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Hypertension and nephrology

OCTOBER 23, 2019

[The importance of brain-derived neurotrophic factor in psychopathology and cardiovascular conditions: psychosomatic connections]

LÁSZLÓ Andrea, LÉNÁRT Lilla, ILLÉSY Lilla, FEKETE Andrea, NEMCSIK János

[Cardiovascular diseases and mood disorders are common public health problems worldwide. Their connections are widely studied, and the role of neurotrophins, especially brain derived neurotrophic factor (BDNF) is already supposed in both conditions. However, no reviews are available describing possible associations between cardiovascular risk and mood disorders based on BDNF. Decreased level of BDNF is observed in depression and its connection to hypertension has also been demonstrated with affecting the arterial baroreceptors, reninangiotensin system and endothelial nitric oxide synthase activity. BDNF was also found to be the predictor of cardiovascular outcome in different patient populations. Our aim was to overview the present knowledge in this area demonstrating a new aspect of the associations between mood disorders and cardiovascular diseases through the mediation of BDNF. These findings might enlighten a new psychosomatic connection and suggest a new therapeutic target that is beneficial both in respect of mood disorders and cardiovascular pathology.]

Clinical Oncology

MAY 10, 2018

[Recent strategies in the chemoterapy of soft tissue tumors]

PÁPAI Zsuzsanna, KISS Nóra

[Conventional adjuvant therapy is, in most cases, either the well-known standard doxorubicin monotherapy or the combination of doxorubicin + ifosfamide. No clear guideline has been developed yet - adjuvant therapy is recommended in cases with high grade, larger than 10 cm, sarcoma, where surgery hasn’t been suffi ciently radical, and adjuvant radiotherapy may not be advisable. In locally advanced tumors, due to the requirements of limb salvage, isolated limb perfusion is recommended. As a new compound, hafnium-oxide nanoparticles (NBTXR3) can be useful in local therapy: combining intratumoral injection and radiotherapy may be a fl agship initiative, however further investigations are necessary. In the treatment of metastatic tumors, beside the standard methods, new, targeted treatments are becoming more and more prevalent: in leiomyosarcomas trabectedine, pazopanib and olaratumab; in liposarcomas trabectedine and eribulin; in synovial sarcomas pazopanib; and in imatinib-resistant GIST, sunitinib and regorafenib. Soft tissue sarcomas are rare tumors categorized as heterogeneous histological subtypes. In their treatment, it is key to customize the treatment based on these subtypes and interdisciplinary collaboration with the orthopedic surgeon, the pathologist and the radiotherapist to determine the suitable therapy for each individual.]

Clinical Neuroscience

MARCH 30, 2017

Electrophysiological alterations and general toxic signs obtained by subacute administration of titanium dioxide nanoparticles to the airways of rats

HORVÁTH Tamara, PAPP András, KOVÁCS Dávid, KÁLOMISTA Ildikó, KOZMA Gábor, VEZÉR Tünde

Introduction and aims - Particles of titanium dioxide (TiO2) with typical size below 100 nm have gained a broad range of application by now, partly involving direct human exposure. Their known properties - high specific surface, mobility within the organism, induction of oxidative stress, release of inflammation mediators etc. - raise the possibility of nervous system damage but the available data regarding this are scarce and contradictory. Based on that, and the experiences with other metal oxide nanoparticles, the aim of the present study was to investigate certain general end nervous system toxic effects of TiO2 nanoparticles applied in the airways of rats. Materials and methods - Young adult Wistar rats (5 groups of 10 rats each) received, daily for 28 days, intratracheal instillations of titanium dioxide nanoparticles of ca. 10 nm diameter, suspended in 1% hydroxyethyl cellulose dissolved in phosphate-buffered saline, in the doses of 1, 3, and 10 mg/kg b. w. Vehicle controls received the suspension medium and there was also an untreated control group. During treatment, the rats’ body weight was measured, and their clinical state observed, daily. After the 28 days, spontaneous cortical activity, sensory evoked potentials and tail nerve action potential was recorded in urethane anesthesia, then the rats were dissected and tissue samples were taken for Ti level determination and biochemical measurements of some oxidative stress indicators. Results - The two higher doses reduced the rate of body weight gain significantly. Sensory evoked potentials and tail nerve action potential were significantly slowed, but the change in the spectrum of spontaneous cortical activity was not significant. Correlation of moderate strength was found between certain evoked potential parameters and brain Ti level and oxidative stress data. Conclusion - Our results underlined the possible neurotoxicity of TiO2 NPs but also the need for further investigations.

