Biomedical subjects

Bing Lu

Publications and source records attributed to Bing Lu.

At least 19 recordsLinked to original sources

PubMed2006

In vitro and in vivo CYP3A64 induction and inhibition studies in rhesus monkeys: a preclinical approach for CYP3A-mediated drug interaction studies.

In this study, induction and inhibition of rhesus monkey CYP3A64 versus human CYP3A4 were characterized in vitro, and the corresponding pharmacokinetic consequences were evaluated in rhesus monkeys. In monkey hepatocytes, rifampin markedly induced CYP3A64 mRNA (EC50 = 0.5 microM; Emax = 6-fold) and midazolam (MDZ) 1'-hydroxylase activity (EC50 = 0.2 microM; Emax = 2-fold). Compound A (N-[2(R)-hydroxy-1(S)-indanyl-5-[2(S)-(1,1-dimethylethylaminocarbonyl)-4-[(furo[2,3-b]pyridin-5-yl)-methyl]piperazin-1-yl]-4(S)-hydroxy-2(R)-phenylmethylpentanamide), a known potent and mechanism-based inhibitor of CYP3A4, strongly inhibited the formation of 1'-hydroxy MDZ by recombinant CYP3A64 in a concentration- and time-dependent manner (KI = 0.25 microM; k(inact) = 0.4 min(-1)). Similar corresponding results also were obtained with human CYP3A4 in the presence of rifampin or compound A. In rhesus monkeys, MDZ exhibited a relatively high metabolic clearance (primarily via 1'-hydroxylation followed by glucuronidation) and a low hepatic availability (Fh = 16%). Consistent with the induction of hepatic metabolism of a high-clearance compound, pretreatment with rifampin (18 mg/kg p.o. for 5 days) did not significantly affect the i.v. kinetics of MDZ, but caused a pronounced reduction (approximately 10-fold) in the systemic exposure to MDZ and, consequently, its Fh following intrahepatic portal vein administration (i.pv.) of MDZ. A comparable extent of the pharmacokinetic interaction also was obtained after a 1.8 mg/kg rifampin dose. Also consistent with the in vitro CYP3A64 inhibition finding, compound A (6 mg/kg i.v.) markedly increased (10-fold) the i.pv. administered MDZ exposure. At the doses studied, plasma concentrations of rifampin or compound A reached or exceeded their respective in vitro EC50 or KI values. These findings suggest the potential applicability of the in vitro-in vivo relationship approach in rhesus monkeys for studying CYP3A-mediated interactions in humans.

Adolescent↗

PubMed2006

Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5-alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of the mitotic kinesin KSP.

Molecular modeling in combination with X-ray crystallographic information was employed to identify a region of the kinesin spindle protein (KSP) binding site not fully utilized by our first generation inhibitors. We discovered that by appending a propylamine substituent at the C5 carbon of a dihydropyrazole core, we could effectively fill this unoccupied region of space and engage in a hydrogen-bonding interaction with the enzyme backbone. This change led to a second generation compound with increased potency, a 400-fold enhancement in aqueous solubility at pH 4, and improved dog pharmacokinetics relative to the first generation compound.

Alkylation↗

PubMed2006

Effect of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits.

OBJECTIVE: To determine the efficacy of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits. METHODS: Twenty-four Japanese white rabbits underwent laminectomy (including the attached ligaments) at L(2 ) and L(5). After laminectomy at L(5), polylactic acid glue was sprayed on the dura and nerve roots and this segment was taken as the experimental group. After laminectomy at L(2), nothing was used and this segment was enrolled as the self control group. Four rabbits were killed every two weeks postoperatively till the end of the experiment at 12 weeks. Then the operated spine was observed grossly, histologically and ultrastructurally to check the degree of scar formation, the status of epidural scar adhesion, the absorption of the glue, and the intracellular structure of fibroblasts. RESULTS: The glue coagulated immediately after spraying and showed excellent hemostatic effect. The glue membrane was easy to be taken away from the dura mater of the samples for 2 weeks and there were no cells in the epidural space in the experimental group. But the dura mater was covered by hematoma in the control group, which formed mild adhesion, with fibroblasts proliferating actively. In the 4th week, some glue shivers remained in the epidural space with fibroblasts increasing a little, and the dura mater was smooth in the experimental group. However, in the control group, the formed scar was fragile and conglutinated with the dura mater diffusely and fibroblasts were much more than those in the experimental group. In the 6th-12th weeks, there was a potential interspace between the scar and the dura mater, and the polylactic acid glue was absorbed completely in the experimental group. Much tough scar was found in the control group, which was very difficult to dissect from the dura mater and the surrounding tissues. From the ultrastructural observation of the fibroblasts, the nucleus became much bigger and the rough endoplasmic reticulum was much more plentiful in the control group than that in the experimental group. CONCLUSIONS: Polylactic acid glue can effectively reduce epidural cicatrization and adhesion.

