The Z-drugs (zolpidem, zopiclone, and zaleplon), as the innovative hypnotics, have an improvement over the traditional benzodiazepines in the management of insomnia. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. As benzodiazepines, Z-drugs exert their effects through increasing the transmission of γ-aminobutyric acid. Z-drugs overdose are less likely to be fatal, more likely would result in poisoning. Z-drugs can be detected in blood, urine, saliva, and other postmortem specimens through liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Z-drugs have improved pharmacokinetic profiles, but incidence of neuropsychiatric sequelae, poisoning, and death may prove to be similar to the other hypnotics. This review focuses on the pharmacology and toxicology of Z-drugs with respect to their adverse effect profile and toxicity and toxicology data in the field of forensic medicine.
Acetamides/poisoning* ; Azabicyclo Compounds/poisoning* ; Drug Overdose ; Forensic Medicine/trends* ; Forensic Toxicology/trends* ; Humans ; Hypnotics and Sedatives/poisoning* ; Piperazines/poisoning* ; Pyridines/poisoning* ; Pyrimidines/poisoning* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Zolpidem

SUMMARY Objective:To investigate the influence of cryoprotectants and cooling rates in vitrificationmethod on the spindles of rabbit M Ⅱ oocytes.Methods:Rabbit oocytes were verified by using cryoloopwith ethylene glycol(EG)singly or EG combined with dimethyl sulphoxide(DMSO)as cryoprotectants,and cooled by taking oocytes directly into liquid nitrogen or by vitrification machine.After frozen rabbit o-ocytes thawed,the microtubulin and chromosome of the spindles were fixation and stained by immunofluo-rescent method.Confocal microscope was used to reveal spindle configuration.Results:In the two proto-cols of single EG used and EG combined with DMSO,the spindles were severely injured.But in protocolof EG combined with DMSO and at ultra-rapid cooling rate,the normal configuration of spindle rate ofthawed rabbit oobytes was similar to that of the control group.Conclusion:The protocol of EG combinedwith DMSO as cryoprotectants and with extremely high cooling rate by vitrification machine can producethe best effect on conservation of spindle configuration in vitrification of rabbit oocytes.

Objective To study the clinical features, therapy and prognosis of neurosyphilis typically manifested as dementia to improve its diagnosis and treatment. Methods A retrospective analysis of patients with neurosyphilis typically manifested as dementia, searched in Medline and Chinese Biomedical Literature Datebase (CBM) from 1989 to 2010, was performed. Results Forty-four studies involving 62 patients (61 cases of general paresis and 1 case of syphilitic psychoneurosis) were evaluated;the clinical features of them included the follows: male are more common;most of them had insidious onset;memory impairment and personality changes were the first common symptoms;diffuse cerebral atrophy was found in MRI and CT;serum and cerebrospinal fluid (CSF) syphilis antibody reaction was positive with some exceptional case;definite diagnosis was difficult;after anti-syphilitic therapy, symptoms could be improved more or less in a short time;and evidence of long-term prognosis was insufficient. Conclusion Both general paresis and syphilitic psychoneurosis could cause dementia. Dementia patients should be given serum and CSF syphilis antibody examination routinely if the causes of dementia are unknown. Anti-syphilitic and symptomatic treatments mostly enjoy good curative effects in a short term. Close follow-up is necessary in observing the forward effects.

OBJECTIVETo investigate nuclear factor kappa B (NF-kappaB) activation induced by lipopolysaccharide (LPS) in rat peritoneal macrophages (PMAs) and the inhibitory effect of resveratrol on NF-kappaB activation.

METHODSPMAS from normal SD rats were randomly divided into 7 groups, including a control group, a LPS group and 5 resveratrol groups (I-V). PMAs of the control group were incubated in DMEM, and those in LPS group in DMEM containing LPS (10 microg/ml). PMAS of resveratrol groups I-V were incubated in DMEM containing LPS (10 microg/ml) and different concentrations of resveratrol. After 24 h of incubation, NF-kappaB activation in the PMAs was determined, and the expression levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and nitric oxide (NO) in the culture medium were measured.

