Angioplasty, stenting, or both - rescue maneuvers and reperfusion after endovascular therapy for intracranial atherosclerosis-related occlusion.

PURPOSE: Data concerning reperfusion strategies of intracranial atherosclerosis-related occlusion (ICARO) and clinico-angiographic outcomes remain scarce, particularly in Caucasians. We aim to compare the reperfusion rate and functional outcome between reperfusion strategies in the setting of the ICARO. METHODS: Retrospective analysis of prospectively maintained endovascular thrombectomy (EVT) registries at three high-volume stroke centers were retrospectively analyzed for consecutive ICARO patients from January 2015 to December 2019. We defined ICARO as any fixed high-degree (> 70%) focal narrowing or stenosis of any degree with a perpetual tendency for reocclusion. We categorized reperfusion strategies into four groups: EVT [group 1], balloon angioplasty [(BAp), group 2], placement of self-expandable stents [(SES), group 3], and BAp combined with implantation of SES; or direct placement of balloon mounted stents (BMS) [(BAp-SES/BMS), group 4]. We evaluated the association with the successful reperfusion [mTICI 2b - 3] and favorable outcome [mRS 0-2] with logistic regression analysis. RESULTS: Out of 2550 EVT, 124 patients (median age, 70 (61-80) years; 76 men) with ICARO and 130 reperfusion attempts [36 EVT, 38 BAp, 17 SES, and 39 BAp + SES/BMS] were analyzed. SES implantation showed the highest frequency of post-procedural symptomatic intracranial hemorrhage [(18%, 3/17), p = .03]; however, we observed no significant differences in the mortality rate. Overall, we achieved successful reperfusion in 71% (92/130) and favorable outcomes in 42% (52/124) of the patients. BAp + SES/BMS was the only independent predictor of the final successful reperfusion [aOR, 4.488 (95% CI, 1.364-14.773); p = .01], which was significantly associated with the 90-day favorable outcome [aOR, 10.837 (95% CI, 3.609-32.541); p = < .001] after adjustment for confounding variables between the reperfusion strategies. CONCLUSION: Among patients with ICARO, the rescue angioplasty stenting effectively contributed to higher odds of successful reperfusion with no increased risk for intracranial hemorrhage.

Frontline thrombectomy strategy and outcome in acute basilar artery occlusion.

BACKGROUND: Novel thrombectomy strategies emanate expeditiously day-by-day counting on access system, clot retriever device, proximity to and integration with the thrombus, and microcatheter disengagement. Nonetheless, the relationship between native thrombectomy strategies and revascularization success remains to be evaluated in basilar artery occlusion (BAO). PURPOSE: To compare the safety and efficacy profile of key frontline thrombectomy strategies in BAO. METHODS: Retrospective analyses of prospectively maintained stroke registries at two comprehensive stroke centers were performed between January 2015 and December 2019. Patients with BAO selected after MR imaging were categorized into three groups based on the frontline thrombectomy strategy (contact aspiration (CA), stent retriever (SR), or combined (SR+CA)). Patients who experienced failure of clot retrieval followed by an interchanging strategy were categorized as a fourth (switch) group. Clinicoradiological features and procedural variables were compared. The primary outcome measure was the rate of complete revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) grade 2c-3). Favorable outcome was defined as a 90 day modified Rankin Scale score of 0-2. RESULTS: Of 1823 patients, we included 128 (33 underwent CA, 35 SR, 35 SR +CA, and 25 switch techniques). Complete revascularization was achieved in 83/140 (59%) primarily analyzed patients. SR +CA was associated with higher odds of complete revascularization (adjusted OR 3.04, 95% CI 1.077 to 8.593, p=0.04) which was an independent predictor of favorable outcome (adjusted OR 2.73. 95% CI 1.152 to 6.458, p=0.02). No significant differences were observed for symptomatic intracranial hemorrhage, functional outcome, or mortality rate. CONCLUSION: Among BAO patients, the combined technique effectively contributed to complete revascularization that showed a 90 day favorable outcome with an equivalent complication rate after thrombectomy.

