The effects of five phospholipases A2 from the venom of king brown snake, Pseudechis australis, on nerve and muscle

The effects on vertebrate neuromuscular function of five homologous phospholipases A₂ (PLA₂) (Pa-3, Pa-8, Pa-9C, Pa-10F and Pa-12B) from the venom of the Australian king brown snake, Pseudechis australis, were determined. These isoenzymes (0.2–1.6 μM) reduced, with different potencies, responses of chick biventer cervicis preparations to nerve stimulation and to exogenously applied acetylcholine, carbachol and KCl in a time- and concentration-dependent way but with different potencies. They also blocked twitches of mouse hemidiaphragm preparations evoked by nerve and by direct muscle stimulation. Pa-8 was the most active and Pa-9C was the least potent. There was a strong correlation between the enzymatic activity and the effect of toxins on the responses of mouse hemidiaphragm to direct muscle stimulation, but weak correlation between the effects on indirect responses and enzymatic activity. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations showed that Pa-10F and Pa-12B at 0.2 μM significantly reduced quantal content after 10 min. Pa-8 (0.2 μM) reduced the amplitude of endplate potentials by about 25% and abolished miniature endplate potentials within 15 min. Pa-3 (0.2 μM) and Pa-9C (0.8 μM) also significantly reduced quantal content by about 30% of control after 30 min. Among these toxins, Pa-3 and Pa-8 at 0.2 μM depolarised mouse muscle fibres after 30 min. Extracellular recording of action potentials at motor nerve terminals of mouse triangularis sterni preparations indicated that these isoenzymes reduced the waveforms associated with both Na⁺ and K⁺ conductances. Since no facilitatory effect on the release process has been observed, the apparent blockade of K⁺ conductance by some of these toxins may not be a selective action on K⁺ channels, but may be secondary to membrane depolarisation. An in vivo study with Pa-8 and Pa-10F demonstrated myotoxic effects. Light microscopic examination showed a degeneration of mouse and rat skeletal muscle fibres caused by Pa-8 and Pa-10F. For the in vivo study, rats received 80 μg/kg of the toxins s.c. and mice were injected i.m. with the toxins (40 μg/kg). Myotoxicity appears to be the predominant effect of these five toxins.     

Clinical evaluation of two methods of subdural pressure monitoring

Recordings from two different types of subdural pressure monitor with simultaneous intraventricular pressure (IVP) tracings are compared in 20 head-injured patients. In the first 10 patients a fluid-filled catheter was placed subdurally and connected to an external transducer, and in the second 10 the Gaeltec model ICT/b solid state miniature transducer was used. The latter system has the advantage that both zero and calibration checks can be carried out after insertion. Only 44% of the fluid-filled catheter readings corresponded with IVP in series of 10-mm Hg ranges, while 53% of readings were lower; this tendency was more marked at higher pressures. With the Gaeltec transducer, 72% of subdural pressure readings corresponded with IVP, while only 9% were lower and 19% were higher than IVP. The differences may have been due to technical causes or to true pressure differentials. The subdural catheter appears too unreliable for routine clinical use, but the Gaeltec transducer may be a satisfactory alternative to ventricular pressure monitoring.     

Effects of intrahippocampal administration of colchicine on incentive contrast and on radial maze performance

The behavior of rats given intradentate injections of the neurotoxin colchicine was examined in three experimental settings. In Experiment 1, colchicine-treated, artificial cerebrospinal fluid (CSF)-treated, and untreated animals did not differ in the intake of 32% and 4% sucrose solutions, nor did they differ in degree of successive negative contrast when the 32% solution was changed to 4% sucrose. In Experiment 2, the colchicine-treated and CSF-treated animals did not differ in degree of suppression in the intake of a 0.15% saccharin solution when it preceded 32% sucrose in once-daily pairings (anticipatory contrast), nor did they differ in reversal performance when saccharin-sucrose and saccharin-saccharin pairings were reversed. In Experiment 3, the colchicine-treated animals were substantially impaired in radial-arm maze performance compared with CSF-treated controls. These results suggest that a completely functioning hippocampus is not necessary for the memory of reward quality, the comparison of rewards, the suppression of behavior when reward is decreased, the formation of associations between two levels of reward, and the reversal of this association, as long as these processes are reflected in consummatory behavior. The data are interpreted in terms of differences between instrumental behavior and sensory memory and/or consummatory behavior--an interpretation that is not incompatible with a deficiency in working memory in the animals with lesions.     

Carbon monoxide exposure reduces the rewarding quality of brain-stimulation reward in rats

The effect of carbon monoxide (CO) exposure on hypothalamic brain-stimulation reward (BSR) was examined. Rats were trained in a procedure that daily determined their stimulus duration threshold (SDT), that is, the shortest electrical stimulus to the posterior lateral hypothalamus that would support discrete-trial leverpress responding for BSR. After a stable SDT baseline was established using a single response lever, rats were exposed to 0, 5, 10, 20, and 40 ml/kg pure CO by IP injection. The SDT was significantly elevated by the 40 ml/kg exposure (corresponding to approximately 65% carboxyhemoglobin in the blood) compared to control exposures of an equal volume. No change was observed in response rate at any dose in this 1-lever task. No tolerance was observed when 40 ml/kg CO exposure was repeated on alternating days for 14 exposures, but a small reduction in response rate was observed in this procedure. When rats of a second group were required to alternate responses on two levers some distance apart, SDT was elevated by the highest exposure (40 ml/kg) as before. Additionally, response rate was also significantly suppressed by the highest exposure in this 2-lever task. The results support the view that CO has a direct effect on brain reward systems assessed by the SDT task. Response rate changes due to CO exposure may be due to both direct effects on brain reward systems and other effects such as hypoxia-induced fatigue.     

Exercice d'endurance et métabolisme osseux

The effects on bone metabolism of an endurance exercise combining running, mountain bike riding and skiing for 7 days was studied in seven adult men competing in “Chamineige 96”. Such an exercise did not appear to significantly influence bone remodelling as it did not have any significant effect upon plasma osteocalcin concentration (marker of osteoblastic activity) and urinary calcium and deoxypyridinoline excretion (marker of bone resorption).     

肾脏病学的新创意:"肾脏疾病:改善全球预后"(KDIGO)

慢性肾脏病（CKD）是世界范围的医疗和公共卫生问题，并开始呈现流行性的特点。美国肾脏数据系统（USRDS）的数据提示，终末期肾衰的发病率呈上升趋势，因此对于这一问题的重视日益增加。根据近期USRDS登记系统提供的资料，世界范围内需要肾脏替代治疗（RRT）的终末期肾病（ESRD）患者数目持续上升，其中我国台湾、美国和日本最多（254-365人／100万人）。