Ceskoslovenska fysiologie最新文献

Integrity of multicellular organisms is maintained by balance between cell proliferation and programmed cell death (apoptosis). Apoptosis is programmed cell death by regulated active process characterized by specific morphological and biochemical changes, whereas necrosis is a passive and genetically uncontrolled process followed by an inflammatory reaction of surrounding tissue. Suppression of apoptosis may contribute to the development of malignant tumours by means of accumulation of continuously proliferating cells and disruption of elimination of genetically altered cells with increasing malignant potential. Cell proliferation, differentiation and apoptosis are regulated by p16-cyclin D1-CDK4-Rb and p19ARF-p53-p21WAF1 pathways, which interact through multifunctional genes Rb and p53. Malignant tumours result from an accumulation of mutations of oncogenes, tumour-suppressor genes, pro-apoptotic and anti-apoptotic genes or from functional alterations of protein products of these genes as well. That results in dysregulation of the cell cycle and apoptosis and in the development of other signs of tumour phenotype (chromosomal instability, disruption of DNA repair, disruption of cell-cell communications and interactions between cells and extracellular matrix, suppression of the cell differentiation and replicative senescence, angiogenesis and changes in cell motile activity). Alteration of apoptosis, and/or genes involved in its regulation, is expressed in most manifestations of tumour phenotype. Thus, alteration of apoptosis strongly affects biological properties of malignant tumours and efficacy of their multimodal therapy. Present-day multimodal therapy of malignant tumours is specifically aimed at promoting the rate of apoptosis within tumours.

The neural system, responsible for language comprehension, must quickly process and integrate a large amount of heterogenous linguistic data. There is no appropriate and generally acceptable description of the architecture of this system. This means that no model of language processing is available that will allow, without problems, to interpret the wide range of disorders of language functions in neurological patients with focal lesions and explain the no less inconsistent results of experiments dealing with various aspects of language processing both in healthy people and in patients. In this paper are summed up the main findings from works of several authors who with electrophysiological recording techniques and metabolic imaging techniques (PET and MRI) sought answers to the question "where" and "how" in the brain are processed open class words and closed class words, nouns and verbs, or perhaps what is the temporal co-ordination and laterality of semantic and syntactic processes in language processing. The frequent contradictions in the findings, which a reader may quickly discover, are probably due to the design of the experiment, the properties of the stimulus applied, the type of the task to be solved during the experiment by its participants. In patients it may be also due to the accuracy of the determination of the anatomical localization and the extent of the lesions in nervous structures. In this context, however, it is necessary to be reminded that applied methods have their strong as well as weak points. Metabolic imaging techniques reliably inform of the exact localization of metabolically active brain structures, but they only give a rough picture of temporal dynamics of brain processes. On the other hand, electrophysiological techniques reflect precisely the temporal dynamics of neuronal activation near the recording electrode, but they say little about the activity of neuronal assemblies in areas remote from the site of registration.

Even though the alkaloids of opium, such as morphine and codeine, were isolated at the beginning of 19th century, the opioid receptors were not determined until 1970's. The discovery of endogenous opioid peptides, such as endorphins, enkephalins and dynorphins, has helped to differentiate between the specific opioid receptor subtypes, mu, delta and kappa, that are used up to now. Opioid receptors are distributed in the central nervous system unevenly. Each receptor subtype has its own specific and nonspecific agonists and antagonists. Opioides, as exogenous opioid receptor agonists, are drugs that are often used in medicine for their analgesic effects, but they are also some of the most heavily abused drugs in the world. Opioides may also induce long-term changes in the numbers and binding activities of opioid receptors. Some of our studies in fact demonstrate that prenatal morphine exposure can alter opioid receptors of adult rats. This may begin to provide insight into the sources of some of the morphological and behavioral changes in the progeny of mothers that received or abused opioides during pregnancy.

