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.     

Focus cleaning using mini-thoracotomy for cavitary pulmonary tuberculosis or pulmonary tuberculoma: case study of 18 human subjects

Zusammenfassung GRUNDLAGEN: Das Ziel dieser Untersuchung war, die Machbarkeit und Wirksamkeit der Fokus-Sanierung via Mini-Thorakotomie zur Therapie einer kavernösen Lungentuberkulose zu prüfen. METHODIK: Der Mini-Thorakotomie-Zugang wurde in 18 Patienten angewendet (Alter, 25–75 Jahre; median, 47,5 Jahre). Die Patienten hatten eine kavernöse Lungentuberkulose oder ein Lungentuberkulom nach tuberkulostatischer Therapie oder waren Patienten, die auf diese Therapie nicht angesprochen haben. 8 Patienten mit chronischer kavernöser Lungentuberkulose und 10 Patienten mit Tuberkulom haben sich der Fokus-Sanierung, Spülung und Faltnaht unterzogen. ERGEBNISSE: Es gab keine operative Mortalität. Alle Patienten waren klinisch saniert, hatten keinen Nachweis für Bakterien im Sputum, im Röntgen hatten die Lungenschatten abgenommen. Die Dauer der Operation betrug 30–120 min (median, 75 min), der intraoperative Blutverlust war 100–200 ml (median, 153 ml). Der postoperative Spitalsaufenthalt betrug 21–42 Tage (median, 30 Tage). Das Follow-up nach 1–4 Jahren (median, 2,5 Jahre) zeigte keine Komplikation und kein Rezidiv der Grunderkrankung. SCHLUSSFOLGERUNGEN: MTFC ist eine sichere und technisch machbare Methode zur Therapie der Lungentuberkulose oder des Tuberkuloms bei Schonung der Lungenfunktion.     

Revascularization of the renal artery in renovascular hypertension with progressive renal insufficiency

Sixteen patients underwent surgical treatment for severe renovascular hypertension with rapidly progressive renal failure. These patients were assessed preoperatively with the measurement of serum creatinine and blood-urea levels (means 271 +/- 204 mumol/l and 15.6 +/- 10.3 mmol/l respectively), and renal clearances. 5 patients underwent aorto-renal bypass (bilateral in one case) and 11 patients were treated by autotransplantation of the kidney. Operative mortality was 6.2%. Early results were assessed at 1 and 6 months postoperatively. Renal function was normal in 8 patients, improved in 5 (p less than 0.05), unchanged in 1 and worse in 1 by aorto-renal bypass thrombosis. At long-term with a minimum follow-up of 12 months (mean 31 +/- 12 months), the initial improvement in renal function remained steady in 12 patients whilst 1 patient has gone on to hemodialysis. At middle and long-term, 81% of the patients were normotensive without medication or had improved blood pressure (p less than 0.001). These good results confirm the reversibility of renal ischemic lesions and support an aggressive attitude towards the use of revascularization in the surgical treatment of such patients with renovascular hypertension and renal failure.     

Enhanced myocardial necrosis induced in rats by the combined administration of hydralazine and prenalterol

The cardiotoxic effects of hydralazine and prenalterol, given alone and in combination, were assessed in rats and rabbits. Acute myocardial necrosis was induced by a single administration of each drug alone in rats. However, the incidence and severity of lesions were markedly enhanced when both drugs were given in combination. Rats that received the same treatment for 10 consecutive days showed minimal or no acute necrosis, demonstrating the development of a resistance to further cardiotoxic effects of the drugs. Rabbits showed only minimal lesions when either drug was used alone and no enhancement of lesions when they were given in combination. From these data, it is concluded that the possibility of a cardiotoxic interaction exists when these drugs are used in combination and that the heavy rat (500-600 g) is a more sensitive model than the rabbit for studies of this nature.     

Utility of the coefficient of determination (r2) in assessing the accuracy of interspecies allometric predictions: illumination or illusion?

The appropriateness of relying on the coefficient of determination (r(2)) as a statistical metric for judging the predictability of human clearance (CL) based on interspecies animal data was assessed. An explicit mathematical expression was derived for r(2) as a function of species body weight and the corresponding measured value of CL. The derived mathematical function demonstrated that r(2) is numerically large in most instances. Simulations using random CL generated from a common combination of species of mouse, rat, and monkey resulted in an r(2) of 0.75 as the minimum, and 0.95 and 0.98 at 50th and 75th percentiles, respectively, given that total CL values increase with increasing species body weight. Analysis of literature data also indicated that the prediction accuracy of human CL was not correlated with values of r(2). Therefore, it is concluded that r(2) is a limited statistical measure when assessing allometric scaling for the purpose of predicting human CL.     

TNF-α和低氧对胰腺癌细胞表达VEGF-A、C的调节

目的:探讨细胞活素肿瘤坏死因子-α(TNF-α)、SNAP(S-Nitroso-Nacetyl-penicillamine)对胰腺癌细胞产生血管内皮生长因子A、C(VEGF-A、C)的调节.方法:用Northern杂交和Western杂交法分析6种人胰腺癌细胞株中VEGF-A、C基因和蛋白的表达;以TNF-α或SNAP刺激其中两个细胞株后用逆转录-聚合酶链式反应技术(RT-PCR)分析其VEGF-A、C基因的表达.结果:Northern杂交法显示这6种胰腺癌细胞株均有4.1kb VEGF-A基因和2.4kb VEGF-C基因的表达;Western杂交法显示它们均有分子量为43kD的VEGF-A蛋白质和分子量为55kD的VEGF-C蛋白质的表达.RT-PCR分析法显示:TNF-α使细胞株COLO-357产生VEGF-A、VEGF-C mRNA分别减少约1～2.5倍、1～2倍,使细胞株CAPAN-1产生VEGF-A、VEGF-C mRNA分别减少约1倍、1.6～2.5倍;而SNAP刺激细胞株COLO-357产生VEGF-A mRNA增加约5倍,刺激细胞株CAPAN-1产生VEGF-A mRNA增加约4倍,但对这两种细胞株产生VEGF-C mRNA均无明显刺激作用.结论:细胞活素TNF-α和低氧通过调节血管内皮生长因子A、C的表达而影响胰腺癌细胞的生物学特性,抑制癌细胞的增殖,促进其凋亡、死亡或进展、恶化.     

ULTRASTRUCTURAL INVESTIGATION OF EXPERIMENTAL FRACTURE HEALING ROLE OF OSTEOGENESIS PLAYED BY FIBROBLASTS

Transmission electron microscopic investigation of standardized fractures of radii in 50 rabbits re vealed that fibroblasts took part in the formation of bony callus. The osteogenetic role played by the fibroblasts can be categorized into the following 5 aspects: a. Fibroblasts synthesize and secrete Type collagen fibrils and induce deposition of calcium salt crystals in the collagen fibrils. b. Fibroblasts produce matrix vesicles in their surroundings. These matrix vesicles become calcified and turn into floccu- lent calcospherules which coalesce and fuse into bone tissues. c. Fibroblasts harbor calcium granules in their mitochondria, thus providing calcium for calci- fication of the intercellular matrix and bone forma tion between the cells. d. Fibroblasts can transform directly into osteocytes; there is bone formation around the fibroblasts, the bone tissues surround the fibroblast in the form of bony lacuna, then the fibro- blast in the lacuna transforms into osteocyte. e. Fibroblasts can undergo degenerative changes leading to decease and replacement by bone tissues.