A pilot case-control study on the alveolar bone density measurement in risk assessment for bisphosphonate-related osteonecrosis of the jaw.

UNLABELLED: Alveolar bone mineral density (BMD) measured by radiography standardized by aluminum step wedge pasted on the film and digitized by a computer system was significantly higher around osteonecrosis lesions than in control cases in a pilot case-control study. High alveolar bone density appears useful as a local risk factor for bisphosphonate-related osteonecrosis of the jaw (BRONJ). INTRODUCTION: In an attempt to find a reliable test method predicting the occurrence of BRONJ in addition to various risk factors suggested, an increase of alveolar bone density near the necrotic lesions was found by computerized radiogrammetry using dental films pasted with an aluminum step wedge (Bone Right, Dentalgraphic.Com Company, Himeji) in six cases of BRONJ. METHODS: The bone mineral density surrounding the osteonecrosis lesions showed distinctly higher density in BRONJ cases compared with age-matched controls. In one subject on bisphosphonate treatment in whom two extractions were simultaneously carried out, BRONJ occurred only at the location with extremely high alveolar bone density, but not at the other site with normal density. CONCLUSION: This method may be useful in detecting a rise of alveolar BMD frequently occurring near the necrotic lesion in subjects with impending risk for BRONJ.

Association of thalamic hyperactivity with treatment-resistant depression and poor response in early treatment for major depression: a resting-state fMRI study using fractional amplitude of low-frequency fluctuations.

Despite novel antidepressant development, 10-30% of patients with major depressive disorder (MDD) have antidepressant treatment-resistant depression (TRD). Although new therapies are needed, lack of knowledge regarding the neural mechanisms underlying TRD hinders development of new therapeutic options. We aimed to identify brain regions in which spontaneous neural activity is not only altered in TRD but also associated with early treatment resistance in MDD. Sixteen patients with TRD, 16 patients with early-phase non-TRD and 26 healthy control (HC) subjects underwent resting-state functional magnetic resonance imaging. To identify brain region differences in spontaneous neural activity between patients with and without TRD, we assessed fractional amplitude of low-frequency fluctuations (fALFF). We also calculated correlations between the percent change in the Hamilton Rating Scale for Depression (HRSD17) scores and fALFF values in brain regions with differing activity for patients with and without TRD. Patients with TRD had increased right-thalamic fALFF values compared with patients without TRD. The percent change in HRSD17 scores negatively correlated with fALFF values in patients with non-TRD. In addition, patients with TRD showed increased fALFF values in the right inferior frontal gyrus (IFG), inferior parietal lobule (IPL) and vermis, compared with patients with non-TRD and HC subjects. Our results show that spontaneous activity in the right thalamus correlates with antidepressant treatment response. We also demonstrate that spontaneous activity in the right IFG, IPL and vermis may be specifically implicated in the neural pathophysiology of TRD.

A comparative study on interactions of alpha-aminoisobutyric acid containing antibiotic peptides, trichopolyn I and hypelcin A with phosphatidylcholine bilayers.

Interactions of alpha-aminoisobutyric acid containing antibiotic peptides, trichopolyn I and hypelcin A with phosphatidylcholine bilayers were investigated to obtain some basic information on their bioactive mechanisms. Trichopolyn I as well as hypelcin A induced the leakage of a fluorescent dye, calcein, entrapped in sonicated egg yolk L-alpha-phosphatidylcholine vesicles. A quantitative analysis revealed that both the binding affinity and the 'membrane-perturbing activity' of trichopolyn I to the vesicles are about one-third of those of hypelcin A. The conformations and the orientations of the peptide and lipid molecules in the membranes were studied using polarized Fourier transform infrared-attenuated total reflection spectroscopy, circular dichroism, and differential scanning calorimetry. In phosphatidylcholine bilayers, both peptides mainly conformed to helical structures irrespective of the membrane physical state (gel or liquid-crystalline). The helix axes, penetrating the hydrophobic region of the bilayers, were oriented neither parallel nor perpendicular to the membrane normal. The disruption in the lipid packing induced by the peptide insertion seems to be responsible for the leakage by these peptides.

