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Sample records for amiodarone destabilizes intracellular

  1. Treatment with Amiodaron

    DEFF Research Database (Denmark)

    Adelborg, Kasper; Ebbehøj, Eva; Nielsen, Jens Cosedis;

    2014-01-01

    Amiodarone is an effective antiarrhythmic drug for supra-ven-tri-cular and ventricular arrhythmias. A majority of patients treated with amiodarone suffer from mild adverse events, however, serious life-threatening adverse events caused by amiodarone are also seen. This review describes the...... pharmacology, interac-tions, side and adverse effects of amiodarone and highlights the importance of a systematic interdisciplinary follow-up protocol for outpatients treated with amiodarone....

  2. Behandling med amiodaron

    DEFF Research Database (Denmark)

    Adelborg, Kasper; Ebbehøj, Eva; Nielsen, Jens Cosedis;

    2015-01-01

    Amiodarone is an effective antiarrhythmic drug for supra­ven­tri­cular and ventricular arrhythmias. A majority of patients treated with amiodarone suffer from mild adverse events, however, serious life-threatening adverse events caused by amiodarone are also seen. This review describes the...... pharmacology, interac­tions, side and adverse effects of amiodarone and highlights the importance of a systematic interdisciplinary follow-up protocol for outpatients treated with amiodarone....

  3. Hepatotoxicity of amiodarone

    DEFF Research Database (Denmark)

    Rumessen, J J

    1986-01-01

    Amiodarone has proved very effective in the treatment of otherwise resistant cardiac tachyarrhythmias. The use of amiodarone has, however, been limited due to its serious side-effects. A patient with cholestatic hepatitis due to amiodarone treatment is presented below and a review of the...... hepatotoxicity of amiodarone is given. It is concluded that solid evidence exists of hepatic injury due to amiodarone treatment, including steatosis, alterations resembling alcoholic hepatitis, cholestatic hepatitis and micronodular cirrhosis of the liver. Patients receiving amiodarone should be regularly...

  4. Amiodarone and thyroid

    NARCIS (Netherlands)

    S.A. Eskes; W.M. Wiersinga

    2009-01-01

    Assessment of TSH and TPO-Ab before starting amiodarone (AM) treatment is recommended The usefulness of periodic TSH measurement every 6 months during AM treatment is limited by the often sudden explosive onset of AIT, and the spontaneous return Of a Suppressed TSH to not mal values in half of the c

  5. Compound list: amiodarone [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available amiodarone AM 00033 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/amiodaron...e.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/amiodaron...e.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/amiodaron...ve/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/amiodarone.Rat.in_vivo.Liver.Repeat.zip ...

  6. Amiodarone for the treatment and prevention of ventricular fibrillation and ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Hugo Van Herendael

    2010-06-01

    Full Text Available Hugo Van Herendael, Paul DorianDivision of Cardiology, St. Michael’s Hospital, University of Toronto, Toronto, CanadaAbstract: Amiodarone has emerged as the leading antiarrhythmic therapy for termination and prevention of ventricular arrhythmia in different clinical settings because of its proven efficacy and safety. In patients with shock refractory out-of-hospital cardiac arrest and hemodynamically destabilizing ventricular arrhythmia, amiodarone is the most effective drug available to assist in resuscitation. Although the superiority of the transvenous implantable cardioverter defibrillator (ICD over amiodarone has been well established in the preventive treatment of patients at high risk of life-threatening ventricular arrhythmias, amiodarone (if used with a beta-blocker is the most effective antiarrhythmic drug to prevent ICD shocks and treat electrical storm. Both the pharmacokinetics and the electrophysiologic profile of amiodarone are complex, and its optimal and safe use requires careful patient surveillance with respect to potential adverse effects.Keywords: amiodarone, ventricular fibrillation, unstable ventricular tachycardia

  7. A Chimeric Cetuximab-Functionalized Corona as a Potent Delivery System for Microtubule-Destabilizing Nanocomplexes to Hepatocellular Carcinoma Cells: A Focus on EGFR and Tubulin Intracellular Dynamics.

    Science.gov (United States)

    Poojari, Radhika; Kini, Sudarshan; Srivastava, Rohit; Panda, Dulal

    2015-11-01

    In this study, we have developed microtubule destabilizing agents combretastatin A4 (CA4) or 2-methoxyestradiol (2ME) encapsulated poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) nanocomplexes for targeted delivery to human hepatocellular carcinoma (HCC) cells. An epidermal growth factor receptor (EGFR) is known to be overexpressed in HCC cells. Therefore, the targeting moiety cetuximab (Cet), an anti-EGFR chimeric monoclonal antibody, is functionalized on the surface of these diblock copolymeric coronas. Cetuximab is associated with the extracellular domain of the EGFR; therefore, the uptake of the cetuximab conjugated nanocomplexes occurred efficiently in EGFR overexpressing HCC cells indicating potent internalization of the complex. The cetuximab targeted-PLGA-b-PEG nanocomplexes encapsulating CA4 or 2ME strongly inhibited phospho-EGFR expression, depolymerized microtubules, produced spindle abnormalities, stalled mitosis, and induced apoptosis in Huh7 cells compared to the free drugs, CA4 or 2ME. Further, the combinatorial strategy of targeted nanocomplexes, Cet-PLGA-b-PEG-CA4 NP and Cet-PLGA-b-PEG-2ME NP, significantly reduced the migration of Huh7 cells, and markedly enhanced the anticancer effects of the microtubule-targeted drugs in Huh7 cells compared to the free drugs, CA4 or 2ME. The results indicated that EGFR receptor-mediated internalization via cetuximab facilitated enhanced uptake of the nanocomplexes leading to potent anticancer efficacy in Huh7 cells. Cetuximab-functionalized PLGA-b-PEG nanocomplexes possess a strong potential for the targeted delivery of CA4 or 2ME in EGFR overexpressed HCC cells, and the strategy may be useful for selectively targeting microtubules in these cells.

  8. Bronchiolitis obliterans organizing pneumonia during low-dose amiodarone therapy

    NARCIS (Netherlands)

    Jessurun, GAJ; Hoogenberg, K; Crijns, HJGM

    1997-01-01

    Two cases of amiodarone-induced pulmonary toxicity during a relatively short period of low-dose amiodarone treatment are reported. The toxicity risk of amiodarone is determined by cumulative factors in individual patients.

  9. Amiodarone -- waxed and waned and waxed again.

    Science.gov (United States)

    Doggrell, S A

    2001-11-01

    Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. Amiodarone is a structural analogue of thyroid hormone and some of its anti-arrhythmic properties and toxicity may be attributable to interactions with nuclear thyroid hormone receptors. The lipid solubility of amiodarone gives it an exceptionally long half-life. Oral amiodarone takes days to work in ventricular tachyarrhythmias, but iv. amiodarone has immediate effect and can be used in life threatening ventricular arrhythmias. Intravenous amiodarone administered after out-of-hospital cardiac arrest due to ventricular fibrillation improves survival to hospital admission. Many survivors of myocardial infarction (MI) die during the subsequent year, probably due to ventricular arrhythmia. Amiodarone reduces sudden death after MI and this benefit is predominantly observed in patients with preserved cardiac function. Sudden cardiac death, predominantly due to ventricular arrhythmias, is also commonly seen in patients with heart failure. The Grupo de Estudio de la Sobrevida en lsuficiencia Cardiaca en Argentina (GESICA) and Estudio Piloto Argentino de Muerte Subita y Amiodarona (EPAMSA) trials showed survival benefit of amiodarone in heart failure, whereas Congestive Heart Failure-Survival Trial of Anti-arrhythmic Therapy (CHF-STAT) did not. Subsequent meta-analysis established a survival benefit of amiodarone in heart failure. Implanted Cardioverter Def ibrillators (ICDs) also give survival benefit to patients at risk of sudden death. In patients with a history of ventricular fibrillation or haemodynamically-compromising ventricular tachycardia, ICDs have been shown to be superior to anti-arrhythmic drugs, principally amiodarone. Further analysis has been

  10. Amiodarone -- waxed and waned and waxed again.

    Science.gov (United States)

    Doggrell, S A

    2001-11-01

    Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. Amiodarone is a structural analogue of thyroid hormone and some of its anti-arrhythmic properties and toxicity may be attributable to interactions with nuclear thyroid hormone receptors. The lipid solubility of amiodarone gives it an exceptionally long half-life. Oral amiodarone takes days to work in ventricular tachyarrhythmias, but iv. amiodarone has immediate effect and can be used in life threatening ventricular arrhythmias. Intravenous amiodarone administered after out-of-hospital cardiac arrest due to ventricular fibrillation improves survival to hospital admission. Many survivors of myocardial infarction (MI) die during the subsequent year, probably due to ventricular arrhythmia. Amiodarone reduces sudden death after MI and this benefit is predominantly observed in patients with preserved cardiac function. Sudden cardiac death, predominantly due to ventricular arrhythmias, is also commonly seen in patients with heart failure. The Grupo de Estudio de la Sobrevida en lsuficiencia Cardiaca en Argentina (GESICA) and Estudio Piloto Argentino de Muerte Subita y Amiodarona (EPAMSA) trials showed survival benefit of amiodarone in heart failure, whereas Congestive Heart Failure-Survival Trial of Anti-arrhythmic Therapy (CHF-STAT) did not. Subsequent meta-analysis established a survival benefit of amiodarone in heart failure. Implanted Cardioverter Def ibrillators (ICDs) also give survival benefit to patients at risk of sudden death. In patients with a history of ventricular fibrillation or haemodynamically-compromising ventricular tachycardia, ICDs have been shown to be superior to anti-arrhythmic drugs, principally amiodarone. Further analysis has been

  11. [Complications of low-dose amiodarone].

    Science.gov (United States)

    Feigl, D; Gilad, R; Katz, E

    1991-11-15

    Complications of low-dose amiodarone in 83 patients, in whom the drug was effective and who were followed for 1-13 years, are presented. Hypothyroidism was diagnosed in 11 (in 8 by the finding of elevated TSH). In 2 of the 3 in whom clinical signs of hypothyroidism were evident, amiodarone was continued, but thyroxine was also given. In 5 others thyrotoxicosis ensued. Propylthiouracil (PTU) was given and amiodarone was discontinued. PTU was then stopped within 4-8 months, without recurrence of the hyperthyroidism. In 1 patient pneumonitis resolved spontaneously a few weeks after stopping amiodarone. Because of gastrointestinal distress amiodarone was stopped in 1 patient. In none were liver enzymes elevated, nor was the nervous system affected clinically. Photosensitivity in 6 patients and skin discoloration in 2 did not necessitate discontinuation of the drug. Blurred vision was reported by 4, but its connection with amiodarone was not proven. There was sinus bradycardia in 2. There was no arrhythmic effect of amiodarone seen on ECG nor on Holter monitoring, nor was there any mortality. We conclude that amiodarone in low doses causes many complications, most of them mild and transient. However, in only a few cases is discontinuation of the drug indicated. PMID:1752553

  12. Acute pancreatitis and amiodarone: A case report

    Institute of Scientific and Technical Information of China (English)

    Yen-Yuan Chen; Ching-Yu Chen; Kai-Kuen Leung

    2007-01-01

    Amiodarone, a class m antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia. Adverse effects of amiodarone including pulmonary toxicity, hepatotoxicity, aggravation of arrhythmia, and thyroid diseases are well understood. A 66-year old woman with acute pancreatitis was admitted to our hospital with the complaint of epigastralgia radiating to both flanks for two months. Her symptoms and elevation of pancreatic enzymes did not respond to conventional medical treatment of pancreatitis for 18 d. No known causal factors for pancreatitis such as biliary tract stone, hypertriglyceridemia and alcohol consumption could be identified. Under the suspicion of amiodarone-induced acute pancreatitis, amiodarone was substituted by propafenone. Her symptoms soon alleviated and serum lipase level declined. Three months after hospital discharge, the abdominal pain did not recur. Amiodarone was approved to treat recurrent ventricular fibrillation or sustained ventricular tachyarrhythmia that has been resistant to other medications since 1986. Pancreatitis is a very rare adverse effect associated with the use of amiodarone, and only four cases of amiodarone-induced pancreatitis have been reported in literature. We report a patient who developed acute pancreatitis during amiodarone therapy.

  13. Geometrical Destabilization of Inflation

    Science.gov (United States)

    Renaux-Petel, Sébastien; Turzyński, Krzysztof

    2016-09-01

    We show the existence of a general mechanism by which heavy scalar fields can be destabilized during inflation, relying on the fact that the curvature of the field space manifold can dominate the stabilizing force from the potential and destabilize inflationary trajectories. We describe a simple and rather universal setup in which higher-order operators suppressed by a large energy scale trigger this instability. This phenomenon can prematurely end inflation, thereby leading to important observational consequences and sometimes excluding models that would otherwise perfectly fit the data. More generally, it modifies the interpretation of cosmological constraints in terms of fundamental physics. We also explain how the geometrical destabilization can lead to powerful selection criteria on the field space curvature of inflationary models.

  14. Anticonvulsant and hypnotic effects of amiodarone

    Institute of Scientific and Technical Information of China (English)

    Gunnur OZBAKIS-DENGIZ; Aysegul BAKIRCI

    2009-01-01

    Amiodarone hydrochloride is a potent anti-arrhythmic agent, known as a multiple ion-channel blocker in the heart.Although it has been detected in the rat brain, there are no data related to its central nervous system (CNS) effects. In this study, we evaluated anticonvulsant and hypnotic effects of amiodarone. Convulsions were induced by phentylenetetrazole (PTZ) (100 mg/kg) or caffeine (300 mg/kg) in mice. In both models, amiodarone prolonged both latency period and time to death, and acted as an anticonvulsant drug. It was found to be more effective in the PTZ model than in the caffeine model; none of the animals treated with 150 mg/kg dose amiodarone had died in the PTZ model. For hypnotic effect, sleeping was induced with pentobarbital (35 mg/kg) in rats. Amiodarone dose-dependently increased the sleeping time (677.7%~725.9%). In the sleeping test, all rats in 200 mg/kg amiodarone group died. In conclusion, anticonvulsant and hypnotic effects of amiodarone have shown the depressant effects on CNS. These effects may be dependent on its pharmacological properties.

