Dietary Chitosan Attenuates High-Fat Diet-Induced Oxidative Stress, Apoptosis, and Inflammation in Nile Tilapia (Oreochromis niloticus) through Regulation of Nrf2/Kaep1 and Bcl-2/Bax Pathways.

Fatty liver injury is a prevalent condition in most farmed fish, yet the molecular mechanisms underpinning this pathology remain largely elusive. A comprehensive feeding trial spanning eight weeks was conducted to discern the potential of dietary chitosan in mitigating the deleterious effects of a high-fat diet (HFD) while concurrently exploring the underlying mechanism. Growth performance, haemato-biochemical capacity, antioxidant capacity, apoptotic/anti-apoptotic gene expression, inflammatory gene expression, and histopathological changes in the liver, kidney, and intestine were meticulously assessed in Nile tilapia. Six experimental diets were formulated with varying concentrations of chitosan. The first three groups were administered a diet comprising 6% fat with chitosan concentrations of 0%, 5%, and 10% and were designated as F6Ch0, F6Ch5, and F6Ch10, respectively. Conversely, the fourth, fifth, and sixth groups were fed a diet containing 12% fat with chitosan concentrations of 0%, 5%, and 10%, respectively, for 60 days and were termed F12Ch0, F12Ch5, and F12Ch10. The results showed that fish fed an HFD demonstrated enhanced growth rates and a significant accumulation of fat in the perivisceral tissue, accompanied by markedly elevated serum hepatic injury biomarkers and serum lipid levels, along with upregulation of pro-apoptotic and inflammatory markers. In stark contrast, the expression levels of nrf2, sod, gpx, and bcl-2 were notably decreased when compared with the control normal fat group. These observations were accompanied by marked diffuse hepatic steatosis, diffuse tubular damage, and shortened intestinal villi. Intriguingly, chitosan supplementation effectively mitigated the aforementioned findings and alleviated intestinal injury by upregulating the expression of tight junction-related genes. It could be concluded that dietary chitosan alleviates the adverse impacts of an HFD on the liver, kidney, and intestine by modulating the impaired antioxidant defense system, inflammation, and apoptosis through the variation in nrf2 and cox2 signaling pathways.

Aminothiol supported dialdehyde cellulose for efficient and selective removal of Hg(II) from aquatic solutions.

The increasingly serious problem of mercury pollution has caused wide concern, and exploring adsorbent materials with high adsorption capacity is a simple and effective approach to address this concern. In the recent study, dialdehyde cellulose (DAC), cyanoacetohydrazide (CAH), and carbon disulfide (CS2) are used as raw materials for the (DAC@CAH@SK2) preparation material through the three-steps method. By utilizing the following characterization techniques; thermogravimetric analysis (TGA), N2 adsorption-desorption isotherm (BET), elemental analysis, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD), 1HNMR and Energy Dispersive X-ray Spectroscopy (EDS) of DAC@CAH@SK2 composite. The point of zero charge (pHPZC) for the prepared DAC@CAH@SK2 also was examined. From the batch experiments, the optimum conditions were found to be pH (5-8), an Hg2+ concentration of 150 mg/L, a DAC@CAH@SK2 dose of 0.01 g, and a contact time of 180 min with a maximum adsorption quantity of 139.6 mg/g. The process of Hg2+ adsorption on the DAC@CAH@SK2 material was spontaneous exothermic, monolayer chemisorption, and well-fitted to Langmuir and pseudo-2nd-order models. The DAC@CAH@SK2 selectivity towards the Hg2+ was examined by investigating the interfering metal ions effect. The DAC@CAH@SK2 was successfully applied for the Hg2+ removal from synthetic effluents and real wastewater samples with a recovery % exceeding 95%. The prepared DAC@CAH@SK2 was regenerated using a mixture of EDTA and thiourea. Also, FT-IR analysis indicates that the synergistic complexation of N and S atoms on DAC@CAH@SK2 with Hg(II) is an essential factor leading to the high adsorption capacity.

Surfactant supported chitosan for efficient removal of Cr(VI) and anionic food stuff dyes from aquatic solutions.

