The majority of our genes may be regulated in a daily rhythm, including the genes for cell cycle control. Epidemiological and genetic evidences suggest that disruption of circadian timing mechanisms makes our cells more vulnerable to cancer formation. The aim of this study was to investigate the relationship between expression patterns of circadian clock genes (period homolog (per)1, per2, clock, and cry1) and tumor development by analyzing human skin biopsies of malignant melanoma and nonmalignant naevus tumors. We found that mRNA levels and nuclear immunopositivity for the investigated clock genes were reduced by 30-60 % in both melanoma and in naevus biopsies if compared with adjacent nontumorous samples. The alterations in melanoma presented significant associations with clinicopathological characteristics (e.g., Breslow thickness). Contrary to previous reports, the moderate decrease of per1 expression seen in malignant tissues could not be linked to malignant transformation itself; rather, it reflects only the alterations in tissue composition. In turn, clock expression was upregulated in nontumorous cells of melanoma biopsies but not in melanoma cells or naevus cells. As this gene (clock) is closely related to cellular metabolism, our data suggest its role in the impaired regulation of metabolism in malignant tumors. Our results present the first clinical evidence for a possible link between circadian clock genes and human skin tumorigenesis.

A stroke világszerte a harmadik leggyakoribb halálok, a szívinfarktus és a daganatos betegségek után, funkcionális kimenetele pedig valamennyi betegség közül a legrosszabb. A koleszterin, különösen az LDL-C-szint kulcsszerepet játszik az érelmeszesedésben, a plakkok kialakulásában. Az elmúlt években bebizonyosodott, hogy az LDL-C-szint növekedésével arányosan emelkedik a cerebrovascularis betegségek incidenciája és halálozása. A statinterápia egyér-telműen csökkenti a stroke-rizikót, de a más módszerekkel elért lipidszintcsökkentő kezelésnek eddig nem volt igazoltan szignifikáns hatása. A magasabb dózisú statinkezelés preventív hatása egyértelmű, ugyanakkor az ilyen dózis alkalmazása fokozott óvatosságot igényel korábbi intracerebralis vérzést elszenvedett betegeknél, és kockáztathatjuk az új keletű diabetes kialakulását is. A közelmúltban közzétett IMPROVE-IT vizsgálat elsőként igazolta, hogy a statinterápia mellé adott nem statin típusú ezetimibbel az LDL-C-szint tovább csökkenthető, ezzel párhuzamosan tovább mérséklődik a cardio-és cerebrovascularis események incidenciája, a mellékhatások számának növekedése nélkül. Ezek az eredmények újra megerősítették a minél nagyobb mértékű LDL-C-szint-csökkentés jelentőségét. A statin-ezetimib kombináció révén a célértékek elérése alacsony és közepes statindózissal is lehetséges, csökkentve ezáltal a magas dózisú statinkezelés mellékhatásainak veszélyét. Orv. Hetil., 2016Hetil., , 157(52), 2059Hetil., -2065 Kulcsszavak: LDL-koleszterin, stroke, statinok, ezetimib Lipids and cerebrovascular disease -New therapeutic options in lowering LDL-cholesterolStroke is the third most common cause of death worldwide following myocardial infaction and malignancies, furthermore, its functional outcome is the worst of all conditions. Cholesterol, especially LDL-cholesterol plays a key role in the formation of atherosclerotic plaques. It has been verified recently that escalating incidence and mortality of cerebrovascular diseases are proportional to increased levels of LDL-cholesterol. Statin therapy undeniably reduces the risk of stroke, however other methods for decreasing lipid levels have not been proved significantly effective. Preventive effect of high-dose statin treatment is without doubt, although administration of such high dosage might require special precautions for patients with prior intracerebral hemorrhage and it also risks development of incident diabetes. The recently published IMPROVE-IT study is the first to prove that the addition of ezetimibe as a nonstatin type drug, to statin treatment contributes to further reduction of LDL-cholesterol. The combination treatment results in additional decrease in the incidence and mortality of cerebrovascular events, without any expansion in the number or adverse effects. These results confirm the importance of any further reduction of LDL-cholesterol levels. Achieving target values with statin-ezetimibe combination allows administration of low to moderate dose of statin, which decreases risks of adverse effects related to hig...

Stroke, as a complex, multidimensional cerebrovascular disease, is one of the key issues in the present day's healthcare. Recently, the emerging numbers of studies provide a wide range of future potential solutions in stroke care, implying an imminent change in the aspects of therapy. In this paper, we are going to give a brief insight into the most determinant aspects and factors of the disease, focusing on the very recent findings in research, as well as the practical approach in stroke prevention.

Despite their very recent discovery and only couple decade-long existence, cerebral microbleeds are progressively investigated, trending radiological concepts in today's scientific era. In this paper, we are going to provide a short review on the most important details of cerebral microbleeds, with special focus on their clinical relevance and particular emphasis on their practical aspects with stroke prevention and therapy.