Animals↗

PubMed2005

Reversed phase ion-pair high performance liquid chromatographic gradient separation of related impurities in 2,4-disulfonic acid benzaldehyde di-sodium salt.

A reversed phase ion-pair gradient liquid chromatographic method has been developed and validated for purity determination of the hydrophilic compound 2,4-disulfonic acid benzaldehyde di-sodium salt (2,4-DSAD) containing both hydrophilic and more lipophilic related impurities. Mixtures of acetonitrile-phosphate buffer containing tetrahexylammonium hydrogen sulfate as the ion-pairing reagent were used as the mobile phase. A linear gradient, which generated simultaneous change in the concentration of organic modifier, buffer concentration and the concentration of ion-pairing reagent, was applied. The method allows detection of impurities at low levels (0.01% w/w). Excellent repeatability for both retention time (RSD< or =0.3%, n = 6) and detector response (RSD = 0.03%, n = 6 for the main peak and RSD = 6%, n = 6, for an impurity at 0.01 area% level) was obtained. The method was shown to be robust for routine analysis and has been successfully transferred to the quality control laboratory.

Acetonitriles↗

PubMed2005

A universal plasmid library encoding all permutations of small interfering RNA.

Small interfering RNA (siRNA) is normally designed to silence preselected known genes. Such selections are inevitably prone to bias as a result of limited knowledge about the biological process, transcript identity, and functions. A library that contains all permutations of siRNA could avoid such problems. In this paper, it is shown that 5 x 10(7) siRNA-encoding plasmids can be constructed in a single tube by using vectors with two mutated RNA polymerase III promoters arranged in a convergent manner. Such a library was used to carry out genomewide screening of functional genes in a phenotype-driven manner. Multiple siRNAs that induce a significant increase of cell proliferation speed were identified.

Base Sequence↗

PubMed2005

Prospective evaluation of the systemic inflammatory marker C-reactive protein in patients with end-stage periodontitis getting teeth replaced with dental implants: a pilot investigation.

OBJECTIVES: Serum C-reactive protein (CRP) has been shown to be a risk predictor for cardiovascular disease. Periodontal treatment reduces elevated CRP levels. The aim of this pilot investigation was to evaluate if dental implants placed after extractions in patients with end-stage periodontitis affect the serum CRP levels. MATERIAL AND METHODS: Serum CRP levels in 10 subjects with end-stage periodontitis were measured prior to tooth extraction and placement of dental implants, and at 3-month intervals for a year post-operatively. Univariate repeated measures analysis of variance was used to estimate and test the changes in CRP levels over time. RESULTS: Mean CRP levels decreased significantly following tooth extraction and replacement with dental implants from 3.45 to 1.55 mg/dl after 12 months (P < 0.01). Six-, 9-, and 12-month post-implant placement mean CRP values were statistically significantly different from the mean pre-operative CRP value (P < 0.01). CONCLUSIONS: The pilot data suggest that extraction of advanced periodontally involved teeth and their replacement with dental implants lead to a decrease in CRP levels, and dental implant placement does not change the lowered CRP levels over a 12-month period.

Aged↗

PubMed2005

[Experimental study on the polylactic acid glue in preventing epidural adhesion].

