Institute of Pathophysiology

Sankt Radegund bei Graz, Austria

Institute of Pathophysiology

Sankt Radegund bei Graz, Austria
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Kobal J.,University of Ljubljana | Melik Z.,Institute of Physiology | Cankar K.,Institute of Physiology | Bajrovic F.F.,University of Ljubljana | And 4 more authors.
Acta Neurologica Scandinavica | Year: 2010

Objectives-Although autonomic dysfunction was found in advanced Huntington's disease (HD) patients it is not clear whether there is autonomic dysfunction in presymptomatic and early symptomatic HD. Material & methods-Different cardiovascular autonomic tests were performed in 14 presymptomatic HD mutation carriers (PHD), 11 early symptomatic HD patients (EHD) and in 25 sex and age matched controls. Results-We found attenuated response to simple mental arithmetic test (relative heart rate in PHD and EHD was 10% lower than in controls; diastolic pressure was 10.6% lower in EHD than in controls; P < 0.05) and exaggerated response to the late phase of cold pressor test (relative heart rate was 10% higher in PHD and 7% higher in EHD than in controls; P < 0.05). The rest of the cardiovascular autonomic tests did not reveal significant differences between patients and controls. Conclusions-Our results suggest that subtle autonomic dysfunction occurs even in PHD and EHD. © 2009 Blackwell Munksgaard.

Bartolic A.,Institute of Pathophysiology | Pirtosek Z.,University of Ljubljana | Rozman J.,ITIS d.o.o. Ljubljana | Ribaric S.,Institute of Pathophysiology
Medical Hypotheses | Year: 2010

Rest tremor is one of the four main clinical features of Parkinson's disease (PD), besides rigidity, bradykinesia and postural instability. While rigidity, bradykinesia and postural instability can be explained with changes in neurotransmitter concentrations and neuronal activity in basal ganglia, the pathogenesis of parkinsonian tremor is not fully understood. According to the leading hypothesis tremor is generated by neurons or groups of neurons in the basal ganglia which act as central oscillators and generate repetitive impulses to the muscles of the body parts involved. The exact morphological substrate for central oscillators and the mechanisms leading to their activation are still an object of debate. Peripheral neural structures exert modulatory influence on tremor amplitude, but not on tremor frequency. We hypothesise that rest tremor in PD is the result of two mechanisms: increased activity and increased synchronisation of central oscillators. We tested our hypothesis by demonstrating that the reduction in rest tremor amplitude is accompanied by increased variability of tremor frequency. The reduction of tremor amplitude is attributed to decreased activity and poor synchronisation of central oscillators in basal ganglia; the increased variability of tremor frequency is attributed to poor synchronisation of the central oscillators. In addition, we demonstrated that the recurrence of clinically visible rest tremor is accompanied by a reduction in tremor frequency variability. This reduction is attributed to increased synchronisation of central oscillators in basal ganglia. We argue that both mechanisms, increased activity of central oscillators and increased synchronisation of central oscillators, are equally important and we predict that tremor becomes clinically evident only when both mechanisms are active at the same time. In circumstances when one of the mechanisms is suppressed tremor amplitude becomes markedly reduced. On the one hand, if the number of active central oscillators is very low, the muscle-stimulating impulses are too weak to cause clinically evident tremor. On the other hand, if central oscillator synchronisation is poor, the impulses originating from different central oscillators are not in phase and thus cancel out, again leading to reduced stimulation of muscles and reduced tremor amplitude. Our hypothesis is supported by our measurements on patients with PD and by experimental data cited in the literature. The proposed two mechanisms could have clinical implications. New medical treatments, which would specifically target only one of the proposed mechanisms (oscillator activity or synchronisation), could be effective in reducing tremor amplitude and thus supplement established antiparkinsonian treatments. © 2009 Elsevier Ltd. All rights reserved.

