Biomedical subjects

Yan Li

Publications and source records attributed to Yan Li.

At least 343 records · Page 19Linked to original sources

PubMed2005

Serum-free derivation of human embryonic stem cell lines on human placental fibroblast feeders.

OBJECTIVE: To derive new human embryonic stem cell (hESC) lines on pathogen-free human placental fibroblast feeders under serum-free conditions. Because the embryo develops in close contact with extraembryonic membranes, we hypothesized that placental mesenchyme might replicate the stem cell niche in situ. DESIGN: We isolated and characterized human placental fibroblast lines from individual donors and tested their ability to support growth of federally registered hESC lines. Moreover, we performed extensive pathogen testing to ensure their suitability as feeders for the derivation of therapy-grade hESCs. RESULT(S): Human placental fibroblasts were comparable or superior to mouse embryo fibroblasts as hESC feeders. We used these qualified placental fibroblasts to derive two new hESC lines in knockout Dulbecco's modified Eagle's medium with serum-free 20% knockout serum replacement. The cells, which had a normal karyotype, were grown for more than 25 passages, expressed markers of stemness including Oct-3/4, Tra 1-60, Tra 1-80, and SSEA-4, exhibited high telomerase activity, and differentiated in vitro and in vivo into cells derived from all three germ layers, confirming their pluripotency. Additionally, newly derived hESCs were adapted to growth on a human placental laminin substrate in a defined medium. CONCLUSION(S): To our knowledge, this is the first report of hESC derivation in the absence of serum on qualified pathogen-free human feeders.

Cell Differentiation↗

PubMed2005

Esophageal injury with external esophageal perfusion.

BACKGROUND: External esophageal perfusion (EEP) with the idea that esophageal perfusion can be controlled with a single ingredient at a constant rate and concentration, might be used to dissect the injurious role of gastro-duodenal secretions for the progression from esophagitis to Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). This study is to evaluate the EEP rat model for esophagitis induced by using a micro-osmotic pump with bile perfusion. METHODS: Eighteen adult rats underwent the EEP procedure. Bile (0.5% bovine bile, pH 7.4) was used as perfusion agent and three types of perfusions were performed: 1 week perfusion, 2 weeks perfusion, and 4 weeks perfusion compared to saline perfusion and sham operation. Histological changes, cell proliferation, apoptosis, 8-hydroxy-deoxyguanosine (8-OH-dG) and Manganese superoxide dismutase (MnSOD) were observed after perfusion and compared. RESULTS: The bile perfusion for 1 week, 2 weeks, and 4 weeks induced mucosa infiltration of inflammatory cells, basal cell hyperproliferation, and papillae hypertrophy in all animals. Histopathology and cellular changes consistent with the findings associated with reflux esophagitis. The apoptotic index, the proliferating index, and expression of 8-OH-dG were significantly increased in the esophageal mucosa compared to controls. MnSOD expression was decreased with bile perfusion compared to saline controls. CONCLUSIONS: The external esophageal perfusion model enabled precise control of the injurious agent. It induced the typical histological injury and cellular changes seen in severe reflux esophagitis. The cellular changes in apoptosis, proliferation and anti-oxidant defense make this model unique for reflux esophagitis studies. Further studies are needed to induce Barrett's esophagus and esophageal adenocarcinoma.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

No association between the C-1562T polymorphism in the promoter of matrix metalloproteinase-9 gene and non-small cell lung carcinoma.