Complete recanalization predicts favorable outcome in patients with distal M2-M3 middle cerebral artery occlusions following endovascular thrombectomy.

BACKGROUND: - scanty articles illustrate the prognostic factors for favorable outcome after endovascular thrombectomy (EVT) in distal vessel occlusion (DMVO). Moreover, the current literature is diversified; conglomerating both primary, secondary, and anterior, posterior circulations embolic strokes in the same shell. PURPOSE: to identify the association between complete reperfusion and favorable outcome following EVT for DMVO in the middle cerebral artery (MCA) territory. METHODS: -we performed a retrospective analysis of prospectively maintained EVT registries at two comprehensive stroke centers between January 2015 and December 2019 for consecutive stroke patients with MCA-DMVO. DMVO was defined as an occlusion of distal M2 and M3 segments of the MCA. Only patients with primary isolated occlusions were included. A multivariate logistic regression was utilized to identify clinical and procedural-related factors associated with the 90-day favorable clinical outcome [defined as modified Rankin score (mRS) 0-2] after EVT. RESULTS: -Out of 1823 within the registries; 66 patients (median age was 72 (60-78) and 59% were males) with primary isolated DMVO of the MCA were eligible for inclusion in the current study. Complete reperfusion was achieved in 56% (37/66) of the patients with no difference among the reperfusion strategies while the favorable outcome was observed in 68% (45/66). In the multivariate analysis, final complete reperfusion [modified Thrombolysis In Cerebral Infarction (mTICI) score 2c-3] was significantly associated with favorable outcome [aOR=7.69; (95% CI 1.73-34.17); p=.01], while higher baseline NIHSS score [aOR=0.82; (95% CI 0.69-0.98); p=.03] and increased imaging to puncture interval [aOR=0.99; (95% CI 0.98, 1.00); p=.01] decreased the probability of the favorable outcome. CONCLUSION: according to our results, complete reperfusion was the most significant predictor of the favorable outcome, while higher baseline NIHSS and longer imaging to puncture interval decreased the probability of the favorable outcome.

Negative susceptibility vessel sign might be predictive of complete reperfusion in patients with acute basilar artery occlusion managed with thrombectomy.

OBJECTIVES: Negative susceptibility vessel sign (SVS) on pre-thrombectomy MRI has been linked to fibrin-rich thrombus and difficult retrieval in anterior ischemic stroke. However, its impact in posterior circulation-large vessel occlusion stroke (PC-LVOS) has not yet been elucidated. We aim to investigate the relationship of SVS parameters with stroke subtypes and their influence on angiographic and functional outcomes. METHODS: Prospective thrombectomy registries at two-comprehensive stroke centers were retrospectively reviewed between January 2015 and December 2019 for consecutive MRI-selected patients with PC-LVOS. Two groups were assigned by two independent readers, based on the presence or absence of the SVS (SVS +, SVS -) on MRI-GRE sequence. Multivariate logistic regression analysis was utilized to study primarily the impact of the SVS on the rate of complete recanalization (defined as mTICI 2c/3) at the final series following endovascular thrombectomy (EVT) and whether or not it might influence the efficacy of the frontline EVT strategy. Secondarily, we studied whether the absence of the SVS was predictive of the rate of 90-day functional independence (defined as mRS score < 2). Lastly, both qualitative (SVS +, SVS-) and quantitative (SVS length and diameter) parameters of the SVS were analyzed in association with the puncture to recanalization interval and various stroke etiological subtypes based on TOAST criteria. RESULTS: Among 1823 patients, 116 were qualified for final analysis (median age, 68 (59-75) years; male, 65%); SVS was detected in 62.9% (73/116) of cases. SVS length was an independent predictor of procedural duration (p = .01) whilst two-layered SVS was inversely associated with the atherosclerosis etiological subtype (aOR = 0.27, 95% CI 0.08-0.89; p = .03). Successful recanalization was achieved in 82% (60/73) vs. 86% (37/43), p = .80 of patients with SVS (+, -) respectively. Only in SVS (+), stentriever (RR 0.59 (0.4-0.88), p = .009), and contact-aspiration (RR 0.82 (0.7-0.96), p = .01) achieved a lower rate of successful recanalization compared to combined technique. SVS (-) was significantly associated with a higher rate of mTICI 2c/3 (aOR = 4.444; 95% CI 1.466-13.473; p = .008) and showed an indirect effect of 9% towards functional independence mediated by mTICI 2c/3. CONCLUSION: SVS parameters in PC-LVOS might predict stroke subtype and indirectly influence the functional outcome by virtue of complete recanalization. KEY POINTS: • Negative susceptibility vessel sign (SVS) in patients with basilar occlusion independently predict complete recanalization that indirectly instigated a 3-month favorable outcome following thrombectomy. • The longer the SVS, the higher likelihood of large artery atherosclerosis and the longer the thrombectomy procedure. • Two-layered SVS might be negatively associated with the presence of atherosclerosis, yet already-known limitations of TOAST classification and the absence of pathological analysis should be taken into consideration.

