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Introduction: Tinnitus is defined as the perception of sound without its actual presence in the environment. It has been the subject of a great number of studies, especially considering its consequences on patient's quality of life. Objective: This study aimed to investigate the effect of hearing aids and/or Ginkgo biloba extract EGb 761 on tinnitus in patients with hearing loss. Methods: This is a trial randomized-controlled treatment, parallel, double-blind, with three-arm. Thirty-three adults subjects were divided into three groups: group 1 — subjects undergoing drug therapy with Ginkgo biloba extract EGb 761; group 2 — individuals fitted with digital hearing aids; group 3 — individuals submitted to drug therapy with Ginkgo biloba extract EGb 761 and using hearing aids. The tinnitus handicap inventory and visual analogue scale were used to evaluate self-perception of tinnitus loudness and severity before treatment and 90 days after treatment. Results: This study demonstrated a significant correlation between tinnitus handicap inventory and visual analogue scale, before and after treatment. We observed a significant improvement in self-perception of tinnitus loudness and severity after 90 days of treatment with Ginkgo biloba extract EGb 761 and/or hearing aids. No correlation was found between tinnitus onset time and self-perception of tinnitus loudness and severity. Hearing aids were more effective in patients with a shorter tinnitus onset time and Ginkgo biloba extract was effective regardless of tinnitus duration. Conclusions: It was possible to prove the effectiveness of the hearing aids and/or Ginkgo biloba extract EGb 761 treatment, which shows success in the control of tinnitus contributing to the improvement of this symptom. Resumo: Introdução: O zumbido é definido como a percepção de um som sem a sua presença real no ambiente e tem sido objeto de um grande número de estudos, especialmente devido às suas consequências na qualidade de vida do paciente. Objetivo: Investigar o efeito de próteses auditivas e / ou extrato de Ginkgo biloba EGb 761 sobre o zumbido em pacientes com perda auditiva. Método: Ensaio clínico randomizado controlado, paralelo, duplo-cego, com três braços. Trinta e três indivíduos adultos foram divididos em três grupos: Grupo 1- indivíduos submetidos à terapia medicamentosa com extrato de Ginkgo biloba EGb 761; Grupo 2- indivíduos equipados com próteses auditivas digitais; Grupo 3 - indivíduos submetidos à terapia medicamentosa com extrato de Ginkgo biloba EGb 761 e próteses auditivas. O Tinnitus handicap inventory e a escala visual analógica foram usados para avaliar a autopercepção de intensidade e da gravidade do zumbido antes do tratamento e 90 dias após o tratamento. Resultados: Este estudo demonstrou uma correlação significante entre o Tinnitus handicap inventory e a escala visual analógica, antes e após o tratamento. Observou-se melhoria significativa na autopercepção de loudness e da intensidade do zumbido após 90 dias de tratamento com extrato de Ginkgo biloba EGb 761 e/ou prótese auditiva. Não foi encontrada correlação entre o tempo de início do zumbido e a autopercepção da intensidade e gravidade do zumbido. As próteses auditivas foram mais eficazes em pacientes com menor tempo de início de zumbido e o extrato de Ginkgo biloba foi eficaz, independentemente da duração do zumbido. Conclusões: Foi possível comprovar a eficácia do tratamento com a prótese auditiva e/ou extrato de Ginkgo biloba EGb 761, o que demonstra sucesso no controle do zumbido e contribui para a melhoria desse sintoma.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disease caused by mutations in the cytochrome P450(27) (CYP27) gene. This disease is characterized by the accumulation of a bile alcohol, cholestanol, in diverse tissues. Accumulation in the central nervous system leads to neurological dysfunction including dementia, spinal cord paresis, and cerebellar ataxia. Accumulation in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. In a Japanese family with CTX, we identified two points mutations in the CYP27 gene at different sites. One is a novel transversion, which substitutes G for C at Pro 368 (CCC) to Arg (CGC). The other is a transition, which substitutes A for G at Arg441 (CGG) to Gln (CAG), this being the same mutation that Kim et al. reported (1994. J. Lipid Res. 35: 1031 - 1039). Allele-specific polymerase chain reaction analysis indicated that the father and mother of this family, who themselves had no clinical manifestations of CTX, had the former and latter mutations heterozygously, respectively. On the other hand, the patients each had both mutations heterozygously. These results are highly suggestive, but not conclusive, that the newly identified transversion in the CYP27 gene accounts for the sterol 27-hydroxylase (EC 1.14.13.15) deficiency in these patients.

