Computed tomography is better than echocardiography in predicting balloon-expandable transcutaneous implantation valve size in a real-world clinical practice single-center study.

AIMS: Transcatheter aortic valve replacement (TAVR) has become the standard of care for selected patients with severe aortic stenosis. Multidetector computed tomography (MDCT) and transoesophageal 2D/3D (two-dimensional/three-dimensional) echocardiography (ECHO) are used for aortic annulus (AA) sizing. The aim of this study was to compare the accuracy of AA sizing by ECHO versus MDCT for Edwards Sapien balloon expandable valve in a single center. METHODS AND RESULTS: Data from 145 consecutive patients with TAVR (Sapien XT or Sapien S3) were analyzed retrospectively. A total of 139 (96%) patients had favorable outcomes after TAVR (at most mild aortic regurgitation and only one valve implanted). The 3D ECHO AA area and area-derived diameter were smaller than the corresponding MDCT parameters (464 ± 99 vs. 479 ± 88 mm2 , p < .001, and 24.2 ± 2.7 vs. 25.0 ± 5.5 mm, p = .002, respectively). The 2D ECHO annulus measurement was smaller than both the MDCT and 3D ECHO area-derived diameters (22.6 ± 2.9 vs. 25.0 ± 5.5 mm, p = .013, and 22.6 ± 2.9 vs. 24.2 ± 2.7 mm, p < .001, respectively) but larger than the minor axis diameter of the AA derived from MDCT and 3D ECHO by multiplanar reconstruction (p < .001). The 3D ECHO circumference-derived diameter was also smaller than the MDCT circumference-derived diameter (24.3 ± 2.5 vs. 25.0 ± 2.3, p = .007). The sphericity index by 3D ECHO was smaller than that by MDCT (1.2 ± .1 vs. 1.3 ± .1, p < .001). In up to 1/3 of the patients, 3D ECHO measurements would have predicted different (generally smaller) valve size than was the valve size implanted with favorable result. The concordance of the implanted valve size with the recommended size based on preprocedural MDCT and 3D ECHO AA area was 79.4% versus 61% (p = .001), and for the area-derived diameter, the concordance was 80.1% versus 61.7% (p = .001). 2D ECHO diameter concordance was similar to MDCT (78.7%). CONCLUSIONS: 3D ECHO AA measurements are smaller than MDCT measurements. If 3D ECHO-based parameters alone are used to size the Edwards Sapien balloon expandable valve, then the selected valve size would have been smaller than the valve size implanted with favorable result in 1/3 of the patients. MDCT preprocedural TAVR assessment should be the preferred method over 3D ECHO in routine clinical practice to determine Edwards Sapien valve size.

Ecotoxicity and Biodegradation of Sustainable Environment-Friendly Bone-Glue-Based Adhesive Suitable for Insulation Materials.

Bone glue with sodium lignosulfonate is a protein-based adhesive. Their combination leads to strong binding necessary for the achievement of adhesive properties. However, biodegradation and ecotoxicity of materials composed of bone glue and sodium lignosulfonate has never been studied before. In this paper, the biodegradation potential of the mixture of bone glue, lignosulfonate and rape straw modified by water or NaOH on an agar test with aerial molds and in acute aquatic tests with mustard, yeasts, algae and crustaceans was analyzed. Epoxy resin as an ecologically unfriendly binder was used as a negative control and pure rape straw as a background. The results indicated that all samples were covered by molds, but the samples containing straw treated by NaOH showed lower biodegradability. The ecotoxicological effects varied among the applied model organisms. Artemia salina was not able to survive and S. alba could not prolong roots in the eluates of all samples (100% inhibition). Freshwater algae (D. subspicatus) were not significantly affected by the samples (max. 12% inhibition, max. 16% stimulation). The biomass of yeasts (S. cerevisae) was strongly stimulated in the presence of eluates in a comparison to control (max. 38% stimulation).

The relationship between symptom onset-to-needle time and ischemic outcomes in patients with acute myocardial infarction treated with primary PCI: Observations from Prague-18 Study.

