Anal Canal/surgery* ; Anorectal Malformations ; Constriction ; Fecal Incontinence ; Humans ; Rectal Prolapse

Thienorphine is a chemically-new opioid developed in Beijing Institute of Pharmacology and Toxicology. To elucidate the chemical basis for the unique pharmacological effects of thienorphine, 15 derivatives were synthesized according to combinatorial chemistry and the structure-activity relationships of these compounds were studied. It is demonstrated that thienorphine is a potent long-acting partial agonist. N-Cyclopropylmethyl is responsible for the antagonist effect of thienorphine. More importantly, thiophene at the end of side chain is most likely the pharmacophore accounts for the long-lasting effect of thienorphine. Change of the connection of thiophene and the side chain does not result in changes in the antinociceptive activity.
Animals ; Buprenorphine ; analogs & derivatives ; pharmacokinetics ; pharmacology ; Combinatorial Chemistry Techniques ; Dose-Response Relationship, Drug ; Female ; Male ; Mice ; Mice, Inbred Strains ; Morphine ; pharmacology ; Rats ; Rats, Wistar ; Receptors, Opioid ; agonists ; Structure-Activity Relationship

To investigate the effects of Losartan,an angiotensinⅡ(AngⅡ)receptor(AT_1) antagonist,on pancreatic stellate cells(PSCs)and its possible mechanisms.Methods (1)PSCs were isolated from pancreatic cancerous samples to test the expressions of AT_1 and collagenⅠafter incubated with AngⅡor/and Losartan.(2)Ninety S-D rats were divided into normal group,control group and treatment group,with 30 rats in each.The rats in control and treatment groups were induced pancreatic fibrosis by injection of 2% trinitrobenenze sulfonic acid(TNBS)into biliopancreatic duct.Rats in treat- ment group were then treated with Losartan by garage daily and rats in control group were only given distilled water.The rats were sacrificed on day 3,7,14,21 and 28,respectively,and pancreas were removed.The histological abnormalities were observed by electron microscope.The mRNAs of trans- forming growth factor?_1(TGF?_1)and procollagenⅠwere detected by reverse transcription-polymerase chain reaction(RT-PCR).The expression of TGF?_1 and?-smooth muscle actin(?-SMA)proteins was assessed by immunohistochemistry and the level of?-SMA protein was quantified by Western blot. Results In vitro,there existed AT_1 expression in PSCs,and Losartan reduced expression of collagenⅠ.Losartan treatment reversed the histological abnormalities observed by electron microscope,com- pared to treatment with distill water.The expression of?-SMA,TGF?_1 and procollagenⅠwere signifi- cantly higher in the control group than those in normal group and were reduced by Losartan to different extent in treatment group.Conclusion AT_1 antagonist can inhibit the activation and the profibrogenic action of PSCs by blocking AT_1 receptor-mediated pathways.

OBJECTIVETo evaluate the antimicrobial effects of erythromycin microspheres against Mycoplasma pneumoniae in rats.

METHODSWith erythromycin lactobionate as the positive control, erythromycin microspheres at 3 non-toxic doses (0.1, 0.5, and 1.2 g.kg(-1).d(-1)) were administered intragastrically for 6 consecutive days in Wistar rats with Mycoplasma pneumoniae infection. The general condition and lung index of the rats were observed and measured to assess the therapeutic effects of the treatments against Mycoplasma pneumoniae infection.

RESULTSThe erythromycin microspheres at 0.1, 0.5, 1.2 g.kg(-1).d(-1) significantly alleviated the symptoms of the rats infected with Mycoplasma pneumoniae and reduced the pulmonary index of the infected rats from 1.75 to 1.45, 1.38 and 1.25, respectively (P < 0.01). An obvious dosage-effect relationship was noted between the dose of erythromycin microsphere and the tissue pathologies due to the infection.

CONCLUSIONErythromycin microspheres possess strong activity against Mycoplasma pneumoniae in rats.

