Biomedical subjects

Liang Liu

Publications and source records attributed to Liang Liu.

At least 37 records · Page 2Linked to original sources

PubMed2006

Factor VIIa inhibitors: a prodrug strategy to improve oral bioavailability.

We have developed a series of potent and selective factor VIIa inhibitors based on the 2-[5-(5-carbamimidoyl-1H-benzoimidazol-2-yl)-6-hydroxy-biphenyl-3-yl]-succinic acid scaffold. These amidine-containing compounds have low oral bioavailability. Herein, we describe our efforts to improve the oral bioavailability of the parent amidine via a prodrug strategy where the amidine basicity and polarity were reduced with either an alkoxy-amidine or a carbamate prodrug.

Administration, Oral↗

PubMed2006

Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model.

Highly selective and potent factor VIIa-tissue factor (fVIIa.TF) complex inhibitors were generated through structure-based design. The pharmacokinetic properties of an optimized analog (9) were characterized in several preclinical species, demonstrating pharmacokinetic characteristics suitable for once-a-day dosing in humans. Analog 9 inhibited platelet and fibrin deposition in a dose-dependent manner after intravenous administration in a baboon thrombosis model, and a pharmacodynamic concentration-response model was developed to describe the platelet deposition data. Results for heparin and enoxaparin (Lovenox) in the baboon model are also presented.

Animals↗

PubMed2006

Efficacy and safety of herbal medicines for idiopathic Parkinson's disease: a systematic review.

The objective of this study is to assess the efficacy and safety of herbal medicines (HMs), as a monotherapy or adjunct therapy, compared to placebo or conventional approaches in the treatment of idiopathic Parkinson's disease (PD). We conducted a systematic review of randomized controlled trials from both conventional and alternative medicine sources. Outcome measures were overall improvement, quality of life, reduction of levodopa dose, and adverse events. Nine studies were included, each testing a different HM. Six of the trials had limited internal validity due to major flaws in design, including the lack of proper randomization; insufficient blinding; unclear inclusive criteria in terms of diagnostic criteria, baseline staging, and duration of disease; lack of proper sample size calculation; and insufficient data analysis. Imbalances in gender and ethnicity among the patients in the included trials were observed. No major adverse events emerged, and no specific pattern was detected from the trials describing such data. In addition to major methodological defects, heterogeneity in (1) HM tested, (2) control treatment, and (3) outcome measure hindered in-depth data analysis and synthesis. Current evidence is insufficient to evaluate the efficacy and safety of various HMs. Further studies with improved trial design and reporting, with assessment on cost-effectiveness, quality of life, and qualitative data are warranted.

Antiparkinson Agents↗

PubMed2006

Comparative study of two vitreous humor sampling methods in rabbits.

To compare and evaluate two methodologies, entire-sampling and micro-sampling for the harvesting of vitreous humor, the vitreous humor of rabbits were sampled with the two methods respectively, and the concentrations of calcium, chlorine, potassium, sodium and phosphorus of the were measured. The results showed that the differences in the variance coefficient and two-eye concentrations of micro-sampled specimens were less than those of the entire-sampled specimens. In the micro-sampling group, the concentrations of repeated micro-sampling showed no differences among different groups (P > 0.05) and the intra-ocular fluid dynamics did not have significant influence on post-mortem sampling. The sampling technique may affect the concentrations of specimen collected. Our study suggests that micro-sampling is less influenced by the human factor and is reliable, reproducible, and more suitable for forensic investigation.