  15. Cytotoxicity effects of amiodarone on cultured cells.

    Science.gov (United States)

    Golli-Bennour, Emna El; Bouslimi, Amel; Zouaoui, Olfa; Nouira, Safa; Achour, Abdellatif; Bacha, Hassen

    2012-07-01

    Amiodarone is a potent anti-arrhythmic drug used for the treatment of cardiac arrhythmias. Although, the effects of amiodarone are well characterized on post-ischemic heart and cardiomyocytes, its toxicity on extra-cardiac tissues is still poorly understood. To this aim, we have monitored the cytotoxicity effects of this drug on three cultured cell lines including hepatocytes (HepG2), epithelial cells (EAhy 926) and renal cells (Vero). We have investigated the effects of amiodarone on (i) cell viabilities, (ii) heat shock protein expressions (Hsp 70) as a parameter of protective and adaptive response and (iii) oxidative damage.Our results clearly showed that amiodarone inhibits cell proliferation, induces an over-expression of Hsp 70 and generates significant amount of reactive oxygen species as measured by lipid peroxidation occurrence. However, toxicity of amiodarone was significantly higher in renal and epithelial cells than in hepatocytes. Vitamin E supplement restores the major part of cell mortalities induced by amiodarone showing that oxidative damage is the predominant toxic effect of the drug.Except its toxicity for the cardiac system, our findings demonstrated that amiodarone can target other tissues. Therefore, kidneys present a high sensibility to this drug which may limit its use with subjects suffering from renal disorders.

  16. Amiodarone

    Science.gov (United States)

    ... ventricular arrhythmias (a certain type of abnormal heart rhythm when other medications did not help or could ... that you cannot control poor coordination or trouble walking numbness or tingling in the hands, legs, and ...

  17. Amiodarone Induced Morphological Changes in Rabbit Pneumocytes

    Directory of Open Access Journals (Sweden)

    Fereshteh Mehraein

    2009-01-01

    Full Text Available Objective: Amiodarone as an iodinated benzofuran derivative is a potent antiarrhythmicagent currently used for the treatment of ventricular arrhythmias. Pulmonary toxicityis one of the complications of Amiodarone therapy. The aim of this study was todetermine the toxicity of Amiodarone for pneumocytes.Materials and Methods: 14 male white New Zealand rabbits were divided in a controlgroup and an experimental group. The experimental group was subjected to intraperitoneal injection with a single daily dose of 80 mg/kg Amiodarone for two weeks.The control group received only normal saline. At the end of the injection period, thetwo groups were anesthetized and perfused with Karnovsky fixative. The lung tissuewas removed and fixed, then prepared for light and electron microscope studies.Morphometric studies were made on sections to find nucleus profile dimensions.Results: Light microscope observation showed acute changes in the alveolus includingcongestion of alveolar capillaries and infiltration of red blood cells (RBCs intothe lumen of the alveoli. Electron microscope study of lung tissue revealed abnormalinclusion bodies within type ΙΙ & Ι pneumocytes. The micrographs also showedthe presence of vacuoles in 5% of the type ΙΙ pneumocytes. Morphometric studiesshowed that the nucleus of the cells in the experimental group were smaller than inthe control group (p<0.01.Conclusion: These results indicate that Amiodarone administration can cause damageto pnuemocytes and the alveolus of rabbit lung, so the effectiveness of Amiodaronein long term treatment of heart failure patients is limited because of the developmentof lung toxicity.

  18. Amiodarone Pulmonary, Neuromuscular and Ophthalmologic Toxicity

    Directory of Open Access Journals (Sweden)

    Karen EA Burns

    2000-01-01

    Full Text Available Amiodarone is an iodinated benzofuran derivative class III antiarrhythmic that is highly effective in suppressing ventricular and supraventricular arrhythmias. It is also associated with an imposing side effect profile, which often limits its use. Numerous adverse effects have been documented including skin discolouration, photosensitivity, hepatitis, thyroid dysfunction, corneal deposits, pulmonary fibrosis, bone marrow suppression and drug interactions. These side effects are thought to be correlated with the total cumulative dose of amiodarone, but idiopathic reactions have been reported. The majority of adverse reactions resolve with discontinuation of the drug; however, rapid progression may occur, which may be fatal. The present report documents a patient who had a combination of serious amiodarone toxicities that, once recognized, were treated and eventually resulted in a good outcome.

  19. Tissue distribution of amiodarone and desethylamiodarone in rats after multiple intraperitoneal administration of various amiodarone dosages.

    Science.gov (United States)

    Plomp, T A; Wiersinga, W M; Maes, R A

    1985-01-01

    Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was studied after repeated intraperitoneal administration of the drug. Tissue and serum concentrations of amiodarone and desethylamiodarone were determined by high-performance liquid chromatography. The levels of amiodarone and desethylamiodarone in serum and tissues obtained after repeated intraperitoneal application of doses varying from 25 mg to 200 mg/kg show that the accumulation of amiodarone and desethylamiodarone in the rat is dose-dependent and both drugs are preferentially distributed in decreasing order in adipose tissue, lung, liver, kidney and thyroid gland. The penetration of the drug and its metabolite into brain was poor and with all the applied dosages brain levels were considerably lower than the corresponding serum levels. Desethylamiodarone serum and tissue concentrations were substantially lower than the corresponding amiodarone concentrations and varied from 1 to 48% (mean 15%) depending on the dosage used and the kind of tissue. The amiodarone tissue/serum concentration ratios were exceptionally high in adipose tissue (1,000-4,000) and moderate to high in the other tissues except brain (5-90), and indicate an extensive distribution of the drug with fat as a reservoir with a large storage capacity. The levels of amiodarone and desethylamiodarone, obtained with 50 mg/kg and 100 mg/kg dosages, showed in function of time clearly an increase in serum and tissues. The observed amiodarone tissue/serum ratios in function of time revealed no further significant increase (p less than or equal to 0.05) after 3 injections over a 6-day period, indicating the attainment of "steady-state".(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4039141

  20. Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation : a randomized trial

    NARCIS (Netherlands)

    Ahmed, Sheba; Rienstra, Michiel; Crijns, Harry J. G. M.; Links, Thera P.; Wiesfeld, Ans C. P.; Hillege, Hans L.; Bosker, Hans A.; Lok, Dirk J. A.; Van Veldhuisen, Dirk J.; Van Gelder, Isabelle C.

    2008-01-01

    Context Amiodarone effectively suppresses atrial fibrillation but causes many adverse events. Objective To compare major events in patients randomized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment while still aiming to prevent atrial fibrillation. D

  1. Amiodarone-induced pulmonary toxicity mimicking acute pulmonary edema.

    Science.gov (United States)

    Fabiani, Iacopo; Tacconi, Danilo; Grotti, Simone; Brandini, Rossella; Salvadori, Claudia; Caremani, Marcello; Bolognese, Leonardo

    2011-05-01

    Amiodarone is a highly effective antiarrhythmic drug. Its long-term use may, however, lead to several adverse effects, with pulmonary toxicity being the most serious. The article presents the case of a 78-year-old woman with a history of cardiac surgery, who after 2 years of amiodarone therapy for prophylactic treatment of atrial fibrillation developed amiodarone pneumonitis mimicking an acute pulmonary edema. The patient failed to respond to diuretic therapy and several courses of anti-infective therapy. Differential diagnosis of different causes of pulmonary infiltrates did not demonstrate any other abnormality. Lung biopsy findings were consistent with the diagnosis of amiodarone pneumonitis. Given the widespread use of amiodarone as an antiarrhythmic agent, pneumologists and cardiologists should consider this important adverse effect as a differential diagnosis of pulmonary distress refractory to therapy in all patients treated with amiodarone who present with respiratory symptoms and pneumonia-like illness. PMID:19924000

  2. The Incidence and Risk of Inducing Hyperthyroidism Following Amiodarone Treatment

    Directory of Open Access Journals (Sweden)

    Cozlea D L

    2013-06-01

    Full Text Available Introduction: Amiodarone, a frequently used antiarrhythmic drug in cardiology, is very efficient in the treatment of ventricular and supraventricular tachiarrithmyas. The iodine content of amiodarone is 39%. Its chemical structure is similar to tyrosine. It is estimated that 1-23% of patients treated with amiodarone can develop hyperthyroidism. The purpose of this study is to assess and monitor the incidence of hyperthyroidism induced by amiodarone in patients admitted for various types of cardiac dysrhythmias, considering that most of the patients included in the study came from an endemic goitre area.

  3. Amiodarone: review of pulmonary effects and toxicity.

    Science.gov (United States)

    Papiris, Spyros A; Triantafillidou, Christina; Kolilekas, Likurgos; Markoulaki, Despoina; Manali, Effrosyni D

    2010-07-01

    Amiodarone, a bi-iodinated benzofuran derivative, is, because of its high effectiveness, one of the most widely used antiarrhythmic agents. However, adverse effects, especially potentially fatal and non-reversible acute and chronic pulmonary toxicity, continue to be observed. This review provides an update of the epidemiology, pathophysiology, clinical presentation, treatment and outcome of amiodarone pulmonary effects and toxicity. Lung adverse effects occur in approximately 5% of treated patients. The development of lung complications appears to be associated with older age, duration of treatment and cumulative dosage, high levels of its desethyl metabolite, history of cardiothoracic surgery and/or use of high oxygen mixtures, use of iodinated contrast media, and probably pre-existing lung disease as well as co-existing respiratory infections. Amiodarone-related adverse pulmonary effects may develop as early as from the first few days of treatment to several years later. The onset of pulmonary toxicity may be either insidious or rapidly progressive. Cough, new chest infiltrates in imaging studies and reduced lung diffusing capacity in the appropriate clinical setting of amiodarone use, after the meticulous exclusion of infection, malignancy and pulmonary oedema, are the cardinal clinical and laboratory elements for diagnosis. Pulmonary involvement falls into two categories of different grades of clinical significance: (i) the ubiquitous 'lipoid pneumonia', the so-called 'amiodarone effect', which is usually asymptomatic; and (ii) the more appropriately named 'amiodarone toxicity', which includes several distinct clinical entities related to the differing patterns of lung inflammatory reaction, such as eosinophilic pneumonia, chronic organizing pneumonia, acute fibrinous organizing pneumonia, nodules or mass-like lesions, nonspecific interstitial pneumonia-like and idiopathic pulmonary fibrosis-like interstitial pneumonia, desquamative interstitial pneumonia

  4. Drug induced lung disease - amiodarone in focus

    Directory of Open Access Journals (Sweden)

    Vasić Nada R.

    2014-01-01

    Full Text Available More than 380 medications are known to cause pulmonary toxicity. Selected drugs that are important causes of pulmonary toxicity fall into the following classes: cytotoxic, cardiovascular, anti-inflammatory, antimicrobial, illicit drugs, miscellaneous. The adverse reactions can involve the pulmonary parenchyma, pleura, the airways, pulmonary vascular system, and mediastinum. Drug-induced lung diseases have no pathognomonic clinical, laboratory, physical, radiographic or histological findings. A drug-induced lung disease is usually considered a diagnosis of exclusion of other diseases. The diagnosis of drug-mediated pulmonary toxicity is usually made based on clinical findings. In general, laboratory analyses do not help in establishing the diagnosis. High-resolution computed tomography scanning is more sensitive than chest radiography for defining radiographic abnormalities. The treatment of drug-induced lung disease consists of immediate discontinuation of the offending drug and appropriate management of the pulmonary symptoms. Glucocorticoids have been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. Before starting any medication, patients should be educated about the potential adverse effects of the drug. Amiodarone is an antiarrhythmic agent used in the treatment of many types of tachyarrhythmia. Amiodarone-caused pulmonary toxicity is a well-known side effect (complication of this medication. The incidence of amiodarone-induced lung disease is approximately 5-7%.

  5. Chronic amiodarone remodels expression of ion channel transcripts in the mouse heart

    Institute of Scientific and Technical Information of China (English)

    S.LEBOUTER; A.ELHARCHI; C.MARIONNEAU; C.BELLOCQ; A.CHAMBELLAN; K.LEQUANG; JCBELLOCQ; JCCHEVALIER; GLANDE; JJLEGER; FCHARPENTIER; DESCANDE; SDEMOLOMBE

    2004-01-01

    AIM: The basis for the unique effectiveness of chronic amiodarone on cardiac arrhythmias is incompletely understood. The present study investigated the pharmacogenomics profile of amiodarone on genes encoding ion channel subunits. METHODS AND RESULTS: Adult male mice were treated for 6 weeks with vehicle or oral amiodarone at 30,90,or 180 mg·kg-1·d-1, Plasma and myocardial levels of amiodarone and n-desethyl-amiodarone in

  6. Moduli destabilization via gravitational collapse

    International Nuclear Information System (INIS)

    We examine the interplay between gravitational collapse and moduli stability in the context of black hole formation. We perform numerical simulations of the collapse using the double null formalism and show that the very dense regions one expects to find in the process of black hole formation are able to destabilize the volume modulus. We establish that the effects of the destabilization will be visible to an observer at infinity, opening up a window to a region in spacetime where standard model's couplings and masses can differ significantly from their background values.

  7. Moduli destabilization via gravitational collapse

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Dong-il [Sogang Univ., Seoul (Korea, Republic of). Center for Quantum Spacetime; Pedro, Francisco G. [Deutsches Elektronen-Synchrotron DESY, Hamburg (Germany). Theory Group; Yeom, Dong-han [Sogang Univ., Seoul (Korea, Republic of). Center for Quantum Spacetime; Kyoto Univ. (Japan). Yukawa Inst. for Theoretical Physics

    2013-06-15

    We examine the interplay between gravitational collapse and moduli stability in the context of black hole formation. We perform numerical simulations of the collapse using the double null formalism and show that the very dense regions one expects to find in the process of black hole formation are able to destabilize the volume modulus. We establish that the effects of the destabilization will be visible to an observer at infinity, opening up a window to a region in spacetime where standard model's couplings and masses can differ significantly from their background values.

  8. Inhibition of intermediary metabolism by amiodarone in dog thyroid slices

    Energy Technology Data Exchange (ETDEWEB)

    Pasquali, D.; Tseng, F.Y.; Rani, C.S.; Field, J.B. (Baylor College of Medicine, Houston, TX (USA))

    1990-10-01

    Amiodarone, an iodine-containing antiarrhythmic drug, has been reported to interfere with thyroid function and thyroid hormone metabolism. We studied the effects of amiodarone on basal and agonist (thyroid-stimulating hormone (TSH), phorbol ester, or carbachol)-stimulated glucose oxidation, 32PO4 incorporation into phospholipids, and adenosine 3',5'-cyclic monophosphate (cAMP) concentration in dog thyroid slices. Slices were preincubated with amiodarone at 37 degrees C for 1 h before the addition of agonist and the appropriate radioisotope. cAMP stimulation was measured after 20 min, glucose oxidation for 45 min, and 32PO4 incorporation into phospholipids for 2 h. Amiodarone (0.5 mM) had no effect on basal 14CO2 formation or 32PO4 incorporation into phospholipids but significantly inhibited TSH, phorbol ester, and carbachol stimulation of these parameters. It also inhibited cAMP stimulation by TSH. Inhibition of TSH-stimulated (14C)glucose oxidation was also obtained with another iodide-containing compound, iopanoic acid (0.5 mM), but not with iothalamate (up to 10 mM). Inhibition by amiodarone was still present, but to a lesser extent, when it was added at the same time as the agonist. Inhibition of stimulated (14C)glucose oxidation persisted even after the slices were incubated without amiodarone for 6 h. Inhibition by amiodarone, in contrast to that by inorganic iodide, was not prevented by 1 mM methimazole added at the same time as amiodarone. These results indicate that the inhibitory effects of amiodarone on thyroid function are not due to dissociation of iodide from the molecule.