Value of therapeutic drug monitoring of endoxifen in Egyptian premenopausal patients with breast cancer given tamoxifen adjuvant therapy: A pilot study.

BACKGROUND: The complex metabolic profile of tamoxifen anticancer drug and polymorphism in its metabolizing enzymes particularly CYP2D6 contribute to the high-observed inter-individual variability in its main active metabolite endoxifen. Therapeutic drug monitoring of endoxifen may play a key role in optimizing tamoxifen therapy, and control of both adverse effects and cancer recurrence. This pilot study aims to assess the clinical benefits of applying endoxifen measurement during tamoxifen therapy in patients with breast cancer. METHODS: Adult premenopausal breast cancer patients ≥ 18 years who received tamoxifen at a fixed dose of 20 mg daily were included. The primary endpoint was to identify the inter-subject variability in serum concentration of the drug and its metabolites especially endoxifen, through fixation of the tamoxifen dose. The secondary endpoint was to check the correlation between endoxifen metabolite concentration and the development of tamoxifen's adverse effects and cancer recurrence. RESULTS: Sixty patients were included in the study with a mean age of 38.4 ± 0.6 years (range: 26-50). The mean concentration of tamoxifen and endoxifen was 181 ± 9.6 ng/mL and 31.49 ng/mL, respectively. The inter-individual variability in concentrations for the drug and its active metabolite as estimated by the coefficient of variation percentage was in 41% and 31%, respectively. Cancer recurrence was observed in a group of patients (n = 16) with an average endoxifen level of 24.48 ng/mL. Another group of patients (n = 25) developed different tamoxifen adverse effects including hot flashes, vaginal bleeding, endometrial thickness, and ovarian cysts with the average endoxifen level of 38.61 ng/mL. The rest of the patients (n = 19) who responded smoothly to the drug with no complications had an average endoxifen level of 31.37 ng/mL. Analysis of variance test showed a significant difference in endoxifen levels between the three groups (p = 0.002). CONCLUSION: The measurement of the endoxifen active metabolite of tamoxifen in breast cancer patients can help dose optimization in light of the observed wide inter-individual variability in drug fixed-dose related concentration of the metabolite. Monitoring of serum concentration of endoxifen can help to reveal, reduce and control tamoxifen's adverse effects and cancer recurrence.

Outcomes Following Mechanical Thrombectomy in Different Etiological Subtypes of Acute Basilar Artery Occlusion : Stroke Etiology and Outcome after EVT in BAO.

