Adaptive frequency tracking of the baseline ECG identifies the site of atrial fibrillation termination by catheter ablation

Multiple organization indices have been used to predict the outcome of stepwise catheter ablation in long-standing persistent atrial fibrillation (AF), however with limited success. Our study aims at developing innovative organization indices from baseline ECG (i.e. during the procedure, before ablation) in order to identify the site of AF termination by catheter ablation. Seventeen consecutive male patients (age 60 ± 5 years, AF duration 7 ± 5 years) underwent a stepwise catheter ablation. Chest lead V6 was placed in the back (V6b). QRST cancelation was performed from chest leads V1 to V6b. Using an innovative adaptive harmonic frequency tracking, two measures of AF organization were computed to quantify the harmonics components of ECG activity: (1) the adaptive phase difference variance (APD) between the AF harmonic components as a measure of AF regularity, and (2) and adaptive organization index (AOI) evaluating the cyclicity of the AF oscillations. Both adaptive indices were compared to indices computed using a time-invariant approach: (1) ECG AF cycle length (AFCL), (2) the spectrum based organization index (OI), and (3) the time-invariant phase difference TIPD. Long-standing persistent AF was terminated into sinus rhythm or atrial tachycardia in 13/17 patients during stepwise ablation, 11 during left atrium ablation (left terminated patients – LT), 2 during the right atrium ablation (right terminated patients – RT), and 4 were non terminated (NT) and required electrical cardioversion. Our findings showed that LT patients were best separated from RT/NT before ablation by the duration of sustained AF and by AOI on chest lead V1 and APD from the dorsal lead V6b as compared to ECG AFCL, OI and TIPD, respectively. Our results suggest that adaptive measures of AF organization computed before ablation perform better than time-invariant based indices for identifying patients whose AF will terminate during ablation within the left atrium. These findings are indicative of a higher baseline organization in these patients that could be used to select candidates for the termination of AF by stepwise catheter ablation.     

Nonlinear synchronization assessment between atrial and ventricular activations series from the surface ECG in atrial fibrillation

Atrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice. Its presence causes a rapid and irregular ventricular response, being the topic of intensive research in rate control therapies of AF. To this respect, recent studies suggest that ventricular response is notably influenced by atrial activity (AA) temporal organization. However, the interdependency between atrial and ventricular activations has not been adequately explored to date in real-life AF patients. The present work introduces a novel methodology to quantitatively assess synchronization and coupling between real atrial and ventricular activation series. Furthermore, the method operates on surface ECG recordings, thus providing an easy and cost-effective way to be applied. The method is based on a nonlinear index, such as cross-sample entropy (CSE), which estimates the conditional probability to find similar patterns within both activation series. The study has been carried out on patients with paroxysmal and persistent AF in order to be applied over atrial activation series with different properties in their organization. Results showed a statistically significant positive correlation between AA organization and the synchronization between atrial and ventricular activations (R = 0.53, p < 0.01). Furthermore, higher CSE values were observed for persistent (0.759 ± 0.053) than for paroxysmal AF episodes (0.662 ± 0.091), thus suggesting more synchronization between atrial and ventricular activations in paroxysmal AF. As a consequence, CSE provided findings consistent with previous works and could be used to reveal clinically useful information in the improvement of current rate control therapies, which are mainly focused on controlling ventricular rate without paying much attention to the atrial fibrillatory process.     

Atrial flutter and atrial tachycardia detection using Bayesian approach with high resolution time–frequency spectrum from ECG recordings