Animals ; Erythromycin ; administration & dosage ; Male ; Microspheres ; Mycoplasma pneumoniae ; drug effects ; Pneumonia, Mycoplasma ; drug therapy ; Random Allocation ; Rats ; Rats, Wistar

This paper retrospectively summarized and analyzed observation of the disease and nursing care of 17 patients with pregnancy-associated fulminant type 1 diabetes and intrauterine fetal demise.Through timely supplying blood capacity and improving renal perfusion,maintaining blood glucose homeostasis and acid-alkali,potassium balance,safety of the patients was guaranteed;by providing effective psychological nursing,puerperal dietary guidance and discharge guidance,patients' rehabilitation was improved.As a result,16 patients were in stable condition,and dead babies were delivered.Major bleeding event occurred in one patient after delivering the dead baby,and the patient developed shock as well as liver and kidney failure.The patient was transferred to ICU for further treatment and became stable and was discharged after two months.

This study investigates whether kappa-opioid receptor and ORL1 receptor may interact to form a heterodimer. In immunofluorescence and co-immunoprecipitation experiments, differentially epitope-tagged receptors, colocalization and heterodimerization of kappa-opioid receptor and ORL1 receptor were used and examined in primary culturing rat neurons, Chinese hamster ovary (CHO) or human embryonic kidney 293 (HEK293) cells. The results show that fluorescence of both kappa-opioid receptor and ORL1 receptor were overlapping in primary culturing hippocampal and cortical neurons. Similarly in co-expressing CHO or HEK293 cells, HA-KOR and Myc-ORL1 were almost exclusively confined to the membranes, revealing extensive colocalization. When Flag-KOR and Myc-ORL1 were co-expressing in CHO cells, heterodimerization was identified to have the ability to co-immunoprecipitate ORL1-receptors with kappa-opioid receptor and vice versa. In the current study, further evidence was provided for the direct interaction of two subtypes of opioid receptors, kappa-opioid receptor and ORL1-receptor, to form the heterodimerization. The finding represents the novel pharmacological mechanism for modulation of opioid receptor function as well as diversity of G protein-coupled receptors.
Animals ; CHO Cells ; Cells, Cultured ; Cerebral Cortex ; cytology ; metabolism ; Cricetinae ; Cricetulus ; Dimerization ; Female ; HEK293 Cells ; Hippocampus ; cytology ; metabolism ; Humans ; Immunoprecipitation ; Male ; Neurons ; cytology ; metabolism ; Rats ; Rats, Wistar ; Receptors, Opioid ; metabolism ; Receptors, Opioid, kappa ; metabolism

OBJECTIVETo investigate the effect of sodium butyrate (NaB) on inhibition of human oral squamous carcinoma cell line.

METHODSHuman oral squamous carcinoma cell line Tca8113 was treated with different concentration of NaB. Light microscope was used to observe the morphological changes of the carcinoma cells. The cell cycle was analyzed by flow cytometry. Expression of p27(Kip1) was determined with immunocytochemical assay.

RESULTSNaB significantly inhibited the proliferation of Tca8113 in a time- and dose-dependent manner. Tca8113 cells treated with NaB was arrested in G(0)-G(1) phase. The fraction of cells in G(0)-G(1) were (63.2 ± 2.4)% and (77.2 ± 3.8)% after treated with NaB at the concentration of 2 and 4 mmol/L alternatively, whereas (48.1 ± 2.4)% in G(0)-G(1) phase were observed in control group (P < 0.05). The expression of p27(Kip1) was markedly up-regulated after being treated with NaB.

CONCLUSIONSNaB treatment can inhibit the growth of oral squamous carcinoma cell line in vitro and induce cell cycle arrest, which might be associated with the increased expression of p27(Kip1) protein.