The matrix metalloproteinases (MMPs) are a family of highly conserved metal-dependent proteolytic enzymes, their main function is to degrade different components of extracellular matrix (ECM). Moreover, they play roles in regulation of cell growth, apoptosis, angiogenesis and immune surveillance. Natural sequence variations in the MMP genes may result in differential expression of MMPs in different individuals and therefore may be associated with the development and progression of diseases. The aim of this study is to assess the effects of the C-1562T polymorphism in the MMP-9 promoter on the risk of occurrence and lymphatic metastasis of non-small cell lung carcinoma (NSCLC). The MMP-9 genotyping was performed in 243 pathologically diagnosed NSCLC patients and 350 healthy controls without overt cancer by using polymerase chain reaction-restriction fragment length polymorphism analysis. The distribution of the MMP-9 genotypes in NSCLC patients and healthy controls was in consistent with Hardy-Weinberg equilibrium. The frequency of the C/C, C/T and T/T genotypes in healthy controls was 79.4, 20.6 and 0%, respectively. Neither the overall genotype nor allelotype distribution in NSCLC patients showed significant difference from that in healthy controls (P=0.21 and 0.43, respectively). Compared with the C/C genotype, genotypes with the T allele did not show significant influence on the risk of NSCLC development (age and gender adjusted OR=1.13, 95% CI=0.76-1.68). Stratification by onset age, smoking status and tumor histological type also showed no association between the MMP-9 polymorphism and the risk of NSCLC. Furthermore, the genotype distribution between NSCLC patients with and without lymphatic metastasis was not significantly different. Therefore, the present study suggests that the MMP-9 C-1562T polymorphism may not be used as a useful marker to predicate susceptibility and lymphatic metastasis in NSCLC.

Adenocarcinoma↗

PubMed2005

Anterior chamber width measurement by high-speed optical coherence tomography.

OBJECTIVE: To measure anterior chamber (AC) width and other dimensions relevant to the sizing of phakic intraocular lenses (IOLs) with a high-speed optical coherence tomography (OCT) system. DESIGN: Cross-sectional observational study. PARTICIPANTS: Both eyes of 20 normal volunteers. METHODS: A novel high-speed (4000 axial scans/second) OCT prototype was developed for anterior segment scanning. The system uses long wavelength (1310 nm) for deeper angle penetration, rectangular scanning for undistorted imaging, and short image acquisition time (0.125 seconds) to reduce motion error. Three horizontal cross-sectional OCT images (15.5 mm wide and 6 mm deep) of the anterior segment were obtained from each eye with real-time image display to guide centration on the corneal apex. Image processing software was developed to correct for image warping resulting from index transitions. Anterior chamber dimensions were measured using computer calipers by 3 expert raters (ophthalmologists). Analysis of variance was used to determine interrater, interimage, right versus left eye, and intersubject standard deviation (SD) of OCT measurements. MAIN OUTCOME MEASURES: Anterior chamber width (recess to recess), AC depth, and crystalline lens vault as measured by OCT; external white-to-white (WTW) corneal diameter (CD) as measured by Holladay-Godwin gauge. RESULTS: The mean AC width was 12.53+/-0.47 mm (intereye SD), and the mean corneal diameter was 11.78+/-0.57 mm. Optical coherence tomography measurement of AC width has good repeatability from image to image (SD, 0.134 mm), but there was significant difference between raters (SD, 0.215 mm). Estimation of AC width from WTW CD by linear regression was relatively inaccurate (residual SD, 0.41 mm). The mean AC depth was 2.99+/-0.323 mm (intereye SD), with repeatability of less than 0.001 mm (interimage SD), and the mean crystalline lens vault was 0.39+/-0.27 mm with 0.023 mm repeatability. CONCLUSIONS: Reproducible OCT AC biometry was demonstrated using a high-speed OCT prototype. Further improvement in reproducibility may be achieved by automating the measurements with a computer. Direct OCT AC width measurement may improve sizing of angle-supported AC IOLs over conventional estimation by WTW CD. The measurement of AC depth and lens vault also may be useful for other types of phakic AC IOLs.

Adult↗

PubMed2005

Cardiac metallothionein synthesis in streptozotocin-induced diabetic mice, and its protection against diabetes-induced cardiac injury.

Oxidative stress is involved in the pathogenesis of diabetes and its cardiovascular complications. Metallothionein (MT), a stress-response protein, is significantly increased in the liver and kidney of diabetic animals. We examined whether diabetes also induces cardiac MT synthesis through oxidative damage and whether MT overexpression protects the heart from injury. Diabetes was induced in mice by single injection of streptozotocin (STZ), and cardiac MT mRNA and protein levels were measured 2 weeks and 2 months after STZ treatment. Diabetes significantly increased cardiac MT synthesis 2 weeks and 2 months after STZ treatment, with no change in cardiac metals including zinc, copper, and iron. Serum and cardiac vasopeptide endothelin and inflammatory cytokine tumor necrosis factor-alpha were also significantly increased in diabetic hearts, as were the ratio of oxidized to reduced glutathione and the immunohistochemical staining of 3-nitrotyrosine and 4-hydroxynonenal. To explore the biological importance of increased MT synthesis in the heart, MT-overexpressing transgenic mice were treated with STZ and then examined 2 months later. A loss of inotropic reserve, uncovered during beta-adrenergic stimulation, and the presence of cardiac fibrosis, shown by increased Sirius red staining of collagen, were evident in the wild-type diabetic mice but not in the MT-overexpressing transgenic diabetic mice. These results suggest that diabetes-induced cardiac MT expression likely associates with systemic increases in endothelin-1 and tumor necrosis factor-alpha and the resulting cardiac oxidative stress. Overexpressing cardiac MT significantly protects the heart from diabetes-induced injury.