Sex steroid hormones influence the mammalian brain and modulate its activity during the lifespan. They are involved in regulation of gene transcription, neuronal excitability and neuronal survival. During development, sex hormones produce organizing effects in discrete brain regions. These regions include not only structures regulating sexual behavior but also other brain regions such as substantia nigra, hippocampus, cortex or amygdala. In mature brain, sex hormones have activational effects and modulate brain activity through excitatory or inhibitory mechanisms. Effects of sex hormones on seizure susceptibility and neuroprotective effects of beta-estradiol on status epilepticus-induced hippocampal damage will be discussed.

Catecholamines (norepinephrine, dopamine, epinephrine) act in the brain as chemical neurotransmitters and represent integrative component of many anatomical and functional interrelationships, which play important role in the maintenance of the basic physiological processes and homeostasis of living organism. In the brain, several well circumscribed conglomerations of catecholaminergic neurons and dopaminergic and noradrenergic pathways can be recognized. Although they are represented by only a few thousands of catecholaminergic neurons (in rat about 5) located only in certain brain areas, their rich arborization provides extensive innervation over the whole brain. Catecholamines are significantly involved in conveying of viscero- and somato-sensitive signals to integrative centrers located in higher brain areas and participate in the regulation of all vitally important systems under basal conditions as well as during stress. Their normal physiological activity is important for the maintenance of healthy functioning of the organism. Brainstem aggregations of catecholaminergic neurons, localized predominantly in autonomic regions, are involved in conveying the afferent peripheral stress and cardiovascular signals. The hypothalamic paraventricular nucleus, which represents an integrative center of the stress response, receives a rich catecholaminergic innervation from the caudal brain. On the other hand, catecholaminergic neurons localized in the ventrolateral rostral medulla form an important component of circuits involved in the regulation of the cardiovascular system. Central catecholamines are also involved in many other important brain circuits, however, with respect to the limited space of this review, they could not be included.

Mechanisms responsible for coughing in patients with rhinitis are not completely elucidated, because afferent innervation of nasal mucosa is not able to mediate cough reflex. There are several mechanisms that can participate in this pathogenetic process. The group of these mechanisms include: postnasal dripping of nasal mucus into the larynx, complete obstruction of the nasal cavity with inappropriate air conditioning, incomplete obstruction of nasal cavity with a possibility of microaspiration of nasal exudate, nasobronchial reflex, facilitating interaction between afferent inputs from nasal mucosa and central neuronal network responsible for coughing or propagation of the inflammatory process from the nose via airways or via systemic circulation into the lower airways mucosa. The most important mechanism that should be taken into consideration is hightened cough sensitivity (decreased threshold of afferent nerve endings in the larynx, trachea and more peripheral airways mediating cough) due to different effects of mechanisms mentioned above on the structure and/or function of afferent nerve endings in the lower airways responsible for inception and modulation of the cough reflex.

Enzyme cyclooxygenase plays an important role in many cellular processes. It is necessary for a synthesis prostaglandines, which belong to the most important mediators of inflammatory and pain processes. Many studies show an importance of this enzyme not only in periphery but in central nervous system as well. The main unsolved question is, if the cyclooxygenase-1 or cyclooxygenase-2 play the main role in synaptic transmission. In this review we try to summarise the current overview in relation to this topic.

Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable.

Much progress has taken place in knowledge of actions and use of opioids in pain in the last quarter century. There would be much less unnecessary pain and suffering if this knowledge would be applied properly in clinical practice. Why is it not? The major reasons appear to be ignorance, false prejudices (myths) and exaggerated limitations in availability of opioids for medical treatment of pain. Even the strongest opioid analgesics do not need to relieve pain in everybody. Their effect should be monitored and if inadequate, proper measures should be taken (e.g. adjusting a dose or changing an opioid). Weak opioids (codeine, tramadol) alone are mostly not stronger then non-opioid analgesics. However, combinations of opioid analgesics with paracetamol often show synergistic analgesic effect (without increased toxicity). Opioids actually represent very safe analgesics. Exaggerated opiophobia is a major myth causing much unnecessary pain and suffering in patients. Undue fear of drug abuse and/or political considerations have resulted in laws and regulations, that make it unnecessarily difficult to obtain opioids for medical use. An example of this might be a recent re-scheduling of buprenorphine in the Czech Republic and Slovakia among drugs with a very high abuse potential (e.g. morphine, fentanyl, amphetamine).