Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes.

Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin levels. However, data regarding the expression of UCP3 in patients with type 2 diabetes is inconsistent, and so far, there have been no reports of UCP3 protein content. Here we compared, for the first time, the protein levels of UCP3 in vastus lateralis muscle in 14 male type 2 diabetic patients (age 49.8 +/- 2.1 years; BMI 27.2 +/- 1.2 kg/m(2); mean +/- SE) with 16 male control subjects (age 48.0 +/- 1.9 years; BMI 23.4 +/- 0.6 kg/m(2)). We found that UCP3 protein levels were twice as low in patients with type 2 diabetes compared with control subjects (117 +/- 16 vs. 58 +/- 12 AU; P = 0.007). There was no correlation between UCP3 content and BMI. In conclusion, UCP3 content is lower in type 2 diabetic patients compared with healthy control subjects. These results are consistent with a role for UCP3 in glucose homeostasis and suggest a role for UCP3 in type 2 diabetes.     

Two step procedure for early diagnosis of polycystic kidney disease with polymorphic DNA markers on both sides of the gene.

Polymorphic DNA markers can now be used for presymptomatic and prenatal diagnosis of the autosomal dominant form of polycystic kidney disease (PKD). A detailed map is known for the chromosomal region around the PKD1 gene on the short arm of chromosome 16. We present here a simple, two step procedure for diagnosis of PKD1 by family studies. Using this approach, at least 92% of random subjects are informative for polymorphic DNA markers bracketing the PKD1 gene. The recombination rate between these flanking markers is on average 10%. In non-recombinants (90% of family members), the accuracy of diagnosis using DNA markers is greater than 99%. We conclude that sufficient well defined DNA markers are now available for routine diagnosis of PKD1. We recommend, however, that prenatal diagnosis of PKD by chorionic villi sampling should be attempted only after the linkage phase of the DNA markers has been established by haplotyping the index family. Since autosomal dominant PKD has been found to be genetically heterogeneous, families should be of sufficient size to rule out the rare form of PKD not caused by a mutation on the short arm of chromosome 16.     

Impact of 3-year lifestyle intervention on postprandial glucose metabolism: the SLIM study

Objective To determine the effect of a 3-year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT). Methods The study was a randomized controlled lifestyle intervention over 3 years. A total of 147 IGT subjects (75 male, 72 female) were randomized to the intervention (INT) group or control (CON) group; 106 subjects (52 INT, 54 CON) completed 3 years of intervention. Annually, glucose, insulin and free fatty acid (FFA) concentrations were determined fasting and after an oral glucose tolerance test. Measurements of body weight, serum lipids, blood pressure and maximal aerobic capacity were also performed. Results Analysis of those who completed the 3-year trial, showed that the lifestyle intervention improved body weight (INT −1.08 ± 4.30 kg; CON +0.16 ± 4.91 kg, P = 0.01), homeostatis model assessment index for insulin resistance and 2-h FFA. Two-hour glucose concentrations improved in the INT group, the difference being most pronounced after 1 year, with a return to baseline values after 3 years, from 8.59 ± 1.55 to 8.55 ± 0.34 mm ; in contrast, 2-h glucose deteriorated in the CON group—from 8.46 ± 1.84 to 9.35 ± 2.50 mm (P = 0.02). In the INT group, diabetes incidence was reduced by 58% (P = 0.025). Conclusion Our lifestyle intervention showed a sustained beneficial effect on 2-h glucose concentrations, insulin resistance and 2-h FFA, even after 3 years. Our lifestyle intervention is effective, but for implementation more information is needed about factors influencing adherence.     

脾切除对结直肠癌切除术后的影响：一项多中心、嵌入式、配对队列研究

目的探讨医源性脾脏损伤脾切除对结直肠癌切除患者术后长期生存的影响。方法对1990年1月1日至1999年12月31日10年间行结直肠癌手术切除并附带脾切除患者进行病例配对回顾研究。分析患者年龄、性别、依据美国麻醉学医师协会（ASA）标准评估的身体状况、疾病分期、手术类型及预后等资料。配对病例来自同一医疗中心，性别、年龄、疾病分期及手术类型完全相同。手术附带脾切除患者为试验组，未切脾者为对照组。结果55例患者行医源性脾切除术，对照组在年龄、性别、身体状况、疾病分期及手术类型上与之匹配。随访时间（从手术开始到患者死亡或者最后一次随访1为2～205个月（中位随访时间为43个月）。Cox比例危险度模型进行Kaplan-Meier法生存分析发现两组间差异有显著性意义，不切除脾脏对患者生存有利（危险度1．8，95％可信区间为1-3．3，P=0．0399），未切脾组与切脾组5年生存率分别为70％和47％，10年生存率分别为55％和38％。结论结直肠癌患者在行结肠或直肠切除时，因医源性脾脏损伤而切除脾脏者，预后较差。     

Effects of addition of exercise to energy restriction on 24-hour energy expenditure, sleeping metabolic rate and daily physical activity

