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Objective(s): Recently, we showed that some new synthetic compounds structurally related to cilostamide (4-(1,2-dihydro-2-oxoquinolin-6-hydroxy)- N-cyclohexyl-N-methylbutanamide), a selective phosphodiesterase 3 (PDE3) inhibitor, produce inotropic effect comparable to that of IBMX (3-isobutyl-1-methylxanthine), a non-selective PDE inhibitor, but with differential chronotropic effect. In this investigation, we compared the pharmacological effects of these compounds as potential cardiotonic agents using the spontaneously beating atria model. Materials and Methods: In each experiment, rats were treated with reserpine. The atrium was isolated and mounted in an organ bath. We assessed chronotropic and inotropic effects using cumulativelogconcentration-response curves of isoprenaline alone or in combination of each test-compound. Results: Majority of test compounds augment atria contraction force (ACF) significantly but with different potencies on atrium contraction rate. Cilostamide, MCPIP ([4-(4-methyl piperazin-1-yl)-4-oxobutoxy)-4-methylquinolin-2(1H)-one]), methyl carbostyril compounds- (mc1), mc2 and mc5 increased the isoprenaline effect on ACF synergistically. But, mc6 failed to potentiate the effect of isoprenalin; mc3 and mc4 did not increase ACF, which may be because of their higher hydrophilic nature. It was interesting that mc2, alone or in combination with isoprenaline, produced the highest inotropic effect while it did not affect the basal contraction rate and almost blocked the isoprenaline chronotropic effect. Conclusion: Combination of mc2 with isoprenaline had synergistic effect on inotropic effect, but this combination reduced isoprenaline chronotropic effect; therefore, these effects cannot be related to reducing B-adrenergic receptors activity. These compounds showed different effects; probably all of them were not mediated via PDE3 inhibition and other mechanisms are involving.

Abstract Background Piroxicam (PX) is a nonsteroidal anti-inflammatory drug of the oxicam category that has been known worth as a chemopreventative, anti-tumor agent, for acute and chronic musculoskeletal. To the best of our knowledge, no paper has been published until now reporting the simultaneous electrocatalytic detection of isoprenaline and PX by using any type of modified electrodes. Methods The glassy carbon electrode modified with multiwalled carbon nanotubes chemically modified with (z)-1-(3,4-dihydroxybenzylidene)-2-methylthiosemicarbazide (DBT–CNT/GCE). The electrocatalytic behavior of analytes was examined using cyclic voltammetry (CV), chronoamperometry, and differential pulse voltammetry (DPV) on the modified electrode. Results In order to determine kinetic parameters such as the anodic transfer coefficient (α = 0.47) and the electron transfer rate constant between the nanocomposite and glassy carbon electrode (ks/s = 0.51), cyclic voltammetry was applied. The results represented a linear relationship versus isoprenaline concentrations in the wide range of 0.5–1500.0 μM and a detection limit of 0.35 μM. Furthermore, DPV was applied successfully for the simultaneous determination of isoprenaline and piroxicam. Conclusions This proposed sensor has been successfully applied to determine the IP and PX in blood serum human, which demonstrates that it has excellent potential application for detection of different concentrations of IP and PX.

The aim of this study was to evaluate the effect of l-carnitine (L-CAR) treatment on isoprenaline (ISO) administered kidney and heart impairment in male Long Evans rats. Four groups of rats were engaged in this study such as control, ISO, control + L-CAR, and ISO + L-CAR, where n = 6 in each group. The rats were also provided with chow food and water ad libitum. At the end of the study, all rats were sacrificed, and blood and tissue samples were collected for bio-chemical analysis. Oxidative stress parameters and antioxidant enzyme activities were determined in plasma and tissues. Antioxidant and inflammatory genes expression were analyzed in the kidney cortex, and histopathological studies of kidney tissues were performed. This study showed that creatinine and uric acid in plasma were significantly increased in ISO-administered rats. l-carnitine treatment lowered the uric acid and creatinine level. ISO-administered rats showed increased lipid peroxidation and declined levels of antioxidant enzymes activities in kidneys and heart. l-carnitine treatment restored antioxidant enzymes activities and protect against oxidative stress in kidney and heart. This effect is correlated with the restoration of Nrf-2-HO-1 genes expression followed by increased SOD and catalase genes expression in the kidney. l-carnitine treatment also prevented the TNF-α, IL-6, and NF-кB expression in kidneys of ISO administered rats. Histopathology staining showed that l-carnitine treatment prevented kidney damage and collagen deposition in ISO administered rats. The result of this study exhibited that l-carnitine treatment reduced oxidative stress and increased antioxidant enzyme activities by enhancing antioxidant genes expression in ISO administered rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Isoprenaline (ISO), a synthetic catecholamine and a β-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats., Methods: For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated., Results: FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change., Conclusion: It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI.

Introduction: Oxidative stress is a major instigator of various cardiovascular diseases, including myocardial infarction (MI). Despite available drugs, there is still an increased need to look for alternative therapies or identify new bioactive compounds. Sanguisorba minor ( S. minor ) is a native herb characterized by its potent antioxidant activity. This study was designed to evaluate the effect of S. minor against isoprenaline-induced MI. Methods: Rats were treated with the hydro-ethanolic extract of the aerial parts of S. minor at doses of 100 or 300 mg/kg orally for 9 days. Isoprenaline was injected subcutaneously at the dose of 85 mg/kg on days 8 and 9. Then, the activities of various cardiac injury markers including cardiac troponin (cTnT), lactate dehydrogenase (LDH), creatinine kinase muscle brain (CK-MB), creatinine phosphokinase (CPK), and antioxidant enzymes in serum were determined. Malondialdehyde (MDA) and thiol content were measured in cardiac tissue, and histopathological analysis was conducted. Results: Our results show that isoprenaline increased the serum levels of cTnT, LDH, CK-MB, and CPK ( p < 0.001) and elevated MDA levels ( p < 0.001) in cardiac tissue. Isoprenaline also reduced superoxide dismutase (SOD), catalase, and thiol content ( p < 0.001). Importantly, the extract abolished isoprenaline-induced MI by elevating SOD and catalase ( p < 0.001), reducing levels of MDA, and diminishing levels of cTnT, LDH, CK-MB, and CPK cardiac markers ( p < 0.001). Histopathological studies of the cardiac tissue showed isoprenaline-induced injury that was significantly attenuated by the extract. Conclusion: Our results suggest that S. minor could abrogate isoprenaline-induced cardiac toxicity due to its ability to mitigate oxidative stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that they were editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Hosseini, Ghorbani, Alavi, Forouhi, Rajabian, Boroumand-Noughabi, Sahebkar and Eid.)