OBJECTIVE: To determine the ability of the polylactic acid glue (PLA-G) in preventing epidural adhesion after laminectomy. METHODS: Each of the 24 randomly selected rats was done laminectomy of L2 and L5. The PLA-G, which would change from liquid to solid when meets with serum, was used in the epidural site of L5 to become a half-solid membrane (the experimental group, EG). The PLA-G was not used in the same site of L2 (the control group, CG). The gross anatomical, histological, and microscopical evaluation were made 2, 4, 6, 8, 10 and 12 weeks after operation; electron microscope observation was also made on two rats 4 weeks after operation(both EG and CG). RESULTS: Obvious epidural space was observed between dura mater and scar tissue (ST), but no cells in the epidural space were observed in EG 2 weeks after operation. Corps of the red cells between dura mater and ST and proliferation of fibroblast cell (FB) were observed in CG 2 weeks after operation. Some remaining glue shivered in the epidural space with lightly increasing fibroblast and smooth dura mater were observed in EG 4 weeks after operation. However, fragile scar adhered with dura mater diffusely and more FB were observed in CG. From the 6th week to the 12th week, a potential interspace between scar and dura mater was observed and PLA glue was absorbed completely in EG. However, tougher scar, which was very difficult to dissect from dura mater and surrounding tissues, was observed. According to the fibroblast ultrastructure observation, bigger nucleus and more plentiful rough endoplasmic reticulum were observed in CG. CONCLUSION: The PLA-G can effectively reduce the epidural scar and adhesion in animal experiment.

Adhesives↗

PubMed2005

[Bowel control of elderly low rectal cancer patients after anus-retained operation].

BACKGROUND & OBJECTIVE: Though anus-retained operation has became the first choice in radical cure operation for rectal cancer, most surgeons whom fear of dissatisfied bowel control after operation recommend permanent bowel stoma in abdomen for elderly low rectal cancer patients rather than anus-retained operation. This study was to evaluate the bowel control of elderly low rectal cancer patients after anus-retained operation. METHODS: A total of 80 elderly low rectal cancer patients were divided into > or =75-year old group (39 patients) and 60-74-year old group (41 patients). Clinical data and follow-up data of the 80 patients were analyzed; bowel function and continence of the 2 groups were compared. RESULTS: The postoperative 18-month survival rate of all patients was 98.8%. The bowel control statuses of 76 patients were evaluable, of which 36 were in > or =75-year old group, 40 were in 60-74-year old group. Three months after operation, the bowel function was significantly poorer in > or =75-year old group than in 60-74-year old group (P<0.05), but the difference dissolved 6 months after operation (P>0.05). The time of recovering normal defecation frequency was slightly longer in > or =75-year old group than in 60-74-year old group (P>0.05). The prevalence of grade I incontinence 6 months after operation was significantly higher in > or =75-year old group than in 60-74-year old group (36.1% vs. 12.5%, P<0.05), but all symptoms of incontinence were relieved after treatment. CONCLUSIONS: Most elderly low rectal cancer patients could maintain bowel control after anus-retained operation. Age alone should not be a contraindication to a restorative resection for low rectal cancer.

Adenocarcinoma↗

PubMed2005

[Clinical comparison on the classical versus extensive Whipple's resection for adenocarcinoma of head of pancreas].

OBJECTIVE: To evaluate the effect of extensive Whipple's resection to the adenocarcinoma of head of pancreas on the survival, complications, and surgical mortality. METHOD: Ninety three patients who received Whipple's surgery between January 1995 and March 2003 were divided into classical group (n = 51) and extensive group (n = 42). Their short-term outcome and survival rate were compared retrospectively. RESULTS: The postoperative complication rate and mortality in classical group and extensive group were 19.61%/3.92% and 16.67%/2.38%, respectively. And 1- and 2- year survival rates in classical group and extensive group were 58.82%/20.59% and 63.33%/23.33%, respectively. CONCLUSIONS: Postoperative complications and mortality will not increase in extensive Whipple's resection for adenocarcinoma of head of pancreas. However, whether extensive Whipple's resection will improve long-term survival still requires further investigation.

