Unsolved Issues in the Management of High Blood Pressure in Acute Ischemic Stroke

High blood pressure is common in acute stroke patients. Very high as well as very low blood pressure is associated with poor outcome. Spontaneous fall of blood pressure within the first few days after stroke was associated both with neurological improvement and impairment. Several randomized trials investigated the pharmacological reduction of blood pressure versus control. Most trials showed no significant difference in their primary outcome apart from the INWEST trial which found an increase of poor outcome when giving intravenous nimodipine. Nevertheless, useful information can be extracted from the published data to help guide the clinician's decision. Blood pressure should only be lowered when it is clearly elevated, and early after onset, reduction should be moderate but may be achieved rapidly. No clear recommendations can be given on the substances to use; however, care should be taken with intravenous calcium channel blockers and angiotensin receptor antagonists. Two ongoing randomized trials will help to solve the questions on blood pressure management in acute stroke

Di-cationic arylimidamides Act Against Neospora caninum tachyzoites by Interference in Membrane Structure and Nucleolar Integrity and are Active Against Challenge Infection in Mice

Neospora caninum is considered to be the main cause of bovine abortion in Europe and the USA, leading to considerable financial impact. Losses are caused directly by abortions or indirectly through breeding of calves with impaired viability. Due to the lack of effective chemotherapy against bovine neosporosis, there is a need to develop new anti-protozoal compounds, which would either eliminate the parasite or avoid its transmission. In order to identify compounds of interest, the in vitro activities of 41 di-cationic pentamidine derivatives were studied employing a transgenic N. caninum clone expressing beta-galactosidase as a reporter gene. The arylimidamide DB745, previously shown to be highly active against Leishmania donovani in vitro and in vivo, appeared as the most promising compound, with an IC50 of 80 nM in 3-day growth assays and severely affecting both host cell invasion as well as intracellular proliferation. TEM of intracellular tachyzoites identified distinct alterations related to the nucleolus and the nuclear and cellular membrane. Long-term growth assays showed that DB745 acted parasiticidal upon the Nc-Liv isolate, but not against the Nc-1 isolate of N. caninum. In vivo studies in N. caninum (Nc-1 isolate) infected mice showed that daily intraperitoneal application of DB745 for a period of 14 days resulted in a decreased number of clinically affected animals, and lower cerebral parasite burdens in DB745-treated mice compared to non-treated mice. These results illustrate the potential of dicationic arylimidamides for the treatment of N. caninum infections

Circulating periostin level in asthmatic pregnancy

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Ionfolyadékok katalitikus és elektrokémiai alkalmazása = Catalytic and electrochemical application of ionic liquids

A pályázat keretében egy elméleti és gyakorlati szempontból egyaránt az érdeklődés homlokterében álló területtel, ionfolyadékok széleskörű vizsgálatával foglalkoztunk. Kutatásaink kiterjedtek új típusú ionfolyadékok szintézisére, szerkezetének vizsgálatára, elektrokémiai és katalitikus alkalmazására. Legfontosabb eredményeknek a következőket tartjuk. Imidazolium alapú ionfolyadékok szerkezetének pontosabb megállapítása céljából a kation-anion pár koordinációt tanulmányoztuk kvantumkémiai módszerekkel. Megállapítottuk, hogy az imidazolium kation alapú ionfolyadékok kristályos polimorfizmusa közvetlen összefüggésben van a kation-anion koordináció esetében kimutatott konformerek szerkezetével. Különböző redoxi-rendszerekben vizsgált anyagok (elsősorban ferrocén-származékok) elektrokémiai vizsgálata során megállapítottuk, hogy az általunk vizsgált ionfolyadékok széles potenciál-ablakukkal, nagy elektromos vezetésükkel voltammetriás mérésekhez ideálisan alkalmazható alap-elektrolitok. Számos Pt(difoszfin)Cl2 típusú komplex elemi reakcióit vizsgáltuk ionfolyadékokban 31P NMR segítségével. A platina-, valamint az analóg palládium-komplexeket karbonilezési és kapcsolási reakciókban alkalmaztuk. Farmakológiai szempontból jelentős vegyületek (elsősorban szteroidok) szintézisét valósítottuk meg mind hagyományos oldószerekben, mind ionfolyadékokban. | Within the framework of this project the investigation of a field of both high theoretical and practical importance, namely, the wide-ranging research of ionic liquids has been carried out. The synthesis and structural investigation of novel ionic liquids, as well as their application in electrochemistry and catalysis were comprised in our research project. The most important results are considered as follows. In order to get a deeper insight into the structure of imidazolium-based ionic liquids, the cation-anion coordination was studied by quantum-chemical methods. The polymorphism of these systems is closely related to the structure of conformers observed in cation-anion coordination. During the electrochemical investigation of redox-active compounds (primarily ferrocene derivatives) the ionic liquids with wide potential-window and large conductivity proved to be highly suitable media (base-electrolites) for voltammetric measurements. The elementary reactions of several Pt(diphosphine)Cl2 type complexes have been investigated in ionic liquids by 31P NMR. The platinum complexes and their palladium analogues have been used in carbonylation and cross-coupling reactions. The synthesis of compounds of pharmacological importance (steroids, tropanes, ferrocenes) have been accomplished both in ionic liquids and conventional organic solvents

