[Knobloch syndrome on multimodal imaging: a case report].

A 12-year-old boy presented to the hospital because of poor vision for half a year. Examination revealed nystagmus in both eyes. Examination of the anterior segment of both eyes showed no obvious abnormalities, and the vitreous bodies of both eyes were concentrated and agglutinated. Fundus showed clear boundary of optic disc, pale white, leopard striated retina, and characteristic atrophy of pigment epithelium, choroid, and macular atrophy. Knobloch syndrome was confirmed by multimodal imaging and genetic testing.

A crystal plasticity model for metal matrix composites considering thermal mismatch stress induced dislocations and twins.

Originated at heterogeneous interfaces with distinct coefficient of thermal expansion (CTE), thermal mismatch stress is one of the critical influential factors to mechanical properties of metal matrix composites (MMCs). This stress is normally accommodated plastically by various defects, for example, high-density dislocations and twins in Al near heterogeneous interfaces in SiC/Al composites. Basic knowledge on the influence of defect characteristics is important but difficult to extrapolate from experimental results. However, existed theoretical models more focus on the influence of dislocation density, but less focus on defects variety, volume and distribution. In this paper, we propose a physics-based crystal plasticity model that has the capability of dealing with thermal mismatch stress induced dislocations and twins (denoted as TMDT model). The proposed TMDT model that is implemented in the Visco-Plastic Self-Consistent (VPSC) method considers defect heterogeneous distribution (gradient range), defect type (dislocations vs. twins) and defect volume fraction (twin spacing vs. twin volume). We demonstrate the validity and the capability of the VPSC-TMDT model in SiC/Al composites with thermal mismatch induced dislocations or twins. Furthermore, this model predicts the ultra-high strength of Graphene/Copper composites with high-density nanoscale twins, which is in turn the future aim for such nanocomposites.

Distribution of enantiomers of trans-tramadol and trans-O-demethyltramadol in central nervous system of rats.

AIM: To investigate the distribution of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1), in the central nervous system (CNS). METHODS: After a single ip dose of trans-T hydrochloride or M1, the rats were killed by decapitation. A high performance capillary electrophoresis (HPCE) method was used to determine the concentrations of enantiomers of trans-T and M1 in the serum and different brain tissues, including cerebrospinal fluid (CF), cerebral cortex (CC), corpus striatum (CS), hypothalamus (HY), cerebellum (CE), and medulla oblongata (MO). RESULTS: After ip trans-T hydrochloride, the concentrations of (+)-trans-T were higher than those of (-)-trans-T in the serum and all tested brain tissues; The concentrations of (+)-M1 were lower than those of (-)-M1 in the all tested brain tissues; The concentrations of the enantiomers of trans-T and M1 were the highest in the CC, the lowest in the CF. After ip M1, the concentrations of (+)-M1 were higher than those of (-)-M1 in the serum and all tested brain tissues; The concentrations of the enantiomers of M1 were the highest in the CC, the lowest in the CF. CONCLUSION: The concentrations of the enantiomers of trans-T and M1 varied in the serum and different brain tissues. The distribution of trans-T and M1 in the CNS of rats was stereoselective. The stereoselectivity in the distribution of M1 after M1 injection was different with that after trans-T injection.

Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-O-demethyltramadol, in human subjects.

AIM: To study the stereoselectivity in pharmacokinetics of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1) in human subjects. METHODS: Trans-T hydrochloride sustained-release tablets were taken orally by 12 healthy male volunteers. After a multiple dosage schedule, the serum concentrations of (+)-trans-T, (-)-trans-T, (+)-M1, and (-)-M1 were determined in serum by high performance capillary electrophoresis (HPCE). RESULTS: (+)-Trans-T, (-)-trans-T, (+)-M1 and (-)-M1 in human serum were separated by HPCE. The linear range was 2.5-320 microg/L for the enantiomers of trans-T, and 2.5-50 microg/L for the enantiomers of M1. For the enantiomers of trans-T and M1, the intra-day and inter-day RSD were less than 15 % and 20 %, and the relative recoveries were 94.3 %-106.2 % and 90.4 %-107.8 %, respectively; the limit of quantitation was 1.25 microg/L. The serum concentrations of the enantiomers of trans-T reached a steady state in 12 subjects on d 4 after the initial administration. The steady state serum concentrations of (+)-trans-T were higher than that of (-)-trans-T at every sampling points in the subjects. The differences were significant in the main pharmacokinetic parameters between (+)-trans-T and (-)-trans-T except Tmax. The serum concentrations of (-)-M1 were higher than that of (+)-M1 in most subjects and at most sampling time points. There were significant differences in Cmax and Cmin between the enantiomers of M1. CONCLUSION: The pharmacokinetics of trans-T and M1 was found to be stereoselective. (+)-Trans-T was shown to be absorbed completely, but eliminated more slowly. The pharmacokinetic stereoselectivity of M1 was different among human subjects.

