% of those receiving inhaled indomethacin did so (P =.003). CONCLUSION: Inhalation of indomethacin can reduce asthma exacerbations induced by reduction of high-dose inhaled corticosteroid in steroid-dependent asthma.

Phylogenetic relationship of six Glycyrrhiza species based on rbcL sequences and chemical constituents.

The nucleotide sequences of ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G. echinata, G. macedonica and G. pallidiflora have been determined to construct their phylogenetic tree. Based on these sequences, the six Glycyrrhiza species were divided into two groups: three, G. glabra, G. uralensis, and G. inflata, which produce glycyrrhizin as a major saponin, and the others, G. echinata, G. macedonica and G. pallidiflora, which produce macedonoside C as a major saponin. Among the three glycyrrhizin-producing species, only two nucleotide substitutions were observed between the rbcL sequences of G. glabra and G. uralensis, and the sequence of G. uralensis was identical to that of G. inflata, indicating that G. uralensis and G. inflata are closely related. Among the three macedonoside C-producing species, only one nucleotide substitution was observed between those of G. echinata and G. macedonica, indicating that these two species are also closely related.

Combined treatment with TNP-470 and 5-fluorouracil effectively inhibits growth of murine colon cancer cells in vitro and liver metastasis in vivo.

The combined effects of TNP-470 (TNP), a semisynthetic analogue of fumagillin, and 5-fluorouracil (5FU), a representative chemotherapeutic agent for colorectal cancer, were investigated using murine colon 26 adenocarcinoma (CT 26) cells. In a cell-proliferation study in vitro, 50% inhibitory concentrations (IC50) were determined to be 5.2 microg/ml and 240 ng/ml for TNP and 5FU, respectively. When CT 26 cells were treated with TNP and 5FU in combination, a remarkable cytotoxic effect was obtained. Isobologram analysis revealed synergism of these two agents in inhibition of the cell growth. In vivo, using a dorsal air sac assay, we found that TNP significantly inhibited the CT 26-induced angiogenesis. In addition, the combination of TNP and 5FU exerted a synergistic anti-tumor effect in a model of hepatic metastasis by portal injection of CT 26 cells. Since TNP is known to exert inhibitory effects on tumor cell growth through suppression of cell cycle progress from the G1 to S phases as well as neovascularization, it is speculated that the treatment with TNP enhanced the anti-tumor effect of 5FU through suppression of the cell cycle and tumor-derived angiogenesis. Taken together, these results suggest that combined treatment with TNP and 5FU is potentially useful for inhibition of tumor cell growth and liver metastasis of colorectal cancer.

Effect of vitamin E on aspirin-induced gastric mucosal injury in rats.

We investigated the effect of vitamin E on aspirin-induced gastric mucosal injury in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups and were fed for 20 weeks with a diet containing <0.1 mg/100 g of alpha-tocopherol (vitamin E-deficient), 2 mg/100 g of alpha-tocopherol (normal and vitamin E-sufficient), or 50 mg/100 g of alpha-tocopherol (vitamin E-supplemented). In vitamin E-deficient rats, oral administration of aspirin (200 mg/kg) plus HCI created more severe hemorrhagic erosions than in other rats. Vitamin E-deficient rats had higher levels of thiobarbituric acid reactive substances, myeloperoxidase activity, and cytokine-induced neutrophil chemoattractant in the gastric mucosa. Flow cytometry showed that CD18 expression on stimulated neutrophils was higher in vitamin E-deficient rats than in vitamin E-supplemented rats. These results suggest that vitamin E protects against aspirin-induced gastric mucosal injury by inhibiting lipid peroxidation and accumulation of activated neutrophils.

Selective inhibition of cyclooxygenase-2 with antisense oligodeoxynucleotide restricts induction of rat adjuvant-induced arthritis.

The effects of cyclooxygenase (COX)-2 antisense oligodeoxynucleotide (ODN) in induction of adjuvant-induced arthritis were investigated. Female Lewis rats were injected with Mycobacterium butyricum intradermally at the base of tails to induce arthritis. Synthetic 18 mer phosphorothioate ODNs corresponding to the translation initiation site of rat COX-2 mRNA were prepared. The antisense (AS), sense (S), and "scrambled" (Sc) ODNs were intraperitoneally administered. Arthropathy was evaluated with arthritis score, paw edema, and histological examination. Expression of COX-1 and -2 protein and mRNA were examined with immunostaining and reverse-transcription polymerase chain reaction, respectively. COX-2 AS ODN significantly suppressed induction of arthritis in a dose-dependent manner without severe adverse effects, whereas S and Sc ODNs did not show significant inhibitory effects. COX-2 mRNA and protein expression were also suppressed only by COX-2 AS ODN without any alteration of COX-1 expression. These data suggest that selective inhibition of COX-2 with AS ODN may have a therapeutic potency in the treatment of rheumatoid arthritis.

Alpha-tocopherol protects against monocyte Mac-1 (CD11b/CD18) expression and Mac-1-dependent adhesion to endothelial cells induced by oxidized low-density lipoprotein.