Circulating Clusterin and Osteopontin Levels in Asthma and Asthmatic Pregnancy

Asthma in pregnancy poses a risk of adverse outcomes. Osteopontin and clusterin emerged as asthma biomarkers; however, their circulating levels during pregnancy are unknown yet. This cross-sectional study investigated peripheral osteopontin and clusterin levels and their relationship to disease control in 26 asthmatic pregnant (AP), 22 asthmatic nonpregnant (ANP), and 25 healthy pregnant (HP) women and 12 healthy controls (HNP). Osteopontin levels of ANP and HNP were similar (2.142 [1.483-2.701] versus 2.075 [1.680-2.331] ng/mL, p = 0.7331). Pregnancy caused a marked elevation in both healthy (HP: 3.037 [2.439-4.015] ng/ml, p = 0.003 versus HNP) and asthmatic (AP: 2.693 [1.581-3.620] ng/ml) patients; thus the pregnant groups did not differ (p = 0.3541). Circulating clusterin levels were comparable in ANP and HNP (109.2 [95.59-116.3] versus 108.8 [97.94-115.3] mu g/mL, p = 0.8730) and the level was lower in HP (98.80 [84.26-105.5] mu g/mL, p = 0.0344 versus HNP). In contrast, the level was higher in AP (111.7 [98.84-125.6] mu g/mL, p = 0.0091 versus HP). In ANP, a positive correlation of PEF (r = 0.3405; p = 0.0221) and a negative correlation of R-aw (r = -0.3723; p = 0.0128) to clusterin level were detected. Circulating osteopontin level increases in pregnancy regardless of concomitant well-controlled asthma, indicating its gestational role. Clusterin level decreases in healthy but not in asthmatic pregnancy and correlates directly with lung function

Relationship of Circulating Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels to Disease Control in Asthma and Asthmatic Pregnancy

Asthma has a high burden of morbidity if not controlled and may frequently complicate pregnancy, posing a risk for pregnancy outcomes. Elevated plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is related to a worse prognosis in many conditions such as infectious, autoimmune, or pregnancy-related diseases; however the value of suPAR in asthma and asthmatic pregnancy is unknown. The present study aimed to investigate the suPAR, CRP and IL-6 levels in asthma (asthmatic non-pregnant, ANP; N = 38; female N = 27) and asthmatic pregnancy (AP; N = 15), compared to healthy non-pregnant controls (HNP; N = 29; female N = 19) and to healthy pregnant women (HP; N = 58). The relationship between suPAR levels and asthma control was also evaluated. The diagnostic efficacy of suPAR in asthma control was analyzed using ROC analysis. IL-6 and CRP levels were comparable in all study groups. Circulating suPAR levels were lower in HP and AP than in HNP and ANP subjects, respectively (2.01 [1.81-2.38] and 2.39 [2.07-2.69] vs. 2.60 [1.82-3.49] and 2.84 [2.33-3.72] ng/mL, respectively, p = 0.0001). suPAR and airway resistance correlated in ANP (r = 0.47, p = 0.004). ROC analysis of suPAR values in ANP patients with PEF above and below 80% yielded an AUC of 0.75 (95% CI: 0.57-0.92, p = 0.023) and with ACT total score above and below 20 an AUC of 0.80 (95% CI: 0.64-0.95, p = 0.006). The cut-off value of suPAR to discriminate between controlled and not controlled AP and ANP was 4.04 ng/mL. In conclusion, suPAR may help the objective assessment of asthma control, since it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease in circulating suPAR levels detected both in healthy and asthmatic pregnant women presumably represents pregnancy induced immune tolerance