Introduction: The efficacy of radiotherapy for symptomatic relief of malignant psoas syndrome (MPS) remains unknown because there are limited publications with high level evidence, including analyses with sufficient number of cases, clinical trials, and systematic reviews about radiotherapy for MPS. We aimed to investigate the characteristics of and symptom relief rates in patients treated with radiotherapy for MPS in palliative intent., Methods: In this single-center retrospective study, we analyzed data of 22 consecutive patients treated with radiotherapy for MPS at our institution in Japan between 2012 and 2022. We recorded patient characteristics, including primary site, invasion pattern, recognition of MPS by the attending physician, radiation regimen, biological effective dose with α/β = 10 Gy (BED 10 ), and adverse events. Since no objective evaluation index for palliative radiotherapy for non-bone metastases has been established, we modified and used an International Consensus on Palliative Radiotherapy Endpoint, which was originally used for bone metastases, to evaluate symptom relief in the present retrospective study. "Response" was defined as symptom relief described in medical records or the use of analgesic medications reduced by ≥25% within 3 months post-initiation of radiotherapy., Results: Genitourinary organs (41%) were the most common primary-tumor sites. MPS was caused by metastasis in the iliopsoas muscle in 14 patients (64%) and by direct invasion of the primary tumor in eight patients (36%). Since the optimal radiation dose for MPS has not been established, the radiation dose varied from low dose, which are used in palliative radiotherapy for painful bone metastases, to high dose with conventional fraction using 1.8 to 2 Gy per fraction, with a median BED 10 of 48 Gy (range, 10.6-79.2 Gy). Fifteen patients (68%) achieved a response. No acute nor late adverse events of grade 2 or higher, according to Common Terminology Criteria for Adverse Events version 5.0, were reported during the observation period., Conclusion: Radiotherapy for symptomatic MPS might be an effective treatment option with a high response rate (68%) and minimal adverse events. Since the present study is a retrospective study with small number of cases, a prospective study with a larger sample size is required., (Copyright © 2023. Published by Elsevier Inc.)

The release of ATP from the epithelium of the urinary bladder (urothelium) in response to mechanical/chemical stimuli contributes to the visceral sensation in the micturition reflex. The nitric oxide (NO)-mediated induction of cyclic guanosine monophosphate (cGMP) has been detected in urothelial cells and may inhibit the micturition reflex. However, the function of the NO-cGMP pathway in the regulation of urothelial ATP release remains poorly understood in contrast to its effects on smooth muscles or primary afferent nerves. Therefore, we investigated the relevance of the NO-cGMP pathway to ATP release on the mucosal side in the present study. The administration of l-arginine (NO precursor) or NOC 12 (NO donor) significantly reduced ATP release to the mucosal side at a physiologically normal urine storage pressure (5 cmH 2 O). L-NAME (NO synthase inhibitor) significantly increased the distention-induced release of ATP. The phosphodiesterase-5 inhibitor, sildenafil, which increases cGMP levels, inhibited distention-induced ATP release. Furthermore, sildenafil significantly reduced ATP release in response to the administration of lipopolysaccharide. These results suggest that the NO-cGMP pathway inhibited urothelial ATP release during the storage phase under both physiological and pathological conditions., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

The differences in prognoses or progression patterns between T4b non-N4 and non-T4b N4 esophageal squamous cell carcinoma post chemoradiotherapy (CRT) is unclear. This study compared the outcomes of CRT for stage IVa esophageal squamous cell carcinoma according to T/N factors. We retrospectively identified 66 patients with stage IVa esophageal squamous cell carcinoma who underwent definitive CRT at our center between January 2009 and March 2013. The treatment outcomes, i.e., progression patterns, prognostic factors, and toxicities based on version 5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events, were studied. The patients (56 men and 10 women) had a median age of 67 (range: 37-87) years. The T/N classifications were T4b non-N4 (28/66), non-T4b N4 (24/66), and T4b N4 (14/66). Objective response was achieved in 57 patients (86.4%, (95% confidence interval, 74.6-94.1%)). There were no significant differences between the T/N groups in terms of overall survival, progression-free survival, and progression pattern. We found no significant differences in prognoses or progression patterns among patients with T4b non-N4, non-T4b N4, and T4b N4 esophageal squamous cell carcinoma. Thus, it seems impractical to modify CRT regimens based on T/N factors.