Contemporary methods of atrial flutter (AFL), atrial tachycardia (AT), and atrial fibrillation (AF) monitoring, although superior to the standard 12-lead ECG and symptom-based monitoring, are unable to accurately discriminate between AF, AFL and AT. Thus, there is a need to develop accurate, automated, and comprehensive atrial arrhythmia detection algorithms using standard ECG recorders. To this end, we have developed a sensitive and real-time realizable algorithm for accurate AFL and AT detection using any standard electrocardiographic recording. Our novel method for automatic detection of atrial flutter and atrial tachycardia uses a Bayesian approach followed by a high resolution time–frequency spectrum. We find the TQ interval of the electrocardiogram (ECG) corresponding to atrial activity by using a particle filter (PF), and analyze the atrial activity with a high resolution time–frequency spectral method: variable frequency complex demodulation (VFCDM). The rationale for using a high-resolution time–frequency algorithm is that our approach tracks the time-varying fundamental frequency of atrial activity, where AT is within 2.0–4.0 Hz, AFL is within 4.0–5.3 Hz and NSR is found at frequencies less than 2.0 Hz. For classifications of AFL (n = 22), AT (n = 10) and normal sinus rhythms (NSR) (n = 29), we found that our approach resulted in accuracies of 0.89, 0.87 and 0.91, respectively; the overall accuracy was 0.88.     

The AV synchrogram: A novel approach to quantify atrioventricular coupling during atrial arrhythmias

The generation of ventricular response during atrial arrhythmias and its dependence on atrial activity is poorly understood. This paper introduces the atrioventricular (AV) synchrogram, a novel method for the beat-to-beat assessment of AV coupling during atrial arrhythmias, based on the stroboscopic observation of the ventricular phase at times triggered by atrial activation. The method was applied on a database of 120 atrial electrograms and ECG signals recorded in patients during typical atrial flutter (AFL), rapid atrial flutter (rAFL), and atrial fibrillation (AF). Synchronized epochs of different n:m order were automatically detected in the AV synchrogram and characterized in terms of percentage of significantly coupled beats (p_lb), maximal length of coupling segments (l_max), average conduction ratio (CR). Synchrogram analysis demonstrated that AV coupling and degree of conduction were significantly affected by the rate and regularity of atrial activity. The occurrence and stability of AV coupled epochs was maximal during regular atrial activation in AFL (median (interquartile range) of p_lb = 100 (100–100)%, l_max = 29.0 (28.5–29.4) s), and significantly (p < 0.001) decreased at faster atrial rates in rAFL (p_lb = 74.3 (57.6–100)%, l_max = 7.4 (3.9–28.7) s). A further decrease of coupling indexes occurred at higher irregularity of atrial activity in AF (p_lb = 25.7 (19.9–30.2)%, l_max = 2.1 (1.8–2.6) s). The increase of atrial rate led to a significant (p < 0.001) reduction of CRs from 0.50 (0.29–0.50) in AFL to 0.25 (0.22–0.25) in rAFL and 0.30 (0.24–0.35) in AF. Application of the analysis to the time course of AF showed the presence of a Farey sequence structure in n:m coupling patterns at increasing atrial rate, which was consistent with the scaling effect of nodal recovery on atrial beats. In conclusion, AV synchrogram analysis enables beat-to-beat assessment of AV coupling and dynamical tracking of AV response during atrial arrhythmias, which may favor mechanistic insight about the genesis of ventricular rhythms and potentially the development of efficacious rate control strategies.     

Atrioventricular nodal function during atrial fibrillation: Model building and robust estimation

Statistical modeling of atrioventricular (AV) nodal function during atrial fibrillation (AF) is revisited for the purpose of defining model properties and improving parameter estimation. The characterization of AV nodal pathways is made more detailed and the number of pathways is now determined by the Bayesian information criterion, rather than just producing a probability as was previously done. Robust estimation of the shorter refractory period (i.e., of the slow pathway) is accomplished by a Hough-based technique which is applied to a Poincaré plot of RR intervals. The performance is evaluated on simulated data as well as on ECG data acquired from AF patients during rest and head-up tilt test. The simulation results suggest that the refractory period of the slow pathway can be accurately estimated even in the presence of many artifacts. They also show that the number of pathways can be accurately determined. The results from ECG data show that the refined AV node model provides significantly better fit than did the original model, increasing from 85 ± 5% to 88 ± 4% during rest, and from 86 ± 5% to 87 ± 3% during tilt. When assessing the effect of sympathetic stimulation, the AF frequency increased significantly during tilt (6.25 ± 0.58 Hz vs. 6.32 ± 0.61 Hz, p < 0.05, rest vs. tilt) and the prolongation of the refractory periods of both pathways decreased significantly (slow pathway: 0.23 ± 0.20 s vs. 0.11 ± 0.10 s, p < 0.001, rest vs. tilt; fast pathway: 0.24 ± 0.31 s vs. 0.16 ± 0.19 s, p < 0.05, rest vs. tilt). The results show that AV node characteristics can be assessed noninvasively for the purpose of quantifying changes induced by autonomic stimulation.     

