Congenital dilation of seminal vesicle with agenesis of ipsilateral kidney: Symptoms and treatment

International Urology and Nephrology -     

Inositol derivatives modulate spontaneous transmitter release at the frog neuromuscular junction

One of the consequences of G-protein-coupled receptor activation is stimulation of phosphoinositol metabolism, leading to the generation of IP3 and its metabolites 1,3,4,5-tetrakisphosphate (IP4) and inositol 1,2,3,4,5,6-hexakisphosphate (IP6). Previous reports indicate that high inositol polyphosphates (IP4 and IP6) are involved in clathrin-coated vesicular recycling. In this study, we examined the effects of IP4 and IP6 on spontaneous transmitter release in the form of miniature endplate potentials (MEPP) and on enhanced vesicular recycling by high K+ at frog motor nerve endings. In resting conditions, IP4 and IP6 delivered intracellularly via liposomes, caused concentration-dependent increases in MEPP frequency and amplitude. Pretreatment with the protein kinase A (PKA) inhibitor H-89 or KT 5720 reduced the IP4-mediated MEPP frequency increase by 60% and abolished the IP6-mediated MEPP frequency increases as well as the enhancement in MEPP amplitude. Pretreatment with antibodies against phosphatidylinositol 3-kinase (PI 3-K), enzyme also associated with clathrin-coated vesicular recycling, did not alter the IP4 and IP6-mediated MEPP frequency increases, but reduced the MEPP amplitude increase by 50%. In our previous reports, IP3, but not other second messengers releasing Ca2+ from internal Ca2+ stores, is able to enhance the MEPP amplitude. In order to dissociate the effect of Ca2+ release vs. metabolism to IP4 and IP6, we evaluated the effects of 3-deoxy-3-fluoro-inositol 1,4,5-trisphosphate (3F-IP3), which is not converted to IP4 or IP6. 3F-IP3 produced an increase then decrease in MEPP frequency and a decrease in MEPP amplitude. In elevated vesicle recycling induced by high K+-Ringer solution, IP4 and IP6 have similar effects, except decreasing MEPP frequency at a higher concentration (10(-4) M). We conclude that (1) high inositol polyphosphates may represent a link between IP3 and cAMP pathways; (2) the IP3-induced increase of MEPP amplitude is likely to be due to its high inositol metabolites; (3) PI 3-K is not involved in the IP4 and IP6-mediated MEPP frequency increases, but may be involved in MEPP size.     

G2/M transition of pig oocytes: How do oocytes initiate maturation?

In the ovary, mammalian oocytes resume meiosis and mature to the second metaphase when they are stimulated with gonadotrophins. Similarly, oocytes can mature in vitro when they are liberated from ovarian follicles and cultured under appropriate conditions. Early in the process of maturation, oocytes undergo dramatic but well-ordered changes at the G2/M transition in the cell cycle including: (i) chromosome condensation; (ii) nucleolus disassembly; (iii) germinal vesicle breakdown (GVBD); and (iv) spindle formation in the first metaphase (MI-spindle). These events have been thought to be induced by MPF (maturation-promoting factor or M-phase promoting factor), now known as Cdc2 kinase or Cdk1 kinase, which consists of a catalytic subunit, Cdc2, and a cyclin B regulatory subunit. In fact, nuclear lamins are phosphorylated by Cdc2 kinase, and nuclear membrane breakdown occurs concomitantly with the activation of Cdc2 kinase in the M-phase of both somatic cells and oocytes. Based on the classical and recent studies of the pig oocyte, however, the chromosomes start to condense and the nucleolus disassembles before full activation of Cdc2 kinase, and the MI-spindle is formed after activation of both Cdc2 kinase and MAP kinase; another kinase known to become activated during oocyte maturation. These findings suggest that chromosome condensation and nucleolus disassembly in oocytes are induced by either some kinase(s) other than Cdc2 kinase and MAP kinase or some phosphatase(s). The accumulation of new results regarding the molecular nature of oocyte maturation is important for improving the reproductive technologies in domestic animals as well as in humans. (Reprod Med Biol 2003; 2 : 91–99)     

Translocation of presynaptic delta opioid receptors in the ventrolateral periaqueductal gray after swim stress

Immunolabeling for the delta opioid receptor (DOR) is localized primarily to axon terminals in the ventrolateral periaqueductal gray (vlPAG). However, rather than on the plasma membrane, DOR immunoreactivity is usually located within the cytoplasmic compartment, often associated with dense-core vesicles. In this study, the hypothesis that a behavioral stimulus, a cold water swim stress (3 minutes at 4 degrees C; CWSS), could initiate the translocation of the DOR was tested. The subcellular distribution of DOR was examined using a preembedding immunogold-labeling method and ultrastructural analysis in control rats and in rats that had a CWSS. In both cases, dense-core vesicles associated with DOR labeling were often within 100 nm of the plasma membrane. When the dense-core vesicles were near the plasma membrane, sometimes electron-dense "tethers" appeared between the vesicle and the plasma membrane. However, in rats exposed to CWSS, there was a decrease in immunolabeling associated with dense-core vesicles that were near the plasma membrane and a significant increase in DOR immunoreactivity associated with the plasma membrane. In addition, there was a significant increase in the fraction of DOR immunoreactivity associated with large clear-core vesicles; possibly early endosomes. Moreover, after a CWSS, dense-core vesicles containing DOR immunoreactivity could be visualized fusing with the plasma membrane of synaptic boutons. These data suggest the involvement of DOR in the vlPAG in the behavioral response to CWSS. Furthermore, the results support the hypothesis that the cell surface distribution of presynaptic receptors can be regulated in an activity-dependent manner by virtue of transport via dense-core vesicles.     

Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brain

Lithium salts are used to treat manic-depressive disorders; however, the mechanism by which lithium produces its therapeutic benefit remains obscure. The action of lithium may involve alterations of proteins important for regulating synaptic function. In this context, we observed recently that lithium at therapeutically relevant concentrations enhanced expression of cysteine string protein (csp) at the level of both mRNA and protein, in cell culture and in rat brain. Several lines of evidence have shown that csps are vital components of the regulated secretory pathway. We were interested whether lithium modulates expression of csp in specific brain regions. To study this issue, we analyzed the effects of chronic lithium administration (21 days) on csp mRNA levels in rat brain using in situ hybridization. Densitometric analysis revealed that lithium upregulated csp mRNA in several brain areas that are important for mood and behavior. This effect may be germane to understanding the beneficial action of lithium in mood disorders.     

Electron microscopic examination of the endomorphin 2-like immunoreactive neurons in the rat hypothalamus

Endomorphins are endogenous opioid peptides with high affinity and selectivity for the mu-opioid receptor. In the present study, we examined the morphology of the endomorphin 2-like immunoreactive (EM2-LI) neurons in the hypothalamus at the light and electron microscopic levels. At the light microscopic level, EM2-LI neurons were found mostly distributed in the regions between the dorsomedial and ventromedial hypothalamic nuclei and the region near the third ventricle. At the electron microscopic level, EM2-LI perikarya could be divided into two groups. Type I perikarya contained relatively undeveloped endoplasmic reticulum and Golgi apparatus while type II perikarya contained well-developed rough-surfaced endoplasmic reticulum and Golgi apparatus. Both type I and type II neurons contained numerous EM2-LI dense-cored vesicles. Type II perikarya and dendrites received synapses and showed immunoreactivity in the endoplasmic reticulum and Golgi apparatus. EM2-LI axon terminals formed synapses with both immunonegative and immunopositive dendrites. In some cases, the axon terminals contained both immunonegative and immunopositive dense-cored vesicles. EM2-LI neurons often had synaptic relationships with neurons containing immunonegative dense-cored vesicles. Myelinated axon shafts containing EM2-LI were also found. This first demonstration of the ultrastructure and synaptic relationships of EM2-LI neurons in the hypothalamus provides morphological evidence that suggests (1) endomorphin 2-containing neurons modulate physiological function through synaptic relationships; (2) endomorphin 2 may coexist with other neurotransmitters in the same neurons; and (3) endomorphin 2-containing neurons could modulate other endomorphin 2-containing neurons as well as those containing other neurotransmitters.     

涂碳式聚氯乙烯膜双嘧达莫选择电极的研制与应用

目的建立用涂碳式聚氯乙烯膜双嘧达莫电极测定双嘧达莫片含量的方法。方法利用该电极对双嘧达莫的响应 ,测定双嘧达莫片含量。结果平均回收率为 98 6 % ,RSD≤ 4 37% ,响应范围为 4 2× 10 -3 ～ 3 0× 10 -5mol·L-1,检测限为 1 7× 10 -5mol·L-1。结论涂碳式聚氯乙烯膜电极法可简便、快速、准确地检测片剂中双嘧达莫的含量。     

结肠定位释药双氯芬酸钠包衣片的制备及其体外释放

 目的以3种不同包衣材料制备时间依赖型结肠定位释药包衣片，并考察其体外释放影响因素。方法以双氯芬酸钠为模型药物，分别以乙基纤维素、Surelease和醋酸纤维素为包衣材料制备包衣片，用释放度测定法考察影响药物释放的因素。结果膨胀剂种类、包衣增重和包衣液中致孔剂浓度是影响药物释放的关键因素。3种包衣材料制备的双氯芬酸钠包衣片体外延时时间均可达到5～6 h。结论本实验为时间作为开关的结肠定位释药系统的进一步研究奠定了基础。     

抗肿瘤药物脂质体粒径对肿瘤靶向性的影响

脂质体抗癌药物的粒径在它将药物运载到肿瘤组织的过程中是一个重要的因素。在本文中，脂质体粒径在药代动力学中所发挥的作用从以下几方面进行了研究：（1）脂质体在血液中的分布和滞留时间；（2）脂质体在肿瘤组织中的积聚；（3）脂质体从肿瘤毛细血管中渗漏和它们在肿瘤组织中的滞留。最后，讨论了脂质体粒径在设计抗肿瘤脂质体药物时的重要性。