Acellular human amniotic fluid protects the ischemic-reperfused rat myocardium.

Amniotic products are potent immunomodulators used clinically to repair tissue injury. Little information exists regarding the potential of cell-free human amniotic fluid (hAF) to treat cardiovascular disease. Herein, we sought to determine the influence and efficacy of acellular hAF on myocardial ischemia-reperfusion injury. Processed hAF was obtained from volunteer donors at the time of elective caesarean section and manufactured using proprietary methods. Left anterior descending coronary artery ligation was performed on rats for 60 min. Thirty minutes after release and reperfusion, either saline or hAF was injected intramyocardially. Serial echocardiography revealed that compared with saline-injected rats, hAF animals maintained their ejection fraction and did not adversely remodel through the 4-wk period. This preserved ventricular function correlated with decreased infarct size, less fibrosis, and reduced expression of cytokines and infiltrating inflammatory cells. Comparative arrays of different donor hAF lots confirmed the presence of a wide array of immunomodulatory and host-defense proteins. The observed functional cardioprotection was furthermore evident when given intravenously and across multiple hAF donors. In conclusion, our data demonstrate, for the first time, the cardioprotective effect of acellular hAF on myocardial injury. These observations spanned across diverse donors and likely result from the mixture of a plethora of naturally produced cytokines, chemokines, and immune-modulating proteins rather than a single, defined mechanistic culprit. The ubiquitous availability of hAF as a cell-free solution further suggests its potential for widespread adoption as a therapy for myocardial ischemia-reperfusion injury.NEW & NOTEWORTHY Rather than targeting a single pathway implicated in myocardial reperfusion injury, cell-free human amniotic fluid-a naturally derived cocktail composed of thousands of proteins involved with innate immunity and anti-inflammation-markedly reduces injury and preserves cardiac function in a model of rodent myocardial ischemia-reperfusion. With its ubiquitous availability as well as its anti-inflammatory and nonimmunogenic properties, human cell-free amniotic fluid offers potential for use as a cardioprotective adjunct.

The Oleaster (Elaeagnus angustifolia): A Comprehensive Review on Its Composition, Ethnobotanical and Prebiotic Values>.

BACKGROUND: Oleaster or Elaeagnus angustifolia is a deciduous plant from Elaegnacea family and is well-known for its remedial applications. OBJECTIVE: This paper presents a comprehensive review of the potential application of Oleaster's flour incorporated in some food products. Emphasis is given to the physicochemical, biochemical, and functional properties of Oleaster's flour. METHODS: A comprehensive search was carried out to find publications on Oleaster's flour and its application as a prebiotic. The results of the related studies were extracted and summarized in this paper. RESULTS: Oleaster's flour as a prebiotic ingredient enhances antioxidants, polyphenols, fiber, flavonoids, Sterols, carbohydrates, and protein content of food products. CONCLUSION: Further advanced investigations on Oleaster and its functional ingredients revealed that these are efficacious and can be applied as a substitute source in pharmacological industries for medical applications.

Fecal metabolomics based on mass spectrometry to investigate the mechanism of qishen granules against isoproterenol-induced chronic heart failure in rats.

Qishen granules, derived from clinical experience formula, has been widely used to improve and treat myocardial ischemic chronic heart failure in China. However, the mechanism of action of Qishen granules in the treatment of chronic heart failure is unclear. This study aimed to discover potential biomarkers of isoproterenol-induced chronic heart failure rats and investigate the potential mechanism of Qishen granules treatment of chronic heart failure. The fecal metabolomics method based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the therapeutic effect and metabolic changes of Qishen granules on chronic heart failure rats. Totally, 17 potential biomarkers were identified, involving bile acid metabolism, fatty acid metabolism, inflammatory response, and amino acid metabolism. For bile acid metabolism, we selected 12 bile acids (two of which were potential biomarkers in nontargeted metabolomics) for quantitative analysis. The quantitative results of bile acids showed that after Qishen granules treatment, the contents of bile acids such as ursodeoxycholic acid and glycodeoxycholic acid were similar to those of health group. This study helps to understand the pathogenesis of isoproterenol-induced chronic heart failure and the therapeutic mechanism of Qishen granules from the perspective of metabolic pathways.

