Changes in the Plasma and Platelet Nitric Oxide Biotransformation Metabolites during Ischemic Stroke-A Dynamic Human LC/MS Metabolomic Study.

Despite improvement in the management of modifiable cardiovascular risk factors, ischemic stroke remains the leading cause of morbidity and mortality in the adult population. The aim of this study was to analyze the time-dependent dynamic differences in expression of the nitric oxide (NO) metabolic pathway in the platelet and plasma compartment between subjects with and without ischemic stroke. Additionally, the interplay between these parameters and platelet aggregation was investigated. A total of 418 patients in acute phase of non-cardioembolic stroke were investigated. Following the inclusion and exclusion criteria, finally 40 subjects with stroke and 39 demographically matched healthy participants were enrolled. Neurological physical examination, followed by assessment of the platelet and plasma levels of the nitric oxide synthase (NOS) inhibitors, including asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), as well as NOS substrate-L-Arginine were performed dynamically three times within the first 24-h, then on the 3rd and 7th day after the stroke onset, which was compared with the healthy control. The platelet L-Arginine concentration was significantly higher on the 1st and 3rd day of stroke, while the plasma levels were significantly lower on exact days in comparison to the control. The competitive NOS-inhibitors in platelets were stably elevated in stroke subjects, whereas no significant differences in plasma compartment were noted. The arachidonic-acid-induced platelet aggregation was negatively associated with the platelet NOS substrate bioavailability, as assessed by the L−Arginine ADMA-ratio on the 3rd and 7th day. Subjects with non-cardioembolic ischemic stroke are characterized by elevated platelet levels of NOS inhibitors. Management of stroke results in increasing the platelet L-Arginine concentration and subsequent NO bioavailability in the platelet compartment.

The relationship between panic disorder and hypertension. A review of literature. / Zwiazek pomiedzy zaburzeniem lekowym z napadami leku a nadcisnieniem tetniczym. Przeglad pismiennictwa.

About 1/4 of the world's adult population suffers from hypertension. Due to the high prevalence of the disease, its impact on mortality and socio-economic costs, it is important to search for modifiable causes of its development. This review analyses studies in order to answer the question: Is there a higher prevalence of panic disorder in adults (≥18 years of age) with hypertension, than in normotensive group? There have been found 10 cross-sectional studies describing correlation between hypertension and panic disorder. Odds ratio for this two clinical entities ranged from OR = 3.31 (2.99-3.67) to OR = 1.19 (0.87-1.62). Moreover, frequency of coincidence of those two clinical entities was found between 4.2% and 18.75%. In the prospective studies there have been found a positive association between panic disorder and subsequent life-long development of hypertension OR= 1.7 (1.4-2.0). On the other hand, association between hypertension and subsequent development of panic disorder in the 12-months observation was OR = 3.23 (1.51-6.93), but in 3 years of observation it was insignificant OR = 1.12 (0.80-1.57). Based on the literaturereview, dueto the differences in methodology and the small number of prospective studies, it can only be suggested to clinicians that in some cases they should search for panic disorder in patients with hypertension, especially paroxysmal one.

Role of the Platelets and Nitric Oxide Biotransformation in Ischemic Stroke: A Translative Review from Bench to Bedside.

Ischemic stroke remains the fifth cause of death, as reported worldwide annually. Endothelial dysfunction (ED) manifesting with lower nitric oxide (NO) bioavailability leads to increased vascular tone, inflammation, and platelet activation and remains among the major contributors to cardiovascular diseases (CVD). Moreover, temporal fluctuations in the NO bioavailability during ischemic stroke point to its key role in the cerebral blood flow (CBF) regulation, and some data suggest that they may be responsible for the maintenance of CBF within the ischemic penumbra in order to reduce infarct size. Several years ago, the inhibitory role of the platelet NO production on a thrombus formation has been discovered, which initiated the era of extensive studies on the platelet-derived nitric oxide (PDNO) as a platelet negative feedback regulator. Very recently, Radziwon-Balicka et al. discovered two subpopulations of human platelets, based on the expression of the endothelial nitric oxide synthase (eNOS-positive or eNOS-negative platelets, respectively). The e-NOS-negative ones fail to produce NO, which attenuates their cyclic guanosine monophosphate (cGMP) signaling pathway and-as result-promotes adhesion and aggregation while the e-NOS-positive ones limit thrombus formation. Asymmetric dimethylarginine (ADMA), a competitive NOS inhibitor, is an independent cardiovascular risk factor, and its expression alongside with the enzymes responsible for its synthesis and degradation was recently shown also in platelets. Overproduction of ADMA in this compartment may increase platelet activation and cause endothelial damage, additionally to that induced by its plasma pool. All the recent discoveries of diverse eNOS expression in platelets and its role in regulation of thrombus formation together with studies on the NOS inhibitors have opened a new chapter in translational medicine investigating the onset of acute cardiovascular events of ischemic origin. This translative review briefly summarizes the role of platelets and NO biotransformation in the pathogenesis and clinical course of ischemic stroke.

The estimation of excessive daytime sleepiness in post-stroke patients - a polysomnographic study.

Excessive daytime sleepiness (EDS) has been reported in stroke patients. EDS in acute stroke was studied repeatedly, but there is a modest amount of data in post-stroke patients. The aim of this study was to assess the frequency of EDS and characterize sleep architecture in patients >3 months after stroke and identify factors which may affect EDS. 66 patients were enrolled, of which 33 had experienced stroke. All underwent a standardized overnight, diagnostic single night polysomnography, including electrocephalogram (EEG) leads, electrooculograms (EOG), chin electromyogram (EMG), and electrocardiogram (ECG). Epworth Sleepiness Scale (ESS) was used to measure subjects' level of daytime sleepiness. We observed similar total ESS score, total sleep time (TST), sleep efficiency, as well as respiratory disturbance index /apnea-hypopnea index (RDI/AHI), oxygen desaturation index (ODI) and mean heart rate in both groups. We observed positive linear correlation between EDS and mean heart rate in the stroke group (r = 0.46, p < 0.05) as well as between EDS and REM duration (r = 0.23, p < 0.05). In the non-stroke group EDS didn't correlate with the heart rate or with the REM duration. In the non-stroke group EDS correlated positively with RDI/AHI and ODI index (r = 0.46; p = <0.05 r = 0.41, p < 0.05 and maximal desaturation (r = 0.55, p < 0.05), this correlation was not observed in post-stroke group. In the both groups we observed negative linear correlation between BMI and saturation (stroke group - mean as well as minimal saturation (r = -0.458, p < 0.05; r = -0.578, p < 0.05), non stroke group - minimal but not mean saturation rate (r = -0.544, p < 0.05). We also noticed in both groups positive correlation between BMI and both AHI and ODI index (stroke group respectively: r = 0.430, p < 0.05; r = 0.451, p < 0.05; non-stroke group - BMI and ODI: r = 0.405, p < 0.05). The positive BMI correlation with RDI/AHI was not significant in the non-stroke group. We noticed that BMI correlates with non-REM sleep N1 (r = 0.760, p < 0.05) in post-stroke group, while it correlates negatively with REM sleep (r = -0.709, p < 0.05). There was no such correlation in the non-stroke group. In summary, in stroke patients subjective daytime sleepiness is associated with heart rate, but not with the severity of OSA. Thus ESS (Epworth Scale Score) may be not as useful as a marker of obstructive sleep apnea (OSA) presence or severity in post stroke patient as in the general population.