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MedlinePlus

... Cyanogen chloride (CK) Digitalis Case Definition: Digitalis Poisoning Ethylene glycol Fentanyls and other opioids Case Definition: Opioids ( ... Thallium Toxic alcohols Case Definition: Toxic Alcohol Poisoning Ethylene glycol Trichothecene Case Definition: Trichothecene Mycotoxin Poisoning Unidentified ...

Summary of a symposium on natriuretic and digitalis-like factors.

PubMed

Buckalew, V M; Gonick, H C

1998-01-01

An international symposium on natriuretic and digitalis-like factors was convened for the first time since 1992. Topics discussed included structures and biosynthesis of endogenous digitalis-like factors (EDLF), biologic activities, physiology function and role of EDLF in hypertension, and novel natriuretic factors. Progress was reported in determining the exact structure of an isomer of ouabain isolated from bovine hypothalamus. Evidence was presented supporting the existence of a second mammalian EDLF that resembles steroids found in toads (bufodienolides). Support for endogenous synthesis of mammalian EDLF was also presented. Mammalian EDLF were reported to have effects which are different from those possessed by digitalis like steroids derived from plants. New evidence was presented implicating EDLF in various forms of hypertension in humans and animal models. Finally, several unique natriuretic factors that do not inhibit Na, K ATPase and that appear to play a role in mammalian volume regulation were discussed.

Action of acetylstrophanthidin on experimental myocardial infarction.

NASA Technical Reports Server (NTRS)

Nola, G. T.; Pope, S. E.; Harrison, D. C.

1972-01-01

An experimental animal model with acute myocardial infarction of a size insufficient to produce profound heart failure or shock was used to study the effects of acute infarction on digitalis tolerance and the hemodynamic changes produced by moderate and large doses of acetylstrophanthidin. With acute myocardial infarction, digitalis toxic arrhythmias could be precipitated with significantly lower doses of digitalis than in animals without myocardial infarction. There was no precise correlation between the size of infarction and the toxic dose of glycoside. Coronary artery ligation produced a stable but relatively depressed circulatory state, as evidenced by lowered cardiac output and stroke volume and elevated systemic vascular resistance and left atrial mean pressure. When digitalis was infused, the following significant changes were observed at nontoxic doses: (1) elevation of aortic and left ventricular pressures; (2) further decline in cardiac output; and (3) decreased left atrial mean pressure.

[A dangerous "risotto"].

PubMed

Cardano, Sergio; Beldì, Federico; Bignoli, Cristina; Monteverde, Anna; Uglietti, Enrica

2002-04-01

We report an unusual digitalis poisoning case, with a positive result, caused by the swallowing of digitalis purpurea leaves. They were taken for borage leaves, usually used to prepare "risotto". Be careful not to eat vegetables you don't usually eat, because some of them may have different toxicity levels.

Antibodies and digitalis: the modern revolution in the use of an ancient drug.

PubMed

Haber, E

1985-05-01

Although digitalis glycosides have been widely used in clinical medicine since the classic description by William Withering in 1785, it was not until the advent of a specific immunoassay that their clinical pharmacology could be examined intensively under a wide variety of circumstances. The insights gained into the relations among dosage, plasma concentration, bioavailability, distribution, metabolism, excretion and interactions with other drugs and the manifestations of toxicity certainly have reduced the frequency of adverse reactions to this highly toxic but useful group of drugs. More recently, antibodies have also been utilized as specific antidotes for digitalis toxicity, with dramatic life-saving effect.

Heterogeneity and lability of endogenous digitalis-like substances in the plasma of the toad, Bufo marinus.

PubMed

Butler, V P; Morris, J F; Akizawa, T; Matsukawa, M; Keating, P; Hardart, A; Furman, I

1996-08-01

Three major groups of endogenous digitalis-like substances (EDLS) have been identified in the plasma of the toad, Bufo marinus. One group of compounds, present in fresh plasma, is composed of chromatographically homogeneous polar conjugates, principally bufadienolide 3-sulfates, which exhibit relatively weak Na(+)-K(+)-adenosinetriphosphatase (ATPase) inhibitory activity. A second and larger group of compounds, also found in fresh plasma, includes chromatographically heterogeneous conjugates, which are effective inhibitors of Na(+)-K(+)-ATPase; these compounds possess properties similar to those of bufotoxins. The third group of EDLS consists of free unconjugated bufadienolides, which are also effective Na(+)-K(+)-ATPase inhibitors. These unconjugated bufadienolides are present in relatively low concentrations in fresh toad plasma, but appreciable quantities are enzymatically generated from conjugates (believed to consist principally of bufotoxins) during the in vitro incubation of plasma. We suggest that the extent to which circulating polar EDLS are enzymatically deconjugated in vivo may be important in the regulation of the digitalis-sensitive Na(+)-K(+)-ATPase of toad brain, the only known digitalis-sensitive Na(+)-K(+)-ATPase in the toad.

[The clinical efficacy and safety study of Esculin and Digitalis glycosides Eye Drops in treating ametropic asthenopia].

PubMed

Jiang, Zhen-ying; Qu, Xiao-mei; Li, Xiao-xin; Liu, Yu-ling; Shen, Nian-ci; Zhang, Lin; Ke, Bi-lian; Zhao, Pei-quan; Jiang, Jun; Yao, Ke; Zeng, Jin; Yang, Xiao; Chu, Ren-yuan

2010-12-01

To study the clinical efficacy and safety of the Esculin and Digitalis glycosides Eye Drops used in the patients of ametropic asthenopia. Multicenter clinical trial. Asthenopia patients were chosen from eleven hospitals cross China from July, 2008 to January, 2009. The experiment was conducted asthenopia patients who used the Esculin and Digitalis glycosides Eye Drops for 4 weeks continuously. Symptoms of asthenopia, UCVA (uncorrected vision acuity), refraction, amplitude of accommodation, accommodative lag, accommodative sensitivity and positive/negative relative accommodation were measured at different time points, such as treated before, 1 week and 4 week in treated after. After the 4-week's use of Esculin and Digitalis glycosides Eye Drops, each subjective symptom of the patients was decreased significantly (F=353.30, P<0.05). In addition, most of the objective exams of accommodation ability were significantly improved, such as UCVA (left eye: F=23.39, P<0.05; right eye: F=15.62, P<0.05), refraction (left eye: F=10.34, P<0.05; right eye: F=17.13, P<0.05), amplitude of accommodation (left eye: F=14.46, P<0.05; right eye: F=8.29, P<0.05; eyes: F=13.86, P<0.05), accommodative lag (F=14.89, P<0.05) and accommodative sensitivity (left eye: F=62.67, P<0.05; right eye: F=68.77, P<0.05; eyes: F=82.74, P<0.05). And no patient appeared any adverse reaction in whole experiment. Esculin and Digitalis glycosides Eye Drops is effective and safety for use in the patients of ametropia asthenopia.

Digitalis metabolism and human liver alcohol dehydrogenase.

PubMed Central

Frey, W A; Vallee, B L

1980-01-01

Human liver alcohol dehydrogenase (alcohol: NAD" oxidoreductase, EC 1.1.1.1) catalyzes the oxidation of the 3 beta-OH group of digitoxigenin, digoxigenin, and gitoxigenin to their 3-keto derivatives, which have been characterized by high performance liquid chromatography and mass spectrometry. These studies have identified human liver alcohol dehydrogenase as the unknown NAD(H)-dependent liver enzyme specific for the free hydroxyl group at C3 of the cardiac genins; this hydroxyl is the critical site of the genins' enzymatic oxidation and concomitant pharmacological inactivation in humans. Several kinetic approaches have demonstrated that ethanol and the pharmacologically active components of the digitalis glycosides are oxidized with closely similar kcat/Km values at the same site on human liver alcohol dehydrogenase, for which they compete. Human liver alcohol dehydrogenase thereby becomes an important biochemical link in the metabolism, pharmacology, and toxicology of ethanol and these glycosides, structurally unrelated agents that are both used widely. Both the competition of ethanol with these cardiac sterols and the narrow margin of safety in the therapeutic use of digitalis derivatives would seem to place at increased risk those individuals who receive digitalis and simultaneously consume large amounts of ethanol or whose alcohol dehydrogenase function is impaired. PMID:6987673

Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system.

PubMed

Balenovic, Dijana; Bencic, Martina Lovric; Udovicic, Mario; Simonji, Karol; Hanzevacki, Jadranka Separovic; Barisic, Ivan; Kranjcevic, Stjepan; Prkacin, Ingrid; Coric, Vedran; Brcic, Luka; Coric, Marijana; Brcic, Iva; Borovic, Suzana; Radic, Bozo; Drmic, Domagoj; Vrcic, Hrvoje; Seiwerth, Sven; Sikiric, Predrag

2009-08-07

Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 microg, 10 microg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (microg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 microg), or markedly reduced (10 microg, 10 ng). Fatal outcome was either avoided (50 microg), reduced (10 microg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME+l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME+l-arginine). In this respect, BPC 157 (50 microg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.

Is digitalis compound-induced cardiotoxicity, mediated through guinea-pig cardiomyocytes apoptosis?

PubMed

Ramirez-Ortega, Margarita; Zarco, Gabriela; Maldonado, Vilma; Carrillo, Jose F; Ramos, Pilar; Ceballos, Guillermo; Melendez-Zajgla, Jorge; Garcia, Noemí; Zazueta, Cecilia; Chanona, Jose; Suarez, Jorge; Pastelin, Gustavo

2007-07-02

Our aim in performing this study was to analyze in vivo the cell death mechanism induced by toxic doses of digitalis compounds on guinea-pig cardiomyocytes. We analyzed three study groups of five male guinea pigs each. Guinea pigs were intoxicated under anesthesia with ouabain or digoxin (at a 50-60% lethal dose); the control group did not receive digitalis. A 5-hours period elapsed before guinea pig hearts were extracted to obtain left ventricle tissue. We carried out isolation of mitochondria and cytosol, cytochrome c and caspase-3 and -9 determination, and electrophoretic analysis of nuclear DNA. TdT-mediated DUTP-X nick end labeling (TUNEL) reaction was performed in histologic preparations to identify in situ apoptotic cell death. Ultrastructural analysis was performed by electron microscopy. Electrophoretic analysis of DNA showed degradation into fragments of 200-400 base pairs in digitalis-treated groups. TUNEL reaction demonstrated the following: in the control group, <10 positive nuclei per field; in the digoxin-treated group, 2-14 positive nuclei per field, while in the ouabain-treated group counts ranged from 9-30 positive nuclei per field. Extracts from ouabain-treated hearts had an elevation of cytochrome c in cytosol and a corresponding decrease in mitochondria; this release of cytochrome c provoked activation of caspase-9 and -3. Electron microscopy revealed presence of autophagic vesicles in cytoplasm of treated hearts. Toxic dosages of digitalis at 50-60% of the lethal dose are capable of inducing cytochrome c release from mitochondria, processing of procaspase-9 and -3, and DNA fragmentation; these observations are mainly indicative of apoptosis, although a mixed mechanism of cell death cannot be ruled out.

Anticoagulation for nonvalvular atrial fibrillation: effects of type of practice on physicians' self-reported behavior.

PubMed

Bush, D; Tayback, M

1998-02-01

This study examines whether social and economic factors affect physician practice and attitude with regard to warfarin anticoagulation in patients with nonvalvular atrial fibrillation. We identified physicians in Baltimore City, Baltimore County, and Prince George's County who (1) had written one or more prescriptions for a digitalis compound during the preceding year, and (2) were classified as general practitioners, family practice specialists, internists, or cardiologists. All 358 physicians fulfilling these criteria were surveyed by questionnaire. The overall response rate was 43%. Physicians who wrote 15% or more of their digitalis prescriptions for Medicaid patients said they used warfarin at significantly lower rates for patients with nonvalvular AF than other (66% versus 79%, P <0.01). The opposite pattern was seen with regard to aspirin. There were no significant differences in practice pattern between physicians located in urban vs. suburban counties. In our sample, self-reported anticoagulant practices for patients with nonvalvular AF were associated with the percentage of digitalis prescriptions written for Medicaid patients. In this metropolitan area, anticoagulant therapy was reportedly prescribed for approximately 75% of patients with nonvalvular atrial fibrillation.

Recognition and management of digitalis toxicity.

PubMed

Kelly, R A; Smith, T W

1992-06-04

The most important step in the management of toxicity due to any of the cardiac glycosides is its recognition. Despite the development of an accurate clinical assay for serum levels of digoxin greater than 20 years ago, digitalis toxicity remains common and difficult to confirm, even if suspected, due primarily to 2 factors. First, the signs and symptoms of digitalis toxicity, most commonly an abnormal electrocardiogram showing ventricular or atrial arrhythmias, with or without some degree of concurrent atrioventricular block, often also occur in patients with congestive heart failure (CHF) and underlying coronary atherosclerosis who are not receiving a cardiac glycoside. Second, due to digoxin's narrow therapeutic ratio, the marked degree of variability in the sensitivity of individual patients to its toxic effects, and the common problem of obtaining blood samples inappropriately during the early distribution phase following dosing, a serum digoxin concentration often does not serve as a reliable indicator of toxicity. Despite these difficulties in diagnosis, the management of digoxin toxicity has been made much more effective with the widespread availability of F(ab) fragments of anti-digoxin antibodies. This drug provides the clinician with a rapidly acting, safe antidote for all commonly used digitalis preparations. Conventional therapy for digoxin toxicity remains the maintenance of serum potassium levels greater than or equal to 4 mEq/liter, reversal of decompensated CHF or overt myocardial ischemia, attention to serum magnesium levels and the patient's acid-base status, appropriate antiarrhythmics in the event of ventricular arrhythmias, and a temporary pacemaker for high-grade atrioventricular block. Nevertheless, the high specificity and documented safety of the antibody preparation provides a needed safety net for the continuing use of cardiac glycosides as first-line inotropic agents in the modern therapy of chronic CHF.

Characterization of digitalis-like factors in human plasma. Interactions with NaK-ATPase and cross-reactivity with cardiac glycoside-specific antibodies.

PubMed

Kelly, R A; O'Hara, D S; Canessa, M L; Mitch, W E; Smith, T W

1985-09-25

Much of the evidence for a physiologically important endogenous inhibitor of the sodium pump has been either contradictory or indirect. We have identified three discrete fractions in desalted deproteinized plasma from normal humans that resemble the digitalis glycosides in that they: are of low molecular weight; are resistant to acid and enzymatic proteolysis; inhibit NaK-ATPase activity; inhibit Na+ pump activity in human erythrocytes; displace [3H]ouabain bound to the enzyme; and cross-react with high-affinity polyclonal and monoclonal digoxin-specific antibodies but not with anti-ouabain or anti-digitoxin antibodies. An additional fraction cross-reacted with digoxin-specific antibodies but had no detectable activity against NaK-ATPase. The three inhibitory fractions differed from cardiac glycosides in that their concentration-effect curves in a NaK-ATPase inhibition and [3H]ouabain radioreceptor assays were steeper than unlabeled ouabain. This suggests that these inhibitors are not simple competitive ligands for binding to NaK-ATPase. In the presence of sodium, no fraction required ATP for binding to NaK-ATPase, and in the presence of potassium, only one fraction had the reduced affinity for the enzyme that is characteristic of cardiac glycosides. Unlike digitalis, all three NaK-ATPase inhibitory fractions stimulated the activity of skeletal muscle sarcoplasmic reticulum Ca-ATPase. The presence of at least three fractions in human plasma that inhibit NaK-ATPase and cross-react to a variable degree with different digoxin-specific antibody populations could explain much of the conflicting evidence for the existence of endogenous digitalis-like compounds in plasma.

The basic mechanism of inotropic action of digitalis glycosides.

PubMed

Smith, T W

1984-01-01

A broad survey of the experimental literature suggests that the only unifying concept of digitalis action is that these drugs, at pharmacologically relevant doses, bind with high affinity and specificity to sites on the NaK-ATPase complex that face the outer surface of nearly all eukaryotic cells. Alternative receptors, if they exist, have not been defined. As might be expected, a broad range of biologic effects results from this basic interaction. The clinical therapeutic effects of digitalis include enhancement of myocardial contractility and changes in the properties of the cardiac conduction system; the latter, in turn, result from both direct and autonomically mediated effects [44]. Autonomic effects involve alterations in both parasympathetic and sympathetic activity, and these are attributable to both central and peripheral neural mechanisms [44]. As we have reviewed, there is compelling evidence that one mechanism leading to sustained positive inotropic effects of digitalis glycosides in heart muscle is partial inhibition of sodium transport. Earlier evidence [16, 17] is now supported by electrophysiologic studies [29, 30, 45, 46], intracellular ion-sensitive microelectrode methods [47, 48], and ion flux measurements using radioisotope tracers [14, 15, 49]. Inhibition of myocardial monovalent cation transport has been documented in intact glycoside-sensitive animal models at doses and plasma and myocardial levels causing a positive inotropic effect without overt toxicity [12]. However, these findings do not preclude other mechanisms that may be operative in addition to, or in some circumstances instead of, myocardial Na-K pump inhibition. In the context of much seemingly conflicting evidence [35, 36, 37, 50, 51], the hypothesis advanced by Akera and Brody is of interest [17]. These authors suggest that interaction of subtoxic digitalis concentrations with myocardial NaK-ATPase reduces maximum sodium transport capacity, resulting in an enhanced transient increase in [Na]i during the early phase of the cardiac cycle. Such an increase in subsarcolemmal [Na+] could cause increased Ca++ influx via Na+-Ca++ exchange, with a consequent positive inotropic effect. If the Na+ increase were cyclic and not cumulative, cell Na+ content could return to normal by the end of a cycle due to enhanced turnover of unblocked Na-K pump sites. This hypothesis suggests a mechanism by which Na-K pump inhibition could cause a positive inotropic effect without any measurable increase in steady-state [Na+]i or decrease in [K+]i.(ABSTRACT TRUNCATED AT 400 WORDS)

Phenotypic selection to increase floral scent emission, but not flower size or colour in bee-pollinated Penstemon digitalis.

PubMed

Parachnowitsch, Amy L; Raguso, Robert A; Kessler, André

2012-08-01

Fragrance is a putatively important character in the evolution of flowering plants, but natural selection on scent is rarely studied and thus poorly understood. We characterized floral scent composition and emission in a common garden of Penstemon digitalis from three nearby source populations. We measured phenotypic selection on scent as well as floral traits more frequently examined, such as floral phenology, display size, corolla pigment, and inflorescence height. Scent differed among populations in a common garden, underscoring the potential for scent to be shaped by differential selection pressures. Phenotypic selection on flower number and display size was strong. However, selection favoured scent rather than flower size or colour, suggesting that smelling stronger benefits reproductive success in P. digitalis. Linalool was a direct target of selection and its high frequency in floral-scent bouquets suggests that further studies of both pollinator- and antagonist-mediated selection on this compound would further our understanding of scent evolution. Our results indicate that chemical dimensions of floral display are just as likely as other components to experience selective pressure in a nonspecialized flowering herb. Therefore, studies that integrate visual and chemical floral traits should better reflect the true nature of floral evolutionary ecology. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Digitalis-like and vasoconstrictor effects of endogenous digoxin-like factor(s) from the venom of Bufo marinus toad.

PubMed

Bagrov, A Y; Roukoyatkina, N I; Fedorova, O V; Pinaev, A G; Ukhanova, M V

1993-04-06

Digitalis glycoside-like properties of the Bufo marinus toad crude venom and one of its constituents, bufalin, were studied in various assay systems. In concentrations 0.3-30 micrograms/ml crude venom increased the contractility of isolated electrically driven rat atria, constricted rat aortic rings, inhibited ouabain-sensitive Na+,K(+)-ATPase in rat erythrocytes and the Na+,K(+)-pump in rat aorta, and cross-reacted with antidigoxin antibody from the dissociation enhanced lanthanide fluoroimmunoassay (DELFIA). These effects were unaffected by adrenoceptor blockers and the 5-HT antagonist, deseril, but were blocked by antidigoxin antibody. Bufalin (10-30 microM) increased myocardial contractility and inhibited Na+,K(+)-ATPase in rat erythrocytes similarly to crude Bufo marinus venom. In rat aorta bufalin showed weak and delayed vasoconstrictor activity which was antagonized by 2 microM phentolamine, and had a biphasic effect on the Na+,K(+)-pump; 0.5-1.0 microM bufalin stimulated the pump, while higher concentrations inhibited its activity. Although the effects of bufalin were blocked by antidigoxin antibody, bufalin showed very low digoxin-like immunoreactivity in the DELFIA. These observations suggest that, in addition to bufalin, Bufo marinus venom contains at least one more digitalis-like steroid with significant intrinsic vasoconstrictor activity which, unlike bufalin, constricts the blood vessels acting directly via inhibition of the sodium pump in the vascular smooth muscle membrane.

Cascara

MedlinePlus

... heart damage. Herbs that contain cardiac glycosides include black hellebore, Canadian hemp roots, digitalis leaf, hedge mustard, ... Other stimulant laxative herbs are aloe, alder buckthorn, black root, blue flag, butternut bark, colocynth, European buckthorn, ...

Foxglove poisoning

MedlinePlus

Foxglove poisoning most often occurs from sucking the flowers or eating the seeds, stems, or leaves of ... The poisonous substances are found in: Flowers, leaves, stems, and seeds of the foxglove plant Heart medicine (digitalis glycoside)

Digitalis toxicity

MedlinePlus

... Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 152. Goldberger AL, Goldberger ZD, ... Electrocardiography: A Simplified Approach . 8th ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 18. Nelson LS, Ford MD. ...

Endogenous digitalis-like factors.

PubMed

Schoner, W

1992-01-01

The postulate of a natriuretic factor inhibiting the sodium pump in the kidney led to the detection of increased concentrations of endogenous digitalis-like factors in blood after salt loading, in essential hypertension, in pregnancy-induced hypertension and in chronic hypervolaemia. The recent isolation of ouabain or a close isomer thereof from human plasma and the demonstration of a compound similar if not identical to digoxin in adrenals and human urine shows that mammals like non-vertebrates and toads may synthesize cardiac glycosides in their adrenals and possibly in hypothalamus. The hypothalamus also forms other compounds of unknown structure which bind to the cardiac glycoside receptor site. The differential functions of endogenously formed ouabain and of a digoxin-like substance are unclear. The detailed knowledge of the physiological role of both endogenously formed cardiac glycosides in the regulation of blood pressure has still to be worked out.

Pollinator-mediated natural selection in Penstemon digitalis.

PubMed

Parachnowitsch, Amy; Kessler, André

2010-12-01

Measuring the agents of natural selection is important because it allows us to understand not only which traits are expected to evolve but also why they will evolve. Natural selection by pollinators on floral traits is often assumed because in outcrossing animal-pollinated plants flowers are generally thought to function as advertisements of rewards directed at pollinators. We tested the role of bee pollinators in selection on Penstemon digitalis and found that pollinators were driving selection for larger and more flowers. However, what makes our publication unique is the additional information we gained from reviewing the few other studies that also directly tested whether pollinators were agents of selection on floral traits. As we would expect if pollinators are important agents of selection, selection on floral traits was significantly stronger when pollinators were present than when they were experimentally removed. Taken together, these results suggest that pollinators can be important drivers of selection in contemporary populations.

Annual Variation in the Sterol Content of Digitalis purpurea L. Seedlings 1

PubMed Central

Jacobsohn, Myra K.; Jacobsohn, Gert M.

1976-01-01

Seedings from a single lot of Digitalis purpurea L. seeds were germinated in batches over a period of 13 months. A total lipid extract was made which was resolved into esterified and unconjugated plus glycosylated sterol fractions. The amounts of sterol in each fraction and in the total were compared for seedlings germinated at different times of the year. The amount of esterified sterols reached a maximum value from March until June, and a low value from July until January. In January, a sharp increase began which lasted until March. Amounts of unconjugated and glycosylated sterols were elevated from March until June, low from July until October, and on the rise from November until March. These data correlate with an annual cycle in seed germination. The phase of maximum sterol content of seedlings is followed by a period of null germination. PMID:16659713

Novel digitalis-like factor, marinobufotoxin, isolated from cultured Y-1 cells, and its hypertensive effect in rats.

PubMed

Yoshika, Masamichi; Komiyama, Yutaka; Konishi, Motomi; Akizawa, Toshifumi; Kobayashi, Takahisa; Date, Mutsuhiro; Kobatake, Shinzo; Masuda, Midori; Masaki, Hiroya; Takahashi, Hakuo

2007-01-01

Marinobufagenin and telecinobufagin have been identified as digitalis-like factors in mammals. In toads, marinobufagenin-related compounds, such as marinobufotoxin (MBT), have been isolated in some tissues but not in mammals, and its biological action has not been elucidated. Herein, we aimed to explore the possible production and/or secretion of MBT and the biological action in rats. First, the MBT in culture supernatant of the adrenocortical-originated cell line Y-1 was analyzed by high-performance liquid chromatography and sensitive ELISA for marinobufagenin-like immunoreactivity. Moreover, the structural information was obtained by mass spectrometry. To determine the biological action, MBT (9.6 and 0.96 microg/kg per day) was intraperitoneally infused via an osmotic minipump for 1 week. Blood pressure and renal excretion of marinobufagenin-like immunoreactivity were measured. Marinobufagenin-like immunoreactivity was found in Y-1 cell culture media, and the concentration increased until 24 hours. The structural analysis suggested that marinobufagenin-like immunoreactivities were marinobufagenin and MBT, and tandem mass spectrum analysis revealed them with the specific daughter ions. The highest sensitive ELISA-positive peak of marinobufagenin-like immunoreactivity in the media was MBT. Continuous administration of MBT in rats for 1 week significantly increased systolic blood pressure and renal excretion of marinobufagenin-like immunoreactivity compared with control rats (135+/-3.0 versus 126+/-2.0 mm Hg and 1.41+/-0.286 versus 0.34+/-0.064 ng/day, respectively). These data suggest that MBT, arginine-suberoyl ester of marinobufagenin, can be a novel digitalis-like factor with hypertensive action and is secreted from the adrenocortical cells.

Effect of salt acclimation on digitalis-like compounds in the toad.

PubMed

Lichtstein, D; Gati, I; Babila, T; Haver, E; Katz, U

1991-01-23

Digitalis-like compounds (DLC) were shown to be a normal constituent of the skin and plasma of toads. In order to assess the possible physiological role of these compounds in the toad, their levels were determined in the brain, plasma and skin following acclimation in different NaCl solutions. We demonstrate that an increase in salt concentrations in the animal medium from 0 to 1.2% decreased the levels of DLC in the brain by 50% without altering significantly its levels in the plasma and skin. An increase in medium salt concentration to 1.5% resulted in a 50% increase of DLC levels in the skin without changing its levels in the plasma or brain. These results suggest that skin and brain DLC may participate in the long-term salt and water homeostasis in the toad, while the plasma compound either participates in the short-term regulations of salt and water homeostasis or have some other, unknown, function.

Pollinators exert natural selection on flower size and floral display in Penstemon digitalis.

PubMed

Parachnowitsch, Amy L; Kessler, André

2010-10-01

• A major gap in our understanding of floral evolution, especially micro-evolutionary processes, is the role of pollinators in generating patterns of natural selection on floral traits. Here we explicitly tested the role of pollinators in selecting floral traits in a herbaceous perennial, Penstemon digitalis. • We manipulated the effect of pollinators on fitness through hand pollinations and compared phenotypic selection in open- and hand-pollinated plants. • Despite the lack of pollen limitation in our population, pollinators mediated selection on floral size and floral display. Hand pollinations removed directional selection for larger flowers and stabilizing selection on flower number, suggesting that pollinators were the agents of selection on both of these traits. • We reviewed studies that measured natural selection on floral traits by biotic agents and generally found stronger signatures of selection imposed by pollinators than by herbivores and co-flowering plant species. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

[A patient with depression due to digitalis poisoning].

PubMed

Schouten, J; van der Aa, G C

1984-04-01

A 85 year old lady suffering from depression is described. The depression was caused by digoxin intoxication. At first this was not recognized because of the low level of creatinine in the serum. This was the result of the decreased lean body mass, the patient weighing only 40 kilo!

First Report of Peronospora digitalidis causing downy mildew disease on foxglove in Oregon

USDA-ARS?s Scientific Manuscript database

Foxglove (Digitalis purpurea) is a biennial plant in the Plantaginaceae family. Widely cultivated as a striking flowering ornamental plant, foxglove is also a source of toxic cardiac glycosides that may be fatal if ingested at high doses, or used pharmaceutically to treat human heart failure. In the...

Epizoic zoanthids reduce pumping in two Caribbean vase sponges

NASA Astrophysics Data System (ADS)

Lewis, T. B.; Finelli, C. M.

2015-03-01

Sponges are common sessile benthic suspension feeders that play a critical role in carbon and nitrogen cycling within reef ecosystems via their filtration capabilities. Due to the contribution of sponges in benthic-pelagic coupling, it is critical to assess factors that may affect their role in the healthy function of coral reefs. Several factors can influence the rate at which an individual sponge pumps water, including body size, environmental conditions, mechanical blockage, and reduction of inhalant pores (ostia). Symbiotic zoanthid colonization is a common occurrence on Caribbean sponges, and the presence of zoanthids on the surface of a sponge may occlude or displace the inhalant ostia. We quantified pumping rates of the giant barrel sponge, Xestospongia muta ( N = 22 uncolonized, 37 colonized) and the common vase sponge, Niphates digitalis ( N = 21 uncolonized, 17 colonized), with and without zoanthid symbionts, Parazoanthus catenularis and Parazoanthus parasiticus, respectively. For X. muta, biovolume-normalized pumping rates of individuals colonized by zoanthids were approximately 75 % lower than those of uncolonized sponges. Moreover, colonization with zoanthids was related to a difference in morphology relative to uncolonized individuals: Colonized sponges exhibited an osculum area to biovolume ratio that was nearly 65 % less than uncolonized sponges. In contrast, the presence of zoanthids on N. digitalis resulted in only a marginal decrease in pumping rates and no detectable difference in morphology. The difference in zoanthid effects between X. muta and N. digitalis is likely due to the differences in wall thickness and architecture between the two species. The probable cause of reduced pumping in affected sponges is occupation of the sponge surface that leads to blockage or displacement of inhalant ostia. To partially test this hypothesis, zoanthid colonization on specimens of X. muta was simulated by wrapping sponges with plastic mesh of varying porosity. Mechanical blockage of ostia resulted in a 20-50 % reduction in pumping rates compared with controls.

[Digoxin poisoning: new prospects for therapy].

PubMed

Marino, Alfonsina; Giordano, Lorenzo; Ardu, Francesco

2017-04-01

The filter has been approved by the Food and Drug Administration for the removal of beta-2 microglobulin in patient undergoing hemodialysis. We used the filter (the patient agrees) off label, in the course of digitalis intoxication and we have shown that the filter is capable of removing the drug effectively. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Crystallization and preliminary crystallographic analysis of selenomethionine-labelled progesterone 5β-reductase from Digitalis lanata Ehrh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Egerer-Sieber, Claudia; Herl, Vanessa; Müller-Uri, Frieder

2006-03-01

Progesterone 5β-reductase is the first stereospecific enzyme in the pathway for the synthesis of cardenolides. To elucidate the structural mechanism of this reaction, we crystallized the selenomethionine-labelled enzyme from D. lanata and report the preliminary analysis of a MAD data set collected from these crystals. Progesterone 5β-reductase (5β-POR) catalyzes the reduction of progesterone to 5β-pregnane-3,20-dione and is the first stereospecific enzyme in the putative biosynthetic pathway of Digitalis cardenolides. Selenomethionine-derivatized 5β-POR from D. lanata was successfully overproduced and crystallized. The crystals belong to space group P4{sub 3}2{sub 1}2, with unit-cell parameters a = 71.73, c = 186.64 Å. A MADmore » data set collected at 2.7 Å resolution allowed the identification of six out of eight possible Se-atom positions. A first inspection of the MAD-phased electron-density map shows that 5β-POR is a Rossmann-type reductase and the quality of the map is such that it is anticipated that a complete atomic model of 5β-POR will readily be built.« less

Characterization and localization of progesterone 5 alpha-reductase from cell cultures of foxglove (Digitalis lanata EHRH).

PubMed Central

Wendroth, S; Seitz, H U

1990-01-01

Progesterone 5 alpha-reductase, which catalyses the reduction of progesterone to 5 alpha-pregnane-3,20-dione, was isolated and characterized from cell cultures of Digitalis lanata (foxglove). Optimum enzyme activity was observed at pH 7.0, and the enzyme had an apparent Km value of 30 microM for its substrate progesterone. The enzyme needs NADPH as reductant, which could not be replaced by NADH. For NADPH, the apparent Km value is 130 microM. The optimum temperature was 40 degrees C; at temperatures below 45 degrees C, the product 5 alpha-pregnane-3,20-dione was reduced by a second reaction to 5 alpha-pregnan-3 beta-ol-20-one. Progesterone 5 alpha-reductase activity was not dependent on bivalent cations. In the presence of EDTA, 0.1 mM-Mn2+ had no influence on enzyme activity, whereas 0.1 mM-Ca2+, -Co2+ and -Zn2+ decreased progesterone 5 alpha-reductase activity. Only 0.1 mM-Mg2+ was slightly stimulatory. EDTA and thiol reagents such as dithiothreitol stimulate progesterone 5 alpha-reductase activity. By means of linear sucrose gradient fractionation of the cellular membranes, progesterone 5 alpha-reductase was found to be located in the endoplasmic reticulum. PMID:2106876

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation.

PubMed

Buttà, Carmelo; Tuttolomondo, Antonino; Casuccio, Alessandra; Petrantoni, Rossella; Miceli, Giuseppe; Cuttitta, Francesco; Pinto, Antonio

2016-12-01

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.

Drug-induced gynecomastia.

PubMed

Thompson, D F; Carter, J R

1993-01-01

Gynecomastia is a relatively common physical finding in men. A wide variety of drugs have been implicated in its cause. Sufficient evidence in the literature suggests that calcium-channel blockers, cancer chemotherapeutic agents, and histamine2-receptor blockers may play a role in the disorder. Evidence for digitalis glycosides and neuroleptic agents is insufficient. Ketoconazole and spironolactone can also produce gynecomastia, and data for marijuana are contradictory. Large numbers of drugs have only case reports of temporal association with the disorder.

Modification of Tamoxifen Effectiveness by Gene Polymorphisms and Other Drugs

DTIC Science & Technology

2009-05-01

digitalis-like steroid hormones: new mechanisms of action and biological significance. Life Sci 2007, 80:2093-2107. 27. Rifka SM, Pita JC Jr, Loriaux DL ...Wolmark N, Wickerham DL , Cronin WM. Reanalysis and results after 12 years of follow- up in a randomized clinical trial comparing total mastectomy with...Hilton E, Lennard MS, Tucker GT, Ellis SW (2001) Influence of phenylalanine -481 subsitutions on the catalytic activity of cytochrome P-450 2D6

Heterogeneous transport of digitalis-like compounds by P-glycoprotein in vesicular and cellular assays.

PubMed

Gozalpour, Elnaz; Wilmer, Martijn J; Bilos, Albert; Masereeuw, Rosalinde; Russel, Frans G M; Koenderink, Jan B

2016-04-01

Digitalis-like compounds (DLCs), the ancient medication of heart failure and Na,K-ATPase inhibitors, are characterized by their toxicity. Drug-drug interactions (DDIs) at absorption and excretion levels play a key role in their toxicity, hence, knowledge about the transporters involved might prevent these unwanted interactions. In the present study, the transport of fourteen DLCs with human P-glycoprotein (P-gp; ABCB1) was studied using a liquid chromatography-mass spectrometry (LC-MS) quantification method. DLC transport by P-gp overexpressing Madin-Darby canine kidney (MDCK) and immortalized human renal cells (ciPTEC) was compared to vesicular DLC transport. Previously, we identified convallatoxin as a substrate using membrane vesicles overexpressing P-gp; however, we could not measure transport of other DLCs in this assay (Gozalpour et al., 2014a). Here, we showed that lipophilic digitoxin, digoxigenin, strophanthidin and proscillaridin A are P-gp substrates in cellular accumulation assays, whereas the less lipophilic convallatoxin was not. P-gp function in the cellular accumulation assays depends on the entrance of lipophilic compounds by passive diffusion, whereas the vesicular transport assay is more appropriate for hydrophilic substrates. In conclusion, we identified digitoxin, digoxigenin, strophanthidin and proscillaridin A as P-gp substrates using cellular accumulation assays and recognized lipophilicity as an important factor in selecting a suitable transport assay. Copyright © 2016 Elsevier B.V. All rights reserved.

Thyroid hormone stimulates myoglobin expression in soleus and extensorum digitalis longus muscles of rats: concomitant alterations in the activities of Krebs cycle oxidative enzymes.

PubMed

dos Santos, R A; Giannocco, G; Nunes, M T

2001-06-01

Myoglobin (Mb) gene expression, Citrate Synthase (CS) and Succinate Dehydrogenase (SDH) activities of Soleus (S) and Extensorum Digitalis Longus (EDL) muscles were studied in intact, thyroidectomized and T3-treated (25 microg/100g, BW, ip, 15 days) rats. The fiber type composition of S muscle was also evaluated and used as control of the T3-induced effects. In the S muscle, the T3 treatment increased the Mb mRNA and protein expression, as well as the CS and SDH activity. These changes occurred parallel to the expected increase in type II (fast) and decrease in type I (slow)-fibers in S muscle. In the hypothyroid state, the Mb mRNA was decreased, while the Mb expression and CS activity tended to decrease. In contrast the SDH activity was increased, probably due to the enhanced motor activity that occurs as a short-term response to the hypothermia induced by hypothyroidism. In the EDL, the alterations were milder than those in S muscle in both thyroid states. These findings show that Mb gene expression is induced by T3. This is concomitant with the enhancement of Krebs Cycle enzyme activities and provides additional evidence that thyroid hormone increases the aerobic potential of skeletal muscles, as well as the speed of muscle contraction.

The effect of acetyl strophanthidin on the hearts of normal dogs.

PubMed

Hayes, A H; McShane, W P; Sidell, F R

1970-05-01

1. The ED50 of acetyl strophanthidin for producing ventricular arrhythmias in normal dogs was 54.5 mug/kg intravenously.2. Doses up to and including those which caused ventricular tachycardia did not produce either atrial arrhythmias or significant aberration of A-V conduction.3. Although the classic digitalis-induced rate and e.c.g. waveform changes may appear after administration of acetyl strophanthidin, their presence or absence have no value in predicting the subsequent development of ventricular arrhythmias.

An 88-year-old man with syncope and an alternating axis.

PubMed

Zhao, Yun-Tao; Huang, Yen Shu; Yi, Zhong

2016-05-15

An 88-year-old man, admitted to the emergency room (ER) after three episodes of syncope within 1 day, reported a precursory of syndrome of light-headedness with rapid palpitations that led to an abrupt loss of consciousness. After undergoing percutaneous and surgical revascularisation, he started complaining of chest and back discomfort for the past 20 years and searching for help from Chinese medicine, Fuzi. He had history of chronic renal failure and heart failure, but denied neither taking digitalis nor having family history related to sudden death.On arrival, heart rate was 150 bpm and blood pressure (BP) by cuff was 91/81 mm Hg (non-invasive BP could not be accurately obtained during tachycardia) plus oedema on both lower extremities. There were diffuse crackles and indistinct heart sounds on auscultation.The admission ECG was performed in the ER (figure 1). His serum creatinine was 139.7 mmol/L, serum K(+) was 4.7 mmol/L, N-terminal of the prohormone brain natriuretic peptide was highly elevated (12 000 pg/mL) and troponin I was negative. What is the most likely diagnosis suggested based on the patient's ECG and history? Aconite poisoningDigitalis toxicityCatecholaminergic polymorphic ventricular tachycardia (CPVT)Andersen-Tawil syndrome (ATS). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The role of stochastic thermal environments in modulating the thermal physiology of an intertidal limpet, Lottia digitalis.

PubMed

Drake, Madeline J; Miller, Nathan A; Todgham, Anne E

2017-09-01

Much of our understanding of the thermal physiology of intertidal organisms comes from experiments with animals acclimated under constant conditions and exposed to a single heat stress. In nature, however, the thermal environment is more complex. Aerial exposure and the unpredictable nature of thermal stress during low tides may be critical factors in defining the thermal physiology of intertidal organisms. In the fingered limpet, Lottia digitalis , we investigated whether upper temperature tolerance and thermal sensitivity were influenced by the pattern of fluctuation with which thermal stress was applied. Specifically, we examined whether there was a differential response (measured as cardiac performance) to repeated heat stress of a constant and predictable magnitude compared with heat stress applied in a stochastic and unpredictable nature. We also investigated differences in cellular metabolism and damage following immersion for insights into biochemical mechanisms of tolerance. Upper temperature tolerance increased with aerial exposure, but no significant differences were found between predictable treatments of varying magnitudes (13°C versus 24°C versus 32°C). Significant differences in thermal tolerance were found between unpredictable trials with different heating patterns. There were no significant differences among treatments in basal citrate synthase activity, glycogen content, oxidative stress or antioxidants. Our results suggest that aerial exposure and recent thermal history, paired with relief from high low-tide temperatures, are important factors modulating the capacity of limpets to deal with thermal stress. © 2017. Published by The Company of Biologists Ltd.

The pathogenesis of hypertension: black-white differences.

PubMed

Blaustein, M P; Grim, C E

1991-01-01

In summary, for reasons that are not clear, some persons seem to be extremely good at retaining sodium on a high-sodium diet or poor at excreting sodium on a high-sodium intake. This is more frequent in Western hemisphere blacks than in whites in the West or in blacks in Africa. These geographic/ethnic differences in sodium handling ability may be related to environmental factors or, more likely, to inherited differences in the ability to conserve sodium based on the evolutionary principle of survival fo the fittest for the ability to conserve sodium. The frequency of this salt-conserving (thrifty) genotype in Western hemisphere blacks may have been further increased as a consequence of severe selection pressures for survival based on the ability to conserve sodium during the slavery period of history in the West. One characteristic of the blood pressure control systems of Western hemisphere blacks is suppression of plasma renin activity without suppression of aldosterone production. In addition there is greater nephrosclerosis in blacks than whites and a more rapid decline in creatinine clearance with age. When more sodium is ingested than the kidneys are able to handle (excrete), there is a (transient) slight positive sodium balance; as a result sodium, chloride, and water are retained, resulting in an expansion of plasma volume (Fig. 7-3). The initial physiologic responses include (increased) secretion of atrial natriuretic peptides and the digitalis-like substance (natriuretic hormone), and inhibition of vasopressin and aldosterone secretion. The net effect is directly enhanced natriuresis and diuresis, and a reduction in plasma volume, with no significant effect on blood pressure. However, if there is a continuing tendency to sodium retention and volume expansion, the capacity of the aforementioned mechanisms to control plasma volume will be exceeded; then, the chronically elevated level of the digitalis-like substance will inhibit the sodium pumps in the arterial and venous smooth muscle cells and in the sympathetic neurons. The increased venous tone will help to reduce plasma volume directly by reducing central venous volume. Arterial tone will be increased by direct action of the digitalis-like substance on the arterial smooth muscle and, indirectly, via the hormone's action on the sympathetic neurons. Initially, of course, blood pressure will be maintained in the normal range (but will be labile) because of the compensating cardiovascular reflexes. Once the capacity of these reflexes to control blood pressure is exceeded, however, the blood pressure will begin to rise; this will induce a pressure natriuresis to help restore plasma volume to normal.(ABSTRACT TRUNCATED AT 400 WORDS)

In Carthage ruins: the illness of Sir Winston Churchill at Carthage, December 1943.

PubMed

Vale, J A; Scadding, J W

2017-09-01

This paper reviews Churchill's illness in Carthage in December 1943. It was characterised by fever that lasted 6 days, left lower lobe pneumonia and two episodes of atrial fibrillation. He was managed in a private villa by Lord Moran, his personal physician, with the assistance of two nurses and the expert advice of colleagues. Sulphadiazine and digitalis leaf were prescribed and Churchill recovered. It is remarkable that, despite the severity of his illness, he continued to direct the affairs of State from his bed.

Digitalis-like compounds in the toad Bufo viridis: tissue and plasma levels and significance in osmotic stress.

PubMed

Lichtstein, D; Gati, I; Haver, E; Katz, U

1992-01-01

Digitalis-like compounds (DLC), constituents of animal tissues, are possible regulators of the Na+, K(+)-ATPase implicated in water and salt homeostasis. The distribution of DLC in the toad (Bufo viridis) was determined following methanol extraction and partial purification. DLC highest levels were found in the skin but it was also detected in the plasma and many internal organs. Short term (hours) exposure of the toad to hypertonic shock (1.5% NaCl) induced an increase in plasma osmolarity due to an increase in Na+ and Cl- levels. This treatment induced a transient, three fold, increase of DLC levels in the brain and transient reduction of its levels in the ventral skin. Acclimation of the toads to burrowing conditions for six weeks resulted in an increase in plasma osmolarity due to a large increase in plasma urea with a small increase in ion concentrations. Under these conditions DLC levels in the dorsal skin increased by 100% without alteration of its levels in the plasma, brain and ventral skin. DLC levels in the toad brain of control animals, showed a significant dependence on season, being highest in the summer and lowest in the winter. DLC levels in the skin peaked in May while the levels in the plasma were season independent. The changes in DLC levels induced by the short- as well as long-term perturbations in the animal environmental salinity together with the seasonal differences suggest that DLC in the toad is involved in water and salt homeostasis of these animals, but may also participate in other unknown functions.