Isoprenaline was used as the template to synthesize a molecularly imprinted polymer that was able to simultaneously recognize ten β-agonists. The simulation showed that the three-dimensional conformation of the template was the main factor responsible for the polymer's recognition. The polymer particles were coated in the wells of a conventional microplate as the recognition reagent to prepare a chemiluminescence sensor. The light signal was initiated with a highly effective bis(2,4,6-trichlorophenyl) oxalate-H2O2-imidazole system. The assay contained only one sample-loading step followed by immediate data acquisition, so one measurement was complete within 12 min. The sensor was used to determine the ten analytes in porcine urine. The results showed that the senor achieved ultrahigh sensitivity, with limits of detection from 2.0 to 7.0 pg/mL, high recoveries from 78.6% to 99.4%, and satisfactory recycle performance up to seven times. This is the first study reporting a molecularly imprinted polymer based microtiter chemiluminescence sensor for the determination of β-agonists. [ABSTRACT FROM AUTHOR]

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Myocardial infarction (MI) is indicated by the symptoms like sharp chest pain, sweating, palpitations, and nervousness finally leading to heart attack. MI occurs mainly due to the risk factors like smoking, elevated blood pressure, diabetes, hypercholesterolemia, obesity, decreased HDL level, elevated LDL level, hyperlipoproteinemia and aging consequently leads to demandable coronary blood supply, oxidative stress, and acute necrosis of the myocardium. Cardioprotective potential of the phloroglucinol (PG) was assessed by treating isoprenaline hydrochloride (ISO; 85 mg/kg b.w., s.c.) induced MI model in rats. Pretreatment with PG in a dose of 30 mg/kg was done for 28 days and followed by ISO (for MI induction) on 29th and 30th days, exhibited decline in the abnormalities in the ECG patterns, cardiac marker enzymes, enzymic and nonenzymic antioxidants, lipid peroxidation, lipid profiles, and histopathological investigations compared to isoprenaline alone treated group. On the whole, the present investigations elucidate the significance of PG in alleviating the pathological process and appreciably prevent the induction of MI in experimental rats. [ABSTRACT FROM AUTHOR]

Beetroot (Beta vulgaris) has been reported to possess many benefits and medicinal properties. However, the protective effect of beetroot against isoproterenol (ISO) induced myocardial damage has not been clarified sufficiently yet. The present study was aimed to investigate the effects of beetroot on oxidative stress, fibrosis, and myocardial damage in ISO-induced rats. Our investigation revealed that ISO administration markedly increased the oxidative stress parameters, while the level of cellular antioxidants and catalase activities were decreased in ISO-administered rats. Beetroot supplementation and gallic acid treatment to ISO-administered rats prevented the rises of lipid peroxidation products malondialdehyde, nitric oxide and advanced protein oxidation product concentration. Moreover, elevated activities of alanine aminotransferase, aspartate aminotransferase, and creatinine kinase-muscle brain enzymes activities in ISO-administered rats were also lowered by both gallic acid and beetroot supplementation. Furthermore, gallic acid and beetroot supplementation prevented the inflammatory cells infiltration and fibrosis in ISO-induced rats. In conclusion, these results suggest that beetroot supplementation is capable of protecting ISO-administered myocardial infarction in rats probably by preventing oxidative stress. [ABSTRACT FROM AUTHOR]

The type 2 diabetes epidemic makes it important to find insulin-independent ways to improve glucose homeostasis. This study examines the mechanisms activated by a dual β2-/β3-adrenoceptor agonist, BRL37344, to increase glucose uptake in skeletal muscle and its effects on glucose homeostasis in vivo. We measured the effect of BRL37344 on glucose uptake, glucose transporter 4 (GLUT4) translocation, cAMP levels, β2-adrenoceptor desensitization, β-arrestin recruitment, Akt, AMPK, and mammalian target of rapamycin (mTOR) phosphorylation using L6 skeletal muscle cells as a model. We further tested the ability of BRL37344 to modulate skeletal muscle glucose metabolism in animal models (glucose tolerance tests and in vivo and ex vivo skeletal muscle glucose uptake). In L6 cells, BRL37344 increased GLUT4 translocation and glucose uptake only by activation of β2-adrenoceptors, with a similar potency and efficacy to that of the nonselective β-adrenoceptor agonist isoprenaline, despite being a partial agonist with respect to cAMP generation. GLUT4 translocation occurred independently of Akt and AMPK phosphorylation but was dependent on mTORC2. Furthermore, in contrast to isoprenaline, BRL37344 did not promote agonist-mediated desensitization and failed to recruit β-arrestin1/2 to the β2-adrenoceptor. In conclusion, BRL37344 improved glucose tolerance and increased glucose uptake into skeletal muscle in vivo and ex vivo through a β2-adrenoceptor-mediated mechanism independently of Akt. BRL37344 was a partial agonist with respect to cAMP, but a full agonist for glucose uptake, and importantly did not cause classical receptor desensitization or internalization of the receptor. [ABSTRACT FROM AUTHOR]

