Binding of estradiol to synaptosomal mitochondria: physiological significance

The subsynaptosomal distribution and specific binding of 17beta-estradiol in vitro to mitochondria isolated from presynaptic nerve endings of female rat brain were examined. 17Beta-estradiol is (i) distributed unequally in synaptosomes and mitochondria posses the highest capacity to bind estradiol with respect to the available amount of the hormone. (ii) Estradiol binds specifically to isolated synaptosomal mitochondria. A Michaelis-Menten plot of specific binding was sigmoidal within a concentration range of 0.1-5 nM of added estradiol, with a saturation plateau at 3 nM. Binding of higher estradiol concentrations demonstrated an exponential Michaelis-Menten plot, indicating non-specific binding to mitochondria. Vmax and Km for the sigmoidal-shape range were estimated as 46 +/- 6 fmol of estradiol/mg of mitochondrial proteins and 0.46 +/- 0.07 nM free estradiol respectively. (iii) Estradiol binding is not affected by the removal of ovaries. The results show that inhibition of Na-dependent Ca2+ efflux from mitochondria by estradiol occurs according to an affinity change of the translocator for Na+, at the same estradiol concentrations that show specific binding to mitochondrial membranes. These data imply that physiological concentrations of estradiol, acting on mitochondrial membrane properties, extragenomically modulate the mitochondrial, and consequently the synaptosomal content of Ca2+, and in that way exert a significant change in nerve cell homeostasis.     

Frequency-dependent effect of verapamil on rat soleus muscle

Summary In the presence of verapamil (0.1 mM) rat soleus muscle fibers failed to generate action potentials with overshoots. In fibers with their V_m set to a local level of –90 mV, verapamil produces a gradual reduction in the amplitude of the repetitive action potentials; this effect is more pronounced at high rates of stimulation (100 Hz). Our results suggest a local anesthetic action of this drug that could contribute with its calcium channel blocking effect to the diminished mechanical tension observed in the presence of the drug.Acknowledgments. We thank A. Losavio and M. Stefanolo for technical assistance. This work was supported by grants from CONICET and SUBCYT, Buenos Aires, Argentina and Muscular Dystrophy Association, USA.     

LHI注射液抗野百合碱致大鼠肺动脉高压的实验研究

目的 :观察LHI注射液抗野百合碱 (MCT)致大鼠肺动脉高压 (PH)和右心室肥大的影响。方法 :给SD大鼠一次腹腔注射MCT(60mg.kg-1)复制PH模型 ,2wk后用LHI注射液进行治疗 ,连续8d,然后用孙波法测定肺动脉压。结果 :MCT所致大鼠肺动脉高压和右心室肥大模型效果确切 ,平均肺动脉压升高、右心室/心脏重量比、肺湿/干重比值增大 ,与对照组相比 ,P<0.001(18.47±1.32VS11.02±1.21) ;使用LHI治疗后 ,肺动脉压有所降低 ,与模型组相比P<0.05(13.31±1.12VS18.47±1.32)。结论 :MCT造成肺动脉高压模型效果确切 ,LHI注射液对MCT所致的肺动脉高压有一定的对抗作用。     

大鼠生殖道肺支原体的分离与探讨

从１１只普通雌性大鼠生殖道分离出７株肺支原体，同时从它们的呼吸道也分离出肺支原体；另有１只大鼠生殖道和呼吸道均未分离出肺支原体。从该试验说明生殖道也可感染肺支原体。     

《水浒》绰号趣谈

燕青原是一个风流放荡的“浪子”;“一丈青”原是一个歌妓。鲁智深原是一个飞飞儿“花和尚”;龚旺因“浑身上刺着虎斑”故有“花项虎”的绰号。王定六走跳的快,象神女“活闪婆”那样;白胜的绰号“白日鼠”,即“白日贼”。“病关索”、“病尉迟”之“病”与“赛”同义。张横是一个船工,故称“船火儿”;杜兴生得又丑又怪,象戴了个“鬼脸儿”的假面具。张顺的绰号“浪里白跳”是错的,应是“浪里白条”。     

Pineal function cannot prevent the occurrence of castration cells in male rats

Summary The relationship between the pineal gland and the pituitary gland was investigated in male rats. The results indicate that the hypothalamo-adenohypophysial-gonadal axis is affected by the pineal gland, but the appearance of castration cells following gonal ablation may be only slightly modified by alterations in pineal gland function.     

Hypothalamic tyrosine hydroxylase activity,plasma gonadotropin and prolactin levels after aminooxyacetic acid in ovariectomized rats

Summary Plasma concentrations of gonadotropin, prolactin and hypothalamic tyrosine hydroxylase (TH) activity were measured in ovariectomized rats treated with aminooxyacetic acid (AOAA), a drug which elevates brain GABA levels. Hypothalamic TH activity was significantly increased with a significant decrease in prolactin (Prl) release. Plasma levels of gonadotropins were not modified by AOAA. These results support an inhibitory action of GABA on Prl release possibly mediated through hypothalamic dopamine.Supported by grants from Indian Council of Medical Research (ICMR), New Delhi. RIA kits for the estimation of LH, FSH and Prl were kindly supplied by Dr A.F. Parlow, NIAMDD-NIH, Bethesda, Maryland, USA. GNB is a UGC research fellow.     

Serotonin and 5-hydroxyindoleacetic acid concentrations in individual hypothalamic nuclei and other brain areas of rat

Summary Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were measured in individual nuclei of rat hypothalamus and other brain areas using HPLC with electrochemical detection. 5-HIAA levels were first demonstrated in hypothalamic and some discrete brain areas. The 5-HIAA/5-HT ratio was highest in the n. caudatus putamen, high in the n. ventromedialis and lowest in the n. suprachiasmaticus.     

Parenteral soya bean fat emulsions potentiate the hepatotoxicity ofE. coli endotoxin in suckling rats

Summary A dose of soy bean fat emulsion which was injected i.v. in suckling rats accumulated in the cells of liver parenchyma, both in hepatocytes and in reticuloendothelial cells. Subsequent i.p. injection ofE. coli endotoxin was followed by extensive liver tissue necrosis and increased activities of serum aspartic and alanine aminotransferase. These signs of liver damage were markedly more pronounced than those observed after the administration ofE. coli endotoxin only.     

A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles

Poly(MePEG₂₀₀₀cyanoacrylate-co-hexadecylcyanoacrylate) (PEG-PHDCA) nanoparticles have demonstrated their capacity to reach the rat central nervous system after intravenous injection. For insight into the transport of colloidal systems across the blood-brain barrier (BBB), we developed a relevant in vitro rat BBB model consisting of a coculture of rat brain endothelial cells (RBECs) and rat astrocytes. The RBECs used in our model displayed and retained structural characteristics of brain endothelial cells, such as expression of P-glycoprotein, occludin and ZO-1, and immunofluorescence studies showed the specific localization of occludin and ZO1. The high values of transendothelial electrical resistance and low permeability coefficients of marker molecules demonstrated the functionality of this model. The comparative passage of polyhexadecylcyanoacrylate and PEG-PHDCA nanoparticles through this model was investigated, showing a higher passage of PEGylated nanoparticles, presumably by endocytosis. This result was confirmed by confocal microscopy. Thanks to a good in vitro/in vivo correlation, this rat BBB model will help in understanding the mechanisms of nanoparticle translocation and in designing new types of colloidal carriers as brain delivery systems.Received 4 March 2005; accepted 14 April 2005