Alpha-tocopherol supplementation is reported to protect against cardiovascular disease and to influence cells involved in atherogenesis, such as monocytes. Interactions between monocytes and vascular endothelial cells occur early in atherogenesis, and adhesion is mediated by integrins. We evaluated the effects of alpha-tocopherol on expression of Mac-1 (CD11b/CD18) by monocytes after stimulation with oxidized low-density lipoprotein (LDL), which is implicated as a potent chemotactic agent in atherogenesis. Incubation of whole blood with oxidized LDL (100 microg/ml) increased Mac-1 expression on monocytes, and preincubation with alpha-tocopherol reduced this upregulation in a concentration dependent manner. In another experiment, whole blood was obtained from healthy adult volunteers after 10 days of alpha-tocopherol administration (600 mg/day) and was incubated with oxidized LDL (100 microg/ml). There was a decrease in the upregulation of Mac-1 compared with that measured before administration. Adherence of oxidized LDL-stimulated monocytes to human umbilical vein endothelial cells was reduced by pretreatment with alpha-tocopherol, and was also inhibited by an anti-CD18 monoclonal antibody. Experiments with protein kinase C inhibitors suggested that reduction of Mac-1 upregulation by alpha-tocopherol was secondary to a decrease of protein kinase C activity. In conclusion, alpha-tocopherol suppressed the upregulation of Mac-1 expression on monocytes by oxidized LDL.

[X-linked sideroblastic anemia].

A 20-year-old man presented with microcytic hypochromic anemia (hemoglobin: 9.3 g/dl, MCV: 82.0 fl, MCHC: 29.5 g/dl) and dimorphism RBCs in circulating blood (RDW: 26.8%). Ringed sideroblasts accounted for 29.5% of bone marrow erythroblasts. Iron overload was also observed. Because the patient had a clear family history of anemia, he was given a diagnosis of X-linked sideroblastic anemia. The activity of delta-aminolevulinic acid synthase (ALAS) in bone marrow erythroblasts was low. However, we did not detect mutation of the gene for ALAS. The patient has responded well to a treatment regimen consisting of oral vitamin B6, Fe-chelation therapy, and phlebotomy.

Effect of vitamin E in gastric mucosal injury induced by ischaemia-reperfusion in nitric oxide-depleted rats.

BACKGROUND: Neutrophil infiltration and lipid peroxide accumulation are involved in reperfusion-induced gastric mucosal injury in nitric oxide-depleted rats. AIM: To assess the effect of vitamin E on this injury. METHODS: After ischaemia-reperfusion, the total area of erosions, lipid peroxide contents in gastric mucosa, and gastric neutrophil accumulation were compared between nitric oxide-depleted rats with deficient, normal, and increased vitamin E intake over 8 weeks. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. RESULTS: The total area of erosions was significantly increased in the vitamin E-deficient group compared with the sufficient-intake and vitamin-supplemented groups. Both thiobarbituric acid-reactive substances and myeloperoxidase activity also were significantly increased in the vitamin E-deficient group compared with others. The total area of erosions closely paralleled the increases in both thiobarbituric acid-reactive substances and myeloperoxidase activity. CONCLUSION: These results indicate that the inhibition of lipid peroxidation and interference with neutrophil infiltration by vitamin E may be responsible for its cytoprotective effect in ischaemia-reperfusion.

Ginkgo biloba leaf extract: review of biological actions and clinical applications.

The number of studies on Ginkgo biloba leaves is rapidly increasing. A variety of effects of Ginkgo biloba leaf extract (GBLE) have been identified. GBLE contains many different flavone glycosides and terpenoides. GBLE has an antioxidant action as a free radical scavenger, a relaxing effect on vascular walls, an antagonistic action on platelet-activating factor, an improving effect on blood flow or microcirculation, and a stimulating effect on neurotransmitters. Besides a direct scavenging action on active oxygen species, GBLE exerts an anti-inflammatory effect on inflammatory cells by suppressing the production of active oxygen and nitrogen species. GBLE inhibited the increase in the products of the oxidative decomposition low-density lipoprotein (LDL), reduced the cell death in various types of neuropathy, and prevented the oxidative damage to mitochondria, suggesting that GBLE exhibits beneficial effects on neuron degenerative diseases by preventing chronic oxidative damage. The study using a model of ischemia-reperfusion injury has also demonstrated the protective effect of GBLE on cardiac muscle and its antioxidative action in vivo. Favorable results have been obtained in double-blind, placebo-controlled, comparative trials of patients with memory disorders, obstructive arteriosclerosis, and dementia. We review the recent studies on GBLE with respect to its various pharmacological actions, such as a scavenging activity on free radicals and an inhibitory action on lipid peroxidation. GBLE shows a very strong scavenging action on free radicals, and is thus considered to be useful for the treatment of diseases related to the production of free radicals, such as ischemic heart disease, cerebral infarction, chronic inflammation, and aging.