  9. Increased Density of the Liver and Amiodarone-Associated Phospholipidosis

    Directory of Open Access Journals (Sweden)

    Sunao Kojima

    2009-01-01

    Full Text Available This is a case report in which a 60-year-old man who suffered from ventricular tachycardia with dilated cardiomyopathy was prescribed amiodarone. After taking amiodarone, liver enzymes were increased and computed tomographic (CT scanning of the abdomen showed a significant increase in the density of the liver without contrast medium. He was suspected as hemochromatosis and liver biopsy was performed. An abnormal high density of liver tissue may be observed in an unenhanced CT in patients treated with amiodarone and we suggest that periodic monitoring of liver function and/or liver biopsy is warranted before an irreversible stage is reached.

  10. Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone

    OpenAIRE

    Varró, András; Takács, János; Németh, Miklós; Hála, Ottó; Virág, László; Iost, Norbert; Baláti, Beáta; Ágoston, Márta; Vereckei, András; Pastor, Gilbert; Delbruyère, Martine; Gautier, Patrick; Nisato, Dino; Papp, Julius Gy

    2001-01-01

    The electrophysiological effects of dronedarone, a new nonionidated analogue of amiodarone were studied after chronic and acute administration in dog Purkinje fibres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode and patch-clamp techniques.Chronic treatment with dronedarone (2×25 mg−1 kg−1 day p.o. for 4 weeks), unlike chronic administration of amiodarone (50 mg−1 kg−1 day p.o. for 4 weeks), did not lengthen s...

  11. Destabilizing force of labyrinth seal

    Science.gov (United States)

    Kanki, Hiroshi; Morit, Shigeki

    1987-01-01

    A great deal of research has recently been conducted to solve the subsynchronous rotor vibration problems in high-performance turbomachinery. Particularly, the destabilizing effect of the labyrinth seal on compressors or turbines has been investigated for many years. In spite of many efforts the dynamic effect of the labyrinth seal had not been fully determined from qualitative and quantitative points of view. But from theoretical and experimental work, the dynamic characteristics of the labyrinth seal have been established. The results of recent theoretical and experimental works are presented.

  12. Amiodarone-induced pulmonary toxicity - Predisposing factors, clinical symptoms and treatment

    NARCIS (Netherlands)

    Jessurun, GAJ; Boersma, WG; Crijns, HJGM

    1998-01-01

    Amiodarone is frequently used for the treatment of cardiac arrhythmias. Although the therapeutic efficacy of amiodarone has been established, its use is limited by its safety profile. Amiodarone-induced pulmonary toxicity is one of the most life-threatening complications of this therapy. It is a rel

  13. Amiodarone-Associated Optic Neuropathy: A Critical Review

    Science.gov (United States)

    Passman, Rod S.; Bennett, Charles L.; Purpura, Joseph M.; Kapur, Rashmi; Johnson, Lenworth N.; Raisch, Dennis W.; West, Dennis P.; Edwards, Beatrice J.; Belknap, Steven M.; Liebling, Dustin B.; Fisher, Mathew J.; Samaras, Athena T.; Jones, Lisa-Gaye A.; Tulas, Katrina-Marie E.; McKoy, June M.

    2011-01-01

    Although amiodarone is the most commonly prescribed antiarrhythmic drug, its use is limited by serious toxicities, including optic neuropathy. Current reports of amiodarone associated optic neuropathy identified from the Food and Drug Administration's Adverse Event Reporting System (FDA-AERS) and published case reports were reviewed. A total of 296 reports were identified: 214 from AERS, 59 from published case reports, and 23 from adverse events reports for patients enrolled in clinical trials. Mean duration of amiodarone therapy before vision loss was 9 months (range 1-84 months). Insidious onset of amiodarone associated optic neuropathy (44%) was the most common presentation, and nearly one-third were asymptomatic. Optic disc edema was present in 85% of cases. Following drug cessation, 58% had improved visual acuity, 21% were unchanged, and 21% had further decreased visual acuity. Legal blindness (< 20/200) was noted in at least one eye in 20% of cases. Close ophthalmologic surveillance of patients during the tenure of amiodarone administration is warranted. PMID:22385784

  14. Linking progression of fibrotic lung remodeling and ultrastructural alterations of alveolar epithelial type II cells in the amiodarone mouse model.

    Science.gov (United States)

    Birkelbach, Bastian; Lutz, Dennis; Ruppert, Clemens; Henneke, Ingrid; Lopez-Rodriguez, Elena; Günther, Andreas; Ochs, Matthias; Mahavadi, Poornima; Knudsen, Lars

    2015-07-01

    Chronic injury of alveolar epithelial type II cells (AE2 cells) represents a key event in the development of lung fibrosis in animal models and in humans, such as idiopathic pulmonary fibrosis (IPF). Intratracheal delivery of amiodarone to mice results in a profound injury and macroautophagy-dependent apoptosis of AE2 cells. Increased autophagy manifested in AE2 cells by disturbances of the intracellular surfactant. Hence, we hypothesized that ultrastructural alterations of the intracellular surfactant pool are signs of epithelial stress correlating with the severity of fibrotic remodeling. With the use of design-based stereology, the amiodarone model of pulmonary fibrosis in mice was characterized at the light and ultrastructural level during progression. Mean volume of AE2 cells, volume of lamellar bodies per AE2 cell, and mean size of lamellar bodies were correlated to structural parameters reflecting severity of fibrosis like collagen content. Within 2 wk amiodarone leads to an increase in septal wall thickness and a decrease in alveolar numbers due to irreversible alveolar collapse associated with alveolar surfactant dysfunction. Progressive hypertrophy of AE2 cells and increase in mean individual size and total volume of lamellar bodies per AE2 cell were observed. A high positive correlation of these AE2 cell-related ultrastructural changes and the deposition of collagen fibrils within septal walls were established. Qualitatively, similar alterations could be found in IPF samples with mild to moderate fibrosis. We conclude that ultrastructural alterations of AE2 cells including the surfactant system are tightly correlated with the progression of fibrotic remodeling. PMID:25957292

  15. Amiodarone: Effects on thyroid function and the peripheral metabolism of the thyroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Braverman, L.E.; Safran, M.; Bambini, G.; Pinchera, A.; Martino, E.

    1985-11-01

    In addition to the effects of Amiodarone on the peripheral metabolism of the thyroid hormones and on pituitary TSH secretion, a major complication of therapy is the relatively high frequency of iodide-induced thyroid dysfunction. The mean T/sub 4/ and T/sub 3/ concentration following Amiodarone application was measured in euthyroid, hypothyroid and hyperthyroid patients and in control patients with and without cardiac disorders. Furthermore, the serum TSH was determined in euthyroid Amiodarone-treated euthyroid patients. /sup 131/I uptake was studied in patients with Amiodarone-associated thyrotoxicosis. The difficulties of the therapy of Amiodarone-induced hyperthyroidism are outlined. Preliminary studied of the effect of Amiodarone and its analogues on the metabolism of thyroid hormones in the rat indicate that Amiodarone may act as a thyroid hormone agonist in the pituitary. (MG).

  16. Phenytoin in treatment of amiodarone-induced Torsades de pointes

    Directory of Open Access Journals (Sweden)

    Saibal Mukhopadhyay

    2012-01-01

    Full Text Available Phenytoin, a class IB anti-arrhythmic agent, is considered the drug of choice for ventricular arrhythmias due to digoxin toxicity. We report successful reversion of polymorphic ventricular tachycardia secondary to amiodarone toxicity by phenytoin administration that was resistant to the conventional drugs (magnesium sulphate, lidocaine and atropine.

  17. INVITRO AND INVIVO MODULATION OF MULTIDRUG RESISTANCE WITH AMIODARONE

    NARCIS (Netherlands)

    VANDERGRAAF, WTA; DEVRIES, EGE; UGES, DRA; NANNINGA, AG; MEIJER, C; VELLENGA, E; MULDER, POM; MULDER, NH

    1991-01-01

    The modulating effect on drug resistance of amiodarone (AM) and its metabolite desethylamiodarone (DEA) was studied in a P-glycoprotein-positive human colon carcinoma cell line COLO 320, and a human small-cell lung carcinoma cell line GLC4 and its adriamycin (Adr)-resistant subline GLC4-Adr (both P-

  18. Amiodarone-Induced Pulmonary Toxicity – A Frequently Missed Complication

    Science.gov (United States)

    Sweidan, Alexander J.; Singh, Navneet K.; Dang, Natasha; Lam, Vinh; Datta, Jyoti

    2016-01-01

    INTRODUCTION Amiodarone is often used in the suppression of tachyarrhythmias. One of the more serious adverse effects includes amiodarone pulmonary toxicity (APT). Several pulmonary diseases can manifest including interstitial pneumonitis, organizing pneumonia, acute respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary nodules or masses, and pleural effusion. Incidence of APT varies from 5–15% and is correlated to dosage, age of the patient, and preexisting lung disease. DESCRIPTION A 56-year-old male with a past medical history of coronary artery disease and chronic obstructive pulmonary disease was admitted for a coronary artery bypass graft. Post-operatively, the patient was admitted to the ICU for ventilator management and continued to receive his home dose of amiodarone 400 mg orally twice daily, which he had been taking for the past 3 months. The patient was found to be hypoxemic with a PaO2 52 mmHg and bilateral infiltrates on chest x-ray. Patient also complained of new onset dyspnea. Physical exam found bilateral rhonchi with bibasilar crackles and subcutaneous emphysema along the left anterior chest wall. Daily chest x-rays showed worsening of bilateral interstitial infiltrates and pleural effusions. A chest high-resolution computed tomography on post-operative day 3 showed extensive and severe bilateral ground glass opacities. APT was suspected and amiodarone was discontinued. A course of oral prednisone without antibiotics was initiated, and after one week of treatment the chest film cleared, the PaO2 value normalized and dyspnea resolved. DISCUSSION APT occurs via cytotoxic T cells and indirectly by immunological reaction. Typically the lungs manifest a diffuse interstitial pneumonitis with varying degrees of fibrosis. Infiltrates with a ‘ground-glass’ appearance appreciated on HRCT are more definitive than chest x-ray. Pulmonary nodules can be seen, frequently in the upper lobes. These are postulated to be accumulations of

  19. Effects of amiodarone on the pharmacokinetics and toxicity of digoxin in laboratory animals.

    Science.gov (United States)

    Staneva-Stoytcheva, D; Kristeva, E

    1992-04-01

    Some pharmacokinetic interactions between digoxin and amiodarone were studied in experiments on rabbits. An increase of digoxin serum levels was established in amiodarone-treated rabbits (amiodarone 30 mg/kg s.c. for five days alone or together with digoxin). The calculated elimination half-life (t 1/2) and the area under the curve (AUC) of digoxin were increased and the digoxin clearance was decreased, being most pronounced in animals receiving amiodarone-digoxin combination for five days. There were no changes either in digoxin toxicity in amiodarone-treated guinea pigs or in serum levels of T4, T3 and TTH. The possible mechanisms of digoxin-amiodarone interactions are discussed.

  20. THE USE OF AMIODARONE IN CLINICAL PRACTICE: THE PROBLEM OF SIDE EFFECTS

    Directory of Open Access Journals (Sweden)

    O. V. Gaisenok

    2016-01-01

    Full Text Available Characteristics of amiodarone in clinical practice are focused on. Amiodarone pharmacological mode of action and its pro-arrhythmic effect is presented. As well as various side effects that can happen in clinical practice. Special attention is paid to the problem of amiodarone-induced thyrotoxicosis, its classification, diagnosis and treatment. Prospects of new anti-arrhythmic drugs class III, in particular dronedaron are also discussed.

  1. Amiodarone-induced multiorgan toxicity with ocular findings on confocal microscopy

    Directory of Open Access Journals (Sweden)

    Ugur Turk

    2015-01-01

    Full Text Available Amiodarone is an antiarrhythmic medication that can adversely effect various organs including lungs, thyroid gland, liver, eyes, skin, and nerves. The risk of adverse effects increases with high doses and prolonged use. We report a 54-year-old female who presented with multiorgan toxicity after 8 months of low dose (200 mg/day amiodarone treatment. The findings of confocal microscopy due to amiodarone-induced keratopathy are described. Amiodarone may cause multiorgan toxicity even at lower doses and for shorter treatment periods.

  2. Antiproliferative, Ultrastructural, and Physiological Effects of Amiodarone on Promastigote and Amastigote Forms of Leishmania amazonensis

    Directory of Open Access Journals (Sweden)

    Sara Teixeira de Macedo-Silva

    2011-01-01

    Full Text Available Amiodarone (AMIO, the most frequently antiarrhythmic drug used for the symptomatic treatment of chronic Chagas' disease patients with cardiac compromise, has recently been shown to have also specific activity against fungi, Trypanosoma cruzi and Leishmania. In this work, we characterized the effects of AMIO on proliferation, mitochondrial physiology, and ultrastructure of Leishmania amazonensis promastigotes and intracellular amastigotes. The IC50 values were 4.21 and 0.46 μM against promastigotes and intracellular amastigotes, respectively, indicating high selectivity for the clinically relevant stage. We also found that treatment with AMIO leads to a collapse of the mitochondrial membrane potential (ΔΨm and to an increase in the production of reactive oxygen species, in a dose-dependent manner. Fluorescence microscopy of cells labeled with JC-1, a marker for mitochondrial energization, and transmission electron microscopy confirmed severe alterations of the mitochondrion, including intense swelling and modification of its membranes. Other ultrastructural alterations included (1 presence of numerous lipid-storage bodies, (2 presence of large autophagosomes containing part of the cytoplasm and membrane profiles, sometimes in close association with the mitochondrion and endoplasmic reticulum, and (3 alterations in the chromatin condensation and plasma membrane integrity. Taken together, our results indicate that AMIO is a potent inhibitor of L. amazonensis growth, acting through irreversible alterations in the mitochondrial structure and function, which lead to cell death by necrosis, apoptosis and/or autophagy.