Structural basis of potent antiperoxidation activity of the triterpene celastrol in mitochondria: effect of negative membrane surface charge on lipid peroxidation.

The structural basis of the potent inhibitory effect of the triterpene celastrol on lipid peroxidation of rat liver mitochondria initiated by adenosine 5'-diphosphate (ADP) and Fe2+ was studied in comparison with the effects of its analogs, pristimerin and acetylcelastrol. The dienone-phenol moiety and the anionic carboxyl group of celastrol were concluded to be important for their antiperoxidative action: The former moiety directly scavenges radicals and the latter donates the membrane with a negative surface charge, making it more resistant to peroxidation. Celastrol is suggested to inhibit the peroxidation of the outer and inner mitochondrial membrane by direct radical scavenging, and also to prevent the attack of oxygen radicals on the inner membrane by increasing its negative surface charge.

Inhibitory effects of triptogelin A-1 on 12-O-tetradecanoylphorbol-13- acetate-induced skin tumor promotion.

Dihydroagarofuran sesquiterpenes, which were isolated from Tripterygium wilfordii Hook fil. var. regelii Makino and Euonymus sieboldianus Blume, showed inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Triptogelin A-1, one of the active dihydroagarofuran sesquiterpenes, exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. Interestingly, triptogelin A-1 was more effective when applied after TPA-treatment (post-treatment) than before TPA-treatment (pretreatment). The findings indicate that these dihydroagarofuran sesquiterpenes might be valuable antitumor promoters.

Inhibitory effects of dihydroagarofuran sesquiterpenes on Epstein-Barr virus activation.

To search for possible antitumor promoters, we carried out a primary screening of thirty-seven dihydroagarofuran sesquiterpenes from Tripterygium wilfordii Hook fil. var. regelii Makino and Euonymus sieboldianus Blume, using their possible inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation which is induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of these sesquiterpenes, triptofordin F-2 (Takaishi et al., 1988), 1,2,6,8,15-pentaacetoxy-9-benzoyloxy-4-hydroxy-beta-dihydroagarofuran and triptogelin A-1 (Takaishi et al., 1990) were observed to significantly inhibit the EBV-EA activation at low doses. Based on the results, the structural requirements for the activity of these compounds were discussed [corrected].

Macrophyllols A and B, two unusual novel sesquiterpene and monoterpene dimers from the bark of Inula macrophylla.

[structure: see text] Two novel sesquiterpene and monoterpene dimers, macrophyllols A (1) and B (2), were isolated from the bark of Inula macrophylla. Their structures were determined on the basis of spectral evidence (especially HREIMS and 2D NMR) as well as chemical transformation. The structure of macrophyllol A (1) was confirmed by X-ray analysis. The possible biosynthetic pathways of macrophyllols A (1) and B (2) are discussed.

A saponin with anti-ulcerogenic effect from the flowers of Spartium junceum.

A new oleanene-type saponin with potent anti-ulcerogenic activity was isolated from the flowers of Spartium junceum. The various techniques of NMR spectral analysis, viz. 1H, 13C, DEPT, C-H COSY, H-H COSY, COLOC, NOESY, HMBC, HMQC, in conjunction with EI- and FAB-mass spectrometry, revealed that the structure of the isolated saponin was 3-O-[alpha-L-rhamnopyranosyl-(1-->2) -O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]-3 beta,16beta,22 beta,24-tetrahydroxy-olean-12-ene and named as spartitrioside.

Terpenoids from Tripterigyum hypoglaucum.

Six terpenoids have been isolated from the root bark of Tripterygium hypoglaucum, along with 14 known compounds. The structures of the terpenoids were elucidated as 3,11,14-oxo-abieta-8,12-diene, 3beta-hydroxy-12,14-dimethoxyabieta-8,11,13-triene, 3beta-hydroxy-11alpha-ethoxyurs-12-ene, 3beta-hydroxy-11alpha-methoxyurs-12-ene, 3beta-hydroxy-11alpha-methoxyolean-12-ene-28-oic acid, and 1beta-benzoyl-8alpha-cinnamoyl-4alpha,5alpha- dihydroxydihydroagarofuran.

