Mechanical properties, water sorption characteristics, and compound release of grape seed extract-incorporated resins.

OBJECTIVE: This study evaluated the effect of grape seed extract (GSE) incorporation on the mechanical properties, water sorption, solubility, and GSE release from the experimental adhesive resins. MATERIAL AND METHODS: An experimental comonomer mixture, consisting of 40% Bis-GMA, 30% Bis MP, 28% HEMA, 0.26% camphorquinone and 1% EDMAB, was used to prepare four GSE-incorporated adhesive resins at concentrations of 0.5, 1, 1.5, and 2 wt%. The neat resin without GSE was used as the control. Six resin beams (25 mm x 2 mm x 2 mm) per group were prepared for flexural strength and modulus of elasticity evaluations using a universal testing machine at a crosshead speed of 1 mm/min. Five disks (6 mm in diameter and 2 mm in thickness) per group were used for microhardness measurements using a Leitz micro-hardness tester with Leica Qgo software. Five disks (7 mm in diameter and 2 mm in thickness) per group were prepared and stored in deionized water for 28 days. Water sorption, solubility, and GSE release in deionized water were calculated for each GSE-incorporated adhesive at the end of 28th day. Data was evaluated using one-way ANOVA and Tukey multiple comparisons. RESULTS: Flexural strength, modulus of elasticity and microhardness of GSE-incorporated adhesive decreased significantly with incorporation of 1.5% of GSE (p<0.05). Addition of GSE had no effect on the water sorption of the adhesive resins (p=0.33). The solubility of the resin also increased significantly with incorporation of 1.5% of GSE (p<0.05). Quantities of GSE release increased with increased concentration of GSE in the adhesive resin. CONCLUSION: Up to 1% of GSE can be incorporated into a dental adhesive resin without interfering with the mechanical properties or solubility of the resins.

Mechanical properties, water sorption characteristics, and compound release of grape seed extract-incorporated resins

Abstract Objective This study evaluated the effect of grape seed extract (GSE) incorporation on the mechanical properties, water sorption, solubility, and GSE release from the experimental adhesive resins. Material and Methods An experimental comonomer mixture, consisting of 40% Bis-GMA, 30% Bis MP, 28% HEMA, 0.26% camphorquinone and 1% EDMAB, was used to prepare four GSE-incorporated adhesive resins at concentrations of 0.5, 1, 1.5, and 2 wt%. The neat resin without GSE was used as the control. Six resin beams (25 mm x 2 mm x 2 mm) per group were prepared for flexural strength and modulus of elasticity evaluations using a universal testing machine at a crosshead speed of 1 mm/min. Five disks (6 mm in diameter and 2 mm in thickness) per group were used for microhardness measurements using a Leitz micro-hardness tester with Leica Qgo software. Five disks (7 mm in diameter and 2 mm in thickness) per group were prepared and stored in deionized water for 28 days. Water sorption, solubility, and GSE release in deionized water were calculated for each GSE-incorporated adhesive at the end of 28th day. Data was evaluated using one-way ANOVA and Tukey multiple comparisons. Results Flexural strength, modulus of elasticity and microhardness of GSE-incorporated adhesive decreased significantly with incorporation of 1.5% of GSE (p<0.05). Addition of GSE had no effect on the water sorption of the adhesive resins (p=0.33). The solubility of the resin also increased significantly with incorporation of 1.5% of GSE (p<0.05). Quantities of GSE release increased with increased concentration of GSE in the adhesive resin. Conclusion Up to 1% of GSE can be incorporated into a dental adhesive resin without interfering with the mechanical properties or solubility of the resins.

Effect of resin and photoinitiator on color, translucency and color stability of conventional and low-shrinkage model composites.

OBJECTIVE: To study the effect of a low-shrinkage methacrylate monomer and monoacylphosphine oxide photoinitiator on color, translucency, and color stability of model resin-based composites (RBCs). METHODS: Four micro-hybrid RBCs were prepared containing barium-glass fillers in bisphenol A-glycidyl-methacrylate (BisGMA) and triethyleneglycol-dimethacrylate (TEGDMA) or urethane-based low-shrinkage monomer FIT-852 (FIT; Esstech Inc.) and TEGDMA matrix. Camphorquinone (CQ)/amine or Lucirin TPO were used as photoinitiators. Commercial low-shrinkage RBCs (Charisma Diamond, Heraeus Kulzer and N'Durance, Septodont) and conventional RBCs (Tetric EvoCeram, Ivoclar Vivadent and Filtek Z250, 3M ESPE) were used as controls. Color and translucency were measured using Thermo Scientific Evolution (Thermo Fisher Scientific) and SpectroShade™ Micro (MHT Optic Research) spectrophotometers. Color stability was evaluated after immersion in black tea (pure, with milk or lemon) and distilled water. Data were analyzed using analyses of variance with Tukey's post-test (α=0.05). RESULTS: Photoinitiators had no significant effect on baseline color. Initially whiter FIT-based RBCs showed greater staining in all staining solutions than BisGMA-based RBCs. TPO-containing RBCs showed better color stability than CQ-containing RBCs irrespective of the base monomer. Tea and tea with lemon induced greatest color changes. Adding milk to tea significantly reduced material staining. SIGNIFICANCE: Urethane-based low-shrinkage monomer FIT and conventional BisGMA affected color, translucency and color stability of their respective RBCs. Despite being used in posterior teeth, low-shrinkage RBCs are expected to have favorable optical and esthetic properties. Manufacturers are urged to provide information on optical properties of monomers and monomer mixtures in their low-shrinkage RBCs to allow understanding of interaction with fillers and photoinitiators.

