Adult ; Aminosalicylic Acid ; therapeutic use ; Female ; Humans ; Manganese Poisoning ; drug therapy

The study on the pharmacokinetics of traditional Chinese medicines (TCMs) is a linking science during the modernization of TCMs, and plays an important role in the studies on the complex material base of TCMs, the in vivo process of ingredient/ component and the pharmacokinetics-pharmacodynamics correlation. However, because of the multi-ingredient/component system of TCMs, how to scientifically reveal the pharmacokinetics that is consistent with TCMs' characteristics has long been a hotspot and difficulty for the exploration. The optimal composition structure of the material basis of TCMs shows the best efficacy, while the difference between the multi-ingredient/component composition structures in the efficacy is closely related to their absorption, transport, metabolism and excretion in vivo. In this article, the authors systematically review the study methods for pharmacokinetics of TCMs and their compounds, and explore the pharmacokinetics of TCMs based on the "component structure theory". As a result, the method for integrating TCM component structure and the TCM pharmacokinetics was proposed to be adopted to intensively study the effect of the component structure on the in vivo TCM multi-ingredient/component pharmacokinetic characteristics, in order to promote the TCM modernization and innovation in China.
Animals ; Area Under Curve ; Chemistry, Pharmaceutical ; Humans ; Medicine, Chinese Traditional ; methods ; Pharmacokinetics ; Structure-Activity Relationship

OBJECTIVETo investigate the plasticity and the role of plasticity in the auditory cortex of rats which experienced tinnitus by screening the plasticity markers immediately early gene c-fos and the NMDA receptor's subtype NR2A.

METHODSThirty white Wistar rats were randomly distributed into 3 groups: sodium salicylate group (n = 12), physiological saline group (n = 12) and normal control group (n = 6). Tinnitus were induced by salicylate administration and tested by behavioral conditioning studies, and then immunohistochemical staining was used to observe the expression of c-fos and NR2A in the auditory cortex of each group.

RESULTSBehavioral evidence indicated that all of the twelve rats in the sodium salicylate group perceived tinnitus. Fos-positive neurons were observed in all rats, while they appeared as typical dark dots, corresponding to a labeling restricted to their nucleus. NR2A protein was mainly expressed in the cytoplast and membrane of the cortical pyramidal cells. The expression of c-fos and NR2A immunoreactive neurons in auditory cortexes of the sodium salicylate group was significantly higher than that of other two control groups.

CONCLUSIONSThe higher expression of c-fos and NR2A indicate that the neurotransmitters and receptors should be involved in the tinnitus, as well as suggest that neuronal plasticity occurs in the auditory cortex of rats experienced tinnitus, which may be played an important role in the mechanism of tinnitus.

Animals ; Auditory Cortex ; metabolism ; Neurons ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Tinnitus ; metabolism

Objective To identify the differential serum proteins in patients with hepatic injury resulting from coal-burning type of arsenism. Methods Six serum samples were collected from patients with liver injury resulting from coal-burning type of arsenism and healthy subjects(control gruop) in endemic arsenism area. Twodimensional gel electrophoresis(2-DE) was performed to separate serum proteins, after silver staining, the differential expression of proteins were analyzed and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS). Results The 2-DE map of serum protein patterns of patients and normal control were established successfully. The results showed that there were an average of (824 ± 31 ) spots and (782 ± 42) spots on 2-DE matching of the patients and control groups and the matching rate was 94.9%(782/824). From these two groups 49 differential protein spots were identified, of which over 3 times the difference in the expression of 30 protein spots were singled out and MALDI-TOF-MS analysis was carried out. Ten proteins were identified. Upregulated expression was observed in alpha-2-macroglobulin, B-cell receptor-associated protein, keratin 1,apolipoprotein A-I, and down-regulated expression was observed in haptoglobin, α2-heremans-schimid-glycoprotein,mitogen-activated protein kinase 4, zinc finger protein 323, ZAP-70 and SP40 in the patient group. Conclusions The well-resolved and reproducible 2-DE serum patterns of patients are established and some differentially expressed proteins are characterized. Whether these proteins of differential expression are serum markers for liver injury resulting from coal-burning type of arsenism need to be further verified.

A biosurfactant-producing strain(S_6)was isolated from oil-containing wastewater in oxidation ditch and identified as Pseudomonas aeruginosa based on physiological and biochemical experiments and 16S rDNA sequence analysis.Infrared spectrum analysis revealed that S_6 produced glucolipid in the process of metabolism.It was observed that S_6 decreased the surface tension of water from 72 mN/m to 33.9 mN/m with the critical micelle concentration(CMC)of 50mg/L.The measurement of oil displacement and surface tension demonstrated that the fermented liquid had stable surface activity at varying range of salinity,pH,amount of dissolved oxygen.The optimal culture condition was obtained through orthogonal experiment:glucose 10g/L,urea 5g/L,KH_2PO_4 1g/L,liquor of microelement 2mL,pH 8.0,water 1000mL;and the biosurfactant production under optimal culture condition was 0.173g/L.

