Reduced susceptibility to amoxicillin of oral streptococci following amoxicillin exposure.

As antibiotic pressure often triggers bacterial resistance, the use of short-duration therapies is increasingly recommended. The objective of the present study was to evaluate both the clinical efficiency and the impact on oral streptococci of a 3 day versus a 7 day amoxicillin therapy for odontogenic infection requiring tooth extraction. On day 0, patients were randomly assigned to a 3 day or 7 day amoxicillin treatment. The tooth was extracted on day 2 and the post-operative follow-up was carried out on day 9. Oral flora was collected on days 0, 9 and 30, and the susceptibility of the streptococci to amoxicillin was determined. The results showed that treatment with amoxicillin for 3 or 7 days had a similar clinical efficiency, and also induced similar selection of oral streptococci with reduced susceptibility to amoxicillin, suggesting that the selection of strains with reduced susceptibility to amoxicillin is a rapid phenomenon, appearing even with short-duration therapies.

Inhibition of trypsin and chymotrypsin by anti-inflammatory triterpenoids from Compositae flowers.

Taraxastane, oleanane, ursane, lupane, taraxane, cycloartane, dammarane and tirucallane triterpenoids isolated from flowers of Compositae plants have been previously reported to exhibit anti-inflammatory effects and are variously competitive and non-competitive inhibitors of the serine proteases trypsin and chymotrypsin. The general features of those triterpenoids found to be protease inhibitors are having a hydroxy group and an appropriate side chain in the region of the molecule distal to the 3-hydroxy group. However, fatty acid esterification of the triterpenoid 3-hydroxy group can have a marked effect on inhibitor effectiveness. This suggests a possible means of rapid alteration of the plant defensive complement in vivo and of the bioactivity of these anti-inflammatory compounds.

Constituents of compositae plants. 2. Triterpene diols, triols, and their 3-o-fatty acid esters from edible chrysanthemum flower extract and their anti-inflammatory effects.

The n-hexane soluble and the nonsaponifiable lipid fractions of the edible flower extract of chrysanthemum (Chrysanthemum morifolium) were investigated for triterpene diol and triol constituents. These triterpenes occur as the 3-O-fatty acid esters in the n-hexane soluble fraction from which 26 new and 6 known fatty acid esters were isolated and characterized. From the nonsaponifiable lipid fraction, 24 triterpene diols and triols were isolated, of which 3 were new compounds: (24S)-25-methoxycycloartane-3beta,24-diol (11), (24S)-25-methoxycycloartane-3beta,24,28-triol (22), and 22alpha-methoxyfaradiol (23). Faradiol (9) and heliantriol C (19), present in the nonsaponifiable lipid fraction and as the 3-O-palmitoyl esters in the n-hexane soluble fraction, were the most predominant triterpene diol and triol constituents. Fourteen triterpene diols and triols and 9 fatty acid esters were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. All of the triterpenes examined showed marked inhibitory activity, with a 50% inhibitory dose (ID50) of 0.03-1.0 mg/ear, which was more inhibitive than quercetin (ID50 = 1.6 mg/ear), a known inhibitor of TPA-induced inflammation in mice.

Inhibitory effect of cycloartenol ferulate, a component of rice bran, on tumor promotion in two-stage carcinogenesis in mouse skin.

Inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice was observed in the methanol extract of rice bran and gamma-oryzanol. The active components of rice bran, sitosterol ferulate, 24-methylcholesterol ferulate, cycloartenol ferulate and 24-methylenecycloartanol ferulate inhibited markedly the TPA-induced inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.2-0.3 mg/ear. Furthermore, cycloartenol ferulate markedly inhibited the tumor-promoting effect of TPA in 7,12-dimethylbenz[a]anthracene-initiated mice.

3 beta-p-hydroxybenzoyldehydrotumulosic acid from Poria cocos, and its anti-inflammatory effect.

The structure of a new triterpene derivative isolated from Poria cocos was determined to be 3 beta-p-hydroxybenzoyldehydrotumulosic acid by spectral and chemical methods. 3 beta-p-hydroxybenzoyldehydrotumulosic acid showed marked inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)- and arachidonic acid (AA)-induced ear inflammation in mice. The 50% inhibitory doses of 3 beta-p-hydroxybenzoyldehydrotumulosic acid were 0.27 and 1.25 mg per ear on TPA- and AA-induced inflammation, respectively.

