Heart failure and angiotensin converting enzyme inhibition: problems and perspectives.

Heart failure has become the most widely studied syndrome in cardiology over the recent years. Despite the encouraging achievements by angiotensin converting enzyme (ACE) inhibitors, the mortality of patients with chronic heart failure remains high. There are several factors which can potentially be responsible for the fact that about 80% of patients with a failing heart defy protection by ACE inhibitors: different activation of tissue and systemic renin-angiotensin system (RAS) in a particular heart disease and the distinct ability of various ACE inhibitors to block cardiac ACE, alternative pathways for angiotensin II formation (chymase), genetic polymorphism of the RAS system and the complexity of neuroendocrine activation. Moreover, chronic heart failure can provoke disturbances in the reactivity of peripheral vessels and metabolism of striated muscles. These factors may then potentiate the vicious circle of heart failure. New therapeutic approaches, which could further reduce the mortality in patients with heart failure involve angiotensin II type 1 receptor antagonists, beta-blockers, aldosterone antagonists and blockers of the endothelin receptor. A number of questions associated with functions of the RAS still remain open and their solution could be of substantial benefit for patients with a failing heart.     

Neural induction: new achievements and perspectives

Neural differentiation is specified for the first time during vertebrate's development in a part of cells of the embryonic ectoderm under the influence of signals emanating from neighboring tissues: the phenomenon of neural induction. As it was established more then 10 years ago by experiments with the Xenopus embryos, the inhibition of BMP signaling cascade in precocious of neural cells plays the main role in this phenomenon. As a result, the epidermal differentiation program is blocked in these cells, and instead the neural program appears to be activated in them on default. This so-called the default model of neural induction was also confirmed by experiments in other organisms. At the same time, an important role of FGF and Wnt signaling cascades in modulation of BMP cascade during neural induction was recently established. Identification and investigation of many novel proteins involved in the process of neural induction allows one to come back at the novel level, namely at the level of mathematical modeling, to one of the basic challenge of developmental biology: the problem of spatial patterning of cell differentiation during embryogenesis.     

Heart failure: advances through genomics

Heart failure is an increasingly prevalent and highly lethal disease that is most often caused by underlying pathologies, such as myocardial infarction or hypertension, but it can also be the result of a single gene mutation. Comprehensive genetic and genomic approaches are starting to disentangle the diverse molecular underpinnings of both forms of the disease and promise to yield much-needed novel diagnostic and therapeutic options for specific subtypes of heart failure.     

Mechanics of the brain: perspectives,challenges, and opportunities

The human brain is the continuous subject of extensive investigation aimed at understanding its behavior and function. Despite a clear evidence that mechanical factors play an important role in regulating brain activity, current research efforts focus mainly on the biochemical or electrophysiological activity of the brain. Here, we show that classical mechanical concepts including deformations, stretch, strain, strain rate, pressure, and stress play a crucial role in modulating both brain form and brain function. This opinion piece synthesizes expertise in applied mathematics, solid and fluid mechanics, biomechanics, experimentation, material sciences, neuropathology, and neurosurgery to address today’s open questions at the forefront of neuromechanics. We critically review the current literature and discuss challenges related to neurodevelopment, cerebral edema, lissencephaly, polymicrogyria, hydrocephaly, craniectomy, spinal cord injury, tumor growth, traumatic brain injury, and shaken baby syndrome. The multi-disciplinary analysis of these various phenomena and pathologies presents new opportunities and suggests that mechanical modeling is a central tool to bridge the scales by synthesizing information from the molecular via the cellular and tissue all the way to the organ level.     

Reproductive senescence: new perspectives in the wild

According to recent empirical studies, reproductive senescence, the decline in reproductive success with increasing age, seems to be nearly ubiquitous in the wild. However, a clear understanding of the evolutionary causes and consequences of reproductive senescence is still lacking and requires new and integrative approaches. After identifying the sequential and complex nature of female reproductive senescence, we show that the relative contributions of physiological decline and alterations in the efficiency of parental care to reproductive senescence remain unknown and need to be assessed in the light of current evolutionary theories of ageing. We demonstrate that, although reproductive senescence is generally studied only from the female viewpoint, age‐specific female reproductive success strongly depends on male–female interactions. Thus, a reduction in male fertilization efficiency with increasing age has detrimental consequences for female fitness. Lastly, we call for investigations of the role of environmental conditions on reproductive senescence, which could provide salient insights into the underlying sex‐specific mechanisms of reproductive success. We suggest that embracing such directions should allow building new bridges between reproductive senescence and the study of sperm competition, parental care, mate choice and environmental conditions.     

