Obesity: determinants and therapeutic initiatives.

There are several possible determinants of obesity, including impaired thermogenesis and the differential utilization of fuels in different tissues. Whereas hypometabolism may initiate obesity in some people, once obese, individuals tend to manifest a higher resting metabolic rate because of their greater fat-free mass, exhibit an impaired thermic response to food, and expend more calories than lean individuals for equivalent amounts of activity. As a result, over a 24-h period, obese people generally expend more energy than lean people. A second determinant of obesity is related to fuel utilization and suggests that those predisposed to be obese may have an innate insulin resistance in muscle, leading to decreased uptake, oxidation, and storage of glucose in this tissue. As a result, the glucose is shunted to adipose tissue, where it is stored. With regard to treatment of obesity, emphasis on increased energy expenditure through the inclusion of reasonable amounts of activity is essential. However, this must always be combined with restraint in caloric intake.     

大鼠成骨细胞增殖及护骨素蛋白含量与甲状旁腺激素的调节效应

目的:体外观察甲状旁腺激素对大鼠成骨细胞增殖和护骨素分泌的调节作用。方法:实验于2005-06/2006-05在四川大学华西医院生物治疗国家重点实验室干细胞与组织工程研究室完成。采用酶消化法和骨组织块法联合分离培养新生SD大鼠颅骨成骨细胞,间歇加药方法将不同浓度0,10-6,10-7,10-8,10-9mol/L甲状旁腺激素作用于大鼠成骨细胞(0mol/L作为空白对照组),经碱性磷酸酶染色及钙结节茜素红染色证实培养的成骨细胞后,采用四甲基偶氮唑盐比色法检测细胞增殖能力,蛋白免疫印迹测定护骨素的分泌量。结果:①成骨细胞的形态变化:倒置相差显微镜下可见培养的成骨细胞呈短梭形、三角形和多边形。碱性磷酸酶染色光镜下可见成骨细胞胞浆中分布特征性蓝紫色细颗粒;成骨细胞的钙结节在镜下可见部分细胞聚集一起呈"集落状"生长。②成骨细胞增殖率:10-6～10-9mol/L浓度甲状旁腺激素对成骨细胞增殖均显示刺激作用,与空白对照组相比,差异显著(P<0.05),增殖率以10-8mol/L甲状旁腺激素组最高。③成骨细胞护骨素的表达:甲状旁腺激素下调成骨细胞中护骨素的分泌,与空白对照组相比,10-6mol/L甲状旁腺激素组抑制作用最明显(P<0.01),无显著剂量依赖性。结论:甲状旁腺激素对体外培养成骨细胞的增殖具有明显促进作用,通过下调成骨细胞中护骨素的分泌,促进破骨细胞生成、活化,促进骨吸收。     

Myocardial perfusion imaging with technetium-99m sestamibi SPECT in the evaluation of coronary artery disease

Technetium-99m hexakis-2-methoxy-isobutyl-isonitrile(^99mTc sestamibi) has been used for myocardial perfusion imaging in the evaluation of coronary artery disease (CAD) since 1990. The experience of its use in an Asian population with and without previous myocardial infarction (Ml), diabetes mellitus (DM), hypertension (HPT) and collateral circulation (COL) is reported. One hundred and thirty-nine patients who underwent treadmill exercise testing with ^99mTc sestamibi single photon emission computed tomography (SPECT) and coronary angiogram were studied. The overall sensitivity for the detection of CAD was 91.0% and specificity was 64.7%. For patients without previous myocardial infarction, the sensitivity was 83.8% and specificity was 83.3%. Patients with COL had a higher sensitivity while those with HPT had a lower specificity. Sensitivity was higher in patients with multi-vessel disease (MVD) than single vessel disease (SVD). The overall detection for individual artery stenosis was 74.1% with a specificity of 73.1 %. Amongst the three major coronary arteries, sensitivity was highest for the right coronary artery and specificity was highest for the left circumflex artery. Specificity was higher in patients without MI or COL. We found that the agreement between ^99mTc sestamibi SPECT and coronary angiogram for the extent of CAD was only 52.5%. The concordance rate was higher for patients with MVD than SVD. It is concluded that ^99mTc sestamibi SPECT is a sensitive and specific test for the detection of CAD and localization of disease to individual coronary arteries in our patients with some differences in the subgroups. Agreement between coronary angiogram and ^99mTc sestamibi for the extent of coronary artery disease was also satisfactory.     