OBJECTIVES: Based on previous studies with clopidogrel, the time between acute myocardial infarction (AMI) symptoms onset and primary percutaneous coronary intervention (PCI) was proven as important prognostic factor. Our aim was to assess the relationship between symptoms onset to needle time (SNT) and procedural results and the occurrence of ischemic endpoints in primary angioplasty patients treated with potent P2Y12 inhibitors. METHODS: A total of 1,131 out of 1,230 patients randomized to the Prague-18 study (prasugrel vs. ticagrelor in primary PCI) were divided into a high and a low-risk group. The effect of defined SNT on patients' ischemic endpoints and prognosis by their risk status at admission was tested. RESULTS: The median SNT was 3.2 hours. Longer SNTs resulted in a more frequent incidence of TIMI flow <3 post PCI (p=0.015). There were significant differences in the occurrence of the combined ischemic endpoint among the compared SNT groups at 30 days (p=0.032), and 1 year (p=0.011), with the highest incidence in the ≤1 h SNT group of patients. "Latecomers" (SNT>4 hs) in the high-risk group experienced more reinfarction within 1 year [OR (95% CI) 3.23 (1.09-9.62) p=0.035]; no difference was found in the low-risk group. CONCLUSIONS: In the era of intense antithrombotic medication, stratification of MI patients undergoing primary angioplasty, based on initial ischemic risk assessment affected prognosis more than symptom onset to needle time. Longer time delay was significantly related to increased incidence of ischemic events and all-cause mortality only in patients with high ischemic risk.

Stent Selection for Primary Angioplasty and Outcomes in the Era of Potent Antiplatelets. Data from the Multicenter Randomized Prague-18 Trial.

Drug-eluting stents (DES) are the recommended stents for primary percutaneous coronary intervention (PCI). This study aimed to determine why interventional cardiologists used non-DES and how it influenced patient prognoses. The efficacy and safety outcomes of the different stents were also compared in patients treated with either prasugrel or ticagrelor. Of the PRAGUE-18 study patients, 749 (67.4%) were treated with DES, 296 (26.6%) with bare-metal stents (BMS), and 66 (5.9%) with bioabsorbable vascular scaffold/stents (BVS) between 2013 and 2016. Cardiogenic shock at presentation, left main coronary artery disease, especially as the culprit lesion, and right coronary artery stenosis were the reasons for selecting a BMS. The incidence of the primary composite net-clinical endpoint (EP) (death, nonfatal myocardial infarction, stroke, serious bleeding, or revascularization) at seven days was 2.5% vs. 6.3% and 3.0% in the DES, vs. with BMS and BVS, respectively (HR 2.7; 95% CI 1.419-5.15, p = 0.002 for BMS vs. DES and 1.25 (0.29-5.39) p = 0.76 for BVS vs. DES). Patients with BMS were at higher risk of death at 30 days (HR 2.20; 95% CI 1.01-4.76; for BMS vs. DES, p = 0.045) and at one year (HR 2.1; 95% CI 1.19-3.69; p = 0.01); they also had a higher composite of cardiac death, reinfarction, and stroke (HR 1.66; 95% CI 1.0-2.74; p = 0.047) at one year. BMS were associated with a significantly higher rate of primary EP whether treated with prasugrel or ticagrelor. In conclusion, patients with the highest initial risk profile were preferably treated with BMS over BVS. BMS were associated with a significantly higher rate of cardiovascular events whether treated with prasugrel or ticagrelor.

The Effect of Diabetes on Prognosis Following Myocardial Infarction Treated with Primary Angioplasty and Potent Antiplatelet Therapy.