In order to develop a novel and cost-effective adsorbent with outstanding adsorption capacity and excellent recyclability for anionic pollutants, the chitosan-modified cetyltrimethylammonium bromide sorbent (CS@CTAB) was fabricated. Fourier-transform infrared spectroscopy, N2 adsorption-desorption isotherm, elemental analysis, Thermogravimetric analysis, X-ray diffraction, and Scanning electron microscopy have been applied to evaluate both raw and surfactant modified chitosan (CS@CTAB). Azorubine, Sunset Yellow, and hexavalent chromium were used to study the adsorption behavior of CS@CTAB under various parameters such as adsorbent dose, initial dye and metal ion concentration, contact time, and temperature. Adsorption equilibrium, kinetics models and thermodynamic parameters were investigated. The adsorption isotherm fitted well with the Langmuir isotherm model, with a maximum adsorption capacity of 492.6 mg/g, 492.6 mg/g, and 490.196 mg/g for Azorubine, Sunset Yellow, and Hexavalent Chromium, respectively. The kinetic studies showed that the pseudo-second-order model provided a better correlation between experimental data. Furthermore, the calculated thermodynamic parameters confirmed that the adsorption of Cr(VI), E110, and E122 by CS@CTAB material is a spontaneous and exothermic process. The fabricated CS@CTAB adsorbent was employed for the efficient elimination of Azorubine, Sunset Yellow, and hexavalent chromium from real water samples, synthetic mixtures, and colored soft drinks, with a percentage of recovery of ~ 96%. The plausible adsorption mechanisms of Azorubine, Sunset Yellow, and hexavalent chromium on the surface of CS@CTAB are elucidated. The adsorption anticipated to be due to electrostatic interaction and hydrogen bond formation for hexavalent chromium; while the adsorption of Azorubine and Sunset Yellow, was assumed to be due to electrostatic interaction, hydrogen bonding, and n-π interaction. Finally, the study demonstrates the efficiency of CS@CTAB for the removal of anionic species from several samples, including natural water and colored beverages.

Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells.

Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine, and spermine. These metabolites play critical roles in activation-induced T cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eukaryotic translation initiation factor 5A (eIF5A). Here, we demonstrated that the glutamine/polyamine/hypusine axis controlled the expression of CD69, an important regulator of tissue-resident memory T cells (Trm). Inhibition of this circuit augmented the development of Trm cells ex vivo and in vivo in the BM, a well-established niche for Trm cells. Furthermore, blocking the polyamine/hypusine axis augmented CD69 expression as well as IFN-γ and TNF-α production in (a) human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes and (b) human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate Trm cells for therapeutic benefit.

Flax fiber based semicarbazide biosorbent for removal of Cr(VI) and Alizarin Red S dye from wastewater.

In the present study, flax fiber based semicarbazide biosorbent was prepared in two successive steps. In the first step, flax fibers were oxidized using potassium periodate (KIO4) to yield diadehyde cellulose (DAC). Dialdehyde cellulose was, then, refluxed with semicarbazide.HCl to produce the semicarbazide functionalized dialdehyde cellulose (DAC@SC). The prepared DAC@SC biosorbent was characterized using Brunauer, Emmett and Teller (BET) and N2 adsorption isotherm, point of zero charge (pHPZC), elemental analysis (C:H:N), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses. The DAC@SC biosorbent was applied for the removal of the hexavalent chromium (Cr(VI)) ions and the alizarin red S (ARS) anionic dye (individually and in mixture). Experimental variables such as temperature, pH, and concentrations were optimized in detail. The monolayer adsorption capacities from the Langmuir isotherm model were 97.4 mg/g and 18.84 for Cr(VI) and ARS, respectively. The adsorption kinetics of DAC@SC indicated that the adsorption process fit PSO kinetic model. The obtained negative values of ΔG and ΔH indicated that the adsorption of Cr(VI) and ARS onto DAC@SC is a spontaneous and exothermic process. The DAC@SC biocomposite was successfully applied for the removal of Cr(VI) and ARS from synthetic effluents and real wastewater samples with a recovery (R, %) more than 90%. The prepared DAC@SC was regenerated using 0.1 M K2CO3 eluent. The plausible adsorption mechanism of Cr(VI) and ARS onto the surface of DAC@SC biocomposite was elucidated.