BACKGROUND AND PURPOSE: Vertebrobasilar occlusion stroke (VBOS) is innately associated with high morbimortality despite advances in endovascular thrombectomy (EVT). Nonetheless, notable outcome dissimilarities exist between angiographically categorized stroke subtypes. We aim to evaluate potential differences concerning clinical angiographic outcomes among etiological subtypes of VBOS based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. METHODS: We retrospectively reviewed prospective EVT databases at two tertiary care stroke centers for consecutive patients with VBOS who had preinterventional MRI and underwent EVT from January 2015 to December 2019. We identified three groups: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and embolic stroke of undetermined source (ESUS). The primary endpoints were the rates of poor outcome (identified as 90-day modified Rankin scale score of 3-6) and mortality, while the secondary endpoint included the rates of incomplete reperfusion (identified as modified treatment in cerebral infarction scale mTICI 0-2b), and periprocedural symptomatic intracranial hemorrhage. We evaluated the association between the etiology and clinical angiographic outcomes through stepwise logistic regression analysis. RESULTS: Out of 1823 patients, 139 (91 men; median age, 69 (61-76) years) with VBOS were qualified for the final analysis with incidence as follows: LAA (41%, n = 57), CES (35%, n = 48), and ESUS (24%, n = 34). Overall, incomplete reperfusion was realized in 41% (57/139) of the patients, a poor outcome in 65% (90/139), and mortality in 40% (55/139). Longer puncture to reperfusion interval (aOR 1.0182 [95% CI: 1.008-1.029]; p < 0.001) and utilization of combined aspiration-retriever technique (aOR 0.1998 [95% CI: 0.066-0.604]; p = 0.004) were associated with a greater likelihood of incomplete reperfusion (mTICI 0-2b) irrespective of the stroke etiology. After adjustment for confounding factors in the regression analysis, ESUS was an independent predictor of poor outcome (aOR 5.315 [95% CI: 1.646-17.163]; p = 0.005) and mortality (aOR 4.667 [95% CI: 1.883-11.564]; p < 0.001) at 90 days following EVT. CONCLUSION: The functional outcome following EVT for VBOS might depend on stroke etiology. According to our results, ESUS seems to be associated with the worst outcome, which needs further investigation to tailor the appropriate therapeutic plan.

Comparison of the effect of adding midazolam versus fentanyl to intrathecal levobupivacaine in patients undergoing cesarean section: double-blind, randomized clinical trial.

BACKGROUND: Many adjuvants are added to prolong the effects of spinal analgesia. We investigated the postoperative analgesic efficacy of the addition of midazolam or fentanyl to intrathecal levobupivacaine in women undergoing cesarean delivery. METHODS: Eighty patients were randomly assigned to two groups (n = 40). Group M received 10 mg of 0.5% levobupivacaine plus 2 mg of midazolam. Group F received 10 mg of 0.5% levobupivacaine plus 25 µg of fentanyl. Assessments included motor and sensory block, APGAR score, time to first request for analgesia, postoperative pain score, total consumption of rescue analgesics, and adverse effects. RESULTS: Sensory blockade was prolonged in Group M compared with Group F (215.58 ± 27.94 vs. 199.43 ± 19.77 min; p = 0.004), with no differences in other characteristics of the spinal block in intraoperative hemodynamics or APGAR score. The mean time to first request for rescue analgesia was longer in Group M (351.45 ± 11.05 min) than in Group F (268.83 ± 10.35 min; p = 0.000). The median total consumption of rescue analgesics in the first 24 hours postoperatively was 30 mg in Group M vs. 60 mg in Group F (p = 0.003). The median Visual Analog Scale (VAS) scores were lower in Group Ethan in Group F from the 8th to the 12th hour postoperatively, with no differences between the groups at other time points. The incidence of adverse effects was higher in Group F than in Group M. CONCLUSION: Intrathecal midazolam (2 mg) was superior to intrathecal fentanyl (25 µg) in increasing the duration of the sensory blockade and postoperative analgesia with lower postoperative pain scores and decreasing the incidence of adverse effects.

Safety and Efficacy of Cangrelor Among Three Antiplatelet Regimens During Stent-Assisted Endovascular Treatment of Unruptured Intracranial Aneurysm: A Single-Center Retrospective Study.