Animals↗

PubMed2006

Effectiveness of the Chinese herbal formula TongXieYaoFang for irritable bowel syndrome: a systematic review.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common problem, but treatment is unsatisfactory. Although Chinese herbal medicines have been tried, there are limited data to support their usage. The authors set out to systematically review the effectiveness of the Chinese herbal medicine TongXieYaoFang (TXYF) and TXYF with different Chinese herbal additions (TXYF-A) in the management of IBS in order to make evidence-based recommendations. METHODS: The authors searched the literature to identify randomized trials of TXYF or TXYF-A for patients with IBS by using MEDLINE, EMBASE, the Cochrane Controlled Trials Register (CCTR), the Cochrane Complementary Medicine Fields Specialized Register from 1966 to 2004, the CMB Disc database from January 1978 to December 1988, and the Full Text Chinese Journal database from January 1994 to December 2004. Standard forms regarding study design, treatment course, outcome measures, and adverse events were used to abstract data. Studies were assigned a quality score based on published methodology. Relative risk (RR) and 95% confidence interval (CI) were analyzed. RESULTS: Twelve studies (n = 1125) that met the criteria for review were identified. There was heterogeneity in the studies with regard to herbal formulas, control medicine, treatment course, and outcome measurement. The quality of all studies was low. The pooled analyses of effectiveness for the near-term (immediately after finishing the treatment course), short-term (3 months after finishing the treatment course), and long-term (6 months or more after finishing the treatment course) effectiveness showed that the effect of TXYF-A was better than that of conventional medicine in four, two, and six studies, respectively. The RRs were 1.34 (95% CI 1.16-1.54, p < 0.05), 1.39 (95% CI 1.17-1.64, p < 0.05), and 1.34 (95% CI 1.12-1.61, p < 0.05), respectively. Overall, combining all data from the 12 studies, the effectiveness of TXYF-As was higher than that in control groups, with statistical significance and RR of 1.35 (95% CI 1.21-1.50, p < 0.05). CONCLUSIONS: There is evidence to indicate the potential usefulness of TXYF-A for IBS patients. The results were limited by the poor quality and heterogeneity of these studies. Further studies with carefully designed, randomized double-blinded placebo-controlled trials will be needed to confirm the effectiveness of TXYF or TXYF-A for IBS.

Drugs, Chinese Herbal↗

PubMed2006

Heat stroke deaths caused by electric blankets: case report and review of the literature.

Heat stroke is the most serious and potentially life-threatening condition of the heat-related illnesses. Heat stroke deaths caused by electric blanket are rarely reported. In this paper, we report 2 cases of fatal heat stroke caused by overheating from electric blankets in winter. One was a 41-year-old man who was found unresponsive in bed on an electric blanket. His wife shared the same bed with him and was found unconscious. The wife's axillary temperature was 40 degrees C (104 degrees C) when she was admitted to the hospital. She fully recovered after medical treatment. The husband was pronounced dead at scene, with rectal temperature at 41.2 degrees C (106.2 degrees C). The other was a 13-year-old girl who was found dead in bed on an electric blanket, with rectal temperature at 41 degrees C (105.8 degrees F). The literature is reviewed, and the pertinent findings, including scene investigations, postmortem examination, the risk and mechanism of fatal heat stroke caused by using electric blanket, are discussed.

Adolescent↗

PubMed2006

CRA-024781: a novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo.

CRA-024781 is a novel, broad spectrum hydroxamic acid-based inhibitor of histone deacetylase (HDAC) that shows antitumor activity in vitro and in vivo preclinically and is under evaluation in phase I clinical trials for cancer. CRA-024781 inhibited pure recombinant HDAC1 with a K(i) of 0.007 mumol/L, and also inhibited the other HDAC isozymes HDAC2, HDAC3/SMRT, HDAC6, HDAC8, and HDAC10 in the nanomolar range. Treatment of cultured tumor cell lines grown in vitro with CRA-024781 resulted in the accumulation of acetylated histone and acetylated tubulin, resulting in an inhibition of tumor cell growth and the induction of apoptosis. CRA-024781 parenterally administered to mice harboring HCT116 or DLD-1 colon tumor xenografts resulted in a statistically significant reduction in tumor growth at doses that were well tolerated as measured by body weight. Inhibition of tumor growth was accompanied by an increase in the acetylation of alpha-tubulin in peripheral blood mononuclear cells, and an alteration in the expression of many genes in the tumors, including several involved in apoptosis and cell growth. These results reveal CRA-024781 to be a novel HDAC inhibitor with potent antitumor activity.

