GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in the Fmr1 Knockout Mouse Model of Fragile X Syndrome.

Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some individuals with FXS but has become unavailable after unsuccessful clinical trials, prompting interest in publicly available, racemic baclofen. The present study investigated whether racemic baclofen can remediate abnormalities of neural circuit function, sensory processing, and behavior in Fmr1 knockout mice, a rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline and auditory-evoked high-frequency gamma (30-80 Hz) power relative to C57BL/6 controls, as measured by electroencephalography. These deficits were accompanied by decreased T maze spontaneous alternation, decreased social interactions, and increased open field center time, suggestive of diminished working memory, sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked gamma oscillations, working memory, and anxiety-related behavior were normalized by treatment with baclofen, but impaired sociability was not. Improvements in working memory were evident predominantly in mice whose auditory-evoked gamma oscillations were dampened by baclofen. These findings suggest that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome.

Biostability of the Proanthocyanidins-Dentin Complex and Adhesion Studies.

Oligomeric proanthocyanidins (OPACs) are potent and renewable natural bioactives possible to be refined into chemically standardized mixtures for biological applications. Herein, we found that multiscale interactions of OPACs with the dentin matrix create tight biointerfaces with hydrophobic methacrylate adhesives on wet surfaces. An enriched mixture of OPACs, with a known phytochemical profile, was produced from grape seed crude extract ( Vitis vinifera; enriched grape seed extract [e-GSE]) and applied to dentin matrices to determine changes to the mechanical properties and biodegradability of the dentin matrix and favorable resin adhesion mechanisms. Methods included a 3-point flexural test, quantification of hydroxyproline (collagen solubilization), static and dynamic nanomechanical analyses, resin-dentin microtensile bond strength, and micropermeability at the adhesive interface. The e-GSE-modified dentin matrix exhibited remarkably low collagen solubilization and sustained the bulk elastic properties over 12 mo. Tan δ findings reveal a more elastic-like behavior of the e-GSE-modified dentin matrix, which was not affected by H-bond destabilization by urea. Dentin-methacrylate biointerfaces with robust and stable adhesion were created on e-GSE-primed dentin surfaces, leading to a dramatic decrease of the interfacial permeability. Standardized OPAC mixtures provide a new mechanism of adhesion to type I collagen-rich tissues that does not rely on hydrophilic monomers. The bioadhesion mechanism involves physicochemical modifications to the dentin matrix, reduced tissue biodegradation, and bridging to methacrylate resins.

Kinetics of microbial hydrogenation of free linoleic acid to conjugated linoleic acids.

AIMS: To investigate the ability of selected probiotic bacterial strains to produce conjugated linoleic acid (CLA) and also to estimate the biohydrogenation kinetics of Lactobacillus acidophilus on the production of CLA from free linoleic acid (LA). METHODS AND RESULTS: Six probiotic bacteria, Lact. paracasei, Lact. rhamnosus GG, Lact. acidophilus ADH, and Bifidobacterium longum B6, Lact. brevis, and Lact. casei, were used to examine their ability to convert LA to CLA. LA tolerance was evaluated by addition of different LA concentrations in MRS broth. Lact. acidophilus showed the major tolerant to LA and the greatest CLA-producing ability (36-48 microg ml(-1) of CLA). The rate-controlling steps were k(2) and k(1) for the addition of 1 and 3 mg ml(-1) of LA, respectively. The percentage of CLA conversion was higher in MRS broth supplemented with 1 mg ml(-1) (65%) than 3 mg ml(-1) (26%). CONCLUSION: The results provide useful information and new approach for understanding the biohydrogenation mechanisms of CLA production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study would help elucidate the pathway from LA to stearic acid (SA), known as biohydrogenation. In addition, the use of selected probiotic bacteria might lead to a significant improvement in food safety.

Reduction of prolonged bilateral temporomandibular joint dislocation by midline mandibulotomy.

Various surgical procedures have been used to reduce prolonged bilateral dislocation of the temporomandibular joint, but with some complications. A prolonged bilateral dislocation of the mandibular condyle was simply reduced by a midline mandibulotomy without any complications. One year postoperatively, joint function was unimpeded and there was no recurrence of condylar dislocation.

Relationships of urinary phyto-oestrogen excretion to BMD in postmenopausal women.

OBJECTIVE: Phyto-oestrogens are plant compounds with both oestrogenic and anti-oestrogenic properties. However, it is not known whether natural phyto-oestrogens are beneficial or harmful in human osteoporosis. This study was performed to investigate the relationships between urinary phyto-oestrogens and bone mineral density (BMD) in Korean postmenopausal women. DESIGN: The subjects were classified into osteoporotic, osteopenic and normal groups according to their BMD as defined by WHO criteria. We compared the urinary phyto-oestrogens of each group and studied whether urinary phyto-oestrogens correlate with BMD. PATIENTS: The subjects were 75 Korean postmenopausal women with ages ranging from 52 to 65 years (mean 58 +/- 1.1 years). Mean number of years after menopause was 7.3 +/- 1.3. MEASUREMENTS: Twenty-four-hour urinary phyto-oestrogens were measured by gas chromatography-mass spectrometry (GCMS) and BMD by dual-energy X-ray absorptiometry (DXA, Lunar Expert-XL, Lunar Co., WI, USA). RESULTS: In Korean postmenopausal women, urinary enterolactone (1.46 +/- 1.11 micromol/day) was lower and daidzein (2.59 +/- 3.25 micromol/day) was higher than in western women, and both levels were comparable to those in Japanese women. Daily urinary excretion of genistein and apigenin were 1.09 +/- 0.912 and 0.48 +/- 0.40 micromol/day, respectively. In subjects with osteoporosis, urinary enterolactone was lower (P < 0.05) but apigenin was significantly higher (P < 0.05) than in the controls. BMD of L2-L4 correlated positively with urinary enterolactone (r = 0.388, P < 0.01), and BMD of the femoral neck and Ward's triangle correlated positively with urinary enterolactone (r = 0.271, P < 0.05 and r = 0.322, P < 0.05) but negatively with apigenin (r = -0.412, P < 0.01 and r = -0.395, P < 0.01). By multiple stepwise regression, the variables associated with spinal BMD were age, the amount of urinary apigenin and body mass index (BMI). The variables associated with femoral neck BMD were age and urinary apigenin. CONCLUSIONS: From these results, we conclude that urinary phyto-oestrogens, especially enterolactone and apigenin, are related to BMD in Korean postmenopausal women. Our results also suggest the possibility that phyto-oestrogens have differential effects on bone density. Further studies are needed to clarify the exact biological roles of phyto-oestrogenic components on bone metabolism.

