Invertebrate neuropeptides resembling vasotocin and some analogues: synthesis and pharmacological properties

The solid phase synthesis of three invertebrate vasopressin-oxytocin homologs: AVP-like factor, F1(1), ([Leu2, Thr4] AVT)2 isolated from subesophageal and thoracic ganglia of Locusta migratoria3, Arg-conopressin-S4. ([Ile2, Arg4] AVT), Lys-conopressin-G4 ([Phe2, Arg4] LVT), both isolated from the venom of fish-hunting marine snails of the genus Conus and six of their analogues is reported. These analogues are: [Arg4] AVT, [Ile2] AVT, [Leu2] AVT, [Phe2, Arg4] AVT, [Arg4] LVT and [Ile2, Arg4] LVT. All peptides were tested for antidiuretic and vasopressor activities.     

Fluorimetric assay of 3-o-methyldopamine and 4-0-methyldopamine in rat urine and o-methylation of dopamine]

A new method for the isolation and determination of 3-O-methyldopamine (3 MD) and 4-O-methyldopamine (4 MD) in the urine of Rat has been described. The administration of L-dopa enabled us to detect 4 MD in the urine with a molar ratio 4 MD/3 MD = 0.07. This ratio decreased with the simultaneous treatment of S-adenosylmethionine (SAM). This result might explain the therapeutic L-dopa+SAM in the treatment of parkinsonism, 4 MD being neurotoxic. The low level of 4 MD compared with the level of isovanillic acid, found by other authors, seems to indicate that the 4-O-methylation pathway takes place via dihydroxyphenylacetic acid.     

Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA

Voltage-dependent K+ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K+ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K+ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K+ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K+ channels in frog nerves depends on fiber diameter. The size dependence was used to determine the relative sensitivity of nodal and internodal K+ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K+ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K+ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.     

eIF4E和 VEGF C在大肠癌中的表达及其意义

目的探讨大肠癌组织中真核细胞翻译起始因子4E(eIF4E)和血管内皮生长因子 C(VEGF C)的表达及意义.方法应用免疫组织化学技术检测46例大肠癌及20例正常大肠组织中 eIF4E和 VEGF C的表达,同时结合患者的临床病理资料进行分析.结果46例大肠癌组织中的 elF4E和 VEGF C的表达阳性率分别为91.3和76.1%.而正常大肠组织中 elF4E和 VEGF C的表达阳性率分别为10%和20%.eIF4E和 VEGF的表达都与大肠癌患者性别、年龄、肿瘤病理分化程度无明显相关,但与肿瘤浸润深度、临床分期、有无淋巴结转移有关(P<0.05);两者的表达具有正相关(r=0.347,P<0.05).结论 eIF4E和 VEGF C与大肠癌的发生发展密切相关,可作为判断大肠癌侵袭转移及预后的重要指标     

Invertebrate neuropeptides resembling vasotocin and some analogues: Synthesis and pharmacological properties

Summary The solid phase synthesis of three invertebrate vasopressin-oxytocin homologs: AVP-like factor, F₁ ¹, ([Leu², Thr⁴] AVT)² isolated from subesophageal and thoracic ganglia ofLocusta migratoria ³, Arg-conopressin-S⁴. ([Ile², Arg⁴] AVT), Lys-conopressin-G⁴ ([Phe², Arg⁴] LVT), both isolated from the venom of fish-hunting marine snails of the genusConus and six of their analogues is reported. These analogues are: [Arg⁴] AVT, [Ile²] AVT, [Leu²] AVT, [Phe², Arg⁴] AVT, [Arg⁴] LVT and [Ile², Arg⁴] LVT. All peptides were tested for antidiuretic and vasopressor activities.     

