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Lege Artis Medicinae

DECEMBER 15, 2015

[Rare genetic disease of copper metabolism]

SZILI Károly, VANYA Melinda, MÁGORI Krisztina, LAJOS György

[INTRODUCTION - Wilson’s disease is a rare genetic disease of copper metabolism. Nearly, 300 patients in Hungary suffering from Wilson’s disease CASE - 25-year-old male patients were examined because of because speech impairment and ocular symptoms. The increase in blood copper and ceruloplasmin and point mutations in the ATP7B proven confirmed the diagnosis of Wilson’s disease. DISCUSSION - In diagnosis of rare disease is not easy because of the variety of symptoms and the high costs of genetic testing, we would like to draw the attention to it.]

Clinical Neuroscience

NOVEMBER 30, 2013

[Assessment of the role of multidrug resistance-associated proteins in MPTP neurotoxicity in mice]

PLANGÁR Imola, ZÁDORI Dénes, SZALÁRDY Levente, VÉCSEI László, KLIVÉNYI Péter

[Goals - The available scientific data indicate that the pathomechanism of Parkinson's disease (PD) involves the accumulation of endogenous and exogenous toxic substances. The disruption of the proper functioning of certain transporters in the blood-brain barrier and in the blood-cerebrospinal fluid barrier in PD would accompany to that accumulation. Although there is an emerging role of the dysfunction of multidrug resistance-associated proteins (MRPs), members of ATP-binding cassette (ABC) transporter superfamily, in neurodegenerative disorders, there is only a few available data as regards PD. So the aim of our study was the assessment of the role of certain MRPs (1,2,4 and 5) in neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods - Following the intraperitoneal administration of silymarin (with MRP1, 2, 4 and 5 inhibitory effects), naringenin (with MRP1, 2 and 4 stimulatory effects), sulfinpyrazone (with MRP1, 4 and 5 inhibitory and MRP2 stimulatory effects) and allopurinol (with MRP4 stimulatory effect) in doses of 100 mg/kg, 100 mg/kg, 100 mg/kg and 60 mg/kg, respectively, for one week before and after the administration of MPTP in C57B/6 mice in acute dosing regimen, the striatal concentrations of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid has been measured using high-performance liquid chromatography. Results - Although the results of these experiments showed that neither of these substances exerted significant influence on MPTP-induced striatal depletion of dopamine and its metabolites, naringenin exerted a slight prevention of dopamine decrease, while allopurinol considerably enhanced the MPTP-induced lethality in mice. The explanation of these findings would be that the stimulation of MRP1- and MRP2-mediated transport of glutathione conjugates of toxic substances may have slight beneficial effects, while stimulation of MRP4-mediated efflux of brain urate, which has an important antioxidant potency, may worsen the effects of oxidative stress.]

LAM Extra for General Practicioners

MARCH 20, 2013

[EXPERIENCE WITH COENZYME Q10 IN HEART FAILURE]

KOHUT László

[INTRODUCTION - The protein complex coenzyme Q10 (CoQ10) has a role in ATP production as a mitochondrial electron transport molecule, and it also has a strong antioxidant effect. Several studies have proved the correlation between the decrease in CoQ10 level and the severity of heart failure. Heart failure is a multifactorial syndrome, the development of which is greatly influenced by an abnormal energy metabolism. CASE REPORT - The 61-year-old woman developed heart failure after a myocardial infarction. She complained of fatigue, dyspnoea and reduced physical endurance even with optimal treatment. When her therapy was completed by CoQ10, her endurance and life quality significantly improved and her symptoms ameliorated. CONCLUSIONS - Medical treatment of chronic heart failure is an evidence-based, complex therapy. Despite the complex management, morbidity and mortality of this condition remain high. A number of studies have shown that CoQ10 substitution can improve the clinical and haemodynamical parameters of patients with heart failure. On the basis of these results, the use of CoQ10 as an adjuvant therapy to complex treatment has an increasing role.]