Sasanquol, a 3,4-seco-triterpene alcohol from sasanqua oil, and its anti-inflammatory effect.

A novel 3,4-seco-triterpene alcohol, named sasanquol, was isolated from the non-saponifiable lipid of sasanqua oil from the seeds of Camellia sasanqua. Its structure was established to be 3,4-seco-D:B-friedobacchara-4,21-dien-3-ol by spectroscopic methods. This is the first example of naturally occurring triterpene with a D:B-friedobaccharane skeleton. The 50% inhibitory dose of this compound against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation (1 microgram per ear) in mice was 0.4 mg per ear.

Effect of monoclonal anti-human gp130 antibody (GPX7) on bone turnover in normal and ovariectomized rats.

We examined the effects of a monoclonal antihuman gp130 antibody (GPX7), which is known to inhibit interleukin-6 (IL-6) and leukemia inhibitory factor-mediated responses in human cells on the bone metabolism in normal and ovariectomized (OVX), 7-month-old, Wistar rats for 8 weeks. After confirming the cross-reactivity of the antibody in suppressing the IL-6-mediated proliferation of rat liver cells, GPX7 was injected once a week at doses of 1 (low dose) or 4 (high dose) mg/kg body weight (BW). In the lumbar body, bone mineral density values and the trabecular bone volume (BV/TV) were maintained in the GPX7 groups. The values of the trabecular osteoclast surface and number in the GPX7 high-dose group were significantly smaller than those in the OVX controls. The double-labeled surface and bone formation rates in the GPX7 high-dose group were significantly increased. In the proximal tibia, however, the bone mineral content and BV/ TV values in the GPX7 groups were smaller, but the trabecular thickness value in the GPX7 high-dose group was larger than in the OVX control. The single-labeled surface in the GPX7 high-dose group was significantly larger than that in the OVX control rats. Though the parameter values of trabecular osteoclasts were apparently smaller, the differences were not significant. 17-beta estradiol (0.125 mg/kg BW a week) administration prevented the bone loss by reducing the parameters of bone formation and resorption in both the lumbar and the proximal tibia. The antibody administration to the normal rats did not cause any significant changes in the parameters of bone mass and turnover. These data demonstrate that while GPX7 modulates the bone turnover after ovariectomy in rats, it does not compensate for the action of estrogen after ovariectomy in rats.

Inhibitory effect of heliantriol C; a component of edible Chrysanthemum, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Two hydroxy taraxastane-type triterpenes, faradiol and heliantriol C, have been isolated from the ligulate flowers of Chrysanthemum morifolium Ramat. var. sinense Makino fa. esculentum Makino, the edible Chrysanthemum. These compounds showed strong inhibitory activity against 12-O-tetradecanoyl-phorbol-13-aetate (TPA)-induced inflammation in mice. At 0.2 µmol/mouse, these compounds markedly inhibited the promoting effect of TPA (1 µg/mouse) on skin tumor formation followed by 7,12-dimethylbenz[a]anthracene (50 µg/mouse).

Triterpene alcohols from camellia and sasanqua oils and their anti-inflammatory effects.

The nonsaponifiable lipids of camellia and sasanqua oils from the seeds of Camellia japonica L. and C. sasanqua THUNB., respectively, were investigated for their triterpene alcohol constituents. This led to the isolation of twenty-seven triterpene alcohols of which seven were novel naturally occurring compounds, tirucalla-5,7,24-trien-3 beta-ol (1), lemmaphylla-7,21-dien-3 beta-ol (2), isoeuphol (3), isotirucallol (4), (24R)-24,25-epoxybutyrospermol (5) and its 24S-epimer (6), and isoaglaiol (7). The structures were determined by spectroscopic and chemical methods. The inhibitory effects of 3, 4 a mixture of 5 and 6, a mixture of 7 and its 24S-epimer (aglaiol), and eight known triterpene alcohols isolated in this study were evaluated in ear inflammation in mice induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The 50% inhibitory dose of these triterpenes for TPA-induced inflammation (1 microgram per ear) was 0.2-0.9 mg/ear.

Administration of bisphosphonate prevents disuse bone atrophy induced by tail suspension.

