猪肾近端小管的超微结构

目的 研究猪肾近端小管的超微结构。方法 树脂包埋一超薄切片、透射电子显微镜技术。结果 猪肾近端小管可分S1、S2、S3和S4段构成，其中S1、S2段构成了近端小管曲部，S3、S4段构成了近端小管直部。本文对各段细胞超微结构特点进行详细的描述。结论 猪肾近端小管的超微结构与人肾近端小管最接近。     

On the mechanism of increased potassium conductance by the potassium channel opener BRL 34915 in Isolated ventricular myocytes

The potassium conductance increased by BRL 34915 (BRL, cromakalim) was studied in single guinea pig ventricular myocytes by using a whole cell voltage-clamp technique. In control voltage-clamp recordings, the late current-voltage relation showed a distinct inward rectification. BRL (1–100 μM) shortened the action potential and diminished or abolished inward rectification but had no effect on the slope conductance and currents flowing during hyperpolarizing clamp steps. BRL did not decrease the slow inward current but accelerated the time constant of activation and amplitude of the outward current. Cd markedly decreased (0.2 mM) or abolished (0.4–0.6 mM) the slow inward current and BRL induced a faster outward shift of late current to a greater value. Glybenclamide (10 μM), a blocker of ATP-sensitive K⁺ channels, had little effect of its own on action potential, membrane currents, and I-V relation. However, in the presence of BRL, glybenclamide abolished BRL effects on action potential and currents and restored inward rectification. It is concluded that the mechanism by which BRL shortens the action potential is a faster growth of an outward current due to the reduction or abolition of the inward rectification of an ATP-dependent potassium channel. The reduction in force in non-isolated tissues appears to be an indirect result of the action potential shortening and not of a decreased slow inward current.     

Conditions to optimise the reversal action of neostigmine upon a vecuronium-induced neuromuscular block

Background: Since neostigmine was introduced for reversal of neuromuscular block, there has been controversy about the optimum dose for antagonizing neuromuscular block. The purpose of this study was to characterise recovery of neuromuscular transmission following a vecuronium-induced block 15 min after neostigmine administration using different stimulation patterns, and to determine the effects of different doses of neostigmine given at various pre-reversal twitch heights. Methods: Adductor pollicis (AP) mechanical activity in response to low (0.1 and 2 Hz) and high (50 and 100 Hz) frequency stimulation, was recorded 15 min after 20, 40 and 80 μg/kg neostigmine, given to reverse a vecuronium-induced block at 10, 25 and 50% pre-reversal twitch height (TH). Fifty four ASA class I and II anaesthetised (methohexital, fentanyl, N₂O/O₂) young adult patients were studied and randomly allocated into 9 groups of 6 patients each. Results: In contrast to twitch height (TH) and residual force after 50 Hz, 5 s tetanic stimulation (RF50_Hz), the greater sensitivity of train-of-four (TOF) ratio and residual force after 100 Hz, 5 s tetanic stimulation (RF100_Hz) points out the best reversal conditions (prereversal TH and the optimal neostigmine dose) (P<0.001, two-way analysis of variance). The highest reversal scores (about 0.9 TOF ratio and RF100_Hz) were obtained when 40 μg/ kg of neostigmine was given at 25 and 50% TH. A 0.9 TOF ratio was also observed when 40 μg/kg of neostigmine was given at 10% TH, but, under these conditions, RF100_Hz was only 0.6 (P<0.05, Duncan test). Conclusion: To optimise the reversal action of neostigmine in order to obtain the highest neuromuscular transmission recovery (0.9 TOF ratio and RF100_Hz) during a vecuronium-induced neuromuscular block, the 40 μg/kg dose has to be given at 25 to 50% recovery of TH.     

Testing for skin sensitization according to the notification procedure for new chemicals: the Magnusson and Kligman test

The notification procedure for new chemicals in the European Union (called the Chemicals Act in Germany) requires a skin sensitization test when the amount of a new chemical produced exceeds 100 kg/year. The preferred test is that of Magnusson and Kligman; more than 90% of the tests submitted are performed with it. Though the Magnusson and Kligman test is described in the literature, and in the test guidelines of the European Union and of the OECD, discrepancies do occur in the performance of the test between test laboratories. In this paper, recommendations are given for standardized performance of the Magnusson and Kligman test.     

