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Lege Artis Medicinae

JUNE 21, 2006


FARKAS Katalin

[Dyslipidaemia is one of the known main risk factors of atherosclerosis by causing endothelial dysfunction that initiates and promotes vascular remodelling. Recent data from experimental and clinical studies suggest the existence of lipoprotein- neurohormonal interactions that may adversely affect vascular structure and function. Elevated lipid levels enhance the activation of the renin-angiotensin system, and, on the other hand, activation of the renin-angiotensin system leads to increased LDL cholesterol biosynthesis and oxidized-LDL uptake. These findings may explain the synergistic effect on cardiovascular risk observed in patients with coexisting hypertension and dyslipidaemia. The combined use of cholesterol-lowering drugs and inhibition of the tissue renin-angiotensin system may be more efficient in reducing cardiovascular risk.]

Lege Artis Medicinae

AUGUST 20, 2002

[The importance of endothelial dysfunction and possibilities of its treatment in chronic heart failure]


[Endothelial cells - under autocrine and paracrine control - may have a central role in the regulation of vascular tone. Endothelial dysfunction is a very early sign of heart failure but the clinical consequence is not well understood. Recent evidence suggests that upregulation of the neuro-endocrine-, and the renin-angiotensin-aldosterone system would lead to increased tissue- and circulating angiotensin-II levels. Elevated concentration of angiotensin-II provides a mechanism by which vasomotor responses to nitric oxide, prostaglandins are blunted, while the effects of vasoconstrictors such as thromboxans, endothelin and chatecholamins are enhanced. The higher basal vascular tone leads to the degeneration and atrophy of skeletal muscle, moreover to the the ischaemic damage of myocardial cells. Because renin-angiotensinaldosterone system is under genetic control, the deleterious effects of angiotensin-II depends on the angiotensin-converting enzyme gene. Pharmacological attempts to counteract endothelial dysfunction in heart failure may include the angiotensin-converting enzyme inhibitor, which can potentially improve the endothel dependent vasodilatation response. The importance of measuring endothelial function by non-invasive techniques is yet unknown, thus, before we introduce the widespread testing of patients for endothelial function, more research has to be done.]

Clinical Neuroscience

NOVEMBER 30, 2006


VARGA Hedvig, PÁRDUTZ Árpád, TAJTI János, VÉCSEI László, JEAN Schoenen

[Migraine is one of the most common neurological disorder affecting up to 14% of the population. The disease shows sexual dimorphism, thus gonadal steroids may play an important role in its patophysiology. One model of migraine headache is the systemic administration of nitric oxide (NO) donor nitroglycerin (NTG), which triggers a delayed attack without aura in many migraine patients but not in healthy volunteers. NTG is also able to activate the neurons of the caudal trigeminal nucleus in the rat. In our review we summarise the effect of NTG on the expression of some molecules, in the superficial laminae of the spinal portion of trigeminal nucleus caudalis, which play an important role in the pathomechanism of headaches, and the modulatory effect of chronic estradiol treatment. Our data show that NTG was able to modify all the examined substances in the caudal trigeminal nucleus, while chronic estradiol treatment abolished this effect. These data may help to understand the mechanisms by which estrogens influence trigeminal nociception and how nitric oxide triggers migraine attacks.]

Lege Artis Medicinae

SEPTEMBER 10, 2001

[Endothel dysfunction and hypertension]


[In the past two decade numerous data has been collected about the role of endothelium in the development of several cardiovascular disorders i.e. hypertension, congestive heart failure and atherosclerosis. Endothelial cells had been thought to be passive barriers only, but it turned out that through paracrine and autocrine hormone secretion they take part in modulating and regulating the vasodilator and vasoconstrictor effects being directed to vascular smooth muscle cells. The intact endothelium prevents the adhesion of platelets and monocytes, the platelet aggregation, as well as the migration and proliferation of vascular smooth muscle cells. It has been shown that both in experimental and human hypertension the endothelial function i.e. the so-called endothel-dependent vasodilatation is damaged, being the main feature of endothelial dysfunction. In spite of extensive research it is not clear whether endothelial dysfunction is a cause or a consequence of hypertension, with exact pathomechanism being also unclear. Methods, by which this important parameter could be precisely measured are under development. Researchers also examine whether recently used antihypertensive agents could improve or eliminate endothelial dysfunction and whether this effect may offer benefit to patients in terms of morbidity and mortality. This article attempts to summarize the most up-to-date information about the endothelial dysfunction research.]

