In the reform of medical microbiology education on medical students of 8-year-education pro-gram, we compared the traditional teaching methods with Problem Based Learning (PBL) method. Through our practice, we have found that the combination of traditional lecture-based learning and PBL seems to better match the students’ way of learning. The lack of basic knowledge of the students hindered their learn-ing effect during the bilateral discussion in the PBL education. We also found that the application of PBL in medical microbiology education is an iterative process and should be promoted step by step. The theoretical level and the innovative ideas of the teachers play a crucial role in the dynamic process of education reform.

The distribution fate and solubilization behavior of indomethacin through the intestinal tract were investigated with in vitro lipolysis model, by comparing the Capmul MCM and Labrafil M 1944 CS type I lipid formulations. The results showed that the more favorable solubilization was in the aqueous digestion phase from each lipid formulations for indomethacin. The lipolysis rate and extent were decided with chemical constitution of the lipid excipients, which meant that less indomethacin was transferred from the long chain polar oil lipid solution into the aqueous digestion phase. Increasing the concentration of indomethacin in the lipid formualitons from a solution to a suspension led to a linear increase in the concentration of indomethacin attained in the aqueous digestion phase from lipid formulations. This study also implied that adverse effects of the lipolysis rate and extent on drug absorption were could be taken into consideration when screening lipid formulations. Lipid suspensions likely had better enhancement of drug absorption. Last, this study demonstrated that a potential basis for optimizing and assessing type I lipid formulations and also researching in vivo-in vitro correlations of lipid formulations were provided by an in vitro lipolysis model.
Caprylates ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Digestion ; Excipients ; Glycerides ; chemistry ; Indomethacin ; administration & dosage ; pharmacokinetics ; Lipolysis ; Models, Biological ; Polyethylene Glycols ; chemistry ; Solubility ; Suspensions

This paper report the development of a new dosage form - self-microemulsifying mouth dissolving films, which can improve the oral bioavailability of water insoluble drugs and have good compliance. A three factor, three-level Box-Behnken design was used for optimizing formulation, investigated the effect of amounts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose on the weight, disintegration time, cumulative release of indomethacin after 2 min, microemulsified particle size and stretchability. Optimized self-microemulsifying mouth dissolving films could fast disintegrate in (17.09 +/- 0.72) s; obtain microemulsified particle size at (28.81 +/- 3.26) nm; and release in vitro at 2 min to (66.18 +/- 1.94)%. Self-microemulsifying mouth dissolving films with broad application prospects have good compliance, strong tensile and can be released rapidly in the mouth through fast self-microemulsifying.
Administration, Oral ; Biological Availability ; Cellulose ; analogs & derivatives ; chemistry ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Hypromellose Derivatives ; Indomethacin ; administration & dosage ; Methylcellulose ; analogs & derivatives ; chemistry ; Particle Size ; Solubility ; Surface Properties ; Tensile Strength

Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.
Animals ; Biological Availability ; Drug Delivery Systems ; methods ; Emulsions ; Indomethacin ; administration & dosage ; pharmacokinetics ; Intestinal Absorption ; Lipolysis ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; administration & dosage ; chemistry ; Solubility

A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.
Animals ; Calcium ; metabolism ; Caprylates ; chemistry ; Digestion ; Glucose ; metabolism ; Glycerides ; chemistry ; Indomethacin ; chemistry ; Intestinal Absorption ; Lipids ; chemistry ; Lipolysis ; Models, Biological ; Potassium ; metabolism ; Rats ; Rats, Sprague-Dawley

Toxicity of different processed was evaluated Polygoni Multiflori Radix by determining the hepatotoxic potency for selecting processing technology. Process Polygoni Multiflori Radix using high pressure steamed, Black Bean high pressure steamed, atmospheric steamed for different time. Using normal human hepatocytes (L02) as evaluation model, hepatotoxic potency as index to evaluate hepatotoxic potency of different processed Polygoni Multiflori Radix. Analysis chemical composition of some processed products by UPLC-MS. Hepatotoxic bioassay method cloud evaluate the toxicity of different Polygoni Multiflori Radix samples. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix, high pressure steamed three hours attenuated was better. Different processing methods have different effects on chemical constituents of Polygoni Multiflori Radix. Comparing with crude sample, the contents of gallic acid, 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside, emodin-8-O-beta glucoside and emodin were decreased in processed products with 3 kinds of different methods. The change trend of 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside content was similar with hepatotoxic potency. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix. Processing methods and time attenuated obvious impact on toxicity. Recommended further research on the attehuated standard control of Polygoni Multiflori Radix concocted.
Biological Assay ; Cell Line ; Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Fallopia multiflora ; chemistry ; toxicity ; Hepatocytes ; drug effects ; Humans ; Plant Roots ; chemistry ; toxicity