Lege Artis Medicinae

SEPTEMBER 20, 2011

[Experience with coenzyme Q10 in heart failure]

KOHUT László

[INTRODUCTION - The protein complex coenzyme Q10 (CoQ10) has a role in ATP production as a mitochondrial electron transport molecule, and it also has a strong antioxidant effect. Several studies have proved the correlation between the decrease in CoQ10 level and the severity of heart failure. Heart failure is a multifactorial syndrome, the development of which is greatly influenced by an abnormal energy metabolism. CASE REPORT - The 61-year-old woman developed heart failure after a myocardial infarction. She complained of fatigue, dyspnoea and reduced physical endurance even with optimal treatment. When her therapy was completed by CoQ10, her endurance and life quality significantly improved and her symptoms ameliorated. CONCLUSIONS - Medical treatment of chronic heart failure is an evidence-based, complex therapy. Despite the complex management, morbidity and mortality of this condition remain high. A number of studies have shown that CoQ10 substitution can improve the clinical and haemodynamical parameters of patients with heart failure. On the basis of these results, the use of CoQ10 as an adjuvant therapy to complex treatment has an increasing role.]

Lege Artis Medicinae

FEBRUARY 22, 2007

[CARDIOVASCULAR EFFECTS OF SULFONYLUREAS]

NIESZNER Éva, BARANYI Éva, PRÉDA István

[Sulfonylureas, used as base therapy in type 2 diabetes, specifically block ATP-dependent potassium channels (K+ ATP). While in pancreatic beta cells these channels have an essential role in insulin release, they are also involved in cardiovascular adaptive mechanisms. Ion channels with similar morphology may have different pathophysiological effects in the human body. This raises the question, is it necessary to count with some damage to the cardiovascular protective mechanism when using sulfonylurea to induce insulin secretion. Is this indeed a relevant clinical problem today? The answer may lay in the different organ-specific effects of sulfonylureas.]

Lege Artis Medicinae

NOVEMBER 21, 2004

[LIPID-LOWERING THERAPY BASED ON RISK ASSESSMENT]

PARAGH György, BALOGH Zoltán

[The authors’ brief review follows the changes made to therapeutic guidelines based on primary and secondary prevention trials. They describe the main characteristics of National Cholesterol Education Program Adult Treatment Panel-I (NCEP ATP-I), ATP-II and ATP-III, and the decisions of the Hungarian Consensus Conference with respect to the lowering of lipids. The authors highlight the clinical importance of the evaluation of cardiovascular risk factors before the commencement of lipid-lowering therapy. They emphasize the significance of achieving the target values for low-density lipoprotein. Current dyslipidemia treatment guidelines focus on determining coronary heart disease risk status and matching the intensity of plasma LDL-C reduction to that perceived risk. Adding plasma C-reactive protein measurement to current risk assessment techniques may improve the identification of patients in the primary prevention population who may require more aggressive lipid-lowering therapy.]

Lege Artis Medicinae

JANUARY 21, 2004

[THE METABOLIC SYNDROME CLINICAL APPEARANCE, DIAGNOSIS, PATHOMECHANISM]

KÉKES Ede, CZURIGA István

[The metabolic syndrome has gone by several names over the past two decades. The diagnostic criteria were proposed by the ATP III of NCEP in 2001 and were accepted by European Society of Cardiology and European Society of Hypertension in 2003. The criteria (abnormal waist rate, HDLcholesterol, triglyceride, blood pressure and fasting glucose) are listed and the presence of any three of these factors is considered sufficient for diagnosis. The prevalence of syndrome affects about a quarter of the Hungarian population with hypertension. The metabolic syndrome is associated with premature cardiovascular morbidity and mortality including an excess of sudden deaths. According to the recent literature data the main component of the syndrome, the obesity, especially with abdominal fat distribution is associated with hypertension, hyperinsulinemia and insulin resistance with related abnormalities of carbohydrate and lipid metabolism. The low HDL cholesterol, high triglyceride level and the small, dense LDL cholesterol particles are the parts of lipid component of syndrome. A variety of environmental (obesity, smoking, physical inactivity) and genetic factors (genetic mutations of lipoprotein lipase, hepatic lipase, CETP and PPA receptors) and the impaired FFA metabolism have all been related to lipid abnormalities. Sympathetic hyperfunction participates in the pathogenesis and complications of metabolic syndrome. Possible factors augmenting sympathetic activation include alterations of insulin, leptin, FFA, cytokines, sleep apnoe. Other important factors as the endocrin concept, the hypothalamus-hypophysis- adrenal axis, endothelial dysfunction are discussed. The impaired muscle insulin stimulated glycogen synthesis (FFA induced GLUT-4 inhibition) is the major cellular factor of insulin resistance. There is a continuous process from the insulin resistance state (with hyperinsulinemia) into the 2T diabetes mellitus (with hypoinsulinemia).]