Hypertension and nephrology

DECEMBER 20, 2016

[Deeper analysis of nebivolol effects]

KÉKES Ede

[Author presents the formation of nitric oxide as a largest vasodilator of human endothelium as well as the endothelial dysfunction a result of formation at adrenergic stimulus. He demonstrates in detail the benefits of selective β-1 blocker and β-3 adrenergic agonist nebivolol in the vascular system. This drug has also receptor independent effects. Complex effects of nebivolol causes vasodilation, inhibits oxidative stress and it is capable to neutralize the effects of free oxygen radicals and as a result the endothelial function will be better. Its clinical effects and the less wellknown beneficial properties are listed. The use of drug is discussed especially in hypertensives with smoking, COPD or PAD. The β-3 agonist effect provides positive reactions not only in the adipocytes and the myocardial tissue. but in the skeletal muscle as well: Increase in energy expenditure - as a compensatory mechanism - is increased in obesity and the glucose uptake + storage on skeletal muscle cells are increased in hyperglycemia. The insulin sensitivity will be better, leptin level is decreased, adiponectin level is increased by nebivolol. It is assumed this drug has antidiabetic and anti-obesity effects.]

Clinical Neuroscience

NOVEMBER 30, 2006

[THE MODULATORY EFFECT OF ESTROGEN ON THE CAUDAL TRIGEMINAL NUCLEUS OF THE RAT IN AN ANIMAL MODEL OF MIGRAINE]

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]

KELEMEN Judit, BLASKÓ György

[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

[PLASTICITY OF NOCICEPTION: RECENT ADVANCES IN FUNCTION-ORIENTED STRUCTURAL PAIN RESEARCH]

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

[THE VALUE OF EXHALED NITRIC OXIDE IN ASTHMA BRONCHIALE - DIFFERENTIAL DIAGNOSIS AND MANAGEMENT]

HORVÁTH Ildikó

[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.]

Hypertension and nephrology

NOVEMBER 20, 2010

[Focus on central arterial pressure. Beta blockers - one group of agents with different efficacy]

BARNA István

[Not only have beta blockers excellent antihypertensive effect but both in monotherapy and in combination they exert antiarrhythmic and antiischemic efficacy, as well. They are recommended on A level of evidence in the treatment of patients with primary hypertension. Certain beta blockers differ from each other considering their lipid solubility, membrane stabilizing effect and in many other characteristics which difference can be exploited in the treatment. Nebivolol increases the release of nitrogen oxide, it is metabolically neutral and has vasodilating and antioxidant effect. The consequence of the stiffness of the arterial wall is the rise of systolic blood pressure, the diminshed diastolic circulation in the coronary vessels, the increase of the central pulse pressure and the frequent occurrence of cardiovascular diseases. Various antihypertensive agents have different mode of action on central blood pressure and arterial stiffness. Comparing nebivolol/atenolol and nebivolol/bisoprolol, respectively, nebivolol decreased aortic pulse pressure with greater efficacy than other beta blockers. The extent of the reduction of blood pressure was the same in the nebivolol and atenolol group while the augmentation index decreased significantly among the patients receiving nebivolol. In addition to the well known beneficial effects of nebivolol recent studies proved another, yet still unknown and unique characteristic of this agent, i.e. favourable influence on arterial stiffness. It not only improves endothelial dysfunction which has emphasized role on development of atherosclerosis but - independently of its antihypertensive effect - it has favourable action on arterial stiffness, too. These features guarantee a decisive position in the treatment of arterial hypertension.]