[Legal aspects of the use of footbaths for cattle and sheep].

PubMed

Kleiminger, E

2012-04-24

Claw diseases pose a major problem for dairy and sheep farms. As well as systemic treatments of these illnesses by means of drug injection, veterinarians discuss the application of footbaths for the local treatment of dermatitis digitalis or foot rot. On farms footbaths are used with different substances and for various purposes. The author presents the requirements for veterinary medicinal products (marketing authorization and manufacturing authorization) and demonstrates the operation of the "cascade in case of a treatment crisis". In addition, the distinction between veterinary hygiene biocidal products and veterinary medicinal products and substances to care for claws is explained.

[Drug-induced gynecomastia].

PubMed

Hugues, F C; Gourlot, C; Le Jeunne, C

2000-02-01

Drugs are a very common cause of gynecomastia and should always be entertained as the possible causal agent of such a condition. This drug side-effect is due to an impaired balance in the serum estrogen/serum androgen ratio, whatever the mechanism, or a rise in prolactin level. Sex hormones, antiandrogens, are frequently involved as well as spironolactone, cimetidine, verapamil and cancer chemotherapy (especially alkylating agents). Diazepam, tricyclic antidepressants, neuroleptics, calcium channel blockers, captopril, digitalis glycosides, omeprazole, some antibiotics and growth hormone are all possibly, but less often, the responsible agent. Criteria of the French method for determining drug causality are discussed.

[No effect of digitalis on sex and adrenal hormones in healthy subjects and in patients with congestive heart failure].

PubMed

Kley, H K; Abendroth, H; Hehrmann, R; Müller, A; Keck, E; Schneitler, H; Elsässer, H; Krüskemper, H L

1984-01-16

Digoxin was studied to see whether it impairs adrenal function and feminizes male subjects by changing plasma sexual hormones; both have been reported on previously. In eight healthy male subjects neither estrone (38.7 +/- 7.7 vs 35.4 +/- 3.2 pg/ml) nor estradiol (35.8 +/- 6.4 vs 32.2 +/- 3.9 pg/ml) nor testosterone (6.32 +/- 0.74 vs 6.45 +/- 0.73 ng/ml) were found to be altered by digoxin administration (plasma levels 1.55 +/0- 0.27 ng/ml) lasting 35 days. The same was true of free testosterone (147 +/- 24 vs 142 +/- 19 pg/ml) and free estradiol (657 +/- 77 vs 615 +/- 78 fg/ml). Even maximal stimulation of the adrenal and gonadal glands by adrenocorticotropic hormone (ACTH) and human chorionic gonadotropin (hCG) did not exhibit any digoxin-induced alterations in the synthesizing capacity of steroid hormones, as shown by plasma cortisol (increase from 128 +/- 18 to 389 +/- 18 ng/ml) and testosterone (from 5.96 +/- 0.90 to 10.33 +/- 1.19 ng/ml). Furthermore, seven subjects on digoxin were observed over a period of 150-210 days; they did not show any increase of estrogens. This was also found in three subjects when estrogen levels were elevated initially due to extreme obesity. Also, 35 patients who took beta-methyldigoxin (n = 8), beta-acetyldigoxin (n = 20) and digitoxin (n = 7) from 1 to 9 (mean: 1.9) years demonstrated normal plasma concentrations of gonadal and adrenal steroids, irrespective of duration of application or the digitalis compound.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intoxications with plants].

PubMed

Kupper, Jacqueline; Reichert, Cornelia

2009-05-01

Ingestions of plants rarely lead to life-threatening intoxications. Highly toxic plants, which can cause death, are monkshood (Aconitum sp.), yew (Taxus sp.) and autumn crocus (Colchicum autumnale). Lethal ingestions of monkshood and yew are usually suicides, intoxications with autumn crocus are mostly accidental ingestions of the leaves mistaken for wild garlic (Allium ursinum). Severe intoxications can occur with plants of the nightshade family like deadly nightshade (Atropa belladonna), angel's trumpet (Datura suaveolens) or jimsonweed (Datura stramonium). These plants are ingested for their psychoactive effects. Ingestion of plant material by children most often only causes minor symptoms or no symptoms at all, as children usually do not eat great quantities of the plants. They are especially attracted by the colorful berries. There are plants with mostly cardiovascular effects like monkshood, yew and Digitalis sp. Some of the most dangerous plants belong to this group. Plants of the nightshade family cause an anticholinergic syndrome. With golden chain (Laburnum anagyroides), castor bean (Ricinus communis) and raw beans (Phaseolus vulgaris) we see severe gastrointestinal effects. Autumn crocus contains a cell toxin, colchicine, which leads to multiorgan failure. Different plants are irritative or even caustic to the skin. Treatment is usually symptomatic. Activated charcoal is administered within one hour after ingestion (1 g/kg). Endoscopic removal of plant material can be considered with ingestions of great quantities of highly toxic plants. Administration of repeated doses of charcoal (1-2 g/h every 2-4 hours) may be effective in case of oleander poisoning. There exist only two antidotes: Anti-digoxin Fab fragments can be used with cardenolide glycoside-containing plants (Digitalis sp., Oleander). Physostigmine is the antidote for severe anticholinergic symptoms of the CNS. Antibodies against colchicine, having been developed in France, are not available at the moment.

Effects of salicylic acid on thermotolerance and cardenolide accumulation under high temperature stress in Digitalis trojana Ivanina.

PubMed

Cingoz, Gunce Sahin; Gurel, Ekrem

2016-08-01

Long periods of high temperature or transitory increased temperature, a widespread agricultural problem, may lead to a drastic reduction in economic yield, affecting plant growth and development in many areas of the world. Heat stress causes many anatomical and physiological changes in plants. Its unfavorable effects can be alleviated by thermotolerance induced by exogenous application of plant growth regulators and osmoprotectants or by gradual application of temperature stress. Digitalis trojana Ivanina is an important medicinal plant species well known mainly for its cardenolides. The production of cardenolides via traditional agriculture is commercially inadequate. In this study, elicitation strategies were employed for improving crop thermotolerance and accumulation of cardenolides. For these purposes, the effects of salicylic acid (SA) and/or high temperature treatments in inducing cardenolide accumulation and thermotolerance were tested in callus cultures of D. trojana. Considerable increases in the production of cardenolides (up to 472.28 μg.g(-1) dry weight, dw) and induction of thermotolerance capacity were observed when callus cultures were exposed to high temperature for 2 h after pretreating with SA. High temperature treatments (2 h and 4 h) caused a marked reduction in superoxide dismutase (SOD; EC 1.15.1.1) and catalase (CAT; EC 1.11.1.6) activities, while SA pretreatment increased their activities. High temperature and/or SA appeared to increase the levels of proline, total phenolic, and flavonoid content. Elevated phenolic accumulation could be associated with increased stress protection. These results indicated that SA treatments induced synthesis of antioxidants and cardenolides, which may play a significant role in resistance to high temperature stress. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Thermal physiology of the fingered limpet Lottia digitalis under emersion and immersion.

PubMed

Bjelde, Brittany E; Todgham, Anne E

2013-08-01

Marine animals living high in the rocky intertidal zone experience long durations of aerial emersion, sometimes enduring rapid increases in temperature. To date, much of our understanding of the thermal physiology of intertidal organisms comes from studies in which organisms are exposed to increasing temperatures when immersed, with the added effect of aerial emersion rarely considered. In this study, we examined the physiological response of the finger limpet, Lottia digitalis, to increases in temperature under both immersed and emersed conditions. We investigated the thermal sensitivity and upper temperature tolerance of limpets through assessment of cardiac performance, metabolic rate, glycogen depletion and maintenance of protein integrity. Cardiac performance in response to ecologically relevant increases in temperature was similar in emersed and immersed limpets from 15 to 35°C and showed multiple break patterns in heart rate as temperature was increased. Overall, emersed limpets had a greater upper thermal limit on cardiac performance, with the ability to maintain heart rate at a temperature 3-5°C higher than that for immersed limpets. Metabolism in limpets also differed significantly between emersion and immersion, where a significant depression in aerobic metabolic rate was observed under immersion with increasing temperature. Greater levels of ubiquitin-conjugated proteins were found under emersed conditions compared with immersed limpets. Maintaining cardiac performance and aerobic metabolism to higher temperatures under emersed conditions is likely reflective of physiological adaptations to live in an aerially exposed environment. Measured field temperatures where fingered limpets were collected demonstrated that limpets have a narrow thermal safety margin for aerobic performance, and currently experience multiple days where summer temperatures might exceed their threshold limits.

The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the renin–angiotensin–aldosterone system, oxidative stress and endogenous digitalis in the brain

PubMed Central

Takahashi, Hakuo; Yoshika, Masamichi; Komiyama, Yutaka; Nishimura, Masato

2011-01-01

The central nervous system has a key role in regulating the circulatory system by modulating the sympathetic and parasympathetic nervous systems, pituitary hormone release, and the baroreceptor reflex. Digoxin- and ouabain-like immunoreactive materials were found >20 years ago in the hypothalamic nuclei. These factors appeared to localize to the paraventricular and supraoptic nuclei and the nerve fibers at the circumventricular organs and supposed to affect electrolyte balance and blood pressure. The turnover rate of these materials increases with increasing sodium intake. As intracerebroventricular injection of ouabain increases blood pressure via sympathetic activation, an endogenous digitalis-like factor (EDLF) was thought to regulate cardiovascular system-related functions in the brain, particularly after sodium loading. Experiments conducted mainly in rats revealed that the mechanism of action of ouabain in the brain involves sodium ions, epithelial sodium channels (ENaCs) and the renin–angiotensin–aldosterone system (RAAS), all of which are affected by sodium loading. Rats fed a high-sodium diet develop elevated sodium levels in their cerebrospinal fluid, which activates ENaCs. Activated ENaCs and/or increased intracellular sodium in neurons activate the RAAS; this releases EDLF in the brain, activating the sympathetic nervous system. The RAAS promotes oxidative stress in the brain, further activating the RAAS and augmenting sympathetic outflow. Angiotensin II and aldosterone of peripheral origin act in the brain to activate this cascade, increasing sympathetic outflow and leading to hypertension. Thus, the brain Na+–ENaC–RAAS–EDLF axis activates sympathetic outflow and has a crucial role in essential and secondary hypertension. This report provides an overview of the central mechanism underlying hypertension and discusses the use of antihypertensive agents. PMID:21814209

Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care.

PubMed

García-Iranzo, Emma M; Rodríguez-Lucena, Francisco J; Matoses-Chirivella, Carmen; García-Monsalve, Ana; Murcia-López, Ana Cristina; Navarro-Ruiz, Andrés

2017-07-01

The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment. Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected. 624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven't analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin. Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing. A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

[Musculature of the pelvic limb of the American weasel (Mustela nigripes, Audubon and Bachman)].

PubMed

Bisaillon, A

1976-01-01

The origins and insertions of the muscles of the pelvic limb of the black-footed ferret (Mustela nigripes) are illustrated and described. The results based on the dissection of two adult specimens are compared with those of other investigations on the myology of the Mustelids. The musculature of the pelvic limb of Mustela nigripes is substantially similar to that of other Mustelids investigated except for slight differences of individual muscles. The most obvious differences involve the tendons of the mm. fibularis longus, fibularis brevis and extensor digitalis lateralis. The tendon of the m. fibularis longus contains a small sesamoid bone.

Did some 18th and 19th century treatments for mental disorders act on the brain?

PubMed

Leonard, Edward C

2004-01-01

Review of 18th and 19th century psychiatric therapies raises the possibility that several may have altered the activity of vasopressin or Na-K-ATPase. Bleeding, whirling, nausea created by medicines, and vagus nerve stimulation by application of electricity through the skin all perturb the hypothalamic hormone, arginine vasopressin, while helleborus and digitalis inhibit the sodium pump enzyme, Na-K-ATPase. These approaches were used with reported benefit many years ago, acting on the brain in ways ongoing research suggests may play a role in affective disorders. Study of long-abandoned treatments may clarify their mechanisms of action and the characteristics of responsive patients.

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

NASA Technical Reports Server (NTRS)

Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

1998-01-01

We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

In vitro propagation and production of cardiotonic glycosides in shoot cultures of Digitalis purpurea L. by elicitation and precursor feeding.

PubMed

Patil, Jitendra Gopichand; Ahire, Mahendra Laxman; Nitnaware, Kirti Manik; Panda, Sayantan; Bhatt, Vijay P; Kishor, Polavarapu B Kavi; Nikam, Tukaram Dayaram

2013-03-01

Digitalis purpurea L. (Scrophulariaceae; Foxglove) is a source of cardiotonic glycosides such as digitoxin and digoxin which are commercially applied in the treatment to strengthen cardiac diffusion and to regulate heart rhythm. This investigation deals with in vitro propagation and elicited production of cardiotonic glycosides digitoxin and digoxin in shoot cultures of D. purpurea L. In vitro germinated seedlings were used as a primary source of explants. Multiple shoot formation was achieved for three explant types (nodal, internodal, and leaf) cultured on Murashige and Skoog (MS) medium with several treatments of cytokinins (6-benzyladenine-BA; kinetin-Kin; and thidiazuron-TDZ) and auxins (indole-3-acetic acid-IAA; α-naphthaleneacetic acid-NAA; and 2,4-dichlorophenoxy acetic acid-2,4-D). Maximum multiple shoots (12.7 ± 0.6) were produced from nodal explants on MS + 7.5 μM BA. Shoots were rooted in vitro on MS containing 15 μM IAA. Rooted plantlets were successfully acclimatized. To further maintain the multiple shoot induction, mother tissue was cut into four equal parts and repeatedly sub-cultured on fresh shoot induction liquid medium after each harvest. On adaptation of this strategy, an average of 18 shoots per explant could be produced. This strategy was applied for the production of biomass and glycosides digitoxin and digoxin in shoot cultures on MS medium supplemented with 7.5 μM BA and several treatments with plant growth regulators, incubation period, abiotic (salicylic acid, mannitol, sorbitol, PEG-6000, NaCl, and KCl), biotic (Aspergillus niger, Helminthosporium sp., Alternaria sp., chitin, and yeast extract) elicitors, and precursors (progesterone, cholesterol, and squalene). The treatment of KCl, mycelial mass of Helminthosporium sp., and progesterone were highly effective for the production of cardenolides. In the presence of progesterone (200 to 300 mg/l), digitoxin and digoxin accumulation was enhanced by 9.1- and 11.9-folds respectively.

Somatic embryogenesis, pigment accumulation, and synthetic seed production in Digitalis davisiana Heywood.

PubMed

Verma, Sandeep Kumar; Sahin, Gunce; Gurel, Ekrem

2016-04-01

Digitalis davisiana, commonly called Alanya foxglove, from Turkey, is an important medicinal herb as the main source of cardiac glycosides, cardenolides, anthraquinones, etc. It is also known in the Indian Medicine for treatment of wounds and burns. It has ornamental value as well. Overexploitation of D. davisiana has led this species to be declared protected, and thereby encouraged various methods for its propagation. In this study, an optimized and efficient plant tissue culture protocol was established using cotyledonary leaf, hypocotyl and root explants of D. davisiana. Callus tissues were obtained from the cotyledonary leaf, hypocotyl and root segments cultured on Murashige and Skoog's (MS) medium containing different plant growth regulators. The maximum number of somatic embryos were achieved by the MS medium containing 6-benzyladenine (1.0 mg/L BAP) or 2,4-dichlorophenoxy acetic acids (0.1 mg/L 2,4-D), which produced an average of 8.3 ± 1.5 or 5.3 ± 1.5 embryos per cotyledonary leaf, respectively. After 3 wk of culture in MS medium supplemented with 1.0 mg/L 2,4-D, callus showed a clear accumulation of orange pigmentation. Shoot regeneration was remarkably higher (14.3 indirect shoots) in a combination of α-naphthalene acetic acid (0.25 mg/L NAA) plus 3.0 mg/L BAP than 2.0 mg/L zeatin (10.3 ± 0.5 direct shoots) alone. The shoots were successfully rooted on MS medium supplemented with NAA (0.1-1.0 mg/L). In addition, synthetic seeds were produced by encapsulating shoot tips in 4% sodium alginate solution. Maximum conversion frequency of 76.6% was noted from encapsulated shoot tips cultured on 0.25 mg/L NAA with 1.0 mg/L BAP. The encapsulated shoot tips could be stored up to 60 days at 4 °C. Regenerated plantlets of D. davisiana were successfully acclimatized and transferred to soil. This study has demonstrated successful preservation of elite genotypes of D. davisiana.

Clinical presentation at first heart failure hospitalization does not predict recurrent heart failure admission.

PubMed

Kosztin, Annamaria; Costa, Jason; Moss, Arthur J; Biton, Yitschak; Nagy, Vivien Klaudia; Solomon, Scott D; Geller, Laszlo; McNitt, Scott; Polonsky, Bronislava; Merkely, Bela; Kutyifa, Valentina

2017-11-01

There are limited data on whether clinical presentation at first heart failure (HF) hospitalization predicts recurrent HF events. We aimed to assess predictors of recurrent HF hospitalizations in mild HF patients with an implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Data on HF hospitalizations were prospectively collected for patients enrolled in MADIT-CRT. Predictors of recurrent HF hospitalization (HF2) after the first HF hospitalization were assessed using Cox proportional hazards regression models including baseline covariates and clinical presentation or management at first HF hospitalization. There were 193 patients with first HF hospitalization, and 156 patients with recurrent HF events. Recurrent HF rate after the first HF hospitalization was 43% at 1 year, 52% at 2 years, and 55% at 2.5 years. Clinical signs and symptoms, medical treatment, or clinical management of HF at first HF admission was not predictive for HF2. Baseline covariates predicting recurrent HF hospitalization included prior HF hospitalization (HR = 1.59, 95% CI: 1.15-2.20, P = 0.005), digitalis therapy (HR = 1.58, 95% CI: 1.13-2.20, P = 0.008), and left ventricular end-diastolic volume >240 mL (HR = 1.62, 95% CI: 1.17-2.25, P = 0.004). Recurrent HF events are frequent following the first HF hospitalization in patients with implanted implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Neither clinical presentation nor clinical management during first HF admission was predictive of recurrent HF. Prior HF hospitalization, digitalis therapy, and left ventricular end-diastolic volume at enrolment predicted recurrent HF hospitalization, and these covariates could be used as surrogate markers for identifying a high-risk cohort. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Management of pulmonary arterial hypertension associated with congenital heart disease.

PubMed

Togănel, Rodica; Benedek, I; Suteu, Carmen; Blesneac, Cristina

2007-01-01

Congenital heart diseases are the most common congenital malformations and account for about eight cases per 1000 births and are often associated with pulmonary arterial hypertension. Increased shear stress and the excess flow through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to the development of pulmonary vascular disease and an increase in pulmonary vascular resistance. Without surgical repair approximately 30% of patients develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme end of pulmonary arterial hypertension with congenital heart disease. We summarized the current therapeutic options for pulmonary arterial hypertension; conventional treatments including calcium channel blockers, anticoagulation, digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil, ambrisentan. Preliminary data of new therapies are encouraging with disease significantly improved natural history, but there is need for more evidence-based data.

Aminoglycoside Therapy Manager: An Advanced Computer Program for Decision Support for Drug Dosing and Therapeutic Monitoring

PubMed Central

Lenert, Leslie; Lurie, Jon; Coleman, Robert; Klosterman, Heidrun; Blaschke, Terrence

1990-01-01

In this paper, we will describe an advanced drug dosing program, Aminoglycoside Therapy Manager that reasons using Bayesian pharmacokinetic modeling and symbolic modeling of patient status and drug response. Our design is similar to the design of the Digitalis Therapy Advisor program, but extends previous work by incorporating a Bayesian pharmacokinetic model, a “meta-level” analysis of drug concentrations to identify sampling errors and changes in pharmacokinetics, and including the results of the “meta-level” analysis in reasoning for dosing and therapeutic monitoring recommendations. The program is user friendly and runs on low cost general-purpose hardware. Validation studies show that the program is as accurate in predicting future drug concentrations as an expert using commercial Bayesian forecasting software.

[Heart failure in primary care in Italy: analysis of management and needs by general practitioners].

PubMed

Tarantini, Luigi; Cioffi, Giovanni; Pulignano, Giovanni; Del Sindaco, Donatella; Aspromontes, Nadia; Valle, Roberto; Di Tano, Giuseppe; Misuraca, Gianfranco; Clemenza, Francesco; Di Lenarda, Andrea

2010-09-01

Heart failure (HF) is a major clinical problem and a challenge for healthcare systems. Primary care physicians (PCPs) play an important role in the clinical management of HF patients. The aim of the present investigation was to evaluate the behaviors and problems of Italian PCPs in managing patients with HF. Clinical behaviors and perceived obstacles were evaluated through the administration of a modified version of the Euro-HF questionnaire to a nationwide sample of 385 PCPs. Out of 389 042 persons entitled to receive their medical assistance, all PCPs declared to care 9263 patients with HF (prevalence of HF 2.4%, 24 HF patients/PCP). HF was diagnosed either by symptoms only (14% of cases), or by analysis of symptoms plus signs (57%), by combining the evidence of cardiac dysfunction by echocardiography to the assessment of symptoms and signs (12%) or by adding consultation by a cardiologist to the clinical assessment in the PCP office (17%). Forty-two percent of the PCPs participating in the survey had a free access to echocardiography whereas measurement of natriuretic peptide serum levels was freely available to 14% of PCPs. Pharmacological therapy for HF prescribed by the PCPs included in this survey included: diuretics (91%), inhibitors of the renin-angiotensin system (87%), digitalis (34%), beta-blockers (33%), aldosterone antagonists (23%). Drugs considered to potentially leading to major side effects were: digitalis (51%), beta-blockers (48%) and diuretics (47%), much less angiotensin-converting enzyme-inhibitors (17%) and aldosterone antagonists (14%). Consultation with a cardiologist for starting beta-blocker treatment was judged mandatory by 57% of PCPs. Management of HF patients was considered sufficient by 70% of PCPs. Improvement in the access to echocardiography, laboratory data and consultation with a specialist were the priorities indicated by PCPs for optimizing the management of HF patients. PCPs have a suboptimal approach to the diagnostic evaluation of HF patients and to implementation and management of beta-blocker therapy. These behaviors derive from a difficult access to echocardiography, laboratory parameters and consultation with a cardiologist.