  3. Medical image of the week: acute amiodarone pulmonary toxicity

    Directory of Open Access Journals (Sweden)

    Mazursky K

    2015-10-01

    Full Text Available No abstract available. Article truncated after 150 words. A 71 year old man with a medical history significant for chronic obstructive pulmonary disease, coronary artery disease with post-operative status coronary artery bypass grafting, heart failure with reduced ejection fraction (25% and atrial fibrillation/flutter underwent an elective ablation of the tachyarrhythmia at another facility and was prescribed amiodarone post procedure. He started complaining of cough and dyspnea one day post procedure and was empirically treated with 2 weeks of broad spectrum antibiotics. He subsequently was transferred to our facility due to worsening symptoms. He also complained of nausea, anorexia with resultant weight loss since starting amiodarone, which was stopped 5 days prior to transfer. Infectious work up was negative. On arrival to our facility, he was diagnosed with small sub-segmental pulmonary emboli, pulmonary edema and possible acute amiodarone toxicity. His was profoundly hypoxic requiring high flow nasal cannula or 100% non-rebreather mask at all times. His symptoms persisted despite ...

  4. Treatment of Amiodarone-Induced Thyrotoxicosis Type 2 : A Randomized Clinical Trial

    NARCIS (Netherlands)

    Eskes, Silvia A.; Endert, Erik; Fliers, Eric; Geskus, Ronald B.; Dullaart, Robin P. F.; Links, Thera P.; Wiersinga, Wilmar M.

    2012-01-01

    Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO4) might be useful because ClO4 reduces the cy

  5. Effect of continuous versus episodic amiodarone treatment on quality of life in persistent atrial fibrillation

    NARCIS (Netherlands)

    Ahmed, S.; Ranchor, A.V.; Crijns, H.J.; van Veldhuisen, D.J.; van Gelder, I

    2010-01-01

    Aims Amiodarone is associated with significant adverse effects. We hypothesized that episodic amiodarone treatment would be associated with better quality of life (QoL) compared with continuous treatment in the prevention of recurrent atrial fibrillation (AF). Methods and results Quality of life was

  6. Long-term amiodarone administration remodels expression of ion channel transcripts in the mouse heart

    NARCIS (Netherlands)

    Le Bouter, S; El Harchi, A; Marionneau, C; Bellocq, C; Chambellan, A; van Veen, T; Boixel, C; Gavillet, B; Abriel, H; Le Quang, K; Chevalier, JC; Lande, G; Leger, JJ; Charpentier, F; Escande, D; Demolombe, S

    2004-01-01

    Background-The basis for the unique effectiveness of long-term amiodarone treatment on cardiac arrhythmias is incompletely understood. The present study investigated the pharmacogenomic profile of amiodarone on genes encoding ion-channel subunits. Methods and Results-Adult male mice were treated for

  7. Effect of amiodarone therapy on mortality in patients with left ventricular dysfunction and asymptomatic complex ventricular arrhythmias: Argentine Pilot Study of Sudden Death and Amiodarone (EPAMSA).

    Science.gov (United States)

    Garguichevich, J J; Ramos, J L; Gambarte, A; Gentile, A; Hauad, S; Scapin, O; Sirena, J; Tibaldi, M; Toplikar, J

    1995-09-01

    The efficiency of prophylactic antiarrhythmic treatment with amiodarone in reducing 1-year mortality in patients with reduced left ventricular ejection fraction ( < 35%) and asymptomatic ventricular arrhythmias (Lown classes 2 and 4) was investigated in a prospective, multicenter, randomized, controlled study. Among 127 patients who entered the study, 61 were assigned to no antiarrhythmic therapy (control group [CG] and 66 to amiodarone treatment (amiodarone group [AG]). Amiodarone was administered at a dosage of 800 mg/day for 2 weeks followed by 400 mg/day thereafter. A 12-month follow-up was completed for 106 patients (57 in the AG and 49 in the CG). Amiodarone reduced the overall mortality rate, which was 10.5% in the AG versus 28.6% in the CG (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.10 to 0.84; log-rank test 0.02) and sudden death rate, which was 7.0% in the AG versus 20.4% in the CG (OR 0.29; 95% CI 0.08 to 1.00; log-rank test 0.04). Side effects were rare, and in only three patients did amiodarone treatment have to be discontinued.

  8. Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.

    Science.gov (United States)

    Salata, Cristiano; Baritussio, Aldo; Munegato, Denis; Calistri, Arianna; Ha, Huy Riem; Bigler, Laurent; Fabris, Fabrizio; Parolin, Cristina; Palù, Giorgio; Mirazimi, Ali

    2015-07-01

    Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EVD.

  9. Amiodarone use in patients with documented allergy to iodine-containing compounds.

    Science.gov (United States)

    Brouse, Sara D; Phillips, Stanley M

    2005-03-01

    The popularity of amiodarone has grown due to its effectiveness in converting arrhythmia and its formulation availability. Formulations of the drug also contain iodine; the iodine content is 75 mg in a 200-mg tablet of amiodarone and 18.7 mg/ml in the intravenous solution. Approximately 10% of the iodine content of oral amiodarone is released into the circulatory system and may increase the risks of hypersensitivity reactions in iodine-sensitive patients. Documented allergies to contrast media or shellfish should not imply that a patient is allergic to iodine. Reactions to contrast media are likely due to the high osmolar or ionic content of the dye. The primary allergen in shellfish that stimulates allergic reactions is tropomyosin. Although amiodarone can cause thyroid disorders due to the high iodine load delivered to the body with each dose, no known association exists between amiodarone and reactions to contrast media or shellfish. Three patients whose medical charts listed an allergy to iodine were administered amiodarone for chemical cardioversion of arrhythmia to normal sinus rhythm. No anaphylactic or anaphylactoid reactions were observed in any of the patients during oral or intravenous amiodarone administration. In patients with true iodine hypersensitivity, however, the potential for such reactions exists. PMID:15843290

  10. Thermal island destabilization and the Greenwald limit

    Energy Technology Data Exchange (ETDEWEB)

    White, R. B.; Gates, D. A.; Brennan, D. P. [Plasma Physics Laboratory, Princeton University, P.O.Box 451, Princeton, New Jersey 08543 (United States)

    2015-02-15

    Magnetic reconnection is ubiquitous in the magnetosphere, the solar corona, and in toroidal fusion research discharges. In a fusion device, a magnetic island saturates at a width which produces a minimum in the magnetic energy of the configuration. At saturation, the modified current density profile, a function of the flux in the island, is essentially flat, the growth rate proportional to the difference in the current at the O-point and the X-point. Further modification of the current density profile in the island interior causes a change in the island stability and additional growth or contraction of the saturated island. Because field lines in an island are isolated from the outside plasma, an island can heat or cool preferentially depending on the balance of Ohmic heating and radiation loss in the interior, changing the resistivity and hence the current in the island. A simple model of island destabilization due to radiation cooling of the island is constructed, and the effect of modification of the current within an island is calculated. An additional destabilization effect is described, and it is shown that a small imbalance of heating can lead to exponential growth of the island. A destabilized magnetic island near the plasma edge can lead to plasma loss, and because the radiation is proportional to plasma density and charge, this effect can cause an impurity dependent density limit.

  11. Thermal island destabilization and the Greenwald limit

    Science.gov (United States)

    White, R. B.; Gates, D. A.; Brennan, D. P.

    2015-02-01

    Magnetic reconnection is ubiquitous in the magnetosphere, the solar corona, and in toroidal fusion research discharges. In a fusion device, a magnetic island saturates at a width which produces a minimum in the magnetic energy of the configuration. At saturation, the modified current density profile, a function of the flux in the island, is essentially flat, the growth rate proportional to the difference in the current at the O-point and the X-point. Further modification of the current density profile in the island interior causes a change in the island stability and additional growth or contraction of the saturated island. Because field lines in an island are isolated from the outside plasma, an island can heat or cool preferentially depending on the balance of Ohmic heating and radiation loss in the interior, changing the resistivity and hence the current in the island. A simple model of island destabilization due to radiation cooling of the island is constructed, and the effect of modification of the current within an island is calculated. An additional destabilization effect is described, and it is shown that a small imbalance of heating can lead to exponential growth of the island. A destabilized magnetic island near the plasma edge can lead to plasma loss, and because the radiation is proportional to plasma density and charge, this effect can cause an impurity dependent density limit.

  12. Acute Amiodarone Pulmonary Toxicity after Drug Holiday: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ahmed Abuzaid

    2015-01-01

    Full Text Available Amiodarone is reported to cause a wide continuum of serious clinical effects. It is often challenging to detect Amiodarone-induced pulmonary toxicity (AIPT. Typically, the diagnosis is made based on the clinical settings and may be supported by histopathology results, if available. We describe a 57-year-old patient who developed severe rapidly progressive respiratory failure secondary to AIPT with acute bilateral infiltrates and nodular opacities on chest imaging. Interestingly, Amiodarone was discontinued 3 weeks prior to his presentation. He had normal cardiac filling pressures confirmed by echocardiography. To our knowledge, this is the first case of isolated acute lung injury induced by Amiodarone, three weeks after therapy cessation, with adequate clinical improvement after supportive management and high dose steroid therapy.

  13. Amiodarone cost effectiveness in preventing atrial fibrillation after coronary artery bypass graft surgery

    DEFF Research Database (Denmark)

    Zebis, Lars R; Christensen, Thomas D; Hjortdal, Vibeke E;

    2008-01-01

    was based on a randomized, controlled, double-blind trial (the RASCABG study) using avoidance of atrial fibrillation as the measure of benefit at the Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark. Two hundred and fifty eligible consecutively enrolled CABG......BACKGROUND: The purpose of this study was to estimate the costs and health benefits of routinely administered postoperative amiodarone as prevention of atrial fibrillation for patients undergoing coronary artery bypass grafting (CABG) for stable angina. METHODS: This cost-effectiveness study...... patients were included to receive either 300 mg amiodarone or placebo (5% aqueous dextrose solution) administered intravenously over 20 minutes followed by 600 mg amiodarone/placebo orally twice a day (8 am and 8 pm) for the first 5 postoperative days. RESULTS: In the amiodarone group, there were 14 cases...

  14. Effects of amiodarone and thoracic epidural analgesia on atrial fibrillation after coronary artery bypass grafting

    DEFF Research Database (Denmark)

    Nygård, Eigil; Sørensen, Lars H; Hviid, Lamia B;

    2004-01-01

    OBJECTIVE: This study was designed to assess the effects of a perioperative dosing regimen of amiodarone administration, high thoracic epidural anesthesia (TEA), or a combination of the 2 regimens on atrial fibrillation (AF) after coronary artery bypass grafting (CABG). DESIGN AND SETTING......: The study was prospective, controlled, and randomized and was performed in a tertiary health care center associated with a university. PARTICIPANTS: One hundred sixty-three patients scheduled for coronary artery bypass graft surgery. INTERVENTIONS: In this 2 x 2 factorial-designed study the patients were...... randomized to 1 of 4 regimens in which group E had perioperative TEA, group E+A had TEA and amiodarone, group A had amiodarone, and group C served as control. The epidural catheter was inserted at T1-3 the day before surgery. TEA groups received TEA for 96 hours. The amiodarone regimen consisted of a single...

  15. Effects of Combination Therapy of Amiodarone and Bisoprolol in Patients With Paroxysmal Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    Rong-qiang YAN; Fang-sheng ZHENG; Qing-hai ZHANG

    2009-01-01

    Objectives To examine the long-term efficacy of combination therapy of amiodarone and bisoprolol in patients with paroxysmal atrial fibrillation (P-AF). Methods Eighty-eight patients with P-AF were divided into two groups: 44 pa-tients treated with bisoprolol and amiodarone were enrolled in group A; 44 patients treated with amiodarone alone were enrolled in group B. Survival rates, rates of conversing to permanent atrial fibrillation (AF), subjective symptom im-provement rates and secondary bradyarrhythmia rates of the two groups were measured and analyzed. Results At 12 and 24 months, the survival rates for patients free from atrial fibrillation recurrence were 75 % and 59. 1% in group A, and 54.5 % and 36.4 % in group B (P0.05, group A vs. Group B). Conclusions In patients with P-AF, bisoprolol appears to enhance the efficacy of amiodarone therapy in maintaining sinus rhythm and improving subjective symptoms.

  16. [Population pressure: a factor of political destabilization].

    Science.gov (United States)

    Tallon, F

    1993-04-01

    Political stability throughout the world appears to be greater in countries with slowly growing populations than in those with rapid growth. Population is not the only influence on political stability, however. The relationship between political stability and development is strong. The rich countries with the slowest growth are the most stable, while poor developing countries with rapid growth suffer from chronic instability. Demographic pressure and density are not the same thing and must be distinguished. A fragile environment like that of the Sahel will experience demographic pressure despite low density. Japan has a greater population density than Rwanda and little cultivable land, but the population has a high standard of living. demographic pressure is not comparable in Japan and Rwanda because Japan has slow population growth and stable democratic political institutions. The rate of growth seems to be a more important element in destabilization than density. Rapid growth creates enormous political tensions especially when profound ethnic divisions exist, and it complicates problems of government by encouraging rapid urbanization. The unbalanced age structures resulting from rapid growth hinder the satisfaction of employment, educational, and health care needs for the ever-increasing masses of young people. 49% of Rwanda's population is under 15 and 66% is under 25. Rwanda is already densely populated, with around 300 inhabitants/sq km, and its population is projected to double in 20 years. 95% of the population is dependent on agriculture, but by 1988 the average landholding per family was only 1.25 hectares and 58% of families did not grown sufficient food for household needs. Further reduction in the size of holdings or a growing landless population will have multiple consequences. Urban migration will inevitably increase, bringing with it all the problems so evident in other poor countries where the process is more advanced than in Rwanda. Chaotic

  17. Acute lung affection in an endurance-trained man under amiodarone medication

    Directory of Open Access Journals (Sweden)

    Saurbier, Bernward

    2005-06-01

    Full Text Available Patients undergoing treatment with amiodarone can develop severe pulmonary side effects. This effect, which is often highly underestimated, can lead to dyspnea, pneumonitis, and further fibrosis. A recent change in the labeling of amdiodarone by the American Food and Drug Administration (FDA supports this suspicion. Tracing the symptoms back to the causing agent can be difficult, as shown in our report. The subject of this case report is an endurance-trained 65 year old male marathon runner who appeared with atrial fibrillation during a routine check up in autumn 2003. After medical cardioversion with flecainide a complaint free interval of 8 months was followed by a relapse, which resulted in a change of medication to amiodarone. Due to misunderstandings the patient kept on taking the amiodarone loading dose for six weeks and returned with severe dyspnea on exertion. Losses in CO diffusing capacity, a lowered macrophages count and a positive lymphocyte transformation test were the only first hand clinical evidence of amiodarone intoxication, despite the sensation of dyspnea. This case shows that special care has to be taken in treatment with amiodarone. Side effects can be hard to trace and do not evidently show a clear connection to amiodarone.

  18. Ameliorative effect of grapefruit juice on amiodarone-induced cytogenetic and testicular damage in albino rats

    Institute of Scientific and Technical Information of China (English)

    Saber Abdelruhman Sakr; Mohamed El-said Zoil; Samraa Samy El-shafey

    2013-01-01

    Objective:To evaluate the ameliorative role of grapefruit juice on the cytogenetic and testicular damage induced by the antiarrythmic drug amiodarone in albino rats. Methods: Animals were divided into four groups. Group I was considered as control. Group II was given grapefruit juice at a dose level of 27 mL/kg body weight. Group III was orally administered amiodarone (18 mg/kg body weight) daily for 5 weeks. Animals were sacrificed after 5 weeks of treatment. Bone marrow was collected from the femurs for analysis of chromosomal aberrations and mitotic indices. Testes were removed and stained with H&E for histological examination. Sperms were collected from epidedymis for detection of sperm head abnormalities. Comet assay was used to detect DNA damage. Results: Amiodarone treatment caused a significant increase in the percentage of chromosomal aberrations, decreased the mitotic index and increased DNA damage. The testis showed many histopathological alterations, inhibition of spermatogenesis and morphometric changes. The number of sperm head abnormalities was increased. Treating animals with amiodarone and grapefruit juice caused a reduction in chromosomal aberrations, mitotic index, DNA damage and testicular alterations caused by amiodarone. Conclusions:The results of this study indicated that grapefruit juice ameliorates the cytotoxicty and testicular alterations induced by amiodarone in albino rats and this is may be due to the potent antioxidant effects of its components.

  19. Prevalence of Amiodarone-Induced Thyrotoxicosis and Associated Risk Factors in Japanese Patients

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    Toyoyoshi Uchida

    2014-01-01

    Full Text Available Amiodarone is a widely used agent for life-threatening arrhythmias. Although amiodarone-induced thyrotoxicosis (AIT is a major adverse effect that can cause recurrence of arrhythmias and exacerbation of heart failure, risk factors for AIT among amiodarone-treated Japanese patients have not been elucidated. Here, we investigated the prevalence and predictive factors for AIT. The study subjects were 225 patients treated with amiodarone between 2008 and 2012, who were euthyroid before amiodarone therapy. All patients with AIT were diagnosed by measurement of thyroid hormones and ultrasonography. Among the 225 subjects, 13 patients (5.8% developed AIT and all the patients were classified as Type 2 AIT. Baseline features of patients with AIT were not different from those who did not develop AIT, except for age (AIT, 55.1 ± 13.8, non-AIT, 68.1 ± 12.0 years, P<0.001. Multivariate analyses using the Cox proportional hazard model identified age as the sole determinant of AIT (hazard ratio: 0.927, 95% confidence interval: 0.891–0.964. Receiver operating characteristic curve analysis identified age of 63.5 years as the cutoff value for AIT with sensitivity of 70.3% and specificity of 69.2%. In summary, this study showed that the prevalence of AIT is 5.8% in Japanese patients treated with amiodarone and that young age is a risk factor for AIT.

  20. ECMO for pulmonary rescue in an adult with amiodarone-induced toxicity.

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    Benassi, Filippo; Molardi, Alberto; Righi, Elena; Santangelo, Rosaria; Meli, Marco

    2015-05-01

    Amiodarone is a highly effective antiarrhythmic agent. Unfortunately amiodarone-induced pulmonary toxicity is described for medium-long term therapy. We describe a case of a 65-year-old man admitted to our department for breathlessness and with a history of recurrent episodes of atrial fibrillation for which he had been receiving amiodarone (200 mg/day) since 2008. Despite diuretic therapy, along with aspirin, statins and antibiotics the patient continued to complain of severe dyspnea and had a moderate fever. Thus, diagnostic hypotheses different from acute cardiac failure were considered, in particular non-cardiogenic causes of pulmonary infiltrates. Following suspicion of amiodarone-induced pulmonary toxicity, the drug was discontinued and corticosteroid therapy was initiated. Due to the deterioration of the clinical picture, we proceeded to intubation. After few hours from intubation we were forced to institute a veno-venous extracorporeal membrane oxygenation due to the worsening of pulmonary function. The patient's clinical condition improved which allowed us to remove the ECMO after 15 days of treatment. Indications for use of ECMO have expanded considerably. To our knowledge this is the first successful, reported article of a veno-venous ECMO used to treat amiodarone-induced toxicity in an adult. In patients with severe but potentially reversible pulmonary toxicity caused by amiodarone, extracorporeal life support can maintain pulmonary function and vital organ perfusion at the expense of low morbidity, while allowing time for drug clearance. PMID:24604330

  1. Herb-Drug Interaction of Paullinia cupana (Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats.

    Science.gov (United States)

    Rodrigues, Márcio; Alves, Gilberto; Lourenço, Nulita; Falcão, Amílcar

    2012-01-01

    Paullinia cupana is used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified) Paullinia cupana extract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose of Paullinia cupana (821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days with Paullinia cupana (821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated with Paullinia cupana and amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats. PMID:23304200

  2. Herb-Drug Interaction of Paullinia cupana (Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats

    Science.gov (United States)

    Rodrigues, Márcio; Alves, Gilberto; Lourenço, Nulita; Falcão, Amílcar

    2012-01-01

    Paullinia cupana is used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified) Paullinia cupana extract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose of Paullinia cupana (821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days with Paullinia cupana (821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated with Paullinia cupana and amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats. PMID:23304200

  3. Herb-Drug Interaction of Paullinia cupana (Guarana Seed Extract on the Pharmacokinetics of Amiodarone in Rats

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    Márcio Rodrigues

    2012-01-01

    Full Text Available Paullinia cupana is used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified Paullinia cupana extract and amiodarone (narrow therapeutic index drug in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose of Paullinia cupana (821 mg/kg, p.o. and amiodarone (50 mg/kg, p.o., and in a second study rats were pretreated during 14 days with Paullinia cupana (821 mg/kg/day, p.o. receiving amiodarone (50 mg/kg, p.o. on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose. Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone were measured and analysed. A significant reduction in the peak plasma concentration (73.2% and in the extent of systemic exposure (57.8% to amiodarone was found in rats simultaneously treated with Paullinia cupana and amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats.

  4. Thermodynamics of protein destabilization in live cells.

    Science.gov (United States)

    Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andres; Theillet, François-Xavier; Bekei, Beata; Logan, Derek T; Selenko, Philipp; Wennerström, Håkan; Oliveberg, Mikael

    2015-10-01

    Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.

  5. Magnesium sulphate and amiodarone prophylaxis for prevention of postoperative arrhythmia in coronary by-pass operations

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    Huysal Kagan

    2009-02-01

    Full Text Available Abstract Background The aim of this study was to investigate the use of prophylactic magnesium sulphate and amiodarone in treating arrhythmias that may occur following coronary bypass grafting operations. Methods The study population consisted of 192 consecutive patients who were undergoing coronary artery bypass grafting (CABG. Sixty-four patients were given 3 g of magnesium sulphate (MgSO4 [20 ml = 24.32 mEq/L Mg+2] in 100 cc of isotonic 0.9% solution over 2 hours intravenously at the following times: 12 hours prior to the operation, immediately following the operation, and on postoperative days 1, 2, and 3 (Group 1. Another group of 64 patients was given a preoperative infusion of amiodarone (1200 mg on first post-operative day (Group 2. After the operation amiodarone was administered orally at a dose of 600 mg/day. Sixty-four patients in group 3 (control group had 100 cc. isotonic 0.9% as placebo, during the same time periods. Results In the postoperative period, the magnesium values were significantly higher in Group 1 than in Group 2 for all measurements. The use of amiodarone for total arrhythmia was significantly more effective than prophylactic treatment with magnesium sulphate (p = 0.015. There was no difference between the two drugs in preventing supraventricular arrhythmia, although amiodarone significantly delayed the revealing time of atrial fibrillation (p = 0.026. Ventricular arrhythmia, in the form of ventricular extra systole, was more common in the magnesium prophylaxis group. The two groups showed no significant differences in other operative or postoperative measurements. No side effects of the drugs were observed. Conclusion Prophylactic use of magnesium sulphate and amiodarone are both effective at preventing arrhythmia that may occur following coronary by-pass operations. Magnesium sulphate should be used in prophylactic treatment since it may decrease arrhythmia at low doses. If arrhythmia should occur despite this

  6. May toxicity of amiodarone be prevented by antioxidants? A cell-culture study

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    Durukan Ahmet

    2012-06-01

    Full Text Available Abstract Background Atrial Fibrillation is the most common arrhythmia encountered following cardiac surgery. The most commonly administered drug used in treatment and prophylaxis is amiodarone which has several toxic effects on major organ functions. There are few clinical data concerning prevention of toxic effects and there is no routinely suggested agent. The aim of this study is to document the cytotoxic effects of amiodarone on cell culture media and compare the cytoprotective effects of commonly used antioxidant agents. Methods L929 mouse fibroblast cell line was cultured and 100,000 cells/well-plate were obtained. First group of cells were treated with increasing concentrations of amiodarone (20 to 180 μM alone. Second and third group of cells were incubated with one-fold equimolar dose of vitamin C and N-acetyl cysteine prior to amiodarone exposure. The viability of cells were measured by MTT assay and the cytoprotective effect of each agent was compared. Results The cytotoxicity of amiodarone was significant with concentrations of 100 μM and more. The viabilities of both vitamin C and N-acetyl cysteine treated cells were higher compared to untreated cells. Conclusions Vitamin C and N-acetyl cysteine are commonly used in the clinical setting for different purposes in context of their known antioxidant actions. Their role in prevention of amiodarone induced cytotoxicity is not fully documented. The study fully demonstrates the cytoprotective role of both agents in amiodarone induced cytotoxicity on cell culture media; more pronounced with vitamin C in some concentrations. The findings may be projectile for further clinical studies.

  7. The Characteristics of Amiodarone-induced Thyrotoxicosis in a Moderate Iodine Deficit Area

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    Ancuța-Elena Cota

    2013-08-01

    Full Text Available Introduction: Amiodarone (AMI, a class III anti-arrhythmic drug, is associated with a number of side effects, including thyroid dysfunction (both hypo- and hyperthyroidism, which is due to amiodarone's high iodine content and its direct toxic effect on the thyroid. Objective: To evaluate the incidence of Amiodarone induced thyrotoxicosis (AIT (type, rate of occurrence and to identify the risk factors involved in its occurrence. Material and method: We examined patients treated with amiodarone, between January 2002 and December 2011, who presented to our Department of Endocrinology Târgu Mures for thyroid dysfunctions. Results: The retrospective study included 87 patients with thyroid dysfunctions; 58 (66.7% patients had AIT and 29 (33.3% had Amiodarone induced hypothyroidism (AIH. In the AIT group: 35 were women (60.3%, 23 were men (39.7%; the average age was 61.60 ± 12.39 years. Risk factors identified for the AIT group were male gender (RR = OR = 3.8; Chi-squer = 5.7, p = 0.004 and pre-existing thyroid abnormalities (RR = 2.5, Chi-square = 4.1, p = 0.005. The thyroid dysfunction occurrence was heterogeneous (0.2-183 months. The patients with previous thyroid abnormalities developed earlier thyroid dysfunction compared to those with an apparently normal thyroid gland (22.25 ± 4.14 months versus 32.09 ± 7.69 months, p = 0.02, T test. Conclusion: In the context of the specific iodine geoclimatic intake and the area of origin, amiodarone - induced thyroid dysfunction spectrum is dominated by thyrotoxicosis. Screening and monitoring of thyroid function for patiens under chronic amiodarone treatment is necessary

  8. Comparative efficacy of amiodarone with ivabradin combination or amiodarone with bisoprolol combination in the prevention of atrial fibrillation recurrence in pa- tients with left ventricular diastolic dysfunction

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    K. G. Adamyan

    2015-01-01

    Full Text Available Aim. To study the efficacy of use of amiodarone with ivabradine combination or amiodarone with bisoprolol combination in the prevention of atrial fibrillation (AF recurrence in patients (pts with left ventricular diastolic dysfunction (LVDD after conversion to sinus rhythm. Material and methods. 65 patients (40 males, 25 females aged 53±8 years with persistent AF and LVDD were included into the study and randomized into 3 groups to receive ivabradine and amiodarone (22 pts, bisoprolol and amiodarone (22 pts or amiodarone alone (21 pts. Left atrium (LA volume indices, LA longitudinal strain rate (LASR in systole, LV mass index, mean heart rate (HR, 24-hour HR variability and the incidence of AF by 96 h ECG monitoring were measured after the titration period, and after 3 and 6 months of follow-up. Results. After 6 months of follow-up group 1 revealed significantly lower maximum LA volume index (21.3±2.4 vs 25.2±3.0 and 28.7±3.6 ml/m2 in the 2nd and control groups, respectively, P-wave LA volume index (15.3±3.5 versus 18.1±3.8 and 20.4±4.0 ml/m2 in the 2nd and control groups, respectively, and LA systolic volume index (7.3±1.2 versus 9.4±1.6 and 9.6±1.7 ml/m2 in 2nd and control groups, respectively. The incidence of side effects in group 1 was significantly less than that in group 2 and was not different compared with control group. Conclusion. Ivabradine and amiodarone combination provides better prevention of AF recurrence and less side-effects in pts with LVDD and persistent AF after sinus rhythm restoration as compared with bisoprolol and amiodarone combination, it also reduces LA maximum, conduit and systolic volumes, and increases LASR.

  9. AMIODARONE INDUCES THE SYNTHESIS OF HSPS IN SACCHAROMYCES CEREVISIAE AND ARABIDOPSIS THALIANA CELLS

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    Pyatrikas D.V.

    2012-08-01

    Full Text Available Many biotic and abiotic stresses cause an increase of cytosolic Ca2+ level in cells. Calcium is one of the most important second messengers, regulating many various activities in the cell and was known to affect expression of stress activated genes. Mild heat shock induces the expression of heat shock proteins (Hsps which protect cell from drastic heat shock exposure. There are some literature data permitting to suggest that transient elevation of cytosolic Ca2+ level in plant cells is important for activation of Hsps expression. On the other hand mitochondria are known to regulate the intracellular calcium and reactive oxygen species signaling. It has been shown recently that mild heat shock induces hyperpolarization of inner mitochondrial membrane in plant and yeast cells and this event is critically important for activation of Hsps expression. To reveal the relationship between mitochondrial activity, intracellular calcium homeostasis and Hsps expression an antiarrhythmic drug amiodarone (AMD have been used. AMD is known to cause transient increase of cytosolic Ca2+ level in Saccharomyces cerevisiae. Obtained results have showed that AMD treatment induced the synthesis of Hsp104p in S. cerevisiae cells and Hsp101p in A. thaliana cell culture. Induction of Hsp104p synthesis leads to enhanced yeast capability to survive lethal heat shock exposure. Development of S. cerevisiae thermotolerance depended significantly on the presence of Hsp104p. Elevation of Hsp104p level in the result of AMD treatment was shown to be governed by activity of Msn2p and Msn4p transcription factors. Deletion of the MSN2 and MSN4 genes abrogated the AMD ability to induce Hsp104p synthesis. Mild heat shock and AMD treatment induced the hyperpolarization of the inner mitochondrial membrane in yeast and Arabidopsis cells which accompanied by HSP synthesis and development of thermotolerance. It was suggested that increase of cytosolic Ca2+ level after AMD treatment

  10. SEVERE AMIODARONE-INDUCED BRADICARDIA CONCEALES SICK SINUS SYNDROME: CASE REPORT.

    Science.gov (United States)

    Crăcană, Irina; Vasilcu, T F; Mardare, Alexandra; Alexa, Ioana Dana; Marcu, D T M

    2016-01-01

    Sinus node dysfunction is one of the most common arrhythmias in elderly patients; it is usually associated with intermittent and variable symptoms, thus making it difficult to diagnose. We present the case of an elderly female patient with a personal history of atrial fibrillation treated for the last three years with amiodarone; she was admitted to the Geriatric Clinic for non-specific symptoms with onset two months previously for which she had already sought care in different medical services. Clinical examination showed severe bradycardia; ECG and Holter ECG on admission confirmed severe bradycardia, with a heart rate between 29 and 50 beats/min (bpm). Given her long-term treatment with amiodarone we looked for and found hyperthyroidism; the endocrine examination led to the diagnosis of mixed type Amiodarone-induced thyrotoxicosis and initiation of corticosteroid and antithyroid treatment. The evolution of cardiac arrhythmia was monitored with the help of several Holter ECGs performed after amiodarone washout and return to the euthyroid state, which revealed a tachycardia-bradycardia syndrome initially masked by the side effects of the unsupervised therapy with amiodarone, and properly treated by the implantation of a pacemaker.

  11. A general mechanism for drug promiscuity: Studies with amiodarone and other antiarrhythmics.

    Science.gov (United States)

    Rusinova, Radda; Koeppe, Roger E; Andersen, Olaf S

    2015-12-01

    Amiodarone is a widely prescribed antiarrhythmic drug used to treat the most prevalent type of arrhythmia, atrial fibrillation (AF). At therapeutic concentrations, amiodarone alters the function of many diverse membrane proteins, which results in complex therapeutic and toxicity profiles. Other antiarrhythmics, such as dronedarone, similarly alter the function of multiple membrane proteins, suggesting that a multipronged mechanism may be beneficial for treating AF, but raising questions about how these antiarrhythmics regulate a diverse range of membrane proteins at similar concentrations. One possible mechanism is that these molecules regulate membrane protein function by altering the common environment provided by the host lipid bilayer. We took advantage of the gramicidin (gA) channels' sensitivity to changes in bilayer properties to determine whether commonly used antiarrhythmics--amiodarone, dronedarone, propranolol, and pindolol, whose pharmacological modes of action range from multi-target to specific--perturb lipid bilayer properties at therapeutic concentrations. Using a gA-based fluorescence assay, we found that amiodarone and dronedarone are potent bilayer modifiers at therapeutic concentrations; propranolol alters bilayer properties only at supratherapeutic concentration, and pindolol has little effect. Using single-channel electrophysiology, we found that amiodarone and dronedarone, but not propranolol or pindolol, increase bilayer elasticity. The overlap between therapeutic and bilayer-altering concentrations, which is observed also using plasma membrane-like lipid mixtures, underscores the need to explore the role of the bilayer in therapeutic as well as toxic effects of antiarrhythmic agents. PMID:26573624

  12. [Successful treatment of fetal supraventricular tachycardia with a combination of digoxin and amiodarone].

    Science.gov (United States)

    Hajdú, J; Szabó, I; Német, J

    1996-10-01

    The supraventricular tachycardia is a life threatening state in the intrauterine life. It can cause non-immune hydrops fetalis, intrauterine death or complications during the delivery. The unexplained tachycardia can cause fetal distress and premature delivery. Usually the digoxin is the first drug of choice for transplacental cardioversion. If digitalisation does not achieve cardioversion, the second line antiarrhythmic drugs should be instituted. Amiodarone has been suggested as a therapeutic alternative after failure of digoxin-verapamil combination. We give a drug in standard therapeutic doses for four-five days and after it we determine whether it is effective or not. We should determine the newer therapy or termination of pregnancy. The transplacental administration of amiodarone may be dangerous because of fetal cretinism. Our case is the first in Hungary-in our best knowledge- and we suggest the amiodarone for transplacental therapy. PMID:8927371

  13. Acutely Onset Amiodarone-Induced Angioedema in a Patient with New Atrial Fibrillation

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    Hossein Vakili

    2014-01-01

    Full Text Available A 50-year-old man was admitted to our emergency department due to new episode of palpitation. He had history of angioplasty of right coronary artery (RCA with drug eluting stent 2 years ago. His electrocardiogram revealed atrial fibrillation (AF. Intravenous amiodarone 150 mg during 10 minutes and then 1 mg/min infusion were started to achieve rate control and pharmacologic conversion to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed swelling of the skin around his mouth and eyes, and also mucosa of the mouth, eyes and tongue. To conclude, angioedema should be considered a rare side effect of amiodarone which is used broadly in cardiovascular field.

  14. Amiodarone Induced Hyponatremia Masquerading as Syndrome of Inappropriate Antidiuretic Hormone Secretion by Anaplastic Carcinoma of Prostate

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    Pinaki Dutta

    2014-01-01

    Full Text Available Syndrome of inappropriate antidiuretic hormone secretion (SIADH is one of the most common causes of hyponatremia. The usual causes are malignancies, central nervous system, pulmonary disorders, and drugs. Amiodarone is a broad spectrum antiarrhythmic agent widely used in the management of arrhythmias. The different side effects include thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, drug interactions, corneal microdeposits, skin rashes, and gastrointestinal disturbances. SIADH is a rare but lethal side effect of amiodarone. We describe a 62-year-old male who was suffering from advanced prostatic malignancy, taking amiodarone for underlying heart disease. He developed SIADH which was initially thought to be paraneoplastic in etiology, but later histopathology refuted that. This case emphasizes the importance of detailed drug history and the role of immunohistochemistry in establishing the diagnosis and management of hyponatremia due to SIADH.

  15. Rhythminotropic Reactions of Human Myocardium in Ischemic and Rheumatic Heart Diseases against the Background of Amiodarone

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    Boris N. Kozlov, PhD, ScD

    2012-03-01

    Full Text Available In human heart failure, Ca2+ homeostasis gets disturbed due to a decrease in the function of the sarcoplasmic reticulum (SR. We studied the differences in the SR function in patients with rheumatic and coronary heart disease, against the background of amiodarone. Cardiac preparations from the atrium of 21 patients with coronary artery disease (CAD and 14 patients with rheumatic heart disease (RHD were used in this study. Myocardial strips perfused with oxygenated Krebs-Henzelait solution without and with amiodarone (1 mM/l at 37°C. The steady state stimulation rate of the muscle strips was 0.5 Hz. The single extraordinary impulse was given as 0.2-1.5 sec after the steady state beat. Then, the first beat after a 4- to 60-sec rest period was evaluated. The extrasystoles of the myocardium in both groups, after long intervals, were decreased after amiodarone treatment. The amplitude of post extrasystoles of amiodarone-treated myocardium showed differences only after long intervals in both groups. Two types of inotropic responses of a failing myocardium after rest periods were observed. Type I post-rest contractions maintained the steady state amplitude after all rests. However, type II was characterized by a reduction in the amplitude of the contractions. Amiodarone treatment of the myocardium showing type I reactions led to an increase in the potentiation after rests, but showed no effect on the reaction of the muscle with the type II response. The results suggested that SR dysfunction was different in CAD and RHD. The realization of the therapeutic effect of amiodarone was found to be dependent on the functional activity of the SR.

  16. Drug-induced lupus: simvastatin or amiodarone? A case report in elderly

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    Mauro Turrin

    2013-03-01

    Full Text Available Reports of systemic lupus erythematosus (SLE seen during treatment with amiodarone are rare in the literature. SLE or immunological abnormalities induced by treatment with statins are more frequent. In this issue we report a case of a 81-year-old male who, after a 2-year therapy with amiodarone, developed a clinical and serologic picture of drug-induced SLE (DILE. He was admitted for congestive heart failure in mechanical aortic valve prosthesis, permanent atrial fibrillation (anticoagulation with warfarin, hypercholesterolaemia, and hypothyroidism. Amiodarone was started two years earlier for polymorphic ventricular tachycardia, statin and L-thyroxine the following year. At admission he presented pleuro-pericardical effusion detected by CT-scan (also indicative of interstitial lung involvement and echocardiography. Serological main indicative findings were: elevation of inflammatory markers, ANA (Anti-Nuclear Antibodies titers = 1:320 (indirect immune-fluorescence – IIF – assay on HEp-2, homogeneous/fine speckled pattern, anti-dsDNA titers = 1:80 (IIF on Crithidia luciliae, negative ENA (Extractable Nuclear Antigens and antibodies anti-citrulline, rheumatoid factor = 253 KU/l, normal C3-C4, negative HbsAg and anti-HCV, negative anticardiolipin antibodies IgG and IgM, negative anti-beta2GPI IgG and IgM. Amiodarone was discontinued and methylprednisolone was started, since the patient was severely ill. At discharge, after a month, the patient was better and pleuro-pericardical effusion was reduced. Readmitted few weeks later for bradyarithmia and worsening of dyspnoea, pericardial effusion was further reduced but he died for refractory congestive heart failure and pneumonia. Clinical picture (sierositis, neither skin nor kidney involvement, other typical side effects of amiodarone (hypothyroidism and lung interstitial pathology and serological findings are suggestive of amiodarone-induced SLE.

  17. Alpha particle destabilization of the TAE modes

    International Nuclear Information System (INIS)

    The high frequency, low mode number toroidicity-induced Alfven eigenmodes (TAE) are shown to be driven unstable by the circulating and/or trapped α-particles through the wave-particle resonances. For a poloidal harmonic to satisfy the resonance condition it requires that the α-particle birth speed vα ≥ vA/(2|m-nq|), where vA is the Alfven speed, m is the poloidal mode number, and n is the toroidal mode number. To destabilize the TAE modes, the inverse Landau damping associated with the α-particle pressure gradient free energy must overcome the velocity space Landau damping due to both the slowing-down α-particle and the core Maxwellian electron and ion distributions. Stability criteria in terms of the α-particle beta βα, α-particle pressure gradient parameter (ω*/ωA) (ω* is the α-particle diamagnetic drift frequency), and (vα/vA) parameters are presented for TFTR, CIT, and ITER tokamaks. The volume averaged α-particle beta threshold for TAE instability also depends sensitively on the core electron and ion temperature. Typically the volume averaged α-particle beta threshold is in the order of 10-4 if the continuum damping effect is absent. Typical growth rates of the n = 1 TAE mode can be in the order of 10-2ωA, where ωA = vA/qR. Stability of higher n TAE modes is also studied. Other types of global Alfven waves are stable due to sideband mode continuum damping resulting from toroidal coupling effects. If the Alfven continuum gap does not exist across the whole minor radius, continuum damping exists for some poloidal harmonics. The continuum damping effect is studied by employing both a resistive MHD stability code (NOVA-R) and an analytical matching method, and the results are presented. 1 ref

  18. In vitro kinetics of amiodarone and its major metabolite in two human liver cell models after acute and repeated treatments.

    Science.gov (United States)

    Pomponio, Giuliana; Savary, Camille C; Parmentier, Céline; Bois, Frederic; Guillouzo, André; Romanelli, Luca; Richert, Lysiane; Di Consiglio, Emma; Testai, Emanuela

    2015-12-25

    The limited value of in vitro toxicity data for the in vivo extrapolation has been often attributed to the lack of kinetic data. Here the in vitro kinetics of amiodarone (AMI) and its mono-N-desethyl (MDEA) metabolite was determined and modelled in primary human hepatocytes (PHH) and HepaRG cells, after single and repeated administration of clinically relevant concentrations. AMI bioavailability was influenced by adsorption to the plastic and the presence of protein in the medium (e.g. 10% serum protein reduced the uptake by half in HepaRG cells). The cell uptake was quick (within 3h), AMI metabolism was efficient and a dynamic equilibrium was reached in about a week after multiple dosing. In HepaRG cells the metabolic clearance was higher than in PHH and increased over time, as well as CYP3A4. The interindividual variability in MDEA production in PHHs was not proportional to the differences in CYP3A4 activities, suggesting the involvement of other CYPs and/or AMI-related CYP inhibition. After repeated treatment AMI showed a slight potential for bioaccumulation, whereas much higher intracellular MDEA levels accumulated over time, especially in the HepaRG cells, associated with occurrence of phospholipidosis. The knowledge of in vitro biokinetics is important to transform an actual in vitro concentration-effect into an in vivo dose-effect relationship by using appropriate modelling, thus improving the in vitro-to-in vivo extrapolation.

  19. Recurrence of arrhythmia following short-term oral AMIOdarone after CATheter ablation for atrial fibrillation

    DEFF Research Database (Denmark)

    Darkner, Stine; Chen, Xu; Hansen, Jim;

    2014-01-01

    AIMS: Patients undergoing catheter ablation for atrial fibrillation (AF) often experience recurrent arrhythmias within the first few months post-ablation. We aimed to investigate whether short-term use of amiodarone to prevent early arrhythmias following radiofrequency ablation for AF could reduce...... period. CONCLUSION: Short-term oral amiodarone treatment following ablation for paroxysmal or persistent AF did not significantly reduce recurrence of atrial tachyarrhythmias at the 6-month follow-up, but it more than halved atrial arrhythmia related hospitalization and cardioversion rates during...