Background: Determining the appropriate gross tumor volume is important for irradiation planning in addition to palliative radiation for bone metastases. While irradiation planning is commonly performed using simulation computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, and 18 fluorodeoxyglucose-positron emission tomography-CT ( 18 FDG-PET-CT) are more sensitive for detecting bone metastasis and invasion areas. Therefore, this study evaluated whether pretreatment imaging modalities influenced the response to palliative radiation therapy (i.e., the irradiation effect) for painful bone metastases from solid malignant carcinomas., Methods: Consecutive patients with painful bone metastases treated with palliative radiation between January 2013 and December 2017 at our institution were included. We retrospectively investigated the pretreatment images from the different imaging modalities (CT, MRI, bone scintigraphy, and 18 FDG-PET-CT) obtained between 1 month before and the initiation of palliative radiation and determined the primary site of carcinoma, histological type, metastatic lesion type (osteolytic, osteoblastic, or mixed), pathological fracture, and metastatic site (vertebral or not). We then evaluated the relationship between these factors and treatment response. We defined "response" as the condition in which patients achieved pain relief or reduced the use of painkiller medicines., Results: In total, 131 patients (78 men and 53 women) were included; the median age was 66 years (range, 24-89 years). Prescribed doses were 8-50 Gy/1-25 fractions with 2-8 Gy/fraction. Among the 131 patients, 105 were responders (response rate, 80%). The imaging modalities performed before irradiation were CT in 131 patients, MRI in 54, bone scintigraphy in 56, and 18 FDG-PET-CT in 14. The Welch t-test and chi-square test showed no significant association between treatment response and each factor. Multiple logistic regression analysis including the imaging modality, metastatic site, and pathological fracture also showed no significant association with each factor., Conclusions: There was no significant relationship between the type of pretreatment imaging and treatment response for painful bone metastases. Thus, setting the appropriate radiation field according to CT images and clinical findings could help avoiding further image inspection before palliative radiation for painful bone metastases.

Introduction: We recently reported a variant prothrombin (p.Arg596Leu: prothrombin Yukuhashi) that confers antithrombin resistance to patients with hereditary thrombosis. To detect antithrombin resistance in plasma, we devised a laboratory test analyzing the kinetics of thrombin inactivation using antithrombin., Materials and Methods: After incubation with prothrombin activator components (phospholipids, CaCl2, and snake venom), samples were treated with excess antithrombin in the presence or absence of heparin for various time periods. Subsequently, H-D-Phe-Pip-Arg-p-nitoranilide was added and changes in absorbance/min (ΔA/min) were measured at 405 nm., Results: After 1 min inactivation using antithrombin and heparin, the relative residual thrombin activity of recombinant mutant prothrombin (34.3% ± 2.2%) was higher than that of the wild-type (6.3% ± 1.2 %). After 30 min without heparin, the relative residual thrombin activity of recombinant mutant prothrombin (95.8% ± 0.4%) was higher than that of the wild-type (10.1% ± 1.7%), indicating that this assay could detect antithrombin resistance of the variant 596Leu prothrombin. Moreover, warfarinized plasmas from 2 heterozygous patients with prothrombin Yukuhashi mutation clearly showed higher values of the relative residual thrombin activity than those from 5 thrombosis patients lacking the mutation in the presence or absence of heparin., Conclusions: We have devised a laboratory test to detect antithrombin resistance in plasma by analyzing the kinetics of thrombin inactivation using antithrombin. This assay may be useful for detecting antithrombin resistance in plasma, even in warfarinized patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Syndecan-4, a cell-surface heparan sulfate proteoglycan, can participate in inflammation and wound healing as a host defense molecule. Tumour necrosis factor (TNF)-α, one of the most potent proinflammatory cytokines, is known to upregulate syndecan-4 expression, but the precise mechanisms are unclear. To elucidate these mechanisms in detail, we examined syndecan-4 upregulation by TNF-α in the endothelium-like EAhy926 cell. Of the two putative nuclear factor kappa-B (NF-κB) binding sites in the syndecan-4 gene (SDC4) promoter, deletion or mutation of one or both sites significantly diminished the effects of TNF-α. Electrophoretic mobility shift assays showed that p65 and c-Rel, but not p50, bound to these NF-κB binding sites, whereas pull-down assays showed binding of all three NF-κB components. Chromatin immunoprecipitation assays clearly showed that p65 and phosphorylated p65, but not p50 or c-Rel, bound to the SDC4 promoter. An NF-κB inhibitor, p65 knockdown and a transcriptional elongation inhibitor completely blocked the effect of TNF-α on SDC4 promoter activity and significantly, but not completely, blocked that on SDC4 mRNA expression. These data suggest that NF-κB p65 could be a key mediator of syndecan-4 upregulation by TNF-α through two binding sites in the SDC4 promoter, but other NF-κB-p65 independent pathways might also be involved through transcriptional elongation.