PP087. Deep trial secondary analysis: Digoxin immune fab fragment treatment has additional benefits in endogenous digitalis-like factor positive preeclamptic women.

PubMed

Graves, S W; Hopoate-Sitake, M; Johnston, A; Buckalew, V; Lam, G; Mason, L; Adair, D

2012-07-01

A double blinded placebo controlled clinical trial of a commercial digoxin immune Fab fragment (DIF) in preeclamptic (PE) women provided some benefit to treated subjects (1). In that study DIF, relative to placebo, prevented a decline in CrCl and lowered levels of endogenous digitalis-like factor (EDLF) activity as measured by sodium pump inhibition (SPI). However, some PE subjects had undetectable EDLF. The hypothesis tested was that only PE women with measureable EDLF would respond to DIF treatment and analysis of EDLF positive women might reveal treatment effects masked by inclusion of EDLF negative, and hence non-responding, PE women. Accordingly, analyses of DIF effects in EDLF positive PE women were conducted. Patient characteristics and study design have been published (1). In these subanalyses, subjects were considered to be EDLF positive if their plasma inhibited red cell sodium pump mediated Rb uptake. All analyses were redone for the EDLF positive subgroup by Covance Inc as in the original trial. Continuous data were analyzed by ANCOVA. Categorical data were analyzed by Barnard Exact Test. 45 subjects (23 DIF, 22 placebo) had baseline SPI evaluated. Of these 22% had undetectable SPI. EDLF positive PE women showed greater and more significant reductions of SPI in response to DIF at each time point (12, 24, 48 hr treatment) than in the original analysis. Subjects with undetectable EDLF showed no significant change in response to DIF or placebo. For CrCl, EDLF positive PE women showed greater and more significant preservation of CrCl compared with original analyses. Subjects absent EDLF showed deterioration of CrCl with or without DIF. Among EDLF positive PE women DIF treated women had significantly less maternal pulmonary edema (p=0.035) and significantly less intraventricular hemorrhage in their infants (p=0.015). There was the suggestion of reductions in the incidence of other maternal and neonatal abnormalities. These data indicate that EDLF positive PE women are those that responded to DIF and also raise the possibility of extended benefits of DIF treatment in this group. Results support further research in this area. Copyright © 2012. Published by Elsevier B.V.

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs.

PubMed

de Vries, Max; Seppala, Lotta J; Daams, Joost G; van de Glind, Esther M M; Masud, Tahir; van der Velde, Nathalie

2018-04-01

Use of certain medications is recognized as a major and modifiable risk factor for falls. Although the literature on psychotropic drugs is compelling, the literature on cardiovascular drugs as potential fall-risk-increasing drugs is conflicting. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the associations between cardiovascular medications and fall risk in older adults. Design: A systematic review and meta-analysis. Medline, Embase, and PsycINFO. Key search concepts were "fall," "aged," "causality," and "medication." Studies that investigated cardiovascular medications as risk factors for falls in participants ≥60 years old or participants with a mean age of 70 or older were included. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratios (ORs) separately. In total, 131 studies were included in the qualitative synthesis. Meta-analysis using adjusted ORs showed significant results (pooled OR [95% confidence interval]) for loop diuretics, OR 1.36 (1.17, 1.57), and beta-blocking agents, OR 0.88 (0.80, 0.97). Meta-analysis using unadjusted ORs showed significant results for digitalis, OR 1.60 (1.08, 2.36); digoxin, OR 2.06 (1.56, 2.74); and statins, OR 0.80 (0.65, 0.98). Most of the meta-analyses resulted in substantial heterogeneity that mostly did not disappear after stratification for population and setting. In a descriptive synthesis, consistent associations were not observed. Loop diuretics were significantly associated with increased fall risk, whereas beta-blockers were significantly associated with decreased fall risk. Digitalis and digoxin may increase the risk of falling, and statins may reduce it. For the majority of cardiovascular medication groups, outcomes were inconsistent. Furthermore, recent studies indicate that specific drug properties, such as selectivity of beta-blockers, may affect fall risk, and drug-disease interaction also may play a role. Thus, studies addressing these issues are warranted to obtain a better understanding of drug-related falls. Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

The effect of inhibitors of endogenous opioid degradation, bacitracin, bestatin, captopril, and D-phenylalanine, on digoxin-induced arrhythmias in guinea pigs.

PubMed

Rabkin, S W; Redston, M

1989-08-01

The purpose of this study was to investigate the effect of inhibition of endogenous opioid degradation on digitalis-induced arrhythmias, utilizing the inhibitors bacitracin, bestatin, captopril, and D-phenylalanine. Guinea pigs, anesthetized with pentobarbital, 50 mg/kg i.p., and breathing spontaneously received intracerebroventricular (i.c.v.) injection of bacitracin (6.8 mg/kg), bestatin (1 mg/kg), captopril (2 mg/kg), D-phenylalanine (1.2 mg/kg) or the diluent, saline. Digitalis arrhythmias were induced by a 50 micrograms/kg i.v. bolus of digoxin followed by 500 micrograms.kg-1.h-1 i.v. Bacitracin and bestatin, but not captopril or D-phenylalanine, significantly (p less than 0.05) altered the relationship between the digoxin dose and the first occurrence of arrhythmias, i.e., digoxin-induced ventricular arrhythmias became manifest at lower digoxin doses. The mean digoxin dose and ED50s, at which arrhythmias first occurred, were significantly (p less than 0.05) reduced by bacitracin and bestatin. The findings were similar for fatal arrhythmias, although D-phenylalanine appeared to decrease the digoxin dose at the development of fatal arrhythmias. The opioid antagonist naloxone, in a 50 micrograms/kg bolus and 50 micrograms.kg-1.h-1 i.c.v., completely prevented these effects of bacitracin and reduced the effect of bestatin. The relationship to arrhythmias could not be ascribed to an effect on blood pressure, as the blood pressure response to digoxin was the same in bestatin, D-phenylalanine, and control groups. To examine whether systemic administration of an inhibitor of opioid degradation had similar effects, a second protocol was selected with systemic administration of bacitracin because it altered the dose effect relationship after i.c.v. administration and systemic concentrations could be readily attained. Bacitracin, in a 13.5 mg/kg i.v. bolus and 135 mg.kg-1.h-1 i.v., was followed by 100 micrograms/kg digoxin i.v. every 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolation and characterization of novel endogenous digitalis-like factors in the ovary of the giant toad, Bufo marinus.

PubMed

Matsukawa, M; Mukai, T; Akizawa, T; Miyatake, S; Yoshioka, M; Morris, J F; Butler, V P

1998-12-01

We have previously described the structures of four novel unconjugated bufadienolides in the ovary of the toad, Bufo marinus. In this study, we report the separation and characterization of three novel bufadienolide conjugates. These compounds were purified by HPLC, and their structures were determined to be 11alpha, 19-dihydroxytelocinobufagin-3-(12-hydroxydodecanoic acid) ester, 11alpha,19-dihydroxytelocinobufagin-3-(14-hydroxy-7-tetra decenoic acid) ester, and 11alpha, 19-dihydroxytelocinobufagin-3-(14-hydroxytetradecanoic acid) ester on the basis of NMR and MS data. Numerous dicarboxylic acid esters of bufadienolides have previously been described, but the three bufadienolide conjugates described in this report differ from previously described esters in that they contain hydroxylated monocarboxylic acids. The function of these three conjugates is not known but they are, like bufotoxins, potent inhibitors of Na+, K+-ATPase and may play a developmental role in the differentiation of toad oocytes.

Steroidogenesis in plants--Biosynthesis and conversions of progesterone and other pregnane derivatives.

PubMed

Lindemann, Peter

2015-11-01

In plants androstanes, estranes, pregnanes and corticoids have been described. Sometimes 17β-estradiol, androsterone, testosterone or progesterone were summarized as sex hormones. These steroids influence plant development: cell divisions, root and shoot growth, embryo growth, flowering, pollen tube growth and callus proliferation. First reports on the effect of applicated substances and of their endogenous occurrence date from the early twenties of the last century. This caused later on doubts on the identity of the compounds. Best investigated is the effect of progesterone. Main steps of the progesterone biosynthetic pathway have been analyzed in Digitalis. Cholesterol-side-chain-cleavage, pregnenolone and progesterone formation as well as the stereospecific reduction of progesterone are described and the corresponding enzymes are presented. Biosynthesis of androstanes, estranes and corticoids is discussed. Possible progesterone receptors and physiological reactions on progesterone application are reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

A case of reversible dilated cardiomyopathy after alpha-interferon therapy in a patient with renal cell carcinoma.

PubMed

Kuwata, Akiko; Ohashi, Masuo; Sugiyama, Masaya; Ueda, Ryuzo; Dohi, Yasuaki

2002-12-01

A 47-year-old man with renal cell carcinoma underwent nephrectomy, and postoperative chemotherapy was performed with recombinant alpha-interferon. Five years later, he experienced dyspnea during physical exertion. An echocardiogram revealed dilatation and systolic dysfunction of the left ventricle, and thallium-201 myocardial scintigraphy showed diffuse heterogeneous perfusion. We diagnosed congestive heart failure because of cardiomyopathy induced by alpha-interferon therapy. Withdrawal of interferon therapy and the combination of an angiotensin-converting enzyme inhibitor, diuretics, and digitalis improved left ventricular systolic function. Furthermore, myocardial scintigraphy using [123I] beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) or [123 I]metaiodobenzylguanidine (123I-MIBG) revealed normal perfusion after the improvement of congestive heart failure. This is a rare case of interferon-induced cardiomyopathy that resulted in normal myocardial images in 123I-BMIPP and 123I-MIBG scintigrams after withdrawal of interferon therapy.

Plant-derived cardiac glycosides: Role in heart ailments and cancer management.

PubMed

Patel, Seema

2016-12-01

Cardiac glycosides, the cardiotonic steroids such as digitalis have been in use as heart ailment remedy since ages. They manipulate the renin-angiotensin axis to improve cardiac output. However; their safety and efficacy have come under scrutiny in recent times, as poisoning and accidental mortalities have been observed. In order to better understand and exploit them as cardiac ionotropes, studies are being pursued using different cardiac glycosides such as digitoxin, digoxin, ouabain, oleandrin etc. Several cardiac glycosides as peruvoside have shown promise in cancer control, especially ovary cancer and leukemia. Functional variability of these glycosides has revealed that not all cardiac glycosides are alike. Apart from their specific affinity to sodium-potassium ATPase, their therapeutic dosage and behavior in poly-morbidity conditions needs to be considered. This review presents a concise account of the key findings in recent years with adequate elaboration of the mechanisms. This compilation is expected to contribute towards management of cardiac, cancer, even viral ailments. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Pharmacokinetic/pharmacodynamic modeling of cardiac toxicity in human acute overdoses: utility and limitations.

PubMed

Mégarbane, Bruno; Aslani, Arsia Amir; Deye, Nicolas; Baud, Frédéric J

2008-05-01

Hypotension, cardiac failure, QT interval prolongation, dysrhythmias, and conduction disturbances are common complications of overdoses with cardiotoxicants. Pharmacokinetic/pharmacodynamic (PK/PD) relationships are useful to assess diagnosis, prognosis, and treatment efficacy in acute poisonings. To review the utility and limits of PK/PD studies of cardiac toxicity. Discussion of various models, mainly those obtained in digitalis, cyanide, venlafaxine and citalopram poisonings. A sigmoidal E(max) model appears adequate to represent the PK/PD relationships in cardiotoxic poisonings. PK/PD correlations investigate the discrepancies between the time course of the effect magnitude and its evolving concentrations. They may help in understanding the mechanisms of occurrence as well as disappearance of a cardiotoxic effect. When data are sparse, population-based PK/PD modeling using computer-intensive algorithms is helpful to estimate population mean values of PK parameters as well as their individual variability. Further PK/PD studies are needed in medical toxicology to allow understanding of the meaning of blood toxicant concentration in acute poisonings and thus improve management.

The neuropsychiatric ailment of Vincent Van Gogh

PubMed Central

Bhattacharyya, Kalyan B.; Rai, Saurabh

2015-01-01

Vincent Van Gogh is one of the most celebrated creative artists of all time. All his life, he was afflicted by some kind of neurological or psychiatric disorder, which remains a mystery even today. Many historians and his personal physicians believe that he suffered from epilepsy while others felt that he was affected by Ménière's disease. Features such as hypergraphia, atypical sexuality, and viscosity of thinking suggest the possibility of Gastaut-Geschwind phenomenon, a known complication of complex partial seizure. On the contrary, some historians feel that he was forced to sever his right ear in order to get relief from troublesome tinnitus, a complication of Ménière's disease. He was addicted to the liquor absinthe, which is known to lead to xanthopsia, and many authorities argue that this was the reason for his penchant for the deep and bright yellow color in many of his paintings. Others have suggested the possibility of bipolar disorder, sunstroke, acute intermittent porphyria, and digitalis toxicity as well. PMID:25745302

Neonatal hyperthyroidism: neonatal clinical course of two brothers born to a mother with Graves-Basedow disease, before and after total thyroidectomy.

PubMed

Zuppa, A A; Sindico, P; Savarese, I; D'Andrea, V; Fracchiolla, A; Cota, F; Romagnoli, C

2007-04-01

About 1-2% of infants born to mothers with Graves' disease or Hashimoto's thyroiditis develop neonatal hyperthyroidism because of transplacental passage of IgG stimulating TSH receptors (TRAb). To evaluate the effect of maternal total thyroidectomy on neonatal clinical course. We describe two brothers born to a mother with Graves' disease, before and after total thyroidectomy. The first child showed persistent tachycardia, the presence of TRAb and a laboratory pattern of hyperthyroidism. Lugol's solution was started and then propylthiouracil was added. Digitalis, furosemide and diazepam were necessary for treatment of heart failure, hypertension and irritability. On the 70th day of life, hormone serum levels normalized and treatment was interrupted. TRAb normalized by the third month of life. The second infant was born 2 years after the mother underwent total thyroidectomy. In spite of a laboratory pattern of hyperthyroidism and positivity to TRAb, he showed only considerable weight loss, and no therapy was required. TRAb may persist after total thyroidectomy: clinical and instrumental follow-up of the newborn is recommended.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanaka, T.; Kimata, S.; Hirosawa, K.

To determine whether thallium lung uptake images (TLI) can be used as a noninvasive method to estimate any of hemodynamic changes in patients (pts) with acute myocardial infarction (AMI) TLI were evaluated in 23 pts with AMI. All pts underwent multigated blood pool imaging and cardiac catheterization. TLI were estimated by comparing the intensity of T1-201 activity in the lower right lung with maximal myocardial count (thallium lung heart ratio; LHR). Pts with AMI were classified to 3 grades according to LHR. The classifications were hemodynamically significant. The specificity of LHR <0.6 for mPw <18mmHg was 100% (10/10). The specificitymore » of LHR greater than or equal to 0.8 for mPw greater than or equal to 18mmHg was 85% (11/13) and for EF greater than or equal to 30% was 100% (13/13). The pts with LHR 0.8 showed high mortality (4/9) and high morbidity (all survivors were in NYHA class 2-3 and receiving digitalis and diuretics). TLI were easily obtained after routine T1-myocardial imaging, i.e. another 5 minutes imaging yielded clinically useful information for separating high and low-risk groups of pts with AMI.« less

Interaction of digitalis-like compounds with liver uptake transporters NTCP, OATP1B1, and OATP1B3.

PubMed

Gozalpour, Elnaz; Greupink, Rick; Wortelboer, Heleen M; Bilos, Albert; Schreurs, Marieke; Russel, Frans G M; Koenderink, Jan B

2014-06-02

Digitalis-like compounds (DLCs) such as digoxin, digitoxin, and ouabain, also known as cardiac glycosides, are among the oldest pharmacological treatments for heart failure. The compounds have a narrow therapeutic window, while at the same time, DLC pharmacokinetics is prone to drug-drug interactions at the transport level. Hepatic transporters organic anion transporting polypeptide (OATP) 1B1, OATP1B3, and Na(+)-dependent taurocholate co-transporting polypeptide (NTCP) influence the disposition of a variety of drugs by mediating their uptake from blood into hepatocytes. The interaction of digoxin, digitoxin, and ouabain with hepatic uptake transporters has been studied before. However, here, we systematically investigated a much wider range of structurally related DLCs for their capability to inhibit or to be transported by these transporters in order to better understand the relation between the activity and chemical structure of this compound type. We studied the uptake and inhibitory potency of a series of 14 structurally related DLCs in Chinese hamster ovary cells expressing NTCP (CHO-NTCP) and human embryonic kidney cells expressing OATP1B1 and OATP1B3 (HEK-OATP1B1 and HEK-OATP1B3). The inhibitory effect of the DLCs was measured against taurocholic acid (TCA) uptake in CHO-NTCP cells and against uptake of β-estradiol 17-β-d-glucuronide (E217βG) in HEK-OATP1B1 and HEK-OATP1B3 cells. Proscillaridin A was the most effective inhibitor of NTCP-mediated TCA transport (IC50 = 22 μM), whereas digitoxin and digitoxigenin were the most potent inhibitors of OATP1B1 and OAPTP1B3, with IC50 values of 14.2 and 36 μM, respectively. Additionally, we found that the sugar moiety and hydroxyl groups of the DLCs play different roles in their interaction with NTCP, OATP1B1, and OATP1B3. The sugar moiety decreases the inhibition of NTCP and OATP1B3 transport activity, whereas it enhances the inhibitory potency against OATP1B1. Moreover, the hydroxyl group at position 12 reinforces the inhibition of NTCP but decreases the inhibition of OATP1B1 and OATP1B3. To investigate whether DLCs can be translocated, we quantified their uptake in transporter-expressing cells by LC-MS. We demonstrated that convallatoxin, ouabain, dihydroouabain, and ouabagenin are substrates of OATP1B3. No transport was observed for the other compounds in any of the studied transporters. In summary, this work provides a step toward an improved understanding of the interaction of DLCs with three major hepatic uptake transporters. Ultimately, this can be of use in the development of DLCs that are less prone to transporter-mediated drug-drug interactions.

Cardioankle vascular index evaluations revealed that cotreatment of ARB Antihypertension medication with traditional Chinese medicine improved arterial functionality.

PubMed

Xu, Yan; Yan, Hua; Yao, Min J; Ma, Jie; Jia, Jun M; Ruan, Fen X; Yao, Zeng C; Huang, Hua M; Zheng, Jing; Chen, Ting; Lv, Hua; Endler, Alexander M

2013-05-01

Qian Yang He Ji (QYHJ) is a traditional Chinese medicine composed of Digitalis purpurea, Uncaria gambir, Fructus tribuli terrestris, and Ligustrum lucidum. Here, we explored whether combining an antihypertensive angiotensin II receptor blocker (ARB) therapy with QYHJ can improve the arterial functionality of hypertensive patients. One hundred and eight hypertensive patients were randomized into 2 groups; 1 group (n = 53) was treated with ARB and the other group (n = 55) was treated with ARB combined with QYHJ. Each of the 2 groups included 3 subgroups (pure hypertension, hypertension with diabetes, and hypertension with coronary heart disease) and was further divided into patients with and without complications. The cardioankle vascular index and intima-media thickness and pulse pressure were the outcome evaluation parameter. Combined QYHJ and ARB treatment reduced the values of cardioankle vascular index, systolic blood pressure, diastolic blood pressure, and pulse pressure to significantly lower levels than ARB treatment alone did in hypertension patients after 6 months of treatment. ARB improves hypertension, but a combined QYHJ treatment can additionally ameliorate the arterial functionality not only in solely hypertensive patients but also in hypertensive patients with diabetes and coronary heart disease complications. QYHJ coapplication might be a choice to further improve the arterial functionality during an ARB hypertension treatment.

Complete atrioventricular canal.

PubMed

Calabrò, Raffaele; Limongelli, Giuseppe

2006-04-05

Complete atrioventricular canal (CAVC), also referred to as complete atrioventricular septal defect, is characterised by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow. CAVC is an uncommon congenital heart disease, accounting for about 3% of cardiac malformations. Atrioventricular canal occurs in two out of every 10,000 live births. Both sexes are equally affected and a striking association with Down syndrome was found. Depending on the morphology of the superior leaflet of the common atrioventricular valve, 3 types of CAVC have been delineated (type A, B and C, according to Rastelli's classification). CAVC results in a significant interatrial and interventricular systemic-to-pulmonary shunt, thus inducing right ventricular pressure and volume overload and pulmonary hypertension. It becomes symptomatic in infancy due to congestive heart failure and failure to thrive. Diagnosis of CAVC might be suspected from electrocardiographic and chest X-ray findings. Echocardiography confirms it and gives anatomical details. Over time, pulmonary hypertension becomes irreversible, thus precluding the surgical therapy. This is the reason why cardiac catheterisation is not mandatory in infants (less than 6 months) but is indicated in older patients if irreversible pulmonary hypertension is suspected. Medical treatment (digitalis, diuretics, vasodilators) plays a role only as a bridge toward surgery, usually performed between the 3rd and 6th month of life.

Adherence to the European Society of Cardiology guidelines for the treatment of chronic heart failure

NASA Astrophysics Data System (ADS)

Sitepu, A.; Hamdani, K.

2018-03-01

Heart failure is a tremendous health problem with significant morbidity and mortality. The treatment of heart failure should be applied appropriately to improve the successful management of patients. This study aims to evaluate the adherence to European Society of Cardiology (ESC) guidelines for the treatment of chronic heart failure and to determine factors associated with guideline adherence. This study is an observational study comprising 97 patients with chronic heart failure with reduced ejection fraction. The guideline adherence was assessed the by the use of guideline adherence indicator (GAI), which consider GAI-3 or GAI-5, by calculating the proportion of recommended drugs was prescribed divided by a number of drugs indicated according to the ESC guidelines, in the absence of contraindications. The results showed the use of each indicated drugs were angiotensin- converting enzyme inhibitors or angiotensin receptor blockers (78.4%), beta-blockers (61.9%), mineralocorticoid receptor antagonists (61.9%), diuretics (89.7%), and digitalis (26.8%). Furthermore, the predominant categories of GAI-3 and GAI-5 were moderate. This study demonstrates that the adherence to ESC guidelines for the treatment of chronic heart failure still needs to be improved compared to recent studies. Also, age, etiology of heart failure and comorbidity were associated factors that influence the implementation of ESC guidelines.

Optimization measurement of muscle oxygen saturation under isometric studies using FNIRS

NASA Astrophysics Data System (ADS)

Halim, A. A. A.; Laili, M. H.; Salikin, M. S.; Rusop, M.

2018-05-01

Development of functional near infrared spectroscopy (fNIRS) technologies has advanced quantification signal using multiple wavelength and detector to investigate hemodynamic response in human muscle. These non-invasive technologies have been widely used to solve the propagation of light inside the tissues including the absorption, scattering coefficient and to quantify the oxygenation level of haemoglobin and myoglobin in human muscle. The goal of this paper is to optimize the measurement of muscle oxygen saturation during isometric exercise using functional near infrared spectroscopy (fNIRS). The experiment was carried out on 15 sedentary healthy male volunteers. All volunteers are required to perform an isometric exercise at three assessment of muscular fatigue's level on flexor digitalis (FDS) muscle in the human forearm using fNIRS. The slopes of the signals have been highlighted to evaluate the muscle oxygen saturation of regional muscle fatigue. As a result, oxygen saturation slope from 10% exercise showed steeper than the first assessment at 30%-50% of fatigues level. The hemodynamic signal response showed significant value (p=0.04) at all three assessment of muscular fatigue's level which produce a p-value (p<0.05) measured by fNIRS. Thus, this highlighted parameter could be used to estimate fatigue's level of human and could open other possibilities to study muscle performance diagnosis.

[Atrial fibrillation].

PubMed

Spinar, J; Vítovec, J

2003-09-01

Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

[I direttori delle riviste vanno avanti: attenersi ai principi accademici, adottare trasparenza e rispetto e applicare le regole.

PubMed

Teixeira da Silva, Jaime A; Dobránszki, Judit

2018-05-01

Nonostante i cambiamenti in corso nell'ambito delle pubblicazioni scientifiche (STEM - scienza, tecnologia, ingegneria e medicina), è indubbio che i direttori delle riviste restano i più importanti custodi del processo editoriale. In questo articolo vengono analizzati i motivi per cui i direttori delle riviste devono continuare ad attenersi ai principi editoriali fondamentali e a utilizzare le nuove tecnologie digitali solo per dare forza al contenuto, ma non per sostituirlo nella sua qualità. Per raggiungere questo obiettivo, in un'epoca caratterizzata da controlli ed equilibri, i direttori delle riviste devono essere attentamente sorvegliati e ritenuti responsabili tanto quanto gli autori che essi stessi valutano. Qualunque scorciatoia potrebbe avere conseguenze negative e inaspettate per quella rivista che non si attenesse a tali regole, che vedrebbe intaccata la propria reputazione e che dovrebbe faticare per recuperare la fiducia dei propri lettori. Quindi, a rischio di sembrare scontati, è meglio prevenire il danno alla reputazione piuttosto che curarlo. L'unico modo per evitarlo è che i direttori delle riviste si adattino a un crescente movimento sempre più critico, che richiede maggiore trasparenza e responsabilità da parte di chi contribuisce a costruire la base delle conoscenze scientifiche e dalla società, specialmente laddove la ricerca è finanziata pubblicamente.

Digoxin use and digoxin toxicity in the post-DIG trial era.

PubMed

Hussain, Zainal; Swindle, Jason; Hauptman, Paul J

2006-06-01

The advent of medical therapies for congestive heart failure that have proven survival benefits, specifically angiotensin-converting enzyme (ACE) inhibitors, beta-adrenergic antagonists, and the aldosterone antagonists, have called into question the use of digoxin for patients with normal sinus rhythm, left ventricular dysfunction, and symptomatic heart failure. This issue appears to have been heightened after the publication of the results of the Digitalis Investigation Group (DIG) Trial in 1997 that did not demonstrate a statistically significant impact of digoxin on mortality. We used data from a large heart failure registry to examine digoxin use at the time of hospital admission for heart failure, a surveillance system for recording toxic drug exposures to describe patterns in digoxin toxicity and industry estimates for the use of digoxin antibody. Digoxin use has decreased significantly from 31.4% in late 2001 to 23.5% in late 2004 (P < .00001) independent of patient age, gender, or baseline creatinine. Conversely, the number of toxic or potentially toxic exposures to digoxin requiring hospitalization has not decreased. Digoxin use is decreasing but there has not been a similar decline in cases of toxicity. Further analyses are required to delineate the reasons underlying these trends and the appropriateness of prescribing practices for both digoxin and its antidote.

Colored floaters as a manifestation of digoxin toxicity.

PubMed

Shi, Lynn; Sun, Linus D; Odel, Jeffrey G

2018-06-01

Since its report in one patient more than 70 years ago, digitalis-induced colored muscae volitantes have not surfaced again in the literature. We report here a case of digoxin induced colored floaters. An 89-year-old man on 0.25 mg digoxin daily developed visual hallucinations and colored floaters. He had floaters in the past but now they were in various colors including yellow, green, blue and red, though predominantly in yellow. These "weirdly" shaped little particles wiggled around as if in a viscous solution and casted shadows in his vision. He also saw geometric shapes, spirals, and cross hatch patterns of various colors that moved and undulated, especially on wallpaper. Ophthalmic examination revealed reduced visual acuity, poor color vision especially in his left eye, along with central depression on Amsler grid and Humphrey visual field in his left eye. Discontinuation of digoxin resulted in complete resolution of his visual symptoms. On subsequent ophthalmic examination, the patient's visual acuity, field testing and color vision improved and he had normal Amsler grid test results. Colored floaters may occur in patients taking cardiac glycosides but this association has not been explored. Unlike optical illusions and visual hallucinations, floaters are entoptic phenomena casting a physical shadow upon the retina and their coloring likely arise from retinal dysfunction. Colored floaters may be a more common visual phenomenon than realized.

Studies on cerebral protection of digoxin against ischemia/reperfusion injury in mice.

PubMed

Kaur, Shaminder; Rehni, Ashish K; Singh, Nirmal; Jaggi, Amteshwar S

2009-04-01

The present study was designed to investigate the possible neuroprotective effect of digoxin induced pharmacological preconditioning (PP) and its probable mechanism. Bilateral carotid artery occlusion (BCAO) of 17 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion (I/R) induced cerebral injury in male swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using elevated plus maze test. Degree of motor incoordination was evaluated using inclined beam walking test, rota rod test and lateral push test. Digoxin (0.08 mg/kg, i.p.) was administered 24 h before surgery in a separate group of animals to induce PP. BCAO followed by reperfusion, produced significant rise in cerebral infarct size along with impairment of memory and motor coordination. Digoxin treatment produced a significant decrease in cerebral infarct size and reversal of I/R induced impairment of memory and motor incoordination. Digoxin induced neuroprotective effect was abolished significantly by verapamil (15 mg/kg, i.p.), a L-type calcium channel blocker, ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker and 3,4-dichlorobenzamil (Na(+)/Ca(2+) exchanger inhibitor). These findings indicate that digoxin preconditioning exerts a marked neuroprotective effect on the ischemic brain, which is possibly linked to digitalis induced increase in intracellular calcium levels eventually leading to the activation of calcium sensitive signal transduction cascades.

[Cases of acute poisoning admitted to a medical intensive care unit].

PubMed

Viertel, A; Weidmann, E; Brodt, H R

2001-10-19

Because of the paucity of information on the epidemiology of acute poisoning requiring intensive medical care, all such patients treated on the medical intensive care unit of the university hospital in Frankfurt am Main, Germany, between January 1993 and December 1999, were retrospectively evaluated. Of the total of 6211 patients, 147 (80 women, 67 men, mean age 41 years, 2,3 %) were treated for acute intoxication in the intensive care unit. Reasons for admission to the intensive care unit were the need for ventilator treatment or intensive monitoring of vital functions. 52 % of the patients (n = 76) had attempted suicide, most of them using anti-depressive drugs (n = 19), paracetamol (n = 16), or benzodiazepines (n = 9). Two patients (2,6 %) died. 48 % of the patients (n = 71) were admitted because of accidental poisoning. Leading toxic agents in this group were heroin (n = 19), alcohol (n = 18) and digitalis (n = 12). 11 patients had taken herbicides, animal poisons or chemicals used at work or for house cleaning. In this cohort, three i. v. drug abusers (4,2 %) had died. Depending on the agents used, a variety of treatments (charcoal, antidots, extracorporal therapy) were undertaken. Due to excellent care in the prehospital phase and in the emergency room the number of patients requiring treatment on the intensive care unit was rather low. The mortality was in the range of other reports.

Heart Failure in Patients with Chronic Kidney Disease: A Systematic Integrative Review

PubMed Central

Segall, Liviu; Nistor, Ionut; Covic, Adrian

2014-01-01

Introduction. Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is strongly associated with mortality in these patients. However, the treatment of HF in this population is largely unclear. Study Design. We conducted a systematic integrative review of the literature to assess the current evidence of HF treatment in CKD patients, searching electronic databases in April 2014. Synthesis used narrative methods. Setting and Population. We focused on adults with a primary diagnosis of CKD and HF. Selection Criteria for Studies. We included studies of any design, quantitative or qualitative. Interventions. HF treatment was defined as any formal means taken to improve the symptoms of HF and/or the heart structure and function abnormalities. Outcomes. Measures of all kinds were considered of interest. Results. Of 1,439 results returned by database searches, 79 articles met inclusion criteria. A further 23 relevant articles were identified by hand searching. Conclusions. Control of fluid overload, the use of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and optimization of dialysis appear to be the most important methods to treat HF in CKD and ESRD patients. Aldosterone antagonists and digitalis glycosides may additionally be considered; however, their use is associated with significant risks. The role of anemia correction, control of CKD-mineral and bone disorder, and cardiac resynchronization therapy are also discussed. PMID:24959595

Herbs in dentistry.

PubMed

Taheri, Jamile B; Azimi, Somayyeh; Rafieian, Nasrin; Zanjani, Hosein Akhavan

2011-12-01

Herbs have been used for centuries to prevent and control disease. Herbal extracts are effective because they interact with specific chemical receptors within the body and are in a pharmacodynamic sense, drugs themselves. By using herbal medicines, patients have averted the many side effects that generally come with traditional medicines, but this does not mean that side effects do not occur. Only knowledgeable practitioners can prescribe the right herb and its proper dosage. Herbal medicines had been considered in every culture, however, pharmaceutical companies overturned this type of thinking. Now, pharmaceuticals are called traditional and herbs are libeled as the 'alternative'. The biggest challenge and problem is lack of information about the effect of herbs in oral tissues, mechanism of effect, and side effects. Several popular conventional drugs on the market are derived from herbs. These include aspirin (from white willow bark), digitalis (from foxglove), and sudafed (modelled after a component in the plant ephedra). Herbal products can vary in their potency. Therefore, care must be taken in selecting herbs, even so, herbal medicines have dramatically fewer side effects and are safer to use than conventional medications. The herbs described in this article are Bloodroot, Caraway, Chamomile, Echinacea, Myrrh, Peppermint, Rosemary, Sage, Thyme, Aloe Vera, Propolis, and a summary of other herbs that are useful in dentistry. Herbs may be good alternatives to current treatments for oral health problems but it is clear that we need more research. © 2011 FDI World Dental Federation.

Fatal cardiac glycoside poisoning due to mistaking foxglove for comfrey.

PubMed

Wu, I-Lin; Yu, Jiun-Hao; Lin, Chih-Chuan; Seak, Chen-June; Olson, Kent R; Chen, Hsien-Yi

2017-08-01

Accidental ingestion of foxglove (Digitalis purpurea) can cause significant cardiac toxicity. We report a patient who ingested foxglove mistaking it for comfrey and developed refractory ventricular arrhythmias. The patient died despite treatment with digoxin-specific antibody fragments (DSFab) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 55-year-old woman presented to the emergency department with nausea, vomiting and generalized weakness eight hours after drinking "comfrey" tea. She had bradycardia (54 beats/min) and hyperkalemia (7.6 mEq/L). Electrocardiogram revealed a first-degree atrioventricular conduction block with premature atrial contractions, followed by polymorphic ventricular tachycardia three hours after arrival. A serum digoxin level was 151.2 ng/mL. The patient developed ventricular fibrillation while waiting for Digibind infusion. Resuscitation was performed and an emergent VA-ECMO was set up. A total of eight vials of Digibind were given over the next 16 hours. She temporarily regained consciousness, but remained hemodynamically unstable and subsequently developed lower limb ischemia and multiple organ failure, and she expired on hospital day seven. A botanist confirmed that the plant was foxglove. The diagnosis of cardiac glycoside plant poisoning can be difficult in the absence of an accurate exposure history. In facilities where DSFab is unavailable or insufficient, early VA-ECMO might be considered in severely cardiotoxic patients unresponsive to conventional therapy.

Gradual disintegration of the floral symmetry gene network is implicated in the evolution of a wind-pollination syndrome

PubMed Central

Preston, Jill C.; Martinez, Ciera C.; Hileman, Lena C.

2011-01-01

Angiosperms exhibit staggering diversity in floral form, and evolution of floral morphology is often correlated with changes in pollination syndrome. The showy, bilaterally symmetrical flowers of the model species Antirrhinum majus (Plantaginaceae) are highly specialized for bee pollination. In A. majus, CYCLOIDEA (CYC), DICHOTOMA (DICH), RADIALIS (RAD), and DIVARICATA (DIV) specify the development of floral bilateral symmetry. However, it is unclear to what extent evolution of these genes has resulted in flower morphological divergence among closely related members of Plantaginaceae differing in pollination syndrome. We compared floral symmetry genes from insect-pollinated Digitalis purpurea, which has bilaterally symmetrical flowers, with those from closely related Aragoa abietina and wind-pollinated Plantago major, both of which have radially symmetrical flowers. We demonstrate that Plantago, but not Aragoa, species have lost a dorsally expressed CYC-like gene and downstream targets RAD and DIV. Furthermore, the single P. major CYC-like gene is expressed across all regions of the flower, similar to expression of its ortholog in closely related Veronica serpyllifolia. We propose that changes in the expression of duplicated CYC-like genes led to the evolution of radial flower symmetry in Aragoa/Plantago, and that further disintegration of the symmetry gene pathway resulted in the wind-pollination syndrome of Plantago. This model underscores the potential importance of gene loss in the evolution of ecologically important traits. PMID:21282634

Traditional production, consumption and storage of Kunu--a non alcoholic cereal beverage.

PubMed

Gaffa, T; Jideani, I A; Nkama, I

2002-01-01

A survey of the production, consumption and storage of Kunu was carried out. Some of the information included consumption rate, processing techniques and equipment, producer's status and grains used. About 73% consume Kunu daily, 26% occasionally; 1% know it is produced but may or may not be consuming it. Millet (Pennisetum typhoideum), sorghum (Sorghum vulgare), maize (Zea mays), rice (Oryza sativa) and acha (Digitalis exilis) were used in its production in decreasing order of preference. The grains were used singly or combined; sorghum/millet was the most common combination in a ratio of 1:2 (w/w). Steeping was done in ordinary water for 12-72 h, depending on the grain type, in local clay pots, plastic buckets, calabashes or basins or 5-7 h in warm water (60-70 degrees C). The grains were dry or wet milled with or without spices such as ginger, red pepper, black pepper, clove and garlic. Other ingredients introduced included: sweet potatoes, malted rice, malted sorghum and Cadaba farinosa crude extract. Both dry and wet milling was done with grinding mills, mill stones or mortar and pestle, depending on locality. The product was then cooked into a thin free flowing gruel. The various types of kunu were: Kunun zaki, Kunun gyada, Kunun akamu, Kunun tsamiya, Kunun baule, Kunun jiko, Amshau and Kunun gayamba. Kunun zaki was the most commonly consumed. Production and consumption cut across all social classes of the society.

DIRECT AND INDIRECT BIOLOGICAL EFFECTS OF RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hobitz, H.

1961-01-01

The primary physical processes, ionization and excitation, induced by radiation in biological materials are discussed. Their effects in causing reduction, decarboxylation, and depolymerization in proteins and deoxyribonucleic acid of the cell nucleus are examined. The action of radiation doses of 100,000- 600,000 r on pollen of Digitalis purpurea maintained at room temperature and at approximates 190 deg C showed that biological activity was destroyed by doses >200,000 r at room temperature, but at approximates 190 deg the pollen retained some activity even after the highest dose. A similar effect was seen with Bacterium cadaveris cells, about 0.5% of which survivedmore » 50000 r given at l8O deg whereas no cells survived 20000 r given at 4 deg . The presence of 1% cysteamine at the higher temperature increased survival 20-fold. Cytochrome c showed markedly different responses to radiation in dry form as compared with aqueous solution. The anhydrous enzyme showed a linear decline in log activity with radiation dose but in aqueous solution the activity declined more slowly at higher doses. The radiation dose to-produce 50% inactivation was 4 x 10/sup 7/ r in dry form and 6 x 10/sup 5/ r in solution, a 67-fold difference. The results suggest that diffusion of the free radicals (H: or OH:) produced in the primary process is considerably hindered at low temperature and by the absence of water. (H.H.D.)« less

CvADH1, a member of short-chain alcohol dehydrogenase family, is inducible by gibberellin and sucrose in developing watermelon seeds.

PubMed

Kim, Joonyul; Kang, Hong-Gyu; Jun, Sung-Hoon; Lee, Jinwon; Yim, Jieun; An, Gynheung

2003-01-01

To understand the molecular mechanisms that control seed formation, we selected a seed-preferential gene (CvADH1) from the ESTs of developing watermelon seeds. RNA blot analysis and in situ localization showed that CvADH1 was preferentially expressed in the nucellar tissue. The CvADH1 protein shared about 50% homology with short-chain alcohol dehydrogenase including ABA2 in Arabidopsis thaliana, stem secoisolariciresinol dehydrogenase in Forsythia intermedia, and 3beta-hydroxysterol dehydrogenase in Digitalis lanata. We investigated gene-expression levels in seeds from both normally pollinated fruits and those made parthenocarpic via N-(2-chloro-4-pyridyl)-N'-phenylurea treatment, the latter of which lack zygotic tissues. Whereas the transcripts of CvADH1 rapidly started to accumulate from about the pre-heart stage in normal seeds, they were not detectable in the parthenocarpic seeds. Treating the parthenogenic fruit with GA(3) strongly induced gene expression, up to the level accumulated in pollinated seeds. These results suggest that the CvADH1 gene is induced in maternal tissues by signals made in the zygotic tissues, and that gibberellin might be one of those signals. We also observed that CvADH1 expression was induced by sucrose in the parthenocarpic seeds. Therefore, we propose that the CvADH1 gene is inducible by gibberellin, and that sucrose plays an important role in the maternal tissues of watermelon during early seed development.

Metal-binding proteins as metal pollution indicators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hennig, H.F.

1986-03-01

The fact that metal-binding proteins are a consequence of elevated metal concentration in organisms is well known. What has been overlooked is that the presence of these proteins provides a unique opportunity to reformulate the criteria of metal pollution. The detoxification effect of metal-binding proteins in animals from polluted areas has been cited, but there have been only very few studies relating metal-binding proteins to pollution. This lack is due partly to the design of most experiments, which were aimed at isolation of metal-binding proteins and hence were of too short duration to allow for correlation to adverse physiological effectsmore » on the organism. In this study metal-binding proteins were isolated and characterized from five different marine animals (rock lobster, Jasus lalandii; hermit crab, Diogenes brevirostris; sandshrimp, Palaemon pacificus; black mussel, Choromytilus meridionalis; and limpet, Patella granularis). These animals were kept under identical metal-enriched conditions, hence eliminating differences in method and seasons. The study animals belonged to different phyla; varied in size, mass, age, behavior, food requirements and life stages; and accumulated metals at different rates. It is possible to link unseasonal moulting in crustacea, a known physiological effect due to a metal-enriched environment, to the production of the metal-binding protein without evidence of obvious metal body burden. Thus a new concept of pollution is defined: the presence of metal-binding proteins confirms toxic metal pollution. This concept was then tested under field conditions in the whelk Bullia digitalis and in metal-enriched grass.« less

Na/K ATPase inhibition by digitalis-like factors in neonates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bottorff, M.B.; Songu-Mize, E.; Hoon, T.J.

1986-03-01

At the authors institution, 48% of neonates < 1 month of age had false-positive digoxin immunoassay determinations while not receiving digoxin, presumably due to an endogenous digoxin-like immunoreactive substance (DLIS) in the plasma. Plasma from 3 neonates positive for DLIS by fluorescence polarization immunoassay (FPIA) was evaluated for inhibitory activity on human red blood cell (RBC) Na/K ATPase. Neonatal plasma aliquots containing DLIS concentrations (conc) of 0.24, 0.37, 0.43, 0.49 and 0.61 ng/ml (3.07 - 7.81 x 10/sup -10/M) were incubated with human RBC and /sup 86/Rb in order to measure /sup 86/Rb uptake inhibition with respect to DLIS negativemore » neonatal plasma. /sup 86/Rb uptake inhibition by digoxin-spiked human serum (1.07 x 10/sup -10/ - 4.57 x 10/sup -6/M) was also measured. Percent inhibition vs. log molar conc plots for DLIS and digoxin were compared. DLIS inhibited Na/K ATPase in a linear fashion over the range studied. Comparing the linear portions of the conc-inhibition curves for digoxin and DLIS, the molar conc of digoxin producing 40% inhibition of /sup 86/Rb uptake is 333 times greater than the molar conc of DLIS producing similar inhibition. Therefore, DLIS in neonatal serum as measured by FPIA has approximately 300 times greater inhibitory activity than digoxin. The presence of circulating DLIS may reflect an adaptive or maladaptive response to some, as yet unknown, process early in life.« less

Dronedarone: current evidence for its safety and efficacy in the management of atrial fibrillation.

PubMed

Schweizer, Patrick A; Becker, Rüdiger; Katus, Hugo A; Thomas, Dierk

2011-01-06

Atrial fibrillation (AF) is the most common sustained arrhythmia. Management of AF includes rate control, rhythm control if necessary, prevention of thromboembolic events, and treatment of the underlying disease. Rate control is usually achieved by pharmacological suppression of calcium currents or by applying β-blockers or digitalis compounds. In contrast, the number of compounds available for rhythm control is still limited. Class Ic agents increase mortality in patients with structural heart disease, and amiodarone harbors an extensive side effect profile despite its efficacy in maintaining sinus rhythm. Furthermore, rhythm control by these compounds has not been shown to reduce patient mortality. Dronedarone is a new anti-arrhythmic drug that has been developed to provide rhythm and rate control in AF patients with fewer side effects compared with amiodarone. This review primarily focuses on clinical trials evaluating efficacy and safety of the novel drug. Conclusions from these studies are critically reviewed, and recommendations for clinical practice are discussed. Dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation (ATHENA trial). However, dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm (DIONYSOS trial) and is contraindicated in severe or deteriorating heart failure (ANDROMEDA trial). In summary, dronedarone represents a valuable addition to the limited spectrum of antiarrhythmic drugs and is currently recommended in patients with paroxysmal and persistent AF to achieve rate and rhythm control, excluding cases of severe or unstable congestive heart failure.