A novel self-powered aptasensor for digoxin monitoring based on the dual-photoelectrode membrane/mediator-free photofuel cell.

Self-powered sensor is considered as a promising, rapid, portable and miniaturized detection device that can work without external power input. In this work, a novel dual-photoelectrode self-powered aptasensor for digoxin detection was designed on the basis of a photofuel cell (PFC) composed of a black TiO2 (B-TiO2) photoanode and a CuBr photocathode in a single-chamber cell. The sensing platform avoided the use of membrane, free mediator, bioactive components and costly metal Pt electrodes. The large inherent bias between the Fermi energy level of B-TiO2 and that of CuBr improved the electricity output of PFC that the open circuit potential (OCP) and the maximum power density (Pmax) reached 0.58 V and 6.78 µW cm-2 respectively. Based on the excellent output of PFC, digoxin aptamer was immobilized on photoanode as the recognition element to capture digoxin molecules, which realized the high sensitive and selective detection of digoxin. The self-powered aptasensor displayed a broad linear in the range from 10-12 M to 10-5 M with a detection limit (3 S/N) of 0.33 pM. This work paved a luciferous way for further rapid, portable, miniaturized and on-site self-powered sensors.

Loss of Endogenous HMGB2 Promotes Cardiac Dysfunction and Pressure Overload-Induced Heart Failure in Mice.

BACKGROUND: The rapid increase in the number of heart failure (HF) patients in parallel with the increase in the number of older people is receiving attention worldwide. HF not only increases mortality but decreases quality of life, creating medical and social problems. Thus, it is necessary to define molecular mechanisms underlying HF development and progression. HMGB2 is a member of the high-mobility group superfamily characterized as nuclear proteins that bind DNA to stabilize nucleosomes and promote transcription. A recent in vitro study revealed that HMGB2 loss in cardiomyocytes causes hypertrophy and increases HF-associated gene expression. However, it's in vivo function in the heart has not been assessed. Methods and Results: Western blotting analysis revealed increased HMGB2 expression in heart tissues undergoing pressure overload by transverse aorta constriction (TAC) in mice. Hmgb2 homozygous knockout (Hmgb2-/-) mice showed cardiac dysfunction due to AKT inactivation and decreased sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a activity. Compared to wild-type mice, Hmgb2-/- mice had worsened cardiac dysfunction after TAC surgery, predisposing mice to HF development and progression. CONCLUSIONS: This study demonstrates that upregulation of cardiac HMGB2 is an adaptive response to cardiac stress, and that loss of this response could accelerate cardiac dysfunction, suggesting that HMGB2 plays a cardioprotective role.

An integrated metabolomic strategy for the characterization of the effects of Chinese yam and its three active components on septic cardiomyopathy.

Chinese yam (CY), used as both a traditional Chinese medicine and a nutritious food, is an excellent candidate for treating septic cardiomyopathy (SCM). Adenosine, arbutin and allantoin are the major active components in the aqueous extract of CY. The aim of the present study was to interpret the roles of CY, adenosine, arbutin and allantoin in SCM treatment. Firstly, significant physiological indexes were examined to assess the model and treatment effects of CY, adenosine, arbutin and allantoin. Then, a metabolomic approach was utilized to reveal the metabolic disorders in SCM concerning the intervention of CY/adenosine/arbutin/allantoin. The integrated results demonstrated that adenosine, arbutin and allantoin are responsible for the efficacy of CY on SCM treatment by regulating amino acid, arachidonic acid, sphingolipid, glycerophospholipid and glycol metabolism. Moreover, adenosine and/or arbutin could be used as a substitute for CY in treating SCM, and allantoin efficacy was slightly weaker. This integrated metabolomic approach performed excellently in understanding the herbal function and the roles of its components.

