miR-10a is aberrantly overexpressed in Nucleophosmin1 mutated acute myeloid leukaemia and its suppression induces cell death

Background

Semaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumours, indicating a role for plexinB1 in the pathogenesis of prostate cancer.

Results

Two specific mutations found in prostate cancer enhance RhoD binding and one other mutation results in loss of inhibition of Rac-dependent Pak1 phosphorylation and lamellipodia formation and in impairment of trafficking of plexinB1 to the membrane. None of the three characterised mutations affect PDZRhoGEF binding, RhoA activity, the interaction of plexinB1with the oncogenes ErbB2 or c-Met or ErbB2 phosphorylation. The mutations have the net effect of increasing cell motility by blocking plexinB1-mediated inhibition of Rac while enhancing the interaction with RhoD, an anti-migratory factor.

Conclusions

PlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell motility.     

Contrast medium precipitation during abdominal CT

Abdominal computed tomography (CT) scans of 55 patients who had ingested Gastrografin (meglumine diatrizoate and diatrizoate sodium) diluted to 2% with tap water and flavored with a commercial fruit juice base were reviewed. Twenty patients (36%) demonstrated intraluminal precipitation of Gastrografin shown by focal areas of markedly increased attenuation within the gastric lumen or trapped within gastric folds. Beam-hardening artifact produced by precipitation was observed, which limited the diagnostic value of some examinations. In vitro CT scans of the same Gastrografin solution titrated with hydrochloric acid or sodium hydroxide showed that by raising the pH of the solution, precipitation was virtually eliminated. Fifty-one CT scans of the abdomen using a buffered Gastrografin solution demonstrated precipitation in only five patients. Properly buffered dilute oral Gastrografin solutions should significantly decrease the prevalence of precipitation during abdominal CT examinations.     

Synergism of atenoloi and nitrendipine on hemodynamic amelioration and organ protection in hypertensive rats

OBJECTIVE： This study was designed to investigate the possible synergism of atenolol and nitrendipine on blood pressure （BP） and blood pressure variability （BPV） reductions, baroreflex sensitivity （BRS） amelioration, and organ protection in hypertensive rats. METHOD： The dose was 20 mg/kg for atenolol, 10 mg/kg for nitrendipine and 20 ＋ 10 mg/kg for the combination of these two drugs. In an acute study, a single dose was given via a catheter previously inserted into the stomach in spontaneously hypertensive rats （SHR）.     

缬昔洛韦的合成

目的;对缬昔洛韦的合成进行了研究。方法：以阿昔洛韦和Ｎ－苄氧羰基－Ｌ－缬氨酸为原料,经酰化,催化氢解反应得到了新型抗疱疹毒药物缬昔洛韦。结果;本品的元素分析,红外,质谱及核磁共振图谱数据与文献报道一致,总收率为４５．２％,结论;采用此法合成缬昔洛韦是可行的,适合于工业生产。     

新型全固态阿托品电极的研制

制备了以脲醛树脂为框架,以KCl粉末为活性组分的Ag/AgCl固体电极。以此固体电极为基体,以阿托品—四苯硼酸根离子缔合物为活性物质,研制了一种新型全固态阿托品选择电极。并对此电极的性质进行了研究,结果表明该电极稳定性较好,并能用于硫酸阿托品制剂的含量测定。     

Phenothiazines induce apoptosis in a B16 mouse melanoma cell line and attenuate in vivo melanoma tumor growth

Phenothiazines and related antipsychotics were reported to have an antiproliferative effect in several tissue cultures. The aims of this study were: a) to screen in vitro, the potential anti-cancer activity of phenothiazines in wild-type and multi-drug resistant (MDR) B16 mouse melanoma cell lines; and b) to determine the in vivo anti-tumor effect of an in vitro selected highly potent phenothiazine (thioridazine) in a murine melanoma model. The following phenothiazines were evaluated: perphenazine, fluphenazine, thioridazine trifluoperazine and chlorpromazine. All agents induced a dose-dependent decrease in cell viability in wild-type and in MDR B16 melanoma cells. Thioridazine displayed the highest antiproliferative activity. Flow cytometric analyses of 24-h treated B16 melanoma cells revealed an increase in fragmented DNA (16.3 vs 71.3% and 87.2% in controls, 25 microM and 50 microM thioridazine-treated, respectively). Apoptosis was confirmed by co-staining of thioridazine-treated B16 cells (12.5 microM) with propidium iodide and Hoechst 33342 reagents. Caspase-3 expression, a typical mediator of apoptosis, was markedly increased following a 4-h exposure of B16 cells to thioridazine (25 microM and 50 microM). This increase could be blocked by a specific caspase-3 inhibitor. In vivo studies were performed using female C57/Bl mice. Animals were inoculated with wild-type B16 cells by i.v. injection into the tail vein. Mice were treated with thioridazine (10 and 15 mg/kg x3/week i.p. or 15, and 25 mg/kg/day p.o.) and control animals received saline. Mice were monitored for 21-30 days. Body weight was recorded. After autopsy, the lung weight and number of pulmonary melanoma colonies were determined. Thioridazine administration (i.p. or p.o.) resulted in the reduction of lung tumor burden and an increase in mice survival. In conclusion, several phenothiazines, and particularly thioridazine, induced apoptosis of B16 melanoma cells and demonstrated in vivo anti-tumor activity.     