Abstract Background Takotsubo syndrome (TS) is an acute cardiac syndrome characterized by regional myocardial akinesia that is not caused by coronary artery occlusion. Exogenous as well as endogenous excess catecholamines can induce TS. The aim of this study was to explore the effects of pharmacological cardio-simulative and cardio-depressing drugs on the development of isoprenaline-induced takotsubo-like cardiac dysfunction, a rat model of TS. Methods We randomized 295 rats into twelve groups. The animals were randomized to pre-treatment with either a low or high dose of metoprolol, propranolol, ICI 118551 (beta 2 -receptor antagonists), milrinone (phosphodiesterase inhibitor), levosimendan or saline (control) before induction of TS with isoprenaline. In one additional group, high dose of milrinone was administered alone. We measured invasively blood pressure and heart rate over a period of 90 min. Cardiac function and morphology were evaluated with high-resolution echocardiography. Results Milrinone alone induced apical ballooning similar to isoprenaline. Pretreatment with propranolol and metoprolol but not with ICI 118551 attenuated takotsubo-like akinesia in a dose-dependent manner. Pretreatment with metoprolol decreased mortality. Pretreatment with levosimendan resulted in higher incidence of apical ballooning while pretreatment with milrinone did not change the degree of akinesia. Conclusion The phosphodiesterase inhibitor milrinone induces takotsubo-like dysfunction in the absence of exogenous catecholamines. This finding challenges the concept that high levels of circulating catecholamines or excessive stimulation of adrenergic receptors are necessary for the development of takotsubo syndrome. Our study provides experimental evidence for the concept of avoidance of inotropes and that selective beta 1 -blockade may be beneficial in the treatment of TS-patients. Highlights • Cardiostimulants exacerbate whereas cardiodepressants attenuate isoprenaline-induced takotsubo-like cardiac dysfunction in rats. • Milrinone administration can induce takotsubo-like dysfunction in rats without concomitant administration of catecholamine. • High levels of circulating catecholamine may not be necessary for the development of takotsubo. [ABSTRACT FROM AUTHOR]

Objectives: Dietary n-3 polyunsaturated fatty acids have positive effects on the heart. The present study investigated the effects of pretreatment with fish oil (FO) and flaxseed oil (FLO) on the heart of the rat, which is associated with the isoprenaline (ISO)-induced myocardial injury. Materials and Methods: The study was conducted on 40 male Wistar rats which were included in control, ISO, FO + ISO, and FLO + ISO groups (each containing 10 rats). In ISO rats, acute myocardial ischemia was induced by ISO while in FO + ISO group, the rats were pretreated with FO orally for 4 weeks. Finally, rats in the FLO + ISO group received pretreatment with FO and flaxseed oil orally for 4 weeks. Eventually, the histopathological examinations of the cardiac tissues and serum activity of creatine kinase-MB (CK-MB) were assessed. Moreover, mitochondria were isolated to examine the mitochondrial swelling. Results: Based on the results, ISO administration significantly increased the serum CK-MB activity compared to the control group. In addition, severe muscular damage to the heart was observed in more than 70% of the rats in ISO group. However, a remarkable decrease in the intensity of heart tissue destruction, as well as the serum levels of CKMB was found in the FO + ISO group compared to the ISO group. Conversely, there was no significant decrease in the serum level of CKMB in FLO + ISO group compared to the ISO group. Conclusions: In general, pretreatment with FLO significantly suppressed the intensity of heart tissue destruction compared to the myocardial ischemic group. FO and FLO led to a decrease in CaCl2-induced swelling in the mitochondria. Therefore, FO and FLO result in protecting against ischemia/reperfusion injury through inhibiting the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The study was designed to assess whether pretreatment with β‐glucan could exert any protective action against isoprenaline‐induced myocardial injury in rats.What is the main finding and its importance?β‐Glucan pretreatment could reduce myocardial injury by restoring cardiac biomarkers, antioxidant status, apoptosis and histopathological changes. Therefore, β‐glucan might have the potential to be used in the prevention and/or treatment of myocardial infarction. This study was designed to investigate the cardioprotective effect of pretreatment with β‐glucan, the glucose polymer derived from the yeast Saccharomyces cerevisiae, against isoprenaline (ISO)‐induced myocardial injury in rats by studying biochemical cardiac markers, antioxidant parameters, apoptosis, ECG and histopathological changes. Male Sprague–Dawley rats were randomly divided into four treatment groups, namely control, β‐glucan, isoprenaline and β‐glucan + isoprenaline. The β‐glucan treatment group received β‐glucan (50 mg kg−1 day−1, p.o.) for 10 days. Myocardial injury was induced by ISO administration (100 mg kg−1, s.c.) twice, at an interval of 24 h, on the 9th and 10th days. Isoprenaline administration resulted in a marked increase in heart rate, ST segment elevation, myocardial malondialdehyde content, cardiac marker levels (lactate dehydrogenase, creatine kinase‐MB and high‐sensitivity cardiac troponin T) and apoptotic index, and a significant decrease in R‐wave amplitude and myocardial superoxide dismutase, catalase and glutathione peroxidase activities. In addition, apoptosis, congestion, necrosis, inflammatory cell infiltration and myofibrillar disorganization were observed histologically in myocardial tissue sections. The oral pretreatment with β‐glucan prevented almost all the parameters of isoprenaline‐induced myocardial injury in rats, and these findings were confirmed by the histopathological analysis. These findings provide evidence that β‐glucan could protect rat myocardium against ISO‐induced myocardial injury, and this was attributed to its antioxidant and anti‐apoptotic properties. [ABSTRACT FROM AUTHOR]