Autism services in low-resource areas.

OBJECTIVES: To explore access to intervention services for children with autism spectrum disorder (ASD) in Jordan. METHODS: We used prospective cross sectional design and survey methodology to collect information from the parents of a convenient sample of children with ASD aged 2.5-17 years and who attended pediatric neurology clinics in 3 different university affiliated hospitals in 3 geographic areas in Jordan from February to December 2018. RESULTS: We interviewed parents of 274 children with ASD. One hundred ninety-six (71.5%) received rehabilitation services. The average age at first session was 3.9 years. The most common services received were behavioral therapy (182; 66.4%). The average weekly hours were highest for speech and behavioral therapy; 6.25 and 6.64 respectively. Private centers for developmental disabilities were the most commonly used followed by private centers for ASD. The most common barriers were costs (138; 58%) and transportation (88; 37.5%). Most parents (198; 72.3%) prefer to receive rehabilitation in a specialized center for autism, and most did not want to receive training to train their child themselves. CONCLUSION: Most children with ASD in Jordan have limited access to recommended autism services. The development of future interventions must consider the needs of those living in limited resource regions.

TCR-Independent Metabolic Reprogramming Precedes Lymphoma-Driven Changes in T-cell Fate.

Chronic T-cell receptor (TCR) signaling in the tumor microenvironment is known to promote T-cell dysfunction. However, we reasoned that poorly immunogenic tumors may also compromise T cells by impairing their metabolism. To address this, we assessed temporal changes in T-cell metabolism, fate, and function in models of B-cell lymphoma driven by Myc, a promoter of energetics and repressor of immunogenicity. Increases in lymphoma burden most significantly impaired CD4+ T-cell function and promoted regulatory T cell (Treg) and Th1-cell differentiation. Metabolomic analyses revealed early reprogramming of CD4+ T-cell metabolism, reduced glucose uptake, and impaired mitochondrial function, which preceded changes in T-cell fate. In contrast, B-cell lymphoma metabolism remained robust during tumor progression. Finally, mitochondrial functions were impaired in CD4+ and CD8+ T cells in lymphoma-transplanted OT-II and OT-I transgenic mice, respectively. These findings support a model, whereby early, TCR-independent, metabolic interactions with developing lymphomas limits T cell-mediated immune surveillance.

Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.

Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape1,2. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape3-5. We also found that amplification of SETDB1 (1q21.3) in human tumours is associated with immune exclusion and resistance to immune checkpoint blockade. SETDB1 represses broad domains, primarily within the open genome compartment. These domains are enriched for transposable elements (TEs) and immune clusters associated with segmental duplication events, a central mechanism of genome evolution6. SETDB1 loss derepresses latent TE-derived regulatory elements, immunostimulatory genes, and TE-encoded retroviral antigens in these regions, and triggers TE-specific cytotoxic T cell responses in vivo. Our study establishes SETDB1 as an epigenetic checkpoint that suppresses tumour-intrinsic immunogenicity, and thus represents a candidate target for immunotherapy.

A new admission method may select applicants with a distinct personality profile.

BACKGROUND: There is little data to suggest that a specific admission method can select students with a distinct personality profile. We have recently introduced a new admission process that combines a computerized personality test, with a single interview. The purpose of the current study was to find whether the new method selects applicants with a different personality profile and attitudes compared with the previous method. METHOD: Using a validated personality questionnaire (HEXACO) and attitudes questionnair, that were filled anonymously between November 2014 and May 2015, the authors compared two groups of students: group A comprising students accepted with the new method (first and second year) with group B comprising students accepted with the previous method (third to sixth year). RESULTS: In group A, 157 responded out of 250 (63%), while in group B 194 out of 352 (55%). Group A students ranked significantly higher in honesty-humility, extraversion, agreeableness and openness to experience, and lower in emotionality. Physicians' role in society was perceived to be more meaningful among Group A students (M = 4.19, SD = 0.50, N = 152) compared to Group B students (M = 3.86, SD = 0.57, N = 184). CONCLUSIONS: The new method may select applicants with a distinct personality profile and different attitudes toward the physicians' role in the society.

