Tibolone: a steroid with a tissue-specific mode of action

In postmenopausal women tibolone has proved to prevent bone-loss and relieve climacteric symptoms as effectively as estrogens, but it does not stimulate the endometrium and the breast. This clinical profile strongly suggests that tibolone is a compound with tissue-specific action. Tibolone is quickly metabolized into its main active metabolites, 3 and 3β-OH, which are also present in an inactive, sulphated, form. In addition a Δ4-metabolite is found in circulation. The 3-OH-metabolites bind only to the estrogen receptor while the Δ4-isomer shows affinity only to the progesterone and androgen receptors. Tibolone prevents bone loss in a similar way to estrogens. Studies on bone mass using anti-estrogen, antiprogestin and anti-androgen in combination with tibolone, confirmed the sole involvement of the estradiol receptor. Increases in skin temperature as well as vaginal atrophy can be prevented by tibolone in a similar way to estrogens. Breast safety studies showed that tibolone clearly inhibited the growth of tumors in a DMBA model. In breast cell lines, tibolone profoundly inhibited sulphatase activity and an increase in apoptosis and decrease in cell proliferation was found. The stimulation of the endometrium is prevented by the local formation of the Δ4-isomer from tibolone or the 3β-OH-metabolite. We conclude that tibolone acts as a tissue-specific compound by mediating its effects via steroid receptors and enzymatic pathways. This dual effect of tibolone explains it's positive clinical effects on bone, vagina and brain, and avoids stimulation of the endometrium and breast tissue.     

Global Positioning System (GPS) location accuracy improvement due to selective availability removal

Global Positioning System (GPS) is an important new technology for spatio-temporal behaviour studies of animals. Differential correction improves location accuracy. Previously, it mostly removed partially the influence of Selective Availability (SA). SA was deactivated in May 2000. The aim of this study was to quantify the influence of SA cancellation on location accuracy of various GPS receivers. We tested the accuracy of locations obtained from non-differential and differential GPS animal collars before and after SA removal. We found a significant improvement in accuracy for both types of GPS collars. However, differential GPS still provides more accurate locations.     

Role of abscissic acid in water stress-induced antioxidant defense in leaves of maize seedlings

Roles of abscisic acid (ABA) in water stress-induced oxidative stress were investigated in leaves of maize ( Zea mays L.) seedlings exposed to water stress induced by polyethylene glycol (PEG 6000). Treatment with PEG at -0.7 MPa for 12 and 24 h led to a reduction in leaf relative water content (RWC) by 7.8 and 14.1%, respectively. Duration of the osmotic treatments is considered as mild and moderate water stress. The mild water stress caused significant increases in the generation of superoxide radical ( O 2 - ) and hydrogen peroxide (H 2 O 2 ), the activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) and the contents of ascorbate (ASC), reduced glutathione (GSH). The moderate water stress failed to further enhance the capacity of antioxidant defense systems, as compared to the mild water stress. The contents of catalytic Fe, which is critical for H 2 O 2 -dependent hydroxyl radical ( •OH) production, and the oxidized forms of ascorbate and glutathione pools, dehydroascorbate (DHA) and oxidized glutathione (GSSG), markedly increased, a significant oxidative damage to lipids and proteins took place under the moderate water stress. Pretreatment with ABA caused an obvious reduction in the content of catalytic Fe and significant increases in the activities of antioxidant enzymes and the contents of non-enzymatic antioxidants, and then significantly reduced the contents of DHA and GSSG and the degrees of oxidative damage in leaves exposed to the moderate water stress. Pretreatment with an ABA biosynthesis inhibitor, tungstate, significantly suppressed the accumulation of ABA induced by water stress, reduced the enhancement in the capacity of antioxidant defense systems, and resulted in an increase in catalytic Fe, DHA and GSSG, and oxidative damage in the water-stressed leaves. These effects were completely prevented by addition of ABA, which raised the internal ABA content. Our data indicate that ABA plays an important role in water stress-induced antioxidant defense against oxidative stress.     