Adenocarcinoma↗

PubMed2005

[Bowel control of anus-preserving operation for low rectal cancer in elderly patients over 75 years].

OBJECTIVE: To evaluate the bowel control of the anus-preserving operation for elderly patients over 75 years with low rectal cancer. METHODS: Thirty-nine elderly patients over 75 years with low rectal carcinoma (4-7 cm from anal verge) were treated during the study period. The patients were divided into different groups according to the surgical procedures and anastomotic locations. The bowel control and patients satisfaction were compared. RESULTS: The time of recovering normal defecation frequency was (9.8+/- 2.9) months. There were no differences in bowel control and anorectal manometric findings between the lower anastomosis group and super-lower anastomosis group, the lower anastomosis group and anorectal anastomosis group. The patients in anorectal anastomosis group displayed significantly better bowel control and anorectal manometric findings than those in the super-lower anastomosis group (P< 0.05). The time of recovering normal defecation frequency in colonic J-pouch-anal anastomosis group was (7.7+/- 1.7) months, shorter than (10.6+/- 2.8) months in direct anastomosis group (P< 0.01). The complication rate of I degree incontinence was 36.1%, but there was no difference between the two groups. The anorectal manometric findings were better in J-pouch-anal anastomosis group than those in direct anastomosis group (P< 0.05). CONCLUSION: Colonic J-pouch-anal anastomosis for lower rectal carcinoma can significantly improve the bowel control in a short term without increasing the complication rate.

Aged↗

PubMed2005

[The separation and identification of the flavonoids from the leaves of Bryophyllum pinnatum].

This study investigated the separation of the effective compositions containing quercetin derivatives from the leaves of Bryophyllum pinnatun by solvent extraction of methanol, polar adsorption by porous polymetric resins, mixed solvent extraction of methanol with chloroform and polyamide chromatography. The results indicated that the yield of product containing 51.23% quercetin in the form of quercetin derivatives was 0.2% (W/W). Through the NMR, Mass spectrum, Infrared spectrum, we try to identify the chemical structure of the flavonoids LEF. As a result we can conclude that the chemical structure of the flavonoids from the leaves of Bryophy Ilum pinnatum is C26H28O15 (quercetin3-alpha-L-rha-beta-D-xyl), molecular weight is 580.

Chromatography, High Pressure Liquid↗

PubMed2004

Utility of nonaqueous capillary electrophoresis for the determination of lidocaine and its metabolites in human plasma: a comparison of ultraviolet and mass spectrometric detection.

A nonaqueous capillary electrophoresis/electrospray mass spectrometry method for the separation of lidocaine (LID) and two of its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), has been developed. The separation medium was: 70 mM ammonium formate and 2.0 M formic acid in acetonitrile/methanol (60:40 v/v). With a sheath liquid of methanol/water (80:20 v/v) containing 2% formic acid and positive ion detection, reproducible determinations (8-11% relative standard deviation (RSD)) of lidocaine and its metabolites were performed in spiked human plasma. The limits of detection (LODs) were between 69.1 and 337 nM. The influences of sheath liquid composition, nebulizing gas pressure and drying gas temperature on the separation were examined.

Electrophoresis, Capillary↗

PubMed2004

[Application of enzyme histochemistry in evaluation of in vitro and in vivo biocompatibility of HA/TCP].

In order to explore the possibility of applying enzyme histochemistry in biocompatibility evaluation, we investigated the effect of biomaterials on the activities of intracellular enzymes in this experiment. It was found that there was no obvious difference in morphology between osteoblasts co-cultured with HA/TCP and with Ti-alloy. However, transient down-regulation of NADH, SDH, LDH and CCO of the osteoblasts co-cultured with HA/TCP was detected by enzyme histochemistry, but these enzymes of osteoblasts the co-cultured with Ti-alloy were not down-regulated. It was indicated that something extracted from HA/TCP injured the co-cultured osteoblasts slightly. Similar early acute inflammatory reactions were observed after HA/TCP and Ti-alloy were separately implanted into the dorsal muscle of rabbit. There was also no obvious difference between the tissue response to HA/TCP and that to Ti-alloy. Activities of enzymes in tissues around implanted materials were down-regulated at the early injury period and recovered gradually within 30 days post-operation. But the mild toxicity of extracts from HA/TCP was demonstrated by the fact that the recovery period of HA/TCP group was longer than that of Ti-alloy group. It was proved that enzyme histochemistry is more sensitive than tissue morphology analysis in detecting the cell or tissue responses to biomaterials. Therefore, it is possible to use enzyme histochemistry in biocompatibility evaluation.

