Serumska razina za neuron specifične enolaze kao biljeg ishemijsko-reperfuzijskog oštećenja u bolesnika podvrgnutih karotidnoj endarterektomiji

In patients with atherosclerotic stenosis of the extracranial segment of internal carotid artery, surgical intervention is an effective method to prevent cerebral ischemic stroke. However, this surgical procedure may cause vascular brain damage. The aim of the study was to investigate consequential brain ischemia-reperfusion injury by measuring the cerebral specific marker, neuronspecific enolase (NSE), in serum of patients having undergone internal carotid endarterectomy (CEA). The study involved 25 patients that underwent CEA due to internal carotid artery stenosis. Blood samples were obtained from each patient on three occasions: within 24 h prior to surgery, 12 h after surgery, and 48 h after surgery. Serum NSE levels were measured by a commercially available enzymelinked immunosorbent assay. The study showed that serum NSE level was statistically significantly increased 48 h after CEA as compared with the level 12 h after surgery and the level before surgery (p0.05). Data from our study showed CEA to affect serum NSE in patients with significant internal carotid artery stenosis. Thus, serum NSE may be used as a biochemical marker of brain ischemia-reperfusion injury following CEA.Kirurška intervencija je učinkovita metoda sprječavanja ishemijskog moždanog udara u bolesnika s aterosklerotskom stenozom ekstrakranijskog dijela unutarnje karotidne arterije. Međutim, ovaj kirurški zahvat može uzrokovati oštećenje moždanog krvožilja. Cilj ovoga istraživanja bio je ispitati posljedično ishemijsko-reperfuzijsko oštećenje mozga mjerenjem za neuron specifične enolaze (neuron-specific enolase, NSE) kao specifičnog moždanog biljega u serumu bolesnika podvrgnutih endarterektomiji unutarnje karotide (internal carotid endarterectomy, CEA). Istraživanje je obuhvatilo 25 bolesnika podvrgnutih CEA zbog stenoze unutarnje karotidne arterije. Uzorci krvi uzeti su u svakog bolesnika tri puta: unutar 24 h prije operacije, 12 h nakon operacije i 48 h nakon operacije. Serumske razine NSE mjerene su komercijalnim testom ELISA. Rezultati su pokazali da je serumska razina NSE bila statistički značajno povišena 48 h nakon CEA u usporedbi s razinom izmjerenom 12 h nakon operacije, kao i u usporedbi s razinom prije operacije (p0,05). Podaci dobiveni u ovom istraživanju pokazuju da CEA utječe na razinu NSE u serumu kod bolesnika sa značajnom stenozom unutarnje karotidne arterije. Stoga bi serumska razina NSE mogla poslužiti kao biokemijski biljeg ishemijsko-reperfuzijskog oštećenja mozga nakon CEA

Serum microtubule associated protein tau and myelin basic protein as the potential markers of brain ischaemia-reperfusion injury in patients undergoing carotid endarterectomy