Brvar M.,University of Ljubljana | Luzar B.,University of Ljubljana | Finderle Z.,Institute of Physiology | Suput D.,Institute of Pathophysiology | And 2 more authors.
Inhalation Toxicology | Year: 2010

Introduction: The progressive clinical course with delayed neurological damage in carbon monoxide (CO) poisoning may be due to neuron apoptosis. The usefulness of hyperbaric oxygen (HBO) in different time periods after CO exposure in neuronal cell apoptosis reduction has not been evaluated thus far. The aim was to evaluate HBO efficacy in reducing neuronal apoptosis in different time periods after CO exposure. Methods:Wistar rats were exposed to 3000ppm CO in air for 60min and 100% oxygen at a pressure of three bar for 30min 012h after CO exposure. The apoptosis was evaluated by immunohistochemical analysis with antibodies against activated caspase-3 and the percentage of caspase-3 positive hippocampal ganglionic cells was reported. Results:It was shown that CO poisoning results in ganglionic cell apoptosis. The percentage of apoptotic cells in rats exposed to CO was the highest (32%), whereas the percentage of apoptotic cells in rats exposed to HBO 0 and 1h after CO was similar with a lower percentage than rats exposed to CO. The percentage of apoptotic cells in rats exposed to HBO 3 and 5h after CO was similar with a lower percentage than rats exposed to HBO 0 and 1h after CO. The percentage of apoptotic cells in rats exposed to HBO 712h after CO was similar with a higher percentage than rats exposed to HBO 5h after CO. Conclusion:HBO has a time-dependent protective effect on CO-induced neuron apoptosis with the highest efficiency at 3 and 5h after CO poisoning. © 2010 Informa Healthcare USA, Inc.

PubMed | Institute of Microbiology and Immunology, University of Ljubljana and Institute of Pathophysiology
Type: | Journal: BMC infectious diseases | Year: 2015

Tick borne encephalitis is the most frequent vector-transmitted infectious disease of the central nervous system in Europe and Asia. The disease caused by European subtype of tick borne encephalitis virus has typically a biphasic clinical course with the second phase presenting as meningitis, meningoencephalitis, or meningoencephalomyelitis. Cerebrospinal fluid pleocytosis is considered a condition sine qua non for the diagnosis of neurologic involvement in tick borne encephalitis, which in routine clinical practice is confirmed by demonstration of serum IgM and IgG antibodies to tick borne encephalitis virus.Here we present a patient from Slovenia, an area highly endemic for tick borne encephalitis, with encephalitis but without cerebrospinal fluid pleocytosis in whom tick borne encephalitis virus infection of the central nervous system was demonstrated.Cerebrospinal fluid pleocytosis is not mandatory in encephalitis caused by tick borne encephalitis virus. In daily clinical practice, in patients with neurologic symptoms/signs compatible with tick borne encephalitis and the risk of exposure to ticks in a tick borne encephalitis endemic region, the search for central nervous system infection with tick borne encephalitis virus is warranted despite the lack of cerebrospinal fluid pleocytosis.

PubMed | Institute of Biochemistry, Academy of Criminalistic and Police Studies, Serbian Institute of Physiology and Institute of Pathophysiology
Type: | Journal: Oxidative medicine and cellular longevity | Year: 2015

Exercise induces a multitude of physiological and biochemical changes in blood affecting its redox status. Tissue damage resulting from exercise induces activation of inflammatory cells followed by the increased activity of myeloperoxidase (MPO) in circulation. Vitamin C readily scavenges free radicals and may thereby prevent oxidative damage of important biological macromolecules. The aim of this study was to examine the effect of vitamin C supplementation on oxidative stress and neutrophil inflammatory response induced by acute and regular exercise. Experiment was conducted on acute exercise group (performing Bruce Treadmill Protocol (BTP)) and regular training group. Markers of lipid peroxidation, malondialdehyde (MDA), MPO activity, and vitamin C status were estimated at rest and after BTP (acute exercise group) and before and after vitamin C supplementation in both groups. Our results showed increased postexercise Asc in serum independently of vitamin supplementation. They also showed that vitamin C can significantly decrease postexercise MDA level in both experimental groups. Increased postexercise MPO activity has been found in both groups and was not affected by vitamin C supplementation. We concluded that vitamin C supplementation can suppress lipid peroxidation process during exercise but cannot affect neutrophil inflammatory response in either exercise group.

