AIM To develop a murine model for investigating the effects of prenatal cocaine exposure on the development of fetal nerve system. METHODS A nutritionally paired control group of dams injected with saline and pair fed with the COC dams were set up. Another two groups were COC groups injected with cocaine HCl and SAL group administrated with saline. After injection twice daily during gestation days 8～17,mice were decapitated on E17 and blood and brain samples were collected for pharmacological analysis and neurotransmitter analysis by HPLC.RESULTS Pharmacological analysis revealed that cocaine was found in maternal and fetal plasma at 15 min following ip administration to embryonic day E17 pregnant mice. Though COC dams and SPF dams had the same feeding condition, compared with the latter, the former had higher maternal concentrations of DA and 5 HT, lower fetal weight, brain weight, striatum weight and higher concentrations of DA and 5 HT in striatum, P

AIM To investigate the effects of in utero cocaine exposure on the fetal development, when fetuses were exposed to equal total dose but different dose and timing. METHODS Pregnant dams were randomly separated into three groups: SAL, COC20 and COC40. On E17, recorded body weight, brain weight and striatum weight of all groups, and examined the concentrations of DA and 5 HT in fetal striatum by HPLC. RESULTS Body weight of SAL, COC40, COC20 groups decreased progressively in turns. Brain weight of COC20 group and COC40 group was lower than that of SAL. Only the brain/body ratio of COC40 was decreased ( P

Objective To study the effects of prenatal cocaine exposure on the development of offspring's brains by building a murine model. Methods We weighted the body weight and brain weight of offspring on P10 from COC and SAL groups and observed the development of neuron and astrocyte in cerebral cortex by toluidine blue staining and immunohistochemistry. Results The brain weight and body weight from COC were both reduced on P10 compared with SAL group.We discovered prenatal cocaine exposure induced polarity disorder and dysplasia of neuron in cerebral cortex;the number of the astrocytes in corpus callosum and hippocampus regions decreased.Conclusion\ Pregnatal cocaine exposure can result in abnormal development of cerebral cortex of offsprings which may play an important role on cocaine induced abnormal behavior.\;[

The aim of the experiments was to develop and characterize a murine model for investigating the effects of prenatal cocaine exposure on the mother and fetus. Pregnant mice were separated into three groups: group 1 was treated with cocaine HCl at 10 mg/kg twice daily (COC); group 2 was treated with saline at 10 ml/kg twice daily (SAL); and group 3 was pair-fed with the COC dams and was injected with saline following the same schedule (SPF) from embryonic day (E) 8 to 17. We utilized high-pressure liquid chromatography (HPLC) with UV detector and electrochemical detector to test the concentrations of cocaine, dopamine and serotonin, as well as HE staining to observe morphological alterations of liver and placenta. Though less food intake and lower weight gain were observed in COC and SPF groups but not in SAL dams, lower fetal body weight and brain weight were only seen in COC offspring. Pharmacological analysis revealed that cocaine was found in fetal plasma at 15 min following intraperitoneal administration on E17, accompanied with elevated concentrations of dopamine (DA) and serotonin (5-HT) in fetal brain. We also observed morphological changes in liver and placenta of cocaine-exposed fetuses. The present study indicates that pregnancy cocaine exposure can lead to maternal undernutrition and developmental abnormality of the fetal brain, liver and placenta. It is suggested that the developmental abnormality of the fetuses induced by cocaine is due to the toxicological effect of cocaine but not to maternal undernutrition.
Animals ; Brain ; metabolism ; pathology ; Cocaine ; adverse effects ; blood ; Disease Models, Animal ; Dopamine ; metabolism ; Female ; Fetus ; drug effects ; pathology ; Liver ; pathology ; Malnutrition ; Maternal Exposure ; adverse effects ; Maternal Nutritional Physiological Phenomena ; Mice ; Mothers ; Placenta ; pathology ; Pregnancy ; Serotonin ; metabolism