Acetylation↗

PubMed2006

CRA-026440: a potent, broad-spectrum, hydroxamic histone deacetylase inhibitor with antiproliferative and antiangiogenic activity in vitro and in vivo.

CRA-026440 is a novel, broad-spectrum, hydroxamic acid-based inhibitor of histone deacetylase (HDAC) that shows antitumor and antiangiogenic activities in vitro and in vivo preclinically. CRA-026440 inhibited pure recombinant isozymes HDAC1, HDAC2, HDAC3/SMRT, HDAC6, HDAC8, and HDAC10 in the nanomolar range. Treatment of cultured tumor cell lines grown in vitro with CRA-026440 resulted in the accumulation of acetylated histone and acetylated tubulin, leading to an inhibition of tumor cell growth and the induction of apoptosis. CRA-026440 inhibited ex vivo angiogenesis in a dose-dependent manner. CRA-026440 parenterally given to mice harboring HCT116 or U937 human tumor xenografts resulted in a statistically significant reduction in tumor growth. CRA-026440, when used in combination with Avastin, achieved greater preclinical efficacy in HCT 116 colorectal tumor model. Inhibition of tumor growth was accompanied by an increase in the acetylation of alpha-tubulin in peripheral blood mononuclear cells and an alteration in the expression of many genes in the tumors, including several involved in angiogenesis, apoptosis, and cell growth. These results reveal CRA-026440 to be a novel HDAC inhibitor with potent antitumor activity.

Acetylation↗

PubMed2006

Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula, on the experimental inflammatory and nociceptive models in rodents.

JCICM-6, the extract of an anti-arthritic herbal formula composed of medicinal herbs of Sinomenium acutum, Aconitum carmichaeli DEBX., Curcuma Longa L., Paeonia lactiflora PALL., and Paeonia suffruticosa ANDR., was examined in the effectiveness and mechanism in reducing experimentally-induced inflammation and nociception using nine animal models. JCICM-6 was extracted from herbs and purified with Amberlite XAD-7HP adsorbent resin and analyzed with HPLC-fingerprint for quality consistency. In acute inflammatory models, the paw edema of rats was induced by subcutaneous injection of carrageenan or pro-inflammatory mediators, including histamine, serotonin, bradykinin, and prostaglandin E(2) (PGE(2)) into the right hind paws of animals; while the ear edema of mice was induced by applying arachidonic acid or 12-O-tetradecanoylphorbol 13-acetate (TPA) on the ear surface. In nociceptive models, the tail-flick response induced by radiant heat stimulation was measured and the numbers of abdominal writhing episodes of mice induced by intraperitoneal injection of acetic acid were recorded. JCICM-6 orally administered in a range of dosages from 0.438 g to 1.75 g/kg significantly and dose-dependently suppressed the paw edema of rats induced by carrageenan or various pro-inflammatory mediators and the ear edema of mice induced by arachidonic acid or TPA. JCICM-6 also significantly prolonged the reaction time of rats to radiant heat stimulation and reduced the numbers of writhing episodes of mice. These results indicated that JCICM-6 possesses significant anti-inflammatory and analgesic effects, which implies that it would be a potential candidate for further investigation as a new anti-arthritic botanical drug for humans.

Animals↗

PubMed2006

Inhibitory effects of magnolol on distal colon of guinea pig in vitro.