Molecular subtypes of ductal carcinoma in situ in African American and Caucasian American Women: Distribution and correlation with pathological features and outcome

Background: Molecular subtypes of breast cancer have been extensively studied in invasive carcinoma. They were shown to have a different distribution within the various ethnic populations. Few studies have applied the same classification to Ductal Carcinoma in Situ (DCIS). We report the distribution of the molecular breast cancer subtypes in DCIS between African American (AA) and Caucasian American (CA) women, their association with pathological features and outcome. Materials and methods: Tissue microarrays were constructed from paraffin blocks of 94 DCIS cases (67 AA and 27 CA) selected from a cohort of AA and CA patients diagnosed with DCIS between 1996 and 2000; mean age at diagnosis was 61 ± 12 for the AA and 58 ± 11 years for the CA group. TMA blocks were labeled with antibodies for ER, PR, HER2, Ki-67, and CK5/6. The cases were subtyped as Luminal A (ER+ and/or PR+; HER2?), Luminal B (ER+ and/or PR+; HER2+), HER2+ (ER?, PR?; HER2+), basal-like (BL) (ER?, PR?, HER2?; CK5/6+) or unclassified triple negative (UTN) (ER?, PR?, HER2?, CK5/6?). Information on grade, size and follow-up were obtained. Results: (1) Most DCIS cases were Luminal A, comprising 80% of the DCIS cases in AA and 92.6% in CA patients. (2) HER2+, BL and UTN DCIS subtypes were not seen in the CA population, and formed 9% of the DCIS cases in the AA population; these cases were all high grade. (3) In the cases with recurrence (8 AA and 1 CA patients), DCIS was Luminal A in 6 AA and 1 CA and Luminal B in 2 AA patients. Conclusion: The distribution of the molecular subtypes of DCIS did not show a significant difference between the two ethnic groups in our study. In addition, the risk of recurrence might not be higher in the non-luminal subtypes than in Luminal A and B.     

Interleukin-2 serum levels variations in recent onset atrial fibrillation are related with cardioversion outcome

We evaluated the hypothesis that a relationship exists between inflammation and the outcome of pharmaceutical cardioversion with amiodarone in recent onset atrial fibrillation. We studied 86 patients with symptomatic recent onset AF and coexisting hypertension and/or chronic stable coronary artery disease. All study participants underwent evaluation with a standardized protocol including echocardiography, cytokine level measurement [interleukin-2 (IL-2), interleukin-6 (IL-6) and high sensitivity C reactive protein (hsCRP)] on admission and at 48 h, and administration of intravenous amiodarone. By 48 h, 70 patients cardioverted to sinus rhythm. Median serum IL-2 levels on admission were higher in non-cardioverted compared to cardioverted patients (P = 0.002). At 48 h, non-cardioverted had significantly higher IL-6 (P = 0.005) and hsCRP values (P = 0.001) compared to cardioverted. Multivariate logistic regression analysis showed that lower IL-2 admission levels were a powerful independent predictor for successful cardioversion (OR: 0.154, 95% CI: 0.043–0.552, P = 0.004). In patients with hypertension and/or chronic stable coronary artery disease and symptomatic recent onset AF, low serum IL-2 levels on admission are associated with successful cardioversion with amiodarone. This observation highlights the role of inflammation in AF and might have further prognostic and therapeutic implications.     