Abstract A chemometrically optimized procedure has been developed for the determination of isoprenaline (ISO) in the parent substance as well as in its respective pharmaceutical preparation. It is worth mentioning that although spectroscopic determination of Isoprenaline metal complexes has been described in literature, yet, no methods for the quantification of Isoprenaline with Samarium nor any other lanthanide metal have been reported. Fractional factorial design (FFD) was implemented in the initial screening procedure of the four designated factors, namely, reaction time (RT), metal volume (MV), pH and temperature (T) followed by Response Surface Methodology (RSM) optimization tool performed by the aid of Box Behnken design (BBD).The proposed techniques are based on a multivariate approach where a complexation reaction between Isoprenaline (ISO) and Samarium III (Sm3+) metal was exploited for the first time to synthesize novel fluorescence and absorbance probes of ISO-Sm. Maximum fluorescence intensity (Y1) as well as maximum absorbance (Y2) of the produced complex were attained at λ ex /λ em = 315/450 and λ 295 nm for spectrofluorimetric and spectrophotometric determinations, respectively, against blank solutions. Using assessment quality tools such as, Pareto charts, normal probability plots and statistical analysis of variance testing (ANOVA), significant factors were successfully indicated (p < 0.05). Furthermore, the proposed methods verified specificity and accuracy for the determination of Isoprenaline in its pure and pharmaceutical preparation using spectrofluorimetric (Technique A) and spectrophotometric (Technique B) techniques, respectively. Linearity was obtained in the range of (0.02–0.50 μg/mL) and (2–12 μg/mL) upon employing both techniques A and B, respectively. Furthermore, limit of detection (LOD) and limit of quantification (LOQ), were found to be 5.1877 ∗ 10−3 μg/mL, 0.01572 μg/mL and 0.5593 μg/mL, 1.6949 μg/mL, upon employing techniques A and B, respectively. Standard addition method was applied for both techniques. The analysis was successfully applied to the assay of pure powder and pharmaceutical dosage forms after which the corresponding mean recoveries were computed and were found to be in the range of 99.546%–100.257% (Technique A) and 99.872%–99.887% (Technique B) with RSD (<1). Graphical Abstract Unlabelled Image Highlights • Synthesis of novel Isoprenaline-Samarium chemosensor employing spectrofluorimetric and spectrophotometric techniques. • Fractional Factorial design for screening and Box-Behnken for optimization of factors. • Applying both techniques to determine ISO in pure powder and pharmaceutical dosage form. [ABSTRACT FROM AUTHOR]

Heart failure-associated morbidity and mortality is largely attributable to extensive and unregulated cardiac remodelling. Roselle (Hibiscus sabdariffa) calyces are enriched with natural polyphenols known for antioxidant and anti-hypertensive effects, yet its effects on early cardiac remodelling in post myocardial infarction (MI) setting are still unclear. Thus, the aim of this study was to investigate the actions of roselle extract on cardiac remodelling in rat model of MI. Male Wistar rats (200-300 g) were randomly allotted into three groups: Control, MI, and MI + Roselle. MI was induced with isoprenaline (ISO) (85 mg/kg, s.c) for two consecutive days followed by roselle treatment (100 mg/kg, orally) for 7 days. Isoprenaline administration showed changes in heart weight to body weight (HW/BW) ratio. MI was especially evident by the elevated cardiac injury marker, troponin-T, and histological observation. Upregulation of plasma levels and cardiac gene expression levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 was seen in MI rats. A relatively high percentage of fibrosis was observed in rat heart tissues with over-expression of collagen (Col)-1 and Col-3 genes following isoprenaline-induced MI. On top of that, cardiomyocyte areas were larger in heart tissues of MI rats with upregulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression, indicating cardiac hypertrophy. Interestingly, roselle supplementation attenuated elevation of plasma troponin-T, IL-6, IL10, and gene expression level of IL-10. Furthermore, reduction of cardiac fibrosis and hypertrophy were observed. In conclusion, roselle treatment was able to limit early cardiac remodelling in MI rat model by alleviating inflammation, fibrosis, and hypertrophy; hence, the potential application of roselle in early adjunctive treatment to prevent heart failure. [ABSTRACT FROM AUTHOR]

Isoprenaline (ISO) is one of synthetic catecholamine that can be used as a model to produce myocardial infarction (MI). Frankincense is a gum resin that possesses anti-inflammatory and antioxidant activity. Gamma-irradiation is used for decontamination of Boswellia tears to achieve satisfactory microbiological quality and public health safety. Hence, examining the effect of gamma-irradiation on the contents of Boswellia oleo-gum resin and also investigating the role of gamma-irradiate frankincense aqueous extract (GFAE) against ISO-induced MI in rats were the two aims of this study. The total phenolic content and total flavonoids of frankincense has been significantly increased under the effect of gamma-rays in this work. Injection of isoprenaline hydrochloride (100 mg/ kg B.Wt./day) to rats resulted in cardiac oxidative stress, inflammation, hyper-lipidemia and increase cardiac marker enzymes. Treatment of rats with GFAE (45 mg/kg/day) prior to injection of ISO provide significant cardio-protective effects evidenced by an obvious reduction in the level of cardiac marker enzymes, inflammatory factors and lipid contents with marked improvement in the cardiac antioxidant status and reduction of lipid peroxidation relative to untreated infarcted group. The study concluded gamma irradiation could be used as an efficient method for sterilization and increasing the active contents of frankincense. Also, gamma-irradiated frankincense can be used as an effective cardio protective natural agent in MI. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction is a major cause of death all over the world. Irisin is a novel myokine released after exercise. This work aimed to study the correlation between the serum irisin level and the severity of the acute myocardial infarction in the exercise-trained rats. Methods: Forty-eight male rats were classified into four groups (12 for each): group I, control sedentary (C); group II, exercise-trained (EX) (swimming for 8 weeks); group III, isoprenaline-induced infarct (MI); and group IV, exercise-trained infarct (EX-MI) (swimming for 8 weeks followed by isoprenaline-induced infarction). ECG was recorded at start and end of the study, before and after induction of infarction. The serum level of irisin, lipid peroxidation [malondialdehyde (MDA)], total antioxidant status (TAS), creatine phosphokinase-MB (CK-MB), and troponin I was determined. The hearts were excised for histopathology and immunohistochemistry for caspase-3. Results: The infarct rats showed significant prolongation in QTc interval and elevation in the ST segment as well as significant elevation of serum CK-MB, troponin I, and MDA, whereas TAS and serum irisin level were significantly decreased. With exercise, we observed a high positive correlation between the serum irisin and QRS duration (+0.643), amplitude (+0.860), and TAS (+0.887). In addition, there was a high negative correlation between the serum irisin and ST elevation (−0.865), QTc (−0.886), CK-MB (−0.891), troponin (−0.882), and MDA (−0.868). This was confirmed by the negative correlation between serum irisin and both collagen deposition and caspase-3 expression (–0.823 and –0.822, respectively). Conclusions: We recommend regular exercise or taking recombinant irisin as a supplement to protect at-risk individuals against acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Lowbush blueberry extract (Vaccinium angustifolium) is abundant with polyphenols (such as chlorogenic acid) with high antioxidant profile. It has received great interest due to its protective role in many disorders such as heart diseases and neurological disorders.Hypothesis: We hypothesized that blueberry leaf extract might have a protective effect against cardiac hypertrophy via suppressing oxidative stress, inflammation and fibrosis.Method: Blueberry leaf nutraceutical extract was administered orally to male albino rats at three different doses (25, 50 and 100 mg/kg/day of the extract, equivalent to 3.4, 6.8 and 13.6 mg of chlorogenic acid, respectively) once daily for 28 consecutive days against a dose of isoprenaline (ISO) (5 mg/kg) for 14 days.Results: The results indicated that isoprenaline induced significant myocardial damage, characterized by conduction abnormalities, increased heart-to-body weight ratio, increased serum CKMB, AST, c-TnI and LDH. Pretreatment with blueberry extract at a dose of 50 mg/kg/day (equivalent to 6.8 mg chlorogenic acid) protected against ISO-induced ECG changes, leakage of cardiac enzymes and histopathological changes. Also, ISO caused significant glutathione depletion, lipid peroxidation and reduction in activities of antioxidant catalase enzyme. These effects were prevented by pretreatment with blueberry extract. Additionally, ISO elicited inflammatory effects by increasing the expression of NF-κB, COX-2, TNF-α and IL-6 while pretreatment with blueberry extract significantly inhibited these inflammatory responses. Furthermore, ISO induced fibrosis by increasing the level of TGF-β while pretreatment with blueberry extract significantly reduced it.Conclusion: These findings indicate that blueberry leaf extract possessed a potent protective effect against ISO-induced cardiac hypertrophy via suppressing oxidative stress, inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