The influence of plant product magnolol (0-100 microM) on the contractile activity of isolated colonic muscle strips in guinea pig and related mechanism were investigated. Magnolol did not affect the base tone of colon muscle strips, but it dose-dependently inhibited 40 mM KCl-, 1 microM carbachol (CCh)- and 10 microM serotonin (5-HT)-induced contractions at concentrations higher than 10 microM. And also, magnolol inhibited the 5-HT- or CCh-induced muscle contraction in calcium-free buffer. Furthermore, magnolol inhibited the KCl-induced contraction under the condition of procaine. In addition, inhibition rate of nifedipine plus magnolol on muscle strips was lower than that of nifedipine alone. Moreover, magnolol dose-dependently decreased the velocity of pellet propulsion in the concentration range of 0.1-10 microM, and totally inhibited pellet propulsion at the concentration higher than 30 microM. Thus, it can be concluded that magnolol may 1) block receptor-operated cation channels and the voltage dependent Ca2+ channel, and 2) inhibit calcium release from the sarcolemmal membrane (SR) through blocking InsP3-sensitive and ryanodine-sensitive pathways. This explains, at least partially, that Cortex magnoliae officinalis exerts therapeutic effects on gastrointestinal disease through relaxation of GI tract smooth muscles.

Anesthetics, Local↗

PubMed2006

Control release effects of binders used in pills of traditional Chinese medicine herbs.

This research investigated the effects of control release of binders that are used in the pills of Chinese herbal medicine, namely, as processed honey, starch paste, beeswax, or mixtures thereof. Aspirin and baicalin were used as the active pharmaceutical ingredients (API). The processed honey was heated to 110 degrees C, 120 degrees C, or 130 degrees C. In these pills, the binders were the only excipients. The pills were prepared by the stir method using a mixer at 80 degrees C without pressure. The differential thermal analysis (DTA) showed that the melting points of aspirin and baicalin were changed by the binders. The Fourier Transform infrared spectra (FT-IR) of aspirin and baicalin suggest that there are different non-covalent molecular interactions between the API and the binders, such as C-H-pi and hydrogen bond interaction. The dissolution profiles indicate that changing the ratio of the binders altered the patterns of dissolution of the API; thus, this ration may be used to control the release of API from the pills.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Improving the quality of randomized controlled trials in Chinese herbal medicine, part I: clinical trial design and methodology.

OBJECTIVE: To discuss the quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) with respect to design and methodology, and provide suggestions for further improvement in future clinical trials. METHODS: A search of the Cochrane Library was conducted to identify RCTs of CHM on line in July 2005. Quality of the RCTs was assessed using a 11-item checklist modified from the revised CONSORT statement, with 2 items specific to CHM (i.e. herb preparation form and quality control of herbs). RESULTS: The search yielded 167 RCTs that were selected for assessment. All trials included statements about the interventions, objectives, primary outcome design, statistical methods, and herb preparation form. Although 163 (97.6%) trials reported inclusion criteria, exclusion criteria were only reported in 26 (15.6%) trials. Fewer than 10% of trials clearly stated the random allocation sequence generation methods, and only 2.4% mentioned allocation concealment. The vast majority (86.8%) of trials were open-label, while only 13.2% used blinding. Almost half (45.5%) administered the CHM intervention as a tea or decoction. Only one trial (0.6%) reported a sample size calculation, and a single trial (0.6%) discussed quality control of the CHM intervention. CONCLUSION: The overall methodologic quality of RCTs in CHM was poor. It is essential to improve the design of future RCTs in this clinical area. RECOMMENDATIONS: (1) Investigator conducting RCTs should have formal training about clinical trial design; (2) A flow chart is recommended to ensure that all essential steps of clinical trial design are included. (3) Conducting pilot studies prior to RCTs may help improve their design; (4) Registration of clinical trials and publishing their protocols prior to enrollment may reduce publication bias and solicit peer reviews of the proposed design; (5) Collaboration between CHM investigators and traditional medicine academic research centers interested in integrative medicine may lead to quality improvement of RCTs of CHM.

Humans↗

PubMed2006

Improving the quality of randomized controlled trials in Chinese herbal medicine, part II: control group design.