First Isolation of Bicyclic Ditellurides from the Reaction of Camphor Hydrazone with Tellurium Tetrachloride.

Reaction of camphor hydrazone with TeCI4 under basic conditions gave an isomeric mixture of vinyl ditelluride and Wagner-Meerwein rearranged ditelluride. Initially formed tellurocamphor enolized and oxidized to give vinyl telluride, whereas tellurocamphor complexed with TeC4 to afford carbocation, which rearranged in a Wagner-Meerwein manner to afford the rearranged ditelluride. Photolysis of ditelluride in methyl methacrylate solution gave the radical polymerization product, PMMA, in which ditelluride acted as a radical initiator.

Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo.

Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we report anti-influenza activity of camphor derivative 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol (camphecene). In in vitro experiments it inhibited influenza viruses A(H1, H1pdm09, H3 and H5 subtypes) and B with EC50's lying in micromolar range. Due to low cytotoxicity it resulted in high selectivity indices (74-661 depending on the virus). This effect did not depend on susceptibility or resistance of the viruses to adamantane derivatives amantadine and rimantadine. The compound appeared the most effective when added at the early stages of viral life cycle (0-2h p.i.). In direct hemagglutinin inhibition tests camphecene was shown to decrease the activity of HA's of influenza viruses A and B. The activity of camphecene was further confirmed in experiments with influenza virus-infected mice, in which, being used orally by therapeutic schedule (once a day, days 1-5 p.i.) it decreased specific mortality of animals infected with both influenza A and B viruses (highest indices of protection 66.7% and 88.9%, respectively). Taken together, these results are encouraging for further development of camphecene-based drug(s) and for exploration of camphor derivatives as highly prospective group of potential antivirals.

Effect of proanthocyanidins and photo-initiators on photo-polymerization of a dental adhesive.

OBJECTIVES: To evaluate the effects of proanthocyanidins (PA) and photoinitiator type on the degree of conversion (DC) and polymerization rate (PR) of a model dental adhesive. METHODS: Three types of photo-initiation systems were introduced into the Bis-GMA/HEMA co-monomer mixture, resulting in four resin formulations including CQ/A (0.5wt% CQ and EDMAB), CQ/A/I-1 (0.5wt% CQ, EDMAB and DPIHP), CQ/A/I-2 (1.0wt% CQ, EDMAB and DPIHP), and TPO (2.1wt% TPO). For each resin formulation, adhesives containing 0%, 2.5%, 5% and 10% of PA with respect to the weight of resin were produced after mixing the resin with various amount of PA/ethanol solution. When light-cured, the RP and DC of each adhesive was determined using ATR-FTIR spectroscopy. RESULTS: Across and within the initiator groups, the DC followed the general trend of CQ/A2.5-PA>5-PA>10-PA, respectively. The change of PR with respect to photo-initiation systems and PA content was in a similar but less pronounced pattern. CONCLUSION: PA hampered the polymerization of all adhesives regardless of photoinitiators used. The initiator formulations CQ/A/I-2 and TPO are better fit for PA-containing adhesives, both leading to >65% DC in the presence of 5% PA. CLINICAL SIGNIFICANCE: The inclusion of PA in dental adhesives has been limited by its interference with the light-curing of adhesive resins. This study found photo-initiation formulations that could maintain a satisfactory degree of monomer conversion while a significant amount of PA is incorporated.

Anti-AIDS agents 87. New bio-isosteric dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-khellactone (DCK) analogues with potent anti-HIV activity.

Six 3'R,4'R-di-O-(S)-camphanoyl-2',2'-dimethyldihydropyrano[2,3-f]chromone (DCP) and two 3'R,4'R-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were designed, synthesized, and evaluated for inhibition of HIV-1(NL4-3) replication in TZM-bl cells. 2-Ethyl-2'-monomethyl-1'-oxa- and -1'-thia-DCP (5a, 6a), as well as 2-ethyl-1'-thia-DCP (7a) exhibited potent anti-HIV activity with EC(50) values of 30, 38 and 54 nM and therapeutic indexes of 152.6, 48.0 and 100.0, respectively, which were better than or comparable to those of the lead compound 2-ethyl-DCP in the same assay. 4-Methyl-1'-thia-DCK (8a) also showed significant inhibitory activity with an EC(50) of 128 nM and TI of 237.9.

