New insights on P2X purinoceptors

Significant advances in understanding of P_2X purinoceptor pharmacology have been made in the last few years. The limitations of nucleotide agonists as drug tools have now been amply demonstrated. Fortunately, inhibitors of the degrading ecto-ATPase enzymes are becoming available and it has become apparent that the complete removal of all divalent cations can be used experimentally in some systems to prevent nucleotide breakdown. Despite these issues, convincing evidence for P_2X receptor heterogeneity, from data with agonists, has recently been reported.A number of new antagonists at P_2X purinoceptors have also recently been described which to some degree appear to be more specific and useful than earlier antagonists like suramin. It is now apparent that suramin is a poor antagonist of ATP in many tissues because it potently inhibits ATPase activity at similar concentrations to those at which it blocks the P_2X purinoceptor.Advances in the use of radiolabelled nucleotides as radioligands for binding studies has allowed the demonstration of P_2X purinoceptors in a variety of tissues throughout the body including the brain. These studies have also provided evidence for receptor heterogeneity. Excitingly, two P_2X purinoceptor genes have been cloned but operational studies suggest that more than two types exist. The cloning studies have also demonstrated a unique structure for the P_2X purinoceptor which differentiates it from all other ligand-gated ion channel receptors. Further studies on P_2X purinoceptor operation and structure are needed to help resolve controversies alluded to regarding the characterization and classification of nucleotide receptors. Hopefully such studies will also lead to a better understanding of the physiological and pathological importance of ATP and its activation of P_2X purinoceptors. This will require the identification of better drug tools, in particular antagonists which may also provide the basis for novel therapeutic agents.     

介入用聚氨酯材料的血液相容性研究

介入导管优良的血液相容性是确保血管内介入技术安全可靠进行的重要因素，我们对自己合成的四种介入导管用聚氨酯材料的血液相容性进行了评价，包括溶血试验、血小板黏试验、动态凝血时间试验和动态血栓形成实验。结果表明，其中的H50-100和H60-100具有优良的血液相容性，完全可以用作介入导管材料。此外，还讨论了聚氨酯结构与血液相容性的关系。     

Grafts of dissociated cerebellar cells containing Purkinje cell precursors organize into zebrin I defined compartments

Summary A prominent feature of the mammalian cerebellum is its organization into parasagittal compartments. One marker of such compartments is the zebrin I molecule that is expressed by bands of Purkinje cells (PC). In order to understand better the basis for the development of this organization, we have transplanted dissociated rat cerebellar anlage, taken during the period of proliferation of PC precursors, into kainic acid lesioned adult rat cerebellum. As previously observed, the resultant grafts exhibited trilaminar structures reminiscent of the normal cerebellum. In every case, the PC in the resultant grafts were organized into zebrin I + and — compartments. In one case, most of the grafted PC were integrated into a region of PC deficient host molecular layer that was induced by pretreatment with kainic acid. Clear bands defined by zebrin I reactivity were seen where groups of the grafted PC had entered the host molecular layer. These bands did not correlate in distribution or size with host bands. Hypotheses compatible with these findings that involve specific and non-specific aggregation of PC are discussed.     

Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion

Alphaviruses have the ability to induce cell-cell fusion after exposure to acid pH. This observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid pH after incorporation into a cell endosome. We have investigated the requirements for the induction of virus-mediated, low pH-induced cell-cell fusion and cell-virus fusion. We have correlated the pH requirements for this process to structural changes they produce in the virus by electron cryo-microscopy. We found that exposure to acid pH was required to establish conditions for membrane fusion but that membrane fusion did not occur until return to neutral pH. Electron cryo-microscopy revealed dramatic changes in the structure of the virion as it was moved to acid pH and then returned to neutral pH. None of these treatments resulted in the disassembly of the virus protein icosahedral shell that is a requisite for the process of virus membrane-cell membrane fusion. The appearance of a prominent protruding structure upon exposure to acid pH and its disappearance upon return to neutral pH suggested that the production of a "pore"-like structure at the fivefold axis may facilitate cell penetration as has been proposed for polio (J. Virol. 74 (2000) 1342) and human rhino virus (Mol. Cell 10 (2002) 317). This transient structural change also provided an explanation for how membrane fusion occurs after return to neutral pH. Examination of virus-cell complexes at neutral pH supported the contention that infection occurs at the cell surface at neutral pH by the production of a virus structure that breaches the plasma membrane bilayer. These data suggest an alternative route of infection for Sindbis virus that occurs by a process that does not involve membrane fusion and does not require disassembly of the virus protein shell.     

