Identification and induction of cytochrome P450 2E1 in rat Kupffer cells

Kupffer cells, the resident macrophages of the liver, have a well characterized role in the removal of blood-born foreign substances by phagocytosis. Because Kupffer cells may contribute to hepatic xenobiotic metabolism, the current studies evaluated the presence and inducibility of P450 2E1 in rat Kupffer cells. Hepatocytes and Kupffer cells were isolated from the livers of control and acetone-treated (1% v/v acetone in the drinking water for 7 days) rats. P450 2E1 was immunochemically detectable at low levels in Kupffer cell homogenates from untreated rats and was induced greater than 10-fold by acetone-treatment. The presence of P450 2E1 in Kupffer cells from untreated rats was confirmed by inhibition of benzene hydroxylation with anti-P450 2E1 immunoglobulin G. Benzene hydroxylase activity was induced 16.3-fold in Kupffer cells isolated from acetone-treated rats and remained 70% inhibitable by anti-P450 2E1 antibody. The benzene hydroxylase activity of hepatocytes from the same animals was induced 3.9-fold by acetone treatment. The specific activity for benzene hydroxylation of Kupffer cell homogenates from acetone-treated rats was nearly equal to that for the hepatocytes from the same animals. The presence and inducibility of P450 2E1 in Kupffer cells suggests that, under conditions where P450 2E1 is induced, Kupffer cell-generated metabolites may contribute to Kupffer cell toxicity, as well as general hepatic injury.     

Carnitine metabolism during exercise in patients on chronic hemodialysis.

Patients on hemodialysis (HD) have impaired exercise performance. Carnitine homeostasis is also abnormal in this population. As carnitine is an important cofactor for muscle energy metabolism, exercise performance and skeletal muscle carnitine metabolism were characterized in eight HD patients, and in five age-matched controls. Each patient underwent graded bicycle exercise testing to define maximal performance, and prolonged exercise at 70% of their peak work capacity. Muscle (vastus lateralis) total carnitine content (carnitine plus all acylcarnitines) at rest was lower in HD patients than in controls (2320 +/- 1190 vs. 3800 +/- 940 nmol/g, P less than 0.05). In patients on HD, muscle carnitine content was inversely correlated to time on HD (r = -0.74, P less than 0.05), and positively correlated to peak exercise performance (r = 0.77, P less than 0.05). In patients on HD, 8 +/- 7% of the muscle carnitine pool at rest was short-chain acylcarnitines (similar to the distribution in controls), but 32 +/- 5% of the plasma carnitine pool consisted of short-chain acylcarnitines. With high-intensity exercise in patients on HD, muscle short-chain acylcarnitine content increased from 130 +/- 130 to 1380 +/- 820 nmol/g (P less than 0.01). The change in muscle short-chain acylcarnitine content with exercise was correlated with the increase in muscle lactate content (r = 0.88, P less than 0.01). In summary, patients on HD had a lower muscle total carnitine content than control subjects which was correlated to exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stroke in former prisoners of war.

Objectives. Physiological changes associated with severe or chronic stress may place susceptible individuals at risk for diseases such as stroke. Methods. A cohort of World War II veterans consisting of former prisoners of war (POWs) and controls was studied. Data were from a follow-up examination in 1986 that included a standardized history, comprehensive examination, and psychiatric interview. Results. Of former POWs, 9.3% (44 of 475) reported strokes compared with 1.2% (1 of 81) for other World War II veterans. The relative risk for this association was 7.50 (95% confidence interval [CI], 1.05 to 53.7; chi(2) = 6.00, 1 df). There was no difference in the prevalence of hypertension or diabetes. Among the 475 former POWs, 12.7% (20 of 158) of those with posttraumatic stress disorder had strokes, compared with 7.6% (24 of 317) without posttraumatic stress disorder (relative risk, 1.67; 95% CI, 0.95 to 2.93; chi(2) = 3.25, 1 df). Conclusions. There appears to be an association between stroke and being a former POW. Our findings may begin to define a new class of stroke risk factors and extend our understanding of interactions between stress and disease.     

小儿止咳冲剂提取工艺的实验研究

目的：寻找小儿止咳冲剂最佳提取工艺。方法：用正交试验法得到最佳提取条件。结果：以１６倍量水煎煮粗颗粒药材２次，每次０．５ｈ。结论：此提取条件为最佳。     

Concanavalin A prevents acetylcholine receptor redistribution in Xenopus nerve-muscle cultures

During neuromuscular junction formation ACh receptors accumulate at the nerve-contact region. It has been shown that this is at least partly due to lateral migration of existing receptors in the membrane (Anderson et al., 1977). Randomly diffusing ACh receptor molecules in the membrane may be trapped at the nerve-contact region to form a high receptor density area. If this were the major mechanism, cross-linking ACh receptors by tetravalent concanavalin A (Con A) should immobilize receptors and prevent nerve-induced receptor accumulation. We examined the effect of Con A on nerve-induced receptor accumulation and on the mobility of ACh receptors in cultured Xenopus muscle cells. ACh receptors were stained with tetramethyl rhodamine conjugated alpha-bungarotoxin. The cells were then treated briefly with Con A, and neural tube cells were added to these cultures. The mobility of ACh receptors was measured by the fluorescence photobleaching recovery method. The Con A treatment prevented rapid diffusion of ACh receptors as well as nerve-induced receptor accumulation. Functional synapse formation was not inhibited by this treatment. In contrast, divalent succinyl Con A did not affect the mobility of ACh receptors nor prevent nerve-induced ACh receptor accumulation. When the Con A concentration was varied, the blocking effect on the nerve-induced receptor accumulation changed in parallel with the mobile fraction of receptors. Newly inserted ACh receptors after the Con A treatment were found to be mobile and to accumulate at the nerve-contact region. In these cultures, new receptors accumulated around old, immobilized receptors in some areas along the nerve contact. This observation suggests that new receptors were inserted elsewhere and migrated to the nerve-contact region surrounding immobilized old ones. In addition to the accumulation of receptors, the nerve disperses preexisting receptor clusters prior to induction of high-density regions along the contact area, and, at this early stage, denervation disperses nerve-induced receptor clusters in Xenopus cultures (Kuromi and Kidokoro, 1984a, b). When cultures were treated with Con A, neither of these events occurred, suggesting that these are also diffusion-mediated.     

The effect of metronidazole on the incidence of postoperative wound infection in elective colon surgery.

A prospective randomized clinical trial assessing the relative effectiveness of erythromycin-neomycin and metronidazole-neomycin as a preoperative bowel preparation was carried out. Bacteriologic studies of feces and colon content revealed no significant difference in the reduction of aerobic bacteria between the two groups. There was, however, a significantly greater reduction in anaerobic bacteria in the feces and colon contents of patients receiving metronidazole. Wound infection rate was 25% in the erythromycin group, and organisms recovered from the wound in all cases were fecal in nature. Two wound infections occurred in the metronidazole group (5%) and in both cases the organisms recovered were staphylococci of presumed skin origin. These studies suggest that anaerobic bacteria are the major contributors to wound infection after colon surgery and that their specific reduction is associated with a lower incidence of wound infection.