It was suggested that impaired β-adrenergic relaxation in spontaneously hypertensive rats (SHR) might contribute to their high blood pressure (BP). Our study was focused on isoprenaline-induced dilatation of conduit femoral or resistance mesenteric arteries and on isoprenaline-induced BP reduction in SHR and Wistar-Kyoto rats (WKY). We confirmed decreased β-adrenergic relaxation of SHR femoral arteries due to the absence of its endothelium-independent component, whereas endothelium-dependent component of β-adrenergic smooth muscle relaxation was similar in both strains. Conversely, isoprenaline-induced relaxation of resistance mesenteric arteries was similar in both strains and this was true for endothelium-dependent and endothelium-independent components. We observed moderately reduced sensitivity of SHR mesenteric arteries to salmeterol (β 2 -adrenergic agonist) and this strain difference disappeared after endothelium removal. However, there was no difference in mesenteric arteries relaxation by dobutamine (β 1 -adrenergic agonist) which was independent of endothelium. The increasing isoprenaline doses elicited similar BP decrease in both rat strains, although BP sensitivity to isoprenaline was slightly decreased in SHR. The blockade of cyclooxygenase (indomethacin) and NO synthase (L-NAME) further reduced BP sensitivity to isoprenaline in SHR. On the other hand, salmeterol elicited similar BP decrease in both strains and the blockade of cyclooxygenase and NO synthase increased BP sensitivity to salmeterol in SHR as compared to WKY. In conclusion, attenuated β-adrenergic vasodilatation of conduit arteries of SHR but similar β-adrenergic relaxation of resistance mesenteric arteries from WKY and SHR and their similar BP response to β-adrenergic agonists do not support major role of altered β-adrenergic vasodilatation for high BP in genetic hypertension. [ABSTRACT FROM AUTHOR]

To investigate the cardioprotective potential of the aqueous extract of Allium cepa Linn. bulb in isoprenaline-induced myocardial injury in Wistar albino rats. In vitro total phenolic, total flavonoid content and 2, 2′-diphenyl-1-picrylhydrazyl hydrate radical scavenging activity was measured. Isoprenaline-induced myocardial injury model was used to evaluate in vivo effect of aqueous extract of A. cepa in Wistar albino rats. Seventy two rats were randomly divided in 6 groups. Rats were treated with A. cepa 400 mg/kg and 800 mg/kg doses for 30 days and myocardial injury was produced by subcutaneous injection of isoprenaline (ISO) 85 mg/kg on day 28 and 29. Carvedilol 1 mg/kg for 30 days served as active control. Electrocardiogram parameters, cardiac injury markers, oxidative stress markers and histopathological changes were evaluated in each group and compared using appropriate statistical tests. In vitro evaluation of aqueous extract of A. cepa showed significant antioxidant property. ISO produced significant myocardial injury as compared to normal control group (P < 0.05). Administration of A. cepa in the dose of 400 mg/kg significantly recovered the altered parameters (Troponin-I, Creatine kinase-MB, glutamate-pyruvate transaminase, HR, R-R interval, and oxidative stress markers) compared to disease control group (P < 0.05) while A. cepa in the dose 800 mg/kg recovered the altered parameters (HR, heart weight/body weight ratio, and superoxide dismutase level) compared to disease control group. Histopathological parameters did not recover in the doses of 400 and 800 mg/kg (P > 0.05). The aqueous extract of A. cepa 400 mg/kg was found to be cardioprotective against myocardial injury while A. cepa 800 mg/kg did not show significant cardioprotective activity. So, we presume that A. cepa might be effective within certain dose range only.