Antihypertensive effect of the methanolic extract from Eruca sativa Mill., (Brassicaceae) in rats: Muscarinic receptor-linked vasorelaxant and cardiotonic effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Eruca sativa Mill., (Brassicaceae) is a popular remedy for the treatment of hypertension in Pakistan. However, direct effect of the extract and its fractions on blood pressure and vascular tone are unknown. AIM OF THE STUDY: This investigation was aimed to explore the pharmacological base for the traditional use of E. sativa in hypertension. MATERIALS AND METHODS: In-vivo blood pressure study was carried out using normotensive and high salt-induced hypertensive rats under anaesthesia. The cardiovascular mechanisms were explored using rat aorta and atria in-vitro. Preliminary phytochemical analysis, spectrophotometric detection of total phenols, flavonoids and HPLC analysis of crude extract were performed using quercetin and erucin as marker compounds. RESULTS: Intravenous injection of crude extract induced a fall in mean arterial pressure (MAP) in both normotensive (max fall: 41.79 ±â€¯1.55% mmHg) and hypertensive (max fall: 58.25 ±â€¯0.91% mmHg) rats. Atropine (1 mg/kg) pretreatment attenuated this effect significantly (p < 0.001), suggesting the involvement of muscarinic receptor in its antihypertensive effect. Fractions also induced atropine-sensitive antihypertensive effect. Similarly, oral administration of crude and aqueous extracts resulted a fall in MAP in the hypertensive rats. In isolated rat aortic rings from normotensive rats, crude extract and fractions induced an endothelium-dependent relaxation. This relaxation was partially inhibited with L-NAME and atropine pretreatment and with denudation of aortic rings, indicating involvement of muscarinic receptor-linked nitric oxide (NO). In aorta from the hypertensive rats, crude extract and fractions induced endothelium-independent relaxation. This relaxation was not affected by pretreatment with L-NAME or atropine. Crude extract and fractions also suppressed phenylephrine contractions in Ca+2 free/EGTA medium. In isolated rat atrial preparations, crude extract and fractions induced negative inotropic and chronotropic effects with a positive inotropic effect by the n-hexane fraction, which were not affected with atropine pretreatment. Phytochemical screening and spectrophotometric analysis indicated the presence of phenols and flavonoids, whereas HPLC analysis of crude extract revealed the presence of quercetin (flavonoid) and erucin (isothiocyanate). CONCLUSION: The results suggest that E. sativa is an antihypertensive remedy which is mainly due to its vasodilatory and partly cardiac effects. Muscarinic receptors-linked NO release and dual inhibitory effect on Ca+2 influx and release underlie the vasodilation. This finding provides pharmacological base to the traditional use of E. sativa in hypertension. The presence of quercetin and erucin further support this finding.

Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia.

Friedreich's ataxia (FA) is caused by reduced levels of frataxin, a highly conserved mitochondrial protein. There is currently no effective treatment for this disease, which is characterized by progressive neurodegeneration and cardiomyopathy, the latter being the most common cause of death in patients. We previously developed a Drosophila melanogaster cardiac model of FA, in which the fly frataxin is inactivated specifically in the heart, leading to heart dilatation and impaired systolic function. Methylene Blue (MB) was highly efficient to prevent these cardiac dysfunctions. Here, we used this model to screen in vivo the Prestwick Chemical Library, comprising 1280 compounds. Eleven drugs significantly reduced the cardiac dilatation, some of which may possibly lead to therapeutic applications in the future. The one with the strongest protective effects was paclitaxel, a microtubule-stabilizing drug. In parallel, we characterized the histological defects induced by frataxin deficiency in cardiomyocytes and observed strong sarcomere alterations with loss of striation of actin fibers, along with full disruption of the microtubule network. Paclitaxel and MB both improved these structural defects. Therefore, we propose that frataxin inactivation induces cardiac dysfunction through impaired sarcomere assembly or renewal due to microtubule destabilization, without excluding additional mechanisms. This study is the first drug screening of this extent performed in vivo on a Drosophila model of cardiac disease. Thus, it also brings the proof of concept that cardiac functional imaging in adult Drosophila flies is usable for medium-scale in vivo pharmacological screening, with potent identification of cardioprotective drugs in various contexts of cardiac diseases.

