Sample records for cardiotonics

  1. Cardiotonic Steroids as Modulators of Neuroinflammation (United States)

    Orellana, Ana Maria; Kinoshita, Paula Fernanda; Leite, Jacqueline Alves; Kawamoto, Elisa Mitiko; Scavone, Cristoforo


    Cardiotonic steroids (CTS) are a class of specific ligands of the Na+, K+- ATPase (NKA). NKA is a P-type ATPase that is ubiquitously expressed and although well known to be responsible for the maintenance of the cell electrochemical gradient through active transport, NKA can also act as a signal transducer in the presence of CTS. Inflammation, in addition to importantly driving organism defense and survival mechanisms, can also modulate NKA activity and memory formation, as well as being relevant to many chronic illnesses, neurodegenerative diseases, and mood disorders. The aim of the current review is to highlight the recent advances as to the role of CTS and NKA in inflammatory process, with a particular focus in the central nervous system. PMID:26909067

  2. Cardiotonic and antidysrhythmic effects of oleanolic and ursolic acids, methyl maslinate and uvaol. (United States)

    Somova, L I; Shode, F O; Mipando, M


    The cardiotonic and antidysrhythmic effects of four triterpenoid derivatives, namely oleanolic acid (OA), ursolic acid (UA), and uvaol (UV), isolated from the leaves of African wild olive (Olea europaea, subsp. africana) as well as methyl maslinate (MM) isolated from the leaves of Olea europaea (Cape cultivar) were examined. The derivatives showed low toxicity on brine shrimp test. They displayed significant, dose-response vasodepressor effect and sinus bradicardia, most prominent for OA and MM. The derivatives acted as beta-adrenergic antagonists, blocking the effect of adrenaline and isoprenaline. The established positive inotropic and dromotropic effects were most distinctive for OA and MM. The antidysrhythmic effects were evaluated on CaCl2- and adrenaline-induced chemical arrhythmias, and on ischemia-reperfusion arrhythmia. OA and UA displayed antidysrhythmic effects on both types of chemical arrhythmia; OA and UV in dose 40 mg/kg conferred significant antidysrhythmic activity on ischemia and reperfusion arrhythmias. The effect was comparable to that of propranolol and suggestive of beta-adrenergic antagonistic activity. On the basis of the vasodepressor, cardiotonic and antidysrhythmic effects of these compounds, it was concluded that OA and UV isolated from wild African olive leaves, or crude extract containing all components, can provide a cheap and accessible source of additive to conventional treatment of hypertension, complicated by stenocardia and cardiac failure.

  3. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension

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    Aneta Paczula


    Full Text Available Endogenous cardiotonic steroids (CTS, also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na+/K+-ATPase. A portion of Na+/K+-ATPase does not seem to actively “pump” sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications.

  4. Phytochemical and pharmacological activity profile of Crataegus oxyacantha L. (hawthorn) - A cardiotonic herb. (United States)

    Orhan, Ilkay Erdogan


    Crataegus oxyacantha L. (syn. C. rhipidophylla Gand.) (Rosaceae) is one of two medicinally recognized hawthorn species in European Pharmacopeia. Standardization of the extract prepared from the berry and flowers of the plant is required according to its oligomeric procyanidins. C. oxyacantha is well-known for its use in the treatment of various heart problems particularly, including heart failure in cases of declining cardiac performance equivalent to stages I and II of the New York Heart Association classification, angina pectoris, hypertension with myocardial insufficiency, mild alterations of cardiac rhythm, and atherosclerosis. C. oxyacantha has been reported to exert several other pharmacological activities such as hypotensive, antihyperlipidemic, antihyperglycemic, anxiolytic, immunomodulatory, and antimutagenic. Oligomeric procyanidins and flavone/flavonol types of flavonoids, which are considered to be the chief groups of active substances, phenolic acids, triterpenes, fatty acids, and sterols are present in the plant. The present review aims mainly to outline cardiotonic effect of C. oxyacantha as well as its brief phytochemistry. Numerous experiments and clinical studies have underlined cardiovascular efficacy of the plant through various mechanisms including positive inotropic and negative chronotropic effects, escalation in coronary blood flow and exercise tolerance, inhibition of the enzymes such as angiotensin-converting enzyme (ACE) and phosphodiesterase, anti-inflammatory and antihyperlipidemic effects, improving status of antioxidant enzymes, etc., which support its cardioactive efficacy. The plant possesses several other bioactivities for human health usually concomitant to its rich polyphenolic content.

  5. Stabilisation of Na,K-ATPase structure by the cardiotonic steroid ouabain

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    Miles, Andrew J. [Institute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX (United Kingdom); Fedosova, Natalya U. [Department of Biomedicine, Aarhus University, DK-8000 Aarhus (Denmark); Hoffmann, Søren V. [ISA, Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus (Denmark); Wallace, B.A. [Institute of Structural and Molecular Biology, Birkbeck College, University of London, London WC1E 7HX (United Kingdom); Esmann, Mikael, E-mail: [Department of Biomedicine, Aarhus University, DK-8000 Aarhus (Denmark)


    Highlights: •Ouabain binding to pig and shark Na,K-ATPase enhances thermal stability. •Ouabain stabilises both membrane-bound and solubilised Na,K-ATPase. •Synchrotron radiation circular dichroism is used for structure determination. •Secondary structure in general is not affected by ouabain binding. •Stabilisation is due to re-arrangement of tertiary structure. -- Abstract: Cardiotonic steroids such as ouabain bind with high affinity to the membrane-bound cation-transporting P-type Na,K-ATPase, leading to complete inhibition of the enzyme. Using synchrotron radiation circular dichroism spectroscopy we show that the enzyme-ouabain complex is less susceptible to thermal denaturation (unfolding) than the ouabain-free enzyme, and this protection is observed with Na,K-ATPase purified from pig kidney as well as from shark rectal glands. It is also shown that detergent-solubilised preparations of Na,K-ATPase are stabilised by ouabain, which could account for the successful crystallisation of Na,K-ATPase in the ouabain-bound form. The secondary structure is not significantly affected by the binding of ouabain. Ouabain appears however, to induce a reorganization of the tertiary structure towards a more compact protein structure which is less prone to unfolding; recent crystal structures of the two enzymes are consistent with this interpretation. These circular dichroism spectroscopic studies in solution therefore provide complementary information to that provided by crystallography.

  6. Biological Evaluation of Polyherbal Ayurvedic Cardiotonic Preparation “Mahamrutyunjaya rasa”

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    Pallavi D. Rai


    Full Text Available Mahamrutyunjaya rasa (MHR, an Ayurvedic formulation, used as cardiotonic, contains potentially toxic compounds like aconitine, which are detoxified during preparation using traditional methods. Comparative toxicological evaluation of laboratory prepared formulation (F1 and two marketed formulations (F2 and F3 were performed based on their effects on viability of H9c2 cells and after single oral dose administration in mice. Cardioprotective effect of formulations at 25 and 50 mg/kg doses were studied in isoproterenol- (ISO- induced myocardial infarcted rats. F1 and F2 did not affect the cell viability, while F3 decreased the cell viability in concentration and time-dependent manner. Rats administered with ISO showed significant increase in the serum levels of glutamate oxaloacetate transaminase, alkaline phosphotase, creatinine kinase isoenzymes, lactate dehydrogenase, and uric acid, while F1 and F2 treatment showed significant reduction in the same. F3 showed further increase in the serum levels of enzymes and uric acid in ISO-challenged rats. High pressure liquid chromatographic analysis of formulations showed higher concentration of aconitine in F3. Study shows that F1 and F2 possess cardioprotective property with higher safety, while formulation F3 cannot be used as cardioprotective due to its cytotoxic effects. Thus, proper quality assessment methods are required during preparation of traditional formulations.

  7. Arterial and venous vasodilator actions of RS-1893, a novel cardiotonic agent, in the hindlimb preparation of the dog. (United States)

    Miyake, S; Shiga, H; Koike, H


    RS-1893, an orally active cardiotonic agent, has been suggested to dilate venous blood vessels, because it markedly decreases central venous pressure in anesthetized dogs. In order to evaluate venous vasodilator action of the agent, we measured hindlimb volume (HLV) in anesthetized dogs using a plethysmographic technique. RS-1893 (1-10 micrograms/kg, i.v.) produced dose-dependent increases in HLV, femoral blood flow, and left ventricular (LV)dP/dt, and a decrease in central venous pressure (CVP). In another series of experiments, we autoperfused the hindlimb with a constant flow and injected the drugs intraarterially (i.a.) to separately evaluate arterial and venous vasodilator actions. In this preparation, a decrease in perfusion pressure and an increase in HLV were considered to reflect arterial vasodilatation and venous vasodilatation, respectively. RS-1893 (0.3-3 micrograms i.a.) produced a dose-dependent increase in HLV and a decrease in perfusion pressure. Comparison of doses which increased HLV by 0.3 ml revealed that RS-1893 was about 20 times more potent than milrinone. The arterial vasodilator action of RS-1893 was about 15 times more potent than that of milrinone. We conclude that RS-1893 is a potent venous and arterial vasodilator with cardiotonic activity.

  8. The effects of low concentrations of cardiotonic steroids on membrane currents and tension in sheep Purkinje fibres. (United States)

    Hart, G; Noble, D; Shimoni, Y


    1. Simultaneous measurements of voltage-clamp currents and tension were made in shortened sheep Purkinje fibres exposed to various concentrations of strophanthidin, ouabain and digoxin.2. In 5.4 mM-K moderate doses (mean 2.4 x 10(-7)M) of the drugs produced an inward shift of the current-voltage relationship at very negative potentials, consistent with an increase in cleft K concentration (Cohen, Daut & Noble, 1976b), which was always accompanied by an increase in tension. This change, which has been attributed to Na-K pump inhibition, was often better correlated with an increase in voltage-dependent tonic tension than in twitch tension.3. Exposure to dihydro-ouabain gave a monotonic increase in tension but a delayed increase in inward current. This suggests (cf. Lee, Kang, Sokol & Lee, 1980) that minor changes in pump activity may not always change the current-voltage relationship.4. Low concentrations of strophanthidin (5 x 10(-9) to 5 x 10(-7) M) produced an outward current shift at very negative potentials, this change becoming smaller with a more rapid onset and reversing on increasing the dose. This change is attributed to pump stimulation.5. The outward current shift was often associated with a negative inotropic effect, which always reversed either spontaneously or on removal of the drug.6. The alternative response at a narrower dose range (1 x 10(-8) to 2 x 10(-7) M) was an increase in twitch (not tonic) tension, termed the low-dose positive inotropic effect.7. After a low concentration of cardiotonic steroid had given an early negative inotropic effect the bulk Ca concentration was reduced and the drug re-applied. The low-dose positive inotropic mechanism was then observed.8. Outward current shifts and negative inotropy were also obtained with low concentrations of the clinically used glycosides digoxin and ouabain.9. Low concentrations of strophanthidin applied to externally stimulated sheep ventricular trabeculae produced negative inotropy with

  9. Effects on the sodium channel of some new cardiotonic drugs: the 4-, 5-, and 6-pyridyl-2(1H)-quinolone derivatives

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    Grima, M.; Beguin, M.F.; Millanvoye-Van Brussel, E.M.; Decker, N.; Schwartz, J.


    To study the action of some new cardiotonic drugs, the 4-, 5-, and 6-pyridyl-2(1H)-quinolone series, on the fast Na+ channel, we compared the effects of eight compounds of this series and milrinone on /sup 22/Na uptake in rat brain synaptosomes and in rat heart muscle cells in culture. The action of tetrodotoxin, a specific Na+ channel blocker, on the positive inotropic effect of these compounds on guinea pig atria was also examined. The new positive inotropic agents enhance /sup 22/Na uptake in synaptosomes in a dose-dependent manner. The activities, expressed as percentage of the maximum activity of protoveratrine B, a classic Na+ channel agonist, reached 70% for milrinone, 60% for compound 7, 57% for compound 6, and less than 50% for the other drugs. For compound 8, but not for milrinone, it was possible to observe a stimulatory effect of the /sup 22/Na uptake on heart muscle cells in culture. Tetrodotoxin (1 and 100 microM) inhibited the stimulatory effects of the inotropic drugs on both preparations. The positive inotropic activities of protoveratrine B, milrinone, and compounds 5 and 8, in guinea pig atria, were inhibited by tetrodotoxin. The affinity and the activity of the other compounds were unchanged in the presence of tetrodotoxin. Our results showed that the stimulation of Na+ influx through the fast Na+ channel might represent a part of the mechanism of action of the inotropic effect of some new cardiotonic drugs.

  10. 3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates--new group of potential cardiotonic drugs. (United States)

    Krauze, A; Vītoliņa, R; Garaliene, V; Sīle, L; Klusa, V; Duburs, G


    3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates 6-11 were prepared by a Michael reaction of N-acetonylpyridinium chloride with 3-aryl-2-cyanothioacrylamides or by a one-pot three-carbon condensation of N-acetonylpyridinium chloride, aromatic aldehyde and 2-cyanothioacetamide, and their cardiotonic properties were studied. 3,4-trans-5-cyano-2-hydroxy-2-methyl-4-(3-nitrophenyl)-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolate 8 was considered as a lead compound in this series since it in vitro experiments (spontaneously beating rat atria) showed a cardiotonic activity similar to that of milrinone 2, however compound 8 induced activity at lover concentrations and without influence on chronotropic action of the heart. Unlike milrinone 2, thiolate 8 in vivo experiments (anaesthetized rats) did not influence blood pressure and heart rate. The acute toxicity of compound 8 was more than 10 times lower than that of milrinone 2.

  11. Cardiac effects of r-79595 and its isomers (r-80122 and r-80123) in an acute heart-failure model - a new class of cardiotonic agents with highly selective phosphodiesterase-iii inhibitory properties

    NARCIS (Netherlands)



    R 79595 (N-cyclohexyl-N-methyl-2-[[[phenyl (1,2,3,5-tetrahydro-2 oxoimidazo [2,1-b]-quinazolin-7-yl) methylene] amin] oxy] acetamide) and its isomers represent a novel class of compounds with phosphodiesterase (PDE) inhibitory and cardiotonic (positive inotropic) actions. The cardiac effects of this

  12. Pharmacological investigation on nigrescigenin-a cardenolide from Parquetina nigrescens (Afzel.) Bullock: comparative studies on cardiotonic effects of Parquetina nigrescens, g-strophanthin and noradrenaline in guinea-pig isolated atria. (United States)

    Datté, J Y; Ziegler, A


    The cardiotonic and catecholamine-like effects of Parquetina nigrescens extract-induced contractile force of guinea-pig left and right atria were investigated in-vitro. Isometric contractions were recorded. P. nigrescens extract, 5-150 microg mL(-1), increased the force of contraction dose dependently in electrically driven left atria. The concentration of P. nigrescens extract producing 50% of the maximal effect (EC50 value) was 7.5 microg mL(-1). The positive inotropic response differed from that of g-strophanthin by its high rate of onset and its complete reversibility upon removal of the extract from the incubation medium. In spontaneously beating right atrial muscle, P. nigrescens extract increased the rate of contractions. Its positive chronotropic and inotropic effects were partly antagonized by propranolol and atenolol indicating the presence of an adrenergic acting principle in P. nigrescens extract. In contrast, the inotropic response to P. nigrescens extract could not be completely suppressed by beta-blocking agents, suggesting that the force of contraction is not only increased by a sympathomimetic ingredient of P. nigrescens extract but also by the cardenolides known to be present in P. nigrescens.

  13. Suppression of Adenovirus Replication by Cardiotonic Steroids. (United States)

    Grosso, Filomena; Stoilov, Peter; Lingwood, Clifford; Brown, Martha; Cochrane, Alan


    The dependence of adenovirus on the host pre-RNA splicing machinery for expression of its complete genome potentially makes it vulnerable to modulators of RNA splicing, such as digoxin and digitoxin. Both drugs reduced the yields of four human adenoviruses (HAdV-A31, -B35, and -C5 and a species D conjunctivitis isolate) by at least 2 to 3 logs by affecting one or more steps needed for genome replication. Immediate early E1A protein levels are unaffected by the drugs, but synthesis of the delayed protein E4orf6 and the major late capsid protein hexon is compromised. Quantitative reverse transcription-PCR (qRT-PCR) analyses revealed that both drugs altered E1A RNA splicing (favoring the production of 13S over 12S RNA) early in infection and partially blocked the transition from 12S and 13S to 9S RNA at late stages of virus replication. Expression of multiple late viral protein mRNAs was lost in the presence of either drug, consistent with the observed block in viral DNA replication. The antiviral effect was dependent on the continued presence of the drug and was rapidly reversible. RIDK34, a derivative of convallotoxin, although having more potent antiviral activity, did not show an improved selectivity index. All three drugs reduced metabolic activity to some degree without evidence of cell death. By blocking adenovirus replication at one or more steps beyond the onset of E1A expression and prior to genome replication, digoxin and digitoxin show potential as antiviral agents for treatment of serious adenovirus infections. Furthermore, understanding the mechanism(s) by which digoxin and digitoxin inhibit adenovirus replication will guide the development of novel antiviral therapies.

  14. Cardiovascular Drugs: Implications for Dental Practice Part 1 — Cardiotonics, Diuretics, and Vasodilators (United States)

    Becker, Daniel E


    Appropriate preoperative assessment of dental patients should always include analysis of their medications. Cardiovascular diseases are the most common group of medical disorders that dentists encounter, and the number of drugs prescribed for managing these conditions is staggering. This justifiably raises concern and probable confusion regarding side effects and possible drug interactions with medications the dentist may deem necessary for dental care. This continuing education article is the first in a series that will address essential pharmacology of medications commonly prescribed for chronic medical care. A reasonable understanding of these agents will allow the dentist to better appreciate the medical status of their patients and avoid adverse interactions with drugs they might administer or prescribe. PMID:18085840

  15. The cardiotonic effect of the crude ethanolic extract of Nerium oleander in the isolated guinea pig hearts. (United States)

    Adome, R O; Gachihi, J W; Onegi, B; Tamale, J; Apio, S O


    Cardiovascular diseases are increasingly becoming one of the leading diseases causing morbidity and mortality in Uganda. Ethnographic evidence suggests that these diseases are often first managed by indigenous and related herbs before patients are referred for allopathic forms of management. One such herb of interest is Nerium oleander. Therefore the crude ethanolic extracts of the dried leaves of this herb were tested against the following parameters in the isolated guinea pig hearts: force of contraction, heart rate and cardiac flow. The extracts brought about dose-dependent increases in all these parameters from their baseline readings. Compared with graded doses of digoxin the effects closely mirrored the activities in a dose dependent manner. At the mechanism of action level, it would appear the extract works in the same as digoxin since their dose-contraction-response curves are parallel. This finding would tend to provide a strong rationale for the herb's traditional use in cardiovascular illness.

  16. The cardiotonic effect of the crude ethanolic extract of Nerium oleander in the isolated guinea pig hearts



    Cardiovascular diseases are increasingly becoming one of the leading diseases causing morbidity and mortality in Uganda. Ethnographic evidence suggests that these diseases are often first managed by indigenous and related herbs before patients are referred for allopathic forms of management. One such herb of interest is Nerium oleander. Therefore the crude ethanolic extracts of the dried leaves of this herb were tested against the following parameters in the isolated guinea pig hearts: force ...


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    V. N. Poptsov


    Full Text Available In our study there were 56 patients (54 men and 2 female in age from 16 to 61 (41,2 ± 2,7 years. Severity of CHF in 36 (64,3% patients were corresponded III class NYHA, in 20 (35,7% patients – IV class. 12 (15,5% patients was in 1B status of UNOS, 44 (60,8 % patients – in II status. In all cases biatrial technique of OHT was used, total ischemic time was 107–330 (170 ± 11 min. All recipients were divided on two investigate groups. In the 1-st group (n = 31 recipients with pretransplant ischemic cardiomyopathy (ICM were included, in the 2-nd group (n = 25 – recipients with pretransplant dilated cardiomyopathy (DCM. There was no difference bet- ween groups in basic preoperative characteristic, ischemic transplant time, duration of cardiopulmonary bypass, type and severity of cardiac transplant dysfunction. Our study showed that ICM-group patients had higher level indexed systemic vascular resistance since 3 postoperative day, required more frequent use of dobutamine and isorbide dinitrate for systemic and pulmonary hemodynamic management in this category of heart recipients. Also ICM-group patients had more preferable systemic hemodynamic conditions for application of prostaglan- din E1 in more effective doses. 

  18. Structure-activity relationships of alkylxanthines: alkyl chain elongation at the N1- or N7-position decreases cardiotonic activity in the isolated guinea pig heart. (United States)

    Sanae, F; Ohmae, S; Kurita, M; Sawanishi, H; Takagi, K; Miyamoto, K


    Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the N1- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.

  19. Is phosphodiesterase inhibition arrhythmogenic? Electrophysiologic effects in pithed rats and in normoxic and hypoxic rabbit atria of enoximone, a new cardiotonic agent. (United States)

    Vaughan Williams, E M


    The positive inotropic and chronotropic actions of enoximone were confirmed. At concentrations within the clinical range, enoximone prolonged the chronotropic and hypotensive action of isoproterenol in pithed rats. Very high doses of both enoximone and isoproterenol caused ventricular fibrillation in only one of six rats. In isolated rabbit atria, the maximum frequency at which pacing stimuli were followed 1:1 was increased by enoximone, and atrial flutter was consistently induced, then terminated by greatly suprathreshold stimulation. Enoximone significantly shortened action potential duration (APD), but did not exacerbate the APD-shortening induced by hypoxia. Since such hypoxia-induced shortening occurred in the presence of glucose 11 mmol/L and oxygen 20%, it was concluded that it was unlikely to have been caused by the opening of ATP-regulated potassium channels. These animal experiments suggest that enoximone, at concentrations encountered clinically in humans, does not have any electrophysiologic actions that would be likely to increase the probability of arrhythmias.

  20. Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery

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    Marco Simonini


    Full Text Available Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO, an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p=0.001, positively with Cardiac End-Diastolic Diameter (p=0.047, and positively with plasmatic NT-proBNP level (p=0.02. Moreover, a different plasmatic EO level (both preoperative and postoperative was found according to NYHA class (p=0.013. All these results have been replicated on an independent cohort of patients (147 subjects from US. Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p=0.023 for 30-day morality. Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery.

