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Lege Artis Medicinae

OCTOBER 21, 2020

[Atherosclerosis: an ancient process in a new interpretation]


[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 Neuroscience

JANUARY 30, 2021

Matrix metalloproteinases and their tissue inhibitors in relapsing remitting multiple sclerosis: Possible markers and treatment agents


Matrix metalloproteinases (MMPs), which are synthesized by many cell groups and responsible for the destruction of matrix proteins, and endogen tissue inhibitors of MMPs (TIMPs) have a role in the pathogenesis of Multiple Sclerosis (MS) by affecting the blood-brain barrier. We aimed to investigate the role of MMPs and TIMPs in the immunopathogenesis and in the course of multiple sclerosis (MS). We enrolled 25 relapsing remitting MS patients, who had a definite MS diagnosis according to McDonald criteria and 25 healthy subjects similar for age and gender as control group. MMP-9- and TIMP-1 levels were measured twice in patient group (one time during an attack and one in remission) and once in healthy subjects. MMP-9- and TIMP-levels of patients during attack and remission period and MMP-9/TIMP-1 ratio were found significantly higher than in the control subjects. In patient group MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratio during attacks were not significantly different than during remission period. However, when subdivided according to their number of attacks, patients with 2 attacks had significantly higher levels during attack period comparing to remission period (p<0.05); in case of patients with more than 2 attacks did not have a statistically significant difference in attack and remission periods. Matrix metalloproteinases are important actors in MS immunopathogenesis, particularly in the early period and inhibitor agents for these enzymes can be used as a treatment option.

Lege Artis Medicinae

SEPTEMBER 30, 2020

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


[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.]