IL-6–174G/C genotype is associated with the bone mineral density response to oestrogen replacement therapy in post-menopausal women

A reduction in interleukin-6 (IL-6) activity may contribute to the beneficial effects of hormone replacement therapy (HRT) on the menopausal decline in bone mineral density (BMD). We have examined this hypothesis using a genetic strategy. The –174C (rather than G) IL-6 gene variant is associated with lower IL-6 expression. As such, we might anticipate the C allele to be associated with a greater response to HRT. We have tested this hypothesis. Mean three-site [spine (L1-L4), neck of femur, and Wards triangle] BMD was measured in 65 women in a 1-year randomised controlled trial of HRT with 0.625 mg oestrogen/day and 0.15 mg norgestrel (n=30). Baseline BMD was genotype-independent for both the control and HRT group. In the control group, the percentage change in BMD after 1 year was similar between genotypes (P=0.45). In contrast, in the HRT group, the rise was genotype-dependent. Those homozygous for the G allele showed a 3.62 (2.14)% increase in BMD compared with 10.44 (4.68)% for the C-homozygous group. Heterozygotes had an intermediate BMD increase of 5.6 (2.82)% [P=0.006 (P value for interaction between HRT and genotype was 0.04)] Although the study was limited by its small sample size, these are the first data to demonstrate the importance of IL-6 genotype in determining response to oestrogen therapy, rather than its physiological withdrawal.     

放松训练对高考学生身心健康的影响

目的　研究放松训练法对高考学生身心健康的影响 ,为考生心理健康水平的提高 ,减轻考前焦虑提供科学措施。方法　选择同一学校两个高中三年级的班级 ,分别作为对照组 ( n=72 )和放松训练组 ( n=70 )。高考前的 3个月开始进行全身放松训练 ,每天约 2 5分钟 ,连续两个半月。比较训练前后两组考生的心理健康水平 ,并评价放松训练法的作用效果。结果　对照组考生在考前半个月 SCL-90的阳性项目数以及焦虑、强迫、躯体化、人际敏感、抑郁等 5项因子分和 SAS总均分均显著高于 3个月前 ;放松训练组考生经 2个半月的放松训练后 ,其 SCL-90的焦虑、强迫、人际敏感、抑郁、躯体化等 5项因子分和 SAS总均分均显著低于放松训练前 ,且阳性项目数、总均分以及焦虑、强迫、抑郁、躯体化、人际敏感等 5项因子分和 SAS总均分均显著低于对照组高考前半月的相应分值。结论　随着高考的临近 ,考生的心身反应增多且加重 ,心理健康水平明显下降 ;全身放松训练法能有效改善考生的各种心身反应和紧张焦虑状况 ,有利于保护考生的心理健康     

Historical evolution,overview, and therapeutic manipulation of co-stimulatory molecules

Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families, structure, and functions has improved in recent decades. Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions. Currently, modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.     

Efficacy and tolerability of estraderm MX, a new estradiol matrix patch

Objectives: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. Methods: A multicenter, double-blin, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. Results: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6–5.5). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. Conclusions: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.     

Liminal therapy: A strategy for the complete and selective destruction of malignant tissue

The property of aerobic glycolysis commonly possessed by malignant cells points to a weakness in oxidative metabolism which has been equated in some tumours with partial uncoupling of oxidative phosphorylation. The suggestions are made, first, that this endogenous defect may account for spontaneous cell death , and, second, that its accentuation would inflict extensive tumour injury upon sensitive neoplasms. Certain drugs not in current use for the treatment of malignant disease are known to be able to interfere selectively with energy metabolism in sensitive tumours to such an extent that widespread necrotisation ensues. The drugs activate an endogenous destructive mechanism that appears to require oxygen. Liminal therapy, the maintenance of continuous destructive pressure on sensitive growths in such a manner that maximal anti-tumour activity in terms of interference with energy production is not achieved at any one time, and under conditions in which the oxygen supply is only partly depleted, is put forward as a possible means of achieving complete and selective tumour destruction .     

Lack of influence of glucagon on glucose homeostasis after prolonged exercise in rats

Summary The significance of glucagon for post-exercise glucose homeostasis has been studied in rats fasted overnight. Immediately after exhaustive swimming either rabbit-antiglucagon serum or normal rabbit serum was injected by cardiac puncture. Cardiac blood and samples of liver and muscle tissue were collected before exercise and repeatedly during a 120 min recovery period after exercise. During the post-exercise period plasma glucagon concentrations decreased but remained above pre-exercise values in rats treated with normal serum, while rats treated with antiglucagon serum had excess antibody in plasma throughout. Nevertheless, all other parameters measured showed similar changes in the two groups. Thus after exercise the grossly diminished hepatic glycogen concentrations remained constant, while the decreased blood glucose concentrations were partially restored. Simultaneously concentrations in blood and serum of the main gluconeogenic substrates, lactate, pyruvate, alanine and glycerol declined markedly. During the post-exercise period NEFA concentrations in serum and plasma insulin concentrations remained increased and decreased, respectively, while plasma catecholamines did not differ from basal values. Muscle glycogen concentrations decreased slightly. These findings suggest that in the recovery period after exhaustive exercise the increased glucagon concentrations in plasma do not influence gluconeogenesis.     

负载乳腺癌抗原单核细胞来源树突状细胞迁移能力的调控因素研究

目的：体外培养乳腺癌抗原负载的人单核细胞来源DC，应用不同刺激因子使其表面CCR7表达上调，在体外观察其迁移能力。方法：用rhGM-CSF和rhIL-4诱导MoDCs，并负载乳腺癌抗原后，分别与PGE2、LTC4或Bryo-1共培养，检测其表型及其功能变化。结果：PGE2、LTC4和Bryo-1在体外不影响MoDCs刺激淋巴细胞增殖能力和自体特异性淋巴细胞杀伤活性。与对照组MoDCs相比，PGE2和LTC4作用MoDCs后CD86表达增高，可以上调CCR7 mRBA和蛋白表达（P〈0．05）。PGE2可以使MoDCs对其配体CCL19和CCL21反应性增强（P〈0．05），而LTC4仅能使MoDCs对CCL19反应性增强。Bryo-1虽然可以促进MoDCs成熟，使其CCR7 mRNA表达增强，但在CCR7蛋白表达、迁移能力方面与对照组相似。结论：以PGE2和LTC4作用MoDCs后可以通过上调其CCR7表达，促进其迁移趋化能力。     

Ethinyl estradiol treats collagen-induced arthritis in DBA/1LacJ mice by inhibiting the production of TNF-alpha and IL-1beta

We previously demonstrated the therapeutic effects of ethinyl estradiol (EE), an orally active estrogen and a component of birth control pills, in encephalitogenic autoimmune encephalomyelitis (EAE). In this study, we report the effectiveness of EE in treating collagen-induced arthritis (CIA) induced with bovine type II collagen (bCII) in DBA/1LacJ mice, a CIA susceptible strain. Both low and high doses of EE notably suppressed clinical and histological signs of CIA in a dose-dependent manner compared to vehicle-treated controls. Oral treatment with EE decreased proliferation and secretion of pro-inflammatory factors, TNF-alpha IFN-gamma, MCP-1 and IL-6 by bCII peptide-specific T cells, production of bCII-specific IgG2a antibodies, and mRNA for cytokines, chemokines and chemokine receptors in joint tissue. This is the first report demonstrating effective treatment of joint inflammation and clinical signs of CIA with orally administered ethinyl estradiol, thus supporting its possible clinical use for treating rheumatoid arthritis in humans.