Introduction: Thromboembolic events represent the most frequent complications of endovascular treatment of unruptured intracranial aneurysm using stent-assisted coilling or flow diverter stents. Dual antiplatelet therapy has become the standard to prevent these but remains unstandardized. We present here a single center experience of 3 standardized antiplatelet regimens during brain aneurysm treatment, while emphasizing the use of the Cangrelor. Method: We retrospectively reviewed data from patients treated using stent-assisted coilling or flow diverter stents from 2016 to 2021. We collected and compared safety and efficacy data within 6 months of three groups of patients corresponding to three antiplatelet standardized regimens: group T with Ticagrelor, with preprocedural preparation; group E with Eptifibatide, injected during procedure; group C with Cangrelor, injected during procedure. Results: Data of 112 patients were analyzed and 76 belonged to group T, 21 to group E, and 15 to group C. Eleven events over the 14 recorded were adjudicated to be related to antiplatelets, their repartition did not differ between the 3 groups (p = 0.43). All symptomatic events (N = 8) were not distributed significantly differently between the 3 groups (p = 0.11) and asymptomatic events were also balanced (p = 1.00). Of these, 6 subjects had a change in the mRS score at 3-6 months. Thrombo-embolic events represented the most encountered events in the sample: 2 acute ischemic strokes were recorded in group E and 1 in group T; 1 transient ischemic stroke was noted in group E; 4 silent infarcts were found on control MRI (2 belonged to group T, 1 to group E and 1 to group C). Among 3 intracranial bleeding events, 1 was symptomatic in group C, 2 were asymptomatic in group T. On the control evaluation performed at 6 months, there was no significant difference on aneurysmal occlusion (p = 0.67). Conclusion: This single-center retrospective study compared 3 antiplatelet regimens, finding no significant difference in the safety and efficacy in the context of endovascular treatments of unruptured aneurysm using stent or flow diverters. This study adds data for the Cangrelor use and suggests its usefulness in the field of neuro-endovascular intervention. Randomized controlled studies are warranted to confirm these results.

Impact of White Matter Hyperintensity Burden on Outcome in Large-Vessel Occlusion Stroke.

Background White matter hyperintensity (WMH) has been linked to poor clinical outcomes after acute ischemic stroke. Purpose To assess whether the WMH burden on pretreatment MRI scans is associated with an increased risk for symptomatic intracranial hemorrhage (sICH) or poor functional outcome in patients with acute ischemic stroke treated with endovascular thrombectomy (EVT). Materials and Methods In this retrospective study, consecutive patients treated with EVT for anterior circulation acute ischemic stroke at a comprehensive stroke center (where MRI was the first-line pretreatment imaging strategy; January 2015 to December 2017) were included and analyzed. WMH volumes were assessed with semiautomated volumetric analysis at fluid-attenuated inversion recovery MRI by readers who were blinded to clinical data. The associations of WMH burden with sICH and 3-month functional outcome (modified Rankin Scale [mRS] score) were assessed. Results A total of 366 patients were included (mean age, 69 years ± 19 [SD]; 188 women [51%]). Median total WMH volume was 3.61 cm3 (IQR, 1.10-10.83 cm3). Patients demonstrated higher mRS scores with increasing WMH volumes (odds ratio [OR], 1.020 [95% CI: 1.003, 1.037] per 1.0-cm3 increase for each mRS point increase; P = .018) after adjustment for patient and clinical variables. There were no significant associations between WMH severity and 90-day mortality (OR, 1.007 [95% CI: 0.990, 1.024]; P = .40) or the occurrence of sICH (OR, 1.001 [95% CI: 0.978, 1.024]; P = .94). Conclusion Higher white matter hyperintensity burden was associated with increased risk for poor 3-month functional outcome after endovascular thrombectomy for large-vessel occlusive stroke. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mossa-Basha and Zhu in this issue.

Parent artery stenting as a rescue management for stretched coils during cerebral aneurysms embolization: Report of three cases and review of literature.