PURPOSE: To investigate the prognostic significance of diabetes mellitus (DM) in patients with high risk acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) in the era of potent antithrombotics. METHODS: Data from 1230 ST-segment elevation myocardial infarction (STEMI) patients enrolled in the PRAGUE-18 (prasugrel vs. ticagrelor in pPCI) study were analyzed. Ischemic and bleeding event rates were calculated for patients with and without diabetes. The independent impact of diabetes on outcomes was evaluated after adjustment for outcome predictors. RESULTS: The prevalence of DM was 20% (N = 250). Diabetics were older and more often female. They were more likely to have hypertension, hyperlipoproteinemia, multivessel coronary disease and left main disease, and be obese. The primary net-clinical endpoint (EP) containing death, spontaneous nonfatal MI, stroke, severe bleeding, and revascularization at day 7 occurred in 6.1% of patients with, and in 3.5% of patients without DM (HR 1.8; 95% CI 0.978-3.315; P = 0.055). At one year, the key secondary endpoint defined as cardiovascular death, spontaneous MI, or stroke occurred in 8.8% with, and 5.5% without DM (HR 1.621; 95% CI 0.987-2.661; P = 0.054). In those with DM the risk of total one-year mortality (6.8% vs. 3.9% (HR 1.773; 95% CI 1.001-3.141; P = 0.047)) and the risk of nonfatal reinfarction (4.8% vs. 2.2% (HR 2.177; 95% CI 1.077-4.398; P = 0.026)) were significantly higher compared to in those without DM. There was no risk of major bleeding associated with DM (HR 0.861; 95% CI 0.554-1.339; P = 0.506). In the multivariate analysis, diabetes was independently associated with the one-year risk of reinfarction (HR 2.176; 95% Confidence Interval, 1.055-4.489; p = 0.035). CONCLUSION: Despite best practices STEMI treatment, diabetes is still associated with significantly worse prognoses, which highlights the importance of further improvements in the management of this high-risk population.

The prognostic significance of periprocedural infarction in the era of potent antithrombotic therapy. The PRAGUE-18 substudy.

BACKGROUND: The prognostic significance of periprocedural myocardial infarction (MI) remains controversial. METHODS AND RESULTS: The study aims to investigate the incidence of periprocedural MI in the era of high sensitivity diagnostic markers and intense antithrombotics, and its impact on early outcomes of patients with acute MI treated with primary angioplasty (pPCI). Data from the PRAGUE-18 (prasugrel versus ticagrelor in pPCI) study were analyzed. The primary net-clinical endpoint (EP) included death, spontaneous MI, stroke, severe bleeding, and revascularization at day 7. The key secondary efficacy EP included cardiovascular death, spontaneous MI, and stroke within 30 days. The incidence of peri-pPCI MI was 2.3% (N = 28) in 1230 study patients. The net-clinical EP occurred in 10.7% of patients with, and in 3.6% of patients without, peri-pPCI MI (HR 2.92; 95% CI 0.91-9.38; P = 0.059). The key efficacy EP was 10.7% and 3.2%, respectively (HR 3.44; 95% CI 1.06-11.13; P = 0.028). Patients with periprocedural MI were at a higher risk of spontaneous MI (HR 6.19; 95% CI 1.41-27.24; P = 0.006) and stent thrombosis (HR 10.77; 95% CI 2.29-50.70; P = 0.003) within 30 days. Age, hyperlipidemia, multi-vessel disease, post-procedural TIMI <3, pPCI on circumflex coronary artery, and periprocedural GP IIb/IIIa inhibitor were independent predictors of peri-pPCI MI. CONCLUSIONS: In the era of intense antithrombotic therapy, the occurrence of peri-pPCI MI is despite highly sensitive diagnostic markers a rare complication, and is associated with an increased risk of early reinfarction and stent thrombosis.

1-Year Outcomes of Patients Undergoing Primary Angioplasty for Myocardial Infarction Treated With Prasugrel Versus Ticagrelor.