Alloys↗

PubMed2004

[Activity of toremifene plus mitomycin, vindesin and cisplatin regimen in unresectable non-small cell lung cancer].

OBJECTIVE: To investigate the activity and clinical efficacy of toremifene plus mitomycin, vindesin and cisplatin regimen (MVP) in non-small cell lung cancer (NSCLC). METHODS: A549 cells were seeded into 96 wells at the concentration of 10 x 10(4)cells/well and exposed to different agents. Seventy-two hours later, the cytotoxicity of the agents were evaluated with the method of MTT. The clinical trial included 63 patients with chemtherapy-naive NSCLC and 30 patients who had received chemotherapy (Pre-treatment arm). The chemotherapy-naive patients were randomly divided into the toremifene-treatment arm and the control arm. Each patient was given MVP chemotherapy. Five days before the chemotherapy, those in the toremifene-treatment group and pre-treatment arm started toremifene 420 mg daily orally for 7 days. The response was evaluated after two cycles of chemotherapy and toxic side effects and the survival of the patients were followed up. RESULTS: Toremifene decreased the IC(50) of chemotherapeutic agents and increased their cytotoxicity. In the clinical trial, the response rate and median survival were 47% and 11 months in the toremifene-treatment arm and 32% and 9 months in the control arm, respectively. The difference between the two arms was not significant. The response rate and median survival were 17% and 7 months in the pre-treatment arm, respectively. The toxicity among the three groups was not significantly different. CONCLUSIONS: Toremifene can improve the cytotoxicity of cisplatin, mitomycin and vindesin. Toremifene plus MVP regimen is safe and effective in the treatment of NSCLC.

Aged↗

PubMed2003

Characterization of sequence-dependent synergy between ZD1839 ("Iressa") and oxaliplatin.

UNLABELLED: ZD1839 ("Iressa"), a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is currently undergoing preclinical and clinical evaluation in several solid tumors. The present study aimed to assess the effect of ZD1839 in combination with oxaliplatin in the colon cancer cell lines HT-29 and LoVo. For in vitro chemosensitivity testing, cells were treated with serial dilutions of each drug sequentially at a fixed ratio of doses that corresponded to 1/20, 1/10, 1/5, 1/2, 1, 1.5 and 2 times the individual IC(50) values. Oxaliplatin followed by ZD1839 produced a synergistic effect. In contrast, oxaliplatin following ZD1839 exhibited an additive effect at best. Mass spectrometry examination revealed that ZD1839 modestly enhanced cellular oxaliplatin accumulation and platinum-DNA (Pt-DNA) adducts (P>0.05). In additional studies, high-performance liquid chromatography revealed that oxaliplatin had no effect on ZD1839 accumulation. In contrast, ZD1839 markedly inhibited removal of Pt-DNA adducts (P<0.05). With oxaliplatin treatment (1 day) followed by ZD1839 (1 day), then incubation with drug-free medium (1 day), 90% of Pt-DNA adducts remained. Apoptosis examination revealed that oxaliplatin-induced apoptosis was prolonged by sequential oxaliplatin followed by ZD1839 treatment compared with oxaliplatin alone. Further experiments revealed that ZD1839 decreased cellular gamma-glutamyltransferase activity. CONCLUSIONS: The above observations provide a mechanistic explanation for the synergy of oxaliplatin followed by ZD1839, and suggest that this treatment combination warrants further preclinical and clinical investigation.

Antineoplastic Agents↗

PubMed2003

Development of a dog microdialysis model for determining synovial fluid pharmacokinetics of anti-arthritis compounds exemplified by methotrexate.

