Tripterygium wilfordii has exihibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anti-tumor and anti-fertility. T. wilfordii have been used for the therapy of inflammation and autoimmune diseases including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus clinically. However, it is well known that T. wilfordii has small margin between the therapeutic and toxic doses and could cause serious injury on digestive, reproductive and urogenital systems. Among all the organs, liver is one of the most remarkable targets of T. wilfordii-induced toxicities, and the damage is more serious than others. It is generally accepted that T. wilfordii-induced liver injury is a result of the combined effects of toxic elements of T. wilfordii. It is reported in several studies that the mechanism of T. wilfordii-induced liver injury may be related to lipid peroxidation, cell apoptosis and immune damage, and so on. Licorice is one of the most commonly used Chinese herbal medicine, with effects of heat- clearing and detoxicating, anti-inflammatory and hepatoprotective, reconciling various drugs, and so on. Licorice often accompany T. wilfordii in clinical application which can significantly reduce the liver injury induced by T. wilfordii. The attenuated effect is exact, but the mechanism is still a lack of in-depth study. This paper reviews the studies on T. wilfordii-induced liver injury and the related mechanism as well as licorice and other traditional Chinese medicine accompany T. wilfordii to reduce the injury in recent years, so as to provide reference for related research in the future.
Animals ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; Glycyrrhiza ; Humans ; Inactivation, Metabolic ; Medicine, Chinese Traditional ; Tripterygium

To analyze the composition regularity of prescriptions containing Scutellaria baicalensis in Drug Standard of Ministry of Public Health of the Peoples Republic of China--Chinese Patent Medicines and Preparations on the basis of the traditional Chinese medicine inheritance support system (TCMISS), in order to provide reference for new drug R&D. the platform's software V2.0 was applied to establish a database of prescriptions containing S. baicalensis. The software's statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze commonly used drugs, combination rules and core combination of S. baicalensis prescriptions. Having analyzed 477 prescriptions containing S. baicalensis, the researchers summarized 45 most commonly used drug combinations, whose ingredients mostly had functions of heat-clearing and damp-drying, purging fire for removing toxin and hemostasis. Drugs adopted in core combinations were relatively concentrated and selected according to definite composition methods. There were 23 diseases that S. baicalensis were most frequently applied in the treatment. Having compared three highly frequent diseases--cold, cough and dizziness, the researchers concluded that S. baicalensis could show different therapeutic effects through different combination ratios. Therefore, TCMISS (V2.0) is an important tool in analyzing the composition regularity of traditional Chinese medicines. The longitudinal and parallel comparison method is an effective method for studying the clinical composition regularity of S. baicalensis, while providing reference for new drug R&D.
China ; Drug Compounding ; statistics & numerical data ; Drug Therapy ; statistics & numerical data ; Humans ; Plant Extracts ; analysis ; therapeutic use ; Scutellaria baicalensis ; chemistry

Some recent studies which are focused on γ-aminobutyric acid (GABA) system indicate that GABA dysfunction may play an important role in the pathogenesis of schizophrenia.In this review,alterations of GABAergic neurotransmission in the prefrontal cortex and hippocampus in schizophrenia brain,novel antipsychotic drugs with GABAergic activity are discussed.

It is popularly accept that blood-brain barrier affects drug transport and distribution.Pharmacokinetic parameters will help us predict the pharmacological action,drug-interactions and adverse reaction.This article reviewed the major pharmacokinetic parameters in central nervous system,such as PS product(permeability surface area product),K_(in) or CL_(in) (influx clearance into the brain),K_(out) or CL_(out) (efflux clearance from the brain),T_(1/2eq,in) (intrinsic brain equilibrium half-life),%ID/g (percent of injected dose per gram brain),K_(p,uu) (unbound brain/unbound plasma concentration ratio at steady state),V_(u,brain) (apparent volume of distribution in brain),T_(1/2,brain) (half time in brain).These pa-rameters describe the aspects of blood-brain permeability and the rate and extent of brain drug delivery.

In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.
Animals ; Apoptosis ; drug effects ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; Fats ; metabolism ; Glucose Tolerance Test ; Humans ; Islets of Langerhans ; cytology ; drug effects ; Male ; Pancreas ; drug effects ; metabolism ; Rats ; Rats, Wistar

Objective To determine the clinical features,neurophysiological characteristics and cervical magnetic resonance imaging of sensory neumnopathy,and to describe the pathology of skin nerve, sural nerve and spinal dorsal columns.Methods Two patients who died from sensory neuron disease (SND)after infection of digestive tract were discussed including clinical features and ancillary tests which included neurophysiology and pathology of peripheral nerve and spinal dorsal columns.Associated documents are reviewed.Results Early ataxia,widespread sensory symptoms and global loss of deep tendon reflex were the distinctive signs of SND,which was characterized by non-length-dependent abnormalities of sensory nerve action potentials,a hallmark of ganglionopathies.The second patient showed normal cervical magnetic resonance imaging possibly because of short course of disease,while diffuse hyperintensity in the spinal posterior columns of SND was reported.Demyelination of spinal posterior columns and loss of mostly large diameter nerve fibers without regeneration clusters were the main pathological features.Conclusions The distinctive clinical features and neurophysiological characteristics of SND indicate that peripheral sensory nerve fibers are widely damaged.Pathology of spinal posterior columns confirm that central sensory pathway are impaired which allow the localization of the pathologic site to the dorsal root ganglion neurons.Cervical spinal MRI of SND are possibly normal at early phase.