BACKGROUND: Early outcomes of patients in the PRAGUE-18 (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction) study did not find any significant differences between 2 potent P2Y12 inhibitors. OBJECTIVES: The 1-year follow-up of the PRAGUE-18 study focused on: 1) a comparison of efficacy and safety between prasugrel and ticagrelor; and 2) the risk of major ischemic events related to an economically motivated post-discharge switch to clopidogrel. METHODS: A total of 1,230 patients with acute myocardial infarction (MI) treated with primary percutaneous coronary intervention were randomized to prasugrel or ticagrelor with an intended treatment duration of 12 months. The combined endpoint was cardiovascular death, MI, or stroke at 1 year. Because patients had to cover the costs of study medication after hospital discharge, some patients decided to switch to clopidogrel. RESULTS: The endpoint occurred in 6.6% of prasugrel patients and in 5.7% of ticagrelor patients (hazard ratio: 1.167; 95% confidence interval: 0.742 to 1.835; p = 0.503). No significant differences were found in: cardiovascular death (3.3% vs. 3.0%; p = 0.769), MI (3.0% vs. 2.5%; p = 0.611), stroke (1.1% vs. 0.7%; p = 0.423), all-cause death (4.7% vs. 4.2%; p = 0.654), definite stent thrombosis (1.1% vs. 1.5%; p = 0.535), all bleeding (10.9% vs. 11.1%; p = 0.999), and TIMI (Thrombolysis In Myocardial Infarction) major bleeding (0.9% vs. 0.7%; p = 0.754). The percentage of patients who switched to clopidogrel for economic reasons was 34.1% (n = 216) for prasugrel and 44.4% (n = 265) for ticagrelor (p = 0.003). Patients who were economically motivated to switch to clopidogrel had (compared with patients who continued the study medications) a lower risk of major cardiovascular events; however, they also had lower ischemic risk. CONCLUSIONS: Prasugrel and ticagrelor are similarly effective during the first year after MI. Economically motivated early post-discharge switches to clopidogrel were not associated with an increased risk of ischemic events. (Comparison of Prasugrel and Ticagrelor in the Treatment of Acute Myocardial Infarction [PRAGUE-18]; NCT02808767).

Prasugrel Versus Ticagrelor in Patients With Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention: Multicenter Randomized PRAGUE-18 Study.

BACKGROUND: No randomized head-to-head comparison of the efficacy and safety of ticagrelor and prasugrel has been published in the 7 years since the higher efficacy of these newer P2Y12 inhibitors were first demonstrated relative to clopidogrel. METHODS: This academic study was designed to compare the efficacy and safety of prasugrel and ticagrelor in acute myocardial infarction treated with primary or immediate percutaneous coronary intervention. A total of 1230 patients were randomly assigned across 14 sites to either prasugrel or ticagrelor, which was initiated before percutaneous coronary intervention. Nearly 4% were in cardiogenic shock, and 5.2% were on mechanical ventilation. The primary end point was defined as death, reinfarction, urgent target vessel revascularization, stroke, or serious bleeding requiring transfusion or prolonging hospitalization at 7 days (to reflect primarily the in-hospital phase). This analysis presents data from the first 30 days (key secondary end point). The total follow-up will be 1 year for all patients and will be completed in 2017. RESULTS: The study was prematurely terminated for futility. The occurrence of the primary end point did not differ between groups receiving prasugrel and ticagrelor (4.0% and 4.1%, respectively; odds ratio, 0.98; 95% confidence interval, 0.55-1.73; P=0.939). No significant difference was found in any of the components of the primary end point. The occurrence of key secondary end point within 30 days, composed of cardiovascular death, nonfatal myocardial infarction, or stroke, did not show any significant difference between prasugrel and ticagrelor (2.7% and 2.5%, respectively; odds ratio, 1.06; 95% confidence interval, 0.53-2.15; P=0.864). CONCLUSIONS: This head-to-head comparison of prasugrel and ticagrelor does not support the hypothesis that one is more effective or safer than the other in preventing ischemic and bleeding events in the acute phase of myocardial infarction treated with a primary percutaneous coronary intervention strategy. The observed rates of major outcomes were similar but with broad confidence intervals around the estimates. These interesting observations need to be confirmed in a larger trial. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02808767.

Application of the DETECT algorithm for detection of risk of pulmonary arterial hypertension in systemic sclerosis: data from a Czech tertiary centre.