A linear ablating system in the left and right atrium: feasibility, catheter performance and clinical results

IntroductionWe describe the use of a ablating system to compartmentalise and regionally isolate the atria in paroxysmal and persistent atrial fibrillation (AF).Methods40 patients were studied, 25 paroxysmal AF and 14 persistent AF. One patient enrolled was later found to be in left atrial flutter and was excluded. The Cardima Revelation® TX catheter system with Intellitemp® Radiofrequency (RF) energy control device and a Medtronic Atakar® RF generator were used to place wide area circumferential ablations to achieve conduction block into the left and right sided pulmonary veins. Roof lines and mitral isthmus lines were also performed. In patients with persistent AF and in repeat procedures, right atrial compartmentalisation was performed with an anterior superior vena cava (SVC) to inferior vena cava (IVC) line and a septal SVC to IVC line.ResultsAt 6 months, 18 of the 39 patients were asymptomatic, 10 had improved symptoms and 22 were in sinus rhythm. In the paroxysmal group, 11 were asymptomatic, 7 had improved symptoms and 16 (64%) were in sinus rhythm. In the persistent group, 7 were asymptomatic, 3 had improved symptoms and 6 (43%) were in sinus rhythm. The total group AF burden was 37.8 ± 5.4 hrs pre-procedure and 23.1 ± 5.1 hrs at 6 months post procedure. Mean temperature, impedance and power recorded at each pole demonstrated effective power delivery at all poles. No catheter charring was observed, complication rates were comparable to standard AF ablation technique.ConclusionLinear ablation in the left and right atria to mimic Cox’s Maze is feasible and safe using this ablating system.     

Discovery of arjunolic acid as a novel non-zinc binding carbonic anhydrase II inhibitor

Elevated levels of carbonic anhydrase II (CA II) have been shown to be associated with cardiac hypertrophy and heart failure. Although arjunolic acid (AA) has a diverse range of therapeutic applications including cardio-protection, there have been no reports on the effect of AA on CA II. The present study describes for the first time, the novel zinc independent inhibition of CA II by AA. The molecular docking studies of AA indicated that the hydroxyl group at C₂ of the A-ring, which hydrogen bonds with the catalytic site residues (His64, Asn62 and Asn67), along with the gem-dimethyl group at C₂₀ of the E-ring, greatly influences the inhibitory activity, independent of the catalytic zinc, unlike the inhibition observed with most CA II inhibitors. Among the triterpenoids tested viz. arjunolic acid, arjunic acid, asiatic acid, oleanolic acid and ursolic acid, AA was the most potent in inhibiting CA II in vitro with an IC₅₀ of 9 μM. It was interesting to note, that in spite of exhibiting very little differences in their structures, these triterpenoids exhibited vast differences in their inhibitory activities, with IC₅₀ values ranging from 9 μM to as high as 333 μM. Furthermore, AA also inhibited the cytosolic activity of CA in H9c2 cardiomyocytes, as reflected by the decrease in acidification of the intracellular pH (pH_i). The decreased acidification reduced the intracellular calcium levels, which further prevented the mitochondrial membrane depolarization. Thus, these studies provide a better understanding for establishing the novel molecular mechanism involved in CA II inhibition by the non-zinc binding inhibitor AA.     

Discovery of a class of potent gap-junction modifiers as novel antiarrhythmic agents

In an effort to discover potent, orally bioavailable compounds for the treatment of atrial fibrillation (AF) and ventricular tachycardia (VT), we developed a class of gap-junction modifiers typified by GAP-134 (1, R¹ = OH, R² = NH₂), a compound currently under clinical evaluation. Selected compounds with the desired in-vitro profile demonstrated positive in vivo results in the mouse CaCl₂ arrhythmia model upon oral administration.     

Genetic association of IL2RA,IL17RA,IL23R,and IL31RA single nucleotide polymorphisms with alopecia areata