Clinical Neuroscience

JANUARY 30, 2010

[Molecular genetic mutation analysis in Menkes-disease with prenatal diagnosis]

LÁSZLÓ Aranka, ENDREFFY Emőke, TÜMER Zeynep, HORN Nina, SZABÓ János

[Menkes disease (MD) is an X-linked recessive multisystemic lethal, heredodegenerative disorder. Progressive neurodegeneration and connective tissue disturbances with microscopically kinky hair are the main symptoms. Molecular genetic mutation analysis was made at a Hungarian male infant suffering from MD and prenatal diagnosis was done in this MD loaded family. Method - The 12th exon of ATP7A gene has been analyzed by dideoxy-finger printing (DDF), polymerase chain reaction (PCR), direct sequencing of exon 12. The specific mutation was screened from chorionic villi of the maternal aunt at the 14th gestational week. Results - In the exon 12th a basic pair substitution with Arg 844 His change was detected leading to very severe fatal missense mutation.]

Clinical Neuroscience

JUNE 20, 2003

[Asymptomatic ischemic cerebrovascular disorders and neuroprotection with vinpocetine]

HADJIEV Dimiter

[The asymptomatic ischemic cerebrovascular disorders (AICVD) is an early manifestation of cerebrovascular disease. It is also known as latent insufficiency of the cerebrovascular circulation or as asymptomatic cerebrovascular disorders. Recently, the term subclinical disease, detected noninvasively, has been introduced by American Heart Association. The diagnosis is based on the following criteria: evidence of vascular risk factors; episodic nonspecific complaints without any focal cerebral symptoms; mild cognitive deficit, detected by neuropsychological tests; carotid ultrasonography often shows intimal-medial thickening, atherosclerotic plaques and carotid stenosis; CT and MRI occasionally reveal silent cerebral infarctions, white matter hyperintensities or cerebral atrophy; regional hypoperfusion above the ischemic threshold is also seen by rCBF measurements. Treatment of the AICVD, modifying the vascular risk factors and using neuroprotective agents, should be the cornerstone of primary prevention of ischemic stroke and cognitive decline, caused by cerebrovascular disorders. Vinpocetine has been found to interfere with various stages of the ischemic cascade: ATP depletion, activation of voltagesensitive Na+- and Ca++-channels, glutamate and free radicals release. The inhibition of the voltage-sensitive Na+- channels appears to be especially relevant to the neuroprotective effect of vinpocetine. Pronounced antioxidant activity of the drug could also contribute to the neuroprotection. PET studies in primates and man showed that 11C labelled vinpocetine passes the blood-brain barrier rapidly. Heterogeneous brain distribution of the compound was observed mainly in the thalamus, basal ganglia, occipital, parietal and temporal cortex, regions which are closely related to the cognitive functions. PET studies in chronic ischemic stroke patients revealed favourable effects of vinpocetine on rCBF and glucose metabolism in the thalamus, basal ganglia and primary visual cortex. It seems, vinpocetine, affecting the multiple mechanisms of the AICVD, could be of benefit for the treatment in this early stage of cerebrovascular disease. Vinpocetine may also become a new therapeutic approach to prophylactic neuroprotection in patients at high risk of ischemic stroke.]

Clinical Neuroscience

APRIL 20, 2002

[Regulatory mechanisms in focal cerebral ischemia. Perspectives in neuroprotective treatment]

NAGY Zoltán, SIMON László, BORI Zoltán

[Permanent or temporary disruption of cerebral blood flow rapidly depletes brain regions of their limited energy reserves (glycogen, glucose, oxygen, ATP) leading to an energy crisis. Tissue damage occurs due to the energy crisis. The central part of the damage, the ischaemic “core” region is surrounded by zones of the shell-like penumbra. Necrotic, as well as apoptotic cell death could be identified in the penumbra. Going away from the ischaemic core different neurochemical processes are occuring by space and time.“Immediate early response” genes (c-fos, fos-B, c-Jun, krox 20, 24) are activated, heatshock proteins (hsp 70, 72, HSF, HSE, HIF), cytokines (TNF-α, IL-1β), inflammatory factors (COX), adhesion and glial factors (ICAM-1, ELAM-1, P-selectin), vasoactive factors (IL -6, -10, PAF), reactive oxigen radicals and connected factors (O2, OH, NO, NOS, SOD) are produced within minutes and hours. Cell deaths, necrosis and apoptosis due to the activation of calpains, caspases and nucleases occur in days. In parallel, growth factors and plasticity proteins (BDNF, NGF, TGF-β, VEGF, PDGF, GAP-43) are activated as a basis of functional rehabilitation.]