Background:β-adrenoceptors play a crucial regulatory role in blood vessel endothelial cells. Isoprenaline (ISO, a β-adrenergic agonist) has been reported to promote angiogenesis through upregulation of vascular endothelial growth factor (VEGF) expression; however, the underlying mechanism remains to be investigated. It is widely accepted that certain noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), can regulate endothelial cell behavior, including their involvement in angiogenesis. Therefore, we aimed to investigate whether noncoding RNAs participate in ISO-mediated angiogenesis using human umbilical vein endothelial cells (HUVECs). Methods: We evaluated VEGF-A messenger RNA (mRNA) and protein levels in ISO-treated HUVECs by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. To establish whether noncoding RNAs are associated with ISO-mediated angiogenesis, we measured expression of the miRNAs miR-210, miR-21, and miR-1, as well as that of the lncRNAs growth arrest-specific transcript 5 (GAS5), maternally expressed 3 (MEG3), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HUVECs exposed to ISO. Furthermore, to ascertain its importance in ISO-mediated angiogenesis, we constructed the HUVECs with overexpressing miR-210 and detected the subsequent expression of VEGF-A and noncoding RNAs. All statistical analyses were performed using SPSS 16.0 software. Intergroup comparisons were carried out by one-way analysis of variance. Results: VEGF-A mRNA levels were elevated in the ISO group (1.57 ± 0.09) compared to those in the control group (P < 0.01). Moreover, concentrations of VEGF-A in culture supernatants significantly differed between the control (113.00 ± 19.21 pg/ml) and ISO groups (287.00 ± 20.27 pg/ml; P< 0.01). Expression of miR-1, miR-21, and miR-210 was higher (3.89 ± 0.44, 2.87 ± 087, and 3.33 ± 1.31, respectively) in ISO-treated cells than that in controls (P < 0.01), whereas that of GAS5 and MEG3 (0.22 ± 0.10 and 0.58 ± 0.16, respectively) was lower as a result of ISO administration (P < 0.05). There was no significant difference in the expression of MALAT1 between the groups. Interestingly, miR-210 overexpression heightened the levels of VEGF-A and miR-21 (5.87 ± 1.24 and 2.74 ± 1.15, respectively; P< 0.01) and reduced those of GAS5 and MEG3 (0.19 ± 0.01 and 0.09 ± 0.05, respectively; P< 0.01). Conclusions: ISO-mediated angiogenesis was associated with altered expression of miR-210, miR-21, and the lncRNAs GAS5 and MEG3. The effects of miR-210 on the expression of VEGF-A and noncoding RNAs were similar to those of ISO, indicating that it might play an important role in ISO-mediated angiogenesis.

Myocardial Infarction (MI) is a major health problem worldwide. Animal models have been used extensively in scientific research. This was intended to help researchers to understand the underlying pathophysiology of MI, compensatory mechanisms involved and efficacy of treatment. Although, it is difficult to create necrosis similar to those found in human heart, various large and small animals were used to create experimental model of MI. Each of these animals and method of selection offers various advantages and disadvantages in relation to clinical studies. In the present review, we aim to highlight the different methods used to induce MI in experimental animals. These methods may be beneficial for academicians and researchers concerned with the treatment of MI.

Objective: Myocardial infarction (MI) is linked to an imbalance in the supply and demand of blood oxygen in the heart muscles. Beta-blockers and calcium antagonists are just two of the common medications used to treat MI. However, these have reportedly been shown to be either ineffective or to have undesirable side effects. Extract of Ginkgo biloba leaves (GBE), a Chinese herbal product offers special compatibility benefits in therapeutic settings relating to inflammatory diseases and oxidative stress. In order to better understand how GBE affects MI in rats insulted by isoprenaline (ISO), the current study was designed., Methods: The heart weight index, serum lipid profile, cardiac marker enzymes, endogenous antioxidants [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), nitrites and malondialdehyde (MDA)], inflammatory mediators [tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6)], immunohistochemical expressions of B-cell lymphoma factor-2 (Bcl-2), extracellular signal-regulated kinase (ERK1/2), and mammalian target of rapamycin (mTOR) and histopathological analysis were used to assess the cardioprotective properties of GBE., Results: The findings showed that GBE effectively attenuated myocardial infarction by boosting the body's natural antioxidant defense system and reducing the release of inflammatory cytokines as well as heart injury marker enzymes. The expression of Bcl-2, ERK1/2 and mTOR was increased while the histomorphological alterations were reversed., Conclusion: The cardioprotective effects of GBE may be due to a mechanism involving increased Bcl-2/mTOR/ERK1/2/Na + , K + -ATPase activity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Unstable and symptomatic complete atrioventricular block represents a potentially fatal condition that requires prompt therapy while waiting for definitive pacemaker implantation. Although transcutaneous pacing is included in acute management, it could be a difficult approach due to its painfulness and the occasional failure of mechanical capture. Drug therapy is a feasible choice, and current guidelines encompass the use of atropine, dopamine, or epinephrine. Isoprenaline has never been investigated in this setting, and no specific indication of its use has been provided despite its potentially more favorable pharmacological profile. The study population included a consecutive series of patients who presented to the emergency department because of unstable third-degree atrioventricular block and were treated with either isoprenaline or dopamine infusion while waiting for definitive pacemaker implantation. Asymptomatic patients or those with reversible causes of complete atrioventricular block were excluded. The clinical response to the drug was deemed poor if, despite achieving a full drug dose, patients remained symptomatic and/or with hemodynamic instability, ventricular rate and rhythm did not improve or worsened, including if ventricular arrhythmias or asystolic pauses and/or irrepressible nausea/vomiting occurred. Isoprenaline infusion has proved to be safe and tolerated with no arrhythmia induction or hypotensive issues. Isoprenaline has also proven to be more satisfactory in achieving an effective clinical response in 84% of patients rather than dopamine (31%, p < 0.001), reducing the need for temporary artificial pacing. Our data point out the efficacy and safety of isoprenaline infusion and its greater tolerability over dopamine in the acute management of unstable third-degree AV block while waiting for definitive pacemaker implantation.