Efficacy of Different Perioperative Statin Regimens on Protection Against Post-Coronary Artery Bypass Grafting Major Adverse Cardiac and Cerebral Events.

OBJECTIVES: Comparing different perioperative statin regimens for the prevention of post-coronary artery bypass grafting adverse events. DESIGN: A randomized, prospective study. SETTING: Cardiothoracic surgical units in a government hospital. PARTICIPANTS: The study comprised 94 patients scheduled for elective, isolated on- or off- pump coronary artery bypass grafting. INTERVENTIONS: Patients were assigned randomly to 1 of the following 3 treatment groups: group I (80 mg of atorvastatin/day for 2 days preoperatively), group II (40 mg of atorvastatin/day for 5-9 days preoperatively), or group III (80 mg of atorvastatin/day for 5-9 days preoperatively). The same preoperative doses were restarted postoperatively and continued for 1 month. MEASUREMENTS AND MAIN RESULTS: Cardiac troponin I, creatine kinase, and C-reactive protein (CRP) levels were assayed preoperatively; at 8, 24, and 48 hours postoperatively; and at discharge. CRP levels at 24 hours (p = 0.045) and 48 hours (p = 0.009) were significantly lower in group III compared with the other 2 groups. However, troponin I levels at 8 hours (p = 0.011) and 48 hours (p = 0.025) after surgery were significantly lower in group II compared with group III. The incidence of postoperative major adverse cardiac and cerebrovascular events was assessed, and there was no significant difference among the 3 groups. CONCLUSION: The 3 regimens did not result in any significant difference in outcomes, but only simple trends. The higher-dose regimen resulted in a significant reduction in the CRP level. Thus, more studies are needed to confirm the benefit of higher-dose statins for the protection from post-coronary artery bypass grafting adverse events.

Tempol prevents genotoxicity induced by vorinostat: role of oxidative DNA damage.

Vorinostat is a member of histone deacetylase inhibitors, which represents a new class of anticancer agents for the treatment of solid and hematological malignancies. Studies have shown that these drugs induce DNA damage in blood lymphocytes, which is proposed to be due to the generation of oxidative lesions. The increase in DNA damage is sometimes associated with risk of developing secondary cancer. Thus, finding a treatment that limits DNA damage caused by anticancer drugs would be beneficial. Tempol is a potent antioxidant that was shown to prevent DNA damage induced by radiation. In this study, we aimed to investigate the harmful effects of vorinostat on DNA damage, and the possible protective effects of tempol against this damage. For that, the spontaneous frequency of sister chromatid exchanges (SCEs), chromosomal aberrations (CAs), and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels were measured in cultured human lymphocytes treated with vorinostat and/or tempol. The results showed that vorinostat significantly increases the frequency of SCEs, CAs and 8-OHdG levels in human lymphocytes as compared to control. These increases were normalized by the treatment of cells with tempol. In conclusion, vorinostat is genotoxic to lymphocytes, and this toxicity is reduced by tempol. Such results could set the stage for future studies investigating the possible usefulness of antioxidants co-treatment in preventing the genotoxicity of vorinostat when used as anticancer in human.

[Splenic artery aneurysm rupture in late pregnancy: a case report and review of the literature]. / Rupture d'un anévrisme de l'artère splénique en fin de grossesse: à propos d'un cas et revue de la littérature.

Haemorrhages during pregnancy may have a non-obstetrical origin, the pregnancy itself favoring some specific aetiologies because of pregnancy-related physiological modifications. These non-obstetrical haemorrhages are rare but are associated with a high maternal and foetal mortality. The prognosis depends on an early diagnosis and a multidisciplinary approach. We report the case of a patient who had a caesarean section for suspicion of acute foetal distress during which was found a large intraperitoneal bleeding due to rupture of an unknown splenic artery aneurysm. We discuss the principal causes of non-obstetrical intra-abdominal bleeding, including subcapsular liver haematoma, rupture of uterine vessels and rupture of splenic artery aneurysm, with a specific focus on this last aetiology.