Aldehydes↗

PubMed2005

Immunohistochemical analysis of the expression of FATE/BJ-HCC-2 antigen in normal and malignant tissues.

FATE/BJ-HCC-2 is a newly identified cancer/testis (CT) antigen, which was detected in tumor tissues and testis. As previous studies of FATE/BJ-HCC-2 expression pattern were mainly based on messenger RNA (mRNA) analysis, it is necessary to investigate its actual protein expression pattern in tumor tissues for the evaluation of its application value. In this study, we produced specific polyclonal antibody (pAb) to the recombinant FATE/BJ-HCC-2 protein and analyzed the FATE/BJ-HCC-2 antigen expression in normal and malignant tissues by the immunohistochemical approach. The results showed that there was no detectable FATE/BJ-HCC-2 antigen expressed in normal tissues except testis. In hepatocellular carcinoma (HCC) tissues, the FATE/BJ-HCC-2 antigen was detected in 20% (7/35) specimens. All samples that expressed the FATE/BJ-HCC-2 antigen were of poorly or moderately differentiated HCC. The stained antigen was located in the cytoplasm and the staining pattern showed heterogeneity from focal to more than 40% of the tumor cells. The FATE/BJ-HCC-2 antigen was also expressed in other tumor tissues. The results of [3H]thymidine incorporation showed that FATE/BJ-HCC-2 protein enhanced tumor cell proliferation after transfection of FATE/BJ-HCC-2 gene in HCC cell line (P<0.01). This effect could be specifically blocked by anti-FATE/BJ-HCC-2 pAb. Serological screening showed that the antibody specific to the FATE/BJ-HCC-2 antigen was detected in 7.7% (4/52) patients. Notably, the four positive patients bore poorly or moderately differentiated HCC. FATE/BJ-HCC-2 mRNA transcript was detected in the peripheral blood mononuclear cells (PBMCs) of 46.67% patients whose resected HCC tissue samples were positive for FATE/BJ-HCC-2 mRNA, which implicated tumor cell dissemination in blood circulation and may relate to the metastasis of HCC. Thus, FATE/BJ-HCC-2 may be a valuable candidate CT antigen for polyvalent vaccines in tumor immunotherapy and an assisting diagnostic marker for prognosis of the disease.

Animals↗

PubMed2005

Path concentration distribution of toluene using remote sensing FTIR and one-dimensional reconstruction method.

A one-dimensional mapping technique coupled with Open-Path remote sensing FTIR was presented in this article. This technique was applied to one of the air toxic volatile organic compounds (VOCs)-toluene. The Path Integrated Concentrations (PICs) of toluene in different path lengths along one beam path were fitted by polynomial fitting method with degrees from 3 to 7. The 6th degree polynomial fitting showed the best fitting result. Moreover, the methods of reconstructing path concentration distribution along the beam path by applying a Gaussian model and the derivative of 6th degree polynomial fitting function were established in this article. The reconstructed concentrations of toluene along the beam path by the two methods were experimentally close. Results showed that the concentration peaks were at 1.05 and 2.40 m from the instrument by applying the Gaussian model with the maximum concentration of 0.85 and 3.19 ppm, and at 0.99 and 2.49 m from the instrument with the maximum concentration of 0.78 and 2.80 ppm by applying the 6th polynomial fitting function. It was obvious that the reconstruction results by these two methods were very close. This approach could be appreciated for its fast calculation, exact peak location orientation and concentration flow tendency mapping. In can be concluded that this method can provide the path concentration distributions of much more releasing gases in a briefly and intuitionistic way. The remote sensing FTIR coupled with these mathematical reconstruction techniques can be applied to the real world environmental and industrial hygiene monitoring, thus works as an alert system for the VOCs pollution.