OBJECTIVE: To investigate the inhibition effects of Tianshen Yizhi Recipe (TSYZR), a compound traditional Chinese herbal medicine, on decreased expression of nicotinic acetylcholine receptor (nAChR) and the neurotoxicity as well as lipid peroxidation induced by beta-amyloid peptide (Abeta) in human SH-SY5Y neuroblastoma cells. METHODS: The SH-SY5Y cells were treated by a certain concentration of TSYZR, and then exposed to Abeta(25-35). Methyl thiazolyl tetrazolium reduction assay was carried out to understand the influences of the drugs on cellular viability. Expressions of nAChR subunits (alpha3 and alpha7) at protein and mRNA levels were detected by Western-blotting and reverse transcription polymerase chain reaction, respectively. Lipid peroxidation was measured by thiobarbituric acid to observe the capacity of antioxidant of the drugs. RESULTS: TSYZR at a safe concentration could increase alpha7 protein in the cells, inhibit decreased expressions of alpha3 and alpha7 nAChR subunit proteins, prevent lower expression of alpha7 mRNA in SH-SY5Y cells induced by Abeta, reduce the neurotoxicity and lipid peroxidation resulting from Abeta, but had no significant effect on the lower expression of alpha3 mRNA. CONCLUSIONS: TSYZR can up-regulate the expression of alpha7 nAChR subunit protein and prevent decreased expressions of nAChRs and neurotoxicity as well as lipid peroxidation induced by Abeta. This drug may play an important therapeutic role in treatment of Alzheimer disease.

BACKGROUNDLipoprotein-associated phospholipase A2 (Lp-PLA2) is mainly secreted by macrophages, serving as a specific marker of atherosclerotic plaque and exerting pro-atherogenic effects. It is known that high-density lipoprotein (HDL) plays an important role against atherosclerosis by inhibiting pro-inflammatory factors, however, the relationship between HDL and Lp-PLA2 remains elusive.

METHODSIn this study, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and a platelet-activating factor (PAF) acetylhydrolase assay were performed to determine the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages upon HDL treatment of different concentrations and durations. To investigate the underlying mechanism of HDL-induced Lp-PLA2 action, pioglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, was introduced to human monocyte-derived macrophages and mRNA and protein levels of Lp-PLA2, as well as its activity, were determined.

RESULTSLp-PLA2 mRNA levels, protein expression and activity were significantly inhibited in response to HDL treatment in a dose and time dependent manner in human monocyte-derived macrophages. Pioglitazone treatment (1 - 10 ng/ml) upregulated the Lp-PLA2 mRNA level, protein expression and activity in human monocyte-derived macrophages, while the effects were markedly reversed by HDL. In addition, pioglitazone resulted in a significant increase in PPARγ phosphorylation in human monocyte-derived macrophages, which could be inhibited by HDL.

CONCLUSIONThese findings indicate that HDL suppresses the expression and activity of Lp-PLA2 in human monocyte-derived macrophages, and the underlying mechanisms may be mediated through the PPARγ pathway.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; genetics ; metabolism ; Cells, Cultured ; Humans ; Lipoproteins, HDL ; pharmacology ; Macrophages ; drug effects ; enzymology ; metabolism ; PPAR gamma ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; genetics

AIMTo develop a high throughput screening assay to identify inhibitors of intercellular adhesion molecule-1 (ICAM-1) expression in human umbilical vein endothelial cells (HUVEC).

METHODSICAM-1 expression in lipopolysaccharide-stimulated endothelial cells was measured by ELISA. The cytotoxicity of the compounds was measured by MTT.

RESULTSLipopolysaccharide (LPS) increased ICAM-1 expression in HUVEC in a concentration- and time-dependent manner. Two thousand compounds were screened and the hit rate was 1.5%. Among these 30 compounds, 24 were cytotoxic.

CONCLUSIONThe ELISA method was inexpensive, reproducible and suitable for high throughput primary cell assay. This assay was feasible to identify inhibitors of ICAM-1 and simultaneously discriminate the activity from the cytotoxic effects.