OBJECTIVE: To discuss the types of control groups in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM), and to provide suggestions for improving the design of control group in future clinical studies in this therapeutic area. METHODS: A search of the Cochrane Library was conducted in July 2005 to identify RCTs of CHM, and 66 RCTs with CHM for type 2 diabetes mellitus were obtained as the basis for further analysis. RESULTS: Of 66 RCTs with CHM for type 2 diabetes mellitus, 61 (92.4%) trials had both a treatment group and a control group. Twenty-seven (40.9%) RCTs compared CHM plus conventional drug vs conventional drug, 24 (36.4%) compared CHM vs conventional drug, 5 (7.6%) compared CHM vs placebo, 3 (4.5%) compared CHM plus conventional drug vs conventional drug plus placebo, 3 (4.5%) compared CHM plus conventional drug vs other CHM, 1 (1.5%) compared CHM vs no treatment, 1 (1.5%) compared CHM plus placebo vs conventional drug plus placebo, 1 (1.5%) compared CHM vs CHM plus conventional drug vs conventional drug vs placebo, and 1 (1.5%) compared CHM vs conventional drug vs CHM plus conventional drug. CONCLUSION: A variety of control groups were used in RCTs of CHM for type 2 diabetes mellitus, including placebo, active, and no treatment control groups. Justification for selecting particular types of control groups were not provided in the trials reviewed in this study. Different control groups may be appropriate according to the study objectives, and several factors should be considered prior to selecting control groups in future RCTs of CHM. RECOMMENDATIONS: (1) Investigators of CHM who design clinical trials should understand the rationale for selecting different types of control groups; (2) Control groups for RCTs should be selected according to study objectives; (3) Active control groups should select interventions for comparisons that have the strongest evidence of efficacy and prescribe them as recommended; (4) Placebo control groups should select a placebo that mimics the physical characteristics of test intervention as closely as possible and is completely inert; (5) No treatment control groups should only be used when withholding treatment is ethical and objectives outcomes will not be subject to bias due to absent blinding; (6) Crossover control groups may be appropriate in chronic and stable conditions.

Control Groups↗

PubMed2006

Improving the quality of randomized controlled trials in Chinese herbal medicine, part III: quality control of Chinese herbal medicine used in randomized controlled trials.

OBJECTIVE: To discuss quality control of Chinese herbal medicine (CHM) in randomized controlled trials (RCTs), and to provide suggestions for improving this aspect in future clinical study in this therapeutic area. METHODS: A search of the Cochrane Library was conducted to identify RCTs of CHM. Quality control information reported in those RCTs was then assessed independently. RESULTS: The search yielded a total of 167 RCTs of CHM for a variety of conditions. A total of 11 CHM preparations were used in those RCTs. Only one trial discussed quality control of the CHM interventions used. Issues affecting the safety and efficacy of CHM products used in RCTs were discussed including standardization of raw herbal materials, processing methods, screening for product contamination, and effects of combination products. CONCLUSION: The overall quality of reporting of RCTs of CHM was poor, reflecting the need for improvements in reporting future clinical trials in this area. RECOMMENDATIONS: To improve quality control of CHM used in RCTs in future, we recommend developing and implementing guidelines such as Good Agricultural Practice (GAP) for Chinese crude drugs, and current Good Manufacturing Practice (GMP) specific to CHM products. Chemical analyses of individual herbs of CHM and combination products are also recommended to provide reference standards for quality control.

Drugs, Chinese Herbal↗

PubMed2006

Improving the quality of randomized controlled trials in Chinese herbal medicine, part IV: applying a revised CONSORT checklist to measure reporting quality.

OBJECTIVE: To discuss the quality of reporting in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM), and to provide suggestions for improving the reporting of future clinical studies in this therapeutic area. METHODS: A search of the Cochrane Library was conducted to identify RCTs of CHM. A revised CONSORT checklist designed for CHM clinical studies was implemented. The revised CONSORT checklist contained 63 items, including the following new items added specifically for CHM: (1) "syndrome of disease" based on Chinese medicine theories; (2) rationale of CHM formula; (3) formula composition; (4) preparation form of CHM; (5) quality control of CHM. RESULTS: The overall reporting quality of the RCTs as assessed with the revised CONSORT checklist varied between 19% and 44%, with a median score of 32% (standard deviation 8%). CONCLUSION: The overall quality of reporting of RCTs of CHM evaluated with a revised CONSORT checklist was poor, reflecting the need for improvements in reporting future clinical trials in this area. RECOMMENDATIONS: To improve the quality of reporting of RCTs of CHM, we recommend adopting a revised CONSORT checklist that includes items specific to CHM. We also recommend that editors of CHM journals require authors to use a structured approach to presenting their trials as a condition of publication.