Air Pollutants↗

PubMed2005

Reconstruction of air contaminant concentration distribution in a two-dimensional plane by computed tomography and remote sensing FTIR spectroscopy.

This research combined open path FTIR (OP-FTIR) technique and computed tomography (CT) to reconstruct air contaminant concentration distribution in a two-dimensional plane. Remote sensing FTIR instrument was used to scan radial beam geometry and obtain path integrated concentration (PIC) data of acetone gas in the measuring plane. Smooth basis function minimization (SBFM) algorithm was adopted to reconstruct gaseous concentration distribution. For the purpose of finding out the preferable number of Gaussians used in SBFM algorithm, single-Gaussian, double-Gaussian, and three-Gaussian models were used respectively. Experimental results showed that the reconstruction result of acetone concentration distribution by SBFM algorithm with double-Gaussian model agreed with real distribution more qualitatively and quantitatively than single-Gaussian and three-Gaussian. Also, it has been proved that simulated annealing algorithm used in the optimization process of SBFM reconstruction was feasible and effective. Although computed tomography and remote sensing FTIR technique (CT-RS-FTIR) is still at the laboratory study stage, with further improvement of SBFM algorithm and beam geometry, it promises to be used in air pollution monitoring widely.

Acetone↗

PubMed2005

Orthogonal signal correction used for noise elimination of open path Fourier transform infrared spectra.

Open path Fourier transform infrared (OP-FTIR) spectroscopy is qualified in detecting mixtures by multivariate calibration methods such as partial least squares (PLS); however, its applications are still restricted by background noise, which is unavoidable for OP-FTIR spectra and cannot be resolved solely by multivariate calibration methods. Hence OP-FTIR spectra are often pretreated before the data are subjected to the multivariate calibration model. A new preprocessing technique, orthogonal signal correction (OSC), was presented in this paper. The principle of OSC is to remove the part in X orthogonal to Y, and it is implemented based on PLS and nonlinear iterative partial least squares (NIPALS) algorithm. The approach was applied to three different data sets of PLS model. It performed much better than classical PLS when handling data with noise but comparably when processing on the simulated data. Moreover, OSC could reduce the complexity of model, which would facilitate the interpretation of the models. The results reveal that the proposed method gives much better prediction than the classical PLS and is very promising for the wide use of OP-FTIR. The preprocessing technique, auto-scaling, and second-order derivatives (SOD) were also considered.

Air Pollutants↗

PubMed2005

The effect of adult day care services on time to nursing home placement in older adults with Alzheimer's disease.

PURPOSE: This longitudinal study examined whether the use of adult day care services delayed time to nursing home placement in persons with Alzheimer's disease. DESIGN AND METHODS: Two hundred and eighteen adult day care clients with Alzheimer's disease were recruited from 16 adult day programs in a large metropolitan area. Two hundred and ninety eight persons with Alzheimer's disease but not using adult day care were recruited from a federally funded Alzheimer's diagnostic center and frequency matched to adult day care users on age, gender, race, and level of cognitive impairment. Participants were followed at 3-month intervals for up to 48 months. Cox proportional hazards models were used to examine the effects of adult day care and other fixed and time-varying factors on risk of nursing home placement. RESULTS: Risk of nursing home placement increased significantly with the number of days of adult day care attendance, with this effect being substantially greater for men (hazard ratio or HR = 1.33; confidence interval or CI = 1.18-1.49) than for women (HR = 1.09; CI = 1.00-1.18). Participant disability and hospitalizations and caregiver age and burden were independent predictors, but their inclusion in the model did not alter the risk associated with adult day care. IMPLICATIONS: More severe disease and greater caregiver burden did not explain the increased risk of nursing home placement among adult day care users with Alzheimer's disease. Rather, it appears that other unmeasured factors, such as a proclivity to institutionalize, may account for the association of adult day care to nursing home risk.

Alzheimer Disease↗

PubMed2005

Marginal dietary copper restriction induces cardiomyopathy in rats.