Cohort study of risk factors for breast cancer in post menopausal women.

PubMed

Hartz, Arthur J; He, Tao

2013-01-01

The present study assessed more than 800 potential risk factors to identify new predictors of breast cancer and compare the independence and relative importance of established risk factors. Data were collected by the Women's Health Initiative and included 147,202 women ages 50 to 79 who were enrolled from 1993 to 1998 and followed for 8 years. Analyses performed in 2011 and 2012 used the Cox proportional hazard regression to test the association between more than 800 baseline risk factors and incident breast cancer. Baseline factors independently associated with subsequent breast cancer at the p<0.001 level (in decreasing order of statistical significance) were breast aspiration, family history, age, weight, history of breast biopsies, estrogen and progestin use, fewer live births, greater age at menopause, history of thyroid cancer, breast tenderness, digitalis use, alcohol intake, white race, not restless, no vaginal dryness, relative with prostate cancer, colon polyps, smoking, no breast augmentation, and no osteoporosis. Risk factors previously reported that were not independently associated with breast cancer in the present study included socioeconomic status, months of breast feeding, age at first birth, adiposity measures, adult weight gain, timing of initiation of hormone therapy, and several dietary, psychological, and exercise variables. Family history was not found to alter the risk associated with other factors. These results suggest that some risk factors not commonly studied may be important for breast cancer and some frequently cited risk factors may be relatively unimportant or secondary.

Heart failure, chronic diuretic use, and increase in mortality and hospitalization: an observational study using propensity score methods

PubMed Central

Ahmed, Ali; Husain, Ahsan; Love, Thomas E.; Gambassi, Giovanni; Dell'Italia, Louis J.; Francis, Gary S.; Gheorghiade, Mihai; Allman, Richard M.; Meleth, Sreelatha; Bourge, Robert C.

2008-01-01

Aims Non-potassium-sparing diuretics are commonly used in heart failure (HF). They activate the neurohormonal system, and are potentially harmful. Yet, the long-term effects of chronic diuretic use in HF are largely unknown. We retrospectively analysed the Digitalis Investigation Group (DIG) data to determine the effects of diuretics on HF outcomes. Methods and results Propensity scores for diuretic use were calculated for each of the 7788 DIG participants using a non-parsimonious multivariable logistic regression model, and were used to match 1391 (81%) no-diuretic patients with 1391 diuretic patients. Effects of diuretics on mortality and hospitalization at 40 months of median follow-up were assessed using matched Cox regression models. All-cause mortality was 21% for no-diuretic patients and 29% for diuretic patients [hazard ratio (HR) 1.31; 95% confidence interval (CI) 1.11−1.55; P = 0.002]. HF hospitalizations occurred in 18% of no-diuretic patients and 23% of diuretic patients (HR 1.37; 95% CI 1.13−1.65; P = 0.001). Conclusion Chronic diuretic use was associated with increased long-term mortality and hospitalizations in a wide spectrum of ambulatory chronic systolic and diastolic HF patients. The findings of the current study challenge the wisdom of routine chronic use of diuretics in HF patients who are asymptomatic or minimally symptomatic without fluid retention, and are on complete neurohormonal blockade. These findings, based on a non-randomized design, need to be further studied in randomized trials. PMID:16709595

A possible molecular mechanism of the action of digitalis: ouabain action on calcium binding to sites associated with a purified sodium-potassium-activated adenosine triphosphatase from kidney.

PubMed

Gervais, A; Lane, L K; Anner, B M; Lindenmayer, G E; Schwartz, A

1977-01-01

Calcium binding at 0 degrees C to a purified sheep kidney Na+,K+-ATPase was described by linear Scatchard plots. Binding at saturating free calcium was 65-80 nmol/mg of protein, or 30-40 mol of calcium/mol of enzyme. Aqueous emulsions of lipids extracted from Na+,K+-ATPase yielded dissociation constants and maximum calcium-binding values that were similar to those for native Na+,K+-ATPase. Phospholipase A treatment markedly reduced calcium binding. Pretreatment of native Na+,K+-ATPase with ouabain increased the dissociation constant for calcium binding from 131 +/- 7 to 192 +/- 7 muM without altering maximum calcium binding. Ouabain pretreatment did not affect calcium binding to extracted phospholipids, ouabain-insensitive ATPases, or heat denatured Na+,K+-ATPase, Na+ and K+ (5-20 mM) increased the dissociation constants for calcium, which suggests competition between the monovalent cations and calcium for the binding sites. At higher concentrations of monovalent cations, ouabain increased the apparent affinity of binding sites for calcium. Extrapolation to physiological cation concentrations revealed that the ouabain-induced increase in apparent affinity for calcium may be as much as 2- to 3-fold. These results suggest: (1) calcium binds to phospholipids associated with Na+,K+-ATPase; (2) ouabain interaction with Na+,K+-ATPase induces a perturbation that is transmitted to adjacent phospholipids, altering their affinity for calcium; and (3) at physiological concentrations of Na+ or K+, or both, ouabain interaction with Na+,K+-ATPase may lead to an increased pool of membrane-bound calcium.

Look what I found! Poison hunting on eBay.

PubMed

Cantrell, F Lee

2005-01-01

Many substances deemed too dangerous for commercial use are still available to the general public. The purchase of these substances may potentially place members of the general public at risk for serious poisonings. This study was designed to document the large variety of dangerous poisons readily available on a popular online auction Web site. Methods. Over a 10-month period, the online auction Web site eBays was searched daily using the terms "poison" and "contents." Product name, active ingredients, what form the product is in, amount in container, and relative toxicity rating (Clinical Toxicology of Commercial Products, Gosselin, et al.) were recorded. If available, pictures of the products were saved. One hundred twenty-one individual products were identified. Fifty-five were in solid/tablet form, 37 were powders, and 29 were liquids. Product containers were full for 56 items and partially full for 65. Twenty-four products contained ingredients rated as "supertoxic" and included strychnine (10), arsenic trioxide (8), cyanide (2) and nicotine, pilocarpine, phosphorus, powdered conium maculatum (1 each). Sixty-three products contained "extremely toxic" ingredients including thallium, picrotoxin, soluble barium, antimony, mercury, arsenates, podophyllin, fluoride, zinc phosphide, atropine, scopolamine, and plant extracts of gelsemium, aconite, larkspur, and croton. Twenty-one products contained "very toxic" ingredients including lead, copper, camphor, caffeine, theobromine, creosote, pyrogallic acid, sparteine, quinine, lindane, warfarin, phenol, and digitalis. The remaining 13 were "moderately-slightly toxic." While the viability of the labeled ingredients could not be verified, the transportation, handling, and potential utilization of these dangerous poisons by the general public could result in serious poisonings.

Medicinal agents in the metabolic syndrome.

PubMed

Baños, G; Pérez-Torres, I; El Hafidi, M

2008-10-01

The metabolic syndrome (MS) has become a worldwide health problem. It is difficult for patients to follow a diet/exercise regime that would improve their symptoms, therefore the investigation of agents that may deal with its more serious aspects is an important medical field for research. The cardiovascular consequences associated with the syndrome and some of the therapeutic approaches are discussed. The different agents can be divided into several groups: Inorganic/ organic: Zinc complexes with garlic components as insulino-mimetics; Selenium as antioxidant; Copper, Zinc and Manganese as microcomponents of antioxidant enzymes. Organic: Natural or Synthetic: Glycine is effective in lowering blood pressure, TBARS, intra-abdominal fat tissue and triglycerides in sucrose-fed rats. Pharmaceutical products: Fibrates, Lipid-lowering drugs. Antidiabetics. Anti-gout agents. On the other hand there are natural products such as those of animal origin: Sex hormones (also synthetic) used in the problems of menopause and hypoandrogenism frequently found in the MS, antioxidant Omega-3-oils (fish oils) or Vegetal: for example Digitalis pupurea, century-old cardiovascular medication as well as Magnolia officinalis; Spirulina maxima with beneficial effects as antioxidant and lipid-lowering agent, among others. Prickly Pear Cacti. (Opuntia Ficus- Indica Cochlospermum vitifolium (Willd.) Spreng) whose many properties against diabetes and hypercholesterolemia have been empirically known for many years. Perezone (from Perezia plants, a.k.a. Peonia) described as an antiplatelet aggregating agent. The mixed elements in the Mediterranean diet: Fish, salads (peppers, tomatoes), olive oil, garlic, red wine which combines fish oils, garlic and avocado as well as antioxidants from the rest of its components.

Gender aspects in heart failure. Pathophysiology and medical therapy.

PubMed

Regitz-Zagrosek, V; Lehmkuhl, E; Lehmkuhl, H B; Hetzer, R

2004-09-01

Gender differences in the syndrome of heart failure (HF) occur in etiology and pathophysiology and lead to differences in the clinical presentation and course of the syndrome. In addition, gender specific treatment responses and gender associated differences in the behavior of treating physicians are found. Hypertension and diabetes play a major role as causes of HF in women and both interact in their pathophysiology with the renin angiotensin system (RAS). Modulation of the RAS by estrogens explains specific differences between pre- and post-menopausal women and men. Myocardial growth processes and myocardial calcium handling are differentially regulated in female and male myocytes. Myocardial remodeling with age and as a consequence of mechanical load differs in women and men. For yet unknown reasons, HF with preserved systolic function seems to be more frequent in women than in men and the clinical course of systolic HF is different in both genders. Medical therapy in heart failure has usually not been specified according to gender and gender specific analysis has been neglected in most large survival trials. Only a post-hoc analysis of gender differences led to the recognition of increased mortality with digitalis therapy in women. Single studies on angiotensin converting enzyme inhibitors (ACEI) or beta-receptor blockers did not reach significant end points in women whereas meta-analyses showed overall positive effects. Side effects of ACEI are more common and pharmacokinetics of beta-blockers are different in women. Angiotensin receptor blockers (ARB) are equally well tolerated in women and men. RAS inhibition may be particularly advantageous in postmenopausal women in whom the natural modulation of the RAS by estrogens is lost.

Epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge in Japan: An exploratory descriptive study using a nationwide claims database.

PubMed

Okumura, Yasuyuki; Sakata, Nobuo; Takahashi, Kunihiko; Nishi, Daisuke; Tachimori, Hisateru

2017-08-01

Little is known about the nationwide epidemiology of the annual rate, causative substance, and clinical course of overdose-related admission. We aimed to describe the epidemiology of overdose episodes from the period prior to hospitalization for drug poisoning until discharge to home. We assessed all cases of admission due to overdose (21,663 episodes) in Japan from October 2012 through September 2013 using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. The annual rate of overdose admission was 17.0 per 100,000 population. Women exhibited two peaks in admission rates at 19-34 years (40.9 per 100,000) and ≥75 years (27.8 per 100,000). Men exhibited one peak in the admission rate at ≥75 years (23.7 per 100,000). Within 90 days prior to overdose, ≥60% and ≥9% of patients aged 19-49 years received a prescription for benzodiazepines and barbiturates, respectively. In addition, 59% of patients aged ≥75 years received a prescription for benzodiazepines prior to overdose, 47% had a history of congestive heart failure, and 24% had a diagnosis of poisoning by cardiovascular drugs. The proportion of patients with recent psychiatric treatments decreased with age (65.1% in those aged 35-49 years and 13.9% in those aged ≥75 years). The findings emphasize the need for overdose prevention programs that focus on psychiatric patients aged 19-49 years who are prescribed benzodiazepines or barbiturates and on non-psychiatric patients aged ≥75 years who are prescribed benzodiazepines or digitalis. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Changes in Implantation Patterns and Therapy Rates of Implantable Cardioverter Defibrillators over Time in Ischemic and Dilated Cardiomyopathy Patients.

PubMed

Vandenberk, Bert; Garweg, Christophe; Voros, Gabor; Floré, Vincent; Marynissen, Thomas; Sticherling, Christian; Zabel, Markus; Ector, Joris; Willems, Rik

2016-08-01

Clinical guidelines on implantable cardioverter defibrillator (ICD) therapy changed significantly in the last decades with potential inherent effects on therapy efficacy. We aimed to study therapy rates in time and the association between therapies and mortality. All patients receiving an ICD, primary and secondary prevention, were included in a single-center retrospective registry. Information on first appropriate and inappropriate therapies was documented. Dates of implant were divided in P1: 1996-2001, P2: 2002-2008, and P3: 2009-2014. A total of 727 patients, 84.9% male-66.4% ischemic cardiomyopathy (ICM)-56% primary prevention-mean follow-up 5.2 ± 4.1 years, were included. There was a shift from secondary to primary prevention indications, from ischemic to non-ICM, and from single chamber to cardiac resynchronization therapy defibrillator devices. The annual 1- and 3-year appropriate shock (AS) rate declined from 29.4% and 15.1% in P1, over 13.3% and 9.2% in P2 to 7.8% and 5.7% in P3 (log-rank P < 0.001), while inappropriate shock (IAS) rates remained unchanged (log-rank P = 0.635). After multivariate regression analysis a higher age at implant, lower left ventricular ejection fraction, history of stroke, diabetes mellitus, intake of loop diuretics or digitalis, higher creatinine, and longer QTc were independent predictors of mortality. These changes in clinical practice with a shift to primary prevention and rise in non-ICM implants caused a significant decrease in AS incidence, while IAS remained stable. Receiving AS or IAS was not an independent predictor of mortality in our real-life cohort. © 2016 Wiley Periodicals, Inc.

Stable gastric pentadecapeptide BPC 157 and bupivacaine.

PubMed

Zivanovic-Posilovic, Gordana; Balenovic, Diana; Barisic, Ivan; Strinic, Dean; Stambolija, Vasilije; Udovicic, Mario; Uzun, Sandra; Drmic, Domagoj; Vlainic, Josipa; Bencic, Martina Lovric; Sindic, Aleksandra; Seiwerth, Sven; Sikiric, Predrag

2016-12-15

Bupivacaine toxicity following accidental overdose still lacks therapeutic solution. However, there are major arguments for testing BPC 157 against bupivacaine toxicity in vivo in rats, in particular, and then finally, in vitro. These are: the lack of any known BPC 157 toxicity, a lifesaving effect via the mitigation of arrhythmias in rats underwent hyperkalemia or digitalis toxicity, the elimination of hyperkalemia and arrhythmias in rats underwent succinylcholine toxicity and finally, the reduction of potassium-induced depolarization in vitro (in HEK293 cells) in severe hyperkalemia. Most importantly, BPC 157 successfully prevents and counteracts bupivacaine cardiotoxicity; BPC 157 is effective even against the worst outcomes such as a severely prolonged QRS complex. Here, rats injected with bupivacaine (100mg/kg IP) exhibited bradycardia, AV-block, ventricular ectopies, ventricular tachycardia, T-wave elevation and asystole. All of the fatalities had developed T-wave elevation, high-degree AV-block, respiratory arrest and asystole. These were largely counteracted by BPC 157 administration (50µg/kg, 10µg/kg, 10ng/kg, or 10pg/kg IP) given 30min before or 1min after the bupivacaine injection. When BPC 157 was given 6min after bupivacaine administration, and after the development of prolonged QRS intervals (20ms), the fatal outcome was markedly postponed. Additionally, the effect of bupivacaine on cell membrane depolarization was explored by measuring membrane voltages (Vm) in HEK293 cells. Bupivacaine (1mM) alone caused depolarization of the cells, while in combination with BPC 157 (1µm), the bupivacaine-induced depolarization was inhibited. Together, these findings suggest that the stable gastric pentadecapeptide BPC 157 should be a potential antidote for bupivacaine cardiotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents).

PubMed

Calixto, J B

2000-02-01

This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

Heavy metals distribution in soils surrounding an abandoned mine in NW Madrid (Spain) and their transference to wild flora.

PubMed

Moreno-Jiménez, Eduardo; Peñalosa, Jesús M; Manzano, Rebeca; Carpena-Ruiz, Ramón O; Gamarra, Roberto; Esteban, Elvira

2009-03-15

The present work concerns the distribution and mobility of heavy metals (Fe, Mn, Cu, Zn and Cd) in the surrounding soils of a mine site and their transfer to wild flora. Thus, soils and plants were sampled from a mining valley in NW Madrid (Spain), and total and extractable heavy metals were analysed. Soils affected by mining activities presented total Cd, Cu and Zn concentrations above toxic thresholds. The percentage of extractable element was highest for Cd and lowest for Cu. A highly significant correlation was observed between the total and extractable concentrations of metals in soils, indicating that, among the factors studied, total metals concentration is the most relevant for heavy metals extractability in these soils. (NH(4))(2)SO(4)-extractable metal concentrations in soils are correlated better with metal concentrations in several plant species than total metals in soils, and thus can be used as a suitable and robust method for the estimation of the phytoavailable fraction present in soils. Twenty-five vascular plant species (3 ferns and 22 flowering plants) were analysed, in order to identify exceptional characteristics that would be interesting for soil phytoremediation and/or reclamation. High Cd and Zn concentrations have been found in the aerial parts of Hypericum perforatum (Cd), Salix atrocinerea (Cd, Zn) and Digitalis thapsi (Cd, Zn). The present paper is, to the best of our knowledge, the first report of the metal accumulation ability of the two latter plant species. The phytoremediation ability of S. atrocinerea for Cd and Zn was estimated, obtaining intervals of time that could be considered suitable for the phytoextraction of polluted soils.

Determining concentration fields of tracer plumes for layered porous media in flow-tank experiments

NASA Astrophysics Data System (ADS)

Yu, Zhongbo; Schwartz, Franklin W.

In the laboratory, computer-assisted image analysis provides an accurate and efficient way to monitor tracer experiments. This paper describes the determination of detailed temporal concentration distributions of tracers in a flow-tank experiment by analyzing photographs of plumes of Rhodamine dye through the glass wall of the tank. The methodology developed for this purpose consists of four steps: (1) digitally scanning black and white negatives obtained from photographs of the flow-tank experiment; (2) calibrating and normalizing each digitized image to a standard optical-density scale by determining the relation between the optical density and pixel value for each image; (3) constructing standard curves relating the concentration in an optical density from five experimental runs with predetermined concentrations (2-97mg/L) and (4) converting the optical density to concentration. The spatial distribution of concentration for two photographs was determined by applying these calibration and conversion procedures to all pixels of the digitized images. This approach provides an efficient way to study patterns of plume evolution and transport mechanisms. Résumé Au laboratoire, l'analyse d'images assistée par ordinateur est un moyen précis et efficace pour suivre certaines expériences de traçage. Ce papier présente comment sont déterminées dans le détail les distributions temporelles de la concentration en traceur au cours d'une expérience d'écoulement en réservoir au moyen de l'analyse de photographies de panaches de rhodamine à travers la paroi de verre du réservoir. La méthodologie développée dans cette expérience suit quatre étapes: (1) digitalisation par balayage des négatifs noir et blanc des prises de vue de l'expérience d'écoulement en réservoir (2) calibration et normalisation de chaque image digitalisée par rapport à une échelle étalon de densité optique en déterminant la relation entre la densité optique et la valeur des pixels de chaque image; (3) étalonnage de concentrations prédéterminées (2 à 97mg/L) et (4) conversion de la densité optique en concentration. La distribution spatiale des concentrations pour deux photos a été déterminée en appliquant ces procédures de calibration et de conversion à tous les pixels des images digitalisées. Cette approche est une façon efficace pour étudier la manière dont évoluent les panaches ainsi que les mécanismes de transport. Resumen El análisis de imágenes por ordenador proporciona un método preciso y eficiente para estudiar los experimentos con trazadores en laboratorio. En este artículo se describe una metodología para la determinación detallada de las distribuciones temporales de concentración, en un ensayo de trazadores realizado en un tanque de flujo, a partir del análisis de fotografías de los penachos de Rodamina obtenidas a través de la pared transparente del tanque. La metodología comprende cuatro pasos: (1) Digitalización mediante escáner de los negativos en blanco y negro de las fotografías realizadas durante el experimento; (2) Calibración y normalización de cada una de las imágenes digitalizadas a una escala estándar de densidades ópticas, a través de la relación entre densidad óptica y el valor asignado a cada pixel en cada una de las imágenes (3) Construcción de un estándar de concentraciones predeterminadas (2-97mg/L) y (4) Conversión de las densidades ópticas a concentraciones de trazador. Mediante este procedimiento de calibración y conversión se determinó la distribución espacial de la concentración para dos fotografías. La metodología presentada proporciona un modo eficiente para estudiar la evolución de los penachos y los mecanismos de transporte.

Pharmacologically active plant metabolites as survival strategy products.

PubMed

Attardo, C; Sartori, F

2003-01-01

The fact that plant organisms produce chemical substances that are able to positively or negatively interfere with the processes which regulate human life has been common knowledge since ancient times. One of the numerous possible examples in the infusion of Conium maculatum, better known as Hemlock, a plant belonging to the family umbelliferae, used by the ancient Egyptians to cure skin diseases. The current official pharmacopoeia includes various chemical substances produced by secondary plant metabolisms. For example, the immunosuppressive drugs used to prevent organ transplant rejection and the majority of antibiotics are metabolites produced by fungal organisms, pilocarpin, digitalis, strophantus, salicylic acid and curare are examples of plant organism metabolites. For this reason, there has been an increase in research into plants, based on information on their medicinal use in the areas where they grow. The study of plants in relation to local culture and traditions is known as "ethnobotany". Careful study of the behaviour of sick animals has also led to the discovery of medicinal plants. The study of this subject is known as "zoopharmacognosy". The aim of this article is to discuss the fact that "ad hoc" production of such chemical substances, defined as "secondary metabolites", is one of the modes in which plant organisms respond to unfavourable environmental stimuli, such as an attack by predatory phytophagous animals or an excessive number of plant individuals, even of the same species, in a terrain. In the latter case, the plant organisms produce toxic substances, called "allelopathic" which limit the growth of other individuals. "Secondary metabolites" are produced by metabolic systems that are shunts of the primary systems which, when required, may be activated from the beginning, or increased to the detriment of others. The study of the manner in which such substances are produced is the subject of a new branch of learning called "ecological biochemistry".

[The concise history of atrial fibrillation].