  1. 21-Benzylidene Digoxin: A Proapoptotic Cardenolide of Cancer Cells That Up-Regulates Na,K-ATPase and Epithelial Tight Junctions (United States)

    Rocha, Sayonarah C.; Pessoa, Marco T. C.; Neves, Luiza D. R.; Alves, Silmara L. G.; Silva, Luciana M.; Santos, Herica L.; Oliveira, Soraya M. F.; Taranto, Alex G.; Comar, Moacyr; Gomes, Isabella V.; Santos, Fabio V.; Paixão, Natasha; Quintas, Luis E. M.; Noël, François; Pereira, Antonio F.; Tessis, Ana C. S. C.; Gomes, Natalia L. S.; Moreira, Otacilio C.; Rincon-Heredia, Ruth; Varotti, Fernando P.; Blanco, Gustavo; Villar, Jose A. F. P.; Contreras, Rubén G.; Barbosa, Leandro A.


    Cardiotonic steroids are used to treat heart failure and arrhythmia and have promising anticancer effects. The prototypic cardiotonic steroid ouabain may also be a hormone that modulates epithelial cell adhesion. Cardiotonic steroids consist of a steroid nucleus and a lactone ring, and their biological effects depend on the binding to their receptor, Na,K-ATPase, through which, they inhibit Na+ and K+ ion transport and activate of several intracellular signaling pathways. In this study, we added a styrene group to the lactone ring of the cardiotonic steroid digoxin, to obtain 21-benzylidene digoxin (21-BD), and investigated the effects of this synthetic cardiotonic steroid in different cell models. Molecular modeling indicates that 21-BD binds to its target Na,K-ATPase with low affinity, adopting a different pharmacophoric conformation when bound to its receptor than digoxin. Accordingly, 21-DB, at relatively high µM amounts inhibits the activity of Na,K-ATPase α1, but not α2 and α3 isoforms. In addition, 21-BD targets other proteins outside the Na,K-ATPase, inhibiting the multidrug exporter Pdr5p. When used on whole cells at low µM concentrations, 21-BD produces several effects, including: 1) up-regulation of Na,K-ATPase expression and activity in HeLa and RKO cancer cells, which is not found for digoxin, 2) cell specific changes in cell viability, reducing it in HeLa and RKO cancer cells, but increasing it in normal epithelial MDCK cells, which is different from the response to digoxin, and 3) changes in cell-cell interaction, altering the molecular composition of tight junctions and elevating transepithelial electrical resistance of MDCK monolayers, an effect previously found for ouabain. These results indicate that modification of the lactone ring of digoxin provides new properties to the compound, and shows that the structural change introduced could be used for the design of cardiotonic steroid with novel functions. PMID:25290152

  2. 21-Benzylidene digoxin: a proapoptotic cardenolide of cancer cells that up-regulates Na,K-ATPase and epithelial tight junctions.

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    Sayonarah C Rocha

    Full Text Available Cardiotonic steroids are used to treat heart failure and arrhythmia and have promising anticancer effects. The prototypic cardiotonic steroid ouabain may also be a hormone that modulates epithelial cell adhesion. Cardiotonic steroids consist of a steroid nucleus and a lactone ring, and their biological effects depend on the binding to their receptor, Na,K-ATPase, through which, they inhibit Na+ and K+ ion transport and activate of several intracellular signaling pathways. In this study, we added a styrene group to the lactone ring of the cardiotonic steroid digoxin, to obtain 21-benzylidene digoxin (21-BD, and investigated the effects of this synthetic cardiotonic steroid in different cell models. Molecular modeling indicates that 21-BD binds to its target Na,K-ATPase with low affinity, adopting a different pharmacophoric conformation when bound to its receptor than digoxin. Accordingly, 21-DB, at relatively high µM amounts inhibits the activity of Na,K-ATPase α1, but not α2 and α3 isoforms. In addition, 21-BD targets other proteins outside the Na,K-ATPase, inhibiting the multidrug exporter Pdr5p. When used on whole cells at low µM concentrations, 21-BD produces several effects, including: 1 up-regulation of Na,K-ATPase expression and activity in HeLa and RKO cancer cells, which is not found for digoxin, 2 cell specific changes in cell viability, reducing it in HeLa and RKO cancer cells, but increasing it in normal epithelial MDCK cells, which is different from the response to digoxin, and 3 changes in cell-cell interaction, altering the molecular composition of tight junctions and elevating transepithelial electrical resistance of MDCK monolayers, an effect previously found for ouabain. These results indicate that modification of the lactone ring of digoxin provides new properties to the compound, and shows that the structural change introduced could be used for the design of cardiotonic steroid with novel functions.

  3. Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models. (United States)

    Deshpande, J R; Choudhari, A A; Mishra, M R; Meghre, V S; Wadodkar, S G; Dorle, A K


    Lagenaria siceraria (Mol.) Standley fruit (bottle gourd), a commonly used vegetable in India is described as cardiotonic and as a general tonic in Ayurveda. Keeping in view the presence of free radical scavenging activity in L. siceraria and involvement of free radicals in the development of various disorders, present studies were designed to evaluate the ethanolic extract of L. siceraria fruit against the disorders where free radicals play a major role in pathogenesis. The extract was found effective as hepatoprotective, antioxidant, antihyperglycemic, immunomodulatory, antihyperlipidemic and cardiotonic agent. The results showed that the radical scavenging capacity of L. siceraria fruit may be responsible for various biological activities studied.

  4. Drug: D05403 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05403 Drug Pelrinone hydrochloride (USAN) C12H11N5O. HCl 277.073 277.7096 D05403.g...if Cardiotonic CAS: 89232-84-8 PubChem: 47207078 LigandBox: D05403 ATOM 19 1 C8y C 14.6300 -20.0200 2 C8y C

  5. ATP1A1-mediated Src signaling inhibits coronavirus entry into host cells

    NARCIS (Netherlands)

    C. Burkard (Christine); M.H. Verheije (Monique); B.L. Haagmans (Bart); F.J.M. van Kuppeveld (Frank ); P.J.M. Rottier (Peter); B.J. Bosch (Berend Jan); C.A.M. de Haan (Cornelis)


    textabstractIn addition to transporting ions, the multisubunit Na+,K+-ATPase also functions by relaying cardiotonic steroid (CTS)-binding- induced signals into cells. In this study, we analyzed the role of Na+,K+-ATPase and, in particular, of its ATP1A1 α subunit during coronavirus (CoV) infection.

  6. Analytical case reports: major discrepancy between digoxin immunoassay results in a context of acute overdose

    Institute of Scientific and Technical Information of China (English)



    AIM: Digoxin, a heteroglycoside drug with cardiotonic effects,has a narrow therapeutic range, so therapeutic drug monitoring has been very helpful in improving patient management and preventing toxic effects. We report two cases of digoxin intoxication where the immunoassay techniques used for drug monitoring produced very different values with important clinical implications. METHODS: Serum levels of digoxin were determined with several analytical immunoassay techniques [Cobas

  7. An account of phytochemicals from Plumbago zeylanica (Family: Plumbaginaceae: A natural gift to human being #

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    Navneet Kishore


    Full Text Available The semi-climbing sub-shrub Plumbago zeylanica (family: Plumbaginaceae is a widely accepted ethnomedicine around the world including India, Pakistan, Bangladesh, Sri Lanka, and Australia. The plant is credited with potential therapeutic properties including antiatherogenic, cardiotonic, hepatoprotective, and neuroprotective properties. The present review highlights the various medicinal and pharmacological aspects along with recent updates on phytochemical contents of the plant.

  8. The Trade-off Between Dietary Salt and Cardiovascular Disease; a role for Na/K-ATPase signaling?


    Joe eXie; Anna Pearl Shapiro; Joseph Isaac Shapiro


    It has been postulated for some time that endogenous digitalis-like substances, also called cardiotonic steroids (CTS), exist, and that these substances are involved in sodium handling. Within the past 20 years, these substances have been unequivocally identified and measurements of circulating and tissue concentrations have been made. More recently, it has been identified that CTS also mediate signal transduction through the Na/K-ATPase, and consequently been implicated in profibrotic pathwa...

  9. Drug: D02409 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02409 Mixture, Drug Caffeine and sodium benzoate (JP16); Sodium caffeine benzoate;...s 211 Cardiotonics 2115 Caffeines D02409 Caffeine and sodium benzoate (JP16) Anatomical Therapeutic Chemical...for gastric secretion V04CG30 Caffeine and sodium benzoate D02409 Caffeine and so...n Japan [BR:br08301] 2 Agents affecting individual organs 21 Cardiovascular agent

  10. 1,2,4-triazine derivatives: Synthesis and biological applications

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    Mohammad Arshad


    Full Text Available 1,2,4-Triazines are the six membered heterocyclic compounds possessing three nitrogen in its structure with general formula C3H3N3. 1,2,4-Triazines and its derivatives have been found to exhibit the variety of biological applications such as antifungal, anti-HIV, anticancer, antiinflammatory, analgesic and antihypertensive, cardiotonic, neuroleptic, nootropic, antihistaminergic, tuberculostatic, antiviral, anti-protozoal, estrogen receptor modulators, antimalarial, cyclin-dependent kinase inhibitors, antimicrobial and antiparasitic activities.

  11. A review of pharmacognostical, phytochemical and pharmacological properties of Lagenaria siceraria: A miracle herb


    Solangi, Muhammad Aslam; Najam, Rahila


    Lagenaria siceraria (Bottle gourd) class Magnoliopsida family Cucurbitaceae is an excellent fruit in the nature consisting of all the essential constituents that are necessary for normal and good health of human beings. Lagenaria siceraria is official in Ayurvedic Pharmacopoeia. Traditionally, Lagenaria siceraria fruits had been used as a general tonic, cardiotonic, and cardioprotective drug. In addition, it had also been used as aphrodisiac, diuretic, antidote to certain poisons, scorpion st...

  12. Study of CNS depressant and behavioral activity of an ethanol extract of Achyranthes Aspera (Chirchita) in mouse model


    Bhosale, Uma; Yegnanarayan, Radha; Prachi, Pophale; Zambare, Mandar; Somani, R.S.


    Background Achyranthes Aspera Linn., known as Chirchira (Hindi), Agadha (Marathi) is an indigenous herb found in India. The herb has been reported to have variety of activities like antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic and cardiotonic, analgesic, anti-inflammatory, hypnotic, antifungal and antibacterial activity. It has been also reported to have central anti-nociceptive activity in thermal induced pain methods in our earlier studies. W...

  13. Effect of herbal medicine on Poststroke cognitive deficit

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    Jae-kyu Kim


    Full Text Available Objectives : The aim of study was to evaluate the effect of Herbal medicine on post stroke cognitive deficit. Methods : All groups were treated with acupunture treatment, moxa treatment, herbal medicines, physical and occupational therapy for 4 weeks, additionally cardiotonic pills(CP were taken in the cardiotonic pills group. The effect of treatment was assessed using Verval fluency, MMSE-KC, Word List Immediate Recall test. Statistical significance was achived if the probability was less than 5%(p,0.05. Results : Verval fluency, MMSE-KC, Word List Immediate Recall test scores increased in both group. MMSEKC, Word List Immediate Recall test scores were significantly increased in the CP group. Verval fluency, MMSE-KC, Word List Immediate Recall test scores were significantly increased in the control group. In the Verval fluency, MMSE-KC, Word List Immediate Recall test of the CP group more increased compared to the control group. There were no significant differences between two groups. In the CP group, the scores of the infarction group more increased compared to the hemorrhage group. Conclusions : According to the these results, herbal medicines are effective to improve post stroke cognitive-deficit. Futher studies are needed to know cardiotonic pills in the ischemic stroke.

  14. On the differences between ouabain and digitalis glycosides. (United States)

    Fuerstenwerth, Hauke


    Digoxin and digitoxin are widely used in the treatment of heart diseases. The exact mechanism of action of these drugs has remained an enigma. Ouabain has become the standard tool to investigate the mode of action of cardiotonic steroids, and results with ouabain are regarded as generally valid for all cardiac glycosides. However, there are marked differences between the effects of ouabain and digitalis glycosides. Ouabain has a different therapeutic profile from digitalis derivatives. Unlike digitalis glycosides, ouabain has a fast onset of action and stimulates myocardial metabolism. The inotropic effect of cardiotonic steroids is not related to inhibition of the Na-K-ATPase. Ouabain and digitalis derivatives develop their effects in different cellular spaces. Digitalis glycosides increase the intracellular calcium concentration by entering the cell interior and acting on the ryanodine receptors and by forming transmembrane calcium channels. Ouabain, by activation of the Na-K-ATPase from the extracellular side, triggers release of calcium from intracellular stores via signal transduction pathways and activates myocardial metabolism. These data no longer support the concept that all cardiotonic steroids exhibit their therapeutic effects by partial inhibition of the ion-pumping function of the Na-K-ATPase. Hence, it is suggested that this deeply rooted dogma be revised.

  15. Forskolin: from an ayurvedic remedy to a modern agent. (United States)

    Ammon, H P; Müller, A B


    Ancient Hindu Ayurvedic texts described the use of extracts from COLEUS species. An isolated diterpene from COLEUS FORSKOHLII, called forskolin, was demonstrated to be a hypotensive agent with spasmolytic, cardiotonic and platelet aggregation inhibitory activity. It has been shown to be a powerful activator of the enzyme adenylate cyclase in various tissues. Forskolin is thought to act on the catalytic subunit and also on the coupling mechanism of guanine regulatory sites (Ns and Ni) with the catalytic subunit. It is now clear that forskolin elicits physiological responses which have been shown to be cAMP-dependent.

  16. Review of Astragali Radix

    Institute of Scientific and Technical Information of China (English)

    LIU Jing; ZHAO Zhong-zhen; CHEN Hu-biao


    Astragali Radix (AR), known as Huangqi in China, is one of the most popular herbal medicines learnt worldwide to reinforce Qi (the vital energy). AR is traditionally prepared from the dried roots of Astragalus membranaceus or A. membranaceus var. mongholicus. It has been reported to have cardiotonic, hepatoprotective, hypotensive, immunostimulant, anti-aging, anti-oxidative, antidiabetic, and anti-inflammatory activities. The bioactive compounds were found to be flavonoids, saponins, polysaccharides, amino acids, and some trace elements. The present paper reviews the studies on AR including history, phytochemistry studies, pharmacological functions, and clinical application in recent years.

  17. Drug: D01573 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01573 Drug Etilefrine hydrochloride (JP16); Etilefrine hydrochloride (TN) C10H15NO...2. HCl 217.087 217.6925 D01573.gif Antihypotensive; Sympathomimetic Therapeutic category: 2119 ATC code: C01CA01 alpha1-adr...tion hsa04270(146+147+148) Vascular smooth muscle contraction hsa04970(146+147+148) Salivary secretion Therapeutic category of dr... 211 Cardiotonics 2119 Others D01573 Etilefrine hydrochloride (JP16) Anatomical T...AC STIMULANTS EXCL. CARDIAC GLYCOSIDES C01CA Adrenergic and dopaminergic agents C01CA01 Etilefrine D01573 Etilefrine hydr

  18. Drug: D00528 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00528 Drug Anhydrous caffeine (JP16); Caffeine (USP); Anhydrous caffeine (TN) C8H1... [BR:br08301] 2 Agents affecting individual organs 21 Cardiovascular agents 211 Cardiotonics 2115 Caffeines ...D00528 Anhydrous caffeine (JP16); Caffeine (USP) Anatomical Therapeutic Chemical (ATC) classification [BR:br...C Xanthine derivatives N06BC01 Caffeine D00528 Anhydrous caffeine (JP16); Caffeine...sine adenosine A1 receptor [HSA:134] [KO:K04265] Caffeine [ATC:N06BC01] D00528 Caffeine (USP) adenosine A2a

  19. Drug: D01453 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01453 Drug Caffeine hydrate (JP16); Caffeine monohydrate; Caffeine (TN) C8H10N4O2....:br08301] 2 Agents affecting individual organs 21 Cardiovascular agents 211 Cardiotonics 2115 Caffeines D01453 Caffeine...M N06 PSYCHOANALEPTICS N06B PSYCHOSTIMULANTS, AGENTS USED FOR ADHD AND NOOTROPICS N06BC Xanthine derivatives N06BC01 Caffeine... D01453 Caffeine hydrate (JP16) Target-based classification of d...rugs [BR:br08310] G Protein-coupled receptors Rhodopsin family Adenosine adenosine A1 receptor [HSA:134] [KO:K04265] Caffeine

  20. Specialized functional diversity and interactions of the Na,K-ATPase

    Directory of Open Access Journals (Sweden)

    Igor I. Krivoi


    Full Text Available Na,K-ATPase is a protein ubiquitously expressed in the plasma membrane of all animal cells and vitally essential for their functions. A specialized functional diversity of the Na,K-ATPase isozymes is provided by molecular heterogeneity, distinct subcellular localizations and functional interactions with molecular environment. Studies over the last decades clearly demonstrated complex and isoform-specific reciprocal functional interactions between the Na,K-ATPase and neighboring proteins and lipids. These interactions are enabled by a spatially restricted ion homeostasis, direct protein-protein/lipid interactions and protein kinase signaling pathways. In addition to its ‘classical’ function in ion translocation, the Na,K-ATPase is now considered as one of the most important signaling molecules in neuronal, epithelial, skeletal, cardiac and vascular tissues. Accordingly, the Na,K-ATPase forms specialized sub-cellular multimolecular microdomains which act as receptors to circulating endogenous cardiotonic steroids triggering a number of signaling pathways. Changes in these endogenous cardiotonic steroid levels and initiated signaling responses have significant adaptive values for tissues and whole organisms under numerous physiological and pathophysiological conditions. This review discusses recent progress in the studies of functional interactions between the Na,K-ATPase and molecular microenvironment, the Na,K-ATPase-dependent signaling pathways and their significance for diversity of cell function.

  1. Cardiac stimulant activity of bark and wood of Premna serratifolia

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    Rekha Rajendran


    Full Text Available Premna serratifolia Lin., (Verbenaceae contains alkaloids and iridoid glycoside and is believed to prevent cardiovascular disease. The stem-bark and stem-wood were extracted with 95% ethanol and distilled water. These extracts were screened for their effects by Isolated Frog Heart Perfusion Technique and biochemical parameters in heart tissue and serum of albino rats after administering the extracts for 7 days. The ethanol extract produced significant positive ionotropic and negative chronotropic actions similar to that of digoxin on frog heart and its effect was inhibited by nifedipine but not by propranolol. A significant decrease in membrane Na+K+ATPase and Mg2+ATPase and an increase in Ca2+ATPase further confirmed its cardiotonic activity. Aqueous extract produced positive ionotropic and chronotropic effects similar to that of adrenaline and its effect was antagonized by propranolol and nifedipine. The results suggest that the ethanol extract produced cardiotonic effect and the aqueous extract produced β-adrenergic effect.

  2. Mammalian cardenolides in cancer prevention and therapeutics. (United States)

    Al-Ghoul, Mohammad; Valdes, Roland


    Digoxin-like immunoreactive factor (DLIF) and ouabain-like factor (OLF) are the mammalian counterparts to the plant-derived cardiotonic steroids digoxin and ouabain. Compelling evidence indicates that the cardiotonic steroids may have anticancer properties. Recent evidence indicates that low (nanomolar) concentrations of DLIF selectively induce cell death in transformed cells, while sparing normal cells, and is even more potent than the plant-derived compounds. The discovery that these endogenous molecules may play a role in the regulation of cancer cell proliferation provides a potentially new paradigm for the physiologic role of DLIF and OLF. In addition, the possible use of digoxin itself as a therapeutic agent in cancer has been explored, and evidence suggests that its conversion to dihydrodigoxin may be involved in regulating anticancer activity. The mechanism(s) for the pro-apoptotic property of these compounds is not known. In this brief review, we will discuss the proposed mechanism of action of digoxin, ouabain, DLIF, and OLF as anticancer compounds and discuss the effects that metabolic conversion to their dihydro-derivatives may have on this activity. From the perspective of therapeutic drug monitoring, these findings suggest some potential new challenges in the need to measure concentrations of digoxin and dihydrodigoxin as well as their endogenous counterparts DLIF and OLF in serum.

  3. Corticosteroid responses of snakes to toxins from toads (bufadienolides) and plants (cardenolides) reflect differences in dietary specializations. (United States)

    Mohammadi, Shabnam; French, Susannah S; Neuman-Lee, Lorin A; Durham, Susan L; Kojima, Yosuke; Mori, Akira; Brodie, Edmund D; Savitzky, Alan H


    Toads are chemically defended by cardiotonic steroids known as bufadienolides. Resistance to the acute effects of bufadienolides in snakes that prey on toads is conferred by target-site insensitivity of the toxin's target enzyme, the Na(+)/K(+)-ATPase. Previous studies have focused largely on the molecular mechanisms of resistance but have not investigated the physiological mechanisms or consequences of exposure to the toxins. Adrenal enlargement in snakes often is associated with specialization on a diet of toads. These endocrine glands are partly composed of interrenal tissue, which produces the corticosteroids corticosterone and aldosterone. Corticosterone is the main hormone released in response to stress in reptiles, and aldosterone plays an important role in maintaining ion balance through upregulation of Na(+)/K(+)-ATPase. We tested the endocrine response of select species of snakes to acute cardiotonic steroid exposure by measuring circulating aldosterone and corticosterone concentrations. We found that Rhabdophis tigrinus, which specializes on a diet of toads, responds with lower corticosterone and higher aldosterone compared to other species that exhibit target-site resistance to the toxins but do not specialize on toads. We also found differences between sexes in R. tigrinus, with males generally responding with higher corticosterone and aldosterone than females. This study provides evidence of physiological adaptations, beyond target-site resistance, associated with tolerance of bufadienolides in a specialized toad-eating snake.

  4. Toxin-resistant isoforms of Na+/K+-ATPase in snakes do not closely track dietary specialization on toads. (United States)

    Mohammadi, Shabnam; Gompert, Zachariah; Gonzalez, Jonathan; Takeuchi, Hirohiko; Mori, Akira; Savitzky, Alan H


    Toads are chemically defended by bufadienolides, a class of cardiotonic steroids that exert toxic effects by binding to and disabling the Na(+)/K(+)-ATPases of cell membranes. Some predators, including a number of snakes, have evolved resistance to the toxic effects of bufadienolides and prey regularly on toads. Resistance in snakes to the acute effects of these toxins is conferred by at least two amino acid substitutions in the cardiotonic steroid binding pocket of the Na(+)/K(+)-ATPase. We surveyed 100 species of snakes from a broad phylogenetic range for the presence or absence of resistance-conferring mutations. We found that such mutations occur in a much wider range of taxa than previously believed. Although all sequenced species known to consume toads exhibited the resistance mutations, many of the species possessing the mutations do not feed on toads, much less specialize on that food source. This suggests that either there is little performance cost associated with these mutations or they provide an unknown benefit. Furthermore, the distribution of the mutation among major clades of advanced snakes suggests that the origin of the mutation reflects evolutionary retention more than dietary constraint.