Objective To observe the effects of Jianpi Huoxue Prescription on the subcutaneous transplantation of tumor cell apoptosis and angiogenesis; To discuss its possible mechanism of action. Methods SMMC-7721 hepatoma mice models were established. 60 tumor bearing male mice were randomly divided into blank group, model group, 5-Fu group, Jianpi Huoxue Prescription high-, medium- and low-dosage groups, with 10 rats in each group. Model group and Jianpi Huoxue Prescription high-, medium- and low-dosage groups were given medicine with relevant concentrations for gavage, once a day. 5-Fu group was given 5-Fu for intraperitoneal injection every other day. The weight, tumor weight and tumor inhibitory rate of each group were compared two weeks later. The protein expressions of VEGF and VEGFR-2 were detected by immunohistochemistry, microvessel density (MVD) were calculated, and the expressions of Survivin and Caspase-3 mRNA were detected by RT-qPCR. Results Compared with model group, protein expressions of VEGF and VEGFR-2, MVD, Caspase-3 and Survivin mRNA decreased in Jianpi Huoxue Prescription high-, medium- and low-dosage groups, and the most obvious differences were in 5-Fu group and Jianpi Huoxue Prescription high-dosage group (P<0.05). Conclusion Jianpi Huoxue Prescription can inhibit tumor growth by inhibiting angiogenesis and inducing apoptosis.

OBJECTIVE: To establish a hepatocyte immunotoxicity model for screening of liver protective medications. METHODS: Cytotoxicity was induced by coincubating BCG-pretreated rat hepatocytes in vivo and with 10 mg/L LPS in vitro. Biphenyldimethylesterate (DDB), malotilate(MLT), silybin(SB) and glycyrrhizin (GRZ) were coincubated along with LPS to prevent the hepatocyte injury and verify the applicability and reliability of the model. AST, LDH and nitric oxide (NO) were measured in both the serum and supernatant. The liver and spleen index were calculated and the liver histopathologic changes were examined microscopically. RESULTS: Supernatant AST, LDH and NO in the BCG combined LPS group were increased in comparison with the control group (P<0.01). This increase was attenuated by the addition of DDB, MLT, SB and GRZ (P<0.05). The serum AST, NO and liver and spleen index were also increased significantly compared with the control group (P<0.01). Microscopic exam revealed serious histopathologic changes in the BCG combined LPS group. Hepatoxicity with associated liver enzyme elevation but histopathologic changes were attenuated by DDB, MLT, SB and GRZ. CONCLUSION: BCG combined LPS-induced hepatocyte immunotoxicity in an in vitro rat model may be a useful technique to assess the effectiveness of liver protective medications.

To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

OBJECTIVETo investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin (EM) on the regulation of gastric motility in diabetic rats.

METHODSThe motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals.

RESULTSDiabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus in the diabetic rats. Intracerebroventricular (i.c.v.) administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM (91.56 nmol, i.c.v.) dose-dependently increased the amplitude by (174.82 +/- 48.62)% (P<0.05), and increased the frequency by (70.43 +/- 27.11)% (P < 0.05) in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109.

CONCLUSIONMotilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; Dose-Response Relationship, Drug ; Erythromycin ; administration & dosage ; pharmacology ; Gastrointestinal Agents ; administration & dosage ; pharmacology ; Gastrointestinal Motility ; drug effects ; physiology ; Hippocampus ; cytology ; metabolism ; Injections, Intraventricular ; Male ; Microinjections ; Motilin ; agonists ; metabolism ; Neurons ; cytology ; metabolism ; Paraventricular Hypothalamic Nucleus ; cytology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Gastrointestinal Hormone ; agonists ; Receptors, Neuropeptide ; agonists ; Statistics, Nonparametric ; Supraoptic Nucleus ; cytology ; metabolism

The present study was designed to observe the expressions of bone morphogenetic protein-7 (BMP-7) and inhibitory Smads in kidney of rats with diabetic nephropathy (DN), and explore the possible mechanism of DN. Male Wistar rats weighing 180-220 g were single injected with streptozocin (STZ, 55 mg/kg body weight) for 2, 4, 8 and 16 weeks to induce DN. Blood glucose, kidney weight/body weight and 24-hour urine protein in the control and DN rats were examined; the expressions of BMP-7, Smad6 and Smad7 were detected by using immunohistochemical techniques, Western blot and real-time PCR. The results showed that blood glucose and 24-hour urine protein in DN rats were higher than that in the control rats and kidney weight/body weight was also elevated in DN rats, especially in 16-week STZ-induced rats. The expressions of BMP-7 and Smad6 proteins in DN rats were elevated, while BMP-7 mRNA expression was increased 2 weeks after STZ injection and decreased 16 weeks after STZ injection. The expressions of Smad7 protein and mRNA were elevated in DN rats 2 weeks after STZ injection and decreased 16 weeks after STZ injection. In addition, the expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type I (COL-I) mRNA were increased in DN rats. These results suggest in the early stage of DN, increase in BMP-7 and inhibitory Smad expression may play a role in the feedback regulation and restrain the development of DN.
Animals ; Bone Morphogenetic Protein 7 ; genetics ; metabolism ; Collagen Type I ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Nephropathies ; metabolism ; Kidney ; metabolism ; pathology ; Male ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Smad6 Protein ; genetics ; metabolism ; Smad7 Protein ; genetics ; metabolism ; Transforming Growth Factor beta1 ; metabolism