Characterization of Rubia cordifolia L. root extract and its evaluation of cardioprotective effect in Wistar rat model.

OBJECTIVES: Rubia cordifolia L. (RC) is a well-known and highly valuable medicinal plant in the Ayurvedic system. The present study involves evaluating antioxidant and cardioprotective property of RC root extract. MATERIALS AND METHODS: The characterization of RC root extract was carried out using standard phytochemical and biochemical analysis. The functional groups were analyzed by Fourier transform infrared (FTIR) spectroscopy and phytotherapeutic compounds were identified using high-resolution mass spectrometry (HR-MS). Cardioprotective activity of RC root extract was investigated against cyclophosphamide (CP; 100 mg/kg, i.p)-induced cardiotoxicity in male albino Wistar rats. RC (100, 200, and 400 mg/kg, p.o) or silymarin (100 mg/kg, p.o) was administered immediately after CP on the 1st day and the next consecutive 10 days. Biochemical and histopathological analysis was performed to observe the cardioprotective effects of RC root extract. RESULTS: Phytochemical analysis revealed the presence of secondary metabolites that include alkaloids, flavonoids, saponins, and anthraquinones in RC root extract. FTIR analysis revealed the presence of several functional groups. Based on HR-MS analysis, eight major phytotherapeutic compounds were identified in methanol root extract of RC. Biochemical analysis in CP-induced rat model administered with RC extract revealed significantly enhanced levels of antioxidant markers such as superoxide dismutase, catalase, and glutathione S-transferase. Histopathological study showed that the rat model treated with the root extract had reduced the cardiac injury. CONCLUSION: Our results have shown that the RC extract contains various antioxidant compounds with cardioprotective effect. Treatment with RC root extract could significantly protect CP-induced rats from cardiac tissue injury by restoring the antioxidant markers.

A screening method for cardiovascular active compounds in marine algae.

The interaction of bioactive compounds from ethanolic extracts of selected marine algae samples, separated on chromatographic plates, with nitric/nitrous acid was investigated. The nature of bioactive compounds in the marine algae extracts was characterised using UV absorption spectra before and after reaction with diluted nitric acid, and from the characteristic colour reaction after derivatization with anisaldehyde. It was found that diterpenes from Dictyota dichotoma, an edible brown algae, and sterols from green algae Caulerpa brachypus, bind nitric oxide and may act as a nitric oxide carrier. Although the carotenoid fucoxanthin, found in all brown marine algae also binds nitric oxide, the bonds between nitrogen and the fucoxanthin molecule are much stronger. Further studies are required to evaluate the effects of diterpenes from Dictyota dichotoma and sterols from green algae Caulerpa brachypus to see if they have beneficial cardiovascular effects. The method reported here should prove useful in screening large numbers of algae species for compounds with cardiovascular activity.

Simultaneous Determination of Acetylsalicylic Acid, Hydrochlorothiazide, Enalapril, and Atorvastatin in a Polypill-Based Quaternary Mixture by TLC.