Clonidine vs. midazolam as premedication in children undergoing adeno-tonsillectomy: a prospective, randomized, controlled clinical trial

BACKGROUND: Clonidine administration in the setting of paediatric anaesthesia is associated with a number of desirable effects, e.g. preoperative sedation, analgesia and reduced anaesthetic requirements. The aim of the current study was to compare postoperative outcome variables using a prospective, randomized, double-blind design after premedication with clonidine or midazolam. METHODS: One hundred paediatric ASA physical status 1 patients (age 1-11 year) scheduled for adeno-tonsillectomy were assigned to receive rectal premedication with midazolam (300 microg kg(-1) and atropine 40 microg kg(-1); group M, n = 52) or clonidine (5 microg kg(-1 and) atropine 40 microg kg(-1); group C, n = 48) prior to a standardized sevoflurane anaesthetic. The incidence of immediate postoperative pain (0-2 h), as assessed by repeated Objective Pain Scale (OPS) scores, was chosen as the primary end-point of the study. Degree of sedation (modified Vancouver sedation scale 0-3), occurrence of postoperative vomiting (POV), and incidence of shivering and immediate postoperative confusion were registered as secondary end-points. After hospital discharge parents were instructed to continue the evaluation of pain, sedation, POV and sleep pattern during a 24-h period. Parents were also asked for their preference concerning the postoperative behaviour of their child (calm, sedated vs. alert, active). RESULTS: In the early postoperative period patients in the clonidine group had a significantly lower sum of 5 OPS scores (median = 8.0) compared to group M (median = 11.5) (P = 0.011). Administration of clonidine was also associated with a slightly higher sum of sedation scores (median = 13) in the early postoperative period compared to children receiving midazolam (median = 12) (P < 0.001). No episode of shivering was observed in the clonidine group but was present in five of the patients in the midazolam group (P = 0.057). In younger children (< 5 years) the incidence of postoperative confusion was lower in the clonidine group (P = 0.001). No difference in the frequencies of POV incidences, degree of postoperative pain, need for analgesics, or sleep pattern during the first 24 postoperative hours could be observed between the groups according to the parental evaluation. Children premedicated with clonidine were more calm and sedated compared to children in the midazolam group (P = 0.024) as judged by their parents. A significant majority of parents (75%; P < 0.001) preferred a calm and sedated child during the first postoperative 24-h period. CONCLUSION: Rectal premedication with clonidine was associated with a significant reduction of pain in the early postoperative period compared to midazolam and was also associated with moderately increased sedation during the first 24 postoperative hours. The sedative effect of clonidine is in agreement with the unambiguous finding of a parental preference for a calm and sedated child during the first 24 postoperative hours.     

Asynchronism of the recovery of baroreflex sensitivity, blood pressure, and consciousness from anesthesia in rats

Anesthesia inhibits arterial baroreflex functions such as baroreflex sensitivity （BRS）. The main objective of the present study was to determine the time course of BRS recovery from anesthesia and to determine whether BRS recovery is synchronous with the recovery of consciousness and blood pressure （BP）. Experiments were performed in male Sprague-Dawley rats using different commonly used anesthetics at routine doses through intraperitoneal administration： （1） diazepam/ketamine,     

Adverse Childhood Experiences and Smoking During Adolescence and Adulthood

Context  In recent years, smoking among adolescents has increased and the decline of adult smoking has slowed to nearly a halt; new insights into tobacco dependency are needed to correct this situation. Long-term use of nicotine has been linked with self-medicating efforts to cope with negative emotional, neurobiological, and social effects of adverse childhood experiences. Objective  To assess the relationship between adverse childhood experiences and 5 smoking behaviors. Design  The ACE Study, a retrospective cohort survey including smoking and exposure to 8 categories of adverse childhood experiences (emotional, physical, and sexual abuse; a battered mother; parental separation or divorce; and growing up with a substance-abusing, mentally ill, or incarcerated household member), conducted from August to November 1995 and January to March 1996. Setting  A primary care clinic for adult members of a large health maintenance organization in San Diego, Calif. Participants  A total of 9215 adults (4958 women and 4257 men with mean [SD] ages of 55.3 [15.7] and 58.1 [14.5] years, respectively) who responded to a survey questionnaire, which was mailed to all patients 1 week after a clinic visit. Main Outcome Measures  Smoking initiation by age 14 years or after age 18 years, and status as ever, current, or heavy smoker. Results  At least 1 of 8 categories of adverse childhood experiences was reported by 63% of respondents. After adjusting for age, sex, race, and education, each category showed an increased risk for each smoking behavior, and these risks were comparable for each category of adverse childhood experiences. Compared with those reporting no adverse childhood experiences, persons reporting 5 or more categories had substantially higher risks of early smoking initiation (odds ratio [OR], 5.4; 95% confidence interval [CI], 4.1-7.1), ever smoking (OR, 3.1; 95% CI, 2.6-3.8), current smoking (OR, 2.1; 95% CI, 1.6-2.7), and heavy smoking (OR, 2.8; 95% CI, 1.9-4.2). Each relationship between smoking behavior and the number of adverse childhood experiences was strong and graded (P<.001). For any given number of adverse childhood experiences, recent problems with depressed affect were more common among smokers than among nonsmokers. Conclusions  Smoking was strongly associated with adverse childhood experiences. Primary prevention of adverse childhood experiences and improved treatment of exposed children could reduce smoking among both adolescents and adults.