Tyrosinase (TYR) plays a pivotal role in the biosynthesis of melanin, and its activity level holds critical implications for vitiligo, melanoma cancer, and food nutritional value. The sensitive determination of TYR activity is of great significance for both fundamental research and clinical investigations. In this work, we successfully synthesized silicon-doped carbon quantum dots (Si-CQDs) through a one-pot hydrothermal method with trans-aconitic acid as carbon source and N-[3-(trimethoxysilyl)propyl]ethylenediamine as the dopant, exhibiting remarkable fluorescence quantum yield (QY) and photostability. Correspondingly, Si-CQDs were used as a probe to construct a sensitive, rapid, and user-friendly fluorescence method for TYR detection. The method relied on the oxidation of isoprenaline (ISO) by TYR, where Si-CQDs were employed as a highly efficient probe. The testing mechanism was the internal filtering effect (IFE) observed between Si-CQDs and the oxidative system of ISO and TYR. Under the optimized conditions, the fluorescence strategy exhibited a detection range of 0.05-2.0 U/mL for TYR with a limit of detection (LOD) of 0.041 U/mL. Furthermore, we successfully demonstrated the accurate determination of TYR levels in human serum, showcasing the promising potential of this method in various practical scenarios.

Myocardial Infarction (MI) is a major health problem worldwide. Animal models have been used extensively in scientific research. This was intended to help researchers to understand the underlying pathophysiology of MI, compensatory mechanisms involved and efficacy of treatment. Although, it is difficult to create necrosis similar to those found in human heart, various large and small animals were used to create experimental model of MI. Each of these animals and method of selection offers various advantages and disadvantages in relation to clinical studies. In the present review, we aim to highlight the different methods used to induce MI in experimental animals. These methods may be beneficial for academicians and researchers concerned with the treatment of MI. [ABSTRACT FROM AUTHOR]

The contractile function of the heart was studied in adult frogs Rana temporaria under the influence of a toxic dose of isoprenaline under conditions of natural sinoatrial rhythm and during heart pacing. The dynamics of ventricular pressure was recorded with a Prucka MacLab 2000 instrument via a catheter introduced into the ventricle through the ventricular wall. Reduced (p<0.05) parameters of the pump function (HR, maximum ventricular systolic pressure, isovolumic indices dP/dtmax and dP/dtmin) and lengthening of QRS complex and QT interval on ECG attested to impairment of contractile function and electrical processes after exposure to isoprenaline. Electrical stimulation of the right atrium improved myocardial contractility and ECG parameters after the administration of isoprenaline. [ABSTRACT FROM AUTHOR]

The present study was undertaken to evaluate the effect of kaempferol in isoprenaline (ISP)-induced myocardial injury in rats. ISP was administered subcutaneously for two subsequent days to induce myocardial injury. Assessment of myocardial injury was done by estimation of hemodynamic functions, myocardial infarcted area, cardiac injury markers, lipid profile, oxidative stress, pro-inflammatory cytokines and histopathology of heart and liver. Rats pretreated with kaempferol showed reduction in the myocardial infarcted area and heart rate. However, no improvement was observed in change in body weight, mean arterial, systolic and diastolic blood pressure. Kaempferol showed significant decrease in serum LDH, CK-MB, troponin-I and lipid profile. However, highest dose of kaempferol did not reduce the serum triglyceride level. Further, antioxidant enzymes, SOD and catalase, were also higher. However, reduced glutathione, serum SGOT and creatinine did not show any improvement. Kaempferol showed reduction in MDA level. Kaempferol at highest dose showed reduction in pro-MMP-2 expression and MMP-9 level. mRNA expression level of TNF-α was not different in kaempferol-pretreated myocardial injured rats with ISP-alone group. Pretreatment with kaempferol at highest dose showed mild mononuclear infiltration and degenerative changes in heart tissue section of myocardial injured rats. Rats pretreated with kaempferol at higher concentration showed normal cordlike arrangement of hepatocytes with moderate swelling of hepatocytes (vacuolar degeneration) around the central vein. Study suggests that kaempferol attenuated lipid profile, infarcted area and oxidative stress in ISP-induced myocardial injury in rats. [ABSTRACT FROM AUTHOR]

In this paper, the use of molecular self-assembled monolayers of 5-(1,3-dithiolan-2-eyl)-3-methyl banzen-1,2-diol (DMD) on gold nanoparticles was described (DMD-AuNPs). The redox properties of modified electrode at various scan rates were investigated by cyclic voltammetry. A pair of well-defined quasi-reversible redox peaks of DMD were obtained at the modified electrode. Dramatically enhanced electrocatalytic activity was exemplified at the DMD-AuNPs, as an electrochemical sensor to investigate the electro-oxidation of isoprenaline (IP). With this modified electrode, the oxidation potential of the IP was shifted about 235 mV toward a less positive potential value than that of an unmodified electrode. The values of electron transfer coefficients (α = 0.5), catalytic rate constant (ks = 9.2 s−1) and diffusion coefficient (D = 8.9 × 10−5 cm2 s−1) were calculated for IP. The response of catalytic current with IP concentration showed a linear relation in the range from 0.5 to 800 µM with a detection limit of 0.21 µM. Finally, this modified electrode was used for the determination of IP in IP injections. [ABSTRACT FROM AUTHOR]

Astragalus polysaccharides (ASP) is extracted from Astragalus , and is the main active ingredient of Astragalus membranaceus. The purpose of this study was to investigate the protective effect of ASP on rat cardiomyocytes damage induced by myocardial ischemia and reperfusion injury (MVRI) and isoprenaline(ISO) in vivo and in vitro . The model of cardiomyocytes damage was induced using MVRI in a rat in vivo and also using ISO in cell. After ASP intervention, the protective effect of ASP on cardiomyocytes was evaluated by animal experimental and cell experimental. The results show that ASP can relieve the increase of cell volume in myocardium, reduce the apoptosis of cell in myocardial tissue caused by MVRI in vivo. At the cellular level, ASP can reverse the decrease of cell activity induced by ISO, inhibit the apoptosis, and decrease the levels of intracellular reactive oxygen species. Mechanistically at the molecular level, these effects are elicited via down-regulation of the protein levels of caspase-3 and bax and up-regulation of the protein levels of bcl-2 in both in vivo and in vitro . These results demonstrate that ASP has a protective efficacy in MVRI/ISO-treated cardiomyocytes by inhibiting the apoptosis. [ABSTRACT FROM AUTHOR]