A new chromatographic-densitometric method has been developed for the qualitative and quantitative determination of the active ingredients in a simulated mixture corresponding to the PolyIran polypill, composed of acetylsalicylic acid, hydrochlorothiazide (HCT), enalapril (ENA), and atorvastatin (ATR), whose efficacy in the treatment and prevention of cardiovascular disease has been documented in clinical trials. Chromatographic separation was performed using TLC silica gel 60 plates with fluorescent indicator F254 as the stationary phase and a mixture of n-hexane-ethyl acetate-methanol-water-acetic acid (8.4 + 8 + 3 + 0.4 + 0.2, v/v/v/v/v) as the mobile phase. Densitometric measurements were carried out at λ = 210 nm when determining ENA and at λ = 265 nm in the case of the other drugs. Peaks of examined substances were well separated in the recorded chromatograms, enabling the evaluation of the results in terms of both qualitative and quantitative analysis. The method was specific for the analyzed components and was characterized by high sensitivity. The LOD was between 0.043 and 0.331 µg/spot, and LOQ was between 0.100 and 0.942 µg/spot. Recovery was in the range of 97.02-101.34%. The linearity range was broad and ranged from 0.600 to 6.000 µg/spot for acetylsalicylic acid, from 0.058 to 1.102 µg/spot for HCT, from 0.505 to 6.560 µg/spot for ENA, and from 0.100 to 1.000 µg/spot for ATR. The method was characterized by good precision, with RSD values that ranged from 0.10 to 2.26%.

Benefits of the beer polyphenols on the gut microbiota / Beneficios de los polifenoles contenidos en la cerveza sobre la microbiota intestinal

Gut microbiota has a central role in the homeostasis of the host. Diet is one of the key factors affecting and modulating gut microbiota profile. Dietary polyphenols, which belongs to the non-digestible part of the diet, reach the colon almost unaltered. Polyphenols and gut microbiota put in contact within the colon, where gut microbiota transforms polyphenols to give their bioactivity. The moderate consumption of alcohol is associated with a lower cardiovascular risk and mortality, with the highest cardioprotective effects from the fermented beverages with a high amount of polyphenols. Beer, with a medium amount of polyphenols, is potentially classified within these beverages with a cardioprotective role. Beer sources and the production of the different varieties are going to change the amount and profiles of the beer polyphenols. Thus, the relationship with the gut microbiota could be different among the different types of beer, with different results for the host. In this manner, it could be said that the healthy benefits reported by the beer consumption could be mediated, at least partially, by the gut microbiota. However, more detailed studies are necessary.

La microbiota intestinal se ha erigido actualmente como un órgano clave para la correcta homeostasis del organismo. La dieta se encuentra entre los factores que más van a influir en el perfil de esta microbiota. Los polifenoles dietéticos que forman parte del componente no digerible de la dieta llegan casi inalterados al intestino grueso, donde entran en contacto con la microbiota colónica. Esta microbiota va a intervenir en el proceso de transformación en metabolitos bioactivos de un menor peso molecular, dotándoles de su poder bioactivo. El consumo moderado de alcohol está asociado a un menor riesgo cardiovascular y de mortalidad, siendo las bebidas fermentadas con un alto contenido en polifenoles aquellas con unos efectos cardioprotectores mayores. La cerveza, con un contenido medio en polifenoles, potencialmente se enmarca dentro de estas bebidas con un efecto cardioprotector. Las materias primas y el proceso de fabricación de los distintos tipos de cerveza van a provocar que los tipos y contenidos en polifenoles varíen y que, por lo tanto, se puedan encontrar diferentes relaciones con la microbiota intestinal, con unos resultados para el hospedador diferentes. Así, se podría inferir que los beneficios para la salud reportados por el consumo de cerveza podrían estar mediados, al menos parcialmente, por la microbiota intestinal, aunque son necesarios estudios pormenorizados al respecto.

Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA.

