Expression of axotomy-inducible and apoptosis-related genes in sensory nerves of rats with experimental diabetes

In diabetes, peripheral nerves suffer deficient neurotrophic support-a situation which resembles axotomy. This raises the question: does inappropriate establishment of an axotomised neuronal phenotype contribute to diabetic neuropathy, and in extremis, does this provoke apoptosis? We hybridized reverse-transcribed RNA, from the dorsal root ganglia (DRG) of 8-week streptozotocin (STZ)-induced diabetic rats, to Affymetrix Rat Genome U34A chips and scanned the array for expression of (a) genes that are upregulated by axotomy, (b) proapoptotic and (c) anti-apoptotic genes. Expression of the axotomy-responsive genes coding for growth-associated protein 43 (GAP-43), galanin, neuropeptide Y (NPY), pre-pro-vasoactive intestinal polypeptide (pre-pro-VIP), neuronal nitric oxide synthase (nNOS), protease nexin 1, heat-shock protein 27 (HSP 27) and myosin light chain kinase II (MLCK II) was unaffected in ganglia from diabetic rats compared to controls; thus, no axotomised phenotype was established. The expression of the majority of proapoptotic genes in the DRG was also unaltered (bax, bad, bid, bok, c-Jun, p38, TNFR1, caspase 3 and NOS2). Similarly there was no change in expression of the majority of antiapoptotic genes (bcl2, bcl-xL, bcl-w, NfkappaB). These alterations in gene expression make it clear that neither axotomy nor apoptotic phenotypes are established in neurones in this model of diabetes.     

Medical researchers evaluate their methodological skills

BACKGROUND AND OBJECTIVE: Clinical epidemiology and statistics skills of clinical researchers are often limited. We assessed methodological skills of medical researchers and identified factors associated with higher skill levels. METHODS: In a cross-sectional mail survey at two Swiss teaching hospitals, participants (N=409) rated their ability to perform 26 research-related activities, such as identifying the research question, selecting a study design, computing the required sample size, performing data analysis, and reporting results. RESULTS: The proportion of respondents who were able to perform a specific activity was 33.2% on average, ranging from 1.5% for "numerical statistics (bootstrap, simulation, cross-validation,...)" to 76.0% for "oral presentation of results." The overall skill level (expressed as a percentage of the 26 activities) was associated with principal investigator experience (+8.7%), greater percentage of time devoted to research (+12.4% for near full-time versus no time commitment), years of research experience (+17.6% for 15-40 years versus 0 years), past number of clinical research projects (+18.0% for 15-230 projects versus 0-1 projects), and hours of formal methodological training (+32.6% for 200-1200 hours versus 0-9 hours). CONCLUSION: Self-reported methodological skills were generally modest. The most important covariates of skill levels were current time commitment to research, past experience, and formal training.     

选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

MEASUREMENT OF THE HEALING OF VENOUS ULCERS

The surface area of 99 leg ulcers was measured from a scaled photograph using a computerized ultrasonic digitizer. This was compared with the area obtained by multiplying the two maximal perpendicular diameters of each ulcer. There was an extremely good correlation between these two methods (r= 0.951). Seventy-four patients were followed up as part of a placebo-controlled double-blind study. In this study, treatment was assessed by the time taken for the ulcerated limb to heal completely. The initial ulcer size was found to be a weak predictor of subsequent ulcer healing (r = 0.49). The healing rates of individual ulcers calculated over 1 month intervals from presentation proved to be a poor predictor of the time required for complete ulcer healing (Spearman rank correlation coefficients ranged from 0.15 to 0.61). The healing curves of individual ulcers showed considerable fluctuations during the process of healing. The product of the maximal dimensions of an ulcer provides an easy and accurate method of monitoring treatment. The reduction in ulcer size within a set time interval, used in many ulcer studies, is a poor predictor of eventual ulcer healing. The percentage of ulcers completely healed within a pre-determined time interval is a better method of assessing new treatments.