Introduction. In the prevention of ischaemic stroke the recommended surgical procedure is carotid endarterectomy (CEA). However, surgical treatment of atherosclerotic stenosis may cause neurological complications. The aim of the study was to investigate consequential brain ischaemia-reperfusion injury by measuring the cerebral specific markers, the microtubule associated protein tau (MAPt) and myelin basic protein (MBP) in the serum of patients that underwent CEA. Material and methods. This study involved 25 participants who underwent CEA due to internal carotid artery stenosis. Blood samples were taken from each patient at three different intervals; within 24 hours prior to surgery, 12 hours after the surgery, and 48 hours after the surgery. Serum MAPt and MBP levels were measured by a commercially available enzyme-linked immunosorbent assay (ELISA). Results. The study showed that serum MAPt and MBP levels were statistically significantly decreased 12 hours after CEA compared to the level before the surgery (p < 0.05), but MAPt and MBP levels were normalized 48 hours after CEA. There was statistically significant correlation in serum MAPt levels with the velocity of blood flow in the internal carotid artery 12 and 48 hours after CEA (p < 0.05). Conclusions. Data from our study showed that CEA affects serum neuromarkers levels, such as MAPt and MBP, in patients with significant internal carotid artery stenosis. MAPt and MBP levels showed characteristic time curve in patients who underwent CEA and did not experience any neurological deficit in perioperative period. Possible alterations of this time curve may potentially be an index of a neurological event occurrence.  Introduction. In the prevention of ischaemic stroke the recommended surgical procedure is carotid endarterectomy (CEA). However, surgical treatment of atherosclerotic stenosis may cause neurological complications. The aim of the study was to investigate consequential brain ischaemia-reperfusion injury by measuring the cerebral specific markers, the microtubule associated protein tau (MAPt) and myelin basic protein (MBP) in the serum of patients that underwent CEA. Material and methods. This study involved 25 participants who underwent CEA due to internal carotid artery stenosis. Blood samples were taken from each patient at three different intervals; within 24 hours prior to surgery, 12 hours after the surgery, and 48 hours after the surgery. Serum MAPt and MBP levels were measured by a commercially available enzyme-linked immunosorbent assay (ELISA). Results. The study showed that serum MAPt and MBP levels were statistically significantly decreased 12 hours after CEA compared to the level before the surgery (p < 0.05), but MAPt and MBP levels were normalized 48 hours after CEA. There was statistically significant correlation in serum MAPt levels with the velocity of blood flow in the internal carotid artery 12 and 48 hours after CEA (p < 0.05). Conclusions. Data from our study showed that CEA affects serum neuromarkers levels, such as MAPt and MBP, in patients with significant internal carotid artery stenosis. MAPt and MBP levels showed characteristic time curve in patients who underwent CEA and did not experience any neurological deficit in perioperative period. Possible alterations of this time curve may potentially be an index of a neurological event occurrence.

Serum glial fibrillary acidic protein as a marker of brain damage in patients after carotid endarterectomy

Introduction. Surgical treatment of the extracranial section of internal carotid artery stenosis is an effective method of preventing cerebral ischaemic stroke. However, this surgical procedure may cause vascular brain damage. The aim of the study was to measure glial fibrillary acidic protein (GFAP) as a marker of brain damage in the serum of patients that underwent internal carotid endarterectomy (CEA). Material and methods. This study involved 25 participants who underwent CEA because of internal carotid artery stenosis. Blood samples were taken from each patient at three different times; within 24 hours prior to surgery, 12 hours after the surgery, and 48 hours after the surgery. Serum GFAP levels were measured by a commercially available enzyme-linked immunosorbent assay (ELISA). Results. The study showed that serum GFAP levels were not statistically different between all the three measurements (p > 0.05). There was also no statistical significant difference in serum GFAP levels between symptomatic and asymptomatic patients (p > 0.05). There was no statistically significant correlation in serum GFAP level 12 and 48 hours after the surgery with the clamping time (p > 0.05). There was also no significant correlation in the serum GFAP levels with the velocity of blood flow in the internal carotid artery before CEA and after surgery (p > 0.05). Conclusions. The study revealed that CEA does not change serum GFAP levels. Thus, GFAP cannot be a biochemical marker of brain damage after this surgery

Synergy, Additivity, and Antagonism between Cisplatin and Selected Coumarins in Human Melanoma Cells

(1) Cisplatin (CDDP) is used in melanoma chemotherapy, but it has many side effects. Hence, the search for natural substances that can reduce the dose of CDDP, and CDDP-related toxicity, is highly desired. Coumarins have many biological properties, including anticancer and antiproliferative effects. (2) An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on two human melanoma cell lines (FM55P and FM55M2) examined the antitumor properties of CDDP and five naturally occurring coumarins (osthole, xanthotoxin, xanthotoxol, isopimpinellin, and imperatorin). The antiproliferative effects produced by combinations of CDDP with the coumarins were assessed using type I isobolographic analysis. (3) The most potent anticancer properties of coumarins were presented by osthole and xanthotoxol. These compounds were characterized by the lowest median inhibitory concentration (IC50) values relative to the FM55P and FM55M2 melanoma cells. Isobolographic analysis showed that for both melanoma cell lines, the combination of CDDP and osthole exerted synergistic and additive interactions, while the combination of CDDP and xanthotoxol exerted additive interactions. Combinations of CDDP with xanthotoxin, isopimpinellin, and imperatorin showed antagonistic and additive interactions in two melanoma cell lines. (4) The combination of CDDP and osthole was characterized by the most desirable synergistic interaction. Isobolographic analysis allows the selection of potential candidates for cancer drugs among natural substances