PubMed

Fazekas, Tamás

2007-01-01

The author reviews the history of atrial fibrillation, the most common sustained cardiac arrhythmia. The chaotic irregularity of arterial pulse was clearly acknowledged by most of physicians of the ancient China, Egypt and Greece. William Harvey (1578-1657), who first described the circulatory system appropriately, was probably the first to describe fibrillation of the auricles in animals in 1628. The French "clinical pathologist", Jean Baptist de Sénac (1693-1770) was the first who assumed a correlation between "rebellious palpitation" and stenosis of the mitral valve. Robert Adams (1791-1875) also reported in 1827 the association of irregular pulses and mitral stenosis. The discovery of digitalis leaf in 1785 by William Withering (1741-1799) brought relief to patients with atrial fibrillation and congestive heart failure by reducing the ventricular rate. From an analysis of simultaneously recorded arterial and venous pressure curves, the Scottish Sir James Mackenzie (1853-11925) demonstrated that a presystolic wave cannot be seen during "pulsus irregularis perpetuus", a term very first used by Heinrich Ewald Hering (1866-1948). Arthur Cushny (1866-1926) noted the similarity between pulse curves in clinical "delirium cordis" and those in dogs with atrial fibrillation. The first human ECG depicting atrial fibrillation was published by Willem Einthoven (1860-1927) in 1906. The proof of a direct connection between absolute arrhythmia and atrial fibrillation was established by two Viennese physicians, Carl Julius Rothberger and Heinrich Winterberg in 1909. Sir Thomas Lewis (1881-1945), the father of modem electrocardiography, studied electrophysiological characteristics of atrial fibrillation and has shown that its basic perpetuating mechanism is circus movement of electrical impulse (re-entry). After him, the major discoveries relating to the pathophysiology and clinical features of atrial fibrillation in the 20th century stemmed from Karel Frederick Wenckebach (1864-1940), Gordon Moe (1915-1989), Bernhard Lown (*1921) and Maurits Allessie. Over the past ten years, awareness has increased of transcatheter radiofrequency and cryoablation of non-valvular atrial fibrillation and the battle against formation of intraatrial thrombi for preventing cerebral thromboembolism.

High doses of digoxin increase the myocardial nuclear factor-kB and CaV1.2 channels in healthy mice. A possible mechanism of digitalis toxicity.

PubMed

Farghaly, Hanan Sayed Mohamed; Ashry, Israa El-Sayed Mohamed; Hareedy, Mohammad Salem

2018-06-06

Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium. The voltage-gated L-type calcium channel CaV1.2 mediates the influx of Ca+2 into the cell in response to membrane depolarization. Our aim was to characterize the role of NF-kB during digoxin toxicity and to assess its correlation with Cav 1.2 in healthy mice in vivo. To address these questions, digoxin was administered in doses of 0.1, 1 or 5 mg/kg orally daily for seven days to the animals. Serum digoxin, serum calcium, atrial and ventricular calcium levels were measured. We, also, looked for NF-kB and CaV1.2 channel expression in cardiac muscle of mice. Digoxin at a dose of 0.1 mg/kg did not enhance serum, atrial, and ventricular Ca+2 levels, but were increased when digoxin dose of 1 and 5 mg/kg were administered. Histologically, myocardial necrosis and cellular infiltration on day 7 were significantly more severe in the 5 mg/kg/day digoxin group. Immunohistochemical studies showed more expression of both NF-kB and CaV1.2 in 1 and 5 mg/kg/day digoxin groups. These data suggest that NF-kB may be responsible for digoxin toxicity, at least partially via modulation of CaV1.2 and intracellular calcium homeostasis in the myocardium. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Assessing the Eligibility Criteria in Phase III Randomized Controlled Trials of Drug Therapy in Heart Failure With Preserved Ejection Fraction: The Critical Play-Off Between a "Pure" Patient Phenotype and the Generalizability of Trial Findings.

PubMed

Patel, Hitesh C; Hayward, Carl; Dungu, Jason N; Papadopoulou, Sofia; Saidmeerasah, Abdel; Ray, Robin; Di Mario, Carlo; Shanmugam, Nesan; Cowie, Martin R; Anderson, Lisa J

2017-07-01

To investigate the effect of the different eligibility criteria used by phase III clinical studies in heart failure with preserved ejection fraction (HFpEF) on patient selection, phenotype, and survival. We applied the key eligibility criteria of 7 phase III HFpEF studies (Digitalis Investigation Group Ancillary, Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction, Perindopril in Elderly People With Chronic Heart Failure, Irbesartan in Heart Failure With Preserved Systolic Function, Japanese Diastolic Heart Failure, Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist, and Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF; ongoing]) to a typical and well-characterized HFpEF population (n = 557) seen in modern European cardiological practice. Follow-up was available for a minimum of 24 months in each patient. Increasing the number of study eligibility criteria identifies a progressively smaller group of patients from real-life practice suitable for recruitment into clinical trials; using the J-DHF criteria, 81% of our clinic patients would have been eligible, whereas the PARAGON-HF criteria significantly reduced this proportion to 32%. The patients identified from our clinical population had similar mortality rates using the different criteria, which were consistently higher than those reported in the actual clinic trials. Trial eligibility criteria have become stricter with time, which reduces the number of eligible patients, affecting both generalizability of any findings and feasibility of completing an adequately powered trial. We could not find evidence that the additional criteria used in more recent randomized trials in HFpEF have identified patients at higher risk of all-cause mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Protective effects of Hawthorn (Crataegus oxyacantha) extract against digoxin-induced arrhythmias in rats.

PubMed

Alp, Hayrullah; Soner, Burak Cem; Baysal, Tamer; Şahin, Ayşe Saide

2015-01-01

Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats. Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 µg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed. The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001). Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans.

Protective effects of Hawthorn (Crataegus oxyacantha) extract against digoxin-induced arrhythmias in rats

PubMed Central

Alp, Hayrullah; Soner, Burak Cem; Baysal, Tamer; Şahin, Ayşe Saide

2016-01-01

Objective: Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats. Methods: Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 μg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed. Results: The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001). Conclusion: Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans. PMID:25880053

Effects of cardiac glycosides on sodium pump expression and function in LLC-PK1 and MDCK cells.

PubMed

Liu, Jiang; Periyasamy, Sankaridrug M; Gunning, William; Fedorova, Olga V; Bagrov, Alexei Y; Malhotra, Deepak; Xie, Zijian; Shapiro, Joseph I

2002-12-01

The decreases in proximal tubule sodium reabsorption seen with chronic renal failure and volume expansion have been ascribed to circulating digitalis-like substances (DLS). However, the circulating concentrations of DLS do not acutely inhibit the sodium pump to a degree consistent with the observed changes in proximal tubule sodium reabsorption. We examined how cell lines that simulated proximal (LLC-PK1) and distal tubule (MDCK) cells responded to acute (30 min) and long-term (up to 12 hours) Na+,K+-ATPase inhibition with DLS. In LLC-PK1, but not MDCK cells, low concentrations of ouabain decreased 86Rb uptake profoundly in a time and dose dependent manner. In LLC-PK1 cells grown to confluence, transcellular 22Na flux was markedly reduced in concert with the decreases in 86Rb uptake. Similar findings were observed with marinobufagenin (MBG) and deproteinated extract of serum derived from patients with chronic renal failure. However, inhibition of the Na+,K+-ATPase with low extracellular potassium concentrations did not produce any of these effects. Western and Northern blots detected no change in alpha1 Na+,K+-ATPase protein and message RNA, respectively, in LLC-PK1 cells treated with ouabain for 12 hours. However, the decrease in enzymatic activity of Na+,K+-ATPase of these cells was comparable to observed decreases in 86Rb uptake. Differential centrifugation as well as biotinylation experiments demonstrated a shift of the Na+,K+-ATPase from the plasmalemma with prolonged ouabain treatment. The results show that binding of cardiac glycosides by proximal (but not distal) tubular cells results in internalization of Na+,K+-ATPase with the net effect to amplify inhibition of the Na+,K+-ATPase. As the circulating concentrations of DLS increase with chronic renal failure and volume expansion, we suggest that this phenomenon explains some of the decreased sodium reabsorption by the proximal tubule seen in these conditions.

Soluble inorganic tissue phosphorus and calcicole-calcifuge behaviour of plants.

PubMed

Zohlen, Angelika; Tyler, Germund

2004-09-01

Natural and semi-natural, non-fertilized calcareous soils are consistently low in soluble and easily exchangeable phosphate. An over-utilization, or possibly an immobilization, of inorganic P in the tissues of calcifuge plants may take place, if such plants are forced to grow on a calcareous soil, though this has not been experimentally demonstrated. The objectives of this study are, therefore, to elucidate if calcifuge plants, when forced to develop on a calcareous soil, not only have lower total P (Ptot) concentrations in their leaves than calcicole plants grown on such soil, but also a lower proportion of Ptot as water-soluble, inorganic phosphate. Such differences may be of importance in understanding the calcicole-calcifuge behaviour of plants. Plants of five calcicole and five calcifuge herbs and three calcicole and three calcifuge grasses were cultivated in a glasshouse on a moderately acid Cambisol and a calcareous Rendzic Leptosol using seeds of wild populations from southern Sweden. The calcifuges were: Corynephorus canescens, Deschampsia flexuosa, Holcus mollis, Digitalis purpurea, Lychnis viscaria, Rumex acetosella, Scleranthus annuus and Silene rupestris. The calcicoles were: Melica ciliata, Phleum phleoides, Sesleria caerulea, Arabis hirsuta, Sanguisorba minor, Scabiosa columbaria, Silene uniflora ssp. petraea and Veronica spicata. At harvest, calcifuges had much lower leaf tissue concentrations of Ptot and Pi than calcicoles when grown on the calcareous soil, and biomass production of the calcifuges was poor on this soil. Moreover, the calcifuge herbs had, on average, a lower proportion of their Ptot as Pi than had the calcicole herbs. The calcifuge herbs were also unable to avoid excessive uptake of Ca from the calcareous soil. The calcifuge grasses maintained a similar proportion of Ptot as Pi as the calcicole grasses, but their growth was still poor on the calcareous soil. On calcareous soil, very little Pi in the tissues of calcifuge herbs is, at any time, available for use in various physiological functions. This is of importance to their photosynthesis, growth, competition and final survival on such soils.

Associations between labial and whole salivary flow rates, systemic diseases and medications in a sample of older people.

PubMed

Smidt, Dorte; Torpet, Lis Andersen; Nauntofte, Birgitte; Heegaard, Karen Margrethe; Pedersen, Anne Marie Lynge

2010-10-01

To investigate the associations between age, gender, systemic diseases, medications and labial and whole salivary flow rates in older people. Unstimulated labial (LS) and unstimulated (UWS) and chewing-stimulated (SWS) whole salivary flow rates were measured in 389 randomly selected community-dwelling Danish women and 279 men aged 65-97 years. Systemic diseases, medications (coded according to the Anatomical Therapeutic Chemical (ATC) Classification System), tobacco and alcohol consumption were registered. The number of diseases and medications was higher and UWS lower in the older age groups. On average, women were slightly older, had more diseases, higher medication intake and lower UWS, SWS and LS than men. High number of diseases and medications was associated with low UWS, SWS and LS. In the healthy (14%) and nonmedicated (19%) participants, flow rates were not associated with age and gender, apart from SWS being lower in nonmedicated women. Low UWS were associated with psychiatric and respiratory disorders, type 2 diabetes and intake of psycholeptics, psychoanaleptics (especially SRRIs), respiratory agents, oral antidiabetics (particularly sulfonylureas), magnesium-hydroxide, cardiac agents, quinine, thiazides, calcium channel blockers, statins, urinary antispasmodics, glucosamine, NSAIDs, opioids and ophthalmologicals. SWS were lower in participants with ophthalmological disorders using ophthalmologicals (especially antiglaucoma agents and miotics), but also in those taking antidepressants, cardiac agents (mostly digitalis glycosides) and calcium channel blockers. Cardiovascular diseases and intake of anti-thrombotics (mainly low dose aspirins), calcium channel blockers and oral antidiabetics were associated with low LS. In older people, low salivary flow rates are associated with specific and high number of diseases and medications, but neither with age and gender per se nor with tobacco and alcohol consumption. Low UWS are associated with more diseases and medications than SWS and LS, which were primarily associated with cardiovascular diseases and medications including preventive agents such as low-dose aspirins and statins. New insights into medications and their association with salivary gland function were achieved using the ATC classification system. © 2010 John Wiley & Sons A/S.

Strengthening your ties to referring physicians through RIS/PACS integration.

PubMed

Worthy, Susan; Rounds, Karla C; Soloway, Connie B

2003-01-01

Many imaging centers are turning to technology solutions to increase refering physician satisfaction, implementing such enhancements as automated report distribution, picture archiving and communications system (PACS), radiology information systems (RIS), and web-based results access. However, without seamless integration, these technology investments don't address the challenge at its core: convenient and reliable, two-way communication and interaction with referring physicians. In an integrated RIS/PACS solution, patient tracking in the RIS and PACS study status are logged and available to users. The time of the patient's registration at the imaging center, the exam start and completion time, the patient's departure time from the imaging center, and results status are all tracked and logged. An integrated RIS/PACS solution provides additional support to the radiologist, a critical factor that can improve the turnaround time of results to referring physicians. The RIS/PACS enhances the interpretation by providing the patient's history, which gives the radiologist additional insight and decreases the likelihood of missing a diagnostic element. In a tightly integrated RIS/PACS solution, results information is more complete. Physicians can view reports with associated images selected by the radiologist. They will also have full order information and complete imaging history including prior reports and images. Referring physicians can access and view images and exam notes at the same time that the radiologist is interpreting the exam. Without the benefit of an integrated RIS/PACS system, the referring physician would have to wait for the signed transcription to be released. In a seamlessly integrated solution, film-tracking modules within the RIS are fused with digital imaging workflow in the PACS. Users can see at a glance if a historical exam is available on film and benefit when a complete study history--both film-based and digital--is presented with the current case. It is up to the imaging center to market the benefits of reduced errors, reduced turnaround times, and a higher level of service to referring physician community, and encourage them to take advantage of the convenience it provides. The savvy imaging center will also regard the integrated RIS/PACS as a valuable marketing tool for use in attracting radiologists.

Effects of Sacubitril/Valsartan in the PARADIGM-HF Trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) According to Background Therapy.

PubMed

Okumura, Naoki; Jhund, Pardeep S; Gong, Jianjian; Lefkowitz, Martin P; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Swedberg, Karl; Zile, Michael R; Solomon, Scott D; Packer, Milton; McMurray, John J V

2016-09-01

In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitorenalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no),and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to β-blocker dose (≥50% and <50% of target dose) and according to whether patients had undergone previous coronary revascularization. We analyzed the primary composite end point of cardiovascular death or heart failure hospitalization, as well as cardiovascular death. Most randomized patients (n=8399)were treated with a diuretic (80%) and β-blocker (93%); 47% of those taking a β-blocker were treated with ≥50% of the recommended dose. In addition, 4671 (56%) were treated with a mineralocorticoid receptor antagonist, 2539 (30%) with digoxin, and 1243 (15%) had a defibrillating device; 2640 (31%) had undergone coronary revascularization. Overall, the sacubitril/valsartan versus enalapril hazard ratio for the primary composite end point was 0.80 (95% confidence interval,0.73-0.87;P<0.001) and for cardiovascular death was0.80 (0.71-0.89;P<0.001). The effect of sacubitril/valsartan was consistent across all subgroups examined. The hazard ratio for primary end point ranged from 0.74 to 0.85 and for cardiovascular death rangedfrom 0.75 to 0.89, with no treatment-by-subgroup interaction. The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previouscoronary revascularization or β-blocker dose. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255. © 2016 American Heart Association, Inc.

Use of epicardial pacing wires after coronary artery bypass surgery.

PubMed

Sorensen, E R; Manna, D; McCourt, K

1994-01-01

To replicate a previous study that described the incidence and characteristics of patients after coronary artery bypass graft surgery who required the use of epicardial pacing wires and to explore the reasons for epicardial pacing wire use in this patient population. Ex post facto descriptive correlational. Cardiothoracic intensive care and step down units of a 500-bed medical center. Convenience sample of 196 patients after coronary artery bypass graft surgery, 165 who did not use the epicardial pacing wires and 31 who used the epicardial pacing wires to augment cardiac output, diagnose dysrhythmias, suppress dysrhythmias, or treat heart block. Patients receiving other surgical techniques in combination with coronary artery bypass graft surgery were not included. Recording of demographic and clinical data for all of the sample population, with additional data collected when the epicardial pacing wires were used. Independent t test and chi-square analysis were used to determine significance between the means and frequencies in the variables of the patients who used the epicardial pacing wires and those who did not. The significance level was set at 0.05. There were no statistically significant differences between the groups in terms of age or previous or recent myocardial infarction, which was opposite of the replicated study's findings. A statistically significant difference (p < 0.001) was found between the groups for the use of inotropic support, which was also opposite of the findings of that study. The group requiring epicardial pacing wire utilization demonstrated a greater need for diuretics in the preoperative phase than those who did not (p < 0.01), as well as a higher use of digitalis therapy before surgery (p < 0.01). Additionally, those who were paced experienced a greater cardiac output (p = 0.013) and cardiac index (p = 0.018) after pacing was initiated. The variation in findings between this study and the one replicated may be the result of variations in the patient populations, treatment practices, or preoperative condition. Replication of this study at a future date may reveal variables not identified here.

Neurohormones and heart failure.

PubMed

Mendzef, Scott D; Slovinski, Jennifer R

2004-12-01

The management of several neurohormonal pathways is crucial to treating the progression of HF, in addition to improving the quality of life for patients diagnosed with HF. Stimulation of the sympathetic and retin-angiogensin-aldosterone systems begins the initial and primary neurohormonal stimulation associated with the progression of this disease. However, it is becoming increasingly evident that other systems, including the cellular immune, endothelin-NO pathway, kallikrein-kinin system, the arachidonic acid cascade, and the natriuretic peptides need to be considered by clinicians when treating HF. Once treated solely with nitrates, diuretics, and morphine, the management of HF is becoming a more complex and intricate balancing act among several interdependent neurohormonal systems. Understanding the complex nature and proper management of these systems are crucial if patients with HF are to enjoy a better quality of life and experience an improvement in their symptoms. Current recommendations for the treatment and management of HF use several medications, which affect multiple neurohormonal pathways. The Heart Failure Society of America and the American Heart Association both recommend in their recent guidelines for management of HF the use of beta-adrenergic receptor blockers (beta-blockers), loop diuretics, digitalis glycosides(digoxin), ACE-I, aldactone antagonists (spironolactone), and in selected instances, ARBs and the combination of hydralazine and isosorbide dinitrate. No discussion of HF is complete without mention of the larger challenges associated with the management of HF. It is a complex syndrome that requires a multidisciplinary approach with expertise in nutrition, exercise, pharmacology, education, and the basic pathophysiology of complex neurohormonal systems. Patients with uncompensated HF are frightened, vulnerable, and require frequent medication adjustments as well as substantial time dedicated to counseling, physical assessment, and innovative educational programs for them and their families. In fact, a majority of hospital readmissions for HF occur because of patients' dietary indiscretions, medication noncompliance, or ignorance about when to call their health providers. The management of HF represents a careful balancing act between powerful neurohormonal pathways and medications but also between the basics of diet, exercise, educating both family and patient, and most importantly, caring.

Poisonous plants in New Zealand: a review of those that are most commonly enquired about to the National Poisons Centre.

PubMed

Slaughter, Robin J; Beasley, D Michael G; Lambie, Bruce S; Wilkins, Gerard T; Schep, Leo J

2012-12-14

New Zealand has a number of plants, both native and introduced, contact with which can lead to poisoning. The New Zealand National Poisons Centre (NZNPC) frequently receives enquiries regarding exposures to poisonous plants. Poisonous plants can cause harm following inadvertent ingestion, via skin contact, eye exposures or inhalation of sawdust or smoked plant matter. The purpose of this article is to determine the 15 most common poisonous plant enquiries to the NZNPC and provide a review of current literature, discussing the symptoms that might arise upon exposure to these poisonous plants and the recommended medical management of such poisonings. Call data from the NZNPC telephone collection databases regarding human plant exposures between 2003 and 2010 were analysed retrospectively. The most common plants causing human poisoning were selected as the basis for this review. An extensive literature review was also performed by systematically searching OVID MEDLINE, ISI Web of Science, Scopus and Google Scholar. Further information was obtained from book chapters, relevant news reports and web material. For the years 2003-2010 inclusive, a total of 256,969 enquiries were received by the NZNPC. Of these enquiries, 11,049 involved exposures to plants and fungi. The most common poisonous plant enquiries, in decreasing order of frequency, were: black nightshade (Solanum nigrum), arum lily (Zantedeschia aethiopica), kowhai (Sophora spp.), euphorbia (Euphorbia spp.), peace lily (Spathiphyllum spp.), agapanthus (Agapanthus spp.), stinking iris (Iris foetidissima), rhubarb (Rheum rhabarbarum), taro (Colocasia esculentum), oleander (Nerium oleander), daffodil (Narcissus spp.), hemlock (Conium maculatum), karaka (Corynocarpus laevigatus), foxglove (Digitalis purpurea) and ongaonga/New Zealand tree nettle (Urtica ferox). The combined total of enquiries for these 15 species was 2754 calls (representing approximately 25% of all enquiries regarding plant exposures). The signs and symptoms resulting from poisoning from these plants are discussed. Medical treatment recommendations are made. Poisoning following ingestion or other forms of exposures to plants in New Zealand is relatively common, particularly among children. However, serious adverse reactions are comparatively rare. Accurate plant identification and details on the type of exposure can be important in assessing the likely risks. Effective medical management of these poisonings can be achieved by following the principles outlined in this review.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogawa, E.; Suzuki, S.; Fukuda, R.

Pharmacological means to accelerate the elimination of Cs-137 introduced into the living organism are studied. Male dd mice and male Wistar rats are individually housed in metal metabolism cages, and provided with commercial solid diet and water. Radioactivity is determined in urine, and feces for 24 hours and 4 days after subcutaneous injection of a tracer dose of Cs/sup 137/Cl, and in various organs after sacrifices at the ends of these periods. Effects of various chemicals on these results are compared. Twenty five chemicals were investigated. They include inorganic Na salts such as Na bicarbonate, Na carbonate, Na suliate, Namore » thiosulfate, primary and secondary Na phosphates, and organic Na salts such as Na lactate, lactated Ringer, Na acetate, Na glucuronate, Na salt of thioctic acid, ATP Na, and Na pentobarbiturate. Na bicarbonate, Na phosphates, Na sulfate, and Na thiosulfate are found as eifective, especially Na bicarbonate, K bicarbonate shows scarcely any effect, nor do other K salts. It is therefore assumed that Cs will exchange with Na ion in the tubular cells. LiCl is found to accelerate the excretion of Cs-137 from mice and rats. This result is of interest with respect to the periodic law, since it is known that for the elimination of Sr-90, Ca salts are ineffective or slightly effective, whereas Mg salts are effective. Of the diuretics, chlorothiazide, which is considered to increase the excretion of K, does nor increase the elimination of Cs-137 in any dose. This result is different from that of Diamox, a diuretic of the same nature. Cardiac glycosides and xanthine derivatives are effective. Out of digitalis preparations, Digitamin (Shionogi), Digilanogen C (Fujisawa), Digosin (Chugai) are effective. Digitoxin and strospeside are ineffective, and after their application, retention of Cs-137 is observed in the heart muscle. G- strophanthin is ineffective in a smaller dose, but increases the elimination of Cs-137 in a larger dose. Caffeine and sodium benzoate are also effective, but theophylline and theobromine are not so effective. Out of osmotic diuretics, Na ferrocyanate alone increases fecal excretion of Cs-137, and decreases the retention in the body. NaI and KI have scarcely any effect. Phosphomolybdic acid inhibits the elimination of Cs-137 and increases its retention. The above mentioned effective chemicals are also investigated for effects on the elimination of Sr-90. (JAIF)« less

Searching Sinks and Sources: CO2 Fluxes Before and After Partial Deforestation of a Spruce Forest

NASA Astrophysics Data System (ADS)

Ney, P.; Graf, A.; Druee, C.; Esser, O.; Klosterhalfen, A.; Valler, V.; Pick, K.; Vereecken, H.