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.
Animals ; Celastraceae ; chemistry ; metabolism ; toxicity ; Chromatography, Liquid ; methods ; Drugs, Chinese Herbal ; metabolism ; toxicity ; Liver ; drug effects ; metabolism ; Male ; Mass Spectrometry ; methods ; Rats ; Rats, Sprague-Dawley

BACKGROUNDRecent studies have demonstrated that dexamethasone (DEX) interferes with immune responses by targeting key functions of dendritic cells (DCs) at the earliest stage. However, the cellular and molecular mechanisms are still incompletely understood. This study aimed to explore the possible mechanisms by investigating the roles of DEX on differentiation, maturation & function of murine DCs and the effects of DEX on DCs via Toll-like receptor 4 (TLR4)-nuclear factor (NF)-kappaB mediated signal pathway.

METHODSImmature DCs (imDCs) were cultured from murine bone marrow (BM) cells. We added DEX into culture medium at different time. The expression of CD11c, CD86 and I-A(b) (mouse MHC class II molecule) was determined by flow cytometry. We determined the expression of NF-kappaB and its inhibitory protein I-kappaBalpha by electrophoretic mobility shift assay (EMSA) and Western blotting, respectively. The productions of interleukin (IL)-12p70 and IL-10 in cell culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTSDEX impaired differentiation of DCs from murine bone marrow progenitors, and inhibited lipopolysaccharide (LPS) induced maturation of DCs. DEX significantly inhibited NF-kappaB expression of normal DCs, the higher the DEX concentration or the longer the DEX treatment time, the more obvious the effect. However, DEX had little effect on LPS-induced NF-kappaB activation, and partially impaired LPS-induced I-kappaBalpha degradation. DEX significantly decreased LPS induced IL-12p70 production by DCs. Interestingly, our results showed a synergistic effect between DEX and LPS on the production of IL-10 by DCs.

CONCLUSIONSDEX inhibits the differentiation and maturation of murine DCs involved in TLR4-I-kappaB-NF-kappaB pathway, and also indirectly impairs Th1 development and interferes with the Th1-Th2 balance through IL-12 and/or IL-10 secretion by DCs.

Animals ; Blotting, Western ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Dendritic Cells ; cytology ; metabolism ; Dexamethasone ; pharmacology ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Male ; Mice ; NF-kappa B ; metabolism ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; metabolism

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Bile Acids and Salts ; metabolism ; Bilirubin ; blood ; Chemical and Drug Induced Liver Injury ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Fallopia multiflora ; chemistry ; HMGB1 Protein ; metabolism ; Hepatocytes ; drug effects ; Interleukin-1beta ; metabolism ; Liver ; drug effects ; pathology ; Plant Extracts ; pharmacology ; Rats ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUNDRecent studies have indicated that chronic stress may give rise to brain damage, which is related to the genesis of depression. The purpose of this study is to investigate the effects of extract of Ginkgo biloba (EGb) and venlafaxine on depression.

METHODSRats were treated with chronic and comprehensive stress to create a depression model. Immunohistochemistry was used to detect the expression of brain-derived neurotrophic factor (BDNF) in the hippocampal CA3 neurons of rats treated with different drugs. Behavioral changes of these rats were also examined.

RESULTSThe expression of BDNF in the hippocampal CA3 neurons of the depression model decreased with a reduction in exploring behavior and a significant increase in fecal production. The expression of neuron nitric-oxide synthase (nNOS) protein also increased in the rats compared to normal controls. The rats treated with EGb and venlafaxine showed an increase in expression of BDNF and exploring behavior compared to untreated rats, but a decrease in nNOS and fecal production.

CONCLUSIONSRats sustain damage to the brain after being subjected to chronic and comprehensive stress. Our research has indicated that combined EGb with venlafaxine enhances the protection of neurons and decreases damage to the brain, while relieving the side effects of synthetic antidepressants.

Animals ; Antidepressive Agents, Second-Generation ; administration & dosage ; Brain Injuries ; complications ; metabolism ; Brain-Derived Neurotrophic Factor ; biosynthesis ; Cyclohexanols ; administration & dosage ; Depression ; drug therapy ; etiology ; Drugs, Chinese Herbal ; administration & dosage ; Ginkgo biloba ; chemistry ; Hippocampus ; metabolism ; Male ; Phytotherapy ; Rats ; Rats, Wistar ; Venlafaxine Hydrochloride