Analgesia for shock wave lithotripsy

PURPOSE: We evaluated the effectiveness of and patient preference for analgesia used during shock wave lithotripsy by comparing diclofenac alone with a combination of diclofenac and patient controlled analgesia, that is alfentanil. MATERIALS AND METHODS: A total of 64 patients were treated using a Lithotriptor S (Dornier Medical Systems, Marietta, Georgia) and randomized to receive diclofenac alone or combined with an alfentanil patient controlled analgesia pump. If treated twice, they crossed over to the alternative form of analgesia. A record was maintained of the site and size of the stone, maximum power achieved, number of shocks, amount of alfentanil used and need for additional analgesia. After treatment patients scored on a visual analog scale the maximum level of pain and satisfaction with analgesia. RESULTS: There was no difference in the mean size of the stone treated (8.6 and 7.5 mm.), energy level (71% and 71% or approximately 17 kV.) or number of shocks (3,000 and 2,900, respectively) in the groups. Only 2 patients in the diclofenac group required additional analgesia and there were no significant side effects from either treatment. The mean pain scores were not significantly different in the diclofenac and patient controlled analgesia groups (3.54 and 2.93, respectively, (p = 0.34), although those on patient controlled analgesia were more satisfied (7.72 versus 9.14, p = 0.04). Of the 38 patients who presented twice 58% preferred diclofenac alone. CONCLUSIONS: This study suggests that there is no significant difference in the level of pain experienced with diclofenac alone or when combined with an alfentanil patient controlled analgesia pump during shock wave lithotripsy. However, patients are more satisfied with treatment when a patient controlled analgesia pump is available.     

Resistance to ketosis during prolonged fasting by rats fed on a diet containing undecanoic acid, an odd-carbon-number fatty acid.

1. Sixty-four male rats were fed on a nutritionally complete diet containing 30% of the dietary energy as fat. For thirty-two rats (control) the fat source was maize oil; for the remaining thirty-two rats (experimental) the fat source was triundecanoin-maize oil (7:3, w/w). 2. After 6 weeks, groups of control and experimental rats were fasted and killed on days 0, 1, 2, and 4 of the fasting period. In the experimental group, adipose-tissue fatty acids contained, on average, 246 mmol undecanoic acid/mol total fatty acids. In contrast, the adipose tissue of the control group did not contain odd-carbon-number fatty acids. 3. Plasma glucose levels were significantly higher for all fasted experimental groups and blood ketone levels were significantly lower for these groups. 4. Thus, during prolonged starvation, animals which accumulated odd-C-number fatty acids resisted the development of ketosis. It appeared that odd-C-number fatty acids mobilized from fat depots during fasting may provide their terminal three-C-residues for gluconeogenesis rather than for acetyl-CoA production, thereby allowing for better maintenance of blood glucose and insulin levels than in control animals. 5. It is concluded that the lower acetyl-CoA production and higher blood insulin levels reduce ketogenesis.     

Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies. A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition

Overweight and obesity are important risk factors for type 2 diabetes. The marked increase in the prevalence of overweight and obesity is presumably responsible for the recent increase in the prevalence of type 2 diabetes. Lifestyle modification aimed at reducing energy intake and increasing physical activity is the principal therapy for overweight and obese patients with type 2 diabetes. Even moderate weight loss in combination with increased activity can improve insulin sensitivity and glycemic control in patients with type 2 diabetes and prevent the development of type 2 diabetes in high-risk persons (ie, those with impaired glucose tolerance). The American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition have joined together to issue this statement on the use of lifestyle modification in the prevention and management of type 2 diabetes.