Nowe kierunki w diagnostyce molekularnej i terapii osłoniaków nerwu przedsionkowego (Vestibular Schwannoma)

W ostatnich latach poznano molekularne podłoże powstawania i wzrostu nerwiaków osłonkowych nerwu przedsionkowego (ang. vestibular schwannoma; VS). Opisano: główne aberracje genetyczne i epigenetyczne, zmiany ekspresji genów oraz specyficzne szlaki sygnałowe, które biorą udział w patogenezie VS sporadycznych oraz związanych z neurofibromatozą typu II (NF2). Odkrycia te pozwoliły na poszukiwanie potencjalnych markerów prognostycznych VS oraz punktów uchwytu dla terapii biologicznych. Poniższa praca podsumowuje główne kierunki badań w zakresie diagnostyki molekularnej oraz terapii farmakologicznej VS, opartej na lekach biologicznych

New directions in molecular diagnostics and therapy of vestibular schwannomas

The molecular basis for the formation and growth of vestibular schwannomas (VS) has been elucidated in the recent years. The main genetic and epigenetic aberrations, changes in gene expression and specific signaling pathways involved in pathogenesis of sporadic VS and neurofibromatosis type II (NF2) have been defined. These findings facilitated the search for prognostic markers in VS and potential targets for biological therapy. This publication summarizes the main directions of research in the field of molecular diagnostics and pharmacotherapy of VS based on biological agents

Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats

Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (−6%) and plasma (−38%), kidney (−71%) and heart (−52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone