烧伤后红细胞损伤的机制——过氧化脂质、维生素E与溶血的关系

本实验发现大鼠体表面积20％Ⅲ°烧伤后,皮肤内产生了大量丙二醛(MDA),第二天达最高,第七天有第二高峰,血浆和红细胞(RBC)MDA第三天达最高,血浆和RBC维生素E(VE)于伤后第二天后迅速下降,RBC溶血第三天最甚。对皮肤MDA、血浆MDA、RBCMDA、血浆VE、BBC VE、1％H_2O_2溶血进行相关分析后发现在不同时相,有不同的相关关系,但基本遵循烧伤皮肤MDA增加、血浆MDA增加、RBC MDA增加、血浆和RBC VE降低,溶血增加的规律。文中讨论了RBC损伤的机制。     

Almitrine bismesylate disposition in the human digestive tract

Summary The absorption of almitrine from the upper gastrointestinal tract has been evaluated in 6 healthy volunteers by an intubation technique. Almitrine bismesylate dissolved in malic acid was introduced into the stomach after homogenization with a meal containing the marker¹⁴C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was infused into the second part of duodenum throughout the experiment. Samples of the luminal content were collected every 15 min for four hours from the stomach and at the ligament of Treitz. Blood was also collected.Almitrine was neither absorbed from nor metabolized in the stomach. About 37% of the quantity of drug emptied from the stomach was absorbed from the duodenum. Almitrine was detected in plasma 50 min after ingestion of the meal and its plasma concentration-time profile reflected the cumulative gastric emptying rate. The metabolite tetrahydroxy almitrine was found in intestinal samples as soon as unchanged drug was detected in plasma. The intraluminal rate of formation of the metabolite increased with time.The results suggest hepatic metabolism of almitrine followed by rapid excretion of the metabolite in the bile.     

Methionine-induced acidosis in the weanling rat

Whole body balances of non-metabolizable base (NB) were studied in weanling rats fed a cereal-based diet with or without added l -methionine. In response to l -methionine loading (2.5 mmol day^-1) the rats exhibited a significant reduction in rates of food intake (109 vs. 160 g per 8 days) and body growth (3 vs. 52 g per 8 days); fractional oxidation of absorbed dietary amino acid sulphur increased from 0.28 to 0.64; and mean urinary sulphate excretion increased from 2.3 to 14.8 mmol per 8 days. Mean rates of renal excretion of NB and filtered titratable organic acid decreased from 20 to ?11 mmol per 8 days and from 22 to 8 mmol per 8 days. Balances of calcium and NB remained at reference values despite a decrease in whole blood ‘base excess’ from ?1.0 to ?6.4 mmol 1–¹. The concentration of NB in plasma rose but slightly. It is concluded that L-methionine loading in the weanling rat leads to extracellular non-carbonic acidosis subject to renal compensation. This acidosis is due not to retention of H⁺ released by ionization of endogenous sulphuric acid but possibly to accumulation of (acid) organic metabolites of methionine which are efficiently conserved by the kidneys. The rise in sulphuric acid production leads to an adaptive decrease in fractional reabsorption of filtered sulphate. Even during inhibited growth, absorbed dietary NB is retained and deposited in the skeleton, probably as calcium carbonate.     

Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers

The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml.kg-1.min-1 in controls to 1.06 and 1.21 ml.kg-1.min-1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine.     

膳食纤维与不同蛋白质联用对大鼠胆固醇代谢的影响

观察４种膳食纤维在两种蛋白来源下，对高脂血症大鼠生长、血脂、肝胆固醇、粪类固醇及胆汁成分的影响。结果表明：①四种膳食纤维均可降低大鼠血清ＴＣ水平，尤以豆胶效果显著。②豆胶显著升高ＨＤＬ－Ｃ／ＬＤＬ－Ｃ。膳食蛋白为大豆蛋白时，豆胶、沙棘皮可显著升高血清ＨＤＬ－Ｃ、ＨＤＬ－Ｃ／ＴＣ。③豆胶显著减少肝胆固醇累积，两种沙棘皮与大豆蛋白联用降脂强于与酪蛋白共用。④蛋白来源显著影响粪类固醇的排出，纤维类型可影响中性固醇排出并与蛋白质有交互作用。提示：蛋白质与膳食纤维之间的交互作用是探讨营养素与脂质代谢不可忽视的因素。     