RESULTSExposure to LPS resulted in an excessive enhancement of cytokine and NO expressions in the PMAs. Resveratrol at 1.25-10 microg/ml produced a dose- dependent inhibition of cytokine and NO expressions and on NF-kappaB activation in LPS-stimulated PMAs.

CONCLUSIONResveratrol can inhibit LPS-induced NF-kappaB activation in rat PMAs and subsequently suppress the expressions of TNF-alpha, IL-1 and NO.

Animals ; Cytokines ; metabolism ; Lipopolysaccharides ; pharmacology ; Macrophage Activation ; drug effects ; Macrophages, Peritoneal ; drug effects ; immunology ; metabolism ; Male ; NF-kappa B ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology

OBJECTIVETo investigate the role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA-GAS5) in breast cancer progression and epithelial-mesenchymal transition (EMT) of the cancer cells.

METHODSReal-time quantitative PCR (qRT-PCR) was used to detect the expression of lncRNA-GAS5 in 37 pairs of breast cancer and adjacent non-tumor tissues and in parental MCF-7 cells and paclitaxel-resistant MCF-7 (MCF-7/PR) cells, and the correlation of lncRNA-GAS5 expression with the clinical stage and lymph node metastasis of breast cancer was investigated. The expressions of the genes related with cell cycle and EMT at both the mRNA and protein levels were detected using qRT-PCR, Western blotting and immunohistochemistry. The changes in the biological behaviors and morphology of breast cancer cells with either lncRNA-GAS5 knockdown or overexpression were observed. Nude mouse models were established bearing breast cancer xenografts derived from MCF-7/PR cells or MCF-7/PR cells over-expressing lncRNA-GAS5, and the inhibitory effect of paclitaxel on tumor growth was evaluated.

RESULTSThe transcriptional levels of lncRNA-GAS5 were significantly lower in breast cancer tissues than in the adjacent non-tumor tissues (P<0.05), and decreased lncRNA-GAS5 expression was significantly correlated with TNM stage and lymph node metastasis of breast cancer (P<0.05). lncRNA-GAS5 expression was also significantly lowered in paclitaxel-resistant breast cancer cells and showed a positive correlation with P21 expression and a negative correlation with CDK6. MCF-7 cells during EMT presented with a lowered expression of lncRNA-GAS5, whereas lncRNA-GAS5 over-expression strongly suppressed MCF-7/PR cell migration and invasion, and increased the susceptibility of the cells to paclitaxel. In the tumor-bearing nude mouse models, lncRNA-GAS5 overexpression in the tumor cells obviously enhanced the inhibitory effect of paclitaxel on tumor growth and lung metastasis by reversing the EMT marker proteins.

CONCLUSIONA decreased expression of lncRNA-GAS5 promotes lung metastasis of breast cancer by inducing EMT, suggesting the potential of lncRNA-GAS5 as a therapeutic target in breast cancer.

OBJECTIVETo approach the treatment efficiency of replication defective adenovirus carrying HSV-tk gene under control of the human telomerase reverse transcriptase (hTERT) promoter in a mouse xenografts model of prostate cancer.

METHODSIt was erected that the model of human prostate cancer in BALB/C nude mouse followed by locally injecting Ad-hTERT-HSV-tk and peritoneal injection of GCV. The anti-tumor efficacy was evaluated by index of tumor volume, tumor weight, relative tumor curative, and tumor growth curve. Afterwards, the TUNEL and transmission electron microscope to overview apoptosis of tumor cells were used. Finally, immunohistochemistry for detecting PCNA of tumor cells were applied.

RESULTSCompared with the control group, all viruses treatment groups demonstrated tumor growth inhibition. Among 3 treatment groups, antitumoral effect of Ad-hTERT-HSV-tk/GCV was much stronger than other two groups (P < 0.05). Obvious necrosis and apoptosis was observed by TUNEL, and PCNA was detected by immunohistochemistry in tumor tissues in all viruses treatment group.