Characterization of free radical defense system in high glucose cultured HeLa-tat cells: consequences for glucose-induced cytotoxicity

HeLa cell line stably transfected with the tat gene from human immunodeficiency virus type 1 has a decreased antioxidant potential. In this work, we used this model to investigate the effect of a high glucose level (20 mM) on the glucose induced cytotoxicity and on the antioxidant system. In comparison to cell culture under control medium, HeLa-wild cell cultured under 20 mM glucose did not exhibit necrosis or apoptosis, contrary to HeLa-tat cell presenting a significant increase in necrotic or apoptotic state. Moreover after 48 h culture under high glucose level the HeLa-tat proliferation rate was not higher than the one of HeLa-wild cells. In HeLa-wild cell high glucose level resulted in an induction of glutathione reductase activity in opposition to HeLa-tat cells where no change was observed. High glucose level resulted in 20% increase in GSSG/GSH ratio in HeLa-wild cells and 38% increase in HeLa-tat cells. Moreover, high glucose level resulted in a dramatic cytosolic thiol decrease and an important lipid peroxidation in HeLa-tat cells. No significant change of these two parameters was observed in HeLa-wild cells. In both cell lines, high glucose resulted in an increase of total SOD activity, as a consequence of the increase in Cu,Zn-SOD activity. High glucose did not result in an increase of Mn-SOD activity in both cell lines. As a consequence of tat tranfection Mn-SOD activity was 50% lower in HeLa-tat cells in comparison to HeLa-wild cells. This work emphasizes the importance of the antioxidant system in the glucose induced cytotoxicity.     

Biochemical implications of sequence comparisons of the cystic fibrosis transmembrane conductance regulator

System A, the Na(+)-dependent amino acid transport activity, is encoded by the ATA2 gene and up-regulated following partial hepatectomy (PH), and its competitive inhibition interferes with liver regeneration. Rabbit polyclonal antibody was raised against a portion of the ATA2 gene product followed by immunodetection of ATA2 in isolated liver plasma membrane and lysate. The level of ATA2 increased in the plasma membrane following PH, while the relatively high quantity of ATA2 found in liver lysate remained constant. We also have shown that Northern analysis of steady-state ATA2 mRNA revealed no significant change following PH. These data show that ATA2-mediated transport is not regulated by the steady-state level of ATA2 mRNA but is regulated by the amount of ATA2 and redistribution to the plasma membrane. We hypothesize that ATA2 activity is regulated by recruitment of ATA2 protein from an intracellular compartment. In addition, the pattern of expression of System A activity in oocytes, transport kinetics, and sensitivity to chemical modification indicate the presence of a second System A isoform in liver that differs substantially from ATA2.     

Cortisol secretion in the elderly. Influence of age,sex and cardiovascular disease in a Chinese population

Adrenal function and aging have been the object of intense interest in recent years. In this study we analyzed morning (08:00 h) serum cortisol concentrations from a sample of Chinese subjects aged from 31 to 110 years. These levels differed according to age, health status and sex, although the sex difference was confirmed only among the healthy elderly. These results suggest that age (older than 60 years), disease and male sex are associated with increased morning serum cortisol levels in a Chinese population.     

Epidemic Spread of the Rust Fungus Puccinia lagenophorae and its Impact on the Competitive Ability of Senecio vulgaris in Celeriac During Early Development

The 'system management approach' of biological weed control was applied in a small-scale field experiment with celeriac (root celery), intersown with an inbred line of the annual weed Senecio vulgaris L. The naturalized rust fungus Puccinia lagenophorae Cooke (Basidiomycetes: Uredinales), a common and widespread pathogen of S. vulgaris in Europe, was introduced into parts of the plots, and its impact on the competitive balance between the crop and weed in the presence and absence of an additional herbicide treatment was studied. Competition by S. vulgaris (at a realized density of only 50 plants/m2) during the first 10 weeks of growth was substantial, reducing the fresh weight of the celeriac bulbs by 28%. The epidemic spread of the rust fungus was relatively fast, and the time to infection was similar to that in full-area applications. Inoculation with the rust fungus strongly reduced crop losses due to competition with S. vulgaris . The fresh weight of the celeriac bulbs in plots with both S. vulgaris and the fungus was not statistically diVerent from the celeriac yield in plots without S. vulgaris . This eVect was mainly the result of the reduced biomass of S. vulgaris , and not reduced survival. Infected plants may, therefore, still contribute to soil cover and may help to suppress later germinating weed species. Older plant stages were found to be infected earlier than younger stages. No significant interactions were observed between the eVects of the fungal infection and a low-dose application of the herbicide chlorbromuron on weed performance. Basic studies necessary to develop the system management approach further are discussed.     

Endogenous opiates: 1997

This paper is the twentieth installment of our annual review of research concerning the opiate system. It summarizes papers published during 1997 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; eating and drinking; alcohol; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunologic responses; and other behaviors.     

医学院校生物技术专业发酵工程实验体系的构建

为建设有特色的生物技术专业和培养创新复合型人才,本研究结合医学院校特点,充分利用"医"和"药"的资源,合理安排实验项目,构建了科学的发酵工程实验教学体系。结果表明该实验教学体系教学效果良好。学生的操作能力显著提高。为强化发酵工程教学,探索产学研联合培养模式将成必然。