Schnedl W.J.,General Practice for General Internal Medicine | Krause R.,Medical University of Graz | Tafeit E.,Institute of Physiological Chemistry | Tillich M.,Diagnostikum Sued West | And 2 more authors.
Nature Reviews Gastroenterology and Hepatology | Year: 2011

Epiploic appendagitis is a rare cause of abdominal pain. Diagnosis of epiploic appendagitis, although infrequent, is easily made with CT or ultrasonography in experienced hands. As reported in the literature, most patients with primary epiploic appendagitis are treated conservatively without surgery, with or without anti-inflammatory drugs. A small number of patients are treated with antibiotics and some patients require surgical intervention to ensure therapeutic success. Symptoms of primary epiploic appendagitis usually resolve with or without treatment within a few days. A correct diagnosis of epiploic appendagitis with imaging procedures enables conservative and successful outpatient management of the condition and avoids unnecessary surgical intervention and associated additional health-care costs. Gastroenterologists and all medical personnel should be aware of this rare disease, which mimics many other intra-abdominal acute and subacute conditions, such as diverticulitis, cholecystitis and appendicitis. This article reviews epiploic appendagitis and includes discussion of clinical findings, pathophysiology, diagnosis and therapeutic possibilities. © 2011 Macmillan Publishers Limited. All rights reserved.

PubMed | Institute of Biochemistry, Institute of Pathophysiology and Institute of Pharmacology
Type: | Journal: Oxidative medicine and cellular longevity | Year: 2016

Chronic kidney disease (CKD) is a worldwide public health problem. Patients with CKD have a number of disorders in the organism, and the presence of oxidative stress and systemic inflammation in these patients is the subject of numerous studies. Chronic inflammation joined with oxidative stress contributes to the development of numerous complications: accelerated atherosclerosis process and cardiovascular disease, emergence of Type 2 diabetes mellitus, development of malnutrition, anaemia, hyperparathyroidism, and so forth, affecting the prognosis and quality of life of patients with CKD. In this review we presented the potential role of the myeloperoxidase enzyme in the production of reactive/chlorinating intermediates and their role in oxidative damage to biomolecules in the body of patients with chronic kidney disease and end-stage renal disease. In addition, we discussed the role of modified lipoprotein particles under the influence of prooxidant MPO intermediates in the development of endothelial changes and cardiovascular complications in renal failure.

Rituper B.,Institute of Pathophysiology | Gucek A.,Institute of Pathophysiology | Jorgacevski J.,Institute of Pathophysiology | Jorgacevski J.,Celica Biomedical Center | And 5 more authors.
Nature Protocols | Year: 2013

In order to understand exocytosis and endocytosis, it is necessary to study these processes directly. An elegant way to do this is by measuring plasma membrane capacitance (Cm), a parameter proportional to cell surface area, the fluctuations of which are due to fusion and fission of secretory and other vesicles. Here we describe protocols that enable high-resolution C m measurements in macroscopic and microscopic modes. Macroscopic mode, performed in whole-cell configuration, is used for measuring bulk C m changes in the entire membrane area, and it enables the introduction of exocytosis stimulators or inhibitors into the cytosol through the patch pipette. Microscopic mode, performed in cell-attached configuration, enables measurements of Cm with attofarad resolution and allows characterization of fusion pore properties. Although we usually apply these protocols to primary pituitary cells and astrocytes, they can be adapted and used for other cell types. After initial hardware setup and culture preparation, several Cm measurements can be performed daily. © 2013 Nature America, Inc. All rights reserved.

