杀螺剂室内筛选实验方法标准化的研究Ⅰ.药液体积对杀螺效果的影响

目的 了解杀螺剂的不同药液体积对杀螺效果的影响。方法 实验室25℃浸泡杀螺。结果 每只钉螺用药液体积分别为0．5、1．0、2．0、3．3、10．0和20．0ml浸杀时，24h的LC50值分别为0．2242、0．1768、0．1064、0．0788、0．0788和0．0654mg/L，随药液体积增加杀螺效果增加，但增加至3.3ml/只后杀螺效果基本一致；48h的LC50值分别为0．0670、0．01167、0．0754、0．0640、0．0611和0．0367mg/L,1.0ml／只以上药液体积杀螺效果与24h组杀螺效果基本一致，但0．5ml/只组杀螺效果反而高于较大药液体积组。结论 实验室浸泡每只钉螺的杀螺药液体积宜大于3.3ml。     

Mechanism-Specific Antiarrhythmic Effects of the Potassium Channel Activator Levcromakalim Against Repolarization-Dependent Tachycardias

Mechanism-Specific Action of Levcromakalim. Introduction: The hypothesis that levcromakalim. a potassium channel (I_K-ATP.) activator with antihypertensive properties, has a mechanism-specific antiarrhythmic action against repolarization-dependent ventricular tachycardias (VTs) was tested in dogs. Methods and Results: A low dose of leveromakalim (0.01 mg/kg) was selected, which decreased blood pressure by 25% but had almost no electrophysiologic effect on AV nodal or ventricular conduction or effective refractory period. In dogs with chronic AV block, the antiarrhythmic action of this dose of levcromakalim was evaluated in three models of abnormal impulse formation: (I) dsotalol (2 mg/kg) induced torsades de pointes VT, initiated by early afterdepolarizations (EADs). (2) sustained ouabain-induced VTs, which are dependent on delayed after depolarizations (DADs), and (3) VT occurring 24 hours after left anterior descending coronary artery occlusion, which are likely based on abnormal automaticity. Levcromakalim abolished d-sotalol induced U waves, ventricular ectopic beats, and self-terminating bouts of torsades de pointes. Induction of torsades de pointes by pacing was also completely prevented. The cycle length of the idioventricular rhythm, which was lengthened after d-sotalol from 1490 ± 515 to 1700 ± 610 msec (P < 0.05), remained similar after levcromakalim (1655 ± 580 msec). The QT(U) duration, which was increased after d-sotalol from 410 ± 55 to 550 ± 40 msec (P < 0.05), normalized to 405 ± 70 msec (P < 0.05). Lcvcromakulim did not suppress but rather enhanced ouabain-induced VT by decreasing the cycle length slightly from 315 ± 35 to 290 ± 35 msec (P < 0.05). Pretreatment with a beta Mocker prevented this acceleration in rate. Finally, levcromakalim had no effect on VT 24 hours after infarction. Conclusion: A low dose of levcromakalim has specific antiarrhythmic properties against repolarization-dependent arrhythmias, but it does not affect VTs based on other mechanisms of abnormal impulse formation.     

Neurohormonal mechanisms and the role of angiotensin-converting enzyme (ACE) inhibitors in heart failure

Summary Clinical evidence accumulated over the past decade suggests that neurohormonal mechanisms significantly influence the pathogenesis and eventual outcome of congestive heart failure (CHF). Pharmacologic modulation of this neuroendocrine activity can, consequently, be expected to improve patient prognosis. Results of several recent clinical trials—the Studies of Left Ventricular Dysfunction (SOLVD), the second Veterans Administration Cooperative Vasodilator Heart Failure Trial (VHeFT-II), and the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)—provide substantial evidence that addition of the angiotensin-converting enzyme (ACE) inhibitor enalapril to conventional therapeutic regimens can significantly reduce mortality and improve prognosis in patients with all grades of heart failure. Moreover, data from all three trials confirm the involvement of neurohormonal systems in the development and progression of CHF and suggest that the beneficial effects of enalapril in heart failure may in part be due to the suppression of this neurohormonal activity. It is now apparent that some form of neurohormonal activation is present early in the course of the disease before the emergence of overt heart failure symptoms. On the basis of such findings, it would seem that early introduction of therapy targeted at neurohormonal influences may well become a central component of any future CHF treatment program.     