Coagulation FVII (Factor VII) is a vitamin K-dependent glycoprotein synthesized in hepatocytes. It was reported previously that FVII gene (F7) expression was up-regulated by ribavirin treatment in hepatitis C virus-infected haemophilia patients; however, its precise mechanism is still unknown. In the present study, we investigated the molecular mechanism of ribavirin-induced up-regulation of F7 expression in HepG2 (human hepatoma cell line). We found that intracellular GTP depletion by ribavirin as well as other IMPDH (inosine-5'-monophosphate dehydrogenase) inhibitors, such as mycophenolic acid and 6-mercaptopurine, up-regulated F7 expression. FVII mRNA transcription was mainly enhanced by accelerated transcription elongation, which was mediated by the P-TEFb (positive-transcription elongation factor b) complex, rather than by promoter activation. Ribavirin unregulated ELL (eleven-nineteen lysine-rich leukaemia) 3 mRNA expression before F7 up-regulation. We observed that ribavirin enhanced ELL3 recruitment to F7, whereas knockdown of ELL3 diminished ribavirin-induced FVII mRNA up-regulation. Ribavirin also enhanced recruitment of CDK9 (cyclin-dependent kinase 9) and AFF4 to F7. These data suggest that ribavirin-induced intracellular GTP depletion recruits a super elongation complex containing P-TEFb, AFF4 and ELL3, to F7, and modulates FVII mRNA transcription elongation. Collectively, we have elucidated a basal mechanism for ribavirin-induced FVII mRNA up-regulation by acceleration of transcription elongation, which may be crucial in understanding its pleiotropic functions in vivo.

Background: Intron 22 inversion (Inv22) of the coagulation factor (F)VIII gene (F8) is a frequent cause of severe hemophilia A. In addition to Inv22, a variety of F8 mutations (1492 unique mutations) causing hemophilia A have been reported, of which 171 involve deletions of over 50 bp (HAMSTeRs database; http://hadb.org.uk/). However, only 10% of these large deletions have been fully characterized at the nucleotide level., Patients and Methods: We investigated gene abnormalities in three unrelated severe hemophilia A patients with high titer FVIII inhibitors. They had previously been shown to carry large deletions of the F8, but the precise gene abnormalities remain to be elucidated., Results: Inverse shifting-PCR (IS-PCR) Inv22 diagnostic tests revealed that these patients carried either type I or II Inv22. However, they showed a wild-type (WT) pattern in the IS-PCR Inv22 complementary tests. We further analyzed their X chromosomes to account for the puzzling results, and found that they had different centromeric breakpoints in the Inv22 X chromosomes, adjacent to the palindromic regions containing int22h-2 or -3, and their spacer region, respectively. The connections appeared to be shifted towards the telomere of the WT F8 Xq28, resulting in a new telomere with an additional intact int22h copy., Conclusions: These gene rearrangements might result from double-strand breaks in the most distal regions of the long arms of the Inv22 X chromosomes, followed by DNA restorations using the WT F8 Xq28 by non-homologous end joining or break-induced replication; thus leading to large F8 deletions in severe hemophilia A patients., (© 2012 International Society on Thrombosis and Haemostasis.)