The effects of brisk walking on markers of bone and calcium metabolism in postmenopausal women

Weight-bearing exercise has been shown to maintain or increase bone mass in younger as well as older individuals but the mechanisms by which mechanical loading affects bone metabolism are not known in detail. Twelve postmenopausal women participated in a single bout of brisk walking (50% of VO_{2 max}) for 90 minuttes. Calciotropic hormones and markers of type I collagen formation (PICP) and degradation (ICTP) were measured before the exercise, and 1, 24, and 72 hours following the exercise. Total body bone mineral content (BMC) and density (BMD) were measured by dual energy X-ray absorptiometry (DXA). Brisk walking did not induce any significant changes in the concentrations of ionized calcium, parathyroid hormone (PTH), calcitonin, or osteocalcin. A significant increase of PICP was noted 24 and 72 hours (P<0.01) after exertion and a significant decrease in the concentration of serum ICTP at 1 hour (P<0.05) was followed by an increase at 72 hours (P<0.001). There was no significant difference between the increases in the concentrations of PICP and ICTP at 72 hours. Strong inverse correlations between the basal levels of PTH and BMD (r=−0.78;P<0.01) as well as between osteocalcin and BMD (r=−0.83;P<0.01) were noticed. The changes in serum levels of bone collagen markers indicate an altered bone collagen turnover due to this moderate endurance exercise. The results also support the fact that serum levels of PTH as well as those of osteocalcin are associated with total body BMD in postmenopausal women.     

Formation of pyridinium species of haloperidol in human liver and brain

Recent interest in the neurotoxicity of haloperidol is based on its oxidation in rodents to the pyridinium derivative, HPP⁺, a structural analog of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP⁺). Recently, we reported that HPP⁺ and a newly identified reduced pyridinium, RHPP⁺, were present in blood and urine of haloperidol-treated schizophrenics and that the concentrations of RHPP⁺ exceeded those of HPP⁺. In this study, we examined pathways for formation of RHPP⁺ in subcellular fractions of human liver (n=5) and brain (basal ganglia;n=5). The major pathway was reduction of HPP⁺ (20 µM) to RHPP⁺ in cytosol (0.17–0.39 and 0.03–0.07 µM RHPP⁺/g cytosolic protein per h in liver and brain, respectively). The reactions were inhibited significantly by menadione and in brain also by daunorubicin. The inhibition profile, cytosolic location and strict NADPH dependence suggest that the enzymes involved are ketone reductases. A second pathway was oxidation of reduced haloperidol (50 µM), a major metabolite of haloperidol in blood and brain, to RHPP⁺. In liver microsomes, 0.17–0.63 µmol RHPP⁺ was formed /g microsomal protein per h. A potent inhibitor of the pathway was ketoconazole (IC₅₀, 0.8 µM), which suggests that P-450 3A isozymes could be involved. In brain mitochondria but not microsomes, reduced haloperidol (120 µM) was oxidised to RHPP⁺ at a small but significant rate (0.005–0.020 µmol RHPP⁺/g mitochondrial protein per h) which was not attenuated by SKF 525A, quinidine, ketoconazole, or monoamine oxidase inhibitors. Further studies are warranted to establish the biological importance of these metabolites in vivo.     