Oxilofrine (4-[1-hydroxy-2-(methylamino)propyl]phenol) is a pharmaceutical stimulant prescribed in dosages of 16 to 40 mg to stimulate the heart and increase blood pressure. It has never been approved for use in the USA as a prescription drug or as a dietary supplement. Several athletes, however, have been banned from sport for testing positive for oxilofrine and have claimed that they inadvertently consumed oxilofrine in sports supplements. Consumption of supplements containing oxilofrine may also pose serious health risks. For example, one brand of supplements containing oxilofrine has been linked to serious adverse events including vomiting, agitation, and cardiac arrest. We designed our study to determine the presence and quantity of oxilofrine in dietary supplements sold in the USA. A validated ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometry method was developed for the identification and quantification of oxilofrine. The separation was achieved using a reversed phase column, mass spectrometry detection, and a water/acetonitrile gradient as the mobile phase. The presence of oxilofrine was confirmed using a reference standard. We analyzed 27 brands of supplements labelled as containing a synonym of oxilofrine ('methylsynephrine') and found that oxilofrine was present in 14 different brands (52%) at dosages ranging from 0.0003 to 75 mg per individual serving. Of the supplements containing oxilofrine, 43% (6/14) contained pharmaceutical or greater dosages of oxilofrine. Following instructions on the label, consumers could ingest as much as 250 mg of oxilofrine per day. The drug oxilofrine was found in pharmacological and greater dosages in supplements labelled as containing methylsynephrine. Copyright © 2016 John Wiley & Sons, Ltd.

A Review on Phytochemistry and Pharmacology of Cortex Periplocae.

Cortex Periplocae, as a traditional Chinese herbal medicine, has been widely used for autoimmune diseases, especially rheumatoid arthritis. Due to its potential pharmaceutical values, more studies about the biological activities of Cortex Periplocae have been conducted recently. Meanwhile, the adverse reaction of Cortex Periplocae is not a negligible problem in clinic. In this article, we reviewed a series of articles and summarized the recent studies of Cortex Periplocae in the areas of phytochemistry and pharmacology. More than 100 constituents have been isolated and identified from Cortex Periplocae, including steroids, cardiac glycosides, terpenoids, and fatty acid compounds. The crude extracts of Cortex Periplocae and its active compounds exhibit various biological activities, such as cardiotonic effect, anticancer action, and anti-inflammatory effect. This paper aims to provide an overall review on the bioactive ingredients, pharmacological effect, and toxicity of this plant. Furthermore, this review suggests investigating and developing new clinical usages according to the above pharmacological effects.

Screening of Bioactive Ingredients in Ligusticum Chuanxiong Hort for Protection against Myocardial Ischemia.

BACKGROUND/AIMS: To study the spectrum-effect relationship and effective components of Ligusticum Chuanxiong Hort. (LCH) on the protection of canine myocardial ischemia. METHODS: Fingerprint spectrum of LCH extracts was developed using high performance liquid chromatography (HPLC), and a canine model of acute myocardial ischemia was established by ligating the coronary artery. Bivariate correlation analysis and multivariate regression analysis were used to correlate the pharmacodynamics of LCH extract and its common peaks in HPLC. RESULTS: The bioactive components of LCH were ligustrazine, ferulic acid, cnidilide and ligustilide. Ligustrazine and ferulic acid could significantly reduce serum lactic acid in canine model of acute myocardial ischemia, while ligustilide could significantly reduce the elevation of serum free fatty acid. CONCLUSIONS: The spectrum-effect relationship study shows that the effective components of LCH are ligustrazine, ferulic acid, cnidilide and ligustilide, which have protective effect on myocardial ischemia.

A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model.

AIM: There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI), for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR) injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury. METHODS AND RESULTS: In a rat IR model, poly(lactic acid/glycolic acid) (PLGA) nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg) at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg) showed no therapeutic effects. The therapeutic effects of Pitavastatin-NP were blunted by a PI3K inhibitor wortmannin, but not by a mitochondrial permeability transition pore inhibitor cyclosporine A. Pitavastatin-NP induced phosphorylation of Akt and GSK3ß, and inhibited inflammation and cardiomyocyte apoptosis in the IR myocardium. CONCLUSIONS: Nanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.