We identified a novel mechanism of hereditary thrombosis associated with antithrombin resistance, with a substitution of arginine for leucine at position 596 (p.Arg596Leu) in the gene encoding prothrombin (called prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild-type prothrombin in clotting assays, but the formation of thrombin-antithrombin complex was substantially impaired. A thrombin-generation assay revealed that the peak activity of the mutant prothrombin was fairly low, but its inactivation was extremely slow in reconstituted plasma. The Leu596 substitution caused a gain-of-function mutation in the prothrombin gene, resulting in resistance to antithrombin and susceptibility to thrombosis.

Background: The Mini-Mental State Examination (MMSE) is one of the most commonly used instruments in the evaluation of global cognitive status. Few studies have investigated the relationship among its components in terms of factorial structure in Japanese individuals suffering from dementia. The aims of this study were: 1) to analyze the factorial structure of MMSE in Japanese dementia patients, 2) to clarify the MMSE static structure in identifying different cognitive profiles and understanding how these profiles are related to levels of dysfunction in subsets of dementia patients., Methods: 30,895 consecutive outpatients with dementia were evaluated. The 11 subtests composing the MMSE and the global MMSE score were analyzed. Factor analysis based on principal component analysis with Promax rotation was applied to the data representing the frequency of failures in each subtest as identified by the MMSE., Results: Factor analysis identified three factors that explained approximately 44.57% of the total variance. The first factor, immediate memory, essentially constituted a simple index of the reading and writing subtests. The second factor, orientation and delayed recall, expressed the ability to handle new information. The third factor, working memory, was most closely related to the severity of dementia at the time of test administration., Conclusions: Japanese dementia patients appear to develop difficulty handling new information in the early stages of their disease. This finding, and our finding that there is a factor associated with disease severity, suggest that understanding the specific factors related to subtest items, which underlie the total MMSE score may be useful to clinicians in planning interventions for Japanese patients in the early stages of dementia.

A 56-year-old woman with hypertension and hypercholesterolemia was admitted to our hospital with acute inferior myocardial infarction. The patient had total occlusion of the right coronary artery (RCA) segment 2, and bare-metal stents were placed. Four months later, plain old balloon angioplasty was performed for in-stent restenosis. Follow-up coronary angiography (CAG) 6 months later showed in-stent total occlusion, so a stent-in-stent procedure was performed using paclitaxel-eluting stents (PESs). Four months later, the patient began complaining of early morning chest pain at rest. CAG showed no in-stent restenosis, so coronary spastic angina was suspected. Intracoronary infusion of ergonovine to the right and left coronary arteries revealed spasm of the RCA with total occlusion just proximal to the PES in segment 1. Her chest pain was reproduced with ST-elevation in leads II, III, and aVF, so the diagnosis of coronary spastic angina was made. Treatment with a Ca-channel blocker and nitrates relieved the symptoms. The PES was the probable cause of the coronary spasm.

"Hierba santa," a Peruvian herbal medicine, is used to alleviate many symptoms, including headache, hemorrhoids, fever, and rheumatism. Several Cestrum species are said to be the origin of hierba santa. Three lots of hierba santa: Cestrum auriculatum (herb 1 and herb 2) and C. hediundinum (herb 3), which were purchased from Peruvian markets at Cuzco (Andes area) and Equitos (Amazon area), respectively, were examined for their pharmacological activities and active components. Herbs 1-3 showed anti-inflammatory and analgesic activities in the in vivo writhing inhibition test in mouse and inhibited prostaglandin E(1)-, E(2)-, or ACh-induced contractions of guinea pig ileum in the Magnus method. Activity-based separation of each extract yielded cestrumines A and B, cestrusides A and B, a mixture of (+)- and (-)-pinoresinol glucosides, nicotiflorin, rutin, sinapoyl glucose, ursolic acid, beta-sitosteryl glucoside, and 2-sec-butyl-4,6-dihydroxyphenyl-beta-D: -glucopyranoside. Among them, cestrumine A and cestrusides A and B are new compounds. All three lots of hierba santa do not contain exactly the same active components.

