三康胶囊对高原移居者运动后NO乳酸及血氨的影响

目的探讨三康胶囊对高原人体运动后一氧化氮(NO)及其合酶(NOS)、乳酸(BLA)、血氨(Ammo)的影响.方法选择进驻海拔3 700 m高原1年的10名健康青年,口服三康胶囊15 d,在服药前后分别采用功量自行车进行渐增负荷运动,测定其血清 NO、NOS、BLA及Ammo含量.结果服药后较服药前运动后NO水平[(101.02±6.49) Vs (77.10±8.11)]和NOS活性[(71.40±7.23) Vs (56.29±6.28)]均增高, BLA[(7.58±0.79)Vs (6.13±0.74)]和Ammo[(80.11±9.44)Vs (69.38±8.86)]降低,有非常显著性差异(P＜0.01).结论 三康胶囊能增强高原移居者运动后NOS活性,加速乳酸清除,减缓运动疲劳的发生.     

Effect of alcohol abuse on human brain histamine and tele-methylhistamine

Inflammation Research -     

Pharmacokinetics in Rat of 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a Drinking Water Mutagen,after a Single Dose

Abstract: The pharmacokinetics of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was evaluated after a single oral or intravenous administration in the rats using ¹⁴C-labelled compound. Twenty to 35% of the dose was absorbed into circulation from the gastrointestinal tract as assessed from the excretion in urine. The mean elimination half-life of the radioactivity in blood (T_1/2 k₁₀) was 3.8 hr. Traces of radioactivity remained in the blood for several days. The tissues lining the gastrointestinal and urinary tract, kidneys, stomach, small intestines and urinary bladder contained the highest radioactivity. The activity declined slowest in the kidneys. Urine was the main excretion route. Seventy-seven % of the total amount excreted appeared in urine in 12 hr and 90% in 24 hr. No radioactivity was exhaled in air suggesting that elimination through respiration did not occur. After an intravenous administration of ¹⁴C-MX, the T_1/2 k₁₀, was much longer, 22.9 hr, and the total elimination half-life (T_1/2 β), 42.1 hr. The results indicate that MX is absorbed from the gastrointestinal tract to a considerable degree and it is excreted in urine very rapidly. A fraction of MX or its metabolites is retained in blood for a longer period of time. The pharmacokinetics of MX does not suggest extensive cumulation of MX in tissues after continuous exposure.     

Ischaemic episodes of less than 5 minutes produce preconditioning but not stunning in the isolated rat heart

The aim of the present study was to examine whether ischaemic episodes of less than 5 min could induce preconditioning or stunning in the isolated rat heart. Hearts were subjected to total global ischaemia of 1, 2 and 4 min followed by 10 min of reperfusion before an 18-min main ischaemic period and 30 min of reperfusion. The effects on physiology, purine metabolism and anaerobic glycolysis were compared with a control group subjected to the main ischaemia only. The brief ischaemic episodes did not produce stunning based on the recovery of left ventricular developed pressure (LVDP) and heart rate (HR) product during the first reperfusion. Preconditioning of 11–14% increased recovery of LVDP x HR during the second reperfusion was observed in the 1- and 4-min group. In the 2-min group a low repayment of flow debt during the first reperfusion was associated with a slightly reduced recovery of LVDP x HR compared to the other preconditioned groups during the second reperfusion. Only in the 4-min group was preconditioning associated with fewer breakdown products of the purine nucleotide pool (adenosine) and anaerobic glycolysis (lactate) in both tissue and effluate after the main ischaemia. Preconditioning (reflected in recovery of function) could be produced with ischaemic episodes of less than 5 min that did not produce stunning. Thus, stunning is probably not the primary cause of preconditioning.     

Feed intake after inhibition of histamine catabolism

It has been reported that histamine and its precursor histidine have a feeding-suppressing effect. The present study shows that metoprine (20 mg/kg i.p.), which increases brain histamine levels by inhibiting its catabolism, also significantly decreases daily feed intake in rats. The reduced feed consumption is evident in different states of water balance. These results agree with an involvement of histaminergic systems in the regulation of feeding behaviour.     