Effectiveness and cost-effectiveness of colorectal cancer screening: Selecting the ideal strategy

Abstract Colorectal cancer is the second most common cancer killer of Americans. Recently developed and tested methods of screening and surveillance can effectively diagnose and treat the disease in most patients before symptoms develop when the chance of cure is high. It is also possible to prevent colorectal cancer by detecting and resecting premalignant adenomatous polyps. Evidence-based guidelines recommend that the average-risk population greater than age 50 be screened with annual faecal occult blood tests plus periodic flexible sigmoidoscopy. This approach is feasible, efficacious, affordable and cost-effective in a high-risk country such as the US. Widespread compliance with these recommendations could reduce the mortality from this malignancy by more than 50%.     

Propolis allergy

87% of the propolis product "LB-1", originally reported to be 1,1-dimethyl-allyl caffeic acid ester, was shown by GC/MS analysis to consist of 3 isomeric pentenyl caffeates, 63% of which are 1,1-dimethylallyl caffeate. These pentenyl caffeates proved to be the major sensitizers of propolis and of poplar bud secretion in our previous study. In addition, 3 further minor allergens have now been investigated. Experimental sensitization indicates that phenylethyl caffeate is as strong a sensitizer as the major allergen "LB-1", while benzyl salicylate is a moderate sensitizer. Benzyl cinnamate plays only a subordinate role. At least 3 further esters of caffeic acid or cinnamic acid remain to be studied. Interestingly, relationships between propolis and balsam of Peru were found. 8 compounds are common to both materials. Thus "cross-reactions" or concomitant reactions in propolis-sensitive individuals to balsam of Peru are explainable.     

Five different tests of reaction time evaluated in HIV seropositive men

In an attempt to develop a short neuropsychological test battery five different tests of reaction time were assessed according to their ability to discriminate between HIV seropositive men and healthy controls. In all tests a patient group with clinical symptoms was slower than the control group. In the complex reaction time test, which has a large cognitive aspect, even a clinically "asymptomatic" group was slower than the control group. The movement test, a new test with a large motor component, identified most slow responders, defining approximately half of the patients with clinical symptoms and one third of the "asymptomatic" patients as such. A test battery consisting of three tests is suggested for serial assessment and screening.     

Pertussis toxin and N-ethylmaleimide inhibit histamine- but not calcium ionophore-induced endothelium-dependent relaxation

Summary Endothelium-dependent relaxation of the guinea pig pulmonary artery induced by histamine was inhibited by preincubation of the tissue with 10 M N-ethylmaleimide (NEM) for 10 min, whereas the endothelium-dependent relaxation induced by the calcium ionophore A 23187 was not affected by NEM. Pretreatment of the preparations with 0.2–1 g/ml pertussis toxin for 120 min inhibited concentration-dependently the histamine-induced relaxation. In contrast, endothelium-dependent relaxation in response to the calcium ionophore A 23187 was not affected by pertussis toxin. Since NEM and pertussis toxin are thought to interfere with membrane located GTP binding proteins, it is suggested that such a coupling protein is involved in the signal transduction of the histamine receptor leading to endothelium-dependent relaxation.A preliminary report of these results was presented at the autumn Meeting of the Deutsche Pharmakologische Gesellschaft, 1986 Send offprint requests to G. Weinheimer at the above address     

Guinea pig maximisation test for skin sensitisation: the use of fewer test animals

Current European Community (Annex V) guidelines recommend the use of 20 test animals in the guinea pig maximisation test for skin sensitisation. The suitability, for classification and labelling purposes, of reducing the number of test animals has been examined by analysing the results of 40 studies submitted to the Health and Safety Executive, and by the use of a mathematical model. Our results suggest that in most cases an experiment with ten test animals can be used to determine satisfactorily whether a substance should be labelled with the risk phrase may cause sensitisation by skin contact. However, serious consideration should be given to the need for additional investigation if two or three of the ten test animals show a sensitisation response. The highest nonirritant concentration of a substance should be used at challenge. Clearer guidance in Annex V on evaluating challenge responses would be beneficial.