Inactivation of viruses infecting ectothermic animals by amphibian and piscine antimicrobial peptides

The ability of five purified amphibian antimicrobial peptides (dermaseptin-1, temporin A, magainin I, and II, PGLa), crude peptide fractions isolated from the skin of Rana pipiens and R. catesbeiana, and four antimicrobial peptides (AMPs) from hybrid striped bass (piscidin-1N, -1H, -2, and -3) were examined for their ability to reduce the infectivity of channel catfish virus (CCV) and frog virus 3 (FV3). All compounds, with the exception of magainin I, markedly reduced the infectivity of CCV. In contrast to CCV, FV3 was 2- to 4-fold less sensitive to these agents. Similar to an earlier study employing two other amphibian peptides, the agents used here acted rapidly and over a wide, physiologically relevant, temperature range to reduce virus infectivity. These results extend our previous findings and strongly suggest that various amphibian and piscine AMPs may play important roles in protecting fish and amphibians from pathogenic viruses.     

Effects of cGMP-dependent phosphorylation on rat and human connexin43 gap junction channels

The effects of 8-bromoguanosine 3:5-cyclic monophosphate (8Br-cGMP), a membrane-permeant activator of protein kinase G (PKG), were studied on rat and human connexin43 (Cx43), the most abundant gap junction protein in mammalian heart, which were exogenously expressed in SKHep1 cells. Under dual whole-cell voltage-clamp conditions, 8Br-cGMP decreased gap junctional conductance (g_j) in rat Cx43-transfected cells by 24.0±3.7% (mean±SEM, n=5), whereas g_j was not affected in human Cx43-transfected cells by the same treatment. The relaxation of g_j in response to steps in transjunctional voltage observed in rat Cx43 transfectants was best fitted with three exponentials. Time constants and amplitudes of the decay phases changed in the presence of 8Br-cGMP. Single rat and human Cx43 gap junction channels were resolved in the presence of halothane. Under control conditions, three single-channel conductance states (_j) of about 20, 40–45 and 70 pS were detected, the events of the intermediate size being most frequently observed. In the presence of 8Br-cGMP, the _j distribution shifted to the lower size in rat Cx43 but not in human Cx43 transfectants. Immunoblot analyses of Cx43 in subconfluent cultures of rat Cx43 or human Cx43 transfectants showed that 8Br-cGMP did not induce changes in the electrophoretic mobility of Cx43 in either species. However, the basal incorporation of [³²P] into rat Cx43 was significantly altered by 8Br-cGMP, whereas this incorporation of [³²P] into human Cx43 was not affected. We conclude that 8Br-cGMP modulates phosphorylation of rat Cx43 in SKHep1 cells, but not of human Cx43. This cGMP-dependent phosphorylation of rat Cx43 is associated with a decreased g_j, which results from both an increase in the relative frequency of the lowest conductance state and a change in the kinetics of these channels.     

Circadian temperature and wake rhythms of rats exposed to prolonged continuous illumination

The purpose of this study was to simultaneously measure temperature and sleep in the rat under continuous illumination in an attempt to reveal properties of the underlying circadian oscillators. At first, the circadian rhythms of temperature and wake free-ran in parallel. Within weeks or months, circadian arrhythmicity developed in most animals. Both circadian rhythms eventually damped out, even at fairly low light intensities. The circadian rhythm of wake was weaker and disintegrated sooner than the circadian rhythm of temperature. Although the data did not rule out control by separate circadian oscillators, one for temperature and one for wake, a single oscillator model was sufficient to explain this phenomenon. Ultradian variations with a period of about 2–5 hr were superimposed upon the circadian rhythms. When the circadian rhythms damped out, the ultradian variations remained. The ultradian bursts of wake preceded the ultradian bursts of temperature, suggesting a causal relationship. On the other hand, the circadian rhythm of temperature could not be dependent on the circadian rhythm of wakefulness, because the temperature rhythm could persist while the wake rhythm was absent.     