  5. Evaluating the Cancer Therapeutic Potential of Cardiac Glycosides

    Directory of Open Access Journals (Sweden)

    José Manuel Calderón-Montaño


    Full Text Available Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na+/K+-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestion and some types of cardiac arrhythmias. Recent data suggest that cardiac glycosides may also be useful in the treatment of cancer. These compounds typically inhibit cancer cell proliferation at nanomolar concentrations, and recent high-throughput screenings of drug libraries have therefore identified cardiac glycosides as potent inhibitors of cancer cell growth. Cardiac glycosides can also block tumor growth in rodent models, which further supports the idea that they have potential for cancer therapy. Evidence also suggests, however, that cardiac glycosides may not inhibit cancer cell proliferation selectively and the potent inhibition of tumor growth induced by cardiac glycosides in mice xenografted with human cancer cells is probably an experimental artifact caused by their ability to selectively kill human cells versus rodent cells. This paper reviews such evidence and discusses experimental approaches that could be used to reveal the cancer therapeutic potential of cardiac glycosides in preclinical studies.

  6. Cellular basis for the species differences in sensitivity to cardiac glycosides (digitalis). (United States)

    Gupta, R S; Chopra, A; Stetsko, D K


    The relative toxicity of numerous cardiotonic steroids (viz. ouabain, digitoxin, digoxin, convallatoxin, SC4453, bufalin, gitaloxin, digoxigenin, actodigin, oleandrin, digitoxigenin, gitoxin, strophanthidin, gitoxigenin, lanatosides A, B and C, alpha- and beta-acetyl digoxin, alpha- and beta-methyl digoxin) and related compounds towards a number of independent cell lines established from human, monkey, mouse, Syrian hamster, and Chinese hamster have been determined. All cardiac glycosides and their genins, as well as the cardiotonic alkaloid cassaine, exhibited greater than 100-fold higher toxicity towards cultured human and monkey cells in comparison to the cell lines of mouse, Syrian hamster, and Chinese hamster origins. These differences are species-related as all cell lines (both normal as well as transformed) from any one species, as well as cells from the closely related species (e.g., man and monkey or mouse, Chinese hamster, and Syrian hamster), showed similar sensitivity towards these drugs. The failure to see any significant differences in cellular toxicity for a larger number of other compounds which either bear limited structural resemblance to cardiac glycosides (viz. estradiol 17-beta-acetate, testosterone propionate, 21-acetoxy pregnenolone, beta-estradiol, digitonin, tigogenin, and tomatine) or interact with the Na+/K+ ATPase in a different manner (viz. veratridine, sanguinarine nitrate, penicillic acid, vanadium pentoxide, harmaline-HCI,5,5'-diphenyl hydantoin, quindonium bromide, and methyl quinolizinum bromide) provides strong evidence that the observed species-related differences are highly specific for cardiotonic steroids. Studies on the binding of [3H]ouabain show that, in comparison to human and monkey cell lines, no significant binding of the drug is observed in cells derived from the resistant species (i.e., mouse and Chinese hamster). The Na+/K+ ATPase from cells of the resistant species is inhibited at much higher concentrations of

  7. Medicinal significance, pharmacological activities, and analytical aspects of solasodine: A concise report of current scientific literature

    Directory of Open Access Journals (Sweden)

    Kanika Patel


    Full Text Available Alkaloids are well known phytoconstituents for their diverse pharmacological properties. Alkaloids are found in all plant parts like roots, stems, leaves, flowers, fruits and seeds. Solasodine occurs as an aglycone part of glycoalkloids, which is a nitrogen analogue to sapogenins. Solanaceae family comprises of a number of plants with variety of natural products of medicinal significance mainly steroidal lactones, glycosides, alkaloids and flavanoids. It is a steroidal alkaloid based on a C27 cholestane skeleton. Literature survey reveals that solasodine has diuretic, anticancer, antifungal, cardiotonic, antispermatogenetic, antiandrogenic, immunomodulatory, antipyretic and various effects on central nervous system. Isolation and quantitative determination was achieved by several analytical techniques. Present review highlights the pharmacological activity of solasodine, with its analytical and tissue culture techniques, which may be helpful to the researchers to develop new molecules for the treatment of various disorders in the future.

  8. Trichosanthes dioica Roxb.: An overview

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    Nitin Kumar


    Full Text Available Trichosanthes , a genus of family Cucurbitaceae, is an annual or perennial herb distributed in tropical Asia and Australia. Pointed gourd (Trichosanthes dioica Roxb. is known by a common name of parwal and is cultivated mainly as a vegetable. Juice of leaves of T. dioica is used as tonic, febrifuge, in edema, alopecia, and in subacute cases of enlargement of liver. In Charaka Samhita, leaves and fruits find mention for treating alcoholism and jaundice. A lot of pharmacological work has been scientifically carried out on various parts of T. dioica, but some other traditionally important therapeutical uses are also remaining to proof till now scientifically. According to Ayurveda, leaves of the plant are used as antipyretic, diuretic, cardiotonic, laxative, antiulcer, etc. The various chemical constituents present in T. dioica are vitamin A, vitamin C, tannins, saponins, alkaloids, mixture of noval peptides, proteins tetra and pentacyclic triterpenes, etc.

  9. Onosma L.: A review of phytochemistry and ethnopharmacology

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    Neeraj Kumar


    Full Text Available The genus Onosma L. (Boraginaceae includes about 150 species distributed world-wide in which only about 75 plants has been described for its morphology and less than 10 plants for their chemical constituents and clinical potential. The phytochemical reports of this genus revels that it comprise mainly aliphatic ketones, lipids, naphthazarins, alkaloids, phenolic compounds, naphthoquinones, flavones while most important are shikonins and onosmins. The plants are traditionally used as laxative, anthelmintic and for alexipharmic effects. The plants are also equally use in eye, blood diseases, bronchitis, abdominal pain, stangury, thirst, itch, lecoderma, fever, wounds, burns, piles and urinary calculi. The flowers of various plants are prescribed as stimulants, cardiotonic, in body swelling while leaves are used as purgative and in cutaneous eruptions. The roots are used for coloring food stuffs, oils and dying wool and in medicinal preparations. This review emphasizes the distribution, morphology, phytochemical constituents, ethnopharmacology, which may help in future research.


    Directory of Open Access Journals (Sweden)

    Selvakumari E


    Full Text Available Nymphaea pubescens Willd (Nymphaeaceae is a fascinating aquatic plant mentioned in siddha system of medicine, in the treatment of bleeding piles, diabetes and as cardiotonic in palpitation of the heart. Nymphaea species was traditionally used for treating cancer. The present study was designed to evaluate the invitro antiproliferative activity of Nymphaea pubescens Willd. The ethanolic extract of different parts such as rhizome, leaf, flower and fruit was subjected for MTT assay. The ethanolic extract of flower part was found to be cytotoxic against human cervical carcinoma Hela cell lines and human breast carcinoma MCF cell lines. The IC50 value of ethanolic flower extract was 91.57µg/ml against Hela cell lines and 99.6µg/ml against MCF-7 cell lines. Significant results were observed thereby justifying the use of plant in the traditional system of medicine.

  11. Bioactive heterocyclic alkaloids with diterpene structure isolated from traditional Chinese medicines. (United States)

    Xu, Tengfei; Liu, Shu; Meng, Lulu; Pi, Zifeng; Song, Fengrui; Liu, Zhiqiang


    The diterpenoid alkaloids as one type of heterocyclic alkaloids have been found in many traditional herbal medicines, such as genus Consolida, Aconitum, and Delphinium (Ranunculaceae). Pharmacological researches have indicated that many diterpenoid alkaloids are the main bioactive components which have analgesic, anti-inflammatory, anti-microbial, anti-tumor, cardiotonic, and anti-arrhythmic activities. Studies focused on the determination, quantitation and pharmacological properties of these alkaloids have dramatically increased during the past few years. Up to now, newly discovered diterpenoid alkaloids with important biological activities have been isolated and synthesized. Considering their significant role and diffusely used in many disease treatments, we summarized the information of their analysis methods, bioactivity, metabolism and biotransformation in vivo as well as the pharmacological mechanisms. Based on above review, the further researches are suggested.

  12. Mangifera Indica (Mango

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    K A Shah


    Full Text Available Mangifera indica, commonly used herb in ayurvedic medicine. Although review articles on this plant are already published, but this review article is presented to compile all the updated information on its phytochemical and pharmacological activities, which were performed widely by different methods. Studies indicate mango possesses antidiabetic, anti-oxidant, anti-viral, cardiotonic, hypotensive, anti-inflammatory properties. Various effects like antibacterial, anti fungal, anthelmintic, anti parasitic, anti tumor, anti HIV, antibone resorption, antispasmodic, antipyretic, antidiarrhoeal, antiallergic, immunomodulation, hypolipidemic, anti microbial, hepatoprotective, gastroprotective have also been studied. These studies are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using mango for a variety of conditions should also be conducted.

  13. Intractable radiation pericarditis and pleuritis developed 20 years after postoperative radiotherapy in a case with breast cancer

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    Tsuji, Misa; Shintani, Uichirou; Ohmoto, Yasuhiro; Isshiki, Noriyuki; Tanaka, Tsuyoshi; Kitamura, Masami; Kato, Shigetake; Misaki, Moriharu [Mie National Central Hospital, Hisai (Japan); Shouin, Hiroshi


    We reported a 64-year-old woman with radiation-related intractable pericarditis and pleuritis which developed 20 years after radiotherapy. She underwent a left total mastectomy for a breast cancer and 50 Gy of radiotherapy postoperatively at the age of 43. She was admitted to our hospital because of facial edema and dyspnea. A chest roentgenogram on admission showed massive bilateral pleural effusion and a echocardiography revealed massive pericardial effusion. Though the symptoms of heart failure subsided after the administration of moderate diuretics and cardiotonics, the pleural effusion and pericardial effusion persisted and, she became worse and died. The histological findings at autopsy, showed chronic fibrous pericarditis with marked pericardial thickening, fibrous pleuritis and myocarditis. These findings were compatible with those of previously reported radiation-induced heart disease. We reported a case of pleuritis and pericarditis probably caused by radiation therapy. A long term observation is necessary for the radiation-related heart disease. (author)

  14. Advancement in research of anti-cancer effects of toad venom (ChanSu) and perspectives

    Institute of Scientific and Technical Information of China (English)

    Miao Liu; Li-Xing Feng; Li-Hong Hu; Xuan Liu; De-An Guo


    Toad venom, called as ChanSu in China, is a widely used traditional Chinese medicine (TCM) whose active components are mainly bufadienolides. ChanSu could exhibit cardiotonic, anti-microbial, anti-inflammatory and, most importantly, anti-cancer effects. In the present review, reports about the in vitro, in vivo and clinical anti-cancer effects of ChanSu or its representative component, bufalin, were summarized. And, reported anti-cancer mechanisms of cardenolides, structure analogues of bufadienolides, were also introduced. Based on the results got from research of ChanSu/bufalin and the results from cardenolides, possible signal network related to the anti-cancer effects of ChanSu/bufalin was predicted. Furthermore, future potential use of ChanSu in anti-cancer therapy was discussed.

  15. Preparative isolation of oligomeric procyanidins from Hawthorn (Crataegus spp.). (United States)

    Zumdick, S; Petereit, F; Luftmann, H; Hensel, A


    The oligomeric procyanidins (OPC) from Hawthorn leaves and flowers (Crataegi folium cum flore) are considered to be in part responsible for the cardiotonic clinical activity of the herbal material. Effective methods for rapid isolation of these heterogenous oligomeric clusters with defined molecular weight as reference compounds are not published until now. Therefore the water soluble fraction of an acetone/water (7 + 3) extract of Hawthorn leaves and flowers was fractionated by a combination of MPLC on RP-18 material and preparative HPLC using a diol stationary phase. This procedure resulted in the effective isolation of procyanidins with a distinct degree of polymerization (DP) from dimers DP2 up to tridecamers DP13. Exact mass measurements with negative ESI-TOF/MS were employed to confirm the respective structures of the isolated procyanidins.

  16. Phytopharmacological overview of Tribulus terrestris. (United States)

    Chhatre, Saurabh; Nesari, Tanuja; Somani, Gauresh; Kanchan, Divya; Sathaye, Sadhana


    Tribulus terrestris (family Zygophyllaceae), commonly known as Gokshur or Gokharu or puncture vine, has been used for a long time in both the Indian and Chinese systems of medicine for treatment of various kinds of diseases. Its various parts contain a variety of chemical constituents which are medicinally important, such as flavonoids, flavonol glycosides, steroidal saponins, and alkaloids. It has diuretic, aphrodisiac, antiurolithic, immunomodulatory, antidiabetic, absorption enhancing, hypolipidemic, cardiotonic, central nervous system, hepatoprotective, anti-inflammatory, analgesic, antispasmodic, anticancer, antibacterial, anthelmintic, larvicidal, and anticariogenic activities. For the last few decades or so, extensive research work has been done to prove its biological activities and the pharmacology of its extracts. The aim of this review is to create a database for further investigations of the discovered phytochemical and pharmacological properties of this plant to promote research. This will help in confirmation of its traditional use along with its value-added utility, eventually leading to higher revenues from the plant.

  17. Phytopharmacological overview of Tribulus terrestris

    Directory of Open Access Journals (Sweden)

    Saurabh Chhatre


    Full Text Available Tribulus terrestris (family Zygophyllaceae, commonly known as Gokshur or Gokharu or puncture vine, has been used for a long time in both the Indian and Chinese systems of medicine for treatment of various kinds of diseases. Its various parts contain a variety of chemical constituents which are medicinally important, such as flavonoids, flavonol glycosides, steroidal saponins, and alkaloids. It has diuretic, aphrodisiac, antiurolithic, immunomodulatory, antidiabetic, absorption enhancing, hypolipidemic, cardiotonic, central nervous system, hepatoprotective, anti-inflammatory, analgesic, antispasmodic, anticancer, antibacterial, anthelmintic, larvicidal, and anticariogenic activities. For the last few decades or so, extensive research work has been done to prove its biological activities and the pharmacology of its extracts. The aim of this review is to create a database for further investigations of the discovered phytochemical and pharmacological properties of this plant to promote research. This will help in confirmation of its traditional use along with its value-added utility, eventually leading to higher revenues from the plant.

  18. Bacopa monniera, a reputed nootropic plant: an overview. (United States)

    Russo, A; Borrelli, F


    Bacopa monniera (BM), a traditional Ayurvedic medicine, used for centuries as a memory enhancing, anti-inflammatory, analgesic, antipyretic, sedative and antiepileptic agent. The plant, plant extract and isolated bacosides (the major active principles) have been extensively investigated in several laboratories for their neuropharmacological effects and a number of reports are available confirming their nootropic action. In addition, researchers have evaluated the anti-inflammatory, cardiotonic and other pharmacological effects of BM preparations/extracts. Therefore, in view of the important activities performed by this plant, investigation must be continued in the recently observed actions described in this paper. Moreover, other clinical studies have to be encouraged, also to evidence any side effects and possible interactions between this herbal medicine and synthetic drugs.

  19. The NA+/K+-ATPase controls gap junctions via membrane microdomain interactions in rat smooth muscles.

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Nilsson, Holger; Aalkjær, Christian

    in regulation of the intercellular communication. We have here shown that gap junctions between SMCs are regulated through an interaction between the Na+/K+-ATPase and the Na+/Ca2+-exchanger leading to an increase in [Ca2+]i in discrete areas near the plasma membrane. We have also suggested that this Na+/K+-pump......The Na+/K+-ATPase is known to interact with many membrane and cytosolic proteins by organizing various signaling complexes. These interactions were suggested to be important in regulation of various cellular responses. Pumping activity of the Na+/K+-ATPase is suggested to be essential for some...... of these interactions, while other responses may be independent of pumping activity. The Na+/K+-pump differs from other P-type ATPases by its sensitivity to cardiotonic steroids such as ouabain. However, rodent tissues express both ouabain-insensitive (α1) and ouabain-sensitive (α2 and α3) isoforms of Na...

  20. The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Krithika Srikanthan


    Full Text Available Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS, which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.


    Directory of Open Access Journals (Sweden)

    Rabbani Syed Arman


    Full Text Available Cardiovascular diseases (CVDs are the leading cause of death and disability in the world. They have emerged as a major health threat in develop¬ing countries contrary to the prior belief that they were confined primarily to industrialized nations. The global burden of disease due to cardiovascular diseases is escalating, principally due to a sharp rise in the developing countries which are experiencing rapid health transition. An estimated 17.3 million people died from CVDs in 2008 and over 80% of CVD deaths take place in low and middle income countries. By 2030, almost 23.6 million people will die from CVDs. Therefore, finding ways to reduce the mortality of cardiovascular disease remains an important public health goal. Traditional Medicines have been an integral part of the healthcare system since time immemorial. WHO reports indicate that around eighty percent of the global population still relies on botanical drugs and several herbal medicines have advanced to clinical use in modern times. Unani occupies an important place in the rich traditional heritage of indigenous systems of medicine in India and contributes significantly to the health care. The core of treatment in Unani System of Medicine is based on drugs of herbal, mineral and animal origin. The ancient classical literature of Unani has mention of numerous drugs possessing cardioprotective and cardiotonic activity, Arjun (Terminalia arjuna and Zafran (Crocus sativus are two of them. The Unani physicians have been using these drugs successfully since ages and this is possible only by inherent quality and safety standards specified in the system.With the advent of new techniques and recent upsurge towards scientific exploration of traditional medicines, empirical data substantiating their safety and efficacy has been generated and had led to better understanding of their role to prevent and cure diseases. The aim of this paper is to review and highlight the work done on Arjun

  2. Analysis of prescriptions compatibility law for treatment coronary disease in uyghur medicines%维吾尔药治疗冠心病方剂的组方配伍规律分析

    Institute of Scientific and Technical Information of China (English)

    买买提依力·努尔买提; 艾尼瓦尔·塔力甫; 吐尔洪·阿西木; 阿布都瓦尔·阿布拉克


    Objective:To analysize prescriptions compatibility law for treatment coronary disease,discuss pathogenesis and therapy characteristics.Methods:To collect effective prescriptions of treatment for palpitation,cardiodynia,chest pain,choking sensation in chest,analysize the medical classification and using frequency,utilizing screen function of the Microsoft Excel to set up database and have a statistic analysis.Results:According to using frequency,cardiotonic drug was used at most,then mature drugs of abnormal body fluid,tonifying brain,kidney and invigorating stomach and cathartic drugs in sequence.Conclusion:The results suggest that cardiotonic drug is the main group of in prescriptions,compatibility of tonifying brain,kidney,stomach and boosting natural force drugs in the treatment of coronary disease.Its statistical analysis reveals the coronary disease prescription drug laws,and has important theoretical and clinical significance.%目的:分析冠心病用药的组方配伍规律,探讨其病机和治法特点.方法:具有以卡伏绀(心悸)、心痛、胸痛、胸闷为主治的有效方剂进行收集、整理、汇总,利用Mcirosotf Exce1建立资料数据表,通过数据筛选功能对药物分类、使用频数进行统计分析.结果:按照使用频次排列强心药最多,27味,537次,其次为异常体液成熟药、补脑药、补肾和健胃顺肠药.讨论:以强心药为主,配伍异常体液成熟药、补脑药、补肾药、健胃顺肠药及增强自然力的药,揭示了冠心病用药的组方配伍规律,具有重要的理论与临床意义.

  3. Analysis of the Inhibitory Effect of Gypenoside on Na+,K+-ATPase in Rats' Heart and Brain and Its Kinetics

    Institute of Scientific and Technical Information of China (English)

    HAN Xiao-yan; WEI Hong-bo; ZHANG Fu-cheng


    ObjectiYe: To study the effects of gypenoside (Gyp) on the activity of microsomal Na+,K+-ATPase in rat's heart and brain in vitro. Methods: The microsomal Na+, K+-ATPase was prepared from rat's heart and brain by differential centrifugation. The activity of microsomal Na+, K+-ATPase was assayed by colorimetric technique. Enzyme kinetic analysis method was used to analyze the effect of Gyp on the microsomal Na+, K+-ATPase of rats. Results: Gyp reversibly inhibited the brain and heart's microsomal Na+, K+-ATPase in a concentration-dependent manner, and showed a more potent effect on enzyme in the brain. The IC50 of Gyp for the heart and brain were 58.79± 8.05 mg/L and 52.07 ±6.25 mg/L, respectively. The inhibition was enhanced by lowering the Na+, or K+ concentrations or increasing the ATP concentration. Enzyme kinetic studies indicated that the inhibitory effect of Gyp on the enzyme is like that of competitive antagonist of Na+, the counter-competitive inhibitor for the substrate ATP, and the mixed-type inhibitor for K+. Conclusion: Gyp displays its cardiotonic and central inhibitory effects by way of inhibiting heart and brain's microsomal Na+, K+-ATPase activities in rats.

  4. Study on diuretic activity of saffron (stigma of Crocus sativus L. Aqueous extract in rat

    Directory of Open Access Journals (Sweden)

    Nabi Shariatifar


    Full Text Available Saffron is the most expensive spice in the world and consists of the dried stigmas of Crocus sativus L. It is used as food coloring and flavoring in food industry and traditional cooking and also in folk medicine as antispasmodic, carminative, stomachic, expectorant, aphrodisiac and cardiotonic. The present study has evaluated the diuretic activity of aqueous extract of dried saffron (stigma of Crocussativus in rat. Aqueous extracts of saffron were administered to experimental rats orally as doses of 60, 120 and 240 mg/kg body weight (BW and compared with hydrochlorothiazide (10 mg/kg B.W., intraperitoneally, a potent diuretic as positive control and normal saline solution as placebo for control group. The measured parameters for diuretic activity were total urine volume, urine electrolytes concentration such as sodium and potassium, creatinine and urea concentration. The treated rats with aqueous extract of saffron as doses of 120 and 240 mg/kg BW showed higher urine output when compared to the control group. Also, it has shown a significant dose-dependent increase in the excretion of electrolytes when compared to the control group. Our findings proved the diuretic activity of saffron which is used in traditional medicine, it can be an effective and safe strategy for related dysfunction. Also further studies are needed to identify the mechanisms of action, probably other effects and interactions with other medicines.

  5. A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae

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    Panthati Murali Krishna


    Full Text Available Sophora is a genus of the Fabaceae family, contains about 52 species, nineteen varieties, and seven forms that are widely distributed in Asia, Oceanica, and the Pacific islands, in the family Fabaceae of herbaceous (Sophora flavescens Aiton to trees (Sophora japonica L.. More than fifteen species in this genus have a long history of use in traditional Chinese medicines. In the last decades the use of this genus in traditional Chinese drugs has led to rapid increase in the information available on active components and reported to posses various pharmacological/therapeutic properties. The paper reviews the ethnopharmacology, the biological activities and the correlated chemical compounds of genus Sophora, Fabaceae. More than 300 compounds has been isolated, among them major are quinolizidine alkaloids particularly matrine and oxymatrine and flavonoids particularly prenylated and isoprenylated flavonoids. Modern pharmacological studies and clinical studies demonstrated that these chemical constituens possess wide reaching pharmacological actions like anti oxidant, anticancer, anti-asthamatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti pyretic, cardiotonic, antinflammatory, diuretic and in the treatment of skin diseases like eczema, colitis and psoriasis.

  6. Effects of cerous nitrate on growth and tanshinone production in salvia miltiorrhiza hairy roots

    Institute of Scientific and Technical Information of China (English)

    韩名宇; 郭万里; 梁宗锁; 杨东风; 闫希军; 朱永宏; 刘岩


    Salvia miltiorrhiza, a popular traditional Chinese medicine, is widely used for treatments in cardiotonic disease. Tanshi-nones are a group of bioactive ingredients in S. miltiorrhiza. In this study, Ce3+was used as an elicitor to enhance tanshinones produc-tion in S. miltiorrhiza hairy roots. The results showed that contents of dihydrotanshinone I (DTI) and cryptotanshinone (CT) were sig-nificantly enhanced by 50μmol/L Ce3+, and reached to 0.875 mg/g and 0.271 mg/g, respectively. However, tanshinone II A (TIIA) and tanshinone I (TI) contents were significantly decreased to 59%and 62%of the control. Simultaneously, expressions of genes (HMGR, DXR, DXS1, DXS2 and GGPPS) involved in tanshinone biosynthesis were upregulated by Ce3+. Responses of DXS1, DXS2 and GGPPS to Ce3+treatments were later than HMGR and DXR. We speculated that branch pathways of DTI and CT biosynthesis were probably different from TIIA and TI. This work will help us understand biosynthetic mechanism of tanshinones in plants.

  7. Ethnopharmacology of the plants of genus Ajuga. (United States)

    Israili, Zafar H; Lyoussi, Badiâa


    The plants of genus Ajuga are evergreen, clump-forming rhizomatous perennial or annual herbaceous flowering species, with Ajuga being one of the 266 genera of the family Lamiaceae. There are at least 301 species of the genus Ajuga with many variations. These plants, growing in Europe, Asia, Africa, Australia and North America, are used in gardens as ground cover or border for their foliage and beautiful flowers. Many of these plants have been used in traditional medicine as a remedy for fever, toothache, dysentery, malaria, high blood pressure, diabetes, gastrointestinal disorders, as anthelmintic, diuretic and antifungal, anti-inflammatory, and antimycobacterial agents. They are also used as insect growth inhibitor s. A large number of compounds have been isolated from the Ajuga plants, including phytoecdysteroids, neo-clerodane-diterpenes and diterpenoids, triterpenes, sterols, anthocyanidin-glucosides and iridoid glycosides, withanolides, flavonoids, triglycerides and essential oils. These compounds possess a broad spectrum of biological, pharmacological and medicinal properties, such as anabolic, analgesic, antibacterial, antiestrogenic, antifungal, anti-inflammatory, antihypertensive, antileukemic, antimalarial, antimycobacterial, antioxidant, antipyretic, cardiotonic, cytotoxic, hypoglycemic, and vasorelaxing activity, as well as antifeedant and insect growth-inhibitory properties. Thus, genus Ajuga has significant medicinal and economic importance.

  8. Effective and Steady Differentiation of a Clonal Derivative of P19CL6 Embryonal Carcinoma Cell Line into Beating Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Itsuki Mueller


    Full Text Available The P19CL6 cell line is a useful model to study cardiac differentiation in vitro. However, large variations were noticed in the differentiation rates among previous reports as well as our individual experiments. To overcome the unstable differentiation, we established P19CL6-A1, a new clonal derivative of P19CL6 that could differentiate into cardiomyocytes more efficiently and stably than the parent using the double stimulation with 5-Aza and DMSO based on the previous report. We also introduced a new software, Visorhythm, that can analyze the temporal variations in the beating rhythms and can chart correlograms displaying the oscillated rhythms. Using P19CL6-A1-derived cardiomyocytes and the software, we demonstrated that the correlograms could clearly display the enhancement of beating rates by cardiotonic reagents. These indicate that a combination of P19CL6-A1 and Visorhythm is a useful tool that can provide invaluable assistance in inotropic drug discovery, drug screening, and toxicity testing.

  9. The history of veterinary cardiology. (United States)

    Buchanan, James W


    Throughout civilization, animals have played a pivotal role in the advancement of science and medicine. From as early as 400 BC when Hippocrates recognized that diseases had natural causes, the steadfast advances made by biologists, scientists, physicians and scholars were fueled by timely and important facts and information- much of it gained through animal observations that contributed importantly to understanding anatomy, physiology, and pathology. There have been many breakthroughs and historic developments. For example, William Harvey in the 16th and 17th centuries clarified the importance of the circulatory system, aided by observations in dogs and pigs, which helped to clarify and confirm his concepts. The nineteenth century witnessed advances in physical examination techniques including auscultation and percussion. These helped create the basis for enhanced proficiency in clinical cardiology. An explosion of technologic advances that followed in the 20th century have made possible sophisticated, accurate, and non-invasive diagnostics. This permitted rapid patient assessment, effective monitoring, the development of new cardiotonic drugs, clinical trials to assess efficacy, and multi-therapy strategies. The latter 20th century has marshaled a dizzying array of advances in medical genetics and molecular science, expanding the frontiers of etiologies and disease mechanisms in man, with important implications for animal health. Veterinary medicine has evolved during the last half century, from a trade designed to serve agrarian cultures, to a diverse profession supporting an array of career opportunities ranging from private, specialty practice, to highly organized, specialized medicine and subspecialty academic training programs in cardiology and allied disciplines.

  10. Identification of a VxP targeting signal in the flagellar Na+/K+-ATPase (United States)

    Laird, Joseph G.; Pan, Yuan; Modestou, Modestos; Yamaguchi, David M.; Song, Hongman; Sokolov, Maxim; Baker, Sheila A.


    Na+/K+-ATPase (NKA) participates in setting electrochemical gradients, cardiotonic steroid signaling, and cellular adhesion. Distinct isoforms of NKA are found in different tissues and subcellular localization patterns. For example, NKA α1 is widely expressed, NKA α3 is enriched in neurons, and NKA α4 is a testes specific isoform found in sperm flagella. In some tissues, ankyrin, a key component of the membrane cytoskeleton, can regulate the trafficking of NKA. In the retina, NKA and ankyrin-B are expressed in multiple cell types and immunostaining for each is striking in the synaptic layers. Labeling for NKA is also prominent along the inner segment plasma membrane of photoreceptors. NKA co-immunoprecipitates with ankyrin-B, but on a subcellular level co-localization of these two proteins varies dependent on the cell type. We used transgenic X. laevis tadpoles to evaluate the subcellular trafficking of NKA in photoreceptors. GFP-NKA α3 and α1 localized to the inner segment plasma membrane, but α4 localized to outer segments. We identified a VxP motif responsible for the outer segment targeting by using a series of chimeric and mutant NKA constructs. This motif is similar to previously identified ciliary targeting motifs. Given the structural similarities between outer segments and flagella, our findings shed light on the subcellular targeting of this testes specific NKA isoform. PMID:26373354

  11. Terminalia arjuna in Chronic Stable Angina: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Navjot Kaur


    Full Text Available Background. Terminalia arjuna is a popular Indian medicinal plant with its bark been used for over centuries as cardiotonic. The bark has been found to contain several bioactive compounds including saponins and flavonoids. A number of experimental and clinical studies have been conducted to explore therapeutic potential of Terminalia arjuna in cardiovascular ailments specially in patients of coronary heart disease. A number of narrative reviews have been done but no systematic review has been conducted to date. Objective. To systematically review and conduct a meta-analysis on the available literature evaluating the efficacy of Terminalia arjuna in patients of chronic stable angina. Study selection. We included randomised, pseudo-randomized and before-after comparative studies which compared Terminalia arjuna/commercial preparation of Terminalia arjuna with current standard/ conventional treatment regimens in patients with chronic stable angina. Findings. Studies were found to be of poor methodological design. We found no significant difference in the Terminalia arjuna group as compared to control arm in the outcomes for which we were able to pool data and undertake meta-analysis. Conclusions. Currently, the evidence is insufficient to draw any definite conclusions in favour of or against Terminalia arjuna in patients of chronic stable angina. Further, well-controlled multicentric clinical trials need to be conducted in large number of patients to explore the therapeutic potential of Terminalia arjuna if any.

  12. Amrinone effects on electromechanical coupling and depolarization-induced automaticity in ventricular muscle of guinea pigs and ferrets. (United States)

    Malécot, C O; Arlock, P; Katzung, B G


    The effects of the cardiotonic agent, amrinone (0.05-4 mM), on electrical and mechanical activities of ferret and guinea-pig papillary muscles were studied using current and voltage clamp (single sucrose gap) techniques. In current clamp studies, amrinone increased, in a dose-dependent manner, contractile force elicited by action potential in both species. Depolarization-induced automaticity was facilitated in ferret muscles at all maximum diastolic potentials between -70 and -15 mV. Facilitation of automaticity in guinea-pig muscles occurred only at potentials more negative than -35 mV and was suppressed at more positive potentials. Cimetidine (10 microM) partially reversed the effects of amrinone on automaticity in both species. In voltage clamp studies, amrinone increased the slow inward current. Steady-state outward current was increased in guinea-pig but not in ferret muscles. A dual effect of amrinone on tension was observed. Amrinone was found to increase phasic tension of ferret papillary muscles only for depolarizations lasting less than 250 to 300 msec. For longer depolarizations, amrinone decreased the phasic tension (in a dose-dependent manner), whereas the tonic tension was not modified. The decrease as well as the increase in tension was associated with an increase of the slow inward current. The results suggest that amrinone may be arrhythmogenic and may have an intracellular action at the sarcoplasmic reticulum level (partial inhibition) in addition to its action on the calcium current.

  13. [Digitalic therapy. Historical outline]. (United States)

    de Micheli-Serra, A


    The action of medical drugs obtained from many vegetables aroused a great interest of naturalists and physicians in all time. Moreover, it was always required that those persons destined to medical practice have a good knowledge of botany. Among the medicinal plants utilized by ancient peoples of the Anahuac, yoloxochitl or heart flower (Talauma mexicana) is mentioned, which seems to have a digitalis-like action. Research in our century demonstrated a positive inotropic and bradycardic effect of the leavels of Magnolia grandiflora or Talauma mexicana extract. Since the end of the XVIII century, digitalis was employed. It was considered initially as a diuretic and later as a cardiotonic agent. The action of digitalic glycosides upon the cardiac tissues was studied experimentally in Mexico. At the present-time there are positive inotropic agents derived from pyridine, as is the case of Milrinone, which have a beneficial action on the failing human myocardium. However, following the opinion of distinguished pharmacologists, "in the case of heart failure associated to atrial fibrillation, digitalis cannot be substituted".

  14. [Neuroendocrine changes in chronic cardiac insufficiency]. (United States)

    Jaeger, P; Cohen-Solal, A; Dahan, M; Juliard, J M; Charlier, P; Gourgon, R


    Throughout the course of chronic congestive heart failure cardiac and peripheral compensatory mechanisms are at play, most of them under the influence of the neuroendocrine system. The reserves of heart rate and contractility are regulated essentially by the noradrenergic system (NAS), but this mechanism is partial and transient owing to the gradual decrease in the density and sensitivity of myocardial beta-adrenergic receptors induced by overstimulation. Adaptation of the heart to exercise may be reduced. This escape phenomenon is also observed with almost all cardiotonic drugs which interfere with cyclic adenosine monophosphate (cAMP), in contrast with the paradoxically favourable effects of beta-blockers in small doses or of drugs that are both agonists and antagonists of beta-adrenergic receptors. The mechanisms which contribute to the induction of left ventricular hypertrophy are imperfectly known. The noradrenergic system and the renin-angiotensin-aldosterone system (RAAS) are probably not the only ones involved. The setting in action of Frank-Sterling heterometric regulation, at first during exercise then permanently, requires an increase in filling pressure obtained by venous constriction (predominantly controlled by the NAS) and, mostly, by an increase in circulating blood volume. NAS and RAAS intervene in the kidneys to produce water-and-salt retention.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. An impression on current developments in the technology, chemistry, and biological activities of ginger (Zingiber officinale Roscoe). (United States)

    Kubra, I Rahath; Rao, L Jagan Mohan


    Ginger rhizome (Zingiber officinale Roscoe) is widely cultivated as a spice for its aromatic and pungent components. The essential oil and oleoresins from ginger are valuable products responsible for the characteristic flavor and pungency. Both are used in several food products such as soft beverages and also in many types of pharmaceutical formulations. More than 100 compounds have been reported from ginger, some of which are isolated and characterized, others are tentatively identified by GC-MS and / or LC-MS. [6]-Gingerol, the major gingerol in ginger rhizomes, has been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, analgesic, and cardiotonic effects. Ginger is considered as "generally recognized as safe" (GRAS) by Food and Drug Administration (FDA), USA. Due to all these properties, ginger has gained considerable attention in developed countries in recent years, especially for its use in the treatment of inflammatory conditions. The present review is a persuasive presentation of the current information on processing, chemistry, biological activities, and medicinal uses of ginger. Further studies are required for the validation of the beneficial uses. Formulation for novel products and new usages may emerge in the years to come, based on the revealed results of various studies.

  16. Valuable Nutrients and Functional Bioactives in Different Parts of Olive (Olea europaea L.—A Review

    Directory of Open Access Journals (Sweden)

    Nazamid Saari


    Full Text Available The Olive tree (Olea europaea L., a native of the Mediterranean basin and parts of Asia, is now widely cultivated in many other parts of the world for production of olive oil and table olives. Olive is a rich source of valuable nutrients and bioactives of medicinal and therapeutic interest. Olive fruit contains appreciable concentration, 1–3% of fresh pulp weight, of hydrophilic (phenolic acids, phenolic alchohols, flavonoids and secoiridoids and lipophilic (cresols phenolic compounds that are known to possess multiple biological activities such as antioxidant, anticarcinogenic, antiinflammatory, antimicrobial, antihypertensive, antidyslipidemic, cardiotonic, laxative, and antiplatelet. Other important compounds present in olive fruit are pectin, organic acids, and pigments. Virgin olive oil (VOO, extracted mechanically from the fruit, is also very popular for its nutritive and health-promoting potential, especially against cardiovascular disorders due to the presence of high levels of monounsaturates and other valuable minor components such as phenolics, phytosterols, tocopherols, carotenoids, chlorophyll and squalene. The cultivar, area of production, harvest time, and the processing techniques employed are some of the factors shown to influence the composition of olive fruit and olive oil. This review focuses comprehensively on the nutrients and high-value bioactives profile as well as medicinal and functional aspects of different parts of olives and its byproducts. Various factors affecting the composition of this food commodity of medicinal value are also discussed.

  17. The determination of hyperoside in the flower and leaf of hawthorn (Crataegus oxycantha and Crataegus monogyna by the spectrophotometric method

    Directory of Open Access Journals (Sweden)

    Mihajlović Dušanka


    Full Text Available The flower and leaf of hawthorn contains many active components, used in the production of pharmaceutical preparations for cardiotonic, anti-hypertonic anti-hypotonic, artherosclerotic, anti-arithmic and anti-anemic groups. According to the ROTTE list (1996, 159 of 1800 pharmaceutical preparations contain components from hawthorn. Due to the remedial action of hyperoside and other flavonoids from hawthorn, their determination is important for the standardization of extract and preparation quality. The extraction of the flavonoids from a mixture of hawthorn (C. oxycantha and C. monogyna flower and leaf was carried out by percolation with 40% and 70% (v/v ethanol. In order to determine the content of total flavonoids calculated as hyperoside spectrophotometric method with aluminium(lll chloride as a colour reagent at 425 nm was applied. The total flavonoid content in the herbal material mixture was 0.483%, in 40% and 70% (v/v ethanolic liquid extract it was 138 mg/100 cm3 and 157 mg/100 cm, respectively. The extraction degree of total flavonoids with 40% and 70% (v/v ethanolic solutions was 57.14% and 65.01% respectively. The yield of total flavonoids in the dry extract was 63% in regard to the herbal mixure content.

  18. Capillary electrophoretic analysis of flavonoids in single-styled hawthorn (Crataegus monogyna Jacq.) ethanolic extracts. (United States)

    Urbonaviciūte, A; Jakstas, V; Kornysova, O; Janulis, V; Maruska, A


    Flavonoids are an important group of natural compounds, which can prevent coronary heart disease and have antioxidant properties. Hawthorn is a well known and widely used medicinal plant due to its cardiotonic activity. Previous studies refer mostly to the HPLC analysis of the flavonoids: vitexin, quercetin, hyperoside, oligomeric procyanidins, which appear to be primarily responsible for the cardiac action of the plant. Aqueous ethanolic extracts of single-styled hawthorn (Crataegus monogyna Jacq., f.: Rosaceae Juss.) leaves and sprouts were analyzed by means of capillary zone electrophoresis (CZE). Influence of vegetation period on the extract qualitative composition and flavonoids quantities was evaluated. Sample preparation by extraction using different concentration of aqueous ethanol (40-96%, v/v) and the influence of extractant composition on the recovery of flavonoids are discussed in detail. The results obtained using CZE are compared to the results of spectrophotometric and HPLC analysis of the extracts. The effect of storage conditions of extracts (solar irradiation, temperature and duration) on degradation of flavonoids was investigated.

  19. Effect of hawthorn (Crataegus oxycantha) crude extract and chromatographic fractions on multiple activities in a cultured cardiomyocyte assay. (United States)

    Long, S R; Carey, R A; Crofoot, K M; Proteau, P J; Filtz, T M


    Extracts of hawthorn (Crataegus oxycantha) have become popular herbal supplements for their well-recognized cardiotonic effects. Many commercial preparations have been used successfully in the treatment of congestive heart failure, although the active principles within these extracts have yet to be conclusively identified. Several hawthorn preparations were studied and found to have negative chronotropic effects in a cultured neonatal murine cardiomyocyte assay using unpaced cells. As compared to conventional cardiac drugs (i.e., epinephrine, milrinone, ouabain, or propranolol), hawthorn extract has a unique activity profile. Hawthorn extract appears to be anti-arrhythmic and capable of inducing rhythmicity in quiescent cardiomyocytes. Hawthorn extract does not cause beta-adrenergic receptor blockade at concentrations which cause negative chronotropic effects. Commercial hawthorn preparations, extracts prepared from dried leaves and those made from dried berries have similar chronotropic activities. When crude extracts are separated using size-exclusion chromatography, several fractions retain multiple cardiac activities. Assays with chromatographic fractions reveal that multiple dissimilar cardioactive components may exist within the extract, making the identification of individual active constituents more challenging.

  20. Biosynthesis of car1ssol and carissic Acid. (United States)

    Nizami, S S; Khan, M A; Naim, Z; Islam, M N; Azeem, S W


    Carissa carandas belongs to family apocynaceae which consists of 300 genera and 1000 species. It is a large shrub with simple thorn and commonly cultivated throughout Pakistan for hedges and is called "Kakronda". The different parts of this plant have been used for various systems of medicine (Kirtikar et al., 1993). Cardiotonic activity was found in root of this plant (Rastogi et al., 1966; Rastogi et al., 1967; Vohra et al., 1963). This plant has been mentioned in the old chemical literature as purgative, stomachic, antihelmintics and antidote for snake-bite (Kirtikar., 1933). The physical characteristics of oil from the fruits of Carissa carandas were determined by using standard methods. In addition to this a study of sugars and amino acids from the fruits of this plant was also undertaken by the present authors (Naim et al., 1986). Our studies in the chemical investigation on this plant had led to the isolation of two new triterpene carissol Ia (Naim et al., 1985) and carissic acid lb (Naim et al., 1988).

  1. Antivenom potential of ethanolic extract of Cordia macleodii bark against Naja venom

    Institute of Scientific and Technical Information of China (English)

    Pranay Soni; Surendra H. Bodakhe


    Objective: To evaluate the antivenom potential of ethanolic extract of bark of Cordia macleodii against Naja venom induced pharmacological effects such as lethality, hemorrhagic lesion, necrotizing lesion, edema, cardiotoxicity and neurotoxicity.Methods:Wistar strain rats were challenged with Naja venom and treated with the ethanolic extract of Cordia macleodii bark. The effectiveness of the extract to neutralize the lethalities ofNaja venom was investigated as recommended by WHO. Results: At the dose of 400 and 800 mg/kg ethanolic extract of Cordia macleodii bark significantly inhibited the Naja venom induced lethality, hemorrhagic lesion, necrotizing lesion and edema in rats. Ethanolic extract of Cordia macleodii bark was effective in neutralizing the coagulant and defibrinogenating activity of Naja venom. The cardiotoxic effects in isolated frog heart and neurotoxic activity studies on frog rectus abdominus muscle were also antagonized by ethanolic extract of Cordia macleodii bark.Conclusions:It is concluded that the protective effect of extract of Cordia macleodii against Naja venom poisoning may be mediated by the cardiotonic, proteolysin neutralization, anti-inflammatory, antiserotonic and antihistaminic activity. It is possible that the protective effect may also be due to precipitation of active venom constituents.


