Formation of the very low density lipoprotein and metabolism of [1-14C]-oleate by perfused livers from rats treated with triiodothyronine or propylthiouracil

To gain insight into the mechanism(s) responsible for changes in plasma lipid concentrations in thyroid disease, the metabolism of [1-¹⁴C]-oleate by perfused livers from hypothyroid [propylthiouracil (PTU) treated], euthyroid and hyperthyroid (T₃ treated) rats was compared. Livers from hyperthyroid animals secreted decreased amounts of very low density lipoprotein (VLDL) and incorporated less [1-¹⁴C]-oleate into VLDL triglyceride, but produced more ketone bodies and incorporated more radioactivity from [1-¹⁴C]-oleate into ketones than did livers from euthyroid animals. Conversely, incorporation of [1-¹⁴C]-oleate into perfusate and VLDL triglyceride was increased in livers from hypothyroid animals, while rates of production of ¹⁴CO₂ were diminished. Plasma T₃ concentration was inversely correlated with VLDL triglyceride (r = ?0.70, p < 0.003) and VLDL apoprotein (r = ?0.72, p < 0.008), but directly correlated with ketogenesis (r = 0.71, p < 0.002). Thyroid hormone diminished esterification of fatty acids, and inhibited the hepatic production of triglyceride and secretion of VLDL and stimulated ketogenesis, whereas thyroid hormone deficiency increased hepatic esterification of fatty acid to triglyceride, tended to increase output of the VLDL, and diminished oxidation of fatty acid through the tricarboxylic acid cycle. The surface lipid (phospholipid, cholesterol) to apoprotein ratio was directly correlated with the output of VLDL triglyceride (r = 0.85, p < 0.0005). Furthermore, the lipid composition of the secreted VLDL particle was influenced by thyroid status. Plasma T₃ concentration was directly correlated with the molar ratios of phospholipid/triglyceride (r = 0.73, p < 0.001), cholesterol/triglyceride (r = 0.85, p < 0.0001), and cholesteryl ester/triglyceride (r = 0.80, p < 0.0002) in the VLDL particle. A direct correlation was also demonstrable between the ratio apoprotein/triglyceride and plasma T₃ concentration (r = 0.72, p < 0.0084), while the ratio was inversely correlated with output of VLDL triglyceride (r = ?0.76, p < 0.0038). The percentage of certain of the polymorphic forms of arginine-rich peptide was increased, while apo C-III₃ was decreased in VLDL produced by livers from hypothyroid rats. These data are consistent with the hypothesis that as output of VLDL diminished in the progression from hypothyroidism to hyperthyroidism, the VLDL particle secreted became smaller with a larger ratio of surface to core components.     

Thyroid hormones and lipolysis in physically trained rats

In rats a single bout of exercise resulted in increased triiodothyronine (T3), thyroxine (T4), and triiodothyronine/reverse triiodothyronine ($\text{T3}\text{rT3}$) ratio 20 hr after exercise. The effect of norepinephrine on lipolysis in vitro was potentiated.In trained rats no changes were found in T4, T3 or rT3 concentrations. The $\text{T3}\text{rT3}$ ratio as well as basal and stimulated TSH concentrations decreased in comparison with sedentary, freely eating rats. Moderate food restriction to produce a body weight similar to that of trained animals caused no changes in T4, T3 or rT3 concentrations but caused a decrease in $\text{T3}\text{rT3}$ and in TSH levels. Training and moderate food restriction groups were not different. T3 in vitro caused a potentiation of catecholamine induced lipolysis in trained and food-restricted animals. With aging the serum concentration of T3 decreased and that of rT3 increased.Acute and chronic exercise both exert an effect on peripheral hormonal responses of lipolysis, while they have different and opposite effects on thyroid hormone concentrations. Physical training seems to have effects in this regard similar to those of moderate energy intake restriction. The results suggest that changes in peripheral effects of thyroid hormones during training should attract more attention.     

Mechanism of chlorpromazine-induced arrhythmia arrhythmia and mitochondrial dysfunction

In this study, we investigated the mechanism of the arrhythmogenic action of chlorpromazine (CPZ). Thirty-two anesthetized mongrel dogs were used. In each, the chest was opened and a stimulating electrode was attached to the apex of the left ventricle and the ventricular multiple response threshold (VMRT) was measured. The carotid artery was cannulated to measure aortic pressure. The dogs were divided into four groups, and the time course of VMRT, blood pressure, and heart rate were determined. All groups were placed under observation for 30 min after CPZ infusion. In the control group, only saline (2ml/kg) was infused; CPZ group: CPZ (1mg/kg) was infused 10 min after saline (2ml/kg) infusion; CoQ₁₀ group: Coenzyme Q₁₀ (CoQ₁₀) (5mg/kg) was infused 10 min before CPZ (1mg/kg) infusion; FAD group: Flavin-adenine-dinucleotide (FAD) (2mg/kg) was infused 10 min before CPZ (1mg/kg) infusion. In each group, myocardial mitochondria were prepared 30 min after CPZ infusion. The mitochondrial functions, respiratory control index, ADP/0, State III rate of oxygen consumption, and activities of two segments of the electron-transport chain (NADH→CoQ→cyt.c and cyt.c→cyt.a, a₃→O₂) were measured separately. Ca⁺⁺-binding activity of the mitochondria was also determined.CPZ administration decreased VMRT and blood pressure, and caused mitochondrial dysfunction which derived from a disturbance in the first segment of the electrontransport chain. Decreased Ca⁺⁺-binding activity was observed when mitochondrial function was disturbed. CoQ₁₀ prevented significantly the decrease in VMRT and the disturbance of mitochondrial function induced by CPZ, but did not prevent the hypotensive effect of CPZ. FAD prevented not only the decrease in VMRT and the disturbance of mitochondrial function, but also the hypotensive effect of CPZ.These results suggest that the decrease in VMRT is closely related to mitochondrial dysfunction induced by CPZ. Moreover, it is suggested that the arrhythmogenic effect of CPZ is derived from the decreased mitochondrial Ca⁺⁺-binding activity.     

