Ajoene, a garlic-derived natural compound, enhances chemotherapy-induced apoptosis in human myeloid leukaemia CD34-positive resistant cells

The reputation of garlic as an effective remedy for tumours extends back to the Egyptian Codex Ebers of 1550 BC. Several garlic compounds, including allicin and its corresponding sulfide, inhibit the proliferation of several human malignant cells. Ajoene is a garlic-derived compound produced most efficiently from pure allicin and has the advantage of a greater chemical stability than allicin. Recently, ajoene was shown to inhibit proliferation and induce apoptosis of human leukaemia CD34-negative cells including HL-60, U937, HEL and OCIM-I. More significantly, ajoene was shown to induce 30% apoptosis in myeloblasts from a chronic myeloid leukaemia patient in blastic crisis. Acute myeloid leukaemia (AML) is a heterogeneous malignant disease in which disease progression at the level of CD34-positive cells has a major impact on resistance to chemotherapy and relapse. MATERIALS AND METHODS: The aim of the present study was to investigate the effect of ajoene on changes in the expression of apoptosis-related proteins: bcl-2 and caspase-3, induced by two principal drugs used in treatment of AML, cytarabine and fludarabine, in KGI human myeloid leukaemia CD34-positive-resistant cells. Both quantitative ELISA measurement of bcl-2 and colourimetric measurement of active caspase-3 were used. RESULTS: Quantitative ELISA measurement of bcl-2 (units per million cells) showed treatment of KG1-resistant leukaemia cells with 40 microM ajoene alone to significantly reduce the bcl-2-expression from 239.5 +/- 1.5 in control cultures to only 22.0 +/- 4.0 in ajoene-treated cultures. Fludarabine had significantly more inhibitory effect on bcl-2-expression than cytarabine in KGI-resistant myeloid leukaemia cells. Ajoene significantly enhanced the inhibitory effect of the two chemotherapeutic drugs, cytarabine and fludarabine, on bcl-2-expression in KGI cells. Bcl-2-expression could not be detected in fludarabine + ajoene-treated cultures. The Western blot of bcl-2-expression in KGI control and treated cells confirmed the quantitative ELISA measurements. Quantitative measurement of activated caspase-3 (pg per million cells) showed the two drugs, cytarabine and fludarabine, significantly increased the activated caspase-3 level in KGI myeloid leukaemia cells. CONCLUSION: The addition of ajoene enhanced the activation of caspase-3 in both cytarabine- and fludarabine-treated KGI cells. In conclusion, the present results suggest a potential role for the combination of ajoene with fludarabine-based chemotherapy in the treatment of refractory and/or relapsed AML patients. Further studies are warranted to evaluate a similar enhancing effect for ajoene in blast cells from AML patients in primary cultures.     

Stimulus Omission and Dishabituation of the Skin Conductance Response

Three experiments investigated the effects on the skin conductance response of S2 omission following 15 S1-S2 presentations. These effects were examined at omission and on the following S1-S2 (re-presentation) trial. In Experiment 1 (N = 36), S1 was a 5-sec slide of a snake and S2 was 1 sec of either 65 or 105 dB white noise. The S1-S2 interval was 4 sec. Both frequency and amplitude of omission responses were a positive function of S2 intensity, and responding to S2 re-presentation was reliably higher than on the preomission trial. Experiment 2 (N = 36) used the same S1, an S2 of 105dB, and two additional groups which controlled for stimulus omission and spontaneous recovery. Omission of S2 again produced increased responding to its re-presentation. In Experiment 3 (N = 72), S1 and S2 were moderately intense tones (80dB) and lights (1089 cd/cm². The procedure for the experimental and two control groups was essentially the same as in Experiment 2, except that S1 modality was counterbalanced across subjects. The experimental group displayed significantly larger responses to S2 on the re-presentation trial than the control groups regardless of its modality. The results are discussed in terms of theories of habituation with special emphasis on the concept of priming utilized by Wagner (1976) and Öhman (1979).     

影响糖尿病患者心血管危险因素集簇现象的因素

目的 分析影响糖尿病患者多种心血管危险因素集簇现象的因素。方法 调查654例糖尿病患者并发症情况和血糖、胰岛素、HbA1c、胆固醇、甘油三酯、LDL-胆固醇、HDL-胆固醇、体重指数、腰围、臀围以及腰臀围比值等因素,采用HOMA公式计算出胰岛素抵抗指数。按照并存心血管危险因素（高血压、全身性肥胖、中心性肥胖、高胆固醇血症、低HDL-胆固醇血症）数量。进行分析。结果 并有3种以上的心血管危险因素明显地高于随机的单一因素并存在计算预测值,餐后胰岛素水平和胰岛素面积随危险因素的增加而增加,采用有性别差异的全身性肥胖和中心性肥胖的诊断标准,女性糖尿病患者有更多的心血管危险因素。如果采用男女性别相同的诊断标准。这种并存多种心血管危险因素的性别差异则消失,多数患者的这些危险因素未得以良好的控制。结论 糖尿病多种心血管危险因素集簇是常见的,可能与高胰岛素血症及性别有关。     

Does physical activity differ between youth with and without intellectual disabilities?

BackgroundChildren and youth with intellectual disabilities (ID) are known to face obstacles to physical activity participation, yet the activity patterns of this population are not well characterized.Objective/Hypothesis: In this study, time spent in moderate to vigorous physical activity (MVPA), type, and frequency of participation in physical activities were assessed in youth with ID and in a comparison group of typically developing (TD) youth.MethodsWeekly participation in MVPA in 38 youth with ID and 60 TD youth was assessed via accelerometry. Participants were also administered an interview about the frequency and type of physical activities they engaged in over the past year.ResultsAfter adjusting for age and sex, youth with ID spent significantly less time in MVPA (33.5 vs. 46.5 min/day, p = 0.03) and were less likely to meet the US Physical Activity Guidelines than TD youth (6% vs. 29%, p = 0.01). Although time in MVPA was lower in youth with ID, females with ID participated in physical activities more frequently than TD females (47.1 vs. 28.2 times/month, p = 0.008) and also reported engaging in a greater variety of physical activities (7.8 vs. 5.2 activities/year, p = 0.01). No differences between males in the frequency of physical activity participation or the number of activities performed were observed. Both groups reported walking/hiking and active video as top activities.ConclusionsFindings emphasize the need for targeted efforts to increase MVPA in youth with ID.