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    A. Krishnaveni


    Full Text Available Traditionally used by the tribal of Rajasthan to prevent conception. Roots are used as appetizer, aphrodisiac, brain tonic, cardiotonic and to treat insanity and synovitis. Leaves, seeds preparations are used to treat epilepsy, diarrhea and nootropic. Leaf materials were collected, dried and coarsely powdered and were subjected to physiochemical constants, behavioral characters of the leaf powder with chemical reagents. Pharmacognostical studies include macroscopical, microscopical observations. Physical chemical constants such as ash values, extractive values, loss on drying, foreign organic matter were determined. Ash values include total ash; acid insoluble and water soluble ash were observed. Extractive values of powder with solvents such as petroleum ether, chloroform, ethyl actetae, ethanol and water were determined. Macroscopical characters help in identifying the leaf. Anatomical observations showed the presence of trichomes, upper and lower epidermal cells with rubiaceous stomata. Sclerenchyma fibers and acicular crystal were observed. The percentage of total ash values (4.3, 1.6 and3.94 % yield of petroleum ether, ethyl acetate, chloroform, ethanol and water showed 3.16,6.4,5.8,10.2 and 7.6% respectively. Preliminary phytochemical screening reported the presence of alkaloids, tannins, phenolic compounds, glycosides and flavanoids.The reported phytoconstitutents of the plant Argyreia nervosa may be responsible for the pharmacological activities. The results obtained add credit to the existing traditional information which will further increase the usage of this plant and provokes towards the investigation of the plant.

  3. The Na/K-ATPase-mediated signal transduction as a target for new drug development. (United States)

    Xie, Zijian; Xie, Joe


    The Na/K-ATPase, or Na+ pump, is a member of the P-type ATPase superfamily. In addition to pumping ions, the Na/K-ATPase is a receptor that not only regulates the function of protein kinases, but also acts as a scaffold, capable of tethering different proteins into a signalplex. The signaling Na/K-ATPase resides in caveolae and forms a "binary receptor" with the tyrosine kinase Src. Endogenous cardiotonic steroids and digitalis drugs such as ouabain act as agonists and provoke this binary receptor, resulting in tyrosine phosphorylation of the proteins that are either associated with, or in close proximity to, the signaling Na/K-ATPase. Subsequently, this initiates protein kinase cascades including ERKs and PKC isozymes. It also increases mitochondrial production of reactive oxygen species (ROS) and regulates intracellular calcium concentration. Like other receptors, activation of the Na/K-ATPase/Src by ouabain induces the endocytosis of the plasma membrane Na/K-ATPase. Significantly, this newly appreciated signaling function of the Na/K-ATPase appears to play an important role in the pathogenesis of many cardiovascular diseases, therefore serving as an important target for development of novel therapeutic agents.

  4. Antimicrobial, Anti-Inflammatory, Antiparasitic, and Cytotoxic Activities of Laennecia confusa

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    María G. Martínez Ruiz


    Full Text Available The current paper investigated the potential benefit of the traditional Mexican medicinal plant Laennecia confusa (Cronquist G. L. Nesom (Asteraceae. Fractions from the hexane, chloroform, methanol, and aqueous extracts were analyzed for antibacterial, antifungal, anti-inflammatory, and antiparasitic activities. The antimicrobial activity of the extracts and fractions was assessed on bacterial and fungal strains, in addition to the protozoa Leishmania donovani, using a microdilution assay. The propensity of the plant's compounds to produce adverse effects on human health was also evaluated using propidium iodine to identify damage to human macrophages. The anti-inflammatory activity of the extracts and fractions was investigated by measuring the secretion of interleukin-6. Chemical analyses demonstrated the presence of flavonoids, cyanogenic and cardiotonic glycosides, saponins, sesquiterpene lactones, and triterpenes in the chloroform extract. A number of extracts and fractions show antibacterial activity. Of particular interest is antibacterial activity against Staphylococcus aureus and its relative methicillin-resistant strain, MRSA. Hexanic and chloroformic fractions also exhibit antifungal activity and two extracts and the fraction CE 2 antiparasitic activity against Leishmania donovani. All bioactive extracts and fractions assayed were also found to be cytotoxic to macrophages. In addition, the hexane and methane extracts show anti-inflammatory activity by suppressing the secretion of interleukine-6.


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    Nidhi Tyagi


    Full Text Available Cucurbitaceae family is major source of medicinal agents since ancient time. Various plants parts including fruits of this family have been established for their pharmacological potential. Lagenaria siceraria (Molina standley (family Cucurbitaceae commonly known as lauki (Hindi and bottle gourd (English is a medicinal plant. It is used as medicine in India, China, European countries, Brazil, Hawaiian island, etc. for its cardiotonic, general tonic and diuretic properties. Further the antihepatotoxic, analgesic and anti-inflammatory, hypolipidemic, antihyperglycemic, immunomodulatory and antioxidant activities of its fruit extract have been evaluated. It is used as vermifuge purgative diuretic and it is also recommended for increasing lactation for lactating women..Fruits are also used in treatment of cancer, pain, ulcer, fever, pectoral cough, asthma and other bronchial disorders. In many countries, this plant has been used traditionally as a single treatment for diabetes mellitus possess immunosuppressive, antitumour, antiviral, antiproliferative and anti-HIV activities. This study is an attempt to compile an up-to-date and comprehensive review of Lagenaria siceraria that covers its traditional and folk medicinal uses, phytochemistry and pharmacology profile.

  6. A review of therapeutic potential ofAjuga bracteosa:A critically endangered plant from Himalaya

    Institute of Scientific and Technical Information of China (English)

    Mubashir Hussain; Yamin Bibi; Naveed Iqbal Raja; Muhammad Iqbal; Sumaira Aslam; Nida Tahir; Muhammad Imran; Anam Iftikhar


    Medicinal plants are the nature’s gift for the humanity to treat various ailments and to spend a prosperous healthy life. There are almost 300 species ofAjuga. Among them,Ajuga bracteosa Wall. ex Benth (A. bracteosa) is an important medicinal plant of Himalaya regions. Its medicinal potential is due to the presence of various pharmacologically active compounds such as neo-clerodane diterpenoids, flavonol glycosides, iridoid glycosides, ergosterol-5,8-endoperoxide and phytoecdysones. The aim of this review article was to gather information aboutA. bracteosa which is currently scattered in form of various publications. This review article tried to attract the attention from people for therapeutic potential ofA. bracteosa. The present review comprises upto date information of botanical aspects, active ingredients, traditional uses, and pharmacological activities such as antitumor, antimicrobial, antimalarial, anti-inflammatory, cardiotonic activity, antiarthritic activity, antioxidant activity andin vitro production of secondary metabolites for pharmaceuticals. Due to remarkable medicinal potential and commercialization, this species is indexed into critically endangered category and it is facing extremely high risk of extinction. Conservation practices and management techniques should be carried out to protect this important species from extinction. Recent biotechnological approaches will be quite helpful for its conservation.

  7. A Chinese Herbal Preparation Containing Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum Reduces Circulating Adhesion Molecules

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    Kylie A. O’Brien


    Full Text Available Circulating adhesion molecules (CAMs, surface proteins expressed in the vascular endothelium, have emerged as risk factors for cardiovascular disease (CVD. CAMs are involved in intercellular communication that are believed to play a role in atherosclerosis. A Chinese medicine, the “Dantonic Pill” (DP (also known as the “Cardiotonic Pill”, containing three Chinese herbal material medica, Radix Salviae Miltiorrhizae, Radix Notoginseng and Borneolum Syntheticum, has been used in China for the prevention and management of CVD. Previous laboratory and animal studies have suggested that this preparation reduces both atherogenesis and adhesion molecule expression. A parallel double blind randomized placebo-controlled study was conducted to assess the effects of the DP on three species of CAM (intercellular cell adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 and endothelial cell selectin (E-selectin in participants with mild-moderate hypercholesterolemia. Secondary endpoints included biochemical and hematological variables and clinical effects. Forty participants were randomized to either treatment or control for 12 weeks. Treatment with DP was associated with a statistically significant decrease in ICAM-1 (9% decrease, P = .03 and E-Selectin (15% decrease, P = .004. There was no significant change in renal function tests, liver function tests, glucose, lipids or C-reactive protein levels and clinical adverse effects did not differ between the active and the control groups. There were no relevant changes in participants receiving placebo. These results suggest that this herbal medicine may contribute to the development of a novel approach to cardiovascular risk reduction.


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    Sahoo Himanshu Bhusan


    Full Text Available In traditional medicine, different parts of Elephantopus scaber Linn are highly valued for the treatment of array of human diseases including cardiotonic, diuretic, hepatoprotective, antimicrobial, anti-inflammatory activity etc. In the present study, single oral dose (200-600 mg/kg/day for 7 days of ethanolic leaf extract of Elephantopus scaber Linn. Leaves were studied for its nephroprotective effect on albino rats. In the study of gentamicin induced nephrotoxicity, thirty adult male Wistar rats were evenly divided into five groups of six animals each. The treated groups, which were pretreated with the dose of 200, 400 and 600 mg/kg body weight per day of leaf extract respectively one hour before each dose of the nephrotoxicants for seven days and compared with control group. On 7th day, the blood samples of all the groups were taken for biochemical examination on different parameters i.e. serum levels of urea, protein and creatinine, as well as quantitative ionic estimation of some ions like sodium, potassium, chloride, bicarbonate etc. Histological analysis of rat kidneys and body weight as well as kidney wt were also observed. In the study of gentamicin induced nephrotoxicity on rats, the dose of tested extract at 200–600 mg/kg/day significantly (p < 0.01 decreases the levels of serum creatinine, total protein and serum urea but shows slightly increase on the electrolyte levels in dose dependent manner. The nephroprotective effect of Elephantopus scaber could be due to flavonoid content and the inherent antioxidant moieties in the extract. The ethanolic extract of Eelphantopus scaber leaves could constitute a lead to discovery of a novel drug for the treatment of drug-induced Nephrotoxicity.Key words: Elephantopus scaber Linn, gentamicin-induced nephrotoxicities, serum creatinine, serum urea, nephroprotective effect.

  9. Pivotal effects of phosphodiesterase inhibitors on myocyte contractility and viability in normal and ischemic hearts

    Institute of Scientific and Technical Information of China (English)

    Yuan James RAO; Lei XI


    Phosphodiesterases (PDEs) are enzymes that degrade cellular cAMP and cGMP and are thus essential for regulating the cyclic nucleotides. At least 11 families of PDEs have been identified, each with a distinctive structure, activity, expression, and tissue distribution. The PDE type-3, -4, and -5 (PDE3, PDE4, PDE5) are localized to specific regions of the cardiomyo-cyte, such as the sarcoplasmic reticulum and Z-disc, where they are likely to influence cAMP/cGMP signaling to the end effectors of contractility. Several PDE inhibitors exhibit remarkable hemodynamic and inotropic properties that may be valuable to clinical practice. In particular, PDE3 inhibitors have potent cardiotonic effects that can be used for short-term inotropic support, especially in situations where adrenergic stimulation is insufficient. Most relevant to this review, PDE in-hibitors have also been found to have cytoprotective effects in the heart. For example, PDE3 inhibitors have been shown to be cardioprotective when given before ischemic attack, whereas PDE5 inhibitors, which include three widely used erectile dysfunction drugs (sildenafil, vardenafil and tadalafil), can induce remarkable cardioprotection when administered either prior to ischemia or upon reperfusion. This article provides an overview of the current laboratory and clinical evidence, as well as the cellular mechanisms by which the inhibitors of PDE3, PDE4 and PDE5 exert their beneficial effects on normal and ischemic hearts. It seems that PDE inhibitors hold great promise as clinically applicable agents that can improve car-diac performance and cell survival under critical situations, such as ischemic heart attack, cardiopulmonary bypass surgery, and heart failure.

  10. Effects of Ouabain on Proliferation of Human Endothelial Cells Correlate with Na+,K+-ATPase Activity and Intracellular Ratio of Na+ and K. (United States)

    Tverskoi, A M; Sidorenko, S V; Klimanova, E A; Akimova, O A; Smolyaninova, L V; Lopina, O D; Orlov, S N


    Side-by-side with inhibition of the Na+,K+-ATPase ouabain and other cardiotonic steroids (CTS) can affect cell functions by mechanisms other than regulation of the intracellular Na+ and K+ ratio ([Na+]i/[K+]i). Thus, we compared the dose- and time-dependences of the effect of ouabain on intracellular [Na+]i/[K+]i ratio, Na+,K+-ATPase activity, and proliferation of human umbilical vein endothelial cells (HUVEC). Treatment of the cells with 1-3 nM ouabain for 24-72 h decreased the [Na+]i/[K+]i ratio and increased cell proliferation by 20-50%. We discovered that the same ouabain concentrations increased Na+,K+-ATPase activity by 25-30%, as measured by the rate of (86)Rb(+) influx. Higher ouabain concentrations inhibited Na+,K+-ATPase, increased [Na+]i/[K+]i ratio, suppressed cell growth, and caused cell death. When cells were treated with low ouabain concentrations for 48 or 72 h, a negative correlation between [Na+]i/[K+]i ratio and cell growth activation was observed. In cells treated with high ouabain concentrations for 24 h, the [Na+]i/[K+]i ratio correlated positively with proliferation inhibition. These data demonstrate that inhibition of HUVEC proliferation at high CTS concentrations correlates with dissipation of the Na+ and K+ concentration gradients, whereas cell growth stimulation by low CTS doses results from activation of Na+,K+-ATPase and decrease in the [Na+]i/[K+]i ratio.

  11. Pandanus odoratissimus (Kewda: A Review on Ethnopharmacology, Phytochemistry, and Nutritional Aspects

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    Prafulla P. Adkar


    Full Text Available Pandanus odoratissimus Linn. (family: Pandanaceae is traditionally recommended by the Indian Ayurvedic medicines for treatment of headache, rheumatism, spasm, cold/flu, epilepsy, wounds, boils, scabies, leucoderma, ulcers, colic, hepatitis, smallpox, leprosy, syphilis, and cancer and as a cardiotonic, antioxidant, dysuric, and aphrodisiac. It contains phytochemicals, namely, lignans and isoflavones, coumestrol, alkaloids, steroids, carbohydrates, phenolic compounds, glycosides, proteins, amino acids as well as vitamins and nutrients, and so forth. It is having immense importance in nutrition. A 100 g edible Pandanus pericarp is mainly comprised of water and carbohydrates (80 and 17 g, resp. and protein (1.3 mg, fat (0.7 mg, and fiber (3.5 g. Pandanus fruits paste provides 321 kilocalories, protein (2.2 g, calcium (134 mg, phosphorus (108 mg, iron (5.7 mg, thiamin (0.04 mg, vitamin C (5 mg, and beta-carotene (19 to 19,000 μg (a carotenoid that is a precursor to vitamin A. Pandanus fruit is an important source of vitamins C, B1, B2, B3, and so forth, usually prepared as a Pandanus floured drink. Traditional claims were scientifically evaluated by the various authors and the phytochemical profile of plant parts was well established. The methods for analytical estimations were developed. However, there is paucity of systematic compilation of scientifically important information about this plant. In the present review we have systematically reviewed and compiled information of pharmacognostic, ethnopharmacology, phytochemistry, pharmacology, nutritional aspects, and analytical methods. This review will enrich knowledge leading the way into the discovery of new therapeutic agents with improved and intriguing pharmacological properties.

  12. Phyto-Pharmacology of Ziziphus jujuba Mill- A plant review

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    R T Mahajan


    Full Text Available Herbs have always been the natural form of medicine in India. Medicinal plants have curative properties due to presence of various complex chemical substances of different composition which contain secondary metabolites such as alkaloids, flavonoids, terpenoids, saponin and phenolic compounds distributed in different parts of the plants. Ziziphus jujuba Mill, a member of the family Rhamnaceae, commonly known as Bor, is used traditionally as tonic and aphrodisiac and sometimes as Hypnotic-sedative and Anxiolytic, anticancer (Melanoma cells, Antifungal, Antibacterial, Antiulcer, Anti-inflammatory, Cognitive, Antispastic, Antifertility/contraception, Hypotensive and Antinephritic, Cardiotonic, Antioxidant, Immunostimulant, and Wound healing properties. It possesses allied compounds viz. Ascorbic acid, thiamine, riboflavin-bioflavonoids and Pectin A and various chemical substances like Mauritine-A; Amphibine-H; Jubanine-A; Jubanine-B; Mucronine-D and Nummularine-B. Sativanine-E. Frangufoline, Ziziphine-A to Q, betulinic acid colubrinic acid, alphitolic acid, 3-O-cis-p-coumaroylalphitolic acid, 3-O-transp-coumaroylalphitolic acid, 3-O-cis-p-coumaroylmaslinic acid, 3-O-trans-pcoumaroylmaslinic acid, oleanolic acid, betulonic acid, oleanonic acid, zizyberenalic acid and betulinic acid, jujubosides A, B, A1 B1 and C and acetyljujuboside B and the protojujubosides A, B and B1, saponin, ziziphin, from the dried leaves of Z. jujube - 3-O-a-L-rhamnopyranosyl (1-2-a-arabinopyranosyl-20-O- (2,3-di-O-acetyl-a-L-rhamnopyranosyl jujubogenin. Saponin from leaves and stem are 3-O- ((2-O- alpha - D - furopyranosyl - 3-O- beta - D -glucopyranosyl - alpha - L - arabinopyranosyl jujubogenin and (6′′′-sinapoylspinosin, 6′′′-feruloylspinosin and 6′′′-p-coumaroylspinosin. The present review discusses photo-chemistry, pharmacology, medicinal properties and biological activities of Za jujuba and its usage in different ailments.

  13. Human breast tumor cells are more resistant to cardiac glycoside toxicity than non-tumorigenic breast cells.

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    Rebecca J Clifford

    Full Text Available Cardiotonic steroids (CTS, specific inhibitors of Na,K-ATPase activity, have been widely used for treating cardiac insufficiency. Recent studies suggest that low levels of endogenous CTS do not inhibit Na,K-ATPase activity but play a role in regulating blood pressure, inducing cellular kinase activity, and promoting cell viability. Higher CTS concentrations inhibit Na,K-ATPase activity and can induce reactive oxygen species, growth arrest, and cell death. CTS are being considered as potential novel therapies in cancer treatment, as they have been shown to limit tumor cell growth. However, there is a lack of information on the relative toxicity of tumor cells and comparable non-tumor cells. We have investigated the effects of CTS compounds, ouabain, digitoxin, and bufalin, on cell growth and survival in cell lines exhibiting the full spectrum of non-cancerous to malignant phenotypes. We show that CTS inhibit membrane Na,K-ATPase activity equally well in all cell lines tested regardless of metastatic potential. In contrast, the cellular responses to the drugs are different in non-tumor and tumor cells. Ouabain causes greater inhibition of proliferation and more extensive apoptosis in non-tumor breast cells compared to malignant or oncogene-transfected cells. In tumor cells, the effects of ouabain are accompanied by activation of anti-apoptotic ERK1/2. However, ERK1/2 or Src inhibition does not sensitize tumor cells to CTS cytotoxicity, suggesting that other mechanisms provide protection to the tumor cells. Reduced CTS-sensitivity in breast tumor cells compared to non-tumor cells indicates that CTS are not good candidates as cancer therapies.

  14. Na/K-ATPase signaling regulates collagen synthesis through microRNA-29b-3p in cardiac fibroblasts. (United States)

    Drummond, Christopher A; Hill, Michael C; Shi, Huilin; Fan, Xiaoming; Xie, Jeffrey X; Haller, Steven T; Kennedy, David J; Liu, Jiang; Garrett, Michael R; Xie, Zijian; Cooper, Christopher J; Shapiro, Joseph I; Tian, Jiang


    Chronic kidney disease (CKD) is accompanied by cardiac fibrosis, hypertrophy, and dysfunction, which are commonly referred to as uremic cardiomyopathy. Our previous studies found that Na/K-ATPase ligands or 5/6th partial nephrectomy (PNx) induces cardiac fibrosis in rats and mice. The current study used in vitro and in vivo models to explore novel roles for microRNA in this mechanism of cardiac fibrosis formation. To accomplish this, we performed microRNA profiling with RT-qPCR based arrays on cardiac tissue from rats subjected to marinobufagenin (MBG) infusion or PNx. The analysis showed that a series of fibrosis-related microRNAs were dysregulated. Among the dysregulated microRNAs, microRNA (miR)-29b-3p, which directly targets mRNA of collagen, was consistently reduced in both PNx and MBG-infused animals. In vitro experiments demonstrated that treatment of primary cultures of adult rat cardiac fibroblasts with Na/K-ATPase ligands induced significant increases in the fibrosis marker, collagen protein, and mRNA expression compared with controls, whereas miR-29b-3p expression decreased >50%. Transfection of miR-29b-3p mimics into cardiac fibroblasts inhibited cardiotonic steroids-induced collagen synthesis. Moreover, a specific Na/K-ATPase signaling antagonist, pNaKtide, prevented ouabain-induced increases in collagen synthesis and decreases in miR-29b-3p expression in these cells. In conclusion, these data are the first to indicate that signaling through Na/K-ATPase regulates miRNAs and specifically, miR-29b-3p expression both in vivo and in vitro. Additionally, these data indicate that miR-29b-3p expression plays an important role in the formation of cardiac fibrosis in CKD.

