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Lege Artis Medicinae

OCTOBER 21, 2020

[Atherosclerosis: an ancient process in a new interpretation]

REIBER István

[The progress of atherosclerosis starts in childhood and lasts until the body dies. Most cardiovascular diseases and deaths can be traced back to atherosclerotic vascular changes. The process is thousands of years old, but its complex pathophysiology becomes recognized and realised only nowadays. Based on the evidence available today, atherosclerosis is such a chronic inflammatory disease of large- and medium-sized arteries, which is characterized by lipoproteins and immune cells transformed through oxidative and other changes and subendothelial accumulation of extracellular matrix. Innate and adaptive immunity provide a complex regulating system of atherogenesis, which while directing specifically the pro-atherogenic inflammatory and atheroprotective anti-inflammatory processes intensify plaque progression or even stabilize them respectively. With our growing knowledge about the pathology of atherogenesis, we can further improve the identification of cardiovascular risk conditions and apply more personalized therapeutic strategies.]

Clinical Oncology

FEBRUARY 28, 2020

[Role of infl ammation in the carcinogenesis]

KOPPER László, TÍMÁR József

[Chronic infl ammation is an important promoter of the carcinogenesis of several cancer types and also an important contributor to mutagenicity beside the known carcinogens. Beside the continous regeneration of the affected epithelia chronic infl ammation provide a special microenvironment intra and extracellular environment which support malignant transformation and block emerging immune reactions. On the other hand, cancer is generating chronic infl ammation itself independent from its role in the carcinogenic process. It is due to cancer necrosis as well as to the production of infl ammatory cytokines. Cancer-induced infl ammatory reactions block antitumoral immune responses and continous monitoring of this process provide valuable clinical parameter of cancer progression.]

Lege Artis Medicinae

SEPTEMBER 30, 2020

[The pain-trigger role of cytokines in the nervous system – the direct analgesic effect of anti-cytokine therapy ]

HODINKA László, VERECKEI Edit

[Nociceptive, neuropathic and central me­chanisms are involved in the perception, transmission and processing of chronic pain and shaping of cerebral pain image. Alar­mins – molecules alarming defence and signing the presence of pathogens and tissue damage - trigger a series of pathogenic events resulting in inflammatory pain stimuli. Proinflammatory cytokines play a determining role in the pain perception at the level of the nervous system. Continuous inflammatory stimuli while sensitizing the periferic and central neurons activate the pain-related cerebral areas and develop the complex pain image, the pain matrix. Ce­reb­ral functional connections are operating in networks and can be visualized by functional MRI. Cytokines activate the neurons directly or indirectly by other neuromediators. Cytokine receptors are expressed on no­ciceptors and even on higher-level neurons and on various non-neural cells, such as microglia and astrocytes. The most ubiquitous cytokines are the Tumour Necrosis Factor and Interleukin 6 in the nervous sys­tem. The signaling pathways are the Nuclear Factor κB and the Janus-kinase enzyme system. The proinflammatory cytokines and the Janus-kinase are therefore primary therapeutic targets. Anti-cytokine biologicals and small molecular kinase inhibitors decrease the pain and improve functional activity in rheumatoid arthritis. Decrease of pain was more pronounced than expected only from the decrease of the clinical biomarkers of inflammation. The early and ra­pid painkiller effect of targeted biological and chemical-biological response modifiers is attributed to their direct analgesic effect on the brain.]

Hypertension and nephrology

SEPTEMBER 10, 2019

[Role of IL-10 family of cytokines in kidney fibrosis]

PAP Domonkos, VERES-SZÉKELY Apor, SZEBENI Beáta, SZIKSZ Erna, KISS József Zoltán, TAKÁCS István Márton, REUSZ György, SZABÓ J. Attila, VANNAY Ádám

[Chronic renal failure is a major health problem, affecting 8 to 16% of the population. Regardless of the etiology the common hallmark of chronic renal failure is inflammation, leading to the activation of renal myofibroblasts. Chronic activation of myofibroblasts lead to abnormal accumulation of extracellular matrix, disruption of the architecture of the kidney and finally to reduced renal function. Although our knowledge is rapidly expanding about the pathomechanism of chronic renal failure, we still have no drug to treat or hinder the progression of the disease. In our present review article, we summarize the role of the cytokines of the IL-10 family in renal scarring.]

Clinical Oncology

MAY 10, 2015

[Nutritional support in cancer anorexia-cachexia syndrome]

HARISI Revekka

[Cancer anorexia-cachexia syndrome (CACS) defi ned by ongoing loss of skeletal muscle mass, with or without loss of fat mass. In contrast to serious non tumorous cachexia it can not be reversed by conventional nutritional support. CACS affects most of cancer patients and has negative impact on physical function, anticancer treatment response, quality of life and survival. It is known that interactions between tumor and reactive host cells are responsible for tumor progression, metastasis formation and chronic infl ammation, as well. All of the processes are induced by cytokines. The CACS associated changes in carbohydrate, protein and lipid metabolism are caused by the elevated level of infl ammatory cytokines. The new anti-CACS drug development aimed at normalizing of the pathologic pathways. Up to now, megestrol-acetate (MA) administration seems to be the most effective drug in CACS treatment. MA has dual effect, stimulates the NPY activation and inhibits the synthesis and expression of infl ammatory cytokines. Its clinical effects are on line with the aboves, improves appetite, calorie intake and increases body weight. There is paradigm shift in CACS treatment, the traditional nutritional support is replaced by combination of pharmaceutical interventions, nutritional support and use of dietary supplements.]