Electrodermal Responsivity in Young Hypotensive and Hypertensive Men

Electrodermal responses were recorded during the presentation of 16 moderately intense (1000 Hz, 90dB) tones in three groups of young men: borderline hypertensives (138/79 mmHg), normotensives (112/65 mmHg), and hypotensives (104/63 mmHg). Electrodermal response habituation was measured as a decline in response over trials, number of trials to a response criterion of three successive nonresponses, and number of inversions of response amplitude (larger responses following smaller responses) in the stimulus sequence. Habituation was fastest in hypotensives. Nonspecific electrodermal responses at rest and during tone presentations were most frequent in borderline hypertensives, least frequent in the hypotensive group, with the normotensive group falling in between. There were no significant differences in electrodermal level. The rapid habituation rate in hypotensives is discussed in terms of cursory information processing associated with impulsive behaviour. The higher nonspecific electrodermal activity in borderline hypertensives is interpreted to indicate increased sympathetic nervous system activity.     

TCDD-induced anorexia and wasting syndrome in rats: effects of diet-induced obesity and nutrition

Interactions of diet and diet-induced obesity, and the characteristic wasting syndrome caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied in TCDD-resistant Han/Wistar and TCDD-sensitive Long-Evans rats. The rats were made obese by feeding them either a high-energy diet (consisting of chocolate, cheese, and chow) or force feeding. TCDD reduced body weight in a parallel manner in lean and obese rats. The high-energy diet diminished the body weight loss and increased the survival time in L-E rats after a lethal dose of TCDD, while energy supplement with high-fat/low-protein food had an opposite effect. In conclusion, diet-induced obesity and TCDD had additive effects on body weight. Dietary manipulations were able to modify the weight loss and survival time after TCDD. Fat seems to have a negative impact, while carbohydrate or protein may have a positive impact in this respect. The results are in agreement with a view that TCDD-exposed rats have a negative fat balance favoring fat loss.     

Differences in binding of epidermal growth factor to liver membranes of TCDD-resistant and TCDD-sensitive rats after a single dose of TCDD

Epidermal growth factor (EGF) receptor has been implied as having a role in certain actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). After a single dose of TCDD, the receptor has been shown to be downregulated in several tissues including the liver. Two rat substrains, the Han/Wistar (Kuopio; H/W) rat and the Long-Evans (Turku AB; L-E) rat exhibit over a 1000-fold difference in their sensitivity to the lethal effect of TCDD. This large sensitivity difference was utilized in the current study to investigate whether or not a correlation exists between TCDD lethality and biochemical endpoints related to the hepatic EGF receptor. In the TCDD-sensitive L-E strain both the B(max) of the EGF receptor and the receptor protein as measured by Western blots, decreased dose and time dependently. Ten days after a lethal dose of TCDD (50 μg/kg), the downregulation was 80%. In the resistant H/W strain, two non-lethal doses were used (50 and 500 μg/kg), since the lethal dose is not known. These doses caused a downregulation already at 4 days after dosing, but no further decrease by day 10. The activity of phosphoenolpyruvate carboxykinase (PEPCK, the main gluconeogenetic enzyme in the liver and a proposed target of TCDD) decreased in H/W rats at least to the same extent as in L-E rats at both 4 and 10 days. It is concluded that EGF receptor downregulation is different in the two rat strains studied, despite the fact that a classical Ah receptor-regulated response (CYP1A1 induction) is similar. The results demonstrate that downregulation of the EGF receptor by TCDD is strain-dependent as well as dose- and time-dependent.     

Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy

McKeown-Eyssen (Cancer Epidemiol. Biomarkers Prevent., 3, 687-695, 1994) and Giovannucci (Cancer Causes Control, 6, 164-179, 1995), noting the striking similarity in lifestyle risk factors for colorectal cancer and insulin resistance, proposed that the hyperinsulinemia, glycemia and hypertriglyceridemia associated with insulin resistance promotes colon cancer. To compare the effect of diet on colon cancer promotion and insulin resistance in the F344 rat, we assessed the effect of fat, n-3 fatty acids and energy in pairwise comparisons on average size of aberrant crypt foci (ACF) and on glucose intolerance in the same animals in a single experiment. Diets high in fat and energy increased and diets with increased n-3 fatty acids and calorie restriction decreased both ACF growth and glucose intolerance compared with control diets. The measures of promotion of colon cancer and insulin resistance were strongly correlated (n = 98, r = 0.67, P < 0.001). In addition, both were highly correlated with daily energy intake (r = 0.62 and 0.66) and were also correlated with basal (post-prandial) insulin, glucose and triglycerides (r = 0.31-0.53, P < 0.01). We concluded that ACF growth and glucose intolerance are correlated for a wide range of diets and that increased circulating energy (glucose and triglycerides) may lead to both colon cancer promotion and insulin resistance.