Objective To investigate the effects of regular dose and toxic dose of quetiapine (QTP) on PXR signaling and downstream CYP3A4 and P-gp mRNA expression in rat brain and liver and also further investigate the effects of PXR agonist (dexamethasone,DEX) on the mRNA expression of PXR,CYP3A4 and P-gp in these tissues in context of drug overdose to illustrate the potential detoxication mechanisms of PXR activation in the brain and liver.Methods Normal group was intraperitoneally injected with QTP 10 mg · kg-1 once,intoxication modeling group was intraperitoneally injected with QTP 100 mg · kg-1 once,and the PXR activation experimental group was intraperitoneally injected with DEX 2.5 mg · kg-1 · d-1 for consecutive 4 days.SD rats were randomly divided into 4 groups:blank group,normal group,model group,and experimental group.SD rats were dosed daily by the vehicle or dexamethasone 2.5 mg · kg-1 · d-1 for 4 days,and were intraperitoneally injected with the vehicle or QTP 10 or 100 mg · kg-1 on the fourth day.After the 4 days of drug treatment,the rats were sacrificed 12,24,48 h after the last dose.The mRNA expression of PXR,cytochrome P4503A4(CYP3A4) and P-glycoprotein (P-gp) of rats in 4 groups were assessed by Real-time PCR method.Results After administration QTP for 24 h,the expression of PXR mRNA in liver in blank group,normal group,model group,and experimental group were (15.8 ± 0.8) × 10-3,(27.8 ± 2.4) × 10-3,(33.3 ± 1.4) × 10-3,(49.2 ± 2.0) × 10-3,the difference between blank group and normal group was statistically significant (P ＜ 0.05),the difference between normal group and model group was statistically significant (P ＜ 0.05),and the difference between model group and experimental group was statistically significant (P ＜ 0.05).The factors in CYP3A4 and P-gp in liver of rats were same with PXR in liver,and the factors in prefrontal cortex and hippocampus of rats were same with in liver.Our data showed that QTP dose-dependently increased the expression of PXR,CYP3A4 and P-gp in both brain and liver.In addition,we found that the combination use of DEX along with the toxic dose of QTP accelerated the drug-induced mRNA expression of PXR,CYP3A4 and P-gp.Conclusion QTP itself could induce the signaling pathway of PXR-CYP3A4/P-gp,which was accelerated by the adjunctive use of PXR agonist,indicating that activation of PXR signaling pathway could activate detoxification system quickly and effectively,resulting in quick detoxification of xenobiotic and protection of organs.

Taking the genome DNA of Infectious Bovine Rhinotracheitis Virus (IBRV) as the template, the gG gene was amplified with PCR and cloned into the T cloning vector pMD18-T. After being identified by restriction digestion and DNA sequencing, the insert was subcloned into the expression vector pGEX-KG. Sodium docecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot assay showed that this gene was expressed as both soluble form and inclusion body by the transformed E. coli BL21 strain (DE3). The fusion protein was purified and used as the coating antigen to develop the indirect Enzyme-Linked Immunosorbent Assay (ELISA). Comparison between this gG-ELISA and commercial IBRV gB-ELISA Kit (IDEXX) was made in the detection of 380 cow serum samples. The results demonstrated an agreement of 92%. By using this novel gG-ELISA, 1248 cow serum samples were tested and the average positive rate of IBRV antibodies for imported cows is 21.7%, while the positive rate ranged greatly from 0.0%-41.5% for Hubei local Chinese Black and White Dairy Cows.
Animals ; Antibodies, Viral ; blood ; immunology ; Antigens, Viral ; genetics ; immunology ; Cattle ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay ; methods ; Escherichia coli ; genetics ; metabolism ; Female ; Herpesvirus 1, Bovine ; genetics ; immunology ; Male ; Recombinant Proteins ; biosynthesis ; genetics ; immunology ; Sensitivity and Specificity ; Viral Proteins ; biosynthesis ; genetics ; immunology

OBJECTIVETo investigate the expression of NF-kappaB in peripheral blood polymorphonuclear leukocyte (PMN) of acute pancreatitis (AP) and to assess the preventive effectiveness of pyrrolidine dithiocarbamate (PDTC) on NF-kappaB in vitro.

METHODSNineteen patients and 16 healthy individuals as control were enrolled in this study. The expression of NF-kappaB in PMNs was determined by gel electrophoretic mobility shift assay (EMSA). Routine clinical examination results and computed tomography findings of AP were recorded in all patients.

RESULTSThe PMNs from the patients with AP showed higher levels of NF-kappaB activities than those from control subjects (P < 0.01), severe acute pancreatitis (SAP) group showed much higher than mild acute pancreatitis (MAP) group (P < 0.05). In vitro, PDTC could reduce the NF-kappaB activity in PMNs of patients with AP, and its effectiveness at 2 mmol/L was stronger than at 1 mmol/L (P < 0.05). The PMNs from control subjects pretreated with 2 mmol/L PDTC before stimulation with the plasma from patients with SAP showed lower levels of NF-kappaB activities than did those untreated (P < 0.05).

CONCLUSIONThe NF-kappaB activation in peripheral blood PMNs participate in the course of acute pancreatitis and can be inhibited by PDTC in vitro.

Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; NF-kappa B ; biosynthesis ; blood ; Neutrophils ; drug effects ; metabolism ; Pancreatitis ; metabolism ; Pyrrolidines ; pharmacology ; Thiocarbamates ; pharmacology

Carcinoma, Hepatocellular ; diagnosis ; therapy ; Humans ; Liver Neoplasms ; diagnosis ; therapy ; United States