[Effect of stilbene polymer (Gn-3) on experimental liver injuries in mice].

AIM: To study the protective effect of Gn-3 (a stilbene polymer isolated from Gnetum parvifolium) against liver injury induced by CCl4, N-acetyl-p-aminophenol (APAP) and Bacillus Calmette-Guerin (BCG) plus bacterial lipopolysaccharide (LPS) in mice. METHODS: The experimental model of liver injury were induced by 0.1% CCl4 i.p. (10 mL.kg-1.d-1 for 3d), APAP i.p. (150 mg.kg-1) or BCG (5 mg) plus LPS (7.5 micrograms) in mice. The levels of ALT in serum, MDA and GSH in liver tissues were detected. The histopathologic changes were observed by light microscope. RESULTS: Gn-3 was shown to markedly reduce the elevated serum ALT levels, liver tissue MDA and improve the histopathological changes in all the three experimental liver injury models. No effect of Gn-3 was observed on the liver GSH level in liver injury mice. CONCLUSION: Gn-3 was found to inhibit the development of liver injury caused by CCl4, APAP, or BCG plus LPS. This means that Gn-3 has liver protective effects.

[Transportation of the enantiomers of trans tramadol and O-demethyltramadol across blood-brain barrier].

AIM: To investigate the transportation of the enantiomers of trans tramadol (trans T) and its active metabolite, O-demethyltramadol (M1) across blood-brain barrier. METHODS: Rats were sacrificed by femoral artery bleeding 1 h after i.p. administration of trans T hydrochloride, 16.7 mg.kg-1 or 50.0 mg.kg-1. Blood, cerebrospinal fluid and cerebral cortex were taken out. The enantiomers of trans T and M1 were analyzed by high performance capillary electrophoresis (HPCE). RESULTS: Among the three tissues, the concentration of each enantiomer of trans T and M1 was the highest in the cerebral cortex, and the lowest in the cerebrospinal fluid. In the serum, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of the enantiomers of M1 were similar. In the cerebrospinal fluid and cerebral cortex, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of (+)-M1 was lower than that of (-)-M1. CONCLUSION: The transportation across blood-brain barrier of the enantiomers of trans T and M1 was stereoselective. In the brain tissues, the concentrations of (+)-trans T and (-)-M1 were higher than those of their enantiomers.

[Effects of baicalin on liver microsomal cytochrome P450 system].

AIM: To investigate the effect of baicalin on liver microsomal cytochrome P450 system and the mechanism of liver protective action of baicalin. METHODS: Liver microsomal cytochrome P450, b5, aminopyrin N-demethylase (ADM), 7-ethoxycoumarin O-deethylase (ECD) and benzopyrene hydroxylase (AHH) activity were quantitated by UV chromatography. Activities of six cytochrome P450 isoforms were assayed with Western Blotting. RESULTS: Baicalin increased liver microsomal cytochrome. P450 level and ADM, ECD and AHH activity significantly. The three P450 isoforms, 1A1, 2B1 and 2C11, were also induced selectively by baicalin, but the b5 level, 3A2, 2D1 and 2E1 were not induced. CONCLUSION: Baicalin increases liver microsomal cytochrome P450 level and induces selectively 1A1, 2B1 and 2C11 of P450 isoforms in mice.

The induction of liver microsomal cytochrome P450 by Glycyrrhiza uralensis and glycyrrhetinic acid in mice.

The effect of Glycyrrhiza uralensis Fisch (GRZ) aqueous extract and one of its active principles Glycyrrhetinic acid (GRT) on hepatic cytochrome P450 in mice were investigated. Oral administration of GRZ at 10 g/kg/d or GRT at 50 mg/kg/d for 7 days was found to increase the P450 contents up to 4.6 fold compared with the controls. The activities of aryl hydrocarbon hydroxylase (AHH, 3.1 and 3.3 fold), aminopyrine N-demethylase (ADM, 4.2 and 3.2 folds), and 7-ethoxycumarin O-deethylase (ECOD, 2.8 and 2.5 fold) were also shown to be increased. Western blot analysis showed that the subtypes of P450 isoforms induced selectively by GRZ and GRT included CYP1A1 (1.8 and 1.5 fold over that of the control, respectively), CYP2B1 (both 1.3 fold), and CYP2C11 (3.2 and 3.0 fold). Moreover, significant positive correlation between the P450 content or the isoforms and the corresponding enzyme activities mentioned above was observed.

[Determination of acemetacin and indometacin in human serum by high performance liquid chromatography].