  15. Determination the Total Flavonoids from Stem and Leaf of Artabotrys.haimanensis

    Institute of Scientific and Technical Information of China (English)

    BI He-ping; SONG Xiao-Ping; HAN Chang-ri; LI Chuan-bao


    The Annonaccac family is a main one of the tropical plants flora and there are totally 127 genus, about 2231 species in the world, wildly distributed in the tropical zone and subtropics areas.China is one of the countries where species of this family are mostly distributed, with 24 genus, 103 species and 6 variant, among which, 45 species and 1 variant are endemic to China. There are about 100 types of plants of Artabotrys genus in the world, among which, 10 species are in China. Scholars from home and abroad have found a series of new substance of biological activities in the plants of Annonaccac family with antimalarial, anti-tumor, anti-leukemia and obvious cardiotonic effects,which has aroused great interest. Plants of Artabotrys genus, Artabotrys Hainanensis are endemic to Hainan, distributed widely in Hainan Island. They have long been used among the ordinary people as medicinal plants with antipyretic, antidotal, antiphlogistic and analgesic effects. The flavonoid is a very important secondary metabolite in plants with many physiological activities such as fat-reduction, antithrombus, antioxidant and blood-sugar-reduction. This paper studies the total flavonoids from stem and leaf of Artabotrys by spectrophotometry. Artabotrys Hainanensis R.E.Fries were collected from Hainan Jianfeng Mountain and were identified. Spectrophotometry was used to determination of the total flavonoids from stem and leaf of Artabotrys. The total flavonoids of Artabotrys were tested with rutin as check sample. By adding aluminium ion agent and controling proper pH, the flavonoids and the aluminium ion were combined into complex compound and the characteristic absorption peak was obtainable in the visible spectrum. The total flavonoids from stem and leaf of Artabotrys were determined to be 2.29% in stem and 6.83% in leaf. The regression equation was Y=0.000786A+0.0058, and the correlation coefficient r=0.9997. This method is easily operated and the result determined is stable and

  16. Bibliographic Studies on the Bufonis Venenum

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    Kye-Sung Kang


    Full Text Available Objectives : Through the literatures on the effets of Bufonis Venenum, we are finding out the clinical possibility and revealing the more effective to intractable diseases. Methods : We investigated the literatures of Oriental Medicine and experimental reports about Bufonis Venenum. Results : 1. Bufonis Venenum is made of bufonidae bufo bufo gargarizans cantor or bufo melanostictus schneider of white serum which secreted from parotid gland or dermato gland, and it is dried for using. 2. In oriental medicine, Bufonis Venenum has been mainly used on the tumors, cacanthrax and dermatic disease, and then it has been clinically used on infantile athrepsia, tetanus, sore throat, toothache, and so on. 3. The pharmacological effects of Bufonis Venenum are cardiotonic, respiration stimulation, depressor or vasopressor, topical anesthcsia, hallucination, striped muscle stimulation, antiasthmatic, antibacterial, antiinflammatory, anticancer, diuretic, immuno effects, etc. 4. Bufonis Venenum is largely divided in ether binding steroid compound, hydroxyl steroid compound, carboxyl or aldehyde steroid compound, indole compound, and adrenaline, cholesterole, etc. 5. Symptoms of Bufonis Venenum poisoning in digestive system are vommitig, abdominal pain, diarrhea, dehydration, in circulatory system are palpitation, shock, bradycardia, in nervous system are vertigo, somnolentia, muscle-tendon reflex weakness, and critical conditions to tissue necrosis and heart attack. 6. Ways to treat Bufonis Venenum poisoning include gastric irrigation with 0.20.5% potassium permanganate fluid and atropine 0.5~1.0mg subcutaneous injection. From the chinese book of Bon Cho Gang Moke(本草綱目, if white serum of Bufonis Venenum enter the eyes, it happens the edema and pain. And then washed the eyes by juice of Lithospermi Radix(紫草 that the edema is removed. Conclusions and Discussion : The results from above literary studies show that prescriptions and Aqua-acupuncture of

  17. Quantitative analysis of some volatile components in Mimusops elengi L.

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    Chantana Aromdee


    Full Text Available Dried pikul flower (Mimusops elengi L., Sapotaceae is used in many recipes of Thai traditional medicine i.e. cardiotonic and stomachic. In this study, fresh and dried pikul flowers were investigated. The odour of pikul flower, even when it was dried, is very strong and characteristic. The constituents of volatile oils in fresh and dried pikul flowers extracted by ether were analysed by gas chromatography-mass spectrometry. 2-Phenylethanol, 4-hydroxybenzenemethanol and cinnamyl alcohol were mainly found in fresh flower, 10.49, 8.69 and 6.17%, respectively. Whereas those mainly found in dried flowers were long chain carboxylic acid ester and (Z-9-octadecenoic acid, 5.37 and 4.71% of ether extract, respectively.An analytical method simultaneously determining benzyl alcohol, 2-phenylethanol and methyl paraben was developed by using the GC-FID method. The percent recoveries were 91.66, 104.59 and 105.28%, respectively. The intraday variations(% RSD were 7.22, 6.67 and 1.86%; and the interday variation were 3.12, 2.52 and 3.55%, respectively. Detection limits were 0.005, 0.014 and 0.001 ppm, and quantitation limits were 0.015, 0.048 and 0.003 ppm, respectively. Benzyl alcohol, 2-phenylethanol and methyl paraben content of dried flowers (9 samples from various drug stores in Thailand and one sample from China were 6.40-13.46, 17.57-196.57 and 27.35-355.53 ppm, respectively.

  18. Peripartum cardiomyopathy in a patient treated for acute myeloid leukemia

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    Čolović Nataša


    Full Text Available Introduction. Peripartum cardiomyopathy usually presents with systolic heart failure during the last months of pregnancy and up to five months postpartum. The disease is rare and can be fatal. Case Outline. We report a 30-year-old female who was diagnosed with acute myeloid leukemia, with maturation and cytogenetic finding of t(8;21(q22;q22,del(9(q22 in January 2004. She was treated with chemotherapy and achieved complete remission that lasts to date. She became pregnant and delivered a healthy newborn with caesarean section in 2009. Seven months later, she again became pregnant and delivered the second child with caesarean section in January 2011. Seven days after delivery she developed symptoms and signs of heart failure. Electrocardiogram showed sinus rhythm, low voltage and negative T-waves in inferior and lateral leads. Echocardiography revealed global left ventricular dysfunction with ejection fraction of 15%, with mobile thrombotic mass of 12 mm attached to the left ventricle wall. She was treated with both unfractionated and low-molecular heparin, diuretics, cardiotonics, and beta-blockers. Within six following weeks left ventricle systolic function improved up to 25-30%. The full clinical recovery was achieved in September 2013, resulting in absence of heart failure and left ventricular ejection fraction of 54%. Conclusion. Peripartum cardiomyopathy is a rare condition. The cause of cardiomyopathy is unknown, but it is believed that it could be triggered by various conditions and risk factors. Although the patient was treated with cardiotoxic drugs (doxorubicin and mitoxantrone in permitted doses, they could have been contributory factors of myocardial damage. Close monitoring of cardiac function in the peripartal period might be beneficial in patients treated with cardiotoxic drugs. [Projekat Ministarstva nauke Republike Srbije, br. 175080 I br. OI 175034

  19. Digoxin-Mediated Upregulation of RGS2 Protein Protects against Cardiac Injury. (United States)

    Sjögren, Benita; Parra, Sergio; Atkins, Kevin B; Karaj, Behirda; Neubig, Richard R


    Regulator of G protein signaling (RGS) proteins have emerged as novel drug targets since their discovery almost two decades ago. RGS2 has received particular interest in cardiovascular research due to its role in regulating Gqsignaling in the heart and vascular smooth muscle. RGS2(-/-)mice are hypertensive, prone to heart failure, and display accelerated kidney fibrosis. RGS2 is rapidly degraded through the proteasome, and human mutations leading to accelerated RGS2 protein degradation correlate with hypertension. Hence, stabilizing RGS2 protein expression could be a novel route in treating cardiovascular disease. We previously identified cardiotonic steroids, including digoxin, as selective stabilizers of RGS2 protein in vitro. In the current study we investigated the functional effects of digoxin-mediated RGS2 protein stabilization in vivo. Using freshly isolated myocytes from wild-type and RGS2(-/-)mice treated with vehicle or low-dose digoxin (2µg/kg/day for 7 days) we demonstrated that agonist-induced cAMP levels and cardiomyocyte contractility was inhibited by digoxin in wild-type but not in RGS2(-/-)mice. This inhibition was accompanied by an increase in RGS2 protein levels in cardiomyocytes as well as in whole heart tissue. Furthermore, digoxin had protective effects in a model of cardiac injury in wild-type mice and this protection was lost in RGS2(-/-)mice. Digoxin is the oldest known therapy for heart failure; however, beyond its activity at the Na(+)/K(+)-ATPase, the exact mechanism of action is not known. The current study adds a novel mechanism, whereby through stabilizing RGS2 protein levels digoxin could exert its protective effects in the failing heart.

  20. Ouabain facilitates cardiac differentiation of mouse embryonic stem cells through ERK1/2 pathway

    Institute of Scientific and Technical Information of China (English)

    Yee-ki LEE; Kwong-man NG; Wing-hon LAI; Cornelia MAN; Deborah K LIEU; Chu-pak LAU; Hung-fat TSE; Chung-wah SIU


    Aim:To investigate the effects of the cardiotonic steroid, ouabain, on cardiac differentiation of murine embyronic stem cells (mESCs).Methods:Cardiac differentiation of murine ESCs was enhanced by standard hanging drop method in the presence of ouabain (20 μmol/L) for 7 d. The dissociated ES derived cardiomyocytes were examined by flow cytometry, RT-PCR and confocal calcium imaging.Results:Compared with control, mESCs treated with ouabain (20 μmol/L) yielded a significantly higher percentage of cardiomyocytesand significantly increased expression of a panel of cardiac markers including Nkx 2.5, α-MHC, and β-MHC. The α1 and 2- isoforms Na+/K+ -ATPase, on which ouabain acted, were also increased in mESCs during differentiation. Among the three MAPKs involved in the cardiac hypertrophy pathway, ouabain enhanced ERK1/2 activation. Blockage of the Erk1/2 pathway by U0126 (10 μmol/L) inhibited cardiac differentiation while ouabain (20 μmol/L) rescued the effect. Interestingly, the expression of calcium handling proteins, includ ing ryanodine receptor (RyR2) and sacroplasmic recticulum Ca2+ ATPase (SERCA2a) was also upregulated in ouabain-treated mESCs.ESC-derived cardiomyocyes (CM) treated with ouabain appeared to have more mature calcium handling. As demonstrated by confocal Ca2+ imaging, cardiomyocytes isolated from ouabain-treated mESCs exhibited higher maximum upstroke velocity (P<0.01) and maximum decay velocity (P<0.05), as well as a higher amplitude of caffeine induced Ca2+ transient (P<0.05), suggesting more mature sarcoplasmic reticulum (SR).Conclusion:Ouabain induces cardiac differentiation and maturation of mESC-derived cardiomyocytes via activation of Erk1/2 and more mature SR for calcium handling.

  1. Dissolution Behavior and Content Uniformity of An Improved Tablet Formulation Assayed by Spectrofluorometric and RIA Methods

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    Morteza Rafiee-Tehrani


    Full Text Available Digoxin 0.25 mg tablets were manufactured by pregranulation of lactose-fcorn starch with 10% corn starch paste and deposition of solvent on pregranules to make digoxin granules. In the preparation of tablet A, granules of lactose-corn Starch was uniformly moistened with a 5% chloroform-ethanol solution (2:lv/vof digoxin by a simple blending. Tablet B was produced by spray granulation system on which the solvent was sprayed on the granules of lactose-corn starch by utilization of a laboratory size fluidized bed drier (Uniglatt . The content uniformity and dissolution of both tablets were determined by the spectrofluorometric and radio¬immunoassay (RIA method modified for the assay of tablet solutious. One available commercially brand of digoxin tablet (C was included in dissolution study for comparison. For the spectrofluorometric method the technique is based on the fluor-ometric measurenent of the dehydration product of the cardiotonic steroid resulting from its reaction with hydrogen peroxide in concentrated hydrochloric acid. For the RIA method, the filtrate was diluted to theoretical concentration of 2.5 ng/ml."nAliquots of this dilution were then assayed for digoxin content using a commercial digoxin125 I RIA kit. Results from both assay methods were extrapolated to the total tablet content and compared with the labeled amount of 20 individual tablets. All tablet assay results were within the USP standards for the content uniformity and"ndissolution of individual. The individual tablet deviations from labeled amount by RIA method were smaller when compared with the spectrofluorometric method.There was no significant difference between the release of digoxin from three products, and thus it is suggested that the Procedure B could be easily applied for manufacturing"nof digoxin tablets in industrial scales.It was also concluded that,the RIA method could be used for the digoxin tablet determination.

  2. Chemical Composition and Antioxidant Activity of the Extract and Essential oil of Rosa damascena from Iran, Population of Guilan

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    N Yassa


    Full Text Available "nBackground and the purpose of study: Rosa damascena Mill. (Rosaceae has cooling, soothing, astringent, and anti-inflammatory effects, and has been used in the north of Iran as a cardiotonic agent. The aim of this study was to identify components of R. damascena (cultivated in Guilan Province extract and essential oil and to study their biological activities. "nMethods: Essential oil of R. damascena was prepared by hydrodistillation and analyzed with GC/MS instrument. The antioxidant activity of hydro-alcohlic extract of petals and essential oil was measured using free radical scavenging activity with 2-2-diphenyl, 1-picrylhydrazyl (DPPH and lipid peroxidation (ferric ammonium thiocyanate methods. "nResults: Hydro-alcoholic extract showed strong free radical scavenging capacity compared to lipid peroxidation inhibitory effects. IC50 values of the extract were 2.24 μg/mL and 520 μg/mL in free radical scavenging and lipid peroxidation assays, respectively. The major components of essential oil were linalool (3.8%, nerol (3.05%, geraniol (15.05%, 1-nonadecene (18.56%, n-tricosane (16.68%, hexatriacontane (24.6% and n-pentacosane (3.37%. The bioassay-guided fractionation of extract led to the isolation of three flavonol glycosides: quercetin-3-O-glucoside, kaempferol-3-O-rhamnoside and kaempferol-3-O-arabinoside. The IC 50 value of the radical scavenging activity of kaempferol-3-O-rhamnoside which was, 530 μg/mL was weaker than the extract. "nMajor conclusion: The petal of this cultivated rose has no bitter taste and because of its potential antioxidant activity and good taste, can be used as food flavor and a preventing agent for many diseases.

  3. Mangiferin: A review of sources and interventions for biological activities. (United States)

    Jyotshna; Khare, Puja; Shanker, Karuna


    Xanthones are naturally synthesized in various biological systems such as plants, lichens, and fungi and are stored as by-products. In addition to taxonomic significance they are also important in the treatment/management of a number of human disorders. Mangiferin and its derived lead molecule have never qualified for use in a clinical trial despite a number of pharmacological studies that have proven its effectiveness as an antioxidant, analgesic, antidiabetic, antiproliferative, chemopreventive, radioprotective, cardiotonic, immunomodulatory, and diuretic. For centuries in the traditional practice of medicine in India and China the use of plants containing mangiferin has been a major component for disease management and health benefits. While it resembles biflavones, the C-glucosyl xanthone (mangiferin) has great nutritional and medicinal significance due to its unique structural characteristics. The C-glycoside link of mangiferin, mimicked to nucleophilic phloroglucinol substitution, facilitates its bioavailability and also is responsible for its antioxidant properties. Researchers have also utilized its xanthonic framework for both pharmacophoric backbone and for its use as a substitution group for synthesis and prospects. To date more than 500 derivatives using about 80 reactions have been generated. These reactions include: lipid peroxidation, phosphorylation, glycosylation, methylation, fermentation, deglycosylation, hydrolysis, polymerization, sulfation, acylation, etherification, peroxidation among others. Multiple studies on efficacy and safety have increased the global demand of mangiferin-based food supplements. This review highlights the distribution of mangiferin in plants, its isolation, and assay methods applicable to different sample matrices. In addition we include updates on various strategies and derived products intended for designated pharmacological actions. © 2016 BioFactors, 42(5):504-514, 2016.

  4. [Comparison of the action of Cordemcura on selected cardiovascular parameters following intraduodenal and intravenous application in beagles]. (United States)

    Hübler, D; Mudhaffar, A A; Schilling, G; Elze, M; Chemnitius, K H


    The novel cardiotonic Cordemcura was tested for its cardiovascular effects after intraduodenal application to anaesthetized dogs. For this purpose, beagles received Cordemcura intraduodenally as a Tylose suspension, with 4 bolus injections (10(-5), 3 X 10(-5), 6 X 10(-5), and 10(-4) mol/kg) given at 30-min intervals. The test parameters used to analyze the onset of action and its course include: heart frequency (HFR), maximum rate of pressure rise (dp/dtmax) and decline (dp/dtmin) in the left ventricle, cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR) and peripheral arterial blood pressure, systolic (Ps) and diastolic (Pd), and dose-effect curves determined for the individual test parameters. There was a dose-dependent increase of dp/dtmax up to a maximum of 130%, which 3 h afterwards was still about 60% above the initial value. The heart frequency, too, rose dose-dependently by a maximum of 80%, though not being significantly different from the initial value any longer 3 h after the last bolus injection. The Ps was slightly, but significantly decreased with the higher dose levels used. The influence on dp/dtmin and Pd was insignificant. A significant rise was found in the cardiac output, whereas the peripheral resistance showed a slight decline. After 3 h, a significant rise was still seen in the contractility (dp/dtmax), whereas the other parameters were no longer significantly different from the initial values. Moreover, selected dose levels of Cordemcura were tested after i. v. application, and a comparison was made of their effect on heart frequency, peripheral blood pressure, and inotropism. The importance of the findings was discussed.

  5. Red maca (Lepidium meyenii reduced prostate size in rats

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    Rubio Julio


    Full Text Available Abstract Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T and estradiol (E2 levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE. Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1 region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl

  6. Sevoflurane-Based Inhalation Induction in High-Risk Elderly Patients During Noncardiac Surgery

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    O. A. Grebenchikov


    Full Text Available Objective: to study the hemodynamic effects of sevoflurane during the induction of anesthesia in elderly patients at high risk for cardiac events. Subjects and methods. This study enrolled 32 patients who had a left ventricular ejection fraction of <30% during preoperative examination. According to the presumptive type of anesthesia, the patients were randomized to one of the study groups: In the sevoflurane group receiving infusion of fentanyl (1 ig^kg”‘^hr”‘, anesthesia was induced by sevoflurane at the maximum concentration of 8 vol% at first inspiration, without the respiratory circuit being prefilled. After loss of consciousness, further saturation was carried out using Fianesth, 5 vol%. Combination anesthesia (CA was that which was induced by successive administration of dormicum, ketamine, propo-fol, and fentanyl. The trachea was intubated during total myoplegia under the control of TOF (TOF-Watch, Organon, the Netherlands. Results. In all the patients under CA, its induction was made during infusion of dopamine (5 lg^kg”‘^min”‘, the dose of which had to be increased up to 10 ig • kg-1 • min-1 in 6 (75% patients. Nevertheless, there were decreases in mean blood pressure (BPmean to 46±6 mm Hg and in cardiac index (CI to 1.5±0.3 fig • kg-1 • min-1 (by 32% of the outcome value. In the sevoflurane inhalation induction group, only 3 (12.5% patients needed dopamine. Its dose producing a cardiotonic effect was near-minimal; its average maintenance infusion rate was 5.3±0.3 ig^kg”‘^min”‘. The reduction in CI was statistically insignificant; despite a 9% decrease in BPmean, this indicator in the sevoflurane group remained within acceptable ranges. Conclusion. The use of a sevoflurane-based inhalation induction technique permits higher hemodynamic stability in patients at high risk for cardiac events. Key words: inhalation induction, sevoflurane, ketamine, elderly patients.

  7. Contractility and protein phosphorylation in cardiomyocytes: effects of isoproterenol and AR-L57. (United States)

    Hayes, J S; Bowling, N; Boder, G B


    The cardiotonic drugs AR-L57 [2-(2,4-dimethoxyphenyl)-1H-imidazo(4,5b)-pyridine] and isoproterenol stimulated contractility in cultured heart cells in concentration-dependent manners; only the effects of isoproterenol were blocked by propranolol. Isoproterenol, but not AR-L57, enhanced the phosphorylation state of seven protein bands [relative molecular weights (MrS) 155,000, 96,000, 27,000, 24,000, 20,000, 16,000, 12,000] and resulted in the dephosphorylation of one protein band (Mr 21,000). Also, only isoproterenol increased the activation states of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase and glycogen phosphorylase. The eight protein bands resolved by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and detected by autoradiography were altered by isoproterenol in time- and concentration-dependent manners. The 24,000-Mr protein substrate phosphorylated in response to isoproterenol was converted to a 12,000-Mr species by heating in the presence of SDS prior to electrophoresis, suggesting that the two substrates were in fact identical proteins. A comparison of the 2-min responses to varying concentrations of isoproterenol resulted in excellent correlations between the phosphorylation states of individual protein bands and contractility. This was true even for the 21,000-Mr species that was dephosphorylated. However, only the 27,000-, 24-12,000-, and 16,000-Mr substrates were phosphorylated rapidly enough to be associated with the onset of the inotropic response. Cultured myocytes are an important feature of these studies as they are 84% pure ventricular cells that remain 100% viable throughout an experiment. Because this system is suitable for biochemical measurements and the effects of agents on heart cell contractility can be determined, it is possible to correlate changes in biochemical parameters with alterations in physiological state.

  8. Pharmaceutical importance and synthetic strategies for imidazolidine-2-thione and imidazole-2-thione derivatives. (United States)

    Savjani, Jignasa K; Gajjar, Anuradha K


    Imidazole heterocycles containing oxygen or sulfur heteroatoms are of considerable pharmaceutical interest. Many synthetic strategies for imidazolidine-2-thione and imidazole-2-thione derivatives were developed in the past years. They have been well documented by a steadily increasing number of publications and patents. Substituted imidazolidine-2-thiones and imidazole-2-thiones display remarkable biological activities. For instance, imidazole-2-thione has been reported to exhibit antimicrobial, antifungal, antithyroid, antioxidant, cardiotonic, antihypertensive, Dopamine beta-Hydroxylase (DBH) inhibitory and anti-HIV properties. Imidazolidine-2-thione derivatives have been reported to exhibit antimicrobial activity, anti-HIV activity, antifungal activity and so forth. The main purpose of this review is to present a survey of the literature on the different methods of synthesis and reactions involving imidazolidine-2-thione and imidazole-2-thione during the last few decades. This article summarizes an efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 3,5-disubstituted-thiohydantoin, also reported previously. Synthesis of metal complexes of imidazolidine-2-thione and its derivatives were reported as antimicrobial agents also discussed in the article. Some of the chiral imidazolidine-2-thione N-and C-nucleoside were reported as precursors for the synthesis of azidonucleosides and fluoronucleosides known for their anti-AIDS activity. Metal complexes of heterocyclic thione ligands were reported to possess antifungal activity. Imidazolidine-2-thione and imidazole-2-thione derivatives have found applications in diverse therapeutic areas. Imidazolidine-2-thiones are also used as a chiral auxiliary and ligand for asymmetric catalysis.