OBJECTIVE: The early, simple and reliable detection of pulmonary arterial hypertension (PAH) in SSc (DETECT) study described a new algorithm for early detection of PAH in patients with SSc. The aim of this retrospective, single-centre, cross-sectional study was to apply a modified DETECT calculator in patients with SSc in the East Bohemian region, Czech Republic, to assess the risk of PAH and to compare these results with PAH screening based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 2009 guidelines. METHODS: Sixty patients were recruited with a diagnosis of SSc (according to ACR criteria), aged 27-78 years. A modified DETECT algorithm using the modified parameter of (1.4 × right ventricle diameter)(2) in place of right atrium area was applied to all patients. Right heart catheterization (RHC) was performed in all patients with an estimated (by echocardiography) increased systolic pulmonary artery pressure ≥50 mm Hg in accordance with the ESC/ERS guidelines; however, RHC was not performed in patients solely recommended for RHC using the modified DETECT algorithm. RESULTS: Using the modified DETECT calculator, 24/58 (41.4%) patients were recommended for RHC, compared with 14/58 (24.1%) when applying the ESC/ERS 2009 guidelines. PAH was diagnosed in 7/58 (12.1%) patients. During follow-up, PAH was diagnosed in six patients. Of these, four were modified DETECT score-positive for 2 years and all for 1 year before PAH diagnosis. CONCLUSION: The modified DETECT algorithm detects all patients with PAH diagnosed according to ECS/ERS 2009 guidelines and RHC. Data of the 2-year follow-up indicate a possible positive predictive role for the modified DETECT calculator.

Histopathology of aspirated thrombi during primary percutaneous coronary intervention in patients with acute myocardial infarction.

Thrombus aspiration in the setting of primary percutaneous coronary intervention is a recently recommended technique that facilitates thrombus removal from the culprit lesions in acute myocardial infarction (AMI) patients. Thrombectomy specimens from 50 patients with symptoms of AMI lasting usually not more than 12 h were examined by methods of routine histology, immunohistochemistry (IHC), and electron microscopy (ELMI). In 36 patients, there were fresh thrombi, in 10 older thrombi (8 of them with simultaneous presence of a fresh thrombi) and in 3 atheroma material only (in additional 7 patients atheroma material was admixed to the thrombi), and in one patient, there was carcinoma embolus. To help to distinguish between fresh and older thrombi, we recommend IHC (presence of macrophages and endothelia) and ELMI (loss of density of the erythrocyte matrix and presence of macrophages). On the other hand, changes of neutrophils (IHC degranulation/lysis) and of platelets (ELMI degranulation) appear early and thus contribute little to distinguishing between fresh and older thrombi. It could be concluded that, in a substantial proportion of patients with AMI, there is a discrepancy between duration of the symptoms and microscopic picture of the coronary thrombus. The thrombus may apparently be symptomless for a period of days or even weeks.

ST-segment elevation myocardial infarction treated by radial or femoral approach in a multicenter randomized clinical trial: the STEMI-RADIAL trial.

OBJECTIVES: This study sought to compare radial and femoral approaches in patients presenting with ST-segment elevation myocardial infarction (STEMI) and undergoing primary percutaneous coronary intervention (PCI) by high-volume operators experienced in both access sites. BACKGROUND: The exact clinical benefit of the radial compared to the femoral approach remains controversial. METHODS: STEMI-RADIAL (ST Elevation Myocardial Infarction treated by RADIAL or femoral approach) was a randomized, multicenter trial. A total of 707 patients referred for STEMI <12 h of symptom onset were randomized in 4 high-volume radial centers. The primary endpoint was the cumulative incidence of major bleeding and vascular access site complications at 30 days. The rate of net adverse clinical events (NACE) was defined as a composite of death, myocardial infarction, stroke, and major bleeding/vascular complications. Access site crossover, contrast volume, duration of intensive care stay, and death at 6 months were secondary endpoints. RESULTS: The primary endpoint occurred in 1.4% of the radial group (n = 348) and 7.2% of the femoral group (n = 359; p = 0.0001). The NACE rate was 4.6% versus 11.0% (p = 0.0028), respectively. Crossover from radial to femoral approach was 3.7%. Intensive care stay (2.5 ± 1.7 days vs. 3.0 ± 2.9 days, p = 0.0038) as well as contrast utilization (170 ± 71 ml vs. 182 ± 60 ml, p = 0.01) were significantly reduced in the radial group. Mortality in the radial and femoral groups was 2.3% versus 3.1% (p = 0.64) at 30 days and 2.3% versus 3.6% (p = 0.31) at 6 months, respectively. CONCLUSIONS: In patients with STEMI undergoing primary PCI by operators experienced in both access sites, the radial approach was associated with significantly lower incidence of major bleeding and access site complications and superior net clinical benefit. These findings support the use of the radial approach in primary PCI as first choice after proper training. (Trial Comparing Radial and Femoral Approach in Primary Percutaneous Coronary Intervention [PCI] [STEMI-RADIAL]; NCT01136187).