Impact of 4-methylbenzylidene camphor, daidzein, and estrogen on intact and osteotomized bone in osteopenic rats.

The study investigated the influence of 4-methylbenzylidene camphor (4-MBC), daidzein, and estradiol-17ß-benzoate (E(2)) on either intact or osteotomized cancellous bone in ovariectomized (Ovx) rats. Three-month old Ovx rats were fed with soy-free (SF) diet over 8 weeks; thereafter, bilateral transverse metaphyseal osteotomy of tibia was performed and rats were divided into groups: rats fed with SF diet and SF diet supplemented with 4-MBC (200 mg), daidzein (50 mg), or E(2) (0.4 mg) per kilogram body weight. After 5 or 10 weeks, computed tomographical, biomechanical, histological, and ashing analyses were performed in lumbar spine and tibia of 12 rats from each group. 4-MBC and E(2) improved bone parameters in lumbar spine and tibia, were not favorable for osteotomy healing, and decreased serum osteocalcin level. However, daidzein improved bone parameters to a lesser extent and facilitated osteotomy healing. For lumbar spine, the bone mineral density was 338±9, 346±5, 361±6, and 360±5 mg/cm(3) in SF, daidzein, 4-MBC, and E(2), respectively, after 10 weeks. For tibia, the yield load was 98±5, 114±3, 90±2, and 52±4 N in SF, daidzein, 4-MBC, and E(2), respectively, after 10 weeks. Serum daidzein was 54±6 ng/ml in daidzein group and equol was not detected. Alp and Igf1 genes were down-regulated in callus after daidzein and E(2) compared with 4-MBC (week 5). The response of bone tissue and serum markers of bone metabolism could be ordered: daidzein<4-MBC

Impact of 4-methylbenzylidene-camphor (4-MBC) during embryonic and fetal development in the neuroendocrine regulation of testicular axis in prepubertal and peripubertal male rats.

4-Methylbenzylidene-camphor (4-MBC), an UV-B ray filter, belongs to the endocrine disrupters involved with alterations in the reproductive axis. Our target was to study the effect of 4-MBC on the neuroendocrine parameters that regulate reproduction in prepubertal and peripubertal male rats, which received this disrupter during embryonic and fetal development. 4-MBC was administered (sc) to female rats since pregnancy onset in doses of 20, 100 and 500 mg/kg/day. The litters were sacrificed at 15 or 30 days old to determine testicular weight, gonadotropin and prolactin serum levels and also GnRH and amino acids release from the hypothalamus. The exposure to 20 mg/kg/day only increased the LH serum levels in 30-day-old males. Doses of 100 and 500 mg/kg/day caused a decrease in testicular weight and in LH, GnRH and glutamate levels, in prepubertal rats (15-day-old specimens), and an increase in, gonadotropin (LH and FSH) con-centration and aspartate levels in peripubertal rats (30-day-old specimens), without changes in testicular weight. Prolactinaemia remained unaltered in all groups. Results obtained show that the administration of high doses of 4-MBC during embryonic and fetal stage inhibits the testicular axis in male rats during the prepubertal stage and stimulates it during peripubertad stage. On the other hand in the case of low doses no significant effects were observed.

Effect of daidzein, 4-methylbenzylidene camphor or estrogen on gastrocnemius muscle of osteoporotic rats undergoing tibia healing period.

The effect of daidzein (D), 4-methylbenzylidene camphor (4-MBC) or estradiol-17beta-benzoate (E(2)) on muscle of osteoporotic rats during fracture healing was studied. After performing a metaphyseal tibia osteotomy in 96 osteoporotic 5-month-old female Sprague-Dawley rats, they received daily 50 mg D, 200 mg 4-MBC or 0.4 mg E(2) per kg body weight, or soy free (SF) diet up to 36 and 72 days. Mitochondrial activity, fiber area, and capillary density were analyzed in M. gastrocnemius. Osseous callus bridging of fracture was observed in half of the rats after 36 days. By day 72, fracture was healed in most of the animals. State 3 mitochondrial respiration significantly enhanced in E(2), 4-MBC and D groups versus SF after 36 days (30, 32 and 32 vs 23 pmol O(2)/s per mg). It declined after 72 days, however, in E(2) group it was still at a higher level versus SF (25, 23 and 21 vs 20 pmol O(2)/s per mg). Size of fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers, capillary density did not differ significantly between the groups, however, at day 36 an increase in D and 4-MBC groups was detectable. FOG diameter was 64, 66, 68, and 58 microm and FG diameter was 88, 98, 95, and 89 microm in SF, D, 4-MBC, and E(2) groups. The ratio of capillaries to muscle fiber was 1.1, 1.4, 1.3, and 1.1 in SF, D, 4-MBC and E(2) groups by day 36. D and 4-MBC react similar to estrogen thereby improving oxidative cell metabolism in severe osteoporotic rats. The level of mitochondrial activity was higher, though no significant morphological differences could be shown.

