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 examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

Objective To understand emotional, behavioral problems and related determinants among rural stranded children and to provide evidence for further psychological support. Methods A total of 3944 caregivers of children in the rural areas and aged 4 to 7 years but without parents around, were randomly selected. Data were collected through Strengths and Difficulties Questionnaires (the edition for parents, SDQ). Results The overall prevalence of children with behavioral/emotional problems was 43.6% among those stranded children including 8.3% having experienced emotional symptoms, 9.5% reported to be displaying 'conduct' problems, 8.7% exhibited significant hyperactivity/inattention, 18.9% experienced peer relationship problems and 16.8% having prosocial behaviors. The prevalence of behavioral/emotional problems was significantly higher in boys than those in girls and in lower age groups. Significant differences were also found in conduct problems, hyperactivity/inattention and prosocial behaviors (P<0.01). The result from logistic regression analysis showed that factors as education level and motivation of the caregivers as well as financial support from the parents were related to emotional/ behavioral problems among the stranded children. Conclusion The prevalence of emotional and behavioral problems was high among children living the rural areas but without their parents around which should call for psychological intervention.

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

OBJECTIVETo establish a rat model of mycoplasma pneumonia (MP) for investigating the pathogenesis of MP and its therapy with drugs.

METHODSThirty Wistar rats were randomly divided into 6 groups (n=5), including a control group, a MP model group, a erythromycin lactobionate group and 3 erythromycin microspheres groups (high, middle, and low dose groups). With the exception of those in the control group, all the rats received intranasal MP administration followed by corresponding treatments administered via tail vein injection. At different time points after inoculation of the pathogen, the lungs of the rats were taken for histopathological scoring.

RESULTSIn the MP model group, the lung pathology was characterized by patchy interstitial pneumonitis with predominantly lymphocyte infiltration and mucosal edema. The bronchiolar walls became thickened and the lumens narrowed. In erythromycin lactobionate and erythromycin microspheres treatment (high and middle dose) groups, clear cell boundaries were observed in the lungs where no obvious pathological changes were found. RT-PCR amplification showed positive results of MP RNA in the model group, erythromycin lactobionate group and erythromycin microsphere groups.

CONCLUSIONThe approach described is practicable to establish rat models of MP. Erythromycin microspheres can effectively relieve the lung inflammations and has therapeutic effect on MP.

Animals ; Disease Models, Animal ; Erythromycin ; therapeutic use ; Female ; Male ; Microspheres ; Pneumonia, Mycoplasma ; drug therapy ; Random Allocation ; Rats ; Rats, Wistar