BACKGROUND: Displacement of a stretched coil into the parent artery during intracranial aneurysm coiling is a challenging situation where the risk of acute intravascular thrombosis might be a life-threatening condition. The usual way of management is coil snaring, yet in some cases, it might not be feasible to retrieve the coil. Parent artery rescue stenting had already been described as a way of management in acutely thrombosed parent arteries during aneurysm coiling. CASE REPORTS: We present three cases with an inadvertent displacement of the unraveled coils into the parent artery for which rescue stenting was carried out to crush the coil against the vessel wall aiming to eliminate its thrombogenic effect. Our preliminary experience is that rescue stenting of the parent artery for stretched coil could be a convenient effective option particularly in case of failed/risky snaring with no notable immediate or long-term complications. REVIEW AND DISCUSSION: We review the reported cases of stretched coils with or without further unraveling and fracture and discuss the possible consequences, salvage methods, and clinical outcomes. Neurointerventionists should be aware of this complication and get acquainted with bailout strategies.

Successful WEBectomy during embolization of temporal arteriovenous malformation-associated flow-related basilar aneurysms.

OBJECTIVE: Intra-procedural WEB device migration is a scarcely reported complication that necessitates prompt intervention. CASE PRESENTATION: Endovascular treatment of two broad necked flow-related aneurysms was planned aided by WEB-SL (Woven EndoBridge-single layer) devices in a 71-year-old female with known left temporal arteriovenous malformation. Inadvertent distal migration occurred while performing a control angiogram with an automated iodine injector. Immediate retrieval was successfully performed using a Solitaire stent-retriever. CONCLUSION: To our knowledge, we report for the first time the successful retrieval of a distally migrated WEB using a stent-retriever device.

White Matter Hyperintensity Burden and Collateral Circulation in Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: White matter hyperintensity (WMH), a marker of chronic cerebral small vessel disease, might impact the recruitment of leptomeningeal collaterals. We aimed to assess whether the WMH burden is associated with collateral circulation in patients treated by endovascular thrombectomy for anterior circulation acute ischemic stroke. METHODS: Consecutive acute ischemic stroke due to anterior circulation large vessel occlusion and treated with endovascular thrombectomy from January 2015 to December 2017 were included. WMH volumes (periventricular, deep, and total) were assessed by a semiautomated volumetric analysis on fluid-attenuated inversion recovery-magnetic resonance imaging. Collateral status was graded on baseline catheter angiography using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system (good when ≥3). We investigated associations of WMH burden with collateral status. RESULTS: A total of 302 patients were included (mean age, 69.1±19.4 years; women, 55.6%). Poor collaterals were observed in 49.3% of patients. Median total WMH volume was 3.76 cm3 (interquartile range, 1.09-11.81 cm3). The regression analyses showed no apparent relationship between WMH burden and the collateral status measured at baseline angiography (adjusted odds ratio, 0.987 [95% CI, 0.971-1.003]; P=0.12). CONCLUSIONS: WMH burden exhibits no overt association with collaterals in large vessel occlusive stroke.

Acute arsenic treatment alters arachidonic acid and its associated metabolite levels in the brain of C57Bl/6 mice.

The toxic effects of arsenic on the whole brain, as well as the discrete regions, has been previously reported for mice. We investigated the effects of acute arsenite (As(III)) on brain levels of arachidonic acid (AA) and its associated metabolites generated through cytochrome P450 (CYP), cyclooxygenase (COX), and lipoxygenase (LOX) pathways. Our results demonstrated that acute As(III) treatment (12.5 mg·(kg body mass)(-1)) decreases cytosolic phospholipase A2 (cPLA2) with a subsequent decrease in its catalytic activity and brain AA levels. In addition, As(III) differentially altered CYP epoxygenases and CYP ω-hydroxylases, but it did not affect brain Ephx2 mRNA or sEH catalytic activity levels. As(III)-mediated effects on Cyps caused an increase in brain 5,6-epoxyeicosatrienoic acid (5,6-EET) and 16/17-hydroxyeicosatetreinoic acid (16/17-HETE) levels, and a decrease in 18- and 20-HETE levels. Furthermore, As(III) increased cyclooxygenase-2 (COX-2) mRNA while decreasing prostaglandins F2α (PGF2α) and PGJ2. As(III) also increased brain 5-lipoxygenase (5-LOX) and 15-LOX mRNA, but decreased 12-LOX mRNA. These changes in LOX mRNA were associated with a decrease in 8/12-HETE levels only. In conclusion, this is the first demonstration that As(III) decreases AA levels coinciding with alterations to EET, HETE, and PG levels, which affects brain development and neurochemistry.