[Use of carbetocin in prevention of uterine atony during cesarean section. Comparison with oxytocin]. / Utilisation de la carbétocine lors de la delivrance dirigée au cours des césariennes. Comparaison avec l'ocytocine.

OBJECTIVES: To compare the efficacy of carbetocin versus oxytocin, during delivery in patients undergoing a caesarian section. PATIENTS AND METHODS: A two phase observational study (before/after design) was conducted. Use of carbetocin was considered as a sentinel event. Data for 155 women who received carbetocin during a caesarian section were compared with 155 patients who received oxytocin. The main parameter evaluated was the need for haemostatic surgical techniques (vascular sutures, uterine compression sutures, emergent hysterectomy) during caesarian section. RESULTS: Both populations were comparable, particularly concerning risk factors of postpartum haemorrhage. In the carbetocin group, there was fewer compression sutures during caesarian section (0.6% versus 4.5%, P=0.06), as well as a significant decrease in postoperative intravenous iron administration (6.5% versus 14.5%, P=0.03). Vascular sutures, frequencies of prostaglandin intravenous injections, and blood transfusions during caesarian section were similar in both populations. There wasn't any emergent hysterectomy during the time of this study. DISCUSSION AND CONCLUSION: Prevention of uterine atony during a caesarian section with carbetocin seems to be as effective as oxytocin. Particularly, decreasing rate of surgical compression sutures with use of carbetocin is not significant, and prospective studies with more patients are necessary to confirm these results.

Some hemostasis variables at the end of the population distributions are risk factors for severe postpartum hemorrhages.

BACKGROUND: Severe postpartum hemorrhages (PPH) represent a significant cause of maternal morbidity/mortality, but little is known about its hemostasis-related risk factors. Among the 32 463 women enrolled in the NOHA First cohort, 317 developed severe PPH (S-PPH group), 1269 non-severe PPH (NS-PPH group) and the remaining individuals were considered as control women (C group). METHODS: We performed a case-control study, including 317 triplets of women allocated from the three groups that shared the same clinical characteristics as the S-PPH group. RESULTS: From values obtained 6-9 months after delivery, low (but not-deficient) levels of fibrinogen, von Willebrand factor (VWF) antigen, factor (F) XI, platelet CD42b, TRAP-induced increase of platelet CD41a and high values of serum residual prothrombin activity or closure aperture times using the collagen-ADP cartridge on the PFA-100 system, and blood group O, were independently associated with a significant risk of severe PPH. Being positive for at least two of these eight variables was found in 1.6%, 3.5% and 20.8% of the women from the C, the NS-PPH and the S-PPH groups, respectively, the odds ratio for S-PPH in such a case being 16.4, 95%CI (6.5-41), P < 0.0001. CONCLUSIONS: Women with some hemostasis-related variables at the low or high end of the population distributions are prone to the severe forms of PPH. Clinical trials will allow us to know if acting on these risk factors can lower the clinical severity of PPH.

[Prophylaxis of thromboembolic complications in obstetrics and gynaecology]. / Maladie thromboembolique périopératoire et obstétricale. Pathologie gynécologique et obstétricale.

Venous thromboembolism is a leading cause of maternal mortality in many countries, including France. Most enquiries have repeatedly demonstrated that many deaths could be avoided, suggesting the need to update and ensure a wider diffusion of recommendations. Although thromboembolism-induced maternal death plays a major role, the absolute incidence of events remains low, reducing the ability to perform well-designed research and the level of recommendations presented. Many personal or pregnancy-related factors have been identified as increasing the risk of thromboembolism in pregnant patients but few of them have been associated with a significantly increased risk. A history of thromboembolic event and some thrombophilic factors (including antithrombin deficiency and antiphospholipid syndrome) carry the greatest risk. Pregnancy itself, caesarean delivery and the postpartum period, although associated with an increased risk play a minor role when not combined with other risk factors. Prophylactic treatment relies mainly on low molecular weight heparins which safety is now well established in pregnant patients. Dose and duration of treatment should be adapted to the perceived level of risk. The occurrence of a thromboembolic event is also increased after gynaecological surgery but major and cancer surgery carry the greatest risk. Here also, low molecular weight heparins play a leading role, although non pharmacologic means are useful. Dose and duration should be dependent on the level of risk.