Movement of the patient and the cone beam computed tomography scanner: objectives and possible solutions.

OBJECTIVE: This study aimed (1) to determine whether scanner arm rotation causes significant movement of the head restraint and (2) to measure patient movement and its variation during the scan. STUDY DESIGN: The iCAT scanner and a high-speed camera were used. The 40 patients were divided into 2 groups: the open-eyed group and the blindfolded group. RESULTS: The mean level of head restraint movement was 0.130 mm, with a significantly higher level at the beginning, probably owing to the accelerating arm. Mean movement of patients was 1.135 mm and 1.119 mm in the open-eyed and blindfolded groups, respectively. Patient movement was also significantly higher at the beginning of the scan, when noise and vibrations are likely to surprise the patient. CONCLUSIONS: Patient instruction and a dry-run scan should be done by clinicians. Manufacturers should consider separating the seat and head restraint from the rest of the scanner to avoid vibration transfer.

Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia.

Sequential use of chemotherapy and reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (SCT) has been proposed to improve the treatment outcomes in patients with high-risk acute myeloid leukemia (AML). Here, we present our experience with this procedure in a cohort of 60 AML patients with primary induction failure (n = 9); early, refractory, or ≥ second relapse (n = 41); or unfavorable cytogenetics (n = 10). A combination of fludarabine (30 mg/m²/day), cytarabine (2 g/m²/day), and amsacrine (100 mg/m²/day) for 4 days was used. After 3 days of rest, RIC was carried out, consisting of 4 Gy total body irradiation, antithymocyte globulin (ATG-Fresenius), and cyclophosphamide (fludarabine, amsacrine, and cytarabine (FLAMSA)-RIC protocol). Prophylactic donor lymphocyte infusions (pDLIs) were given in patients with complete remission (CR) and without evidence of graft-versus-host disease ≥120 days after SCT. The median time of neutrophil engraftment was 17 days. CR was achieved in 47 of 60 patients (78%). Eleven patients received pDLIs resulting in long-term CR in eight of them. Non-relapse mortality after 1 and 3 years was 25 and 28%, respectively. With a median follow-up of 37 months (range, 10-69), 3-year overall survival and 3-year progression-free survival were 42 and 33%, respectively. In a multivariate analysis, dose of CD34(+) cells >5 × 106/kg (p = 0.005; hazard ratio (HR) = 0.276), remission of AML before SCT (p = 0.044; HR = 0.421), and achievement of complete chimerism after SCT (p = 0.001; HR = 0.205) were significant factors of better overall survival. The use of the FLAMSA-RIC protocol in suitable high-risk AML patients results in a long-term survival rate of over 40%.

New synthetic pyridine derivate as potential elicitor in production of isoflavonoids and flavonoids in Trifolium pratense L. suspension culture.

The production of secondary metabolites in Trifolium pratense L. suspension culture of the family of legume plants (Fabaceae) is low, and therefore there was an attempt to increase it by elicitation. New synthetic substance, 2-(2-fluoro-6-nitrobenzylsulfanyl)pyridine-4-carbothioamide, was tested as elicitor--a substance that showed the best elicitation effect after 48-hour application of 1 µmol L⁻¹ concentration. Maximum contents of genistin (11.60 mg g⁻¹ DW), daidzein (8.31 mg g⁻¹ DW), and genistein (1.50 mg g⁻¹ DW) were recorded, and the production of these isoflavonoids thus significantly increased, when compared with the control, by 152%, 151%, and 400%. The maximum content of flavonoids (5.78 mg g⁻¹ DW) and the increase in the production by 142%, when compared with the control, were induced by 6-hour application of 100 µmol L⁻¹ concentration. The tested substance showed to be an effective elicitor of phenylpropane metabolism.

