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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.]

Lege Artis Medicinae

JULY 20, 2004

[ENDOTHELIUM PROTECTION IN HYPERTENSIVE PATIENTS]

KÉKES Ede

[The author presents a review about the fundamental principles of normal endothelial function and the main causes for the development of endothelial dysfunction. First of all, endothelial dysfunction results in structural alterations in the wall of the vessel - the „vascular remodelling” in hypertension - and that is the base of hypertensive microangiopathy and target organ damage. In patients with high blood pressure the reactivity of vessels is impaired by the endothelial dysfunction. The members of the main drug groups can influence the vasoactive factors produced in endothelium differently. This different effects of drugs create different clinical benefits. Especially, the ACE inhibitors, the calcium antagonists (mostly the new generation of dihydropyridines) have endothelial protective effects, but some β-blockers, α-1 adrenergic blockers and - in a totally different way of action - the statins are capable of influencing the endothelial dysfunction.]

Lege Artis Medicinae

JULY 14, 2007

[CONTROVERSIAL EFFECTS OF NITRIC OXIDE: INTEGRITY AND TOXICITY]

KISS Róbert Gábor, BÉRES Bernát János

[Nitric oxide is a key molecule of the human body. Since its discovery, a library of books and papers have been published on its physiological and pathophysiological role. It is involved in almost all pathological processes. In healthy individuals nitric oxide plays a crucial role in the vascular regulation by protecting against atherosclerosis, myocardial infarction and stroke. In the central nervous system, nitric oxide in its function as a neurotransmitter is responsible for synaptic plasticity, long-term potentiation, memory and a number of neuroendocrine control mechanisms. Furthermore, during inflammation and host defense, macrophages and neutrophils produce nitric oxide that has antibacterial, antiviral, and tumour cell killing activity. In pathologic conditions, however, nitric oxide reacts with superoxide anion to form peroxynitrite that damages the enzymes of the mitochondrial respiratory chain, superoxide-dismutase, reduced glutathion and activates or inactivates signalling molecules. During ischaemia- reperfusion, nitric oxide and peroxynitrite contribute to nitrative/nitrosative stress, DNAfragmentation and consequent polyADP-ribosepolymerase- 1 enzyme activation both in coronary thrombosis and ischaemic stroke.]

Lege Artis Medicinae

JUNE 22, 2004

[NEW METHODS FOR NON-INVASIVE ASSESSMENT OF AIRWAY DISEASES]

HORVÁTH Ildikó

[In chronic obstructive airway diseases there are several unsolved questions regarding the early diagnosis, monitoring treatment, simple detection of exacerbations and the questions of differential diagnosis. These problems indicate the need for the development of new diagnostic methods and their application in clinical practice. This need is further emphasized by the fact that in most chronic airway diseases, including asthma and chronic obstructive pulmonary disease inflammation has a central role in the pathomechanism and its suppression is the main aim of treatment, but so far, we do not have adequate method for the assessment of inflammation intensity in clinical practice. In recent decades non-invasive sampling techniques directly from the airways have made a progress in respiratory research and at present some of them are available for clinical use. Among these techniques sputum induction, measurement of exhaled biomarkers including exhaled nitric oxide and mediators in exhaled breath condensate samples are used increasingly. The present review summarises our current knowledge on these methods and the most important findings obtained by their applications.]

Hungarian Immunology

JANUARY 22, 2008

[Kinetic measurement on flow cytometer simultaneous monitoring of intracellular progresses]

MÉSZÁROS Gergő, RÓNAI Katalin Zsuzsanna, TOLDI Gergely, KAPOSI Ambrus, VÁSÁRHELYI Barna, TRESZL András

[INTRODUCTION - Flow cytometry provides an opportunity for real-time monitoring of intracellular processes in several cell populations simultaneously. Cells stained with specific fluorescent dyes are sequentially measured during kinetic FACS measurements. Fluorescent light signals obtained in cells are recorded and analyzed to describe the alteration of the investigated parameter(s) over time. The use of kinetic FACS assays is not spread as there was no mathematic algorithm to characterize objectively the distribution of data and kinetic changes. MATERIALS, METHODS, RESULTS - We developed a new approach which fits functions to measured data sets, describes the statistical distribution and forms a basis for statistical comparison between individual kinetic measurements. We created two FACS assays on BD FACS Aria instrument. The first one monitors calcium flux, generation of reactive oxygen species and mitochondrial membrane potential, while the second one monitors mitochondrial calcium flux, nitric oxide generation and plasma membrane potential in CD4+ and CD8+ lymphocytes simultaneously before and after the administration of a lymphocyte activator. CONCLUSIONS - This technique may be used to investigate purposes (i.e. to test the impact of any agent (such as immunmodulatory drugs) on cellular processes in lymphocytes) and to diagnostic purposes (i.e. to test the alteration of lymphocyte activation characteristics in disease).]

Lege Artis Medicinae

JUNE 21, 2006

[ENDOTHELIAL DYSFUNCTION IN DYSLIPIDAEMIA - THE ROLE OF THE RENIN-ANGIOTENSIN SYSTEM]

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.]