Terpene hydrocarbons in Pimpinella anisum L.

The essential oil of anise (fruits and shoots) was investigated focusing on the composition of the hydrocarbon fraction. Several sesquiterpenes were identified by GC-MS and the relative composition of the fractions was established by GC analysis. -Himachalene and the diterpene neophytadiene were isolated by TLC and column chromatography at low temperatures. Their structures were determined by MS and NMR including¹H-¹H correlated COSY and NOE experiments.     

A novel conotoxin inhibiting vertebrate voltage-sensitive potassium channels.

Toxins from cone snail (Conus species) venoms are multiple disulfide bonded peptides. Based on their pharmacological target (ion channels, receptors) and their disulfide pattern, they have been classified into several toxin families and superfamilies. Here, we report a new conotoxin, which is the first member of a structurally new superfamily of Conus peptides and the first conotoxin affecting vertebrate K+ channels. The new toxin, designated conotoxin ViTx, has been isolated from the venom of Conus virgo and comprises a single chain of 35 amino acids cross-linked by four disulfide bridges. Its amino acid sequence (SRCFPPGIYCTSYLPCCWGICCSTCRNVCHLRIGK) was partially determined by Edman degradation and deduced from the nucleotide sequence of the toxin cDNA. Nucleic acid sequencing also revealed a prepropeptide comprising 67 amino acid residues and demonstrated a posttranslational modification of the protein by releasing a six-residue peptide from the C-terminal. Voltage clamp studies on various ion channels indicated that the toxin inhibits the vertebrate K+ channels Kv1.1 and Kv1.3 but not Kv1.2. The chemically synthesized product exhibited the same physiological activity and identical molecular mass (3933.7 Da) as the native toxin.     

螺旋藻多糖的性质结构研究

采用高效液相色谱、气相色谱、特异性酶降解、高碘酸氧化、Smith降解及各种化学方法进行螺旋藻多糖分子质量、单糖组成、连接方式及糖苷键键型分析,并对各种化学成分进行测定。经检测螺旋藻多糖是一种由多种单糖组成的复杂多糖，具有β-型糖苷键．主链部分以1→3键连接为主。     

Mechanisms governing the differentiation of a serotonergic phenotype in culture

The blood–brain barrier prevents the entry of many potentially therapeutic peptide drugs to the brain. Glycosylation has shown potential as a methodology for improving delivery to the CNS. Previous studies have shown improved bioavailability and improved centrally mediated analgesia of glycosylated opioids. In this study we investigate the effect of glycosylation on the cyclic opioid peptide [ -Cys^2,5,Ser⁶,Gly⁷] enkephalin. The peptide was glycosylated on the Ser⁶ via an O-linkage with various sugar moieties and alignments. The peptides were then investigated for receptor binding, physiochemical attributes, in situ brain uptake in female Sprague–Dawley rats and antinociception in male ICR mice. Glycosylation resulted in a slight decrease in affinity to the δ-opioid receptor, and mixed effect on binding to the μ-opioid receptor. There was a significant decrease in lipophilicity resulting from glycosylation and a slight reduction in binding to bovine serum albumin. In situ perfusion showed that brain uptake was improved by up to 98% for several of the glycosylated peptides, and the nociceptive profiles of the peptides, in general, followed the rank order of peptide entry to the brain with up to a 39-fold increase in A.U.C.     

洱源县小兽类哺乳动物种群结构研究

目的　调查大理州洱源县小兽类哺乳动物种群结构。方法　 2 0 0 1～ 2 0 0 3年春季 ,在不同环境下采用捕鼠笼、鼠夹、电子捕鼠器等工具捕捉小兽 ,研究小兽种群结构。结果　捕获小兽 3目 5科 8属 17种共 661只。野外生境捕获小兽 3目 17种 ,以大绒鼠和齐氏姬鼠为常见种 ,分别占 3 2 .71%和 2 3 .5 9%。室内生境捕获小兽 2目 4种 ,褐家鼠为优势种 ,占 77.43 % ,黄胸鼠次之 ,占 18.75 %。结论　野外生境小兽种群丰富 ,室内较单一。     

Clinical application of neck acupoints in acupuncture

论述了颈部的局部解剖结构及常用穴位,以人迎穴为例,对针刺颈部穴位的刺法和注意事项进行阐述.