Acute mercury toxicity modulates cytochrome P450, soluble epoxide hydrolase and their associated arachidonic acid metabolites in C57Bl/6 mouse heart.

Mercury exposure is associated with increased risk of cardiovascular disease and profound cardiotoxicity. However, the correlation between Hg(2+)-mediated toxicity and alteration in cardiac cytochrome P450s (Cyp) and their dependent arachidonic acid metabolites has never been investigated. Therefore, we investigated the effect of acute mercury toxicity on the expression of Cyp-epoxygenases and Cyp-ω-hydroxylases and their associated arachidonic acid metabolites in mice hearts. In addition, we examined the expression and activity of soluble epoxide hydrolase (sEH) as a key player in arachidonic acid metabolism pathway. Mercury toxicity was induced by a single intraperitoneal injection (IP) of 2.5 mg/kg of mercuric chloride (HgCl2). Our results showed that mercury treatment caused a significant induction of the cardiac hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP); in addition to Cyp1a1, Cyp1b1, Cyp2b9, Cyp2b10, Cyp2b19, Cyp2c29, Cyp2c38, Cyp4a10, Cyp4a12, Cyp4a14, Cyp4f13, Cyp4f15, Cyp4f16 and Cyp4f18 gene expression. Moreover, Hg(2+) significantly increased sEH protein expression and activity levels in hearts of mercury-treated mice, with a consequent decrease in 14,15-, and 11,12-epoxyeicosatrienoic acids (EETs) levels. Whereas the formation of 14,15-, 11,12-, 8,9-dihydroxyeicosatrienoic acids (DHETs) was significantly increased. In conclusion, acute Hg(2+) toxicity modulates the expression of several Cyp and sEH enzymes with a consequent decrease in the cardioprotective EETs which could represent a novel mechanism by which mercury causes progressive cardiotoxicity. Furthermore, inhibiting sEH might represent a novel therapeutic approach to prevent Hg(2+)-induced hypertrophy.

Peak distortion effects in analytical ion chromatography.

The elution profile of chromatographic peaks provides fundamental understanding of the processes that occur in the mobile phase and the stationary phase. Major advances have been made in the column chemistry and suppressor technology in ion chromatography (IC) to handle a variety of sample matrices and ions. However, if the samples contain high concentrations of matrix ions, the overloaded peak elution profile is distorted. Consequently, the trace peaks shift their positions in the chromatogram in a manner that depends on the peak shape of the overloading analyte. In this work, the peak shapes in IC are examined from a fundamental perspective. Three commercial IC columns AS16, AS18, and AS23 were studied with borate, hydroxide and carbonate as suppressible eluents. Monovalent ions (chloride, bromide, and nitrate) are used as model analytes under analytical (0.1 mM) to overload conditions (10-500 mM). Both peak fronting and tailing are observed. On the basis of competitive Langmuir isotherms, if the eluent anion is more strongly retained than the analyte ion on an ion exchanger, the analyte peak is fronting. If the eluent is more weakly retained on the stationary phase, the analyte peak always tails under overload conditions regardless of the stationary phase capacity. If the charge of the analyte and eluent anions are different (e.g., Br(-) vs CO3(2-)), the analyte peak shapes depend on the eluent concentration in a more complex pattern. It was shown that there are interesting similarities with peak distortions due to strongly retained mobile phase components in other modes of liquid chromatography.