Quinidine blockade of calcium-activated potassium channels in dissociated gastric smooth muscle cells

The effects of quinidine, an antiarrhythmic alkaloid, on potassium-selective channels in enzymatically dissociated gastric smooth muscle cells fromRana pipiens andBufo marinus were investigated using excised patches and the patch-clamp technique. The predominant potassium channel in these cells is the calcium- and voltage-activated maxi-K channel with a single-channel conductance > 100 pS. Applications of quinidine (100–600 M) resulted in resolvable rapid flickerings between the open and blocked states with a corresponding reduction in open channel amplitude and an increase in open channel noise. The currentvoltage curves in the presence of internal quinidine and symmetrical potassium gradients displayed inward rectification. The time-constant of open-time distributions was found to decrease with increasing quinidine concentrations and membrane depolarization. The power-density spectrum of the channel current noise induced by internal quinidine showed a second Lorentzian component with a corner frequency larger than 300 Hz, suggesting that the noise is caused by rapid fluctuations between the open and blocked states. Apparent dissociation constants of 253 M and 209 M for membrane potentials of +20 mV and –60 mV, respectively, were obtained for the quinidine-induced blockade of Ca²⁺-activated K⁺ channels in these smooth muscle cells. Another potassium-selective channel with a single-channel conductance of 40 pS was completely blocked in the presence of 100 M qunidine. However, a 15 pS potassium channel was not affected by quinidine but was reversibly blocked by tetraethylammonium. Quinidine (500 M) was also observed to decrease the opening probability of a 40 pS potassium channel fromBufo marinus without affecting its channel amplitude. Thus, quinidine appears to have diverse mechanisms of action on potassium-selective channels in smooth muscle cells, ranging from totally ineffective to highly selective, as a slow blocker for some channels and as intermediate and fast blockers for others.     

发皇古义，继承创新——孙桐教授谈中医基础理论的继承与发展

中医基础理论现代化是整个中医药学现代化的基础,其研究方式可以从文献学角度、实验角度、中西医结合角度等多方面展开,当务之急是统一中医理论中一些最基本的概念和术语,用现代精确的科学术语来表述它们,使之规范化、标准化。     

先秦社会时空方位观对中医理论的影响

先秦社会的五行阴阳以及四风系统的时空方位观对中医理论发展有着很大影响 ,说明中医理论是在接受先秦时期科学技术思想及社会观念发展起来的 ,有许多内容尚待探讨 ,如仅用秦汉后的观点去认识是会有偏误的。     

迎随是针刺补泻的原则

以《灵枢·九针十二原》《难经·七十二难》等篇为据 ,说明在《内经》《难经》中 ,迎随不是某一具体的针刺补泻手法 ,只是一切针刺补泻法的代称和原则。对于迎随 ,后世大多宗于《难经》 ,发展为深浅迎随、针向迎随、流注盛衰时间迎随、补母泻子迎随等。现代多以针向迎随为补泻 ,但在临床上很少单独用。针向迎随在理论上不符合《灵枢》本义 ,在临床上只能在四肢穴作行气法用 ,没必要作为一种具体的针刺补泻手法存在     

实体语法系统与中医药理论现代化

实体语法系统是一种形式化语法系统，可用于形式化地描述复杂系统的组成单位、组织方式、变化规律。本文尝试将实体语法系统引入中医药理论研究，为实现中医药理论的形式化提供一种新的思路，并在此基础上探讨实现中医药理论与微观领域知识的衔接和用中医药理论解释人体复杂系统的可能性。实体语法系统为中医药理论形式化和中医药理论现代化提供了较具体的研究工具，为中医药理论现代化提出了探索性的思路。     

针刺足阳明经穴对大鼠胃运动影响及其与P物质的关系

为了探讨针刺足阳明经穴有运动的调整作用是否与脑肠肽中的Ｐ物质（ＳＰ）有关。以乙醇灌胃造成大鼠胃粘膜损伤模型,气囊法测量胃运动频率和波幅的变化率,采用放免分析法（ＲＩＡ）检测大鼠胃窦及延髓ＳＰ含量。结果显示：模型组胃运动频率和波幅呈抑制状态,胃窦ＳＰ含量降低,延髓ＳＰ含量升高;针刺四白、天枢、足三里穴可促进胃运动恢复,且天枢、足三里组胃ＳＰ含量升高,延髓ＳＰ含量呈下降趋势,针刺非穴组对胃运动和ＳＰ影     

Interaction of topiramate with glycine receptor channels

Glycine receptor channels are pentameric ligand-gated ion channels that respond to the application of inhibitory neurotransmitters by opening of a chloride-selective central pore. Topiramate (TPM) is a broad-spectrum antiepileptic drug used as add-on or monotherapy for focal seizures. In the present study the interaction of TPM with glycine receptor channels was studied on outside-out patches from HEK293 cells expressing alpha1beta glycine receptor channels. The patch clamp techniques combined with ultra fast solution exchange enabled us to investigate the kinetics of receptor channels in presence of TPM. Our study showed no agonistic or potentiating effect for TPM on glycine receptor channels. However, in presence of 1 mM glycine + 1 mM TPM, the desensitization got faster and the peak current amplitude decreased. After the end of glycine + TPM pulses, off-currents occurred, suggestive for a specific channel block mechanism.