We recently demonstrated that osteopenia induced by rat tail-suspension was associated with an initial increase in bone resorption. To study the significance of the increase in early bone resorption for osteopenia, we investigated whether administration of YH529, a third-generation bisphosphonate, prevents the development of osteopenia as evidenced by increased wet weight of the femur, together with its calcium and phosphorus contents, when compared with those of tail-suspended rats treated with the vehicle alone. These results suggested that the initial increase in bone resorption plays an important role in the development of osteopenia induced by tail suspension.

Effect of estrogen on the development of disuse atrophy of bone and muscle induced by tail-supension in rats.

Rat tail-suspension induces disuse atrophy of muscles and bones in hindlimbs. In the present investigation we studied how ovariectomy and estrogen substitution affect the development of the disuse atrophy induced by suspension. Five-week old female Wistar rats were ovariectomized and divided into two groups. One group received intramuscular injection of estradiol dipropionate once a week (OVX-E2 group), and the other received a vehicle injection (OVX group). After the third injection, each group was further divided into two groups, tail-suspended and non-suspended. After 7 days of tail-suspension, a significant decrease in the wet weight of femurs and their Ca and Pi content was observed in the OVX group. However, no significant change in those parameters was observed in the E2 group. In both E2 and OVX groups, a significant decrease in the wet weight of soleus and gastrocnemius muscles was demonstrated after the suspension. This demonstrated that estrogen administration to ovariectomized rats prevents the development of disuse bone atrophy but not that of muscle atrophy, suggesting that estrogen plays important roles in bone remodeling.

Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects.

Eleven tabular and nine ligulate flowers from 15 species of Compositae plants were investigated for their triterpene alcohol constituents. This led to the isolation and identification of 11 triterpene alcohols as follows: heliaol, taraxasterol, psi-taraxasterol, alpha-amyrin, beta-amyrin, lupeol, taraxerol, cycloartenol, 24-methyl-enecycloartanol, tirucalla-7,24-dienol and dammaradienol. The tabular flowers of Calendula officinalis, Carthamus tinctorius, Cosmos bipinnatus, Chrysanthemum morifolium, Helianthus annuus and Matricaria matricarioides showed a characteristic feature by containing helianol as the most predominant component (29-86%) in the triterpene alcohol fractions. The triterpene alcohols from Compositae flowers were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation (1 microgram per ear) in mice. All of these showed marked inhibitory activity, and their 50% inhibitory dose was 0.1-0.8 mg per ear.

Inhibitory effects of lanostane-type triterpene acids, the components of Poria cocos, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Pachymic acid, 3-O-acetyl-16 alpha-hydroxytrametenolic acid, and poricoic acid B had been isolated from the sclerotium of Poria cocos Wolf. These compounds showed a strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice. At 0.2 mumol/mouse, these compounds markedly inhibited the promoting effect of 12-O-tetradecanoylphorbol-13-acetate (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse).

Inhibitory effect of taraxastane-type triterpenes on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Two taraxastane-type hydroxy triterpenes, taraxasterol and faradiol, isolated from the flowers of Compositae plants Cynara scolymus (artichoke) and Chrysanthemum morifilolium (chrysanthemum), respectively, showed strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. At 2.0 mumol/mouse, these compounds inhibited markedly the tumor-promoting effect of TPA (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[alpha]anthracene (50 micrograms/mouse).

Coadministration of interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease.

Interleukin-6 (IL-6), a multipotential cytokine, initiates signal transduction pathways similar to those of ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF). These molecules share the signal transducing receptor component, gp130. IL-6 triggers homodimerization of gp130, whereas CNTF and LIF induce heterodimerization of gp130 and LIF receptor. Although CNTF or LIF treatment attenuates motor deficits in wobbler mouse motor neuron disease (MND), neuroprotective effects of IL-6 on this animal have not yet been clarified. Here we studied whether simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) can ameliorate symptomatic and neuropathological changes in wobbler mouse MND. After clinical diagnosis at postnatal age 3-4 weeks, wobbler mice received subcutaneous injection with human recombinant IL-6 (1.0 mg/kg), human sIL-6R (0.5 mg/kg), IL-6 + sIL-6R or vehicle, daily for 4 weeks in a blind fashion. Compared to vehicle, coadministration with IL-6 and sIL-6R potentiated grip strength, attenuated muscle contractures in the forelimbs, reduced denervation muscle atrophy and prevented degeneration of spinal motor neurons. Single administration with IL-6 or sIL-6R did not retard the symptomatic and neuropathological progression, although IL-6-treated mice did not raise anti-IL-6 antibodies. Treatment with IL-6 + sIL-6R, but not with IL-6 or sIL-6R alone delayed progression of wobbler mouse MND. Our results indicate that the neuroprotective mechanism for IL-6/sIL-6R on wobbler mouse MND differs from that of CNTF or LIF alone. We hypothesize that IL-6/sIL-6R complex may function on motor neurons through activation and homodimerization of gp130.