The signalling of cytokine receptors plays a crucial role in regulating tolerance and immunity. Impaired immunological processes result in autoimmune inflammation that target the hair follicles, causing many hair disorders, mainly alopecia areata (AA). Therefore, polymorphisms in cytokine receptor genes are suggested to have a significant impact on the pathogenesis of AA, a disease with a multifactorial basis and uncertain etiology. In the present study, 152 AA patients of the Jordanian population were investigated for their genetic susceptibility to develop AA compared to 150 control subjects. Genomic DNA extraction and genotyping had conducted for IL17RA (rs879575, rs2229151, and rs4819554), IL2RA (rs3118470), IL23R (rs10889677), and IL31RA (rs161704) using the Sequenom MassARRAY® system. The allele frequency of IL17RA rs879575 is significantly higher in patients, while no statistical differences were found for IL2RA, IL23R, and IL31RA SNPs. Also, the recessive model of IL31RA rs161704 showing that AA genotype is significantly associated with AA development. To date, there is no published data regarding the association between AA and the selected genetic variants in our population. However, this study's findings assert that SNPs of IL17RA and IL31RA are linked to AA susceptibility in Jordanian patients.     

The −251A>T polymorphism of interleukin-8 is associated with longer mechanical ventilation and hospital staying after coronary surgery

Background: Cardiac surgery is associated with inflammatory responses that are known to affect its outcome. The present study was designed to define whether post-operative release of interleukin (IL)-6, 8 and tumor necrosis factor-alpha (TNF-α) is related to the presence of a certain allele in functional polymorphism and its relationship to clinical outcome after off-pump coronary artery bypass (OPCAB). Methods: One hundred and forty-five patients undergoing first time elective OPCAB were genotyped for IL-6(−174G>C), IL-8(−251A>T) and TNF-α(−308G>A) polymorphisms using polymerase chain reaction (PCR) and gene sequencing. Cytokine levels were measured in plasma samples taken before the operation and 4, 24 and 72 h postoperatively by suspension array system. Results: Levels of IL-6 and IL-8 increased significantly after OPCAB. Patients with IL-6−174GG and IL-8−251AA genotypes had higher post-operative circulating levels of IL-6 and IL-8, respectively. Logistic regression showed that IL-8−251AA genotype was an independent risk factor of ventilation time more than 1 day (OR = 11.80, 95% CI: 1.87–74.48) and hospital staying more than 14 days (OR = 38.00, 95% CI: 4.15–347.87) after surgery. Conclusions: OPCAB results in post-operative inflammatory responses. Genetic backgrounds alter the extent of inflammatory response and might relate to clinical outcome of OPCAB.     

Reduced incidence of skin cancer in patients with alopecia areata: A retrospective cohort study

The risk of skin cancer in patients with alopecia areata (AA) is unknown. While the risk of skin cancer in chronic inflammatory alopecias may be elevated, AA shares many characteristics with vitiligo, an autoimmune illness associated with decreased risk of melanoma and non-melanoma skin cancers. In this retrospective cohort study, we determined the risk of developing skin cancer among patients with AA in a validated cohort relative to matched controls at two tertiary care hospitals in Massachusetts. There was a significantly decreased risk of NMSC in AA patients than controls (OR = 0.63, 95% CI = 0.48–0.81). There was a trend towards a protective effect of AA associated with melanoma (OR = 0.65, 95% CI = 0.39–1.09). There was no difference in anatomic distribution of skin cancer between patients with AA and controls. Our study demonstrates a decreased risk of nonmelanoma skin cancer and a trend towards reduced risk of melanoma in patients with AA.     

Synthesis and carbonic anhydrase inhibitory properties of sulfamides structurally related to dopamine

A series of novel sulfamides incorporating the dopamine scaffold were synthesized. Reaction of amines and tert-butyl-alcohol/benzyl alcohol in the presence of chlorosulfonyl isocyanate (CSI) afforded sulfamoyl carbamates, which were converted to the title compounds by treatment with trifluoroacetic acid or by palladium-catalyzed hydrogenolysis. Inhibition of six α-carbonic anhydrases (CAs, EC 4.2.1.1), that is, CA I, CA II, CA VA, CA IX, CA XII and CA XIV, and two β-CAs from Candida glabrata (CgCA) and Mycobacterium tuberculosis (Rv3588) with these sulfamides was investigated. All CA isozymes were inhibited in the low micromolar to nanomolar range by the dopamine sulfamide analogues. K_is were in the range of 0.061–1.822 μM for CA I, 1.47–2.94 nM for CA II, 2.25–3.34 μM for CA VA, 0.041–0.37 μM for CA IX, 0.021–1.52 μM for CA XII, 0.007–0.219 μM for CA XIV, 0.35–5.31 μM for CgCA and 0.465–4.29 μM for Rv3588. The synthesized sulfamides may lead to inhibitors targeting medicinally relevant CA isoforms with potential applications as antiepileptic, antiobesity antitumor agents or anti-infective.     

