Effects of dehydroepiandrosterone sulfate and dizocilpine on memory trace extinction in aggressive and submissive mice

It was shown that injections of NMDA receptor antagonist dizocilpine and neurosteroid dehydroepiandrosterone sulfate (DHEAS) and sequential injections of these substances had different effects on learning and extinction of passive avoidance in aggressive and submissive mice. In aggressive mice, dizocilpine impaired and DHEAS did not change learning and retention. However, being injected after dizocilpine, DHEAS blocked the defect of memory trace retrieval induced by dizocilpine. In submissive mice, dizocilpine impaired learning and prolonged extinction of the learned habit. Injection of DHEAS prolonged the extinction in a similar way. Under conditions of sequential injections, DHEAS did not change the suppressive effect of dizocilpine on learning and was not effective in prolongation of extinction.     

Enzymatic determination of dehydroepiandrosterone sulfate in biological fluids

A simple method is described for the determination of androgens, particularly dehydroepiandrosterone sulfate (DHEAS), in human plasma and urine. The method does not involve extraction or chromatography. An internal standard is used as reference. The androgens are enzymatically converted to estrogens and these latter compounds can be measured by the enzymatic method previously described [1]. The range of accuracy was between 99 and 103%. The precision of the method was 2.5%. The sensitivity was 0.1 pM per sample. The method is suitable for routine use, and one worker can easily perform twenty assays in one day.     

牙龈卟啉单胞菌诱导T淋巴细胞活化、凋亡的体外研究

目的检测牙龈卟啉单胞菌对人外周血中T淋巴细胞活化及凋亡的作用,并检测Fas/FasL在牙龈卟啉单胞菌(Porphyrom onas gingivalis,Pg)诱导的T淋巴细胞凋亡中的表达。方法选取10例全身及牙周组织健康受试者,分离外周血中T淋巴细胞,在有/无Pg情况下培养0~96 h,用荧光探针(Annexin V-FITC、PI、CD69)及特殊的单克隆抗体(Fas、FasL)进行标记,并进行流式细胞仪检测。结果 CD69+淋巴细胞+Pg组Annexin V+/PI-细胞百分数在各个时间点上都明显高于T淋巴细胞+Pg组(P0.01)。Fas和FasL的表达量明显上调。用抗Fas单克隆抗体阻滞Fas-FasL相互作用导致T细胞凋亡的明显减少,百分比为(20.56±2.43)%,未加抗体的为(50.41±2.68)%。但残余的细胞凋亡活动与阴性对照相比仍高。结论 Pg能够诱导人外周血中T淋巴细胞活化,并且能够通过活化促进其凋亡,Pg诱导T淋巴细胞凋亡主要通过Fas-FasL途径,并具有时间依赖性。     

Effect of dehydroepiandrosterone sulfate on uterine cervical ripening in late pregnancy

In order to elucidate the effects of dehydroepiandrosterone sulfate (DHAS) on softening and dilatation of the uterine cervix, changes of oestriol, 17 beta-oestradiol and progesterone levels in serum and cervix, Bishop score and collagenase activity in the cervical tissue were assessed in pregnant women before and after treatment with DHAS. 17 beta-oestradiol level in the serum and cervical tissue markedly increased after the administration of DHAS, while oestriol level remained unchanged. Serum progesterone level did not change in the majority of cases, while it decreased within several hours in patients in whom delivery was accomplished within 24 hours after the administration of DHAS. Among the factors connected with the Bishop score, effacement and consistency of the cervix were remarkably improved by DHAS administration. Total collagenase activity in the cervical tissue of patients treated with DHAS was elevated by an average of 152%. These results suggest that DHAS is potent in ripening the uterine cervix through an activation of collagenase activity induced by the enhanced conversion to 17 beta-oestradiol. Thus, DHAS administration in the late stage of pregnancy is valuable in prepartal treatment for induction of labour.     

Dehydroepiandrosterone and dehydroepiandrosterone sulfate dynamics in obesity.

Dehydroepiandrosterone (D) and dehydroepiandrosterone sulfate (DS) dynamics were studied in three obese female subjects following a single injection of [4-14-CA1D and [7 alpha-3-H]-DS tracers. Dynamic parameters were calculated simultaneously by both the urinary and blood method of compartmentalization; Estimates for the urinary secretion and production rates of D were found to be high, and those of DS varied within normal range. Calculation of the conversion factors, rho DDS and rho DSD, by the urinary method revealed a noraml extraglandular DS yields D conversion, while that for D yields DS appeared deficient in obese female subjects. Estimates of inner and outer pool distribution volumes were extremely increased for free D; in contrast to this, moderately increased inner and decreased outer pool volumes of DS were observed. The metabolic clearance rates of D were normal or decreased and those for DS were greater than normal. The blood production rates of both B and DS were higher in obese female subjects than those estimated for normal women in our previous study; These observations suggest a considerable uptake of unconjugated D by adipose tissue, an overall poor D yields DS conversion and an accelerated DS metabolism in obese female subjects.     

Frequency of large granular lymphocytes in peripheral blood of healthy persons and breast cancer patients

Summary The frequency of large granular lymphocytes (LGL) in the peripheral blood of healthy persons (n=56) and breast cancer patients (31 cases with stage-I and -II disease and 42 cases with stage-III and -IV disease) was studied. The frequency of LGL in peripheral blood was significantly depressed in cancer patients, and particularly in patients with advanced breast cancer.     