Myocardial infarction is commonly considered as a leading cause of cardiovascular disease taking the lives of seven million people annually. Liver dysfunction is associated with cardiac diseases. The profile of abnormal liver functions in heart failure is not clearly defined. This study was designed to investigate the protective effects of betaine on liver injury after myocardial infarction induced by isoprenaline in rats. Forty-eight male rats were divided into four groups: the control group received normal diet and the experimental groups received 50, 150, and 250 mg kg-1 body weight of betaine daily through gastric gavages for 60 days. All of experimental and control groups experienced myocardial infarction, induced by subcutaneous injection of 100 mg kg-1 isoprenaline in two consecutive doses)8:00 AM to 8:00 PM). Liver enzymes including aspartate transaminase (AST) and alanine transaminase (ALT) were significantly reduced in the groups treated with betaine, compared with the control group. The total antioxidant capacity in the experimental groups, treated with betaine, showed a significant increase, compared with the control group. In the control group, severe lesions were created in the liver tissue, while degenerative changes of liver tissue significantly reduced in groups treated with different doses of betaine, showing the repair of liver tissue. Betaine decreased apoptosis in the experimental groups in comparison with the control group. Betaine showed a protective effect against biochemical and histological changes in liver tissue caused by the induction of myocardial infarction via isoprenaline injection. [ABSTRACT FROM AUTHOR]

Isoprenaline, an activator of β-adrenergic receptor, has been found to induce cardiac hypertrophy in vivo and in vitro , but the exact mechanism is still unclear. ClC-3 is a member of the chloride channel family and is highly expressed in mammalian myocardium. In the present study, the role of ClC-3 in isopronaline-induced cardiac hypertrophy was investigated. We found that ClC-3 expression was reduced in isoprenaline-induced hypertrophic H9c2 cells, primary rat neonatal cardiomyocytes and myocardium of C57/BL/6 mice, and this reduction was prevented by the pretreatment of propranolol. Adeno-associated virus 9 (AAV9)-mediated ClC-3 expression in myocardium decreased heart mass index, thinned interventricular septum and left ventricular wall and lowered the mRNA expression of natriuretic peptide type A (ANF) and β-myosin heavy chain (β-MHC). Our results showed that ClC-3 played an important role in β-adrenergic cardiac hypertrophy which could be associated with ANF and β-MHC, and all these findings suggested that ClC-3 may be a novel therapeutic target for the prevention or treatment of myocardiac hypertrophy. [ABSTRACT FROM AUTHOR]

In this paper, we describe a rapid, low-cost and highly sensitive colorimetric method for the detection of isoprenaline, based on 2-amino-5-mercapto-1,3,4-thiadiazol (AMTD) functionalized gold nanoparticles (AMTD-AuNPs) as a sensing element. Hydrogen bonding interaction between isoprenaline and AMTD resulted in the aggregation of AuNPs and a consequent color change of AuNPs from red to blue. The concentration of isoprenaline could be detected with the naked eye or a UV-visible spectrometer. Results showed that the absorbance ratio (A650/A524) was linear with isoprenaline concentrations in the range of 0.2 to 2.6 μM (R = 0.997). The detection limit of this method was 0.08 μM. The proposed method is simple, without using complicated instruments and adding salts for enhancing sensitivity. This probe could be successfully applied to the determination of isoprenaline in human serum samples and urine samples after deproteinization. [ABSTRACT FROM AUTHOR]

A novel electrochemical sensor for isoprenaline (IP) comprising a β-Cyclodextrin (β-CD) functionalized graphene oxide (GO) and an electrochemically generated acid yellow 9 polymer as a composite material modified glassy carbon electrode (GCE) has been developed. The composite material was characterized using infrared spectroscopy and scanning electron microscopy. The functionalization of GO with β-CD was scrutinized by varying the content of the β-CD material. Interestingly, the synergistic electrocatalytic activity was examined at different β-CD loadings functionalized GO in the sensitivity for the detection of IP. The electrochemical characterization of the proposed sensor (β-CD-GO/PAY/GCE) was performed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The developed composite based electrode displayed superior sensitivity towards IP over that of the other modified electrodes. The limit of detection at β-CD-GO/PAY/GCE was found to be 3.3 × 10 − 8 M. Moreover, the detection potential of IP was notably lower at the proposed composite based sensor. The β-CD-GO/PAY/GCE was also successfully applied for simultaneous resolution of IP in the presence of endogenous interfering biomolecule such as uric acid. The recovery results attained for real samples recommend practical utility of the proposed composite electrode an effective and reliable electrochemical sensor for quantification of IP. The sensor is highly stable, reproducible and signifies a feasible platform for the analysis of IP. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AsIV), one of the major active ingredients in Astragalus membranaceus, has demonstrated remarkable antifibrotic effects via its antioxidative activity. Cardiac fibrosis is an important pathological mechanism during cardiac remodelling associated with heart failure. In the present study, the mechanism underlying the antifibrotic effect of AsIV upon isoprenaline (ISO) stimulation was investigated. AsIV significantly improved cardiac fibrosis in vivo and dose-dependently inhibited ISO-induced CF proliferation in vitro. The ISO-triggered elevation in reactive oxygen species (ROS) levels was remarkably inhibited by AsIV, as well as ROS scavenger N-acetylcysteine (NAC), and not affected by cardiotrophin-1 (CT-1) knockdown. In addition, AsIV effectively reversed ISO-induced upregulation of CT-1 expression, which was blunted by pretreatment with NAC. Cardiac fibroblast (CF) proliferation and collagen I overexpression induced by ISO stimulation were effectively abrogated by AsIV, NAC, and CT-1 small interfering RNA transfection. Taken together, these results demonstrated that AsIV was able to effectively inhibit ISO-induced CF proliferation and collagen production through negative regulation of ROS-mediated CT-1 upregulation. [ABSTRACT FROM AUTHOR]