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Hungarian Immunology

MARCH 20, 2006

[The role of nerve growth (NGF) factor in the immune and inflammatory events and in autoimmune thyroid diseases]


[Nerve growth factor (NGF) is a neurotroph cytokine, and beside its effect on the central and peripheral nervous systems NGF plays an important role in the inflammatory and autoimmune processes. There are two types of NGF receptors, the high-affinity (TrkA) and the low-affinity (p75), which activations via signal transduction could lead to the inhibition or induction of apoptosis. Suppression of apoptosis could be induced by cytokines, hormones, antioxidans and increased intracellular Ca2+-levels. In the pathogenesis of many autoimmune diseases (systemic lupus erythematosus, 1-type diabetes mellitus, multiple sclerosis) could detect elevated serum levels of NGF associated with the disease activity. Our study demonstrated increased levels of NGF in autoimmune thyroid diseases (Graves’ disease, Hashimoto’s thyroiditis) in comparison with the controls. Decreased serum levels of NGF were found in Graves’ ophthalmopathy suggesting the role of apoptosis in the development of the eye symptoms. Orbital tissues are characterized with the high expression of TrkA receptors. NGF plays an important role in the pathomechanisms of neuro-immuno-hormonal diseases and its knowledge may be helpful in the diagnosis and therapy.]

Lege Artis Medicinae

JULY 14, 2007



[The beneficial effects of angiotensin-converting enzyme inhibitors on biochemical and vascular markers have been proven by many experimental studies. Reduction of the angiotensin-II level has a positive effect on oxidative stress, lipid peroxidation, apoptosis, inflammatory and prothrombotic processes. Two large multicentric trials, EUROPA and HOPE, showed that perindopril and ramipril significantly reduce mortality and the risk of both fatal and non-fatal cardiovascular events in patients with atherosclerosis, thereby making them the base drugs of secondary prevention of coronary artery disease.]


JUNE 20, 2005

[Mechanotransduction, or the impact of physical activity on bone architecture]


[It has long been known that, along with bone mineral content, bone strength is also fundamentally determined by its architecture.This architecture is shaped primarily by the forces that act on the bone, i.e., gravity and muscle traction conveyed by the tendons.Thus the bone acts as a kind of a mechanostat. The authors provide an overview of the literature on the systems that regulate mechanotransduction turning mechanical strain into bone texture. Regularly performed movements that provide a frequently changing axial load induce an extracellular fluid flow in the lacunar system of the bones.This flow induces prostaglandin synthesis in the osteocytes, which in turn inhibits the Receptor Activator of Nuclear factor κB (RANK) - RANK-Ligand (RANKL) mechanism through the secretion of osteoprotegerin by osteoblasts.This leads to osteoclast inhibition. Furthermore, leptin secretion by osteoblasts increases, which enhances osteoblast activation and inhibits the apoptosis of osteocytes and osteoblasts by both an autocrine and paracrine route. All these together act in the direction of bone formation. Based on the available evidence, the authors conclude that regular exercise results in an increased bone mass, better muscle strength and firmer balance, which leads to a decreased fracture risk.Thus, physical activity, through its beneficial effects on cardiac and bone health described above, contribute to the improvement of the quality of life.]

Hungarian Immunology

MARCH 20, 2006

[Familial autoinflammatory syndromes]

ORBÁN Ilonka, BALOGH Zsolt

[A group of rare inherited disorders, the familial autoinflammatory syndromes are characterised by attacks of seemingly unprovoked inflammation without significantly elevated autoantibody and autoreactive T cell levels. The rare diseases are present from infancy to lifelong, with periodic fever attacks and usually are accompanied by recurrent systemic inflammatory symptoms such as abdominal pain, diarrhoea, rash, arthralgia, polyarthritis, polyserositis, ocular disorders are separated by symptom-free intervals. Referred to as hereditary periodic fever syndromes appear by spontaneous crisis attacks and reveal a severe acute-phase response during the fever. In their pathogenesis there are no evidence neither of infection nor the common characteristics for autoimmune diseases: the production of high-titer auto-antibodies and antigenspecific T cell activation. The basic disease mechanism consists of the recently identified mutations in genes enconding important proteins: pyrin, cryopyrin, tumour necrosis factor (TNF) receptor and other mediators of apoptosis, inflammation and morbid citokine processing. The differential diagnosis of the diseases is not easy, their treatment is not resolved, although in same cases the biological treatment may be efficacious.]