Transcapillary fluid balance in immature rats. Interstitial fluid pressure,serum and interstitial protein concentration,and colloid osmotic pressure

Several of the factors governing transcapillary fluid balance were studied in anesthetized rats from the age of 1 to 60 days. Serum albumin and total protein concentrations rose from 1.7 and 2.4 g/100 ml at birth to 4.1 and 6.2 g/100 ml in adult rats, while colloid osmotic pressure rose from 5.3 to about 20 mm Hg. Interstitial fluid collected from subcutis by the wick technique showed protein concentrations of approximately 60% of serum values in all age groups, and its colloid osmotic pressure rose from about 3 to 10 mm Hg during maturation. Arterial pressure rose from about 50 mm Hg in newborn rats to 120 mm Hg in adult animals. Iliac venous pressure was only 0.5–1 mm Hg in 10-day-old rats compared to 3 mm Hg in adult animals. Interstitial fluid pressures of 0 to ?1 mm Hg were obtained in all age groups with the “wick-in-needle” technique. The data suggest an average capillary pressure of less than 5 mm Hg in newborn animals and a pre- to postcapillary resistance ratio similar to that of adult animals. The safety factors against edema formation seem to be small in immature rats.     

Effect of alcohol administration on plasma growth hormone response to insulin-induced hypoglycemia.

Plasma growth hormone (HGH) response to insulin-induced hypoglycemia was assessed in a group of normal adult volunteers, with and without prior consumption of ethanol. A significant difference was found in peak HGH concentrations on the two occasions, indicating that prior consumption of ethanol attenuates the normal HGH response to insulin-induced hypoglycemia. It is suggested that ethanol may deplete catecholamine stores in the neurons of the ventromedial nucleus of the hypothalamus and may thereby impair secretion of growth hormone releasing factor. Under certain circumstances this could be of importance in the pathogenesis of alcohol-induced hypoglycemia.     

名中医傅晓骏论治肾性蛋白尿经验

目的 总结名中医傅晓骏论治肾性蛋白尿思路方法,用药规律,以推广其临证学术思想及用药经验.方法 通过临证跟随傅晓骏教授中医经典查房,整理其病案医案,从文献认识、药理研究等多方面,阐述傅晓骏教授论治肾性蛋白尿.结果 傅晓骏教授治疗肾性蛋白尿,特别重视从瘀论治,临床注重辨证论治思维,并擅用虫类药物、风类药物以诊治顽固性蛋白尿...     

Nosocomial pseudoepidemics and pseudoinfections: an increasing problem.

The infection control practitioner often relies on microbiologic data in order to conduct nosocomial infection surveillance and control activities. On the basis of a review of the medical literature, false positive culture and stained smear results representing pseudoinfection are being reported with greater frequency. Documented cases and clusters of pseudoinfectons are reviewed, and the epidemiologic characteristics and methods for detection and prevention of this increasingly recognized problem are discussed.     

双标记流式细胞术定量分析5-FU诱导胃癌细胞早期凋亡

目的 以Annexin V-FTTC/PI双标记流式细胞术检测5－FU诱导胃癌细胞株SCG7901早期凋亡。方法 250、125、50以及25mg/L不同浓度5－FU处理SCG7901胃癌细胞0、6、12、18、24、30h,Annexin V-FTTC/PI双标记流式细胞术检测肿瘤细胞凋亡。结果 早期（0－24h)瘤细胞凋亡比例随5－FU作用剂量增加和时间延长而显著提高（P＜0.01)；后期（24-30h)瘤细胞以坏死增加为主（P＜0.01)而凋亡比例反而降低。结论 5－FU诱导细胞凋亡呈时间以及剂量依赖关系。Annexin V/PI双标记法可以清楚区分正常、坏死、机械损伤以及凋亡细胞群落，是定量分析早期细胞凋亡的准确方法。     

Relationship between ADAMTS4 and carotid atherosclerotic plaque vulnerability in humans

Background

Rupture of atherosclerotic plaques and the resulting thrombosis are vital causes of clinical ischemic events. Recent studies have shown that ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) is a pathogenic factor of plaque vulnerability in mice. However, the relationship between ADAMTS4 and carotid atherosclerotic vulnerable plaques in humans remains unclear.