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation(10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue.     

Different forms of locomotion in the spinal lamprey

Forward locomotion has been extensively studied in different vertebrate animals, and the principal role of spinal mechanisms in the generation of this form of locomotion has been demonstrated. Vertebrate animals, however, are capable of other forms of locomotion, such as backward walking and swimming, sideward walking, and crawling. Do the spinal mechanisms play a principal role in the generation of these forms of locomotion? We addressed this question in lampreys, which are capable of five different forms of locomotion – fast forward swimming, slow forward swimming, backward swimming, forward crawling, and backward crawling. To induce locomotion in lampreys spinalised at the second gill level, we used either electrical stimulation of the spinal cord at different rostrocaudal levels, or tactile stimulation of specific cutaneous receptive fields from which a given form of locomotion could be evoked in intact lampreys. We found that any of the five forms of locomotion could be evoked in the spinal lamprey by electrical stimulation of the spinal cord, and some of them by tactile stimulation. These results suggest that spinal mechanisms in the lamprey, in the absence of phasic supraspinal commands, are capable of generating the basic pattern for all five forms of locomotion observed in intact lampreys. In spinal lampreys, the direction of swimming did not depend on the site of spinal cord stimulation, but on the stimulation strength. The direction of crawling strongly depended on the body configuration. The spinal structures presumably activated by spinal cord stimulation and causing different forms of locomotion are discussed.     

Monitoring stroke progression: in vivo imaging of cortical perfusion,blood–brain barrier permeability and cellular damage in the rat photothrombosis model

Focal cerebral ischemia is among the main causes of death and disability worldwide. The ischemic core often progresses, invading the peri-ischemic brain; however, assessing the propensity of the peri-ischemic brain to undergo secondary damage, understanding the underlying mechanisms, and adjusting treatment accordingly remain clinically unmet challenges. A significant hallmark of the peri-ischemic brain is dysfunction of the blood–brain barrier (BBB), yet the role of disturbed vascular permeability in stroke progression is unclear. Here we describe a longitudinal in vivo fluorescence imaging approach for the evaluation of cortical perfusion, BBB dysfunction, free radical formation and cellular injury using the photothrombosis vascular occlusion model in male Sprague Dawley rats. Blood–brain barrier dysfunction propagated within the peri-ischemic brain in the first hours after photothrombosis and was associated with free radical formation and cellular injury. Inhibiting free radical signaling significantly reduced progressive cellular damage after photothrombosis, with no significant effect on blood flow and BBB permeability. Our approach allows a dynamic follow-up of cellular events and their response to therapeutics in the acutely injured cerebral cortex.     

三七总皂苷治疗脑梗死作用机制的网络药理学研究

三七总皂苷（PNS）是从三七中将其主要药理活性成分提纯出来,三七总皂苷近年来在治疗与研究脑梗死方面取得了较佳的效果,而网络药理学是一种网络分析生物系统的新学科,基于系统生物学理论,从生物网络平衡学和系统生物学的角度来对疾病的发生发展过程进行阐释。本文就三七总皂苷治疗脑梗死作用机制的网络药理学进行研究,具有一定的参考价值。     

Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles

Engineered nanoparticles (NPs) are widely used in different technologies but their unique properties might also cause adverse health effects. In reviewing recent in vitro and in vivo genotoxicity studies we discuss potential mechanisms of genotoxicity induced by NPs. Various factors that may influence genotoxic response, including physico-chemical properties and experimental conditions, are highlighted. From 4346 articles on NP toxicity, 112 describe genotoxicity studies (94 in vitro, 22 in vivo). The most used assays are the comet assay (58 in vitro, 9 in vivo), the micronucleus assay (31 in vitro, 14 in vivo), the chromosome aberrations test (10 in vitro, 1 in vivo) and the bacterial reverse mutation assay (13 studies). We describe advantages and potential problems with different methods and suggest the need for appropriate methodologies to be used for investigation of genotoxic effects of NPs, in vitro and in vivo.