Beneficial effect of tibolone on mood, cognition, well-being, and sexuality in menopausal women

Tibolone is a synthetic molecule used extensively for the management of menopausal symptoms, with the proposed additional advantage of enhanced mood and libido. Tibolone, after oral administration, is rapidly converted into 3 major metabolites: 3α-hydroxytibolone and 3β-hydroxytibolone, which have estrogenic effects, and the Δ4-isomer, which has progestogenic and androgenic effects. The tissue-selective effects of tibolone are the result of metabolism, of enzyme regulation, and of receptor activation which vary in different tissues. Tibolone seems to be effective on estrogen-withdrawal symptoms such as hot flushes, sweating, insomnia, headache, and vaginal dryness, with results generally comparable to the effects exerted by estrogen-based treatments, and the additional property of a progestogenic activity on the endometrium. As well as relieving vasomotor symptoms, tibolone has positive effects on sexual well-being and mood, and improves dyspareunia and libido. These effects may depend on both estrogenic and androgenic actions exerted at the genital level and in the central nervous system, and on a reduction of sex-hormone-binding globulin and an increase of free testosterone, without affecting Δ-5 androgens levels. Based on the evidence available, tibolone is a valuable treatment option to relieve menopausal complaints, especially in women suffering persistent fatigue, blunted motivation, and loss of sexual desire despite an adequate estrogen replacement

A spatial model of autocatalytic reactions

Biological cells with all of their surface structure and complex interior stripped away are essentially vesicles - membranes composed of lipid bilayers which form closed sacs. Vesicles are thought to be relevant as models of primitive protocells, and they could have provided the ideal environment for pre-biotic reactions to occur. In this paper, we investigate the stochastic dynamics of a set of autocatalytic reactions, within a spatially bounded domain, so as to mimic a primordial cell. The discreteness of the constituents of the autocatalytic reactions gives rise to large sustained oscillations, even when the number of constituents is quite large. These oscillations are spatio-temporal in nature, unlike those found in previous studies, which consisted only of temporal oscillations. We speculate that these oscillations may have a role in seeding membrane instabilities which lead to vesicle division. In this way synchronization could be achieved between protocell growth and the reproduction rate of the constituents (the protogenetic material) in simple protocells.Comment: Submitted to Phys. Rev.

Pulmonary hypertension and chronic lung disease: where are we headed?

Pulmonary hypertension related to chronic lung disease, mainly represented by COPD and idiopathic pulmonary fibrosis, is associated with a worse outcome when compared with patients only affected by parenchymal lung disease. At present, no therapies are available to reverse or slow down the pathological process of this condition and most of the clinical trials conducted to date have had no clinically significant impact. Nevertheless, the importance of chronic lung diseases is always more widely recognised and, along with its increasing incidence, associated pulmonary hypertension is also expected to be growing in frequency and as a health burden worldwide. Therefore, it is desirable to develop useful and reliable tools to obtain an early diagnosis and to monitor and follow-up this condition, while new insights in the therapeutic approach are explored

Approaches to semi-synthetic minimal cells: a review.

Following is a synthetic review on the minimal living cell, defined as an artificial or a semi-artificial cellhaving the minimal and sufficient number of componentsto be considered alive. We describe concepts and experimentsbased on these constructions, and we point out thatan operational definition of minimal cell does not define asingle species, but rather a broad family of interrelated celllike structures. The relevance of these researches, considering that the minimal cell should also correspond to the early simple cell in the origin of life and early evolution, is also explained. In addition, we present detailed data in relation to minimal genome, with observations cited by several authors who agree on setting the theoretical fullfledged minimal genome to a figure between 200 and 300 genes. However, further theoretical assumptions may significantly reduce this number (i.e. by eliminating ribosomal proteins and by limiting DNA and RNA polymerases to only a few, less specific molecular species). Generally, the experimental approach to minimal cells consists in utilizing liposomes as cell models and in filling them with genes/ enzymes corresponding to minimal cellular functions. To date, a few research groups have successfully induced the expression of single proteins, such as the green fluorescence protein, inside liposomes. Here, different approaches are described and compared. Present constructs are still rather far from the minimal cell, and experimental as well as theoretical difficulties opposing further reduction of complexity are discussed. While most of these minimal cell constructions may represent relatively poor imitations of amodern full-fledged cell, further studies will begin precisely from these constructs. In conclusion, we give a brief outline of the next possible steps on the road map to the minimal cell

From the minimal genome to the minimal cell: theoretical and experimental investigations.

It is known that even the simplest living cells existing on the Earth have several hundredgenes, with hundreds of expressed proteins that catalyse simultaneously hundreds ofreactions within the same tiny compartment the cell representing a maize of anenormous and fascinating complexity. On the other hand, if we think to early cells orprotocells (those that played a key role in the origin of life), it is conceivable that theycould display some living properties with a minor number of biochemicalcomponents. In particular, the present huge complexity is most likely resulted frombillions of years of evolution, that developed a series of defence and securitymechanisms, redundancies, metabolic loops and highly sophisticated regulatoryprocesses.These considerations elicit the question, whether such a complexity is reallyessential for life, or whether instead cellular life might be possible with a much smallernumber of components. In this chapter we describe the basis of the concepts ofminimal genome and of the minimal cell.The question of the minimal genome and minimal cell has been considered sincemany years, and one should in particular recall the work of Morowitz (1967), who,based on the enzymatic components of primary metabolism, estimated that the size of aminimal cell should be about one-tenth smaller than Mycoplasma genitalium.Significant earlier insights into the field are those by Jay and Gilbert (1987) as well asby Woese (1983) and Dyson (1982). More recently, the reviews by Deamer andcoworkers (Pohorille and Deamer, 2002) and Luisis group (Luisi 2002, Oberholzer andLuisi, 2002) have sharpened the question and brought it in the perspective of modernmolecular tools. In fact, the last years have seen a significant revival of interest in thefield of the minimal cell, as witnessed for example by two international meetings held in2004 on the subject (Szathmáry, 2005). A more detailed version of a review on theminimal cell is in press elsewhere (Luisi et al., 2005)