Inhibitory effect of oral administration of Monascus pigment on tumor promotion in two-stage carcinogenesis in mouse skin.

Monascus pigment was extracted from red malted rice, Monascus anka. It has been used as coloring matter for foodstuffs in Japan and certain Asian countries. Oral administration of Monascus pigment suppressed the tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in mice following initiation by 7,12-dimethylbenz[a]anthracene.

Inhibitory effect of rikkunshi-to, a traditional Chinese herbal prescription, on tumor promotion in two-stage carcinogenesis in mouse skin.

We report the inhibitory effect of topical application of extracts of a traditional Chinese herbal prescription on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. Methanol and water extracts obtained from 22 traditional Chinese herbal prescriptions were assayed and their inhibition ratios calculated. In general, the methanol extracts produced more effective inhibition than the water extracts. Of the various traditional Chinese herbal prescriptions, the methanol extract of Rikkunshi-to was more effective than other prescriptions as far as inhibition of TPA-induced inflammation was concerned. Hoelen, Glycyrrhizae Radix, Atractylodis Rhizoma, components of Rikkunshi-to markedly inhibited the inflammatory activity involved by TPA in mice. Furthermore, topical application of the methanol extract of Rikkunshi-to markedly inhibited TPA-induced tumor promotion in two-stage carcinogenesis in mouse skin.

Some lupane-type triterpenes inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

We have found that several lupane-type triterpenes, including lupeol, its acetate, betulin and betulinic acid, inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, and that betulinic acid inhibits tumor promotion in two-stage carcinogenesis in mice. Among seven lupane-type triterpenes assayed, these compounds inhibited the inflammatory activity induced by TPA in mice. The 50 % inhibitory dose of these compounds for TPA-induced inflammation was 0.4-4.0 µmol. Furthermore, topical application of lupeol, lupeol 3-acetate and betulin markedly suppressed the tumor-promoting effect of TPA (1 µg/mouse) in mouse skin initiated with 7,12-dimethyl-benz[a]anthracene (50 µg/mouse), at a grade corresponding to that of betulinic acid.

Five D:C-friedo-oleanane triterpenes from the seeds of Trichosanthes kirilowii Maxim. and their anti-inflammatory effects.

Five triterpenes with a D:C-friedo-oleanane skeleton, D:C-friedo-oleana-7,9(11)-diene-3 beta,29-diol (3-epikarounidiol), 7-oxo-D:C-friedo-olean-8-en-3 beta-ol (7-oxoisomultiflorenol), 7-oxo-8 beta-D:C-friedo-olean-9(11)-ene-3 alpha,29-diol, D:C-friedo-olean-8-ene-3 alpha,29-diol (3-epibryonolol), and D:C-friedo-olean-8-ene-3 beta,29-diol (bryonolol), the first four of which are new naturally occurring compounds, were isolated from the seeds of Trichosanthes kirilowii Maxim. The structures were determined by spectral and chemical methods. 3-Epikarounidiol, 7-oxoisomultiflorenol, and 3-epibryonolol showed marked inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation in mice. The 50% inhibitory dose of these triterpenes for TPA-induced inflammation (1 microgram) was 0.2-0.6 mg/ear.

Atractylodis Rhizoma extract and its component, atractylon, inhibit tumor promotion in mouse skin two-stage carcinogenesis.

The methanol extract of Atractylodis Rhizoma, a traditional Chinese medicine, was found to have antitumor-promoting activity in two-stage carcinogenesis. From the active fraction of the extract, atractylon was isolated. The isolated compound showed inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation in mice. Furthermore, atractylon markedly inhibited tumor promotion by TPA following 7,12-dimethylbenz[a]anthracene initiation in mice.