Cell Adhesion Molecules ; antagonists & inhibitors ; biosynthesis ; Cells, Cultured ; Chemistry, Pharmaceutical ; methods ; Drug Evaluation, Preclinical ; methods ; Endothelium, Vascular ; cytology ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; drug effects ; metabolism ; Lipopolysaccharides ; pharmacology ; Umbilical Veins ; cytology ; metabolism

Objective: This study was designed to investigate the prognostic value of serum β2-micorglobulin(β2-MG) level in non-Hodgkin s lymphoma(NHL) patients and its correlation with Ann Arber staging system and the pathological type. Method: Serum β2-MG levels in 75 de novo NHL patients were measured by radioimmunoassay. Results: The β2-MG level in 75 NHL patients was higher than that in nomal control level in 52％ of the patients and correlated with the Ann Arber stage. There was significant difference between two groups (P<0.01). The international prognostic index (IPI) and the response rate to chemotherapy were also correlated with the β2-MG level in serum. The response rate, the complete response, and partial response were 87.2%, 61.5%, and 25.6% in normal serum β2-MG group, while in the high β2-MG group they were only 75.0%, 50.0%, and 25.0%, respectively, which were significantly different between the two groups (P<0.05). The difference of 5-year survival between the two groups was significant (64.1% vs 27.8%, P<0.05) and favorable in normal β2-MG group. Conclusion: β2-MG level in serum is an independen prognostic factor in de novo NHL, and the patients with abnormal β2-MG level in serum have a unfavorable prognosis.

OBJECTIVETo study the feasibility and clinical efficacy of a minimally invasive sinus tarsi approach in the treatment of Sanders II calcaneus fractures.

METHODSFrom August of 2015 to July of 2016, 13 patients(totally 13 feet) with Sanders II intra-articular calcaneus fractures were treated via the minimally invasive sinus tarsi approach. The Böhler angle, Gissane angle and the length, width and height of calcaneus were compared between pre-operation and post-operation. The AOFAS ankle and foot scoring system of the orthopaedic ankle foot Association was used to evaluate the efficacy.

RESULTSAll the patients were followed up, and the duration ranged from 6 to 15 months, with an average of 9.5 months. No incision complications occurred. The Böhler angle was increased from preoperative (18.82±5.11)° to postoperative(26.63±4.45)°(=-4.16,=0.000). The Gissane angle was increased from preoperative(111.07±15.36)° to postoperative (124.56±8.71)° (=-2.75,=0.011). The length, width, height of calcaneus were absolutely improved from preoperative(69.82±5.95) mm, (42.07±3.68) mm, (41.20±3.90) mm to preoperatively(72.61±5.46) mm, (39.10±4.02) mm, (44.03±3.33) mm. According to the AOFAS, 8 patients got an excellent result, 4 good and 1 poor, and the postoperative mean score was 88.2±5.9.

CONCLUSIONSThe limited open sinus tarsi approach could be used successfully to treat displaced Sanders II fractures with less injury and effectively restored the surface of subtalar joint, however the method is not fit for the patients with comminuted fracture in lateral wall and great change in the length, width, height, varus and valgus of calcaneus.

Objective To investigate the expression of interleukin-3 receptor alpha(CD123)on bone marrow cells in acute myelocytic leukemia(AML)and its clinical significances.Methods By means of Fluorescence-activated cell sorer(FACS)and semi-quantity reverse transcripition polymerase chain reaction(RT-PCR),the expression of IL-3R?(CD123+)protein on CD34+CD38-cells and mRNA in BMMNCs of 62 AML patients of Tianjin Medical University General Hospital from March 2008 to January 2009 and 12 normal controls were detected respectively;Then the correlation between IL-3R? and the clinical stages of AML were analyzed.Results CD34+CD38-CD123+/CD34+CD38-and IL-3R? mRNA in BMMNC of 33 deno-vo or relapsed AML patients were higher than those of control group(P