Cucurbitacin glycosides from Cabeça-de-negro.

Five cucurbitacin glycosides named cabenosides D-L were isolated from 'Cabeça-de-negro', the roots of Caput nigri. Among them, the structures of cabenosides D-H were elucidated as 10 alpha-cucurbit-5-en-11-oxo-3 beta,24R,25-triol-3-O-beta-D-glucopyranoside, 10 alpha-cucurbit-5-en-24-oxo-3 beta, 11 alpha,25-triol-25-O-beta-D- glucopyranosyl, [3,O-beta-D-glucopyranoside, 3-O-beta-D-glucopyranosyl-(1-2)-beta-D-glucopyranoside, 3-O-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranoside] and 10 alpha-cucurbit-5-en-11,24-dioxo-3 beta,25-diol-25-O-beta-D- glucopyranosyl, 3-O-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranoside, respectively, on the basis of chemical and spectral evidence.

Cucurbitacin glycosides from Caput nigri.

The chemical structures of cabenosides I-L were investigated. These are four of the 12 cucurbitacin glycosides isolated from 'Cabeça-de-negro', the roots of Caput nigri. By means of chemical analyses the structures of cabenosides I-L were elucidated as 10 alpha-cucurbit-5-ene-3 beta,11 alpha,20S,24 xi,25-pentaol [3, 25-di-O-beta-D-glucopyranoside, and 3-O-beta-D-glucopyranosyl-(1-2)-beta-D-glucopyranosyl (sophorosyl), 25-O-beta-D-glucopyranoside], and 10 alpha-cucurbit-5,20,24-triene-11-oxo-3 beta,26-diol [3-O-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranosyl (gentiobiosyl), 26-O-beta-D-glucopyranoside and 3,26-di-O-gentiobioside], respectively.

Nor-cucurbitacin glucosides from Caputo nigri.

Three new nor-cucurbitacin glucosides were isolated from the root of Caputo nigri (Cabeça-de-negro) and their structures established as 29-nor-1,2,3,4,5,10-dehydro-2,3,16 alpha,20R, 22 zeta,25-hexahydroxy-11-oxocucurbita-6,23-diene 2-O-beta-D-glucopyranoside and 2-O-beta-D-glucopyranosyl(1-2)beta-D- glucopyranoside(sophorose), and 1,2,3,4,5,10-dehydro-2,3,16 alpha-trihydroxy-4, 9,14-trimethyl-19-norpregn-6-ene-11,20-dione 2-O-beta-D-glucopyranoside on the basis of detailed spectroscopic analysis.

12-Hydroxy steroidal glycosides from the caudex of Yucca gloriosa.

The structures of the new steroidal saponins (tentatively named YS-XI, -XII and -XIII) have been isolated from the caudex of Yucca gloriosa and characterized as 3-O-beta-D-glucopyranosyl-(1----2)-beta-D-galactopyranosyl 5 beta- (25R)-spirostan-3 beta, 12 beta-diol, 3-O-beta-D-glucopyranosyl-(1----2)- [beta-D-glucopyranosyl-(1----3)]-beta-D-glucopyranosyl 5 beta- (25R)-spirostan-3 beta, 12 beta-diol and 3-O-beta-D-glucopyranosyl-(1----2)- beta-D-galactopyranosyl 5 beta-(25R)-spirostan-2 beta,3 beta,12 beta-triol, respectively.

Sesquiterpene polyol esters from Tripterygium wilfordii.