Drugs, Chinese Herbal↗

PubMed2006

[Analysis and consider of technical identification for 32 cases medical tangle in medical association].

OBJECTIVE: To analyze cause of medical accidents and actuality of technical identification in medical tangle. METHODS: 32 cases (17 death, 15 survive) of medical tangle by technical identification (according to sex, age, mostly diseases, sequel) and identified results (whether or not mistake, cause and effect connection, duty degree) have been studied. RESULTS: 13 cases of 32 medical accidents have been determined.19 cases have been attributed to no medical accidents. Causes of medical accidents were most due to negligence of sense of duty. CONCLUSION: The incidence rate of medical accidents can be decreased by strengthen colligated stuff of medical affairs personnal. We suggest that our state bring out more perfect legislation of autopsy in order to gain positive effect of technical identification in medical tangle. The medical mistake among grade of medical accidents should be added so that justice of identification could be improved.

Accidents↗

PubMed2006

[Lymphangiogenes and location of tumor lymphatic vessels induced by VEGF-C in primary breast carcer].

OBJECTIVE: To investigate the lymphangiogenesis and location of tumor lymphatic vessels induced by vascular endothelial growth factor C (VEGF-C) in primary breast cancer. METHODS: The expression of VEGF-C mRNA in 89 cases of primary breast cancer was detected by in situ hybridization, and lymphatic vessels with vascular endothelial growth factor receptor-3 (VEGFR-3) were labeled by immunohistochemistry SP method. RESULTS: VEGF-C mRNA expressed in 49 of all 89 cases of primary breast cancer, and the expression rate was 55.06%. The expression of VEGF-C mRNA was positively correlated with lymphatic vessel density (LVD) and axillary lymph node metastasis, LVD and the rate of axillary lymph node metastasis were significantly higher in VEGF-C mRNA positive group than those in the negative group (both P < 0.05). Different levels of lymphangiogenesis took place in all cases of breast cancer, but it was mainly located in tumor stroma, and apparently mature lymphatic vessels were not found in cancer nests. LVD was positive related with the clinical stage and axillary lymph node metastasis in breast cancer; the clinical stage, the LVD, the axillary lymph node metastasis in positive group were higher than those in the negative group (P < 0.05). CONCLUSION: The expression of VEGF-C mRNA is positively correlated with lymphangiogenesis and axillary lymph node metastasis in primary breast cancer. Lymphangiogenesis induced by VEGF-C predominantly takes place in the tumor stroma tissue, and mature lymphatic vessels are not found in cancer nests.

Adult↗

PubMed2006

[Relationship between expression of nestin in experimental brain contusion and injury time].

OBJECTIVE: To observe the alteration of nestin intervals in the experimental traumatic brain injury and investigate its relation to the injury intervals. METHODS: The rat brain contusion was conducted by falling impact injury. After various survival interval (0.5, 6, 12 h and 1, 3, 7, 14, 28 d), immunohistochemical SP method was used for observing the expression of nestin in the cortex, hippocampal dentate gyrus and the corpus callosum on injury side. RESULTS: Expression of nestin positive cells increased at 0.5 h and reached the maximum level in 7 d after brain contusion, then the expression decreased gradually. The intensity of nestin staining in the the cortex and the hippocampal dentate gyrus decreased to normal on 28 d. As to the corpus callosum of injury side it remained weak on 28 d. CONCLUSION: The changes of nestin immunohistochemical staining can be used as an index for forensic estimation of early injury time.

Animals↗