As Cistus laurifolius has been used traditionally to treat inflammatory and rheumatic disorders, its leaves were tested for prostaglandin (PG) inhibitory and antioxidant activities. The leaf extract showed both activities, i.e., inhibitory effect at 300 microg/ml on PGE1- and E2-induced contractions in guinea pig ileum and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities shown by these dual assays provided sixteen compounds, 1-16. Known compounds 1-12 and 15 were identified as 3-O-methyl quercetin (1), 3,7-O-dimethyl quercetin (2), genkwanin (3), 3,7-O-dimethyl kaempferol (4), 3,4'-O-dimethyl quercetin (5), apigenin (6), 3,4'-O-dimethyl kaempferol (7), ellagic acid (8), beta-sitosterol-3-O-beta-glucoside (9), quercetin 3-O-alpha-rhamnoside (10), 5-O-p-coumaroyl quinic acid methyl ester (11), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-alpha-l-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (12) and 2,3-dihydro-2-(4'-alpha-l-rhamnopyranosyloxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-5-benzofuranpropanol (15). New lignan glycosides 13 and 14 were determined to be olivil 9-O-beta-D-xyloside and berchemol 9-O-rhamnoside, respectively. Compound 16 was isolated as a 2:1 mixture of two diastereomers, the major one of which was determined to be (7S,8R)-dihydrodehydrodiconiferyl alcohol 9'-O-alpha-L-rhamnoside. The structures were determined by detailed 2D NMR analysis together with NOEDF and CD. PG inhibitory effect was observed in 1, 5, 10, 12 and 16 at 30 microg/ml and antioxidant activity, in 1, 2, 8, 10, 12-14 and 16.

Investigation of the inhibitory fraction of Leucas aspera on prostaglandin-induced contraction in guinea pig ileum provided four new diterpenes, leucasperones A (1) and B (2) and leucasperols A (3) and B (4), and three new isopimarane glycosides, leucasperosides A, B, and C (5-7), together with the known compounds asperphenamate, maslinic acid, (-)-isololiolide, and linifolioside. The structures of the compounds were determined by detailed spectroscopic analysis. The configurations of 1 and 2 and the acetylated derivatives of 3 and 4 were determined by differential NOE analysis and CD data. Leucasperone A (1), leucasperosides A (5) and B (6), and linifolioside showed inhibition of prostaglandin-induced contractions.

In a screening study on immunomodulatory fungal metabolites, three known anthraquinones, carviolin (roseo-purpurin) (1), 1-O-methylemodin (2), omega-hydroxyemodin (citreorosein) (4), and a new anthraquinone, omega-acetylcarviolin (3), together with a known steroid, ergosta-4,6,8(14),22-tetraen-3-one (5) and a new steroid, 25-hydroxyergosta-4,6,8(14),22-tetraen-3-one (6) were isolated from an Ascomycete, Zopfiella longicaudata, and found to have moderate immunosuppressive activities. The structure-activity relationships of these metabolites are discussed.

A screening study focusing on immunomodulatory activity of the EtOAc extract of an Ascomycete, Chaetomium seminudum, has afforded a known epipolythiodioxopiperazine, chetomin (1), together with three new chetomin-related metabolites named chetoseminudins A (2), B (3), and C (4). Among these four metabolites, 1 and 2 have been deduced as the immunosuppressive features of this fungus.

Two new pregnane alkaloids, wrightiamines A (1) and B (2), were isolated from the extract of the tropical Apocynaceous plant Wrightia javanica collected in Thailand, and their structures were elucidated by spectral data. Wrightiamine B (2) was preparaed from 3beta-hydroxy-5alpha-pregnan-20-one to establish the configuration of the C-20 position as S. Wrightiamine A (1) exhibited cytotoxic activity against vincristine-resistant murine leukemia P388 cells.