  20. Effect of Lidocaine and Amiodarone on Transmural Heterogeneityricular Repolarization in Isolated Rabbit Hearts Model of Sustained Global Ischemia

    Institute of Scientific and Technical Information of China (English)

    YOU Binquan; PU Jun; LIU Nian; YU Ronghui; RUAN Yanfei; LI Yang; WANG Lin

    2005-01-01

    To study the effect of of lidocaine and amiodarone on the transmural heterogeneity of ventricular repolarization in isolated rabbit hearts model of sustained global ischemia and to explore the mechanisms underlying the antiarrhythmic activity of lidocaine and amiodarone, rabbits were randomly divided into 4 groups: control group, ischemia group, lidocaine group and amiodarone group. By the monophasic action potential (MAP) recording technique, MAPs of recorded across the left ventricular free wall in rabbit hearts perfused transmural dispersion of repolarization (TDR) and arrhythmic induced by ischemia. Our results showed that TDR of three myocardial layers in ischemia group were significantly lengthened after ischemia. TDR was increased from 17.5±3.9 ms to 31.2±4.6 ms at the time that concided with the onset of sustained ventricle arrhythmic. Amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia, and no significant difference was found at other ischemia time points. 5 cases had ventriclar arrhythmia in ischemia group (62.5 %), but no case in lidocaine group (P<0.01) and only 1 case in amiodarone group had ventrilar arrhythmia (P< 0.01). No significant difference was found between amiodarone group and lidocaine group. It is concluded that TDR of of three myocardial layers increases significantly at ischemia and it is closely associated with development of ventricular arrhythmia, and amiodarone could decrease TDR, but lidocaine could increase TDR at initial ischemia and has no effects at other ischemia time points.

  1. Methods to Stabilize and Destabilize Ammonium Borohydride

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Thomas K.; Karkamkar, Abhijeet J.; Bowden, Mark E.; Besenbacher, Fleming; Jensen, Torben R.; Autrey, Thomas

    2013-01-21

    Ammonium borohydride, NH4BH4, has a high hydrogen content of ρm = 24.5 wt% H2 and releases 18 wt% H2 below T = 160 °C. However, the half-life of bulk NH4BH4 at ambient temperatures, ~6 h, is insufficient for practical applications. The decomposition of NH4BH4 (ABH2) was studied at variable hydrogen and argon back pressures to investigate possible pressure mediated stabilization effects. The hydrogen release rate from solid ABH2 at ambient temperatures is reduced by ~16 % upon increasing the hydrogen back pressure from 5 to 54 bar. Similar results were obtained using argon pressure and the observed stabilization may be explained by a positive volume of activation in the transition state leading to hydrogen release. Nanoconfinement in mesoporous silica, MCM-41, was investigated as alternative means to stabilize NH4BH4. However, other factors appear to significantly destabilize NH4BH4 and it rapidly decomposes at ambient temperatures into [(NH3)2BH2][BH4] (DADB) in accordance with the bulk reaction scheme. The hydrogen desorption kinetics from nanoconfined [(NH3)2BH2][BH4] is moderately enhanced as evidenced by a reduction in the DSC decomposition peak temperature of ΔT = -13 °C as compared to the bulk material. Finally, we note a surprising result, storage of DADB at temperature < -30 °C transformed, reversibly, the [(NH3)2BH2][BH4] into a new low temperature polymorph as revealed by both XRD and solid state MAS 11B MAS NMR. TA & AK are thankful for support from the US Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. A portion of the research was performed using EMSL, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory (PNNL). PNNL is operated by Battelle.

  2. Comparison of Ventricular Electrophysiological Effects of Amiodarone in Canine Models With Congestive Heart Failure and Normal Dogs

    Institute of Scientific and Technical Information of China (English)

    Shuxian Zhou; Yuling Zhang; Juan Lei; Wei Wu; Xuming Zhang

    2008-01-01

    Objectives This study compared the effects of amiodarone on ventricular electrophysiological properties in normal dogs and CHF dogs.Methods Dogs(n=44) were randomized into four groups:Group 1(n=10)was the control.Group 2(n=10) was given amiodarone orally 300 mg·d-1 for4 to 5 weeks.Group 3(n=12)was the congestive heart failure(CHF)models induced by right ventricular rapid pacing(240 pulses·rain-1 for 4 to 5 weeks).Group 4 (n=12) was the CHF models given amiodarone orally 300 mg·d-1 for 4 to 5 weeks.The ventricular electrophysiological variables were evaluated by standard electric stimulation and monophasic action potential(MAP)recording.Results Amiodarone prolonged sinus cycle length(SCL),intra-ventricular conduction time(IVCT),MAP duration(MAPD90),ventricular effective period(VERP),ventricular activation time(VAT)and ventficular recovery time(VRT)without significant effects on the ratio of VERP to MAPD90 (VERP/MAPD90),ventricular fibrillation threshold(VFT),the dispersion of VRT(VRTD),and ventricular late repolarization duration(VLRD)in normal dogs.However,amiodarone did not further prolong the prolonged SCL,MAPD90,VERP,VAT and VRT,but further prolonged IVCT in CHF dogs.Amiodarone normalized the abnormal ventficular electrophysiological properties in CHF dogs as manifested by increasing the decreased VERP/MAPD90 and VFT,shortening the prolonged VLRD,and decreasing the increased VRTD.Amiodarone did not worsen the hemodynamic parameters in normal and CHF dogs.Conclusions Amiodarone had different effects on ventricular electrophysiological properties in normal and CHF dogs.The favorable effects of amiodarone in normalizing some abnormal cardiac electrophysiological properties in CHF models may have potential value on the prevention and treatment of ventricular arrhythmias and sudden cardiac death in CHF.

  3. Inhibition and enhancement of contextual fear memory destabilization

    OpenAIRE

    Lee, Jonathan L. C.; Charlotte eFlavell

    2014-01-01

    The reactivation of a memory can result in its destabilization, necessitating a process of memory reconsolidation to maintain its persistence. Here we show that the destabilization of a contextual fear memory is potentiated by the cannabinoid CB1 receptor agonist ACEA. Co-infusion of ACEA and the IKK inhibitor sulfasalazine into the dorsal hippocampus impaired contextual fear memory reconsolidation. This observation was achieved under behavioural conditions that, by themselves, did not result...

  4. Inhibition and enhancement of contextual fear memory destabilization

    Directory of Open Access Journals (Sweden)

    Jonathan L C Lee

    2014-04-01

    Full Text Available The reactivation of a memory can result in its destabilization, necessitating a process of memory reconsolidation to maintain its persistence. Here we show that the destabilization of a contextual fear memory is potentiated by the cannabinoid CB1 receptor agonist ACEA. Co-infusion of ACEA and the IKK inhibitor sulfasalazine into the dorsal hippocampus impaired contextual fear memory reconsolidation. This observation was achieved under behavioural conditions that, by themselves, did not result in either a reconsolidation impairment by sulfasalazine alone or reactivation-induced upregulation of Zif268 expression. Moreover, we show that the destabilization of a contextual fear memory is dependent upon neuronal activity in the dorsal hippocampus, but not memory expression per se. The effect on contextual fear memory destabilization of intra-hippocampal ACEA was replicated by systemic injections, allowing an amnestic effect of MK-801. These results indicate that memory expression and destabilization, while being independent from one another, are both dependent upon memory reactivation. Moreover, memory destabilization can be enhanced pharmacologically, which may be of therapeutic potential.

  5. Amiodarone is a cost-neutral way of preventing atrial fibrillation after surgery for lung cancer

    DEFF Research Database (Denmark)

    Riber, Lars P; Christensen, Thomas D; Pilegaard, Hans K

    2013-01-01

    OBJECTIVES: Our aim was to estimate the costs and health benefits of routinely administered postoperative amiodarone as a prophylactic agent in reducing the risk of atrial fibrillation in patients undergoing surgery for lung cancer. METHODS: This was a cost-effectiveness study, based on the rando......OBJECTIVES: Our aim was to estimate the costs and health benefits of routinely administered postoperative amiodarone as a prophylactic agent in reducing the risk of atrial fibrillation in patients undergoing surgery for lung cancer. METHODS: This was a cost-effectiveness study, based...... on the randomized, controlled, double-blinded PASCART study, using avoidance of atrial fibrillation as the measure of benefit. Two hundred and fifty-four eligible, consecutively enrolled patients, undergoing surgery for lung cancer at the department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital.......23). There were no signs of adverse developments referable to amiodarone in this prophylactic regime. CONCLUSIONS: For patients undergoing surgery for lung cancer, routine use of postoperative prophylactic intravenous bolus and five subsequent days of oral amiodarone therapy reduces the risk of atrial...

  6. Effects of Amiodarone plus Losartan on Electrical Remodeling in Rapid Atrial Pacing in Rabbits

    Institute of Scientific and Technical Information of China (English)

    Liye Wei; Yue Xia; Guoqing Qi; Qingwen Zhang

    2008-01-01

    Objectives To investigate the electrical remodeling and the effects of amiodarone and losartan on electrical remode-ling in rapid atrial pacing on rabbit model. Methods 40 normal rabbits were randomly divided into 4 groups: the sa-line group (control group), amiodarone group, losartan group, ami + los group. All rabbits were raised drugs in a week. The atrial effective refractory period (AERP) was measured. Then, take a rapid atrial pacing (600 bpm) and the AERP was measured after 0. 5, 1, 2, 4, 6 and 8 hours pacing and 30 minutes after the termination of rapid pacing. Results ① In control group, after 8 hours rapid pacing, AERP 200 and AERP 150 were significantly shortened 16. 11%± 3. 1% (P <0. 01) and 9. 99%±4. 2% (P <0. 01). And the degree of AERP shortening induced by rapid pacing was greater at basic cycle lengths of 200 ms (BCL200) than that at BCL150. The AERP of amiodarone, losartan group and anti + los group were not shortened during rapid pacing.② In the control group, after the termination of rapid pacing, the AERP gradually increased. The AERP at all of the BCLS examined recovered to almost the 95.78% and 96. 76% of baseline values within the first 10 minutes and recovered to almost the 99. 07% and 99. 39% of baseline values within the first 30 minutes. Condusions Short-term atrial rapid pacing can induce the atrial electrical remodeling. Amiodarone and losartan can prevent the electrical remodeling.

  7. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Nasser M

    2013-09-01

    Full Text Available Mohammad Nasser, Timothy R Larsen, Barryton Waanbah, Ibrahim Sidiqi, Peter A McCullough Providence Hospitals and Medical Centers, Department of Medicine, Division of Cardiology, Southfield and Novi, MI, USA Abstract: Amiodarone is a benzofuran class III antiarrhythmic drug used to treat a wide spectrum of ventricular tachyarrhythmias. The parenteral formulation is prepared in polysorbate 80 diluent. We report an unusual case of acute elevation of aminotransaminase concentrations after the initiation of intravenous amiodarone. An 88-year-old Caucasian female developed acute hepatitis and renal failure after initiating intravenous amiodarone for atrial fibrillation with a rapid ventricular response in the setting of acutely decompensated heart failure and hepatic congestion. Liver transaminases returned to baseline within 7 days after discontinuing the drug. Researchers hypothesized that this type of injury is related to liver ischemia with possible superimposed direct drug toxicity. The CIOMS/RUCAM scale identifies our patient’s acute hepatitis as a highly probable adverse drug reaction. Future research is needed to understand the mechanisms by which hyperacute drug toxicity occurs in the setting of impaired hepatic perfusion and venous congestion. Keywords: intravenous amiodarone, acute hepatotoxicity, liver transaminases, drug-induced liver toxicity

  8. Effect of prophylactic amiodarone in patients with rheumatic valve disease undergoing valve replacement surgery

    Directory of Open Access Journals (Sweden)

    Kar Sandeep

    2011-01-01

    Full Text Available The study was carried out to evaluate the effect of prophylactic single-dose intravenous amiodarone in patients undergoing valve replacement surgery. Maintenance of sinus rhythm is better than maintenance of fixed ventricular rate in atrial fibrillation (AF especially in the presence of irritable left or right atrium because of enlargement. Fifty-six patients with valvular heart disease with or without AF were randomly divided into two groups. Group I or the amiodarone group (n=28 received amiodarone (3 mg/kg in 100 ml normal saline and group II or the control group received same volume of normal saline. The standardized protocol for cardiopulmonary bypass was maintained for all the patients. AF occurred in 7.14% patients in group I, and in group II, 28.57% (P=0.035; ventricular tachycardia/fibrillation was observed in 21.43% patients in group I and 46.43% patients in group II (P=0.089 after release of aortic clamp. Most of the patients in group I (92.86% maintained sinus rhythm without cardioversion or defibrillation after release of aortic cross clamp (P=0.002. Defibrillation or cardio version was needed in 7.14% patients in group I and 28.57% patients in group II (P=0.078. A single prophylactic intraoperative dose of intravenous amiodarone decreased post bypass arrhythmia in this study in comparison to the control group. Single dose of intraoperative amiodarone may be used to decrease postoperative arrhythmia in open heart surgery.

  9. In vivo probe-based confocal laser endomicroscopy in amiodarone-related pneumonia.

    Science.gov (United States)

    Salaün, Mathieu; Roussel, Francis; Bourg-Heckly, Geneviève; Vever-Bizet, Christine; Dominique, Stéphane; Genevois, Anne; Jounieaux, Vincent; Zalcman, Gérard; Bergot, Emmanuel; Vergnon, Jean-Michel; Thiberville, Luc

    2013-12-01

    Probe-based confocal laser endomicroscopy (pCLE) allows microscopic imaging of the alveoli during bronchoscopy. The objective of the study was to assess the diagnostic accuracy of pCLE for amiodarone-related pneumonia (AMR-IP). Alveolar pCLE was performed in 36 nonsmoking patients, including 33 consecutive patients with acute or subacute interstitial lung disease (ILD), of which 17 were undergoing treatment with amiodarone, and three were amiodarone-treated patients without ILD. Nine out of 17 patients were diagnosed with high-probability AMR-IP (HP-AMR-IP) by four experts, and three separate observers. Bronchoalveolar lavage findings did not differ between HP-AMR-IP and low-probability AMR-IP (LP-AMR-IP) patients. In HP-AMR-IP patients, pCLE showed large (>20 μm) and strongly fluorescent cells in 32 out of 38 alveolar areas. In contrast, these cells were observed in only two out of 39 areas from LP-AMR-IP patients, in one out of 59 areas from ILD patients not receiving amiodarone and in none of the 10 areas from amiodarone-treated patients without ILD (p<0.001; HP-AMR-IP versus other groups). The presence of at least one alveolar area with large and fluorescent cells had a sensitivity, specificity, negative predictive value and positive predictive value for the diagnosis of AMR-IP of 100%, 88%, 100% and 90%, respectively. In conclusion, pCLE appears to be a valuable tool for the in vivo diagnosis of AMR-IP in subacute ILD patients. PMID:23018901

  10. Acute epigastric and low back pain during amiodarone infusion; is it the drug or the vehicle to blame?

    Science.gov (United States)

    Petrou, Emmanouil; Iakovou, Ioannis; Boutsikou, Maria; Girasis, Chrysafios; Mavrogeni, Sophie; Pavlides, Gregory

    2014-01-01

    Amiodarone is a Class III antiarrhythmic agent used for cardioversion and prevention of recurrences of atrial fibrillation. However, its use is limited due to its side-effects resulting from the drug's long-term administration. We have described acute epigastric pain following treatment with intravenous amiodarone for atrial fibrillation in a previous report. Hereby, we describe a second patient who suffered acute epigastric pain, as well as one who suffered acute low back pain. Intravenous amiodarone has been related to a series of minor and major adverse reactions, indicating other constituents of the intravenous solution as the possible cause, possibly polysorbate-80. A possible correlation between acute epigastric and low back pain after intravenous amiodarone loading is unproven; however it is of crucial importance for clinicians to be aware of this phenomenon, and especially since an acute epigastric pain is implicated in the differential diagnosis of cardiac ischemia. PMID:24239300

  11. Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

    Directory of Open Access Journals (Sweden)

    Daniele Fanale

    2015-01-01

    Full Text Available Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.