Levels of l-ascorbic acid and cadmium in the saphenous vein of patients with coronary artery disease are negatively correlated

BackgroundThe aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels.MethodsHuman SV were collected from 40 patients (20 men and 20 women; age, 40–75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS—atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection.ResultsAA concentration (mean ± SD); men: 98,7 ± 13,18 μg/g tissue, women: 96,06 ± 11,98 μg/g tissue. Cadmium concentration(mean ± SD); men: 309 ± 103,71 ng/g tissue, women: 348,5 ± 255,71 ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r = −0,1504, p = 0,5269) and in the group women (Pearson r = −0339, p = 0144).ConclusionsNegative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium.     

STK15 rs2273535 polymorphism and cancer risk: A meta-analysis of 74,896 subjects

Background: It has been suggested that the serine/threonine kinase 15 (STK15) T91A rs2273535 polymorphism is associated with susceptibility to cancer. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. Methods: PubMed was searched to select studies. Case–control studies containing available genotype frequencies of the STK15 rs2273535 polymorphism were chosen, and the odds ratio (OR) with its 95% confidence interval (CI) was utilized to assess the strength of association. Results: 52 studies – including 34,057 cases and 40,839 controls – were identified. A significant effect of the STK15 rs2273535 polymorphism on cancer risk was found (AA vs. TT: OR = 1.13, 95%CI = 1.01–1.26, P_{heterogeneity} < 0.001; AA vs. TA/TT: OR = 1.12, 95%CI = 1.02–1.22, P_{heterogeneity} < 0.001; TA/AA vs. TT: OR = 1.06, 95%CI = 1.01–1.12, P_{heterogeneity} < 0.001). Stratified analysis by cancer type revealed that the STK rs2273535 polymorphism may contribute to the risk of breast cancer (AA vs. TT: OR = 1.21, 95%CI = 1.01–1.44, P_{heterogeneity} = 0.002), colorectal cancer (AA vs. TA/TT: OR = 1.24, 95%CI = 1.05–1.47, P_{heterogeneity} = 0.124), and esophageal cancer (AA vs. TA/TT: OR = 1.19, 95%CI = 1.02–1.39, P_{heterogeneity} = 0.148). Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (AA vs. TA/TT: OR = 1.20, 95%CI = 1.05–1.37, P_{heterogeneity} = 0.004). Conclusion: This meta-analysis suggests that the STK15 rs2273535 polymorphism is a candidate gene polymorphism for cancer susceptibility, especially in Asian populations.     

Multimodal information improves the rapid detection of mental fatigue

One of the major challenge in the detection of mental states is improving the accuracy of brain activity-based detectors with additional information from extracranial signals. We assessed the suitability, for real-time mental fatigue detection, of EEG, EOG and ECG measurements, taken separately or together. Thirteen subjects performed six blocks of switching tasks. For each participant, the block with the lowest error rate from the first two blocks and the block with the highest error rate from the last three blocks were discriminated with a machine learning algorithm (support vector machine). The classification scores obtained with ECG or EOG were greater than would be expected by chance (>50%) for time windows of at least 8 s. EEG was the best single mode of detection, with classification scores ranging from 80 ± 3% with a 4 s time window to 94 ± 2% with a 30 s time window. The addition of ECG and EOG features to EEG features significantly increased classification scores for short time windows (e.g., to 86 ± 3% with a 4 s time window, p < 0.001). For short time windows (up to 12 s), ECG significantly increased the discriminatory power of EEG, whereas EOG did not. These results demonstrate that mental state detection on the basis of extracerebral measurements is feasible and that a combination of EEG and ECG is particularly appropriate for the rapid detection of mental fatigue.     