According to the traditional usage of the plant for antiinflammation and analgesia, Leucas aspera was tested for its prostaglandin (PG) inhibitory and antioxidant activities. The extract showed both activities, i.e., inhibition at 3 x 10(-4) g/ml against PGE(1)- and PGE(2)-induced contractions in guinea pig ileum and a 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities in these dual assay methods provided eight lignans and four flavonoids, LA-1- -12, among which LA-1- -7 and LA-10- -12 were identified as nectandrin B, meso-dihydroguaiaretic acid, macelignan, acacetin, apigenin 7-O-[6"-O-(p-coumaroyl)-beta-D-glucoside], chrysoeriol, apigenin, erythro-2-(4-allyl-2, 6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)propan-1-ol, myristargenol B, and machilin C, respectively. LA-8 was determined to be (-)-chicanine, the new antipode of the (+) compound, by spectroscopic methods including CD and ORD. Chiral-HPLC analysis of LA-9 showed that it was a mixture of two enantiomers, (7R, 8R)- and (7S, 8S)-licarin A. All of these components were first isolated from L. aspera. PG inhibition was observed in LA-1, LA-2, and LA-5, and antioxidant activity in LA-1- -3 and LA-8- -12.

A screening study focusing on monoamine oxidase inhibitory activity on the EtOAc extract of an Ascomycete Chaetomium quadrangulatum, which previously gave five unique chromones possessing this activity (chaetoquadrins A-E (1-5)), this time afforded six new constituents termed chaetoquadrins F-K (6-11) in addition to 1-5. The structures of 6-11 have been deduced on the basis of spectral and chemical data, and 7 and 8 have shown appreciable monoamine oxidase inhibitory activity.

Three new natural onoceranoid triterpenes, lansionic acid (1), 3beta-hydroxyonocera-8(26),14-dien-21-one (2), and 21alpha-hydroxyonocera-8(26),14-dien-3-one (3), were isolated from the fruit peel of Lansium domesticum together with two known triterpenoids (4 and 5), and their structures were elucidated from spectral data. These triterpenoids exhibited mild toxicity against brine shrimp (Artemia salina).

Thirteen seco-prezizaane terpenoids isolated from star anise species (Illcium floridanum, Illcium parviflorum, and Illcium verum) were investigated for their ability to inhibit the specific binding of [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB), a non-competitive antagonist of gamma-aminobutyric acid (GABA) receptors, to housefly-head and rat-brain membranes. Veranisatin A was found to be the most potent inhibitor in both membranes, with an IC(50)(fly) of 78.5 nM and an IC(50)(rat) of 271 nM, followed by anisatin (IC(50)(fly)=123 nM; IC(50)(rat)=282 nM). Six of the other 11 tested compounds were effective only in housefly-head membranes. Pseudoanisatin proved to display a high (>26-fold) selectivity for housefly versus rat GABA receptors (IC(50)(fly)=376 nM; IC(50)(rat) >10,000 nM). Although pseudoanisatin does not structurally resemble EBOB, Scatchard plots indicated that the two compounds bind to the same site in housefly receptors. Anisatin and pseudoanisatin exhibited moderate insecticidal activity against German cockroaches. Comparative molecular field analysis (CoMFA), a method of three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis, demonstrated that seco-prezizaane terpenoids can bind to the same site as do picrotoxane terpenoids such as picrotoxinin and picrodendrins, and the CoMFA maps allowed us to identify the parts of the molecules essential to high activity in housefly GABA receptors.

Five novel chromones (1,4-benzopyran-4-ones), among which three are tetracyclic and one contains a sulfonyl group, have been isolated from an Ascomycete, Chaetomium quadrangulatum, as monoamine oxidase inhibitory features, and named chaetoquadrins A (1)-E (5).

Fractionation guided by immunomodulatory activity of the EtOAc extract of the Ascomycete Eupenicillium crustaceum has afforded two new naturally occurring products, 4'-oxomacrophorin D (1) and 4'-oxomacrophorin A (2), as the immunosuppressive components of this fungus [1: 3-hydroxy-3-methylglutaryl (HMG) conjugate of 2]. The structures including the absolute configurations of 1 and 2 have been determined on the basis of chemical correlation of 1 with macrophorin D (3). The absolute configuration of the HMG moiety in 3 has been revised from 3R to 3S.

Three new 12beta-hydroxymultiflorane triterpenoid acids, sandorinic acids A-C (1-3), were isolated from the stem bark of Sandoricum indicum together with five known triterpenes (4-8). The structures of 1-3 were elucidated by spectral data interpretation. Compounds 1-8 were evaluated for their inhibiting activity against several tumor cell lines and for their effects on lymphocyte proliferation.