Potential new antitumor agents from an innovative combination of camphorato, a ramification of traditional Chinese medicine, with a platinum moiety.

Eight new camphorato platinum complexes have been synthesized and evaluated for their in vitro cytotoxicity against HL-60 human leukemia, 3AO human ovarian carcinoma, BEL-7402 human hepatocarcinoma, and A549 human lung carcinoma cell lines. Most complexes showed good cytotoxic activity against the above-selected cell lines. Among the complexes, two compounds were assayed for their in vivo antitumor activity against LS-174T human colon carcinoma cells implanted in mice. One complex exhibited not only higher in vivo antitumor activity, but also less toxicity than oxaliplatin when it was administered intravenously at a dose of 6 mg/kg three times.

Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens.

4-Methylbenzylidene-camphor (4-MBC) is an organic sunscreen that protects against UV radiation and may therefore help in the prevention of skin cancer. Recent results on the estrogenicity of 4-MBC have raised concerns about a potential of 4-MBC to act as an endocrine disruptor. Here, we investigated the direct interaction of 4-MBC with estrogen receptor (ER) alpha and ERbeta in a series of studies including receptor binding, ER transactivation and functional tests in human and rat cells. 4-MBC induced alkaline phosphatase activity, a surrogate marker for estrogenic activity, in human endometrial Ishikawa cells. Interestingly, 4-MBC induced weakly ERalpha and with a higher potency ERbeta mediated transactivation in Ishikawa cells at doses more than 1 microM, but showed no distinct binding affinity to ERalpha or ERbeta. In addition, 4-MBC was an effective antagonist for ERalpha and ERbeta. In an attempt to put 4-MBC's estrogenic activity into perspective we compared binding affinity and potency to activate ER with phyto- and xenoestrogens. 4-MBC showed lower estrogenic potency than genistein, coumestrol, resveratrol, bisphenol A and also camphor. Analysis of a potential metabolic activation of 4-MBC that could account for 4-MBC's more distinct estrogenic effects observed in vivo revealed that no estrogenic metabolites of 4-MBC are formed in primary rat or human hepatocytes. In conclusion, we were able to show that 4-MBC is able to induce ERalpha and ERbeta activity. However, for a hazard assessment of 4-MBC's estrogenic effects, the very high doses of 4-MBC required to elicit the reported effects, its anti-estrogenic properties as well as its low estrogenic potency compared to phytoestrogens and camphor has to be taken into account.

Anti-AIDS agents part 41: synthesis and anti-HIV activity of 3',4'-di-o-(-)-camphanoyl-(+)-cis-khellactone (DCK) lactam analogues.

DCK lactam analogues were synthesized and evaluated for anti-HIV activity against HIV-1 replication in H9 lymphocyte cells. 4-Methyl-DCK lactam (11a) exhibited potent anti-HIV activity with EC50 and therapeutic index values of 0.00024 microM and 119,333, respectively.

Evaluation of the protective effect of sunscreens on in vitro reconstructed human skin exposed to UVB or UVA irradiation.

We have previously shown that skin reconstructed in vitro is a useful model to study the effects of UVB and UVA exposure. Wavelength-specific biological damage has been identified such as the formation of sunburn cells (SBC) and pyrimidine dimers after UVB irradiation and alterations of dermal fibroblasts after UVA exposure. These specific effects were selected to evaluate the protection afforded by two sunscreens after topical application on the skin surface. Simplified formulations having different absorption spectra but similar sun protection factors were used. One contained a classical UVB absorber, 2-ethylhexyl-p-methoxycinnamate. The other contained a broad-spectrum absorber called Mexoryl SX, characterized by its strong absorbing potency in the UVA range. Both filters were used at 5% in a simple water/oil vehicle. The evaluation of photoprotection on in vitro reconstructed skin revealed good efficiency for both preparations in preventing UVB-induced damage, as shown by SBC counting and pyrimidine dimer immunostaining. By contrast, only the Mexoryl SX-containing preparation was able to efficiently prevent UVA-specific damage such as dermal fibroblast disappearance. Our data further support the fact that skin reconstructed in vitro is a reliable system to evaluate the photoprotection provided by different sunscreens against specific UVB and UVA biological damage.