Clinical Neuroscience

MARCH 30, 2006


KNYIHÁR Erzsébet, CSILLIK Bertalan

[Traditional concept holds that the pain unit consists of three neurons. The first of these, the primary nociceptive neuron, starts with the nociceptors and terminates in the dorsal spinal cord. The second one, called spinothalamic neuron, crosses over in front of the central canal and connects the dorsal horn with the thalamus. The third one, called thalamo- cortical neuron, terminates in the “pain centres” of the cerebral cortex. While this simplistic scheme is useful for didactic purposes, the actual situation is more complex. First, in the periphery it is only nociception that occurs, while pain is restricted to the levels of thalamus and the cortex. Second, pain results from interactions of excitation and inhibition, from divergence and convergence and from attention and distraction, in a diffuse and plastic system, characteristic for all levels of organization. This study describes the major cytochemical markers of primary nociceptive neurons followed by the presentation of recent data on the functional anatomy of nociception and pain, with special focus on the intrinsic antinociceptive system and the role of nitrogen oxide, opiate receptors, nociceptin and nocistatin. In addition to the classic intrinsic antinociceptive centres such as the periaqueductal gray matter and the raphe nuclei, roles of several recently discovered members of the antinociceptive system are discussed, such as the pretectal nucleus, the reticular formation, the nucleus accumbens, the nucleus tractus solitarii, the amygdala and the reticular thalamic nucleus, this latter being a coincidence detector and a centre for attention and distraction. The localisation of cortical centres involved in the generation of pain are presented based on the results of studies using imaging techniques, and the structural basis of corticospinal modulation is also outlined. Seven levels of nociception and pain are highlighted where pharmacological intervention may be successful, 1. the peripheral nociceptor, 2. the spinal ganglion, 3. the multisynaptic system of the dorsal horn, 4. the modulatory system of the brain stem, 5. the antinociceptive system, 6. the multisynaptic system of the thalamus, and 7. the cortical evaluating and localisation system that is also responsible for descending (inhibiting) control. The many levels of nociception and pain opens new ways both for pharmacological research and the general practitioner aiming to alleviate pain.]

Hypertension and nephrology

JUNE 20, 2010

[Changes in endothelial cells caused by cigarette smoke]

WAGNER László, LACZY Boglárka, CSEH Judit, TAMASKÓ Mónika, MAZÁK István, MARKÓ Lajos, MOLNÁR Gergő Attila, WAGNER Zoltán, MOHÁS Márton, FEKETE Andrea, WITTMANN István

[Endothelial nitric oxide synthase enzyme is regulated through the phosphorylation of the Ser(1177) and the Thr(495) sites, which influence the biological availabilaty of nitric oxide. We examined the acute effect of cigarette smoke, which decreases nitric oxide production. Endothelial cells were treated with different concentrations and for different times with cigarette smoke buffer, then with reduced glutathione or different protein kinase inhibitors. We determined the total and the phosphorylated nitric oxide synthase levels with Western blot. Cigarette smoke increased phosphorylation in a concentration- and time dependent manner at the Ser(1177) site and more pronounced at the Thr(495) site. Besides, it also led to the dissociation of the active dimer form of the enzyme. Reduced glutathione inhibited these phosphorylations and prevented the dissociation of endothelial nitric oxide synthase enzyme. The inhibition of protein kinase A or B did not influence the effect of cigarette smoke. However, protein kinase C inhibitors increased the phosphorylation caused by cigarette smoke at Ser(1177), but decreased it at Thr(495) sites. Summarized, cigarette smoke shifts the phosphorylation of the enzyme towards an inhibitory state, further on, it leads to the dissociation of the enzymatically active form. This results in the decreased biological availabilaty of nitric oxide, in which protein kinase C may play an important role.]

Lege Artis Medicinae

APRIL 20, 2005



[Although the differential diagnosis of asthma is simple in most cases, there are cases causing difficulties. Beside as an aid in diagnosis, there is a growing need for new tests to monitor airway inflammation to optimize and monitor the effect of treatment. Following the traditional methods used in everyday clinical practice a new method, the measurement of exhaled nitric oxide was introduced in the past decade. With this method, completely new information can be obtained about asthma supplementing other results in diagnosis making and disease monitoring. It is also expected to become the part of clinical practice in the next few years. The concentration of exhaled nitric oxide is elevated in asthmatic patients and its elevation is positively related to the degree of eosinophilic airway inflammation and symptoms. This measurement is approved in the European Union and in the USA for clinical use to monitor the effectiveness of anti-inflammatory treatment in asthma.]