Changes in mouse liver superoxide dismutase activity and lipid peroxidation during embryonic and postpartum development

Summary In inbred mice possessing high and low tissue superoxide dismutase (SOD) activity, it was observed that the difference in the SOD activities of the liver homogenates during development attains the maximum characteristic of the strain by about the 150th day. Subsequently, the SOD activity change displays a tendency in contrast with the age and the basic state. In the course of the development, a difference was also observed between the 2 mouse strains in the lipid peroxidation variation.Part XVIII of the series Properties of enzymes.     

Mutual replaceability of amide and ester groups in biologically active peptides and depsipeptides

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SLC26A4基因突变与耳聋

耳聋是最常见感觉障碍之一,与遗传关系密切.SLC26A4基因作为第二位的耳聋基因,与Pendred综合征(PS)和非综合征性聋DFNB4密切相关.SLC26A4基因突变主要与PS及DFNB4共同表现出的前庭水管扩大(EVA)相关,且不同种族及地区EVA患者该基因的突变频率及热点突变大不相同.SLC26A4基因的表现型与突变的类型关系不大,而是与等位基因数目相关.但目前SLC26A4基因突变的研究仍不完善.本文主要综述了近年来耳聋及SLC26A4基因的研究进展.     

Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA

Summary Voltage-dependent K⁺ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K⁺ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K⁺ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K⁺ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K⁺ channels in frog nerves depends on fiber diameter. This size dependence was used to determine the relative sensitivity of nodal and internodal K⁺ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K⁺ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K⁺ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.     

Cyclic and linear vasopressin V1 and V1/V2 antagonists containing arginine in the 4-position

Substitution of arginine for glutamine in the 4-position of a vasopressin V1 antagonist has been reported to turn it into an agonist. We resynthesized this 4-arginine analog and synthesized additional cyclic and linear vasopressin antagonists containing a 4-arginine. The presence of a 4-arginine in the resynthesized and new analogs had relatively minor effects on their antivasopressin V1 and V2 antagonistic potencies.     

Interaction of polyene antibiotics and serum lipoproteins

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Roles for interleukin-2 (IL-2) and IL-4 in the generation of allocytotoxic T cells in the primary and secondary responses in vitro.

Roles for interleukin-2 (IL-2) and IL-4 in the generation of murine allocytotoxine T lymphocytes (allo-CTL) in the primary and secondary responses were studied in vitro. The generation of allo-CTL in the primary response was inhibited by anti-IL-2 monoclonal antibody (mAb), but was not inhibited by anti-IL-4 mAb. On the other hand, the generation of allo-CTL in the secondary response was partially inhibited by either anti-IL-2 or anti-IL-4 mAb, and it was almost completely inhibited by the combination of two mAbs. CD8+ cell-depleted splenocytes produced IL-2, but not IL-4, in response to alloantigens in the primary response, and these cells produced both IL-2 and IL-4 in the secondary response. Both exogenous IL-2 and IL-4 induced functionally active allo-CTL in the primary response from CD4+ cell-depleted splenocytes when these cells were stimulated with T cell-depleted allogeneic cells. These results suggest that the allo-CTL induction in the primary response is IL:-2-dependent and secondary allo-CTL induction is both IL-2 and IL-4-dependent, because unprimed CD4+ T cells produce IL-2, but not IL-4, whereas primed cells produce both IL-2 and IL-4 in response to alloantigens.     

视神经脊髓炎与水通道蛋白4的进展研究

水通道蛋白4(AQP4)是 NMO IgG(视神经脊髓炎特异性抗体)的靶抗原.水通道蛋白4抗体(AQP4抗体)通过破坏血脑屏障、参与抗原激活星形胶质细胞的经典补体途径等方法导致中枢神经炎症及细胞毒性而致病.AQP4抗体阳性有助于明确NMO诊断并指导临床治疗用药,从而减少 NMO复发频率及延缓残疾     

Cyclic and linear vasopressin V1 and V1/V2 antagonists containing arginine in the 4-position

Summary Substitution of arginine for glutamine in the 4-position of a vasopressin V₁ antagonist has been reported to turn it into an agonist. We resynthesized this 4-arginine analog and synthesized additional cyclic and linear vasopressin antagonists containing a 4-arginine. The presence of a 4-arginine in the resynthesized and new analogs had relatively minor effects on their antivasopressin V₁ and V₂ antagonistic potencies.     