  9. Natriuretic Hormones, Endogenous Ouabain, and Related Sodium Transport Inhibitors

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    John eHamlyn


    Full Text Available The work of deWardener and colleagues stimulated longstanding interest in natriuretic hormones (NH. In addition to the atrial peptides (APs, the circulation contains unidentified physiologically-relevant NHs. One NH is controlled by the central nervous system (CNS and likely secreted by the pituitary. Its circulating activity is modulated by salt intake and the prevailing sodium concentration of the blood and intracerebroventricular fluid, and contributes to postprandial and dehydration natriuresis. The other NH, mobilized by atrial stretch, promotes natriuresis by increasing the production of intrarenal dopamine and/or nitric oxide. Both NHs have short (<35 minutes circulating half lives, depress renotubular sodium transport, and neither requires the renal nerves. The search for NHs led to endogenous cardiotonic steroids (CTS including ouabain-, digoxin-, and bufadienolide-like materials. These CTS, given acutely in high nanomole to micromole amounts into the general or renal circulations, inhibit sodium pumps and are natriuretic. Among these CTS, only bufalin is cleared sufficiently rapidly to qualify for an NH-like role. Ouabain-like CTS are cleared slowly, and when given chronically in low daily nanomole amounts, promote sodium retention, augment arterial myogenic tone, reduce renal blood flow and glomerular filtration, suppress nitric oxide in the renal vasa recta, and increase sympathetic nerve activity and blood pressure. Moreover, lowering total body sodium raises circulating endogenous ouabain. Thus, ouabain-like CTS have physiological actions that, like aldosterone, support renal sodium retention and blood pressure. In conclusion, the mammalian circulation contains two non-AP NHs. Identification of the CNS NH should be a priority.

  10. 发展农业再保险的财政法律与实践研究%On the Law and Finance for Developing Agricultural Reinsurance and Its Practices

    Institute of Scientific and Technical Information of China (English)



    农业再保险具有保费补贴无法取代的内在优势,是农业保险真正的"强心剂",当前我国农业再保险的财政地位薄弱是导致政府对农业保险不能实现有效供给的关键原因。因此,健全农业再保险体系的主力是政府,无论从财政立法还是财政实践的角度均应有所作为,如制定专门的农业保险法和调整相关的税收立法,给予农业保险公司和再保险公司以更多的税收优惠,以及考虑国家出资设立专门的农业再保险公司或政府设立农业再保险基金等。%Agricultural reinsurance, a real cardiotonic for agricultural insurance, has its intrinsic advantage which can not be replace by premium subsidies. The reason why agricultural reinsurance can not be effectively supplied in China is just that the financial position of agricultural reinsurance is very weak. The government is the main force in society to establish and improve the agricultural reinsurance system, and it should do something in financial legislation and practice, such as formulating special agricultural insurance law, adjusting the relevant taw legislation in order to give more tax benefits to the agricultural insurance and reinsurance companies as well as setting up special agricultural reinsurance company and related funds.

  11. Identificação de espécies da família Asteraceae, revisão sobre usos e triagem fitoquímica do gênero Eremanthus da Reserva Boqueirão, Ingaí-MG Asteraceae species identification, use revision and phytochemical screening of Eremanthus genus in Boqueirão Ecological Reserve, Ingaí - Minas Gerais State, Brazil

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    A.O. Ribeiro


    humans. The phytochemical screening of the hydroalcoholic extracts indicated the presence of reducing sugars, carbohydrates, amino acids, tannins, flavonoids, glycosides cardiotonics, carotenoids, steroids and triterpenoids, depsides and depsidones, coumarin derivatives, soapy saponins, alkaloids, purines, polysaccharides and anthraquinones. On the other hand, organic acids, catechins, sesquiterpene lactones and azulenes were not detected.

  12. Phentolamine plus Ginkgo Dipyridamole Injection for Chronic Pulmonary Heart Disease%酚妥拉明联合银杏达莫治疗慢性肺源性心脏病疗效观察

    Institute of Scientific and Technical Information of China (English)

    马继扬; 高健; 梁民勇; 陈继兴; 文启孝


    Objective: To observe the clinical effect of phentolamine combined with ginkgo dipyridamole injection in the treatment of chronic pulmonary heart disease with heart failure.Methods: A total of 90 patients were randomly divided into control group (n=45) and therapy group (n=45).Two groups were treated with medical treatment such as control infection, oxygentherapy, cardiotonic and diuresis.On the basis of the above therapy, the treatment group were added phentolamine 20 mg combined with ginkgo dipyridamole injection 25 mL with 10% Glucose 500 ml in intravenous drip, quotidie, 10 days for a course of treatment. Results: The therapeutic effect, results of blood gas analysis and blood rheology, and heart function in therapy group were better than the control group, with statistically significant difference (P<0.05). Conclusion: Phentolamine combined with ginkgo dipyridamole injection in treatment of chronic pulmonary heart disease with heart failure is effective and safe. It deserves to be popularized.%观察酚妥拉明联合银杏达莫对慢性肺源性心脏病心衰患者的疗效,为临床治疗提供依据.方法:将90例患者随机分为治疗组和对照组各45例.两组采用常规内科治疗如控制感染、氧疗、强心、利尿等,治疗组在上述治疗基础上加用酚妥拉明20mg+银杏达莫25 mL于10%葡萄糖注射液500mL中静脉滴注,1次/d,疗程均为10d.结果:治疗组的疗效、血气分析、血液流变学、功能的改善优于对照组,差异具有统计学意义(P<0.05).结论:酚妥拉明联合银杏达莫对慢性肺源性心脏病心衰患者具有良好的疗效及安全性,值得临床推广应用.

  13. Crioablação subendocárdica interpapilar (CSIP para o tratamento da taquicardia ventricular recorrente chagásica (TVR Interpapillary subendocardial cryoablation for the treatment of recurrent ventricular chagasic tachicardia

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    Miguel Barbero-Marcial


    . One patient with diffuse myocardiopathy is in functional class 11, exclusively on cardiotonic medication. The results obtained permit credence to be given to the surgical techniques proposed.

  14. Arenobufagin activates p53 to trigger esophageal squamous cell carcinoma cell apoptosis in vitro and in vivo

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    Lv J


    Full Text Available Junhong Lv,1 Shaohuan Lin,1 Panli Peng,2 Changqing Cai,2 Jianming Deng,1 Mingzhi Wang,1 Xuejun Li,1 Rongsheng Lin,3 Yu Lin,4 Ailing Fang,5 Qiling Li5 1Thoracic Surgeons Department, 2Oncology No 2 Department, Guangdong No 2 Provincial People’s Hospital, Guangzhou, 3Department of Oncology, Shunde Longjiang Hospital, Foshan, 4Department of Gastroenterology, Puning Overseas Chinese Hospital, 5Galactophore Department, Puning Maternity and Child Care Hospital, Puning, People’s Republic of China Abstract: Esophageal squamous cell carcinoma (ESCC is often diagnosed at late incurable stage and lacks effective treatment strategy. Bufadienolides are cardiotonic steroids isolated from the skin and parotid venom glands of the toad Bufo bufo gargarizans Cantor with novel anticancer activity. However, there is little information about the effects and action mechanisms of bufadienolides on ESCC cells. In this study, the in vitro and in vivo anti-ESCC activities of bufadienolides, including bufalin (Bu and arenobufagin (ArBu, were examined and the underlying molecular mechanisms were elucidated. The results showed that ArBu exhibited higher anticancer efficacy than Bu against a panel of five ESCC cells, with IC50 values ranging from 0.8 µM to 3.6 µM. However, ArBu showed lower toxicity toward Het-1A human normal esophageal squamous cells, indicating its great selectivity between cancer and normal cells. Moreover, ArBu effectively induced ESCC cell apoptosis mainly by triggering caspase activation through intrinsic and extrinsic pathways. Treatment of ESCC cells also significantly activated p53 signaling by enhancing its phosphorylation. Interestingly, transfection of cells with p53 small interfering RNA significantly inhibited the ArBu-induced p53 phosphorylation and the overall apoptotic cell death. Furthermore, ArBu also demonstrated novel in vivo anticancer efficacy by inhibiting the tumor growth through activation of p53 pathway. Taken together

  15. Modulation of the contractility of guinea pig papillary muscle by the activation of ATP-sensitive K+ channels. (United States)

    Kocić, I


    The influence of activation of ATP-sensitive K+ channels on the positive inotropic action of I-isoproterenol d-bitartrate (isoprenaline), 12b-hydroxydigitoxin (digoxin), 5-amino-[3,4'-bipyridin]-6[1H]-one (amrinone), 1,6-dihydro-2-methyl-6-oxo 3,4-bipyridine-5-carbonitrile (milrinone) and UD-CG 115 BS; 4,5-dihydro-6[2-(4-methoxyphenyl)-1 H-benzimidazol-5-yl]-5-methyl-3(2H)pyridazinone (pimobendan) was investigated in guinea pig papillary muscle. The force of contraction (dF) and the rate of rise of force of contraction (dF/dt) were measured. After activation of ATP-sensitive K+ channels by 1 microM of (3S,4R)-3-hydroxy-2,2-dimethyl-4-(oxo-1 pyrrolidinyl)-6-phenyl-sulfonylchroman hemihydrate (HOE 234) the dose-response curves for isoprenaline were shifted to the right (about 9-fold). The positive inotropic action of digoxin and milrinone was significantly enhanced (about 5-fold). The inotropic action of amrinone and pimobendan before and after pretreatment with HOE 234 was not significantly different. HOE 234 pretreatment decreased irreversibly the maximum effect (Emax) of isoprenaline only for the amplitude of force of contraction, but not for the rate of rise of force. Opposite to this, activation of ATP-sensitive K+ channels evidently enhanced the positive inotropic effects of digoxin and milrinone. In the case of milrinone, the Emax for both parameters (dF and dF/dt) was greater after HOE 234 pretreatment. Only the Emax of digoxin for the amplitude of the force of contraction was significantly increased in the presence of HOE 234. The above mentioned results indicate that activation of ATP-sensitive K+ channels by HOE 234 modulates the positive inotropic action of cardiotonic drugs. This change may be expressed as potentiation (digoxin, milrinone) or attenuation (isoprenaline) of the positive inotropic effects, depending on the mechanism of action.

  16. Clinical efficacy observation of nitroglycerin,dopamine and dobutamine pumped by micro-Injection pump in the treatment of refractory heart failure%微量注射泵泵入硝酸甘油、多巴胺、多巴酚丁胺治疗难治性心力衰竭的临床效果观察

    Institute of Scientific and Technical Information of China (English)

    夏清德; 王军香; 陈育山; 毛润芝; 蒋均仕


    目的:观察应用微量注射泵泵入硝酸甘油、多巴胺、多巴酚丁胺治疗难治性心力衰竭的临床疗效。方法选择2011年1月~2014年1月本院102例心功能Ⅲ~Ⅳ级(NYHA分级法)的住院患者,在卧床休息、控制饮食、吸氧、强心剂及利尿剂治疗的基础上,应用微量注射泵泵入硝酸甘油、多巴胺、多巴酚丁胺,疗程3~5d,观察患者临床症状、体征、心功能改善情况。结果102例患者用药后临床症状和心功能各项参数均明显改善,与治疗前比较,差异有统计学意义(P<0.05)。结论应用微量泵泵入硝酸甘油、多巴胺、多巴酚丁胺治疗难治性心力衰竭患者疗效明显,安全可靠。%Objective To observe the clinical efficacy of nitroglycerin,dopamine and dobutamine pumped by micro-in-jection pump for the treatment of refractory heart failure. Methods 102 hospitalized patients with Grade Ⅲ to Ⅳ(NY-HA grading method) heart function in our hospital from January 2011 to January 2014 were selected and given nitro-glycerin, dopamine and dobutamine pumped by micro-injection pump on the basis of bed rest,diet control,oxygen up-take,cardiotonic and diuretic therapy.The course of treatment was 3 to 5 days.The patients’ clinical symptoms,body signs and cardiac function improvement situation were observed. Results All 102 patients’ clinical symptoms and car-diac function parameters improved significantly after medication.Compared with before treatment,the difference was sta-tistically significant (P<0.05). Conclusion Nitroglycerin,dopamine and dobutamine pumped by micro-injection pump is significantly effective,safe and reliable for the treatment of refractory heart failure.


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    V. A. Kurkin


    Full Text Available Blood-red hawthorn (Crataegi fructus are a popular cardiotonic herbal materials, which widely used in medical practice in our country and abroad. In order to prevent diseases of the cardiovascular system is appropriate to prescribe herbal medicines, because they combine the breadth and softness of therapeutic action, along with the absence of a significant number of side effects and contraindications.The purpose was to study diuretic and antidepressant activity of thick fruit extract of blood-red hawthorn.Material and methods. Under laboratory conditions we obtained a thick extract of blood-red hawthorn fruits. This phytopharmaceutical was studied by us for any diuretic and antidepressant activity. Investiga- tions were carried out on white rats of both sexes weighing 200–220 g. Each experimental group consist- ed of ten animals. Study drug was administered intragastrically by stomach tube. Control in both cases served as purified water. For determination of diuretic activity, we used a thick extract of hawthorn fruits in a dose of 20 mg/kg against the background of the water load in the amount of 3% of body weight of the animal. Reference preparation was chosen dichlorthiazid 20 mg/kg. It was administered once. After ad- ministration the animals were placed in metabolic cages for urine collection for 24 hours. The study de- termined diuresis, natriuresis, kaliuresis, and kreatininuresis for 4 h and 24 h of the experiment. On the day of the experiment the animals of the control group was administered water load of 3%, and experi- enced – intragastrically drug in an identical amount. Animals were placed in a metabolic cage for a day. Collected 4 h and 24-h urine sample. Determined by renal excretion of water was recorded concentration of sodium and potassium by flame photometry in the fiery liquid analyzer PAG-1, creatinine – colorimet- ric method for photocolorimeter CFC-3. For determining antidepressant activity we used a thick hawthorn

  18. 基于机体对寒冷刺激的适应性改变原理探讨阳虚证畏寒肢冷实质%Investigation of the Essenoe of Chilliness and Cold Limbs of Yang Deficiency syndrome in Chinese Medicine based on the Adaptability of Body to Cold Stimulation

    Institute of Scientific and Technical Information of China (English)

    金锐; 张冰


    adaptability to cold stimulation. Then according to a collection of physiological and pathological factors which may cause such reduction, we proposed that the essence of chilliness and cold limbs of yang deficiency patients may probably be the state of reduction of body surface blood flow (heat) due to some pathological factors already known as heart failure, poor circulation, and thyroid dysfunction. Thirdly, by using the method of" syndrome differentiation through formula effects assessment", this recognition was confirmed because the pharmacological activities of cardiotonic or peripheral vasodilating, or surface temperature increasing were found in a great number of single medicines and prescriptions applied to yang deficiency syndrome in CM.

  19. Familial Hypercholesterolemia Complicated with Aortic Valve Stenosis and Carotid Stenosis:A Case Report and Lit-erature Review%家族性高胆固醇血症并发主动脉瓣上及颈动脉狭窄报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    周佳君; 邵森


    目的:探讨家族性高胆固醇血症( familial hypercholesterolemia, FH)的临床特点及诊治要点。方法对我院收治的1例FH临床资料进行回顾性分析。结果本例17岁女性,因活动后胸闷、气促5年,加重1个月入院。4岁时皮肤出现黄色瘤,手术治疗后复发。病程中于外院就诊,考虑先天性心脏病及高脂血症,并予降血脂治疗未见明显效果入我院。经查血脂升高,心脏及颈动脉超声检查示主动脉瓣上狭窄及颈动脉狭窄,并结合有黄色瘤病史,确诊为纯合子型FH,给予降血脂、强心、利尿、抗血小板聚集等治疗,病情好转,因拒绝血浆置换治疗,继续上述治疗,随访1年血脂控制不佳,症状反复发作。结论 FH易出现心血管并发症,预后差,早期容易漏诊,早期诊断与治疗是延缓疾病进展的关键。%Objective To explore the clinical characteristics, and key points of diagnosis and treatment of familial hypercholesterolemia ( FH) . Methods Clinical date of one patient with FH in our hospital was retrospectively analyzed, and related literature was reviewed. Results A 17-year-old female patient was admitted for chest distress and shortness of breath after exercise for 5 years and aggravated for 1 month. The patient developed xanthomas at the elbows at the age of 4 and under-went surgery. However, one year later, the xanthomas relapsed. The patient was diagnosed as having congenital heart disease and hyperglycemia before admission to our hospital. Although she had been given by, the patient failed to respond to lipid-low-ering treatment. After transfer to our hospital, her concentration of cholesterol was elevated significantly. The ultrasound ex-amination indicated aortic valve stenosis and carotid stenosis. In addition, her family members were found to have hyperglyce-mia or xanthoma, then the diagnosis of homozygous FH was made. The symptoms were alleviated after the treatment of cardio-tonic, diuretic, lipid

  20. 慢性心力衰竭伴低钠血症患者102例临床分析%Clinical analysis of 102 cases with chronic heart failure complicated by hyponatremia

    Institute of Scientific and Technical Information of China (English)

    李烨; 刘丽华; 徐莉


    Objective To summarize the clinical experience of 3% sodium chloride in treatment of chronic heart failure with hyponatremia. Methods The 102 patients suffering from chronic heart failure with hyponatremia were treated with water limit, vasodilator, cardiotonic, diuretics, angiotensin-converting enzyme inhibitor, angiotensin Ⅱ receptor antagonist and 3% sodium chloride. Cardiac functional capacity classification (NYHA), treatment effect and hyponatremia level were compared between pre- and post- treatment. Results After treatment, heart function was statistically different as compared with that of pre-treatment (χ2=150.26, P<0.05). The 58 cases showed distinct effect, 37 cases moderate effect, 7 cases no effect, and the percentage of total effect was 93.1%. The hyponatremia of patients with different level of heart function were (139.4±22.6) mmol/L, (138.2±23.3) mmol/L, the difference had a statistics significance compared with pre-treatment hyponatremia which were (122.9±20.5) mmol/L, (120.5±26.8) mmol/L (t=2.02, 2.04, P<0.05). Conclusions Proper diuresis and sodium salt supplement could help to reduce the malignant risk of the patients suffering from chronic heart failure with hyponatremia and to improve the prognosis.%目的 探讨3%氯化钠治疗慢性心力衰竭伴低钠血症患者的临床疗效.方法 对102例慢性心力衰竭(纽约心功能分级Ⅲ-Ⅳ级)伴低钠血症患者,给予限水、扩张血管、强心、利尿、血管紧张素转换酶抑制剂/血管紧张素II受体拮抗剂等常规治疗外,同时给予3%氯化钠.比较治疗前后患者的心功能分级、治疗效果及血钠水平.结果 102例患者治疗后,心功能恢复至Ⅰ级39例,心功能恢复至Ⅱ级47例,心功能Ⅲ级11例,心功能Ⅳ级5例.与治疗前心功能Ⅲ级45例,Ⅳ级者57例比较,差异有统计学意义(χ2=150.26,P<0.05).治疗后显效58例,37例有效,7例无效,总有效率93.1%.治疗后心功能Ⅲ级

  1. 老年慢性心力衰竭合并低钠血症59例临床分析%Clinical Analysis of 59 Old Chronic Heart Failure Patients Complicated with Hyponatremia

    Institute of Scientific and Technical Information of China (English)

    杨云贵; 蔡吉芬; 胡东升; 丁绍平


    Objective To explore the influence of hyponatremia on older chronic heart failure and effective prevention and control measures. Methods We retrospectively analysed 126 old congestive heart failure patients over 60 in our hospital from January 2006 to June 2011, including 59 patients with hyponatremia (hyponatremia group) and 67 patients with normal blood sodium (control group). We compared the mortality, heart failure grade and the concentration of sodium blood between the two groups, and applied high permeability saline to correct hyponatremia and improve the curative effect of heart failure. Results The mortality of hyponatremia group was significantly higher than the control group (P < 0.01). The blood sodium levels of patients in moderate and severe heart failure groups were lower than light and medium heart failure group (P < 0.01). On the basis of conventional treatment including inhalating oxygen, giving cardiotonic, diuresis, and lessen the cardiac afterload, giving high-osmolar sodium chloride injection shortened the recover time of cardiac function. Conclusions For old chronic heart failure patients, the higher the level of heart failure and the lower the serum sodium level, the higher the mortality. Hyponatremia and mortality have a significant relationship. For the elderly patients with chronic heart failure in treatment process, we should regularly monitor the blood sodium concentration, reasonable use diuretics, so that early detection and correction hyponatremia, improve the success rate of chronic heart failure treatment. The high permeability sodium chloride injection can rapidly correct hyponatremia and significantly improve heart function.%目的 探讨低钠血症对老年慢性心力衰竭的影响及有效的防治措施.方法 回顾性分析曲靖市第一人民医院2006年1月至2011年6月60岁以上的慢性充血性心力衰竭住院患者126例,其中并发低钠血症者(低钠组)59例,正常血钠者(对照组)67例,比较两组

  2. Estudo fitoquímico e análise mutagênica das folhas e inflorescências de Erythrina mulungu (Mart. ex Benth. através do teste de micronúcleo em roedores Phytochemical and mutagenic analysis of leaves and inflorescences of Erythrina mulungu (Mart. Ex Benth through micronucleus test in rodents

    Directory of Open Access Journals (Sweden)

    A.P De Bona


    the number of deaths after 48 hours, and the micronucleus test was done by the smear method, after exposure of animals to five days of treatment. Phytochemical results showed the presence of reducing sugars, phenols and tannins, proteins and amino acids, flavonoids, alkaloids, depsides, depsidones and coumarin derivatives in both organs; foaming and steroidal saponins and triterpenes in the leaves and cardiotonic and anthraquinonic glycosides and alkaloids in the inflorescences. Considering the LD50, the leaf was atoxic and the inflorescence was moderately toxic. As regards the micronucleus test, results indicated absence of cytotoxicity while genotoxicity was dose-dependent for leaves and dose-independent for inflorescences. Thus, these results suggest that the plant, under the tested conditions, has the potential to induce damages to the DNA.