FEBRUARY 14, 2007

[The increase of fracture risk in type 1 and type 2 diabetes mellitus]


[Studies in the last couple of years found more and more convincing evidence about the fact that impaired glucose metabolism leads to structural changes in the skeletal system leading toward osteoporosis. While patients with type 1 diabetes mellitus have decreased bone density, measurement showed increased bone mineral density in patients with type 2 diabetes mellitus. Despite these differences, risk of vertebral and nonvertebral fractures is increased in both groups of diabetic patients. Decreased pancreatic beta cell function is accompanied by several hormonal disturbances leading to decreased bone formation even in the early stage of diabetes. Peak bone mass of diabetic children is lower than found in nondiabetic children. Late complications of diabetes, vascular and neuronal impairments, impaired renal function, and secondary hormonal disturbances are added to this process. IGF-1 may have a crucial role in the pathogenesis of osteoporosis in diabetes. The structure of the molecule is similar to insulin. IGF-1 has effect on normal bone formation, inhibits the apoptosis and interferes with several other metabolic pathways. IGF-1 mediates the effect of growth hormone to the muscular and skeletal system. IGF-1 level decreases with age, and lower level of IGF-1 is found in diabetic patients. Long term complications of diabetes can also occur, which may enhance the process of bone resorption. Although the evidence is growing that fracture risk is higher in diabetic patiens, there are still scientists who question the association between the two disorders.]


SEPTEMBER 20, 2005

[The role of calcium in the chemoprevention of colorectal cancer]


[One of the most exciting research areas of the past decade has concerned the chemoprevention of colorectal cancer (CRC). Numerous clinical studies have been conducted on the preventive role of NSAIDs, high fibre intake, selenium, phytooestrogens, hormone replacement therapy, antioxidants, COX-inhibitors, folic acid and calcium, however, their results are controversial. Among the suggested chemopreventive agents, the preventive role of calcium is supported by the strongest evidence.This paper aims to review the available facts on the role of calcium. Recent studies suggest that appropriate calcium intake may partially counterbalance the effect of the genes that contribute to the development of CRC. Experimental data show that calcium directly influences the expression of several genes involved in tumorigenesis and that it is also involved in a number of signalling pathways that control cell proliferation, differentiation and apoptosis.These effects mostly arise through the activation of the calcium sensing receptor. The main goal of this review is to draw attention to the established chemopreventive role of calcium in CRC. Published data suggest that a lifelong daily calcium intake between 1200 to 1500 mg (even 2000 mg in high risk groups) would significantly decrease the incidence of CRC by inhibition of tumorigenesis.]

Lege Artis Medicinae

NOVEMBER 30, 2004


MŰZES Györgyi

[The cyclooxygenase (COX) metabolic pathway and prostaglandin production appear to play a causal role in the promotion and progression of human cancers. Recently COX-2 has received a great deal of interest since it is frequently overexpressed in a wide spectrum of cancers and precancerous lesions. Furthermore, elevated production of prostanoids (particularly PGE2) via COX-2 is associated with several pro-carcinogenic effects including increased proliferation, apoptosis resistance, tumor neoangiogenesis and invasiveness, host immunosuppression, and altered xenobiotic metabolism. Inhibitors of COX-1 and COX-2 (aspirin and most other nonsteroidal anti-inflammatory drugs) and of COX-2 alone (e.g. coxibs) have shown cancer preventive efficacy in epidemiological studies, experimental studies and in human clinical trials. Due to their improved side effect profile, COX-2 selective inhibitors appear to hold substantial promise for long-term administration in the setting of cancer prevention. Emerging data suggest that these agents may have potential in cancer treatment as well. In addition recent results indicate that COX-2 enzyme is also overexpressed in inflammatory processes of the central nervous system, e.g. in Alzheimer’s disease, so its suppression could offer a possible new therapeutic strategy even in the prevention and treatment of Alzheimer’s disease.]

Lege Artis Medicinae

MAY 16, 2007


JENEY András

[This communication intends to give an overview of the cell biological changes that maintain the underlying pathobiological events (invasive growth, metastasis formation, angiogenesis) of tumour progression. The multiple and continuously accumulating mutations of the cells affected by the etiological factors are collectively termed the malignant genotype of the tumour cells, which varies greatly on one hand, but, on the other hand, they are invariably related to an increased survival potential or invasive growth. Properties of the tumour cells produced by the malignant genotype, including immortalization, reduced apoptosis, uncontrolled proliferation, adaptation to hypoxia, resistance, metastatic potency and production of biopolymers harmful to the body are collectively termed the malignant phenotype. The malignant phenotype shows a remarkable variance among the tumours, also, certain forms are present in all stages, while others only appear in specific stages of tumour progression. Consequently, beside clinico-pathological examinations, the identification of the underlying malignant phenotype in each tumour allows a better prediction of tumour progression and a targeted planning of therapy.]

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.]

Clinical Neuroscience

JANUARY 20, 2005

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


[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.]