Quantity not composition of dietary fats represents the dominant contributor to experimental obesity: Relevance to human pathophysiology

Plant fats are low in saturated fats but high in unsaturated fats compared to animal fats, and are supposedly less obesogenic. This study compared the obesogenic effects of plant and animal derived fatty diets in Wistar rats. Rats of each gender were divided into three dietary (standard chow (SC), high fat diet rich in animal fat (HFDaf) and a high fat diet rich in plant fat (HFDpf)) groups of ten each and fed for 17 weeks. Anthropometric, Adiposity and nutritive variables were assessed using standard methods. Comparing HFDpf to HFDaf: Abdominal circumference (AC),initial feed intaken (IFI), final feed intake(FFI), final body weight (FBW), white adipose tissue (WAT) were increased but brown adipose tissue (BAT) decreased in male rats fed with HFDpf; also, there were increased body length, IFI, FFI but decreased AC, FBW, BAT in female rats fed with HFDpf. Comparing male to female rats: Thoracic circumference, IFI, FFI, energy intake were increased while Adiposity index decreased across diet groups in male rats; the AC, FBW increased while WAT, BAT decreased in HFDpf fed group, also, BAT was increased but AC, FBW decreased in HFDaf fed group in male rats. Palatability and high feed efficiency of consumed diets were more associated with obesogenic risk than just the level of saturation. Therefore, Obesogenic effects of fatty diets in both genders is more dependent on the quantity (amount) of fatty diet consumed than the dietary fat composition alone.     

Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

Background

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. Because the pathway may not be completely inhibited after blockade of PI3K itself, due to feedback through mammalian target of rapamycin (mTOR), more effective inhibition might be expected by targeting both PI3K and mTOR inhibition.

Materials and methods

We investigated the effect of two dual PI3K/mTOR (both mTORC1 and mTORC2) inhibitors, NVP-BEZ235 and NVP-BGT226, on SQ20B laryngeal and FaDu hypopharyngeal cancer cells characterised by EGFR overexpression, on T24 bladder tumor cell lines with H-Ras mutation and on endothelial cells. Analysis of target protein phosphorylation, clonogenic survival, number of residual ??H2AX foci, cell cycle and apoptosis after radiation was performed in both tumor and endothelial cells. In vitro angiogenesis assays were conducted as well.

Results

Both compounds effectively inhibited phosphorylation of Akt, mTOR and S6 target proteins and reduced clonogenic survival in irradiated tumor cells. Persistence of DNA damage, as evidenced by increased number of ??H2AX foci, was detected after irradiation in the presence of PI3K/mTOR inhibition, together with enhanced G2 cell cycle delay. Treatment with one of the inhibitors, NVP-BEZ235, also resulted in decreased clonogenicity after irradiation of tumor cells under hypoxic conditions. In addition, NVP-BEZ235 blocked VEGF- and IR-induced Akt phosphorylation and increased radiation killing in human umbilical venous endothelial cells (HUVEC) and human dermal microvascular dermal cells (HDMVC). NVP-BEZ235 inhibited VEGF-induced cell migration and capillary tube formation in vitro and enhanced the antivascular effect of irradiation. Treatment with NVP-BEZ235 moderately increased apoptosis in SQ20B and HUVEC cells but not in FaDu cells, and increased necrosis in both tumor and endothelial all cells tumor.

Conclusions

The results of this study demonstrate that PI3K/mTOR inhibitors can enhance radiation-induced killing in tumor and endothelial cells and may be of benefit when combined with radiotherapy.     

血小板激活因子对大鼠脑血管通透性的影响及药物的保护作用

颈内动脉注射血小板激活因子(PAF),再给伊文思蓝,可见脑实质染色程度加深,而颈内动脉只注射伊文思蓝,脑实质未见染色。而我们合成的新药SZ-1可剂量依赖性地抑制PAF诱导的脑实质伊文思蓝染色程度的加深。在体外培养的脑微血管平滑肌细胞上,PAF能显著刺激~(14)-花生四烯酸的释放,而SZ-1能剂量依赖性地抑制这种释放,提示PAF在脑内产生的损害除与其他因素相关外,还与其刺激花生四烯酸释放有密切关系,SZ-1对PAF引起的脑部损害有保护作用。     

提高人类精液中圆形细胞数量测定的精确度

本研究的目的是提高用过氧化物酶试验检测精液中的白细胞时所得的圆形细胞数量的精确度。精液样本的圆形细胞浓度在（0．6～6）×10^6／mL之间,降低精液的稀释度,增加被测悬浮液的体积。1＋5（1：6）的稀释度适合于测量过氧化物酶活性,并能为细胞检测提供足够清晰的背景。在该稀释度下,测定Neubauer-改良精子计数板两边所有18个网格中的细胞数量,额定细胞浓度为（1．9～3．3）×10^6／mL的10个样本中只有3个样本的圆形细胞数／〉400个。由于更低浓度的精子稀释液不适合测定圆形细胞或其过氧化物酶反应产物,所以无法精确测量（抽样误差5％）参考下限值（1×10^6／mL）。结果表明,正是由于测定精液中的10个样本中圆形细胞很难精确到1×10^6／mL,所以白细胞精液症临界值的确定一直存在诸多分歧。因此需要建立一些统计学上合理的参考限。     