Heart failure induced by pheochromocytoma: laparoscopic treatment and intraoperative changes of several new cardiovascular hormones

Since 1992, adrenalectomy for pheochromocytoma has been recognized as a safe and efficient technique when performed by a laparoscopic approach. Most of the cases of pheochromocytomas treated as such and published in the literature were not associated with malignant hypertension and acute heart failure. We report the case of a 23-year-old woman who presented with this clinical picture and show that laparoscopic adrenalectomy may be as safe and efficient as conventional adrenalectomy when performed in this situation. The intraoperative changes in the secretion of catecholamines, endothelin-1, angiotensin II, N- and C-terminus of atrial natriuretic factor prohormone were also analyzed. Noradrenaline release during tumor dissection was associated with a stimulation of atrial natriuretic factor.     

Reconstructing immune phylogeny: new perspectives

Numerous studies of the mammalian immune system have begun to uncover profound interrelationships, as well as fundamental differences, between the adaptive and innate systems of immune recognition. Coincident with these investigations, the increasing experimental accessibility of non-mammalian jawed vertebrates, jawless vertebrates, protochordates and invertebrates has provided intriguing new information regarding the likely patterns of emergence of immune-related molecules during metazoan phylogeny, as well as the evolution of alternative mechanisms for receptor diversification. Such findings blur traditional distinctions between adaptive and innate immunity and emphasize that, throughout evolution, the immune system has used a remarkably extensive variety of solutions to meet fundamentally similar requirements for host protection.     

Evolution and classification of palms: new perspectives

Abstract

All recent studies of the family and of its relationships with other monocotyledons seem to indicate or confirm that the family represents a discrete monophyletic line, apparently quite isolated from other families.

Modern studies have provided a wealth of information that has called into question some of the groupings in Genera Palmarum (UHL & DRANSFIELD, 1987) and the integrity of some of the genera recognised. The autor propose to discuss some of the more outstanding problem groupings and attempts to give some idea of the wealth of continuing studies that affect our perception of relationships within the palms and between them and other families of monocots.     

Hypertension and new antihypertensive drugs: clinical perspectives

The nature of the clinical problem posed by hypertension has been changed fundamentally by 30 years of successful drug therapy. Cardiovascular pathology directly related to the high pressure is no longer the main problem. Complications of atheroma, particularly in the coronary arteries, are the main cause of hypertension-related deaths. Most patients now starting treatment have mild hypertension and the benefits, although significant, are small (two deaths prevented per 1000 patient-years of treatment). These two considerations dictate that new drugs must have a very low incidence of toxicity, a low incidence of symptomatic side effects, and preferably, a favorable effect on morbidity and mortality from ischemic heart disease. Several possible approaches have promise: 1) reduction of ischemic heart disease mortality by beta-adrenergic blockade; 2) use of calcium entry blocking drugs, which may combine vasodilation with antiarrhythmic effects; 3) non-thiol-converting enzyme inhibitors, which may have a particularly low incidence of side effects; 4) prostanoid derivatives that may combine vasodilatation with an antiplatelet action.     

Malaria drug-sensitivity testing: new assays,new perspectives

Over the past five decades, the drug resistance of Plasmodium falciparum has become an issue of utmost concern. At the same time, in vitro assays for assessing antimalarial drug sensitivity have become indispensable tools for the surveillance of drug resistance and the planning of therapeutic guidelines. Several new in vitro assays have been introduced, designed to be easier to handle than previous tests and allow a faster identification of drug-resistant parasites, as well as for simple evaluation of new drugs. This review examines the various new approaches to the in vitro assessment of malaria drug sensitivity and their limitations.