Inhibition of chitin synthase II by catechins from stem bark of Taxus cuspidata.

Two flavonoids, (+/-)-catechin and (-)-epicatechin, were isolated from the stem bark of Taxus cuspidata by monitoring chitin synthase II inhibitory activity. The compounds inhibit chitin synthase II with an IC50 of 15 and 29 micrograms/ml, respectively and appear to be selective for chitin synthase II. They did not inhibit chitin synthase III.

Expressed sequence tags of fruits, peels, and carpels and analysis of mRNA expression levels of the tagged cDNAs of fruits from the Fuji apple.

In order to understand molecular events during fruit development and provide genetic resources for molecular breeding, 430 expressed sequence tags (ESTs) were generated from randomly selected clones of cDNA libraries prepared from young fruits, peels of mature fruits, and carpels of the Fuji apple (Malus domestica Borkh.). Database comparisons of the ESTs revealed that 180 non-redundant clones showed a high similarity with previously identified genes. Among these, 138 clones exhibited a homology with previously identified plant genes and 12 were identical to genes that were previously identified from apples. The deduced amino acid sequences of 42 clones had a homology to proteins that have not been reported from plants. Eighteen cDNA clones from the young fruit library were selected for studying expression levels and patterns in reproductive organs and leaves. This study revealed that the clones can be classified into 3 different groups based on their expression levels. The first 9 clones were expressed strongly in at least one reproductive organ. Eight of these clones (vacuolar processing protease, sucrose phosphate synthase, arabinogalactan protein, UDP-glucose glucosyl transferase, major allergen D1, cystein proteinase inhibitor, lipoxygenase, and protease subunit SUG2) were highly expressed in mature flowers and young fruits, whereas one clone (z-carotene desaturase protein precursor) was preferentially expressed in mature flowers but weakly in young fruits. The second group includes 6 cDNA clones (glucose transport protein, aminomethyl transferase precursor protein, dTDP-D-glucose-4,6-dehydrogenase, 2 types of protein kinase, and selenium binding protein) that were weakly expressed. These clones were characterized by their preferential expression patterns in mature flowers and young fruits. The transcripts of 3 cDNA clones in the third group (vacuolar aminopetidase, beta-galactosidase, and EREBP-4) were detectable only by RT-PCR and they were preferentially expressed in young fruits. These results indicate that most ESTs that were isolated from young fruits are preferentially expressed in reproductive organs and thereby play important roles during reproductive organ development.

Polyacetylene analogs, isolated from hairy roots of Panax ginseng, inhibit Acyl-CoA : cholesterol acyltransferase.

In the course of our screening program for acyl-CoA : cholesterol acyltransferase (ACAT) inhibitors from Korean herbal medicines, ACAT inhibitors were isolated from the hairy roots of Panax ginseng (Araliaceae) and identified as panaxynol, panaxydol, panaxydiol, and panaxytriol. These active compounds inhibit rat liver ACAT with IC50 values of 94, 80, 45 and 79 microM, respectively.

2'-Hydroxycinnamaldehyde from stem bark of Cinnamomum cassia.

2'-Hydroxycinnamaldehyde, which inhibits farnesyl-protein transferase (FPTase), has been isolated from the stem bark of Cinnamomum cassia Blume. The biologically active agent in the extract has been purified by silica column chromatography and HPLC. The structure of the isolated compound was elucidated on the basis of 500 MHz NMR experiments.

Isolation of cholesteryl ester transfer protein inhibitors from Panax ginseng roots.

We have isolated cholesteryl ester transfer protein (CETP) inhibitors from the extract of Korean Panax ginseng C. A. Meyer roots and identified them as polyacetylene analogs. These compounds inhibit human CETP with IC50 values of around 20-35 mg/ml.

Carcinogenicity tests of certain environmental and industrial chemicals.

Fourteen chemicals of varied uses were tested for carcinogenicity by oral administration in male and female Charles River CD rats. Under the conditions of the tests, propane sultone, propylene imine, and ethylenethiourea, in addition to the positive control N-2-fluorenylacetamide, were carcinogenic. Avadex, bis(2-chloroethyl) ether, the potassium salt of bis(2-hydroxyethyl) dithiocarbamic acid, ethylene carbonate, and semicarbazide hydrochloride were not carcinogenic under the test conditions. Dithiooxamide, glycerol alpha-monochlorohydrin, and thiosemicarbazide gave somewhat ambiguous results, though administered at high enough dose levels to be toxic. An inadequate number of animals survived treatments with sodium azide, sodium bisulfide, and vinylene carbonate, or the animals may not have received sufficiently high doses of the test chemicals to provide maximum test sensitivity. However, there were no indications that these three chemicals were carcinogenic under the test conditions.