Seizure threshold to lidocaine is decreased following repeated ECS (electroconvulsive shock)

Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS all rats received a lidocaine challenge (LC) in the form of an intraperitoneal (IP) injection of lidocaine (65 mg/kg). After the injection the animals were observed for occurrence of motor seizures. A total of 67% (10/15), 47% (7/15), and 0% (0/18) of the daily, weekly, and sham groups, respectively, had motor seizures in response to the LC. In the second experiment five groups of rats received an ECS daily for 0, 1, 6, 18, and 36 days, respectively. Eighteen weeks after the last ECS all rats received an LC and 0% (0/15), 13% (2/15), 20% (3/15), 53% (8/15), and 58% (7/12), respectively, developed seizures in response to the LC. In the third experiment two groups of rats received daily ECS and sham-ECS, respectively. Twenty-four hours after the last ECS all rats received an LC. A total of 60% (9/15) of the ECS group and 0% (0/10) of the sham-ECS group had seizures in response to the LC. The study demonstrates a decrease in seizure threshold to lidocaine in ECS-pretreated rats as early as 1 day and as late as 18 weeks following the last ECS, and a positive correlation between the number of ECS administered and the proportion of animals having seizures in response to the LC was found. The convulsant effect of lidocaine has been proposed to be mediated through binding on the GABA receptor-ionophore complex. Therefore this study suggests that ECS causes long-lasting, possibly permanent, changes within the GABA-ergic system.     

皮炎消净饮I号冲剂治疗异位性皮炎的实验研究

目的：研究皮炎消净饮I号冲剂（PYXJY1）治疗异位性皮炎（AD）的作用机理。方法：①动物实验：二硝基氯苯（DNCB）所致豚鼠耳肿试验,致敏处真皮内单核细胞和淋巴细胞聚集试验;醋酸所致小鼠腹腔毛细血管通透性增加试验。②实验室检测：单克隆抗体免疫荧光标记法检测AD患有治疗前后的CD4／CD8（TH／Ts）水平。结果：PYXJY1可明显抑制二硝基氯苯所致豚鼠耳肿胀及其真皮内单核细胞和淋巴细胞聚集,抑制醋酸所致小鼠腹腔毛细血管通透性的增加,作用与氢化可的松相似。使AD患者升高的CD4／CD8降低至正常。结论：PYXJY1具有良好的抗炎和迟发变态反应作用,并可调节AD患者CD4／CD8水平,对AD有较好的治疗效果。     

Electroconvulsive shock (ECS) does not facilitate the development of kindling

Kragh Jørn, Torben Bruhn, David P.D. Woldbye and Tom G. Bolwig: Electroconvulsive shock (ECS) does not facilitate the. development of kindling. Prog. Neuro. Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 985–989.

1. 1. For many years it has been discussed whether repeated electroconvulsive shock (ECS) may induce a lasting epileptogenic effect on the brain (i.e. a kindling effect). In the present study the authors investigated whether weekly ECS do exert such an effect.

2. 2. Bipolar electrodes were implanted in amygdala of 32 rats. Following a two to three week recovery period the rats were randomly allocated to two groups. One group received 12 weekly ECS, the other 12 weekly sham-ECS.

3. 3. Three months after the last ECS/sham-ECS, kindling was initiated. Daily stimulation, eliciting an EEG-afterdischarge was given to all the rats. The animals received a total of 15 stimulations.

4. 4. ECS-pretreated animals did not kindle faster than the sham-group. The two groups reached stage 4 (clonic rearing) after 5.8 (ECS-group) and 5.7 (sham-group) stimulations, respectively.

5. 5. The authors did not find a facilitated development of kindling following ECS, instead they observed a slight, yet statistically significant inhibition of the development of the maximally generalized kindling-seizure — the stage 5 seizure — in the ECS-group.

6. 6. In conclusion: The present study did not show a kindling effect of weekly ECS suggesting that kindling requires more than repeated elicitation of after-discharge.

Early intervention: Professional views and referral practices of Australian paediatricians

Objective : To gather information from paediatricians concerning their attitudes to early intervention services for young children with developmental disabilities and to study their referral practices.
Methodology : Two hundred and ninety-five Australian paediatricians completed a postal questionnaire.
Results : Paediatricians presented a positive view of early intervention, particularly for its beneficial impact on families, and perceived the quality of services to be comprehensive or adequate. There were few differences between States, or between country or metropolitan areas. Most paediatricians make prompt referrals to early intervention services when a child has an established disability. Referral is much less likely with suspected delay.
Conclusions : Paediatricians are aware of the benefits of early intervention but additional information concerning the role of these services and their significant impact on families and children should be provided.