Rituper B.,Institute of Pathophysiology | Chowdhury H.H.,Institute of Pathophysiology | Chowdhury H.H.,Celica Biomedical Center | Jorgacevski J.,Institute of Pathophysiology | And 6 more authors.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2013

How cholesterol, a key membrane constituent, affects membrane surface area dynamics in secretory cells is unclear. Using methyl-β-cyclodextrin (MβCD) to deplete cholesterol, we imaged melanotrophs from male Wistar rats in real-time and monitored membrane capacitance (Cm), fluctuations of which reflect exocytosis and endocytosis. Treatment with MβCD reduced cellular cholesterol and caused a dose-dependent attenuation of the Ca 2+-evoked increase in Cm (IC50 = 5.3 mM) vs. untreated cells. Cytosol dialysis of MβCD enhanced the attenuation of Cm increase (IC50 = 3.3 mM), suggesting cholesterol depletion at intracellular membrane sites was involved in attenuating exocytosis. Acute extracellular application of MβCD resulted in an immediate Cm decline, which correlated well with the cellular surface area decrease, indicating the involvement of cholesterol in the regulation of membrane surface area dynamics. This decline in Cm was three-fold slower than MβCD-mediated fluorescent cholesterol decay, implying that exocytosis is the likely physiological means for plasma membrane cholesterol replenishment. MβCD had no effect on the specific Cm and the blockade of endocytosis by Dyngo 4a, confirmed by inhibition of dextran uptake, also had no effect on the time-course of MβCD-induced Cm decline. Thus acute exposure to MβCD evokes a Cm decline linked to the removal of membrane cholesterol, which cannot be compensated for by exocytosis. We propose that the primary contribution of cholesterol to surface area dynamics is via its role in regulated exocytosis. © 2013 Elsevier B.V.

Djindjic N.,University of Niš | Jovanovic J.,Institute of Occupational Health | Djindjic B.,Institute of Pathophysiology | Jovanovic M.,University of Niš | And 2 more authors.
Vojnosanitetski Pregled | Year: 2013

Background/Aim. Occupational stress is a term used to define ongoing stress that is related to the workplace. The study was conducted to determine association of occupational stress index (OSI) and its aspects with arterial hypertension and lipid disorders using data from a cross-sectional survey of male professional drivers. Methods. The cross-sectional study was performed in 439 professional drivers divided into groups (city- and intercity bus drivers, truck and taxi drivers). The OSI and OSI aspects (high demands, strictness, underload, extrinsic time pressure, noxious exposure, avoidance and conflict) were calculated using the standardized questionnaire. Determination of serum lipids, blood pressure (BP) and cardiovascular risk factors were done. Results. A significant difference in prevalence of diagnosed hypertension and dyslipidemia was found along with a difference in total OSI and OSI aspects among examined subgroups of drivers. A total OSI was highest in city, high in intercity bus drivers, and the lowest one in truck and taxi drivers (82.79 ± 3.5, 81.28 ± 3.7, 73.75 ± 3.5, 71.61 ± 4.4, respectively; p < 0.01). Similar pattern showed triglycerides (TG), total cholesterol (TC) and LDL cholesterol and BP, while HDL-cholesterol showed reverse order (p < 0.01). Logistic regression analyses with multiple OSI aspects adjusted for age and years of exposure showed associations of total OSI with arterial hypertension OR 5.5; 95% CI (2.24-7.95) and dyslipidemia OR 1.43 95% CI (1.09-2.80). Underload was the most important OSI aspect associated with the arterial hypertension OR 1.18; 95% CI (1.04-2.58) and elevated LDL cholesterol 1.26; 95 CI (1.19-2.1). A total OSI had a significant association with elevated LDL cholesterol 2.64; 95% CI (1.19- 7.7), triglycerides OR 3.27; 95% CI (1.20-5.1) and low HDL cholesterol OR 3.29; 95% CI (1.8-5.8) (p < 0.01). Conclusion. The study provides the evidence for the significant association of total OSI and underload with lipid disorders and elevated blood pressure in professional drivers, which could be a possible link between job stress and coronary heart disease. Regular periodical examinations and workplace interventions aimed to decrease total OSI and underload are important aspects in primary prevention and additional reduction of cardiovascular risk.

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