  3. Research progress on a natural preservative - Forsythia suspense essential oil%天然防腐剂连翘精油的研究进展

    Institute of Scientific and Technical Information of China (English)

    孙倩倩; 姜子涛; 李荣


    连翘是一种具有很高利用价值的药食两用的植物,不仅有抗菌、强心、利尿、镇吐等药理作用,而且还可以应用于食品、化工、医疗保健等方面,具有很大的科研价值.其精油主要是从连翘的种子中提取的一种挥发性活性物质,具有多种生物学功能,如抗氧化、抑菌消炎、抑制病毒等.随着人们对食品安全性的日益重视,近年来以天然防腐剂代替化学合成防腐剂成为一种发展趋势,因而人们热衷于开发安全、天然的防腐剂.连翘作为一种新型的天然食品防腐剂,因其具有价格低廉,对食品风味影响小等特点,已成为了科研领域研究的热点.本文着重介绍了连翘精油的提取方法、包合工艺的研究、不同产地连翘精油的成分差异以及其抑菌和抗氧化作用,并对其应用前景进行了展望,为以后的应用研究提供一定的理论基础.%Forsythia suspense is a higher exploitation value plant because of its edible and clinical function. It has some pharmacological actions including bacteriostasis, cardiotonic, diuresis and antemetic, and can be applied to many fields such as food, chemical industry, and medical care. F. suspense essential oil is extracted from the seeds and has various biological functions, such as anti -oxidation, bacteriostasis and anti -phlogosis, anti - virus. As people pay more and more attention to food safety, natural preservative replacing chemical synthetic preservative has become a developing trend. As a new type of natural preservative, F. suspense has become a hot research project for its characteristic of low price and little effect on food flavor. This paper mainly reviews the extraction methods and conditions, components different from different places; bacteriostasis and anti - oxidation of F. suspense essential oil from. The future application is also discussed. The new trends of research on the essential oil from F. suspense are depicted to provide

  4. Pharmaceutical care on a heart failure patient combined with pulmonary fungal infection after mitral valve replacement surgery due to rheumatic heart disease%1例风湿性心脏病二尖瓣置换术后心衰合并肺部真菌感染患者的药学监护

    Institute of Scientific and Technical Information of China (English)

    陈星伟; 郑英丽; 王冉冉


    1例67岁女性患者,因风湿性心脏病、二尖瓣置换术后心衰入院治疗,入院时合并肺部感染、呼吸衰竭等多种疾病。入院后给予无创呼吸机辅助呼吸,抗凝、强心、利尿、化痰、平喘、抗感染等药物治疗。患者心衰症状逐渐改善,但胸片提示肺部感染加重,结合患者症状体征及辅助检查考虑真菌感染。针对患者的肺部真菌感染,临床药师建议加用伏立康唑(负荷剂量:6 mg·kg-1,q 12 h,维持剂量4 mg·kg-1,q 12 h)进行抗真菌治疗;针对患者国际标准化比值(INR)的波动,临床药师分析了药物间的相互作用对华法林抗凝强度的影响;并对患者由于使用噻嗪类利尿剂导致的电解质紊乱,抗菌药物可能导致的QT间期延长、尖端扭转型室速等不良反应进行了药学监护。经过15 d治疗,患者病情稳定转入普通病房继续治疗。%One 67-year-old female patient with pulmonary infection, respiratory failure and other diseases was hospitalized primary for rheumatic heart disease and heart failure after mitral valve replacement surgery. The patient was treated by non-invasive mechanical ventilation, and anticoagulation, cardiotonic, diuretic, eliminating sputum, antiasthmatic as well as anti-infectious drugs. The heart failure symptom of the patient improved, however the lung infection aggravated. Fungal infection was considered according to the clinical signs and laboratory examinations of the patient. Pharmaceutical cares were given to the patient by clinical pharmacists in respect of the selection and dose adjustment of the antifungal agent, fluctuations analysis of the international normalized ratio (INR) due to the interactions between the warfarin and other drugs, the treatment of electrolyte imbalance after long-term use of thiazide diuretic and monitoring the side effect of the antibacterials such as QT interval prolonged, ventricle speed torsade de pointe

  5. 酚妥拉明联合阿拉明治疗小儿肺炎并发心力衰竭的临床效果分析%Phentolamine combined with aramine in treatment of pediatric pneumonia complicated with heart failure

    Institute of Scientific and Technical Information of China (English)



    目的 评价酚妥拉明联合阿拉明治疗小儿肺炎并发心力衰竭的临床效果.方法 选取2008年6月至2015年6月于本院接受治疗的小儿肺炎并发心力衰竭患儿180例,随机分为对照组(90例)和观察组(90例),其中对照组给予强心、平喘、利尿、氧疗等常规治疗,观察组在对照组基础上酚妥拉明联合阿拉明治疗.比较两组治疗效果.结果 观察组心力衰竭控制时间、热退时间、喘息症状消失时间、啰音消失时间及住院天数均显著短于对照组(P<0.05);观察组治疗总有效率(95.56%)显著高于对照组(76.67%)(P<0.05);两组治疗期间均未出现严重不良反应.结论 酚妥拉明联合阿拉明治疗小儿肺炎并发心力衰竭,疗效确切,且无严重不良反应,值得在临床上推广应用.%Objective To evaluate the clinical effect of phentolamine combined with aramine in the treatment of pediatric pneumonia complicated with heart failure.Methods 180 children with pneumonia complicated with heart failure treated at our hospital from June,2008 to June,2015,were randomly divided into a control group (90 cases) and an observation group (90 cases).The control group received conventional therapy,such as cardiotonic,antiasthma,diuresis,oxygen therapy,etc.;in addition,the observation group was treated with phentolamine and aramine.The efficacies were compared between these two groups.Results The time for controlling heart failure,defervescence time,asthmatic symptom disappearance time,rales disappearance time,and hospital stay were significantly shorter in the observation group than in the control group (P<0.05).The total effective rate was significantly higher in the observation group than in control group (95.56% vs.76.67%,P<0.05).No serious adverse reactions occurred in both groups during the treatment.Conclusions Phentolamine combined aramine in the treatment of pediatric pneumonia complicated with heart failure is effective and has no

  6. 法乐四联症术后肺动脉反流对右心功能的影响%Correlation between pulmonary regurgitation and right ventricular function in patients with repaired tetralogy of fallot

    Institute of Scientific and Technical Information of China (English)

    张惠锋; 贾兵; 陈张根; 李炘; 叶明


    Objective To analyze the correlation between pulmonary regurgitation (PR) and right ventricular function in the patients with repaired tetralogy of fallot (TOF). Methods Fifty eight patients with repaired TOF were enrolled in this study. Pulmonary regurgitation fraction (PRF),right ventricular end-diastolic volume index (RVEDVI),right ventricular end-systolic volume index (RVESVI) and stroke volume index (SVI) were assessed using cardiac-MRI. Linear regression analy-sis was applied to analyze the correlation between PRF and RVEDVI,RVESVI,SVI. The patients whose RVEFIs were less than 45% were treated with digoxin,frusemide and spironolactone to im-prove the heart function; and 3 months later,their right ventricular function was reassessed using car-diac-MRI. Results Linear regression analysis revealed a positive correlation between PRF and RVED-VI (r= 0.700),a positive correlation between PRF and RVESVI (r= 0.685),and a negative correla-tion between PRF and RVEF (r=-0.523). The correlation between SVI and PRF was weak (r =0.334). In the 8 patients treated with 3 months medications,their RVESVIs were significantly de-creased from (76.5±22.5)ml/m~2 to (71.3±21.2)ml/m~2 (P<0.01); their RVEFs were significantly increased from (33.1±7.0)% to (37.9±6.8)% (P<0.05); RVEDVI and PRF remained unchanged (P = 0.650,0.326). Conclusions In the patients with repaired TOF,PR can cause RV enlargement and RVEF decreasing. Cardiotonic and diuretic medication can not lessen PR.%目的 分析肺动脉反流与RVEDV、RVESV、RVEF等右心室功能指标的相关程度以及探讨肺动脉反流的治疗措施.方法 应用c-MRl技术测定58例TOF术后的PRF、RVEDVI、RVESVI、RVEF、SVI,应用线性回归分析PRF与右心功能指标之间的相关性.对于RVEF<45%的病例给予口服强心利尿药物,3个月后随访c-MRI,比较服药前后右心功能的变化.结果 RVEDVI与PRF存在正相关,r值为0.700;RVESVI与PRF正相关,r值为0.685;RVEF与PRF负相关,r值为-0

  7. 17例围生期心肌病临床诊疗分析%Analysis in diagnosis and clinical treatment of peripartum cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    魏晓娟; 陈文博


    目的:通过分析围生期心肌病(PPCM)的临床表现及预后转归,寻找相关危险因素,总结救治经验。方法回顾性分析17例PPCM患者的临床表现、诊断治疗及预后转归。结果 PPCM临床上主要表现为充血性心力衰竭。左室射血分数显著降低(33.69±9.53)%,左室舒张末期内径明显增大(55.43±5.35)mm。在经过有效治疗6个月后复查心脏彩超发现,左室射血分数显著升高(51.93±10.61)%,左室舒张末期内径均显著缩小(46.84±3.29)mm。吸烟、高龄、多胎多产、妊娠高血压或产前子痫病史为危险因素,强心、利尿合用β受体阻滞剂及ACEI类药物可显著改善患者心功能。结论吸烟和妊娠高血压可能是显著的PPCM发病风险因素。经及时正规药物治疗PPCM部分患者心脏的结构和功能可以显著改善。%Objective To analyze the clinical symptom and prognosis of peripartum cardiomyopathy (PPCM) in order to discover the risk factors and summarize the therapeutic experience.Methods A retrospective study was performed on seventeen patients admitted to our hospital with a diagnosis of PPCM by analyzing the clinical manifestations diagnosis, treatment and prognosis of patients.Results The major clinical manifestation of PPCM was congestive heart failure. Left ventricular ejection fractions(LVEF) decreased significantly (33.69±9.53)% and left ventricular internal diameters(LVID) in end-diastole obviously increased (55.43±5.35) mm. After successful treatment during acute episode, LVEF increased while LVID decreased obviously. Smoking, multiparity birth, advanced maternal age and pregnancy-induced hypertension or preeclampsia were risk factors. Cardiotonic and dieresis in combination with angiotensin converting enzyme inhibitor (ACEI) can contribute to the improvement in cardiac function of patients.Conclusion Smoking and pregnancy-induced hypertension appear to be significant risk factors. Heart structure and function

  8. Down 综合征患儿室间隔缺损的手术治疗%Surgical Treatment of Ventricular Septal Defect in Children with Down Syndrome

    Institute of Scientific and Technical Information of China (English)



    目的:总结 Down 综合征患儿室间隔缺损的外科治疗经验。方法48例 Down 综合征患儿室间隔缺损在全身麻醉低温体外循环下行一期根治术。术前对于合并肺部感染、心功能不全、肺动脉高压者,给予有效的抗感染、强心及利尿剂、降肺动脉压等治疗;加强静脉营养,提高机体免疫力。术中提高手术技巧,操作轻柔,选择合适的手术切口及修补材料,避免发生传导阻滞等并发症。术后入 CICU,加强呼吸道管理,合理使用呼吸机;合理使用血管活性药物,维持循环系统的稳定;合理使用抗生素,减少肺部感染的发生。结果48例中无1例死亡,并发呼吸机相关性肺炎10例,心律失常2例,气胸1例,心包填塞1例,低心排1例。术后随访6个月至6年,生长发育好,无死亡。结论Down 综合征室间隔缺损患儿应尽早手术,选择适当的手术时机,合理有效的围术期处理,可提高手术成功率,延长患儿寿命。%Objective To summarize the experience with the surgical treatment of ventricular septal defect in children with Down syndrome.Methods Forty-eight children with Down syn-drome underwent one-stage radical operation under general anesthesia during hypothermic car-diopulmonary bypass.Patients with lung infection,heart failure,and pulmonary hypertension were given anti-infection,cardiotonics and diuretics,and anti-pulmonary hypertension,respectively.In addition,intravenous nutrition was strengthened and immunity was improved in all patients.Dur-ing operation,gentle operation technique was carried out and appropriate surgical incision and re-pair material were selected to avoid conduction block and other complications.After operation,pa-tients were admitted to CICU,and respiratory tract management and rational use of breathing ma-chine were strengthened.Moreover,vasoactive drugs and antibiotics were rationally used to main-tain the stability of

  9. Effect of two volume responsiveness evaluation methods on fluid resuscitation and prognosis in septic shock patients

    Institute of Scientific and Technical Information of China (English)

    Xu Qianghong; Yan Jing; Cai Guolong; Chen Jin; Li Li; Hu Caibao


    Background Few studies have reported the effect of different volume responsiveness evaluation methods on volume therapy results and prognosis.This study was carried out to investigate the effect of two volume responsiveness evaluation methods,stroke volume variation (SW) and stroke volume changes before and after passive leg raising (PLR-ASV),on fluid resuscitation and prognosis in septic shock patients.Methods Septic shock patients admitted to the Department of Critical Care Medicine of Zhejiang Hospital,China,from March 2011 to March 2013,who were under controlled ventilation and without arrhythmia,were studied.Patients were randomly assigned to the SVV group or the PLR-ASV group.The SVV group used the Pulse Indication Continuous Cardiac Output monitoring of SW,and responsiveness was defined as SW->12%.The PLR-ASV group used ASV before and after PLR as the indicator,and responsiveness was defined as ASV >15%.Six hours after fluid resuscitation,changes in tissue perfusion indicators (lactate,lactate clearance rate,central venous oxygen saturation (SCVO2),base excess (BE)),organ function indicators (white blood cell count,neutrophil percentage,platelet count,total protein,albumin,alanine aminotransferase,total and direct bilirubin,blood urea nitrogen,serum creatinine,serum creatine kinase,oxygenation index),fluid balance (6-and 24-hour fluid input) and the use of cardiotonic drugs (dobutamine),prognostic indicators (the time and rate of achieving early goal-directed therapy (EGDT) standards,duration of mechanical ventilation and intensive care unit stay,and 28-day mortality) were observed.Results Six hours after fluid resuscitation,there were no significant differences in temperature,heart rate,blood pressure,SpO2,organ function indicators,or tissue perfusion indicators between the two groups (P >0.06).The 6-and 24-hour fluid input was slightly less in the SW group than in the PLR-ASV group,but the difference was not statistically significant (P >0

  10. Estudo comparativo da evolução e sobrevida de pacientes com claudicação intermitente, com ou sem limitação para exercícios, acompanhados em ambulatório específico Comparative study of evolution and survival of patients with intermittent claudication, with or without limitation for exercises, followed in a specific outpatient setting

    Directory of Open Access Journals (Sweden)

    Ricardo de Alvarenga Yoshida


    established, as well as the benefits of physical training in the treatment of intermittent claudication (IC. However, current data do not provide enough information about the relationship between clinical limitations and risk factors and the performance of physical training and its implications on the evolution and mortality of these patients. OBJECTIVE: To compare the claudication distance and survival of patients with IC throughout time in a specific outpatient setting, with or without limitation for exercises. METHODS: A retrospective cohort study was performed to review the protocols of 185 patients and 469 returns, from 1999 to 2005, evaluating demographic data, average claudication distance and death. The data were analyzed using the software Epi-Info, version 3.2, and SAS, version 8.2. RESULTS: Mean age was 60.9±11.1 years; 61.1% were males and 38.9% were females; 87% were Caucasians and 13% were non-Caucasians. Associated risk factors were hypertension (69.7%, smoking (44.3%, dyslipidemia (32.4%, and diabetes (28.6%. For the patients with claudicating distance lower than 500 m, mean initial distance was 154.0±107.6 m and final distance was 199.8±120.5 m. About 45% of the patients had some clinical limitation to perform the prescribed exercise program, such as angina (26.0%, stroke (4.3%, osteoarthrosis (3.8%, previous minor or major amputation (2.1%, or chronic obstructive pulmonary disease (1.6%. About 11.4% of the patients had previous myocardial infarction, and 5.4% of them were using cardiotonic drugs. Mean follow-up time was 16.0±14.4 months. Mean claudication distance increased 100% (418.47 to 817.74 m throughout 2 years in the group without limitation (p < 0.001 and in nonsmokers (p < 0.001. Survival rate of patients with IC was significantly reduced in the group with limitation for exercises. Logistic regression analysis showed that limitation to exercises was the single factor significantly influencing mortality (p < 0.001. CONCLUSION: Proper and regular

  11. Calogênese em Cissus sicyoides L. a partir de segmentos foliares visando à produção de metabólitos in vitro Calluses from Cissus sicyoides L. leaves

    Directory of Open Access Journals (Sweden)

    F.R. Rodrigues


    faz-se necessário a adição de 6,0 mg L-1 de BAP ao meio de cultivo. Identificou-se a presença de heterosídeos cardiotônicos em calos de Cissus sicyoides L.Secondary metabolites are essentially produced and extracted from plants grown in the field under influence of seasonal variations. The use of biotechnological techniques is an alternative resource for drug production. Among these techniques, tissue culture through callus genesis is highlighted, since callus growth is desirable to induce somaclonal variation and physiological studies, especially when the presence of secondary metabolites can be related to cell growth. The aim of this work was to establish a protocol for Cissus sicyoides L. callus genesis from leaf segments in order to produce metabolites in vitro. Thus, leaf segments removed from adult plants grown in the field were used as explants. After disinfestation, the material was inoculated into MT medium + 1.0 mg L-1 NAA and kept in a BOD chamber, with controlled temperature and luminosity. After 30 days, the percentage of surviving explants and the percentage of contamination were evaluated. For culture, MT medium + 1.0 mg L-1 NAA was used, varying BAP concentrations: 2.0, 4.0, 6.0 and 12.0 mg L-1. In the cultivation, the number of compact and friable calluses was counted. For the first and second subculture, the material was introduced into MT medium + 1.0 mg L-1 NAA, varying the same BAP concentrations; the number of friable calluses formed and the size of callus mass were described. The number of replicates formed during subcultures, and fresh and dry matter (g were also obtained. Then, phytochemical tests were done in order to identify some compounds. The adopted time and concentration of sodium hypochlorite proved to be inefficient for disinfestation. For Cissus sicyoides L. callus genesis from leaf segments, the addition of 6.0 mg L-1 BAP to the culture medium is needed. Cardiotonic heterosides were detected in Cissus sicyoides L. calluses.

  12. Computational simulation of active ingredients and its mechanism of cardiac effect in Qili Qiangxin capsules%芪苈强心胶囊中强心有效成分及其作用机理的计算机模拟

    Institute of Scientific and Technical Information of China (English)

    张碧华; 金毅; 杨明; 杨莉萍


    目的:通过计算机模拟技术研究芪苈强心胶囊中已知结构化合物的分子特征,分析与强心西药分子结构、理化性质相似的中药成分,并寻找比对中西药分子的作用靶点,以期为新药研发或作用机制研究提供思路。方法:通过中西药的分子集构建,进行中西药分子的理化性质分析和结构比对,同时通过反向药效团搜索进行中西药分子的作用靶点结合的探讨。结果:我们利用软件构建了45个中药成分和3个强心类西药成分的平面结构和三维结构,通过分子结构相似度的比较和反向药效团搜索,发现这45个中药分子整体与洋地黄毒苷的相似度最高,同时中药分子中黄芪苷和人参皂苷与各西药分子的结构相似度最高;理化性质对比分析显示,3个强心西药的相对分子质量并不是最大的,然而其表面极性却最大;通过反向药效团搜索发现,这48个小分子中有10个小分子与66个蛋白药效团模型发生了较好的结合,其中西药地高辛只与一个药效团发生接合,而中药有6个成分都与多个药效团发生结合,其中以丹酚酸A结合的药效团最多。结论:与西药仅结合单一蛋白药效团不同,中药分子更易与多个蛋白药效团发生结合,由此推测其作用靶点和作用途径可能更为多样化。%Objective: To research the molecular characteristics of known compounds in Qili Qiangxin capsule by computer simulation, analysis the Traditional Chinese Medicine(TCM) composition which molecular structure and physicochemical property were similar to the cardiotonic western medicine, and to ifnd and compare the targets of the Chinese and Western medicine molecules, so as to provide ideas for the new drug development or mechanism research.Methods: To construct the molecular set of Chinese and Western medicine, so as to analyze the physicochemical property and compare the structure of

  13. BmKⅠ,an α-like scorpion neurotoxin,specifically modulates isolated rat cardiac mechanical and electrical activity%类α-蝎神经毒素BmKⅠ对离体大鼠心脏收缩力及电活动的特异调控

    Institute of Scientific and Technical Information of China (English)

    孙海英; 朱海峰; 吉永华


    本研究探讨了一种特异性钠通道调制剂(Buthus martensi Karsch,BmKⅠ)对离体大鼠心脏收缩力及电活动的调制作用.离体心脏灌流实验显示:(1)BmKⅠ(0.5-10 μmol/L)剂量依赖地增强大鼠心肌收缩力,左心室最大发展压(LVDPmax)以及dp/dtmax与对照组相比均显著增强(n=6,P<0.05),同时可触发正性变时作用(n=6,P<0.05);(2)大剂量BmKⅠ(20μmol/L)引起负性肌力作用及心动过缓;(3)冠脉流量随心脏收缩力的增强反而减小,应用500nmol/L BmKⅠ时冠脉流量由14.5 ml/min降至8.6 ml/min(n=6,P<0.05);此外,心电图记录表明BmKⅠ(0.5-10μmol/L)可触发心动过速及复杂的心律失常等电活动变化;正常灌流液洗脱后BmKI引起的大鼠心脏收缩力及电活动的改变可部分恢复.由于β-肾上腺素能受体阻滞剂普奈洛尔预先应用抑制了儿茶酚胺类神经递质的释放,提示BmKⅠ引起的大鼠心脏收缩力及电活动的改变不是由于其调节儿茶酚胺类神经递质的释放及随后β-肾上腺素能受体的激活,而可能与其对心肌电压门控钠通道的调控有关.%In this study, cardiotonic and cardiotoxic effects of Buthus martensi Karsch (BmK)Ⅰ, a modulator of voltage-gated sodium channels, were investigated on the isolated rat hearts. The results showed that BmKⅠ evoked complex effects characterized by a change in both cardiac mechanical and electrical activity. Langendorff perfusion showed that: ( 1 ) maximal left ventricular developed pressure (LVDPmax) and dp/dtmax were markedly increased by BmKⅠ (0.5 -10 mol/L) in a dose-dependent manner (n =6, P<0.05), positive chronotropic effects were also induced by BmKⅠ (n=6, P<0.05); (2) negative inotropic action and bradycardia could be elicited at a larger dose of BmKⅠ(20μ mol/L); (3) the coronary flow varied inversely with the positive inotropic effects, coronary flow reduced during positive inotropic effects from 14. 5 to 8. 6 ml/min after