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Hypertension and nephrology

SEPTEMBER 20, 2014

[Visualization of glomerular filtration in animals in vivo - significant filtration in afferent arteriola. Regulation of endothelial permeability]

ROSIVALL László

[Recently we have in vivo visualized glomerular filtration and fluid flow from the JGA portion of afferent arteriole into JGA using intravital multiphoton microscopy. Fluorescence of the extracellular fluid marker lucifer yellow appeared in the interstitium around the distal portion of afferent arteriole before the filtration into Bowman's capsule. In isolated microperfused JGA we demonstrated fluid movement from the glomerulus into the MD tubule. All these prove that there is a significant and dynamic fluid flow exists in the JGA. Angiotensin II similar to VEGF plays a role in regulation of permeability/fenestration formation. Angiotensin II acts through AT1 receptor and PV-1 protein synthesis.]

Hypertension and nephrology

SEPTEMBER 21, 2012

[The apparatus which controls our kidney too. - Part 1]

ROSIVALL László

[The series gives a brief overview on the discovery of the juxtaglomerular apparatus (JGA), an interesting story, as well as on details of its structure and function down to the molecular level. The discovery of JGA, i.e., a phylogenetically ancient organ, is a fine example of the close morphological and functional correlations characteristic of living organisms. Presented are the JGA related misconcepts and the underlying theoretical and practical difficulties. Utilization of the most modern methods, such as atomic force microscopy, as well as the in vivo multiphoton laser microscopy revealed previously unrecognized phenomen highlighting the ambiguities of textbook information, accepted paradigms. The author is looking for relationship between the new and provocative theoretical research and clinical consequences of pharmacological interventions. He shows that JGA is not only a participant of the salt-water balance and blood pressure regulation, but it can also play a significant role in the pathogenesis of the major public diseases. Finally, he makes an attempt to analyze the current research directions that predict some potential scientific discoveries and describe some general lessons from his own research career.]

Clinical Neuroscience

JULY 30, 2012

[Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination]

ÁCS Péter, KOMOLY Sámuel

[Background and purpose - It has been reported that multiple sclerosis has four different neuropathological subtypes, and two of them (type III and IV) are characterized by primary oligodendrocyte loss. However, the exact pathomechanism that lead to oligodendrocyte apoptosis in human demyelinating diseases is still elusive. The copper chelator cuprizone induces primary oligodendrocyte apoptosis and consequent demyelination in well defined areas of the mouse brain. Nevertheless, the precise subcellular events that result in oligodendrocyte cell death in the cuprizone model are still unknown. We aimed to study the ultrastructural alterations that might induce oligodendrocyte apoptosis in the cuprizone experimental demyelination model. Methods - C57BL/6 mice were given cuprizone for two, 21 and 35 days to induce demyelination to investigate early pathological events, and different stages of demyelination. In addition, mice were given cuprizone for 35 days and were allowed to recover for two or 14 days to study early and late remyelination. After the cuprizone treatment, mice were sacrificed and the corpus callosum, the superior cerebellar peduncle, the optic nerve and the sciatic nerve were studied by electron microscopy. Results - The ultrastructural analysis revealed that cuprizone induced oligodendrocyte apoptosis is accompanied by the formation of giant mitochondria in the affected cells in the corpus callosum and in the superior cerebellar peduncle. Apoptosis of the myelin producing cells was present through the whole cuprizone challenge. Severe demyelination occurred after three weeks of cuprizone administration associated with massive macrophage infiltration and astrocytosis of the demyelinated areas. Axons and neurons remained unaffected. Conclusion - The formation of giant mitochondria in myelin producing oligodendrocytes is the first pathological sign in the cuprizone experimental demyelination. Mitochondrium pathology in the cuprizone challenge might serve as a useful model to study the pathomechanism of multiple sclerosis subtypes (III and IV) characterized by primary oligodendrocyte degeneration.]