Prior studies have provided evidence of marginal dietary copper restriction in humans. The present study was undertaken to examine in a rat model the effect of a long-term marginal dietary Cu deficiency on the heart. Male adult Sprague-Dawley rats were fed AIN-76 diet containing 6.0 (control), 3.0, or 1.5 mg Cu/kg starting at 11 wk of age. Groups of rats were killed at 6, 9, 12, 15, or 18 mo after initiation of feeding, and the same experiment was repeated once. The only systemic change induced by marginal dietary Cu restriction (P < 0.05) was depression of organ Cu concentrations in rats fed 1.5 mg Cu/kg diet. Cardiac pathological manifestations in rats fed lower Cu diets were evidenced by histopathological, ultrastructural, and functional alterations. Myocyte hypertrophy and excessive collagen deposition in the heart occurred in rats fed 1.5 mg Cu/kg diet. Ultrastructural changes, including increased number and volume of mitochondria along with disruption of cristae structure, diastolic and systolic dysfunction, and electrocardiograph alterations, occurred in rats fed 1.5 or 3.0 mg Cu/kg diet. These results demonstrate that, in the absence of most indications of systemic Cu deficiency, heart morphology and function are sensitive to marginal Cu deficiency.

Animals↗

PubMed2005

Are published characteristics of the ambulatory blood pressure generalizable to rural Chinese? The JingNing population study.

OBJECTIVE: We investigated the ambulatory blood pressure (BP) in rural Chinese and compared its characteristics with those reported in other population-based studies. METHODS: We enrolled inhabitants from six villages of the JingNing County, China. We recorded the ambulatory BP using 90207 SpaceLabs monitors. Trained physicians measured the conventional BP at the participants' homes. Hypertension was defined as a conventional BP of > or = 140/ > or = 90 mmHg or a condition requiring the intake of antihypertensive drugs. Using MEDLINE, we searched for population-based studies on ambulatory BP monitoring. RESULTS: The 356 participants (12-86 years) included 192 (53.9%) women and 117 (32.9%) hypertensive patients. In all participants, systolic/diastolic BP averaged 129/80 mmHg at home. The ambulatory BP means were 121/77 mmHg over 24 h, 126/81 mmHg during daytime (0800 to 1800 h) and 112/70 mmHg during night-time (2200 to 0400 h). The awake and asleep BPs averaged 126/82 and 112/70 mmHg, respectively. Using previously published definitions of daytime (1000 to 2000 h) and night-time (midnight to 0600 h) instead of those given above, inflated the BP differences with the awake and asleep BPs from 0.4/0.2 to 1.2/1.0 mmHg and from 0.3/0 to 1.4/1.6 mmHg, respectively. Compared with daytime values, conventional BP was 2.7/3.1 mmHg lower in normotensive individuals, but 14.9/1.3 mmHg higher in hypertensive patients. In our normotensive individuals, the whole-day and night-time diastolic BPs were from 1 to 4 mmHg and from 3 to 7 mmHg higher than in five other population studies in Caucasians or Japanese, whereas night-time BP in our participants was 9/5 mmHg lower than in Chinese living in Taiwan. CONCLUSIONS: We demonstrated significant differences in the characteristics of the ambulatory blood pressure across Asian and Caucasian populations. To what extent different activity patterns and genetic and environmental factors explain this context-dependency remains to be clarified.

Adolescent↗

PubMed2005

Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population.

OBJECTIVE: The functional ADRA2B I/D polymorphism is associated with various cardiovascular and metabolic phenotypes in Caucasians. The purpose of our study was to investigate whether the ADRA2B I/D polymorphism is associated with such phenotypes in a Chinese population. METHODS: We enrolled 247 women and 234 men in a family-based Chinese study. Our statistical methods included generalized estimating equations and quantitative transmission disequilibrium test. RESULTS: The I allele (62.3 versus 50.8%, P = 0.015) and the II genotype (40.9 versus 23.4%, P = 0.017) were more prevalent among hypertensive than normotensive men. While adjusting for covariates and family clusters, male II homozygotes compared with D-allele carriers had higher systolic pressure (130.0 versus 125.0 mmHg, P = 0.016) and a 2.61 times greater (P = 0.008) risk of hypertension. On the other hand, II homozygous men had lower body weight (65.4 versus 69.6 kg, P = 0.008), body mass index (23.4 versus 24.5 kg/m2, P = 0.037), waist-to-hip ratio (0.838 versus 0.857, P = 0.024), serum insulin concentration (9.5 versus 13.2 mU/l, P = 0.026) and insulin resistance (homeostasis model assessment index 2.4 versus 3.2, P = 0.051). None of these associations reached statistical significance in women. In 65 informative male offspring, transmission of the I allele was associated with higher systolic pressure (+ 6.0 mmHg, P = 0.10), diastolic pressure (+ 5.5 mmHg, P = 0.021), and faster pulse rate (+ 5.8 beats/min, P = 0.019). CONCLUSION: In Chinese men, the I allele of the ADRA2B gene is associated with higher blood pressure, but also with a more favourable metabolic phenotype.