Apoptosis ; Butyric Acid ; pharmacology ; Carcinoma, Squamous Cell ; pathology ; Cell Cycle ; Cell Division ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p27 ; biosynthesis ; Humans ; Mouth Neoplasms ; pathology ; Up-Regulation

Total RNA was isolated from kidney of BaMei pig, a local strain of Chinese pig, and then the cDNA sequence of SOCS-2 gene was cloned by RT-PCR (GenBank accepted number is EF121242). Then the cloned SOCS-2 gene was inserted into PMD19-T vector by T/A cloning, transformed into DH-5alpha, tested by PCR and sequenced. The data show that the homology of the cloned porcine SOCS-2, including 822 bp, is more than 93% and that of the deduced amino acid sequence is 89% when compared with human, rat and mice. And the molecular weight of SOCS-2 protein is about 22.25 kD and PI is 8.03. The cloning of SOCS-2 gene is useful for the further research on the molecular mechanism by which regulating growth and development of organism.
Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; DNA, Complementary ; Humans ; Molecular Sequence Data ; Protein Structure, Secondary ; genetics ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis ; Sequence Homology ; Suppressor of Cytokine Signaling Proteins ; genetics ; Swine ; genetics

The experiments were carried out on guinea pig isolated ventricular myocytes by using whole-cell patch clamp. The effects of angiotensin II (Ang II) on potassium ion channels of acute ischemic myocytes were observed. Whole-cell patch clamp recordings showed that physiological potassium current, including delayed rectifier potassium current and inward rectifier potassium current were inhibited under the condition of simulated ischemia, and then further inhibited by treatment with Ang II. ATP-sensitive potassium currents were increased under simulated ischemia and were further enhanced by Ang II treatment.
Angiotensin II ; pharmacology ; Animals ; Cells, Cultured ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; drug effects ; Male ; Myocardial Ischemia ; pathology ; physiopathology ; Myocytes, Cardiac ; drug effects ; Potassium Channels ; drug effects ; physiology

OBJECTIVETo explore the effect of berberine on lipid metabolism disorder and lipid deposition in liver cells of non-alcoholic fatty liver disease (NAFLD) rats induced by high fat diet.

METHODSAfter one week adaptable feeding, 45 SPF level male SD rats were randomly divided into 3 groups, the normal control group, the model group, and the berberine group, 15 in each group. Except those in the normal control group, all rats were fed with high fat diet to prepare NAFLD model. As for rats in the berberine group, Berberine Hydrochloride was administered by gastrogavage. HE staining and oil red O staining were performed to identify the model after 8 weeks. Hepatocytes were isolated, and their activities and purities were tested by Typan blue staining and flow cytometry (FCM). Serum levels of TC, TG, HDL-C, and LDL-C were detected using automatic biochemical analyzer. mRNA expression levels of LXRα and FAS in liver cells were analyzed by Real-time quantitative polymerase chain reaction (PCR). Protein levels of LXRα and FAS in liver cells were examined by Western blot.

RESULTSThe NAFLD rat model was successfully established by high fat diet. The yields of purified liver cells in each rat were (6.0-7.5) x 10(8). The viability of isolated liver cells with purity over 90% (tested by FCM analysis) was higher than 95%. Compared with the normal control group,the expression of LXRα and FAS at mRNA and protein levels was higher in the model group (P < 0.01). Compared with the model group, the expression of LXRα and FAS at mRNA and protein levels was obviously down-regulated in the berberine group (P < 0.01).

CONCLUSIONSLXRα/FAS signaling pathway was one of important signaling pathways of NAFLD lipid metabolism disorders. Berberine could recover hepatocyte fatty deposits in NAFLD rats by adjusting the LXR/FAS signaling pathway of hepatocytes, which might be one of important mechanisms for fighting against NAFLD.

Animals ; Berberine ; therapeutic use ; Diet, High-Fat ; Down-Regulation ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Liver ; Hepatocytes ; Lipids ; Male ; Non-alcoholic Fatty Liver Disease ; drug therapy ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction