AMPK在妊娠期糖尿病发病机制中的作用

腺苷酸活化蛋白激酶是一种重要的蛋白激酶,主要作用是协调代谢和能量平衡.腺苷酸活化蛋白激酶被激活后,在增加骨骼肌对葡萄糖摄取、增强胰岛素敏感性、增加脂肪酸氧化以及调节基因转录等方面发挥重要作用.已经证实脂联素有调节糖脂代谢的作用,但其作用机制尚不十分清楚,很可能是通过腺苷酸活化蛋白激酶介导,对脂联素信号转导通路的研究将成为进一步理解脂联素作用的关键所在.而脂联素又是妊娠期糖尿病的预测因子,所以腺苷酸活化蛋白激酶逐渐成为对妊娠期糖尿病研究中的焦点.     

The estrous cycle affects cocaine self-administration on a progressive ratio schedule in rats

Although it has been demonstrated that many of the behavioral responses to psychomotor stimulants are gender dependent and hormonally sensitive, few studies have examined the possibility that the estrous cycle interacts with drug reinforcement in laboratory animals. The present experiment assessed the effect of the estrous cycle on two aspects of cocaine self-administration behavior: the breaking point on a progressive ratio (PR) schedule and the rate of cocaine intake on a fixed ratio one (FR1) schedule. On the PR schedule, the first lever response produced a drug infusion. Subsequent response requirements escalated with each injection until the behavior extinguished. Breaking points were defined as the final ratio completed. On a FR1 schedule, the estrous cycle had no effect on the rate of drug intake. On a PR schedule, female rats reached higher breaking points during estrus than during other stages of the estrous cycle. Furthermore, female rats displayed higher breaking points than male rats. It appears that the estrous cycle influences an animal's motivation to self-administer cocaine.     

抗人热休克蛋白60效价增高提示急性心源性胸痛患者的一年预后不良

目的：探讨抗人热休克蛋白60或抗分枝杆菌热休克蛋白65抗体是否能够预测因急性心源性胸痛入院的患者一年预后不良。设计：前瞻性观察研究。地点：教学医院。患者：连续588例急诊收治的疑似急性心源性胸痛患者。主要观察指标：测定入院后晨起血样的抗人热休克蛋白60和抗分枝杆菌热休克蛋白65效价。出院后终点为冠心病死亡、非致死性心肌梗死、冠状动脉搭桥术、经皮穿刺腔内冠状动脉成形术、血管造影或因心脏缺血性胸痛加重再次入院。     

The current cavernosometric criteria for corporovenous dysfunction are too strict.

In an attempt to define the hemodynamic and radiographic parameters of normal erectile function 6 patients 20 to 41 years old (mean age 30.3 years) with erectile dysfunction that spontaneously resolved after a comprehensive evaluation were reviewed. The results included normal hormonal assays, normal penile biothesiometry and normal penile brachial index. The sleep tumescence and rigidity tracings were abnormal according to the criteria that sleep erections occur every 90 minutes, are associated with penile rigidity of greater than 550 gm. plus an increase in penile circumference of greater than 1.5 cm. and last longer than 15 minutes. High resolution ultrasonography, pulse wave Doppler ultrasound, dynamic pharmacocavernosometry and dynamic cavernosography were performed. After testing the patients were informed that no organic abnormalities had been detected. No medical or surgical treatment was given. The hemodynamic values are presented as suggested normal parameters: maintenance rate (mean 11 +/- 3 cc per minute), initial decompression rate (mean 59 +/- 17 mm. Hg/30 seconds) and radiographic findings (visualization of the cavernous, external pudendal and deep dorsal veins during pharmacocavernosography, performed at intracorporeal pressures of 100 mm. Hg). All 6 patients had maintenance rates of greater than 5 cc per minute. Of these 6 patients 5 had initial decompression rates of greater than 48 mm. Hg/30 seconds and 4 had 5-minute, post-infusion steady state values of less than 50 mm. Hg, criteria that have been used to define corporovenous dysfunction.     

Complications associated with maxillary nerve block anaesthesia via the greater palatine canal

This paper documents the type, frequency and duration of complications associated with regional anaesthesia of the maxillary nerve via the greater palatine canal in a series of 101 patients treated in the Oral Surgery Department, United Dental Hospital of Sydney.     

A case of lesser curve ulceration after combined highly selective vagotomy and abdominal aortic aneurysm resection

A 71 year old white male is reported in whom ischaemic ulceration of the lesser curve of the stomach, a variant of lesser curve necrosis, occurred after the combined procedures of highly selective vagotomy (HSV) and abdominal aortic aneurysmectomy. Other operations, particularly fundoplication and incidental splenectomy, have been implicated in the aetiology of lesser curve ischaemia, an otherwise rare complication of HSV. This case suggests that concomitant aortic surgery may also increase the risk of lesser curve ischaemia after HSV. Careful endoscopic monitoring of patients undergoing these combined procedures is therefore recommended to better define the risk.     

5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors.

An 18-kDa leukocyte membrane protein, termed 5-lipoxygenase-activating protein (FLAP), has recently been shown to be the target of two structurally distinct classes of leukotriene biosynthesis inhibitors. These classes of inhibitors are based on indole and quinoline structures and are represented by MK-886 and L-674,573, respectively. A novel class of hybrid structure based on the indole and quinoline classes of inhibitors, termed quindoles, has recently been developed. These compounds, exemplified by L-689,037, are potent inhibitors of leukotriene biosynthesis, both in vitro and in vivo. In the present study, we have developed and characterized a potent radioiodinated photoaffinity analogue of L-689,037, termed [125I]L-691,678. This compound was used in immunoprecipitation studies with FLAP antisera to show that the quindole series of leukotriene biosynthesis inhibitors interact directly with FLAP. In addition, we show that MK-886, L-674,573, and L-689,037 specifically compete, in a concentration-dependent manner, with both [125I]L-691,678 and [125I]L-669,083, a photoaffinity analogue of MK-886, for binding to FLAP. These results suggest that these three classes of leukotriene biosynthesis inhibitors share a common binding site on FLAP, providing further evidence that FLAP represents a suitable target for structurally diverse classes of leukotriene biosynthesis inhibitors.     

Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression.

Recently we reported that human dermal fibroblasts, or conditioned media obtained from such cells, affect the growth of human melanoma cells as a direct function of tumor progression: melanoma cells obtained from early-stage (metastatically incompetent) primary lesions were growth inhibited, whereas cells obtained from more advanced (metastatically competent) primary lesions, or metastases, were growth stimulated. Ion-exchange and gel-filtration chromatography of fibroblast conditioned medium revealed the inhibitor to be a protein of molecular mass between 20 and 30 kDa and distinct from the stimulator. This is the approximate molecular mass of interleukin 6 (IL-6), a ubiquitous multifunctional cytokine known to affect in particular many kinds of hemopoietic and lymphoid cells. Since this cytokine is known to be made by fibroblasts, we attempted to determine if the human fibroblast-derived growth inhibitor (hFDGI) was identical to IL-6. Neutralizing antibodies specific for IL-6 completely eliminated the inhibitory activity of hFDGI. Moreover, exposure to human recombinant IL-6 was found to inhibit the growth of early-stage melanoma cells obtained from radial growth phase (RGP) or early vertical growth phase (VGP) primary lesions in three of four cases. In contrast, melanoma cells from a number of more advanced VGP primary lesions, or from distant metastases, were completely resistant to this IL-6-mediated growth inhibition. Acquisition of an "IL-6-resistant" phenotype by metastatically competent melanoma cell variants may provide such cells with a proliferative advantage within the dermal mesenchyme (a hallmark of melanoma cells that are malignant), helping them eventually to dominate advanced primary lesions and to establish secondary growths elsewhere.