Correlation between CH2DS2-VASc Score and Serum Leptin Levels in Cardioembolic Stroke Patients: The Impact of Metabolic Syndrome

Objective. To determine adipokines levels in patients with different etiologic subtypes of acute ischemic stroke (AIS) and metabolic syndrome (MetS) status. Methods. Serum adiponectin, leptin, and resistin levels were determined by ELISA in 99 AIS patients and 59 stroke-free control group subjects. Stroke patients were grouped based on MetS, modified TOAST classification, and CHA2DS2-VASc scale in case of cardioembolic stroke following atrial fibrillation. Results. No differences were found in all adipokine serum levels between AIS patients and appropriately matched control group. MetS-AIS patients had significantly higher leptin levels (22.71 ± 19.01 ng/ml versus 8.95 ± 9.22 ng/ml, p<0.001) and lower adiponectin levels (10.71 ± 8.59 ng/ml versus 14.93 ± 10.95 ng/ml, p<0.05) than non-MetS-AIS patients. In patients with cardioembolic stroke, leptin levels were significantly higher than in remaining stroke cases (19.57 ± 20.53 ng/ml versus 13.17 ± 12.36 ng/ml, p<0.05) and CHA2DS2-VASc score positively correlated with leptin levels only (p<0.001). Analysis of individual components of CHA2DS2-VASc score showed that hypertension, female gender, and diabetes had greatest impact on elevated serum leptin level. Conclusion. This pilot study revealed that leptin could be a potential biomarker for risk stratification of cardioembolic stroke in MetS patients and that heterogeneity of stroke subtypes should be considered for more refined and precise clinical stroke studies

Serum neuron-specific enolase as a marker of brain ischemia-reperfusion injury in patients undergoing carotid endarterectomy

In patients with atherosclerotic stenosis of the extracranial segment of internal carotid artery, surgical intervention is an effective method to prevent cerebral ischemic stroke. However, this surgical procedure may cause vascular brain damage. The aim of the study was to investigate consequential brain ischemia-reperfusion injury by measuring the cerebral specific marker, neuronspecific enolase (NSE), in serum of patients having undergone internal carotid endarterectomy (CEA). The study involved 25 patients that underwent CEA due to internal carotid artery stenosis. Blood samples were obtained from each patient on three occasions: within 24 h prior to surgery, 12 h after surgery, and 48 h after surgery. Serum NSE levels were measured by a commercially available enzymelinked immunosorbent assay. The study showed that serum NSE level was statistically significantly increased 48 h after CEA as compared with the level 12 h after surgery and the level before surgery (p0.05). Data from our study showed CEA to affect serum NSE in patients with significant internal carotid artery stenosis. Thus, serum NSE may be used as a biochemical marker of brain ischemia-reperfusion injury following CEA

Additive Interactions between Betulinic Acid and Two Taxanes in In Vitro Tests against Four Human Malignant Melanoma Cell Lines

The incidence of melanoma is steadily increasing worldwide. Melanoma is the most lethal skin cancer, and new therapeutic methods are being sought. Our research aimed to investigate the cytotoxic and antiproliferative effects of betulinic acid in vitro, used alone and in combination with taxanes (paclitaxel, docetaxel) in four melanoma cell lines. Isobolographic analysis allowed us to assess the interactions between these compounds. Betulinic acid had no cytotoxic effect on normal human keratinocyte HaCaT cells; the amount of LDH released by them was significantly lower compared to melanoma cell lines. The present study shows that betulinic acid significantly inhibits the growth of melanoma cell lines in vitro. The IC50 values of betulinic acid ranged from 2.21 µM to 15.94 µM against the four melanoma lines. Co-treatment of betulinic acid with paclitaxel or docetaxel generated desirable drug–drug interactions, such as an additive and additive with a tendency to synergy interactions