The extract (T(II)) of Tripterygium wilfordii Hook f. afforded four sesquiterpene esters: 1beta,2beta,5alpha,8beta,11-pentaacetoxy-4alpha-hydroxy-3alpha(2'-methylbutanoyl)-15-nicotinoyl-7-oxo-dihydroagarofuran; 1beta,5alpha,11-triacetoxy-7beta-benzoyl-4alpha-hydroxy-8beta-nicotinoyl-dihydroagarofuran; 1beta,2beta,5alpha,11-tetraacetoxy-8alpha-benzoyl-4alpha-hydroxy-7beta-nicotinoyl-dihydroagarofuran; 5alpha-benzoyl-4alpha-hydroxy-1beta,8alpha-dinicotinoyl-dihydro- agarofuran as well as one other known sesquiterpene ester. Their structures were established on the basis of spectroscopic studies.

Triterpenoids from Tripterygium wilfordii.

The extract (T(II)) of Tripterygium wilfordii Hook f. afforded four triterpenoids: wilforic acid D (3beta,24-epoxy-2alpha-hydroxy-24R*-ethoxy-29-friedelanoic acid); (E) 3beta,24-epoxy-2-oxo-3alpha-hydroxy-29-friedelanoic acid; (F) 2beta-hydroxy-3-oxo-friedelan-29-oic acid; 29-hydroxy-3-oxo-olean-12-en-28-oic acid and 17 known triterpenoids. Their structures were established on the basis of spectroscopic studies. In a bioactivity analysis, only the known dulcioic acid compound showed a significant inhibitory effect on cytokine production.

Phlorigidosides A-C, iridoid glucosides from Phlomis rigida.

From the aerial parts of Phlomis rigida, three iridoid glucosides, phlorigidoside A (2-O-acetyllamiridoside), B (8-O-acetyl-6-beta-hydroxyipolamide) and C (5-deoxysesamoside), were isolated together with the known iridoid glucosides, shanzhiside methyl ester, 8-O-acetylshanzhiside methyl ester, deoxypulcheloside I, lamiridoside, and 6-beta-hydroxyipolamide. The structures of the new compounds were elucidated based on spectral and chemical evidence.

12-Keto steroidal glycosides from the caudex of Yucca gloriosa.

Eight new steroidal glycosides, tentatively named YS-VI, -VII, -VIII, -IX, -X, -XI, -XII and -XIII were isolated from the caudex of Yucca gloriosa along with P-1, YG-2 and YG-3 previously obtained from flowers. The structures of five of these compounds were elucidated as mexogenin 3-O-beta-D-glucopyranosyl-(1----2)-beta-D-galactopyranoside (YS-VI), gloriogenin 3-O-beta-D-glucopyranosyl-(1----2)-[beta- D-glucopyranosyl-(1----3)]-beta-D-glucopyranoside (YS-VII) and 3-O-beta-D-glucopyranosyl-(1----2)-[beta-D-glucopyranosyl)-(1----3)]- beta-D-galactopyranoside (YS-VIII), manogenin 3-O-beta-lycotetraoside (YS-IX) and 3-O-alpha-L-rhamnopyranosyl-beta-lycotetraoside (YS-X), respectively, on the basis of chemical and spectral evidence.

Phenylbutanoids and stilbene derivatives of Rheum maximowiczii.

The methanol extract of the dried roots of Rheum maximowiczii afforded four phenylbutanoid and two stilbene derivatives. Their structures were established on the basis of chemical and spectroscopic studies.

Terpenoids and gamma-pyrone derivatives from Prangos tschimganica.

The methanol extract of the dried aerial parts of Prangos tschimganica afforded seven monoterpenoids and four gamma-pyrone derivatives. Their structures were established on the basis of chemical and spectroscopic evidence.

Coumarins and bicoumarin from Ferula sumbul: anti-HIV activity and inhibition of cytokine release.

The methanol extract of the dried roots of Ferula sumbul afforded two furanocoumarin esters, fesumtuorin A, B, one bicoumarin, fesumtuorin C, five spirobicoumarins, fesumtuorin D, E, F, G and H, along with nineteen known coumarins. Their structures were established on the basis of spectroscopic studies. Some of the isolated compounds showed anti-HIV activity and very weak inhibition of cytokine release.