Favorable effects of epidural analgesia on hemodynamics,oxygenation and metabolic variables in the immediate post-anesthetic period

Fourteen adult patients undergoing elective major abdominal surgery were divided into two groups. One group received epidural and general anesthesia (epidural group), and 20 ml of 0.125% bupivacaine and 2 mg of morphine were administered epidurally about 30 min before the end of the operation for post-anesthetic analgesia. The other group (control group) received general anesthesia alone with nitrous oxide, oxygen and enfiurane. Flow-directed pulmonary arterial and radial arterial catheters were inserted preoperatively, and hemodynamic, respiratory, neuroendocrine and metabolic variables were measured serially. The data were compared during anesthesia and the immediate post-anesthetic recovery period. In the control group, the plasma epinephrine level in the post-anesthetic recovery period increased about four times over the anesthetic period. Oxygen consumption was increased and mixed venous oxygen saturation was decreased significantly. There was a close linear correlation between oxygen consumption (Y) and plasma epinephrine (X) level: Y = 285.7X + 90.5 (P < 0.01, r = 0.72). On the other hand, plasma epinephrine, oxygen consumption and mixed venous oxygen saturation did not change significantly in the epidural group in the post-anesthetic recovery period. There was also a close linear correlation between oxygen consumption (Y) and oxygen delivery (X): Y = 0.22X -32.0 (P < 0.01, r = 0.89). We conclude that the surgical stress and anesthetic reversal may seriously influence neuroendocrine responses and subsequently increase plasma epinephrine. Tissue oxygenation and metabolic imbalance may occur due to the rapid increase of epinephrine in the postanesthetic recovery period. Epidural analgesia at this period may play a more important role and have a more favorable effect on the tissue metabolism.     

Kupffer cell activation in the survival discrepancy between liver grafts from enterally and parenterally fed donors

Abstract This study was designed to investigate the effects of differences in the route of nutritional support of the donor on cold ischemia/reperfusion injury. Participation of Kupffer cells in these effects, based on the analysis of hepatic energy metabolism in early phases of reperfusion was also investigated. Orthotopic liver transplantation was performed between Large-White pigs weighing 20–30 kg after a 4-h cold preservation of the graft in Euro-Collins solution at 4°C. One group was fed orally with a standard laboratory diet (FED group, n = 5), a second group was fasted and given 20% glucose intravenously (12 kJ/kg per day) (PEF group, n = 5), and a third group was fed orally with a standard laboratory diet and given GdCI₃ (10 mg/kg) intravenously 24 h before operation (FEDGD group, n = 5). These treatments were given for 7 days prior to harvesting. The survival time was significantly longer in the PEF (34.8 ± 5.5 days) and FEDGD (28.0 ± 11.9 days) groups than in the FED (9.8 ± 2.0 days) group ( P < 0.05). The serum hyaluronic acid elimination rate determined from 1 to 2 h after reperfusion was significantly lower in the FED group than in the other two groups ( P < 0.001). The glycogen content of the livers 1 h after reperfusion in all three groups had been consumed rapidly, but the ATP content of the livers was significantly reduced in the FED group alone ( P < 0.01). Hepatic FFA clearance (C_FFA) was moderately increased in all three groups in the early phase after reperfusion, but it was higher in the FED group than in the other two groups, with significant differences 1 and 2 h after reperfusion ( P < 0.05). In conclusion, parenteral nutrition of the donors reduced cold ischemia/reperfusion injury which is related to Kupffer cell activation and, thus, was better than enteral nutrition for donor management.     

五种螯合剂对大鼠体内微量元素影响的观察

观察了５种常用螯合剂对大鼠体内微量元素排出量、组织分布的变化。结果表明，５种螯合剂可不同程度地增加机体必需微量元素Ｚｎ、Ｃｕ、Ｍｇ和Ｃａ经尿液排出量。ＥＤＴＡ和ＤＴＰＡ的影响尤为明显。ＥＤＴＡ和ＤＴＰＡ可使Ｚｎ经尿液的排出量增加１６－５２倍，ＤＴＰＡ使肝脏Ｚｎ含量减少１５．９％（Ｐ〈０．０５），肝脏Ｃｕ含量下降６０％（Ｐ〈０．０５）。ＥＤＴＡ和ＤＴＰＡ注射后，肾中Ｚｎ含量明显增高，相当对照大鼠３．