Adult↗

PubMed2005

Histone deacetylation is required for progression through mitosis in tobacco cells.

Post-translational modifications of core histone proteins play a key role in chromatin structure and function. Here, we study histone post-translational modifications during reentry of protoplasts derived from tobacco mesophyll cells into the cell cycle and evaluate their significance for progression through mitosis. Methylation of histone H3 at lysine residues 4 and 9 persisted in chromosomes during all phases of the cell cycle. However, acetylation of H4 and H3 was dramatically reduced during mitosis in a stage-specific manner; while deacetylation of histone H4 commenced at prophase and persisted up to telophase, histone H3 remained acetylated up to metaphase but was deacetylated at anaphase and telophase. Phosphorylation of histone H3 at serine 10 was initiated at prophase, concomitantly with deacetylation of histone H4, and persisted up to telophase. Preventing histone deacetylation by the histone deacetylase inhibitor trichostatin A (TSA) led to accumulation of protoplasts at metaphase-anaphase, and reduced S10 phosphorylation during anaphase and telophase; in cultured tobacco cells, TSA significantly reduced the frequency of mitotic figures. Our results indicate that deacetylation of histone H4 and H3 in tobacco protoplasts occurs during mitosis in a phase-specific manner, and is important for progression through mitosis.

Acetylation↗

PubMed2005

Risk factors for low Kaup index among children in rural ethnic minority areas of Yunnan, China.

BACKGROUND: The general living standard and health level have been greatly improved in China. But the result of a significant change in a child's growth level has not been reported in the Yunnan rural minority area. The aim of this study was to identify the risk factors for low Kaup index in the Dai peoples' autonomous region to construct a better health service system in rural minority areas. METHODS: A total of 1173 mother-child pairs were selected in 36 villages of the Dai peoples' autonomous region. Sampled mothers were interviewed using a structured questionnaire. Sampled children were measured for weight and height. RESULTS: In total, 36.1% of the candidate group was under weight, 12.0% was wasting, and 30.8% had stunted growth. A child's gender (odds ratio; OR, 1.42; 95% confidence interval; 95% CI, 1.07-1.88), existence of a weaning food (OR, 0.35; 95% CI, 0.26-0.46), grasp of the cause of the child's malnutrition (OR, 1.82; 95% CI, 1.16-2.89), positiveness to information on better nutrition (OR, 2.97; 95% CI, 1.07-8.18), coincidence of the child-rearing plan between parents (OR, 3.15; 95% CI, 1.12-4.11), and existence of a doctor who can consult about child-rearing (OR, 3.17; 95% CI, 1.22-8.22) indicated significant relationships to the low value of a child's Kaup index. CONCLUSION: The mother's child-rearing behavior and social support were identified as risk factors. An offer of effective and abundant information to mothers, and the existence of professionals with whom mothers can consult immediately, were required to construct a better health system in the target area.

Child↗

PubMed2005

Mechanism of protective action of bicyclol against CCl-induced liver injury in mice.

Bicyclol is a novel synthetic drug for the treatment of chronic viral hepatitis in China. This paper reports the protective action of bicyclol against experimental liver injury in mice and its mechanism of action. Oral administration of bicyclol markedly reduced the elevated serum transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and the hepatic morphologic changes induced by CCl(4) in mice. Mechanistic studies demonstrated that bicyclol significantly inhibited CCl(4)-induced lipid peroxidation of liver microsomes and (14)CCl(4) covalent binding to microsomal lipids and proteins in vitro, and decreased the level of the trichloromethyl free radical (*CCl(3)) generated from CCl(4) metabolism by NADPH-reduced liver microsomes. On the other hand, bicyclol neither directly inhibited the activity of ALT or AST in vitro nor affected hepatic ALT protein content in mice. These results suggest that bicyclol has remarkable hepatoprotective effects and its mechanism of action may be related to a decrease in free radical-induced damage to hepatocytes.