Body composition, sleeping metabolic rate (SMR), 24-h energy expenditure (24-EE) and daily physical activity were determined in 12 obese women during and after 12 weeks of exercise (4 h per week on 55 per cent of VO2 max) and/or energy restriction (2.9-3.5 MJ/d). Diet(D) and diet-exercise (DE) groups were formed by matching the subjects on their body mass index (BMI, kg/m2; mean 30.3). After 12 weeks no significant differences were shown in loss of weight (D 12.2 and DE 13.2 kg) and loss of fat mass (D 9.4 and DE 10.9 kg). Both groups reduced their SMR (D 29.9 per cent and DE 21.7 per cent) and their metabolic rate during the entire night measured by indirect calorimetry (12-EE) (D 36.4 per cent and DE 28.6 per cent; P less than 0.05). Energy expenditure over 24 h, estimated by means of heart-rate monitoring, was reduced by 22.1 per cent for D and by 19.6 per cent for DE (n.s.). Daily physical activity, which was determined during 5 d using an actometer, was increased after 12 weeks for DE (27 per cent; P less than 0.05) and D (10 per cent; n.s.). The suggestion that a reduction in normal activities of daily life in a diet-exercise group is the explanation for the absence of significant differences in weight and fat loss between a diet-exercise and a diet group is not confirmed in this study. Daily physical activity showed a significantly higher increase for the diet-exercise group than for the diet group, while the decline of SMR and 24-EE tended to be smaller.     

Superparamagnetic iron oxide-enhanced MR imaging: pulse sequence optimization for detection of liver cancer

The effects of magnetic resonance (MR) pulse sequences and timing parameters on tumor-liver contrast were studied in an animal model of metastatic liver cancer. Six spin-echo (SE), three inversion-recovery (IR), and four gradient-echo (GRE) sequences were evaluated at 0.6 T before and after injection of super-paramagnetic iron oxide. GRE techniques, irrespective of echo time and flip angle, showed the greatest change in signal intensity (enhancement) of the liver after administration of iron oxide. Single-acquisition GRE sequences (16 seconds) matched the contrast-to-noise ratio (C/N) performance of the most effective 6.4-minute SE sequences. Multiexcitation GRE sequences showed tumor-liver C/Ns per unit time that were significantly (P less than .05) higher than those achieved with SE and IR sequences. GRE sequences, which recruit intravoxel dephasing as an additional source of transverse relaxation enhancement (T2*), show a higher C/N per unit time and in this respect seem superior to SE and IR sequences for MR imaging with superparamagnetic iron oxide.     

Hypothalamic Syndrome and Central Sleep Apnoea Associated with Toluene Exposure

We describe a young man who developed extensive hypothalamicdysfunction including diabetes insipidus, adipsia, hyperprolactinaemia,and poikiliothermia together with central sleep apnoea followingexposure to toluene.     

60Coγ射线局部辐射后小鼠非辐射区域骨髓巨核细胞的变化

目的:临床局部辐射条件下会造成非辐射区域组织及细胞功能损害,最为突出的是对造血功能的影响。实验建立60Coγ射线左半身辐射动物模型,观察局部电离辐射对其非辐射区域骨髓巨核细胞的影响。方法:实验于2003-10/2005-03在解放军第三军医大学辐照中心和全军复合伤研究所完成。①实验动物:6～8周龄SPF级雄性昆明小鼠180只,随机数字表法分为正常对照组、全身辐射组、左半身辐射组、全身屏蔽辐射组,45只/组。②实验方法:全身辐射组小鼠固定于辐射架内;左半身辐射组小鼠麻醉后固定体位,用铅砖屏蔽右半身;全身屏蔽辐射组小鼠麻醉固定体位,用铅砖屏蔽全身。以60Coγ射线一次性辐射,剂量率68.46cGy/min。正常对照组不作任何干预。③实验评估:辐射后不同时相检测小鼠血清丙二醛含量及超氧化物歧化酶活性变化,计数外周血血小板,检测骨髓巨核祖细胞集落形成单位,观察骨髓组织病理改变及CD41a、CD61的表达。结果:全身辐射组第8天死亡2只,第9天死亡4只,其余各组无脱失。①外周血血小板计数:辐射后第2,7天,左半身辐射组外周血血小板数量显著低于正常对照组(P<0.01),但高于全身辐射组(P<0.01)。②血清丙二醛含量及超氧化物歧化酶活性变化:辐射后第2,9天,左半身辐射组血清丙二醛含量显著高于正常对照组(P<0.01),低于全身辐射组(P<0.01);血清超氧化物歧化酶活性显著低于正常对照组(P<0.01),高于全身辐射组(P<0.01)。③骨髓巨核祖细胞集落形成单位的变化:与正常对照组比较,辐射后6h左半身辐射组非辐射侧的巨核祖细胞集落形成单位显著降低(P<0.01),高于全身辐射组及左半身辐射组(P<0.01)。④骨髓组织病理改变:正常对照组有核细胞比例较高,分布均匀,并见多量散在分布的细胞龛;辐射2d后,左半身辐射组非辐射侧骨髓有核细胞较正常对照组减少,但好于全身辐射组、左半身辐射组。⑤骨髓CD41a及CD61表达的变化:辐射后2d与正常对照组比较,左半身辐射组非辐射侧骨髓CD41a及CD61阳性细胞数和相对荧光强度均显著降低(P<0.01),但高于全身辐射组、左半身辐射组(P<0.01)。结论:局部电离辐射作用后,可导致小鼠非辐射区域骨髓巨核细胞增殖能力降低,血小板减少,产生功能障碍。氧自由基激活可能参与了该损伤过程。