Frequency of large granular lymphocytes in peripheral blood of healthy persons and breast cancer patients

The frequency of large granular lymphocytes (LGL) in the peripheral blood of healthy persons (n = 56) and breast cancer patients (31 cases with stage-I and -II disease and 42 cases with stage-III and -IV disease) was studied. The frequency of LGL in peripheral blood was significantly depressed in cancer patients, and particularly in patients with advanced breast cancer.     

Effect of dehydroepiandrosterone sulfate on stress reactivity: mu-opioid mechanism

The dehydroepiandrosterone sulfate (DHEAS) effect on stress-reactivity and the role of mu-opioid receptors in it, were studied. The experiments were carried out in male rats. The shuttling in single or in multiple (19 days, for 1 hour a day) regimes served as the experimental stress influences. The estimation of stress-reactivity was carried out by the plasma corticosterone level. It had been shown that the subcutaneous injection of dehydroepiandrosterone sulfate in rats reduced the stress-induced increase in corticosterone levels under the multiple influences, whereas naltrexone (0.1 mg/kg, for 20 min before DHEAS injection) blocked this effect. There were no effects of DHEAS or naltrexone on corticosterone levels under the single stress influences.     

Ways of apoptosis development in human lymphocytes, induced by UV-irradiation

The level of DNA damage and cytochrome c content in human lymphocytes in the dynamics of apoptosis induced by UV light (240?C390 nm) at doses of 151, 1510 and 3020 J/m² is studied. DNA fragmentation is revealed in 20 h after UV irradiation of lymphocytes at doses mentioned above. It is shown that DNA damages (single strand breaks) appear immediately after UV irradiation of lymphocytes at doses of 1510 and 3020 J/m² (comets of C1 type) and reach their maximum 6 h after cell modification (comets of C2 and C3 types). It is concluded that p53-dependent and receptor caspase pathways are involved in apoptosis development in the human lymphocytes, modified after UV irradiation.     

Skeletal muscle differentiation: role of dehydroepiandrosterone sulfate

Dehydroepiandrosterone (DHEA) and its sulfonated form dehydroepiandrosterone sulfate (DHEAS) are the main circulating steroid hormones and many epidemiological studies show an inverse relationship between DHEA/DHEAS levels and muscle loss for which the primary cause is the accelerated protein breakdown. The aim of this work was to determine whether DHEA/DHEAS supplementation in differentiating C2C12 skeletal muscle cells might influence the expression of the atrophy-related ubiquitin ligase, MuRF-1, and thereby impact key molecules of the differentiation program. DHEA is the prohormone crucial for sex steroid synthesis, and DHEAS is thought to be its reservoir. However, our preliminary experiments showed that DHEAS, but not DHEA, is able to influence MuRF-1 expression. Therefore, we treated differentiating C2C12 cells with various concentrations of DHEAS and analyzed the expression of MuRF-1, Hsp70, myosin heavy chain (MHC), myogenin, and the activity of creatine kinase. We observed that DHEAS at physiological concentrations downregulates MuRF-1 expression and affects muscle differentiation, as shown by the increased levels of MHC, which is a sarcomeric protein that undergoes MuRF-1-dependent degradation, and also by an increase in creatine kinase activity and myogenin expression, which are two other well-known markers of differentiation. Moreover, we found that DHEAS might have a protective effect on differentiating cells as suggested by the augmented levels of Hsp70, a member of heat shock proteins family that, besides its cytoprotective action, seems to have a regulatory role on key atrophy genes such as MuRF-1. In conclusion, our data shed light on the role of DHEAS at physiologic concentrations in maintaining muscle mass.     

Effect of dehydroepiandrosterone sulfate on collagenase production in rabbit uterine cervix culture

Rabbit uterine cervical explants were found to produce a typical collagenase, latent form, in tissue culture, 4-Aminophenylmercuric acetate and trypsin were potent activators of the enzyme. The enzyme was purified simply in one step of CM-52 cellulose ion-exchange chromatography, and then further characterized. Addition of dehydroepiandrosterone sulfate (DHAS) to culture medium significantly stimulated collagenase production, but DHAS did not directly activate the enzyme. In addition, dehydroepiandrosterone and 17 beta-estradiol, the main metabolites of DHAS in vivo, depressed enzyme production. Our previous result, that increases in cytoplasmic DHAS-binding protein in rabbit uterine cervices parallel the progress of pregnancy, and these results suggest that DHAS might have direct actions toward cervical ripening.     

Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis.

Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1.45 +/- 0.19 micrograms/ml, respectively. In normal women the values for days 5-7 of the cycle were 880 +/- 117 pg/ml and 1.25 +/- 0.12 micrograms/ml which were not different than the values for days 20-22 of 1195 +/- 176 pg/ml and 1.58 +/- 0.29 micrograms/ml. The mean values in post-menopausal women were 250 +/- 33 pg/ml and 0.47 +/- 0.07 micrograms/ml, both lower than the values in young women. In a group of cirrhotic men the mean values were 325 +/- 55 pg/ml and 0.38 +/- 0.12 micrograms/ml, both significantly lower than the normal values. This suggests a defect in sulfurylation in men with hepatic cirrhosis.