Rapid quantification of digitoxin and its metabolites using differential ion mobility spectrometry-tandem mass spectrometry.

This study focuses on the quantitative analysis of the cardiac glycoside drug digitoxin and its three main metabolites digitoxigenin-bisdigitoxose, digitoxigenin-monodigitoxose, and digitoxigenin using electrospray ionization-differential ion mobility spectrometry-tandem mass spectrometry (ESI-DMS-MS/MS). Despite large molecular weight differences, gas-phase separation of the four compounds in the DMS drift cell was not possible, even by utilizing additional volatile chemical modifiers. Baseline separation was achieved after adduct formation with alkali metal ions, however, and efficiency was shown to improve with increasing size of the alkali ion, reaching optimum conditions for the largest cesium ion. Subsequently, an assay was developed for quantification of digitoxin and its metabolites from human serum samples and its analytical performance assessed in a series of proof-of-concept experiments. The method was applied to spiked human serum pools with concentration levels between 2 and 80 ng/mL. After a short reversed-phase chromatographic step for desalting the sample, rapid DMS separation of the analytes was carried out, resulting in a total run time of less than 1.5 min. The instrumental method showed good repeatability; the calculated coefficients of variation ranged from 2% to 13%.

Castanea sativa by-products: a review on added value and sustainable application.

Castanea sativa Mill. is a species of the family Fagaceae abundant in south Europe and Asia. The fruits (chestnut) are an added value resource in producing countries. Chestnut economic value is increasing not only for nutritional qualities but also for the beneficial health effects related with its consumption. During chestnut processing, a large amount of waste material is generated namely inner shell, outer shell and leaves. Studies on chestnut by-products revealed a good profile of bioactive compounds with antioxidant, anticarcinogenic and cardioprotective properties. These agro-industrial wastes, after valorisation, can be used by other industries, such as pharmaceutical, food or cosmetics, generating more profits, reducing pollution costs and improving social, economic and environmental sustainability. The purpose of this review is to provide knowledge about the type of chestnut by-products produced, the studies concerning its chemical composition and biological activity, and also to discuss other possible applications of these materials.

Rapid detection of convallatoxin using five digoxin immunoassays.

CONTEXT: Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detecting foxglove and oleander ingestion has been demonstrated, but no studies have evaluated the structurally similar convallatoxin found in Convallaria majalis (lily of the valley) for rapid laboratory screening, nor has digoxin immune Fab been tested as an antidote for this ingestion. OBJECTIVE: We aimed to (1) evaluate multiple digoxin assays for cross-reactivity to convallatoxin, (2) identify whether convallatoxin could be detected in vivo at clinically significant doses, and (3) determine whether digoxin immune Fab could be an effective antidote to convallatoxin. MATERIALS AND METHODS: Cross-reactivities of purified convallatoxin and oleandrin with five common digoxin immunoassays were determined. Serum from mice challenged with convallatoxin was tested for apparent digoxin levels. Binding of convallatoxin to digoxin immune Fab was determined in vitro. RESULTS: Both convallatoxin and oleandrin were detectable by a panel of commonly used digoxin immunoassays, but cross-reactivity was variable between individual assays. We observed measurable apparent digoxin levels in serum of convallatoxin intoxicated mice at sublethal doses. Convallatoxin demonstrated no binding by digoxin immune Fab. CONCLUSION: Multiple digoxin immunoassays detect botanical cardiac glycosides including convallatoxin and thus may be useful for rapid determination of severe exposures, but neutralization of convallatoxin by digoxin immune Fab is unlikely to provide therapeutic benefit.