2017-12-01

Forest ecosystems in the northern mid-latitudes act as a sink for atmospheric carbon dioxide (CO2) and hence play an important role in the terrestrial carbon cycle. Disturbances of these landscapes may have a significant impact on their ecosystem carbon budget. We present seven years of eddy covariance (EC) measurements (September 2013 to September 2017) over a 70 year old spruce stock, including three years prior to and four years after partial deforestation. We analyzed the seasonal and inter-annual changes of carbon fluxes as affected mainly by the forest transition. The measurements were carried out in a small headwater catchment (38.5 ha) within the TERENO (TERrestrial Environmental Observatories) network in the Eifel National Park Germany (50°30'N, 06°19'E, 595-629 m a.s.l.). An EC system, mounted on the top of a 38 m high tower, continuously samples fluxes of momentum, sensible heat, latent heat and CO2. In August and September 2013, more than 20% of the catchment was deforested and planned for regeneration towards natural deciduous vegetation, and a second EC station (2.5 m height) was installed in the middle of this clearcut. Flux partitioning and gap filling methods were used to calculate full time series and annual carbon budgets of the measured net ecosystem exchange (NEE) and its components gross primary production (GPP) and total ecosystem respiration (Reco). Additionally, soil respiration was measured with manual chambers on a monthly to bi-monthly basis at 25 transect points in the forest and deforested area. Annual sums of NEE represent the forest as a carbon sink with small inter-annual variability. In contrast, the deforested area showed a clear trend. In the first year after partial deforestation, regrowth on the deforested area consisted mainly of grasses and red foxglove (Digitalis purpurea L.), while since the second year also growth of mountain ash (Sorbus aucuparia L.) and broom (Cytisus scoparius L.) increased. The regrowth of biomass is reflected in the annual sums of NEE, which decreased from + 500 g C m-2 y-1 to nearly zero over the past four years, due to an increase in the magnitude of GPP.

Photopsias: A Key to Diagnosis.

PubMed

Brown, Gary C; Brown, Melissa M; Fischer, David H

2015-10-01

To assess the character and cause of photopsias in vitreoretinal patients. Cross-sectional study. A total of 169 consecutive patients (217 eyes) with vitreoretinal disease presenting with a history of photopsias. A total of 217 eyes with photopsias in 169 patients were evaluated. Photopsia assessment included (1) laterality (unilateral, bilateral but not simultaneous, bilateral, and simultaneous); (2) morphology (flash, zig-zag, strobe, scintillating scotoma, twinkling, other); (3) color (white, silver, yellow, combination, other); (4) location (temporal, central, other); (5) duration (quick, prolonged, constant, other); (6) frequency; (7) diurnal appearance (day, night, both); (8) stimuli (turning head or eyes, hypoglycemia, hyperglycemia, other); and (9) associated systemic or ocular signs and symptoms (headache, numbness, weakness, vertigo, syncope, diplopia, hypotension, floaters, other). Clinical photopsia features correlated with the causes of photopsias. Thirty-two photopsia causes were identified. The top 16 included posterior vitreous detachment (PVD) in 39.7% of eyes; retinal tear in 8.9% of eyes; neovascular age-related macular degeneration (AMD) in 7.9% of eyes; rhegmatogenous retinal detachment (RRD) in 7.5% of eyes; classic and ophthalmic migraine in 6.5% of eyes; hypoglycemia in 2.8% of eyes; vertebrobasilar insufficiency in 2.8% of eyes; non-AMD choroidal neovascularization in 2.3% of eyes; retinitis pigmentosa in 1.9% of eyes; severe cough in 1.9% of eyes; central serous chorioretinopathy in 1.4% of eyes; intraocular lens reflections in 0.9% of eyes; blue field entoptic phenomenon in 0.9% of eyes; Charles Bonnet syndrome in 0.9% of eyes; digitalis in 0.9% of eyes; and metastatic adenocarcinoma to the brain in 0.9% of eyes. The photopsias associated with PVD are typically quick (96%), with lightning/flash morphology (96%), white (87%), temporally located (86%), associated with new-onset floaters (85%), preferentially seen in dark (90%) rather than lighted environments (29%), and often initiated by head/eye movements (60%). Retinal detachment had a similar profile, but with more nontemporal photopsias (40%) (P = 0.01). The photopsias from neovascular AMD are more centrally located (83%), quick and repetitive (79%), seen in light (73%) and dark (63%) environments, have no inciting stimuli (84%), and are more likely to be nonwhite (40%). A pointed history for photopsias can reveal a cause that may not initially seem apparent. Thus, the history can play a key role in management decisions. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Balloon mitral valvuloplasty during pregnancy--our experience.

PubMed

Salomé, Nuno; Dias, Carla C; Ribeiro, José; Gonçalves, Manuel; Fonseca, Conceição; Ribeiro, Vasco Gama

2002-12-01

Mitral stenosis is the most common valvular heart lesion found in pregnancy. When severe, it leads to significant maternal and fetal morbidity and mortality, since the hemodynamic adaptations to pregnancy are badly tolerated. Pregnancy can lead to development of heart failure in patients with asymptomatic or even unknown mitral stenosis, as a result of the increased mitral valve pressure gradient caused by the physiologic increase in heart rate and blood volume in pregnancy. When symptoms persist despite optimal medical therapy, the poor prognosis justifies the correction of mitral stenosis during pregnancy. To present our experience in treating severe mitral stenosis in women who develop severe heart failure during pregnancy, using percutaneous balloon mitral valvuloplasty. From 1996 to March 2002, in our department, 47 balloon mitral valvuloplasties were successfully performed in women, three of them pregnant. These were patients with congestive heart failure, New York Heart Association (NYHA) functional class III or IV, at the end of the second trimester of pregnancy, who did not respond positively to drug treatment with diuretics and digitalis. We performed percutaneous balloon mitral valvuloplasty using the Inoue technique in the three pregnant patients, with success, at around 25 weeks of gestation. After the procedure, the patients showed clinical improvement, returning to the NYHA functional class that they were in before becoming pregnant (I-II). The previous mitral valve area was 0.9-1.2 cm2, nearly doubling after valvuloplasty. Mean left atrial pressure decreased on average by 42%, and the maximum pressure (V wave) decreased on average by 40%. The mitral valve pressure gradient decreased from 15, 10 and 28 mmHg to 7, 5 and 5 mmHg after valvuloplasty. During the procedure there were no maternal or fetal complications. All patients were discharged 24 to 48 h after valvuloplasty, continuing their pregnancies without complications. One woman had vaginal delivery, and the other two had cesarean sections at 35 weeks of gestation, all without complications with healthy newborns that developed normally. In follow-up, one patient who had moderate mitral regurgitation after valvuloplasty developed severe mitral regurgitation, requiring surgical correction after two years. In pregnant patients who have severe mitral stenosis and persistent congestive heart failure symptoms despite conventional medical treatment, when feasible, percutaneous balloon mitral valvuloplasty is the best treatment.

Nutrient Dynamics of Estuarine Invertebrates Are Shaped by Feeding Guild Rather than Seasonal River Flow

PubMed Central

Ortega-Cisneros, Kelly; Scharler, Ursula M.

2015-01-01

This study aimed to determine the variability of carbon and nitrogen elemental content, stoichiometry and diet proportions of invertebrates in two sub-tropical estuaries in South Africa experiencing seasonal changes in rainfall and river inflow. The elemental ratios and stable isotopes of abiotic sources, zooplankton and macrozoobenthos taxa were analyzed over a dry/wet seasonal cycle. Nutrient content (C, N) and stoichiometry of suspended particulate matter exhibited significant spatio-temporal variations in both estuaries, which were explained by the variability in river inflow. Sediment particulate matter (%C, %N and C:N) was also influenced by the variability in river flow but to a lesser extent. The nutrient content and ratios of the analyzed invertebrates did not significantly vary among seasons with the exception of the copepod Pseudodiaptomus spp. (C:N) and the tanaid Apseudes digitalis (%N, C:N). These changes did not track the seasonal variations of the suspended or sediment particulate matter. Our results suggest that invertebrates managed to maintain their stoichiometry independent of the seasonality in river flow. A significant variability in nitrogen content among estuarine invertebrates was recorded, with highest % N recorded from predators and lowest %N from detritivores. Due to the otherwise general lack of seasonal differences in elemental content and stoichiometry, feeding guild was a major factor shaping the nutrient dynamics of the estuarine invertebrates. The nutrient richer suspended particulate matter was the preferred food source over sediment particulate matter for most invertebrate consumers in many, but not all seasons. The most distinct preference for suspended POM as a food source was apparent from the temporarily open/closed system after the estuary had breached, highlighting the importance of river flow as a driver of invertebrate nutrient dynamics under extreme events conditions. Moreover, our data showed that estuarine invertebrates concentrated C and N between 10–100 fold from trophic level I (POM) to trophic level II (detritivores/deposit feeders) and thus highlighted their importance not only as links to higher trophic level organisms in the food web, but also as providers of a stoichiometrically homeostatic food source for such consumers. As climate change scenarios for the east coast of South Africa predict increased rainfall as a higher number of rainy days and days with higher rainfall, our results suggest that future changes in rainfall and river inflow will have measurable effects on the nutrient content and stoichiometry of food sources and possibly also in estuarine consumers. PMID:26352433

Nutrient Dynamics of Estuarine Invertebrates Are Shaped by Feeding Guild Rather than Seasonal River Flow.

PubMed

Ortega-Cisneros, Kelly; Scharler, Ursula M

2015-01-01

This study aimed to determine the variability of carbon and nitrogen elemental content, stoichiometry and diet proportions of invertebrates in two sub-tropical estuaries in South Africa experiencing seasonal changes in rainfall and river inflow. The elemental ratios and stable isotopes of abiotic sources, zooplankton and macrozoobenthos taxa were analyzed over a dry/wet seasonal cycle. Nutrient content (C, N) and stoichiometry of suspended particulate matter exhibited significant spatio-temporal variations in both estuaries, which were explained by the variability in river inflow. Sediment particulate matter (%C, %N and C:N) was also influenced by the variability in river flow but to a lesser extent. The nutrient content and ratios of the analyzed invertebrates did not significantly vary among seasons with the exception of the copepod Pseudodiaptomus spp. (C:N) and the tanaid Apseudes digitalis (%N, C:N). These changes did not track the seasonal variations of the suspended or sediment particulate matter. Our results suggest that invertebrates managed to maintain their stoichiometry independent of the seasonality in river flow. A significant variability in nitrogen content among estuarine invertebrates was recorded, with highest % N recorded from predators and lowest %N from detritivores. Due to the otherwise general lack of seasonal differences in elemental content and stoichiometry, feeding guild was a major factor shaping the nutrient dynamics of the estuarine invertebrates. The nutrient richer suspended particulate matter was the preferred food source over sediment particulate matter for most invertebrate consumers in many, but not all seasons. The most distinct preference for suspended POM as a food source was apparent from the temporarily open/closed system after the estuary had breached, highlighting the importance of river flow as a driver of invertebrate nutrient dynamics under extreme events conditions. Moreover, our data showed that estuarine invertebrates concentrated C and N between 10-100 fold from trophic level I (POM) to trophic level II (detritivores/deposit feeders) and thus highlighted their importance not only as links to higher trophic level organisms in the food web, but also as providers of a stoichiometrically homeostatic food source for such consumers. As climate change scenarios for the east coast of South Africa predict increased rainfall as a higher number of rainy days and days with higher rainfall, our results suggest that future changes in rainfall and river inflow will have measurable effects on the nutrient content and stoichiometry of food sources and possibly also in estuarine consumers.

[Early achievements of the Danish pharmaceutical industry-6 Pharmacia].

PubMed

Grevsen, Jørgen V; Kruse, Edith; Kruse, Poul R

2014-01-01

The article series provides a written and pictorial account of the Danish pharmaceutical industry's products from their introduction until about 1950. Part 6 deals with products from A/S Pharmacia. A/S Pharmacia was established in Copenhagen in 1922 as a Danish limited company by the enterprising pharmacist Edward Jacobsen. Pharmacia was not Jacobsen's first pharmaceutical company as previously he had established a pharmaceutical agency already in 1913 which in 1919 was reorganized to a limited company by the name of A/S Edward Jacobsen. This agency was later extended to include a production of generics. Jacobsen remained the co-owner and manager of Pharmacia until 1934 where he resigned and established another company, A/S Ejco, for the manufacture of generics. It is worth mentioning that already in 1911 a Swedish pharmaceutical company was established named AB Pharmacia. Today we do not know whether Edward Jacobsen knew about this Swedish company. Later on in 1936 AB Pharmacia and A/S Pharmacia made a contract concerning mutual market sharing, and a research cooperation was brought about between the two companies which resulted in an increase of turnover for A/S Pharmacia. In 1955 the cooperation between the two companies was increased as the Swedish company joined as principal shareholder with the purpose of continuing and developing the Danish company as an independent pharmaceutical company with its own research and development as well as manufacture, control and marketing. Therefore Pharmacia in Denmark was able to establish a synthesis factory in Koge and move the domicile to new premises in Hillered. In 1993 Pharmacia was presented in a printed matter as "The largest Nordic pharmaceutical company" as a result of the merger between the Swedish Kabi Pharmacia, formerly established by a merger between Kabi Vitrum and AB Pharmacia, and the Italian Farmitalia Carlo Erba. Only two years later in 1995 Pharmacia merged with the American pharmaceutical company The Upjohn Company under the name of Pharmacia & Upjohn. In 2000 this company was merged with the chemical group Monsanto under a new name, Pharmacia Corporation. Pharmacia Corporation was taken over by Pfizer in 2003. The early activities of A/S Pharmacia included not only the import of raw materials and ready-made articles, such as medicinal products, but also the manufacture of own medicinal products. This is not surprising considering the founder Edward Jacobsen's pharmaceutical career. Pharmacia's early manufacture of own medicinal products consisted mainly of generics, however, not only the expensive foreign medicinal products, but also any available Danish generics such as easily manufactured pharmacopeia products. It is thus worth mentioning that Pharmacia's own technological production capacity at that time was limited and required a cooperation with other (Danish) pharmaceutical companies. Pharmacia was able to produce tablet cores, but the sugarcoating had to be made by external business partners. Pharmacia was able to produce digitalis preparations, but the standardization of these had to be effected elsewhere. The total production of one of Pharmacia's products took place at an external business partner. Pharmacia was established at a time where the increasing use of industrially manufactured medicinal products, both Danish and foreign ones, had resulted in a considerable decrease in sales of pharmacy produced medicinal products. This had for a long time worried The Danish Association of Pharmacies, and this resulted in a reaction from the association, namely the DAK-products which by nature were produced in Denmark and thus became the most essential element in the fight against the industrially manufactured products--a fight which according to the association had to be fought with all legal means. Therefore The Danish Association of Pharmacies obviously reacted precipitated when in 1926 the association in writing stated that Pharmacia's products were not manufactured in Denmark in spite of the fact that they were labelled as such according to agreement with Landsforeningen Dansk Arbejde, i.e., The National Association Danish Work, which in 1925 allowed Pharmacia to use the labels of the association. The unemployment was high in the 1920'ies and increasing so when Pharmacia subsequently took legal action against the Association of Pharmacies and claimed that the statement was unjustified and might harm Pharmacia, it may indicate that the public of that time looked positively upon the manufacture and the use of Danish manufactured products. The Danish Association of Pharmacies lost the case as the claim according to the court was unjustified and thus unlawful. The suspicions of the association were not supported by facts, however, they were not either completely groundless. Following this The National Association Danish Work gave notice to terminate the contract with Pharmacia concerning the right to use the labels of the association. By expanding the cooperation and later on by merging with the Swedish Pharmacia AB the Danish A/S Pharmacia succeeded in continuing and developing a company where research, development and production of innovative medicinal products as well as of generics could take place in Denmark.

[Agranulocytosis and acute coronary syndrome in apathetic hyperthyroidism].

PubMed

Ivović, Miomira; Radiojković, Biljena; Penezić, Zorana; Stojković, Mirjana; Tancić, Milina; Vujović, Svetlana; Bogdanović, Andrija; Drezgić, Milka

2003-01-01

Tissue expose to excessive levels of circulating thyroid hormones results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyperactivity of the thyroid gland. Cardiovascular and myopathic manifestations are predominant clinical features in most hyperthyroid patients, aged 60 years and older. Some of patients have apathetic hyperthyroidism which presents with weight loss, small goiter, severe depression and without clinical features of increased sympathetic activity [3, 6]. About 50% of patients with cardiovascular manifestations have no evidence of underlying heart disease. Cardiac problems resolve when euthyroid state is established [3]. Three treatment modalities are available in hyperthyroidism, namely medicament therapy, surgery and radioactive iodine. Antithyroid drug therapy complications, can be mild such as rash, which is managed without cessation of therapy by antihistamines administration. On the other hand, very serious complications such as agranulocytosis, necessitate immediate discontinuation of the medication and appropriate treatment. Although extremely rear, it is life-threatening with highly variable recovery time. A 62-year-old woman with recurrent hyperthyroidism was admitted after treatment of agranulocytosis due to antithyroid drugs in another institution with G-CSF. The patient presented with clinical features of apathetic hyperthyroidism with extremely elevated thyroid hormone levels (total and free T4) and suppressed TSH. Radioactive iodine (5 mCi) was administered after increased thyroid uptake was confirmed. Echocardiography on admission was normal. ECG revealed moderately inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis revealed mild normocytic anemia with normal white blood cell count, hypokaliemia and normal concentration of creatine phosphokinase, lactic dehydrogenase and mildly elevated aspartate transminase in sera. Chest X-ray was consistent with pulmonary emphysema. Because the worsening of ECG changes she was transferred to Coronary unit. The diagnosis of non-Q myocardial infarction was confirmed and treatment with nitrates and beta-adrenergic antagonists was instituted. Four weeks later she became euthyroid and coronarography was performed. Subepicardial coronary arteries were normal (Figure 1). She was dismissed, and still euthyroid three months later. Agranulocytosis is very rare but very serious complication of antithyroid drug therapy. It can be detected in about 0.1-1% patients during the first three months of treatment. Sudden appearance, heralded by sore throat and fever, prompt physicians to seek white blood cell and differential count [1-3]. Confirmation of diagnosis urges cessation of drug therapy and appropriate antibiotic treatment. Recently, it was reported that recombinant human granulocyte colony-stimulating factor (rhG-CSF) is to be effective in shortening the recovery time in the neutropenic patients undergoing chemotherapy and also in patients with other types of neutropenia [5]. Tamai at al. [7] confirmed positive outcome in 34 patients treated with rhG-CSF compared to corticosteroid treatment. Hematologic laboratory abnormalities disappear 7-10 days after session of therapy. Patients completely recover two to three weeks later. Fatal outcome was also described [1-5]. Thyroid hormones have profound effects on cardiovascular physiology, especially on heart rate, cardiac output and systemic vascular resistance. In patients with hyperthyroidism, cardiac output is much higher than in normal persons. This is the result of direct effect of thyroid hormones on cardiac muscle contractility, heart rate and decrease in systemic vascular resistance. Excessive thyroid hormone secretion increases cardiac Na-K-activated plasma membrane ATP-ase and sarcoplasmic reticulum Ca-activated ATP-ase with resultant in increase myocardial contractility [6, 9]. Sinus tachycardia is the most common rhythm disorder in hyperthyroidism, but paroxysmal tachycardia and atrial fibrillation are not rare. This can be explained by increased heart rate, cardiac output, blood volume, coronary artery flow and peripheral oxygen consumption in thyrotoxicosis [9]. Patients with coronary arteriosclerosis can develop angina pectoris during thyrotoxic stage, which can be explained by imbalance between cardiac demand and supply. Myocardial damage is often in thyrotoxic patients with chronic hart failure, together with myocardial infarction in patients without coronary disease [2,6]. Congestive heart failure and atrial fibrillation are relatively resistant to digitalis treatment because of high metabolic turn over of medication and excessive myocardial irritability in hyperthyroidism [6]. Cardiovascular and myopathic manifestations predominate in older hyperthyroid patients (over 60 years) and some of them can have only few symptoms of hyperthyroidism [1-3]. Thyrotoxic state characterized by fatigue, apathy, extreme weakness, low-grade fever and sometimes congestive heart failure are designated as apathetic hyperthyroidism. Such patients have small goiters, mild tachycardia and often cool and dry skin with few eye signs [6]. Patients with subclinical hyperthyroidism are at increased risk for atrial fibrillation [9]. Unstable angina and non-Q myocardial infarction (non ST elevation) are acute manifestation of coronary artery disease. The acute coronary syndrome of unstable angina, non-Q myocardial infarction and Q-wave myocardial infarction have atherosclerotic lesions of the coronary arteries as a common pathogenic substrate. Erosions or ruptures of unstable atherosclerotic plaque triggered pathophysiologic processes, resulted in thrombus formation at the site of arterial injury. This leads to abrupt reduction or cessation through the affected vessel. Clinical manifestations of unstable angina and non-Q myocardial infarction are similar and diagnosis of non-Q myocardial infarction is made on the basis of elevated serum markers indicative of cardiac necrosis, detected in peripheral circulation. Acute coronary syndrome ranging from unstable angina to myocardial infarction an non-Q myocardial infarction represents increasingly severe manifestations of the same pathophysiologic processes [10,11]. In conclusion, these 62-year-old woman presented with apathetic form of recurrent hyperthyroidism associated with two serious complications, life-threatening agranulocytosis and acute coronary syndrome.