Roles for interleukin-2 (IL-2) and IL-4 in the generation of allocytotoxic T cells in the primary and secondary responses in vitro

Roles for interleukin-2(IL-2) and IL-4 in the generation of murine allocytotoxine T lymphocytes (allo-CTL) in the primary and secondary responses were studied in vitro. The generation of allo-CTL in the primary response was inhibited by anti-IL-2 monoclonal antibody (mAb), but was not inhibited by anti-IL-4 mAb. On the other hand, the generation of allo-CTL in the secondary response was partially inhibited by either anti-IL-2 or anti-IL-4 mAb, and it was almost completely inhibited by the combination of two mAbs. CD8⁺ cell-depleted splenocytes produced IL-2, but not IL-4, in response to alloantigens in the primary response, and these cells produced both IL-2 and IL-4 in the secondary response. Both exogenous IL-2 and IL-4 induced functionally active allo-CTL in the primary response from CD4⁺ cell-depleted splenocytes when these cells were stimulated with T cell-depleted allogeneic cells. These results suggest that the allo-CTL induction in the primary response is IL:-2-dependent and secondary allo-CTL induction is both IL-2 and IL-4-dependent, because unprimed CD4⁺ T cells produce IL-2, but not IL-4, whereas primed cells produce both IL-2 and IL-4 in response to alloantigens.     

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy.     

Effects of photoperiod, temperature and testosterone-treatment on plasma T3 and T4 levels in the Djungarian hamster, Phodopus sungorus

The effects of photoperiod, temperature and testosterone treatment on plasma T3 and T4 levels were investigated in the Djungarian hamster. Plasma T3 level was affected by temperature (25 degrees C less than 7 degrees C) but not by photoperiod. Plasma T4 level was affected by photoperiod (short day less than long day) at 25 degrees C. Administration of testosterone increased plasma T4 level under short photoperiod at 25 degrees C. Thus, higher plasma T4 level under long photoperiod at 25 degrees C might be induced by testosterone.     

循环雌二醇及代谢物与绝经后乳腺癌的相关性

目的探讨循环雌二醇（E2）、4-羟雌二醇（4-OHE2）、2-甲氧雌二醇（2-MOE2）水平及4-羟雌二醇：2-甲氧雌二醇（4-OHE2：2-MOE2）比值与绝经后乳腺癌危险性的相关性。方法采用ELISA法检测绝经后34例乳腺癌、40例乳腺良性（乳腺纤维腺瘤与乳腺囊性增生病）疾病患者和20例正常对照循环雌二醇、4-羟雌二醇、2-甲氧雌二醇水平并计算4-羟雌二醇：2-甲氧雌二醇比值。结果乳腺癌组及乳腺良性疾病组循环2-甲氧雌二醇水平差异无统计学意义（P〉0．05）,但均较正常对照组低（P〈0．05）;乳腺癌组及乳腺良性疾病组4-羟雌二醇：2、甲氧雌二醇比值差异无统计学意义（P〉0．05）,但均较正常对照组升高（P〈0．05）。乳腺癌Ⅰ期～Ⅲ期各期循环雌二醇、4．羟雌二醇、2-甲氧雌二醇、4-羟雌二醇：2-甲氧雌二醇比值差异无统计学意义（P〉0．05）。4-羟雌二醇、2．甲氧雌二醇、4．羟雌二醇：2-甲氧雌二醇比值在乳腺癌ER（-）组与ER（＋）组间差异无统计学意义（P〉005）,但ER（＋）组雌二醇水平较ER（-）组明显升高（P〈0．05）。结论2．甲氧雌二醇与绝经后乳腺疾病负相关;4-羟雌二醇：2-甲氧雌二醇比值可能预示绝经后乳腺疾病危险。