Graft polymers of eucalyptus lignosulfonate calcium with acrylic acid: Synthesis and characterization

The graft copolymerization of eucalyptus lignosulfonate calcium (HLS-Ca) from hardwood and acrylic acid (AA) was investigated by using Fenton agent as a coinitiator. The influences of reaction conditions on grafting parameters i.e. product yield (Y%), AA conversion (C%), grafting ratio (G%) and grafting efficiency (GE%) were carefully studied. The effects of the phenolic hydroxyl (Ph-OH) group on the polymerization of AA and grafting reaction were researched. Graft copolymers were identified by the new absorption at 1727 cm^?1, more homogenized morphology and higher decomposition temperature after grafted with AA, as illustrated in FTIR, SEM and TG spectra. The optimum synthesis conditions are as follows: H₂O₂ = 25.2 mol/L, FeCl₂ = 63.0 mol/L, T = 50 °C and t = 2 h and the optimum percentages of Y, C, G and GE are 97.61%, 95.23%, 71.29% and 78.85%, respectively. The Ph-OH group of HLS-Ca cannot inhibit the polymerization of AA and is involved in the grafting reaction as an active center.     

Validation and implementation of a liquid chromatography/tandem mass spectrometry assay to quantitate aminoflavone (NSC 686288) in human plasma

A reverse-phase liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) method was developed and validated for determination of aminoflavone (AF) in human plasma. Sample preparation involved a liquid–liquid extraction by the addition of 0.25 mL of plasma with 1.0 mL ethyl acetate containing 50 ng/mL of the internal standard zileuton. The analytes were separated on a Waters X-Terra? MS C₁₈ column using a mobile phase consisting of methanol/water containing 0.45% formic acid (70:30, v/v) and isocratic flow at 0.2 mL/min for 6 min. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the AF concentration range of 5–2000 ng/mL in human plasma. The lower limit of quantitation (LLOQ) was 5 ng/mL for AF in human plasma. The accuracy and within- and between-day precisions were within the generally accepted criteria for bioanalytical method (<15%). This method was successfully applied to characterize AF plasma concentration-time profile in the cancer patients in a phase I trial.     

Semi-automated program for analysis of local Ca2+ spark release with application for classification of heart cell type

Local Ca²⁺ spark releases are essential to the Ca²⁺ cycling process. Thus, they play an important role in ventricular and atrial cell contraction, as well as in sinoatrial cell automaticity. Characterizing their properties in healthy cells from different regions in the heart can reveal the basic biophysical differences among these regions. We designed a semi-automatic Matlab Graphical User Interface (called Sparkalyzer) to characterize parameters of Ca²⁺ spark release from any major cardiac tissue, as recorded in line-scan mode with a confocal laser-scanning microscope. We validated the algorithm on experimental images from rabbit sinoatrial, atrial, and ventricular cells loaded with Fluo-4 AM. The program characterizes general image parameters of Ca²⁺ transients and sparks: spark duration, which indicates for how long the spark provides Ca²⁺ to the closed intracellular mechanisms (typical value: 25 ± 1, 23 ± 1, 26 ± 1 ms for sinoatrial, atrial, and ventricular cells, respectively); spark amplitude, which indicates the amount of Ca²⁺ released by a single spark (1.6 ± 0.1, 1.6 ± 0.2, 1.4 ± 0.1 F/F₀ for sinoatrial, atrial, and ventricular cells, respectively); spark length, which is the length of the Ca²⁺ wavelets fired out of a row of ryanodine receptors (5 ± 0.1, 5 ± 0.2, 3.4 ± 0.3 μm for sinoatrial, atrial, or ventricular cells, respectively) and number of sparks (0.14 ± 0.02, 0.025 ± 0.01, 0.02 ± 0.01 for 1 μm in 1 s for sinoatrial, atrial, and ventricular cells, respectively). This method is reliable for Ca²⁺ spark analysis of sinoatrial, atrial, or ventricular cells. Moreover, by examining the average value of Ca²⁺ spark characteristics and their scattering around the mean, atrial, ventricular and sinoatrial cells can be differentiated.