A method of HPLC for the quantitative determination of acemetacin and indometacin in human serum is described. After being extracted with diethyl ether, acemetacin and indometacin were analyzed by reversed-phase HPLC(Spherisorb-C8) and UV-detector(254 nm), with tolbutamide as internal standard. The mobile phase was a mixture of V(acetate buffer solution, pH 4.6):V(methyl alcohol):V(acetonitrile) = 55:5:40 and at a rate of 1.0 mL/min. Over the mass concentration range of 12.5 micrograms/L-1.6 mg/L, both the calibration curves were linear, r = 0.9996, n = 8. The average recoveries of acemetacin and indometacin were 77.2% and 86.7% respectively. The within-day and between-day RSD of acemetacin and indometacin were less than 5% and 10% respectively.

Characterization of NMDA- and AMPA-induced enhancement of AP-1 DNA binding activity in rat cerebellar granule cells.

Effects of the glutamate receptor agonists, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), on the activator protein-1 (AP-1) DNA binding activity were studied in primary cultures of rat cerebellar granule cells. Application of NMDA as well as of AMPA produced a concentration-dependent enhancement of AP-1 binding. Further examination revealed that only a brief exposure (10 min) to NMDA or AMPA was required for the initiation of a significant, four- to sixfold enhancement of AP-1 DNA binding activity. Blockade of the desensitization of AMPA receptors by cyclothiazide further reduced the exposure time needed to activate the AP-1 complex. The time needed to achieve a maximal increase of AP-1 binding activity varied depending on the glutamate receptor agonist used. NMDA gave maximal AP-1 stimulation after 60 min exposure, whereas stimulation with AMPA alone reached a maximum after 240 min exposure. When AMPA was applied together with cyclothiazide the maximal enhancement of AP-1 binding was reached much faster, within 120 min. Supershift analysis with specific antibodies against the members of Fos and Jun protein families (c-Fos, Fos B, c-Jun, Jun B, Jun D) revealed that the NMDA-induced AP-1 complex was composed predominantly of Jun D and c-Fos. The composition of the AP-1 complex activated by AMPA alone was similar to that produced by NMDA, but with an additional contribution of Fos B. In contrast, application of AMPA plus cyclothiazide induced an AP-1 transcription with contribution of Jun D, c-Fos, Fos B, c-Jun and Jun B proteins. These findings indicate that glutamate is able to enhance AP-1 DNA binding activity in cerebellar granule cells through both NMDA and AMPA glutamate receptors.

Chronic ethanol enhances NMDA-induced AP-1 activity in cultured rat cerebellar granule cells.

We examined the effects of chronic ethanol exposure (50 mM; 3 days) on N-methyl-D-aspartate (NMDA)- and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induced AP-1 transcription factor DNA binding activity in primary cultures of rat cerebellar granule cells. Chronic ethanol exposure enhanced NMDA-stimulated AP-1 binding activity, with no corresponding change in AMPA-stimulated AP-1 binding. Supershift analysis with specific antibodies against the members of Fos and Jun protein families showed that the NMDA-induced AP-1 protein complex consisted predominantly of c-Fos and Jun D proteins. Chronic ethanol treatment by itself did not change the protein composition of the AP-1 complex.

N-Methyl-D-aspartate-induced enhancement of activator protein-1 DNA binding activity is blocked by ethanol in cerebellar granule cells.

The effects of ethanol on N-methyl-D-aspartate (NMDA) and non-NMDA receptor agonist-stimulated activator protein-1 (AP-1) DNA binding activity in primary cultures of rat cerebellar granule cells were investigated. The application of intoxicating concentrations of ethanol produced a concentration-dependent inhibition of NMDA-enhanced AP-1 binding with a significant reduction obtained at 50 mM ethanol. The inhibitory actions of ethanol on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-stimulated AP-1 binding were considerably weaker as compared to the effects seen following administration of NMDA. The AMPA-induced enhancement of AP-1 DNA binding activity was demonstrated both in the absence and presence of cyclothiazide, a drug, which is known to block the desensitization of AMPA receptors. Our data suggest that moderate concentrations of ethanol modulate glutamate-induced alterations of gene expression in brain neurons.

A mu-receptor opioid agonist induces AP-1 and NF-kappa B transcription factor activity in primary cultures of rat cortical neurons.

Activator protein 1 (AP-1) and nuclear factor kappa B (NF-kappa B) represent mammalian transcription factors which bind to distinct enhancer motifs. The specific mu-receptor opioid agonist, Tyr, D-Ala2, Gly, N-Me-Phe4, Gly-ol5 (DAMGO), was found to increase AP-1 and NF-kappa B activity in primary cultures of neurons from rat cerebral cortex. Acute (2 h, 4 h) and long-term (72 h) treatment with DAMGO time-dependently increased the DNA-binding activity of both AP-1 and NF-kappa B and the stimulation could be abolished or inhibited by concurrent incubation with naloxone. However, acute naloxone-precipitated withdrawal did not significantly change AP-1 or NF-kappa B activity. These results indicate a mu-opioid receptor-related co-induction of AP-1 and NF-kappa B transcription factors in cultured cortical neurons.