Efecto inotrópico positivo ejercido por el derivado de brucina en un modelo de corazón aislado de rata / Inotropic effect exerted by the brucine derivativein an isolated rat heart mode / Efeito inotrópico exercida pelo derivado de brucinaem um modelo de corações isolados de ratos

Existen pocos datos con respecto a los efectos de la brucina y sus derivados en el aparato cardiovascular; además, el mecanismo molecular y su sitio de acción celular no son claros. Para proporcionar información adicional acerca de este fenómeno, en este trabajo fue evaluado el efecto inducido por un derivado de la brucina sobre la presión de perfusión, la resistencia vascular y la presión ventricular izquierda en corazón aislado de rata a flujo constante (modelo de Langendorff). Los resultados mostraron que; 1) el derivado brucina (1×10-9 mM) incrementa la presión de perfusión y la resistencia vascular en comparación con la brucina (1×10-9 mM) y las condiciones de control; 2) los efectos del derivado de brucina en dosis de 1×10-9 a 1×10-4 mM sobre la presión intraventricular no fueron inhibidos por metoprolol, prazosina o nifedipino a dosis de 1×10-6 mM; y 3) la furosemida a dosis de 1×10-6 mM bloquea los efectos ejercidos por el derivado de brucina (1×10-9 a 1×10-4 mM) sobre la presión intraventricular. En conclusión, la actividad ejercida por el derivado de brucina sobre la presión ventricular izquierda, involucra inhibición de la bomba Na+/K+-ATPasa, lo que trae indirectamente cambios en los niveles de calcio intracelular y subsecuentemente un efecto inotrópico positivo.

Few data exist with respect to the effects of brucine and its derivatives at a cardiovascular level; furthermore, the molecular mechanism and its site of cellular action are still unclear. In order to provide additional information about this phenomenon, the effect induced by a brucine derivative on perfusion pressure, vascular resistance and left ventricular pressure was evaluated in anisolated rat heart at constant flow (Langendorff model). The results showed that: 1) The brucine derivative [1×10-9 mM] increased perfusion pressure and vascular resistance in comparison with the brucine [1×10-9 mM] and the control conditions; 2) the effects of brucine derivative [1×10-9 to 1×10-4 mM] on intraventricular pressure were not inhibited by metoprolol, prazosin or nifedipine at a 1×10-6 mM dose; 3) furosemide [1×10-6 mM] blocked the effects exerted by the brucine derivative [1×10-9 a 1×10-4 mM] on intraventricular pressure. In conclusion, the activity exerted by the brucine derivative on perfusion pressure, vascular resistance and left ventricular pressure, involves inhibition of Na+/K+-ATPase, consequently resulting in indirect changes in intracellular calcium levels and subsequently inducing a positive inotropic effect.

Existem poucos dados no que diz respeito aos efeitos da brucina e seus derivados no nível cardiovascular; além disso, o mecanismo molecular e seu local de ação celular não são claros. Para fornecer informações adicionais sobre este fenômeno, neste trabalho foi avaliado o efeito induzido por um derivado de brucina sobre a pressão de perfusão, a resistência vascular e a pressão ventricular esquerda em coração isolado de ratos em fluxo constante (modelo Langendorff). Os resultados mostraram que: 1) o derivado brucina (1×10-9 mM) aumenta a pressão de perfusão e a resistência vascular em comparação com a brucina (1×10-9 mM) e as condições de controle; 2) os efeitos do derivado de brucina em doses de 1×10-9 a 1×10-4 mM sobre a pressão intraventricular não foram inibidos por metoprolol, prazosina ou nifedipino em doses de 1×10-6 mM; e 3) a furosemida, em doses de 1×10-6 mM, bloqueia os efeitos exercidos pelo derivado de brucina (1×10-9 a 1×10-4 mM) sobre a pressão intraventricular. Em conclusão, a atividade exercida pelo derivado de brucina sobre a pressão ventricular esquerda, envolve a inibição da bomba de Na+/K+-ATPase, o que indiretamente traz alterações nos níveis de cálcio intracelular e, subsequentemente, um efeito inotrópico positivo.