Hypertension and nephrology

FEBRUARY 20, 2012

[Multi-photon fluorescence microscopy in the revealance of kidney physiology]

PRÓKAI Ágnes, BERTA Nóra, VANNAY Ádám, SZIKSZ Erna, KIS-PETIK Katalin, FEKETE Andrea, TOMA Ildikó, TULASSAY Tivadar, KELLERMAYER Miklós, PETI-PETERDI János, SZABÓ J. Attila

[In this review we discuss the importance of the multi-photon fluorescence microscopy in the relevance of kidney physiology. Most functions of the kidney, including the clearance of metabolic waste products, maintenance of body fluid, electrolyte homeostasis and blood pressure are achieved by complex interactions between multiple renal cell types and previously inaccessible structures that have been difficult to study. Multi-photon fluorescence microscopy offers an advanced imaging technique for deep optical sectioning of living tissues and organs with minimal deleterious effects. Dynamic regulatory processes and multiple functions in the intact kidney can be quantitatively visualized in real time with submicron resolution. This article reviews the application of multi-photon imaging technology that provided the most complex, spatial and temporal portrayal of renal function, depicting as well as analyzing the components and mechanisms involved in renal (patho)physiology such as glomerular structure and function, tubular transport, tubular-vesicular interaction and the intrarenal renin-angiotensin system.]

Lege Artis Medicinae

FEBRUARY 21, 2006

Lege Artis Medicinae

JANUARY 21, 2006

Clinical Neuroscience

JANUARY 20, 2005

[EXPERIMENTAL DEMYELINATION CAUSED BY PRIMARY OLIGODENDROCYTE DYSTROPHY Regional distribution of the lesions in the nervous system of mice brain]

KOMOLY Sámuel

[Background and purpose - Heterogeneity of multiple sclerosis lesions has been recently indicated: In addition to T-cell-mediated or T-cell plus antibody-mediated autoimmune mechanisms (patterns I-II) two other patterns (III-IV) were described. Patterns III-IV are characterized by primary oligodendrocyte dystrophy, reminiscent of virus- or toxin-induced demyelination rather than autoimmunity. It was described more than 30 years ago that dietary application of a copper-chelating agent called cuprizone results in primary oligodendrocyte degeneration which is followed by demyelination. The aim of the present study was to examine the regional distribution of cuprizone induced oligodendrocyte dystrophy and demyelination in the nervous system of mice. Material a methods - Demyelination was induced in male weanling Swis-Webster mice by feeding them on a diet containing 0.6% (W/W) cuprizone bis(cyclohexanone)-oxalyldihydrazone (G. F. Smith Chemical, Columbus OH) for 8 weeks. Animals were sacrificed after 3, 7, 14, 27, 35, 56 days of cuprizone administration. Samples were taken from corpus callosum, anterior commissure, optic nerve, cervical spinal cord and sciatic nerve. Samples were examined by immunohistochemistry, in situ hybridization for myelin proteins and myelin protein mRNA-s, respectively. Conventional neuropathological stainings and electron microscopy was also performed. Results - Oligodendrocyte degeneration and demyelination followed a particular standard pattern in the central nervous system. Profound myelin loss developed in the superior cerebellar peduncle, anterior comissure and corpus callosum, whereas the optic nerves, velum medullare anterior and spinal cord showed little or no demyelination. Sciatic nerves were unaffected. No infiltration by lymphocytes or blood-brain barrier damage was observed during cuprizone treatment. Conclusion - Cuprizone induced oligodendrocyte damage and demyelination follows a particular standard pattern in the central nervous system of mice. Cuprizone induced demyelination might be considered as a model for human demyelinating disorders with primary oligodendrocyte dystrophy and apoptosis.]