Isoquinoline Alkaloids from <i>Coptis chinensis</i> Franch: Focus on Coptisine as a Potential Therapeutic Candidate against Gastric Cancer Cells

Gastric cancer (GC) has high incidence rates and constitutes a common cause of cancer mortality. Despite advances in treatment, GC remains a challenge in cancer therapy which is why novel treatment strategies are needed. The interest in natural compounds has increased significantly in recent years because of their numerous biological activities, including anti-cancer action. The isolation of the bioactive compounds from Coptis chinensis Franch was carried out with the Centrifugal Partition Chromatography (CPC) technique, using a biphasic solvent system composed of chloroform (CHCl3)—methanol (MeOH)—water (H2O) (4:3:3, v/v) with an addition of hydrochloric acid and trietylamine. The identity of the isolated alkaloids was confirmed using a high resolution HPLC-MS chromatograph. The phytochemical constituents of Coptis chinensis such as berberine, jatrorrhizine, palmatine and coptisine significantly inhibited the viability and growth of gastric cancer cell lines ACC-201 and NCI-N87 in a dose-dependent manner, with coptisine showing the highest efficacy as revealed using MTT and BrdU assays, respectively. Flow cytometry analysis confirmed the coptisine-induced population of gastric cancer cells in sub-G1 phase and apoptosis. The combination of coptisine with cisplatin at the fixed-ratio of 1:1 exerted synergistic and additive interactions in ACC-201 and NCI-N87, respectively, as determined by means of isobolographic analysis. In in vivo assay, coptisine was safe for developing zebrafish at the dose equivalent to the highest dose active in vitro, but higher doses (greater than 10 times) caused morphological abnormalities in larvae. Our findings provide a theoretical foundation to further studies on more detailed mechanisms of the bioactive compounds from Coptis chinensis Franch anti-cancer action that inhibit GC cell survival in in vitro settings

Superior Antioxidant Capacity of Berberis iliensis—HPLC-Q-TOF-MS Based Phytochemical Studies and Spectrophotometric Determinations

The aim of the present study was to determine the composition, antiradical and antimicrobial activity of fruits, leaves and roots of an underestimated species of barberry&mdash;Berberis iliensis&mdash;growing in Kazakhstan. Particular attention was paid to the determination of the composition of its extracts by high-performance liquid chromatography coupled with mass spectrometry (HPLC-ESI-Q-TOF-MS) analysis. As a result of the chromatographic and spectrometric study 33 secondary metabolites from the groups of phenolic acids and their esters, flavonoids, alkaloids and organic acids were identified and 15 of them&mdash;quantified. The isomers of caffeoyl-glucaric acid, caffeic acid derivatives, isoquercetin, berberine and jatrorrhizine were the most abundant components of the tested extracts. The antiradical activity tests were performed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Folin-Ciocalteu assays on four types of extracts (water, ethanol, ethanol-water 7:3 v/v, ethanol-water 1:1 v/v) from the three organs of the plant. The highest antiradical potential (IC50 = 80 &plusmn; 6.36 &micro;g/mL) and phenolic content (440 &plusmn; 17.1 mg gallic acid equivalents/L) was calculated for ethanol- water (1:1 v/v) extracts from the leaves and could be influenced by the abundant presence of simple phenolic acids, flavonoids and glucaric acid esters. Among reference microorganisms, M. luteus, S. epidermidis, some S. aureus and B. cereus belonging to Gram-positive bacteria and yeasts from Candida species were the most sensitive to roots extract that was found the most active among the studied samples. The results of the study classify Berberis iliensis as a strong antioxidant agent and as a plant with an antimicrobial potential