The inhibition activity of selected beta-carboline alkaloids on enzymes of acetylcholinesterase and butyrylcholinesterase.

This thesis deals with testing of inhibition activity beta-carboline alkaloids on activity of enzymes acetylcholinesterase (ACHE) and butyrylcholinesterase (BUCHE) using test "Fast Blue B salt" at TLC desk and Ellman's test using spectrophotometer. It was also investigated how dimethylsulfoxide used as a solvent in combination with water affects activity of enzymes and alkaloids. Results show harmine in form of base and salt in water and in mixture of DMSO and water has the hightest inhibition activity on ACHE using eserine as reference substance. Harmalol in form of salt in water and harmine in form of base and salt in mixture of DMSO and water has the hightest activity on BUCHE. It was find out that DMSO considerably affects activity of enzymes and alkaloids.

Role of ischemia-modified albumin in estimating the extent and scope of cardiac ischemia in patients with ST elevation myocardial infarction.

Ischemia-modified albumin (IMA) is a laboratory biomarker of cardiac ischemia. Our study aims to determine whether IMA can estimate or represent to any degree the extent of myocardial ischemia. We expect that the higher the marker of cardiac necrosis (maximum value after serial measurements) the greater the preceding cardiac ischemia, indicated by IMA in patients diagnosed with STEMI prior to direct percutaneous coronary intervention (PCI). We studied 216 patients indicated for direct PCI with a diagnosis of ST elevation myocardial infarction. Biochemical analysis of IMA was carried out using the albumin cobalt binding (ACB®) test. We also obtained relevant values for markers of myocardial necrosis (CK, CK-MB, cTnT). In all patients, there was an increased level of IMA prior to the procedure (116 ± 16.9 kU/l); also raised were levels of CK (17.32 µkat/l), CK-MB (4.85 µkat/l) and cTnT (2.97 µg/l) taken as the maximum values obtained after serial measurements at 12, 18, and 24 h after the procedure. We observed that there was no significant association between increase in IMA and cTnT (R2 = 0.0068, p = 0.483). This was also the case for CK-MB (R2 = 0.0011, p = 0.637). IMA does not estimate the extent of ischemia in patients with ST elevation myocardial infarction. However, its absence can be used qualitatively to rule out cardiac ischemia.

Elicitation studies in cell suspension cultures of Cannabis sativa L.

Cannabis sativa L. plants produce a diverse array of secondary metabolites. Cannabis cell cultures were treated with biotic and abiotic elicitors to evaluate their effect on secondary metabolism. Metabolic profiles analysed by (1)H NMR spectroscopy and principal component analysis (PCA) showed variations in some of the metabolite pools. However, no cannabinoids were found in either control or elicited cannabis cell cultures. Tetrahydrocannabinolic acid (THCA) synthase gene expression was monitored during a time course. Results suggest that other components in the signaling pathway can be controlling the cannabinoid pathway.

Improved accumulation of ajmalicine and tetrahydroalstonine in Catharanthus cells expressing an ABC transporter.

The biosynthetic pathway of monoterpenoid indole alkaloids in Catharanthus roseus is located throughout various membranes at both the cellular and intercellular levels. ATP-binding cassette (ABC) transporters are known to export vincristine and vinblastine from human cancer cells. It has recently been shown that ABC transporters are also involved in the transport of various monoterpenoid alkaloids in Catharanthus roseus cells. Over-expression of an ABC transporter in this plant might therefore affect the regulation of the alkaloid biosynthetic pathway. CjMDR1, an ABC transporter gene originally isolated from Coptis japonica, was expressed in Catharanthus roseus cell cultures. Cells showing a positive PCR signal of the transgene in both cDNA and genomic DNA samples were subject to transport studies using selected substrates. Unexpectedly, transport of the isoquinoline alkaloid berberine, the main substrate of CjMDR1 transporter in Coptis japonica, was not affected as compared with control and wild-type Catharanthus cells. On the other hand, the endogenous alkaloids ajmalicine and tetrahydroalstonine were accumulated significantly more in Catharanthus roseus cells expressing CjMDR1 in comparison with control lines after feeding these alkaloids.