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats.

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

Release kinetics of cardiac troponin I and cardiac troponin T in effluents from isolated perfused rabbit hearts after graded experimental myocardial contusion.

BACKGROUND: Few experimental studies report effects of direct contusion on cardiac enzyme release. Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. This investigation was designed to determine and compare the acute effects of quantified magnitudes of blunt cardiac trauma upon release of cTnI and cTnT in comparison with creatine kinase (CK) and lactate dehydrogenase (LD). METHODS: In 24 rabbit hearts prepared on a standard Langendorff apparatus, myocardial contusion (MC) was produced by a single blow with a ball falling from a predefined height, delivered directly to the surface of the heart. Hearts were divided into control (n = 6) and various quantified impacts: 75 mJoules (mJ) (n = 6), 100 mJ (n = 6), 200 mJ (n = 6). Coronary effluent samples for cTnI, cTnT, CK, and LD were collected at baseline, immediately after MC and 5, 15, 30, 45, and 60 minutes after MC. At the end of experiment, histologic condition was evaluated. RESULTS: The anti-cTnI and cTnT MAbs used in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rabbit. The time-courses of cTnI, cTnT, CK, and LD were monophasic in form. After MC, all parameters rose significantly compared with baseline and with control group. The maximal release occurred immediately after MC. The area under the cTnI curve and the maximal cTnI concentration were linked to the contusion energy when increased at 200 mJ. Maximal concentrations and areas under cTnT, CK, LD time activity curve were not linked to the contusion energy level and showed no between-energy group differences. The correlation found between maximal cTnI and maximal cTnT concentrations was 0.70 (p = 0.0001). Histologic examination showed cellular disruption and after the more severe impact, the extent of pathologic changes was more extensive. CONCLUSION: After graded experimental MC, maximal cTnI concentration and area under cTnI curve increase with the power of impact kinetic energy. Levels of cTnI allow a much higher accuracy in detecting the extent of myocardial injury postMC in comparison with cTnT, CK, and LD in this experimental study. These results should be consistent with the more extensive cTnI release with more severe impact in patients with blunt chest trauma. Furthermore, because specificity and time-course of release, both cTnI and cTnT should have a role in the diagnosis and evaluation of such patients.

Comparison of proarrhythmogenic effects of two potassium channel openers, levcromakalim (BRL 38227) and nicorandil (RP 46417): a high-resolution mapping study on rabbit heart.

This study was designed (a) to test and (b) to compare proarrhythmic effects of levcromakalim and nicorandil; and (c) determine the mechanism of arrhythmia initiation by using high-resolution ventricular epicardial mapping on 44 Langendorff-perfused rabbit hearts. Eighteen hearts were kept intact and received incremental doses (1-500 microM) of levcromakalim, nicorandil, and isosorbide dinitrate. In 26 hearts, a thin layer of epicardium was obtained after endocardial cryotechnique (frozen hearts). In intact hearts, isosorbide dinitrate did not produce any arrhythmia. In contrast, levcromakalim induced spontaneous ventricular fibrillation (VF) in all hearts at 50 microM, whereas only one VF occurred at 500 microM nicorandil. These three drugs produced a dose-dependent bradycardia in intact hearts. In frozen hearts, arrhythmias were induced by 5 microM levcromakalim and 50 microM nicorandil. Isosorbide dinitrate had no proarrhythmogenic effect. Epicardial mapping showed that most of induced ventricular tachycardias were based on reentry around an arc of functional conduction block. Ventricular conduction velocities did not change, but levcromakalim and nicorandil shortened ventricular effective refractory period. We conclude that (a) levcromakalim and nicorandil, used in toxic concentrations, have direct proarrhythmic effects; (b) nicorandil proarrhythmogenic effects are 10 times less marked than those of levcromakalim (arrhythmia is solely the result of the potassium channel opener property of nicorandil); and (c) most of ventricular tachycardias induced are based on reentry.