PURPOSE: The purpose of this study was to develop and validate an animal model of drug disposition in synovial fluid (SF) by comparing microdialysis with arthrocentesis using the anti-arthritic drug methotrexate (MTX). METHODS: Microdialysis probes were calibrated in vitro with the no net flux method using dog synovial fluid. The probes were implanted surgically into the stifle joint space of four dogs and were dialyzed overnight using a portable microinfusion pump. The membrane integrity of the probes was monitored by retrodialysis using an internal standard. After an intravenous bolus of 2.5 mg/kg of MTX, unbound concentrations in synovial fluid, as well as total plasma concentrations, were measured by liquid chromatography tandam mass spectrometer (LC/MS/MS) in samples collected from 0 to 48 h postdose. RESULTS: The probe membrane remained intact at least 48 h after implantation. The mean probe recovery and unbound fraction of MTX in SF were 46.8% and 44.8%, respectively. The unbound fraction of MTX was 44% in synovial fluid. MTX penetrated into the joint space rapidly, with maximal concentrations of 6.6 microM reached at approximately 1 h postdose. The unbound MTX area under the curve in SF was approximately 40% of the total area under the curve in plasma. These data agree well with the previous data obtained for MTX using arthrocentesis. CONCLUSION: In contrast with arthrocentesis, microdialysis enables the collection of multiple serial SF samples from individual animals with minimal trauma and potential blood contamination. This animal model should prove valuable for studying the disposition of new antiarthritis compounds or biomarkers in SF.

Animals↗

PubMed2002

A new stage of the nutrition transition in China.

OBJECTIVE: To fully explore the long-term shifts in the nutrition transition and the full implications of these changes in the Chinese diet. DESIGN: A descriptive, population-based study. SETTING: Data come from nationally representative surveys: the China Health and Nutrition Survey (1989-1997), the China National Nutrition Survey (1982 and 1992), the annual household consumption surveys of the State Statistical Bureau, and the Annual Death Report of China. RESULTS: During the first part of the major economic transformation in China (before 1985), cereal intake increased but decreased thereafter. There was also a long-term reduction of vegetable consumption that has now stabilised. Intake of animal foods increased slowly before 1979 and more quickly after the economic reforms occurred. While the total energy intake of residents has decreased, as has energy expenditure, large changes in the composition of energy have occurred. The overall proportion of energy from fat increased quickly, reaching an overall average of 27.3% and 32.8% for urban residents in 1997. Over a third of all Chinese adults and 60.1% of those in urban areas consumed over 30% of their energy from fat in 1997. Large shifts towards increased inactivity at work and leisure occurred. These changes are linked with rapid increases of overweight, obesity and diet-related non-communicable diseases (DR-NCDs) as well as total mortality for urban residents. CONCLUSIONS: The long-term trend is a shift towards a high-fat, high-energy-density and low-fibre diet. The Chinese have entered a new stage of the nutrition transition.

Cause of Death↗

PubMed2002

Understanding the nutrition transition: measuring rapid dietary changes in transitional countries.

OBJECTIVE: To understand methodological concerns related to dietary intake collection in transitional societies. DESIGN: Three days of household weighing and measurement of all food used and repeated 24-hour recalls. SETTING: Eight Chinese provinces. SUBJECTS: Five thousand nine hundred and fifty-two and 5152 adults aged 20-45 years in 1989 and 1997, respectively. RESULTS: Great variance exists in the types and quantity of animal products used in common recipes. For example, the proportion of pork from lean cuts in 'stir-fried fresh pepper and pork' varies between 14 and 24% in urban and rural areas and the total pork content for 100 g (dish) varies by 15 to 19 g between rural and urban areas in each of eight provinces. Another challenge relates to the variation in the edible vegetable oil content added during food preparation. Reliance on standard recipes for each fried dish would miss the variations in oil use over time, space and socio-economic status. CONCLUSIONS: Dietary change is rapid in transitional countries. Reliance on recipes standardised for animal food and edible oil contents will lead to very large systematic errors in the measurement of energy, fat and protein intakes.

Adult↗