Hypertension and nephrology

MARCH 20, 2015

[Role of activated cells and local inflammatory mechanisms in the development of hypertension]

LELBACH Ádám, KOLLER Ákos

[In the past decades an increasing attention has been paid regarding the possible role of the immune system in the development of hypertension. In vitro and in vivo animal experiments, as well as human studies provided evidence for the role of the innate and adaptive immune systems in the development of hypertension, especially in connection with the perivascular adipose tissue, heart and kidney. Inflammatory mediators, cytokines, reactive oxygen metabolites have not only local pro-hypertensive effecting the vasculature, but also influence the development of hypertension through other regulatory mechanisms, such as the central nervous system. These findings provide a new understanding of the development of hypertension, as well as offer new potential mechanisms that can be targeted with novel the - rapies.]

Lege Artis Medicinae

JUNE 20, 2014

[The effect of biological therapy on generalised osteoporosis in patients with rheumatoid arthritis]

JUHÁSZ Péter

[In rheumatoid arthritis, the inflammation and damage of multiple joints can lead to generalised osteoporosis. This process is mostly mediaated by cells and cytokines that are also important for maintaining inflammation, by inhibiting bone formation as well as stimulating bone resorption. Data from the literature show that biological therapies that effectively decrease inflammation can also stimulate bone formation and inhibit bone resorption. This results in an increased bone density and bone protection, which is highly important to prevent subseqent fractures.]

LAM KID

MAY 30, 2014

[The effect of biological therapy on generalised osteoporosis in patients with rheumatoid arthritis]

JUHÁSZ Péter

[In rheumatoid arthritis, the inflammation and damage of multiple joints can lead to generalised osteoporosis. This process is mostly mediaated by cells and cytokines that are also important for maintaining inflammation, by inhibiting bone formation as well as stimulating bone resorption. Data from the literature show that biological therapies that effectively decrease inflammation can also stimulate bone formation and inhibit bone resorption. This results in an increased bone density and bone protection, which is highly important to prevent subseqent fractures.]

Lege Artis Medicinae

SEPTEMBER 22, 2013

[A novel rapid IL-6 release assay using blood mononuclear cells of patients with various forms of drug induced skin injuries]

BALÓ-BANGA J. Mátyás, SCHWEITZER Katalin

[INTRODUCTION - IL-6 is a multifunctional cytokine with effects on the haematopoiesis on differentiation of T and B lymphocytes and on the regulation of both inflammatory and allergic reactions. The question arose whether this substance excreted by mononuclear cells could be used as a marker of allergy to drugs or not. Till now equivocal descriptions were lacking. METHOD - The preformed IL-6 present in the mononuclear cells released by any of four standard dilutions of pure substances upon 20 minutes incubation was determined from the supernatants by ELISA technique. In vivo patch, intradermal and provocation tests were carried out along with this assay (483 in vitro and 172 in vivo). RESULTS - Two different groups suspect for drug allergy (100 and 62 patients as well as their matching controls, 24 and 23 persons) were involved with these procedures. In some cases TNF-α, IL-2, IFN-γ and IL-4 was measured simultaneously by flow cytometric assay. Only TNF-α and IL-6 were present in the 20 min. supernatants. The comparisons with in vivo tests have confirmed that the amount of IL-6 release had not depended either on the clinical phenotype of allergy or on the structure of the tested drugs within the molecular mass range between 76-4000 Da. IL-6 released at the lowest or multiple concentrations of drugs coincided with more severe and widespread clinical forms. CONCLUSION - Based on the results we elaborated an in vitro method applicable clinically for detecting drug sensitisation and its differential diagnosis in patients with skin signs of drug sensitisation.]

Clinical Neuroscience

OCTOBER 05, 2013

[The impact of the vitamin D in neurological diseases and neurorehabilitation: from demencia to multiple sclerosis. Part I: The role of the vitamin D in the prevetion and treatment of multiple sclerosis]

SPEER Gábor

[The world-wide incidence of vitamin D deficiency is high, independently of age. Multiple sclerosis is a chronic disorder, occuring in those who possess or are exposed to a combination of genetic and environmental risk factors. One of the environmental factors associated with the development is vitamin D. Vitamin D is an immunomodulatory agent, its role is verified in many of autoimmune diseases. Vitamin D inhibits IL-6, IL-17 and IL-23 secretions which are crucial in Th1 and Th17 differentiation and also decreases proinflammatorical cytokine production. Moreover it enhances the immunosuppressive IL-10 cytokine secretion and inhibits the T-reg cell development. These cytokines and cells are essential for the pathomechanism of multiple sclerosis. Data have shown, that the vitamin D levels above 100 nmol/l (40 ng/ml) is essential for the prevention of multiple sclerosis. Below this level the vitamin D supplementation is reasonable. In pregnancy, the vitamin D deficiency at the last two semester increases the risk for the multiple sclerosis of the infant. The optimal vitamin D level for multiple sclerosis patients is 100-150 nmol/l (40-60 ng/ml). There is no consensus for the role of vitamin D in multiple sclerosis yet, but until the achieving this, the diagnosis and the treatment of the vitamin D deficiency is crucial for scelrosis multiplex patients and in cases of elevated risk. Data shows, that in patient with multiple sclerosis the normal vitamin D level is suboptimal, however the exact role of vitamin D and doses must be clarified by interventional studies.]