CONCLUSIONSAd-hTERT-HSV-tk/GCV system is highly efficacious to inhabit the growth of human prostate cancer.

Adenoviridae ; enzymology ; genetics ; Animals ; Female ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Promoter Regions, Genetic ; genetics ; Prostatic Neoplasms ; pathology ; therapy ; Recombination, Genetic ; Telomerase ; genetics ; Thymidine Kinase ; genetics

Objective: To elucidate the possible mechanism responsible for the improved protection of terminal warm blood cardioplegia (TWBC) after hypothermic cardiopulmonary bypass (CPB) through analysis of tubulin (TB) components changes in myocardial cells exposed to TWBC. Methods: Stable animal models of CPB were established in cats, which were then randomly divided into 2 groups. Group Ⅰ was subjected to intermittent cold blood cardioplegia (ICBC) whereas group Ⅱ to ICBC followed by TWBC before uncross-clamping. Left ventricular performance was then monitored and evaluated by LVSP, LVEDP, ±dp/dtmax and t-dp/dtmax in both groups and semi-quantitive analysis was conducted with Western blot method as to the content and constitution of TB in myocardial cells at 15 min, 120 min after aortic crossclamping (ACC) and 5 min,15 min, 60 min,120 min after reperfusion. Results: Within 120 min after reperfusion, systolic and diastolic functions decreased significantly in group Ⅰ as compared with group Ⅱ(P<0.05). At 115 min after ACC and 15 min after reperfusion, the content of free and polymerized TB in both groups had no difference (P>0.05). At 120 min after ACC and 5 minutes after reperfusion, there was a significant difference between groupⅠ andⅡ (P<0.01). Conclusion: TWBC accelerates the repolymerization of myocardial TB during hypothermic CPB, which may mediate the improved cardiac performance in the early stage of myocardial reperfusion.

Objective To develop a rapid test for the detection of F1 antigen of Yersinia Pestis based on gold-immunochromatography.Methods F1 antibodies were coupled with colloidal gold to prepare collidal gold reagent,which was used to detect F1 antibodies based on double antigen sandwich.The collidal gold reagent was estimated for its sensitivity specificity and stablity in labs and 1798 samples were detected in 17 surveillance spots.Results The reagent was sensitive to 0.0010 g/L F1 antigens.The reagens kept stable when it had been placed at 4℃ or room-temperature for 12 months and did not react to Yersinia pseudotuberculosis and Yersinia enterolitica.In 17 surveillance labs the reagent was used to test 1798 viscera samples from animal.resulting an accordance rate of 97.11%(1746/1798)to bacterial culture and 96.83%(1741/1798)accordance to reverse indirect hemagglutination assay(RIHA),showing a higher detection rate[9.23%(166/1798)]compared with RIHA[6.79%(122/1798)]and bacterial culture[6.28%(113/1798)].Conclusions The collidal gold reagent,sensitive and specific in diagnosing Yersinia pestis infection of both human and animals,is a rapid method in surveillance spot.

Background: This study aimed to explore relationships between job stress and psychological adaptation and how they related to interpersonal needs through mood states among female migrant manufacturing workers. Methods: A cross-sectional survey was conducted in 16 factories in Shenzhen, China. Sociodemographic, job stress, psychological adaptation and other psychological information of was collected. Structural equation modeling was performed to delineate the internal relationship between variables. Results: The hypothetical structural equation model exhibited acceptable model fit among female migrant manufacturing workers (χ2 = 11.635, df = 2, χ2/df = 5.82, p = 0.003, RMSEA = 0.090, CFI = 0.972, SRMR = 0.020). Job stress was directly associated with mood states and interpersonal needs; Psychological adaptation was directly associated with mood states and indirectly associated with interpersonal needs; Bootstrapping tests demonstrated mediation effect of mood states in the way from psychological adaptation to interpersonal needs. Conclusion Female migrant manufacturing workers who suffered stress from job and the process of psychological adaptation may have worse mood states and workers with worse mood states are more likely to develop unmet interpersonal needs, a proximal factor of suicidal ideation.