Hungarian Immunology

FEBRUARY 20, 2005

[Functional measurements of the hand’s circulation in Raynaud’s patients]

CSIKI Zoltán, GALUSKA László, GARAI Ildikó, SZABÓ Nóra, GALAJDA Zoltán, VARGA József, ZEHER Margit

[INTRODUCTION - In patients presenting with isolated tissue perfusion disturbance without large vessel involvement the examination of hand microcirculation is of major importance. In our study we present the results of three examination methods used for hand perfusion monitoring which measure the tissue microcirculation in different depths. PATIENTS AND METHODS - We examined 58 primary Raynaud's patients using capillary microscopy, laser doppler perfusion imaging and hand perfusion scintigraphy with Tc-99m-DTPA. From our patients 38 were smokers, 42 patients frequently suffered from headache. For the validation of our laser Doppler results we involved into the study also 16 non-smoker healthy volunteers. For the standardisation of the results the studies were performed in a climatised room. During the laser examination we performed and analysed also the post-occlusion hyperaemia test. RESULTS - In the majority of our patients no morphological alterations were found with capillary microscopy. In primary Raynaud’s patients the perfusion values measured with laser-Doppler scanner in basic condition were significantly lower both in fingers’ and palm’s regions compared to healthy controls. In the primary Raynaud’s group the smokers had significantly lower hyperaemic response than the non-smokers and we measured also significantly lower FPR (finger-to-palm ratio) values with hand perfusion scintigraphy. Both with laser doppler imaging and hand perfusion scintigraphy there was no difference between the values measured in patients with or without headache. CONCLUSIONS - We consider of benefit the functional examination of hand circulation in all diseases involving the hand microcirculation.]

Hungarian Immunology

MARCH 20, 2002

[Relevances of anti-CD44 immunotherapy for cellular biology]

GÁL István, GLANT T. Tibor, MIKECZ Katalin

[INTRODUCTION - The CD44 molecule - the physiologic hialuronic acid receptor - is one of key mediators that direct the traffic of leukocytes into inflamed tissues. When applied in animal models of autoimmune arthritis, parenteral anti-CD44 antibody treatment exerts a dramatic antiinflammatory effect, but at high doses also a leukopenic effect. The goal of the present work is to elucidate the cellular basis of these phenomena. METHODS - In this study the authors used Western blot, immunoprecipitation, cell adhesion studies, flow chamber system studies (leukocyte rolling) and fluorescence microscopy following fluorescent labeling of actin cytoskeleton. RESULTS - Adhesion of CD44-expressing leukocytes to immobilized hialuronic acid does not result marked changes in cellular morphology. When incubated on immobilized anti-CD44 antibody, however, these cells spread, reorganize the actin cytoskeleton, and they adhere strongly to the surface. Studying the mechanisms of signal transduction, the authors found that engagement of CD44 with anti- CD44 antibody results in its enhanced association with numerous cytoskeletal regulator proteins, including ezrin, ankyrin, spectrin and focal adhesion kinase, thereby increasing the interaction between the cytoskeleton and the plasma membrane. Strong adhesion of the cells to immobilized anti-CD44 also prevents the rolling movement of these cells, mediated by CD44-hialuronic acid interactions, which precedes the extravasation of leukocytes to sites of inflammation. CONCLUSION - These results may provide insight into the antiinflammatory mechanisms of anti- CD44 antibody treatment. Based on these results and results published by other investigators, anti- CD44 antibodies may be uselful in the immunotherapy of rheumatic diseases.]

Hungarian Immunology

OCTOBER 20, 2007

[Examination of leukocyte-endothel interactions in inflammatory animal models]

GONDA Andrea, MIKECZ Katalin, HUNYADI János

[Leukocyte influx into tissues is one of the hallmarks of physiological reactions to inflammatory stimuli, which is followed by a multistep process, resulting in leukocyte extravasation from the postcapillary venules. The different kinds of adhesion molecules, that play role in the rolling and firm adhesion of the leukocytes, have been investigated very intensively. By the help of animal models of inflammation, numerous individuals, being in the same stage of the disease, can be examined. The requirement for the adhesion molecules for inflammatory responses could be investigated with antibodies or, nowadays more often, gene knock out (KO) or transgenic mice. Beside evaluating the morphological and cytokine profile differences, using intravital microscopy is of great importance in the inflammatory experiments, while it allows observing interactions of virtually any blood cell types with the endothelial wall in vivo. The results are sometimes conflicting, indicating that the process of leukocyte-endothel interactions depends on different kind of other factors than the adhesion molecules, and still not fully understood.]