Paläogenetik der Pest

Paleogenetics of the plague Plague has been part of our history since ancient times. Introduced again and again to Europe over centuries, the 'pestilences' killed millions of people before disappearing from the continent in 19^th Century. In the Middle Ages, bacteria were unknown and often the transmission routes of plague remained unrecognized. Plague was considered as a punishment by God disseminated by Miasma. With modern methods, microbiologists and palaeogenetists have now successfully shown that all the three historical recognized plague pandemics indeed were caused by the bacterium Yersinia pestis. In addition, important information has been obtained about the evolution of the bacterium and its origin. New data from ongoing studies on victims of the past epidemics help to shed new light on the past and perhaps even on the present of plague.     

The determination of S-nitrosothiols in biological samples--procedures, problems and precautions

Despite the considerable number of published studies in the field of S-nitrosothiols (RSNO), the determination of these compounds in biological samples still represents an analytical challenge, due to several technical obstacles and often long sample preparation procedures. Other problems derive from the intrinsic lability of RSNO and the absence of certified reference material, analytically validated methods or suitable internal standards. Also, thiols and nitrites are usually present at high concentrations in biological matrices, and all precautions must be adopted in order to prevent artifactual formation of RSNO. Preanalytical steps (sampling, preservation and pre-treatment of samples) are particularly critical for the obtainment of reliable measurements. Three main mechanisms have been identified capable of compromising the assays: metal-catalyzed RSNO decomposition, reduction of the S-NO bond by thiols (transnitrosylation reactions) and enzymatic degradation of S-nitroso-glutathione (GSNO) by endogenous γ-glutamyltransferase (GGT) activity possibly present in the sample. If not adequately controlled, these factors likely contribute to the wide dispersion of values reported in the literature for RSNO and GSNO concentration in biological fluids, blood in the first place. The use of metal chelators, thiol reagents and GGT inhibitors appears therefore mandatory.     

Molecular Bases of Caloric Restriction Regulation of Neuronal Synaptic Plasticity

Aging is associated with the decline of cognitive properties. This situation is magnified when neurodegenerative processes associated with aging appear in human patients. Neuronal synaptic plasticity events underlie cognitive properties in the central nervous system. Caloric restriction (CR; either a decrease in food intake or an intermittent fasting diet) can extend life span and increase disease resistance. Recent studies have shown that CR can have profound effects on brain function and vulnerability to injury and disease. Moreover, CR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which modulate pain sensation, enhance cognitive function, and may increase the ability of the brain to resist aging. The beneficial effects of CR appear to be the result of a cellular stress response stimulating the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors, neurotransmitter receptors, protein chaperones, and mitochondrial biosynthesis regulators. In this review, we will present and discuss the effect of CR in synaptic processes underlying analgesia and cognitive improvement in healthy, sick, and aging animals. We will also discuss the possible role of mitochondrial biogenesis induced by CR in regulation of neuronal synaptic plasticity.     

A prospective, randomised, controlled clinical study on the assessment of tolerability and of clinical efficacy of Merional (hMG-IBSA) administered subcutaneously versus Merional administered intramuscularly in women undergoing multifollicular ovarian stimulation in an ART programme (IVF)

Background  

Multifollicular ovarian stimulation (MOS) is widely used in IVF and the compliance to treatment is deeply influenced by the tolerability of the medication(s) used and by the ease of self-administration. This prospective, controlled, randomised, parallel group open label, multicenter, phase III, equivalence study has been aimed to compare the clinical effectiveness (in terms of oocytes obtained) and tolerability of subcutaneous (s.c.) self-administered versus classical intramuscular (i.m.) injections of Merional, a new highly-purified hMG preparation.     

Integrins, muscle agrin and sarcoglycans during muscular inactivity conditions: an immunohistochemical study

Sarcoglycans are transmembrane proteins that seem to be functionally and pathologically as important as dystrophin. Sarcoglycans cluster together to form a complex, which is localized in the cell membrane of skeletal, cardiac, and smooth muscle. It has been proposed that the dystrophin-glycoprotein complex (DGC) links the actin cytoskeleton with the extracellular matrix and the proper maintenance of this connection is thought to be crucial to the mechanical stability of the sarcolemma. The integrins are a family of heterodimeric cell surface receptors which play a crucial role in cell adhesion including cell-matrix and intracellular interactions and therefore are involved in various biological phenomena, including cell migration, and differentiation tissue repair. Sarcoglycans and integrins play a mechanical and signaling role stabilizing the systems during cycles of contraction and relaxation. Several studies suggested the possibility that integrins might play a role in muscle agrin signalling. On these basis, we performed an immunohistochemical analyzing sarcoglycans, integrins and agrin, on human skeletal muscle affected by sensitive-motor polyneuropathy, in order to better define the correlation between these proteins and neurogenic atrophy due to peripheral neuropathy. Our results showed the existence of a cascade mechanism which provoke a loss of regulatory effects of muscle activity on costameres, due to loss of muscle and neural agrin. This cascade mechanism could determine a quantitative modification of transmembrane receptors and loss of alpha7B could be replaced and reinforced by enhanced expression of the alpha7A integrin to restore muscle fiber viability. Second, it is possible that the reduced cycles of contraction and relaxation of muscle fibers, during muscular atrophy, provoke a loss of mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix. Consequently, these mechanical changes could determine modifications of chemical signals through variations of pathway structural integrins, and alpha7A could replace alpha7B.