Administration, Oral↗

PubMed2005

Taurine inhibits ischemia/reperfusion-induced compartment syndrome in rabbits.

AIM: To investigate effects of taurine on ischemia/reperfusion (I/R)-induced compartment syndrome in rabbit hind limbs. METHODS: Rabbits underwent femoral artery occlusion after ligation of branches from terminal aorta to femoral artery. After a 7-h ischemia, reperfusion was established with the use of heparinized polyethylene shunts. Rabbits received taurine (1g/kg) or normal saline (control) by iv infusion 10 min before shunt placement. During reperfusion, anterior compartment pressure (ACP) was monitored continuously in the left lower extremity. Gastrocnemius muscle triphenyltetrazolium chloride (TTC) level, taurine content and myeloperoxidase activity were assayed. Oxidative stress was induced in the in vitro gastrocnemius muscle slices by free radical generating systems (FRGS), and the malondialdehyde content was measured in presence or absence of taurine. RESULTS: After 7 h of ischemia, none of the parameters that we measured were different from those before ischemia, except that TTC reduction decreased by 80%. In the control group, after 2 h of reperfusion, ACP increased 4.5-fold, and gastrocnemius muscle taurine content was reduced by 33%. In taurine-treated animals, at 2h reperfusion, the mean arterial blood pressure and heart rate were increased, by 6% and 10%. ACP decreased by 39%, muscle edema decreased by 16%, TTC reduction increased by 150%, and lactate dehydrogenase decreased by 36% compared to control group. Plasma and muscle taurine content increased by 70% and 88%, respectively. In the taurine-treated group, at 2 h reperfusion, plasma malondialdehyde and conjugated diene content were decreased by 38% and 23%, respectively, and muscle malondialdehyde and conjugated diene content decreased by 22% and 30%, respectively compared to the control group. At 2 h reperfusion, myeloperoxidase activity was increased 3.5-fold in control animals. In the in vitro study, taurine decreased malondialdehyde content in muscle slices incubated with hypochlorous acid in a dose-dependent manner, but there was no change when incubated with hydrogen peroxide and xanthine oxidase. CONCLUSION: Treatment with taurine inhibited I/R-induced compartment syndrome by at least in part attenuating oxidative stress injury induced by I/R, suggesting clinical application of taurine might be a new strategy for the prevention and treatment of compartment syndrome.

Animals↗

PubMed2005

Identification of some benproperine metabolites in humans and investigation of their antitussive effect.

AIM: To identify 4 unknown metabolites of benproperine (BPP, 1) in human urine after a po dose, and to investigate the antitussive effect of monohydroxylate metabolites. METHODS: The putative metabolite references were prepared using chemical synthesis. Their structures were identified using 1H and 13C nuclear magnetic resonance, and mass spectrometry. The metabolites in human urine were separated and assayed using liquid chromatography-ion trap mass spectrometry (LC/MS/MS), and further confirmed by comparison of their mass spectra and chromatographic retention times with those of synthesized reference substances. The antitussive effects of metabolites were evaluated on coughs induced by 7.5% citric acid in conscious guinea pigs. RESULTS: 1-[1-Methyl-2-[2-(phenylmethyl)phenoxy]-ethyl]-4-piperidinol (2), 1-[1-methyl-2-[2-(phenylmethyl)phenoxy] ethyl]-3-piperidinol (3) and their glucuronides 4 and 5 were obtained from chemical synthesis. Four urinary metabolites in human urine showed peaks with the same chromatographic retention times and mass spectra in LC/MS/MS as synthetic substances 2, 3, 4 and 5. Phosphates of compounds 2 and 3 prolonged the latency of cough and reduced the number of coughs during the 3 min test using citric acid, but did not reduce the number of coughs during the 5 min immediately after the test in conscious guinea pigs. CONCLUSION: Compounds 2, 3, 4, and 5 were identified as the metabolites of BPP in human urine. Among them, compounds 2 and 3 are inactive in the antitussive effect.

Adult↗