  12. Stabilizing versus destabilizing the microtubules: a double-edge sword for an effective cancer treatment option?

    Science.gov (United States)

    Fanale, Daniele; Bronte, Giuseppe; Passiglia, Francesco; Calò, Valentina; Castiglia, Marta; Di Piazza, Florinda; Barraco, Nadia; Cangemi, Antonina; Catarella, Maria Teresa; Insalaco, Lavinia; Listì, Angela; Maragliano, Rossella; Massihnia, Daniela; Perez, Alessandro; Toia, Francesca; Cicero, Giuseppe; Bazan, Viviana

    2015-01-01

    Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy.

  13. Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

    Science.gov (United States)

    Fanale, Daniele; Bronte, Giuseppe; Passiglia, Francesco; Calò, Valentina; Castiglia, Marta; Di Piazza, Florinda; Barraco, Nadia; Cangemi, Antonina; Catarella, Maria Teresa; Insalaco, Lavinia; Listì, Angela; Maragliano, Rossella; Massihnia, Daniela; Perez, Alessandro; Toia, Francesca; Cicero, Giuseppe; Bazan, Viviana

    2015-01-01

    Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines the disruption of the mitotic spindle, halting the cell cycle at the metaphase-anaphase transition and, eventually, resulting in cell death. Clinical application of earlier microtubule inhibitors, however, unfortunately showed several limits, such as neurological and bone marrow toxicity and the emergence of drug-resistant tumor cells. Here we review several natural and synthetic microtubule-targeting agents, which showed antitumor activity and increased efficacy in comparison to traditional drugs in various preclinical and clinical studies. Cryptophycins, combretastatins, ombrabulin, soblidotin, D-24851, epothilones and discodermolide were used in clinical trials. Some of them showed antiangiogenic and antivascular activity and others showed the ability to overcome multidrug resistance, supporting their possible use in chemotherapy. PMID:26484003

  14. Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice

    Energy Technology Data Exchange (ETDEWEB)

    Fromenty, B.; Fisch, C.; Labbe, G.; Degott, C.; Deschamps, D.; Berson, A.; Letteron, P.; Pessayre, D. (Institut National de la Sante et de la Recherche Medicale U24, Clichy (France))

    1990-12-01

    Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from (U-14C)palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of (14C)CO2 from (U-14C)palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of (U-14C)palmitic acid. One hour after 100 mg.kg-1, the exhalation of (14C)CO2 from (1-14C)palmitic acid, (1-14C)octanoic acid or (1-14C)butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of (14C)CO2 from (1-14C)palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice.

  15. Acute effect of amiodarone on cardiovascular reflexes of normotensive and renal hypertensive rats

    Directory of Open Access Journals (Sweden)

    Oliveira P.F.

    2005-01-01

    Full Text Available The aim of the present study was to evaluate the effect of amiodarone on mean arterial pressure (MAP, heart rate (HR, baroreflex, Bezold-Jarisch, and peripheral chemoreflex in normotensive and chronic one-kidney, one-clip (1K1C hypertensive rats (N = 9 to 11 rats in each group. Amiodarone (50 mg/kg, iv elicited hypotension and bradycardia in normotensive (-10 ± 1 mmHg, -57 ± 6 bpm and hypertensive rats (-37 ± 7 mmHg, -39 ± 19 bpm. The baroreflex index (deltaHR/deltaMAP was significantly attenuated by amiodarone in both normotensive (-0.61 ± 0.12 vs -1.47 ± 0.14 bpm/mmHg for reflex bradycardia and -1.15 ± 0.19 vs -2.63 ± 0.26 bpm/mmHg for reflex tachycardia and hypertensive rats (-0.26 ± 0.05 vs -0.72 ± 0.16 bpm/mmHg for reflex bradycardia and -0.92 ± 0.19 vs -1.51 ± 0.19 bpm/mmHg for reflex tachycardia. The slope of linear regression from deltapulse interval/deltaMAP was attenuated for both reflex bradycardia and tachycardia in normotensive rats (-0.47 ± 0.13 vs -0.94 ± 0.19 ms/mmHg and -0.80 ± 0.13 vs -1.11 ± 0.13 ms/mmHg, but only for reflex bradycardia in hypertensive rats (-0.15 ± 0.02 vs -0.23 ± 0.3 ms/mmHg. In addition, the MAP and HR responses to the Bezold-Jarisch reflex were 20-30% smaller in amiodarone-treated normotensive or hypertensive rats. The bradycardic response to peripheral chemoreflex activation with intravenous potassium cyanide was also attenuated by amiodarone in both normotensive (-30 ± 6 vs -49 ± 8 bpm and hypertensive rats (-34 ± 13 vs -42 ± 10 bpm. On the basis of the well-known electrophysiological effects of amiodarone, the sinus node might be the responsible for the attenuation of the cardiovascular reflexes found in the present study.

  16. Interaction of rivaroxaban with amiodarone, verapamil and diltiazem in patients with atrial fibrillation: terra incognita

    Directory of Open Access Journals (Sweden)

    S. N. Bel'diev

    2016-03-01

    Full Text Available Currently there are no generally accepted guidelines for the use of rivaroxaban together with amiodarone, verapamil or diltiazem in patients with creatinine clearance (CrCl<80 ml/min. Some researchers suggest that in renal failure amiodarone, verapamil and diltiazem contribute to a significant increase in plasma concentrations of rivaroxaban that is accompanied by increased risk of bleeding. According to preliminary calculations, it seems rational to reduce the dose of rivaroxaban when co-administered with these drugs: to 15 mg/day in patients with ClCr 50-79 ml/min and to 10 mg/day in patients with ClCr<50 ml/min.

  17. Use of amiodarone and digoxin specific Fab antibodies in digoxin overdosage.

    OpenAIRE

    Nicholls, D P; Murtagh, J. G.; Holt, D W

    1985-01-01

    A 61 year old man with mild aortic stenosis and chronic depression took 12.5 mg digoxin in a suicide attempt. Ventricular tachycardia and fibrillation were resistant to lignocaine and to phenytoin but responded to intravenous amiodarone, with restoration of pacing. Because of persistent hyperkalaemia he was also treated with Fab fragments of digoxin specific antibody, which bound most of the ingested digoxin. It is suggested that the treatment of choice in severe digoxin poisoning is amiodaro...

  18. Comparative in vitro and in vivo evaluation of three tablet formulations of amiodarone in healthy subjects

    Directory of Open Access Journals (Sweden)

    J Emami

    2010-09-01

    Full Text Available "nBackground and the purpose of the study:The relative in vivo bioavailability and in vitro dissolution studies of three chemically equivalent amiodarone generic products in healthy volunteers was evaluated in three separate occasions. The possibility of a correlation between in vitro and in vivo performances of these tablet formulations was also evaluated. "nMethods: The bioequivalence studies were conducted based on a single dose, two-sequence, cross over randomized design. The bioavailability was compared using AUC0-72, AUC0-∞, Cmax and Tmax. Similarity factor, dissolution efficiency (DE, and mean dissolution time (MDT was used to compare the dissolution profiles. Polynomial linear correlation models were tested using either MDT vs mean residence time (MRT or fraction of the drug dissolved (FRD vs fraction of the drug absorbed (FRA. "nResults: Significant differences were found in the dissolution performances of the tested formulations and therefore they were included in the development of the correlation. The 90% confidence intervals of the log-transformed AUC0-72, AUC0-∞, and Cmax of each two formulations in each bioequivalence studies were within the acceptable range of 80-125%. Differences were not observed between the untransformed Tmax values. Poor correlation was found between MRT and MDT of the products. A point-to-point correlation which is essential for a reliable correlation was not obtained between pooled FRD and FRA. The dissolution condition which was used for amiodarone tablets failed for formulations which were bioequivalent in vivo and significant difference between the dissolution characteristics of products (f2<50 did not reflect their in vivo properties. Major conclusions: Bioequivalence studies should be considered as the only acceptable way to ensure the interchangeability and in vivo equivalence of amiodarone generic drug products. The dissolution conditions used of the present study could be used for routine and in

  19. Study with radio aerosol of DTPA technetium-99 m in individuals with pulmonary disease by amiodarone

    International Nuclear Information System (INIS)

    In order to evaluate the role of the clearance of 99 m Technetium chelated to diethylenetriamine-penta-acetate (99 m Tc-DTPA) in amiodarone induced pulmonary disease, 40 individuals were studied in four groups. After spirometry, where a volume-time curve was registered, all individuals inhaled 740 MBq of 99 m Tc-DTPA diluted in 4 ml of saline, for five minutes. Pulmonary images were obtained in a computerized scintillation camera and 9 regions of interest were selected. (author)

  20. [Amiodaron neuropathy: clinical and pathological study of a new drug induced lipidosis (author's transl)].

    Science.gov (United States)

    Dudognon, P; Hauw, J J; de Baecque, C; Derrida, J P; Escourolle, R; Nick, E J

    1979-01-01

    The authors report a case of amiodaron-induced neuropathy in a seventy one years old man. First signs appeared seventeen months after the treatment was started with 400 mg/day for one year and continued with 200 mg/day. Examination on the 29th month disclosed a severe sensory and motor deficit of the limbs with distal predominancy. Motor nerve conduction velocity was strongly impaired without modification of distal latencies. Fundi were normal. The patient improved quickly after drug withdrawal. The authors review the rare similar cases reported in the literature and attempt to describe the clinical caracteristics of amiodaron neuropathy. Qualitative and quantitative light and electron microscopical studies of nerve, muscle and skin biopsies, including teased fibers preparations were performed and they disclosed a marked reduction of the number of myelinated fibers. Wallerian degeneration predominated (31 p. 100) other segmental demyalination (25 p. 100). Numerous polymorphous lipid-laden lysosomes were present in Schwann cells, fibrocytes, pericytes, endothelial and muscle cells. These previously undescribed morphological findings are similar to those present in perhexiline maleate intoxications. We believe amiodaron neuropathy is a new neuropathy with drug-induced lipidosis. PMID:531409

  1. Cryptogenic organizing pneumonia due to amiodarone: long-term follow-up after corticosteroid treatment.

    Science.gov (United States)

    Schindler, Katja; Schima, Wolfgang; Kaliman, Josef F

    2010-08-01

    Cryptogenic organizing pneumonia (formerly known as bronchiolitis obliterans organizing pneumonia) is a clinicopathological entity with characteristical radiographic findings such as bilateral, asymmetrical, sometimes migrating, patchy infiltrates in chest radiograph and ground-glass opacities in computed tomography. The disease has been observed in the context of gastrointestinal disorders, certain lung infections, autoimmune-mediated diseases (such as Wegener granulomatosis), inhalation of toxic fumes, bone marrow transplantation and administration of drugs. The benzofuran amiodarone, a commonly used antiarrythmic drug for atrial fibrillation, can exhibit several pulmonary adverse effects, amongst them cryptogenic organizing pneumonia as a rarely diagnosed and published one. We report a case of cryptogenic organizing pneumonia secondary to amiodarone treatment, its clinical course with significant improvement of clinical symptoms within a few days after discontinuation of amiodarone treatment and administration of corticosteroids. Also the infiltrations found in chest X-ray and computed tomography responded well and showed remarkable resolution tendency quickly. During 5 months of corticoid therapy pulmonary abnormalities gradually resolved almost completely and remained equal during the 8 months follow-up after corticoid termination. PMID:20668958

  2. Effect of Stem Cell Therapy on Amiodarone Induced Fibrosing Interstitial Lung Disease in Albino Rat

    Science.gov (United States)

    Zaglool, Somaya Saad; Zickri, Maha Baligh; Abd El Aziz, Dalia Hussein; Mabrouk, Doaa; Metwally, Hala Gabr

    2011-01-01

    Background and Objectives: The fibrosing forms of interstitial lung disease (ILD) are associated with significant morbidity and mortality. ILD may be idiopathic, secondary to occupational, infection, complicate rheumatic diseases or drug induced. Efficacy of antifibrotic agents is as far as, limited and uncertain. No effective treatment was confirmed for pulmonary fibrosis except lung transplantation. The present study aimed at investigating the possible effect of human cord blood mesenchymal stem cell (MSC) therapy on fibrosing ILD. This was accomplished by using amiodarone as a model of induced lung damage in albino rat. Methods and Results: Seventeen adult male albino rats were divided into 3 groups. Rats of amiodarone group were given 30 mg/kg of amiodarone orally 6 days/ week for 6 weeks. Rats of stem cell therapy group were injected with stem cells in the tail vein following confirmation of lung damage and left for 4 weeks before sacrifice. Obstructed bronchioles, thickened interalveolar septa and thickened wall of pulmonary vessels were found and proved morphometrically. Reduced type I pneumocytes and increased area% of collagen fibers were recorded. All findings regressed on stem cell therapy. Conclusions: Cord blood MSC therapy proved definite amelioration of fibrosing interstitial lung disease provided therapy starts early in the development of the pathogenesis. PMID:24298346

  3. In vitro study of lovastatin interactions with amiodarone and with carbon tetrachloride in isolated rat hepatocytes

    Institute of Scientific and Technical Information of China (English)

    AZ Krasteva; MK Mitcheva; MS Kondeva-Burdina; VA Descatoire

    2007-01-01

    AIM: To investigate the interactions at a metabolic level between lovastatin, amiodarone and carbon tetrachloride in isolated rat hepatocytes.METHODS: For cell isolation two-step collagenase liver perfusion was performed. Lovastatin was administered alone in increasing concentrations (1 μmol/L, 3 μmol/L,5 μmol/L and 10 μmol/L) and in combination with CCl4 (86 μmol/L). The cells were also pretreated with 14 μmol/Lamiodarone and then the other two compounds were added.RESULTS: Lovastatin promoted concentration-dependent significant toxicity estimated by decrease in cell viability and GSH level by 45% and 84%, respectively. LDH-activity increased by 114% and TBARS content by 90%. CCl4 induced the expected severe damage on the examined parameters. CCl4 induced toxicity was attenuated after lovastatin pretreatment, which was expressed in less increased values of LDH activity and TBARS levels, as well as in less decreased cell viability and GSH concentrations. However, the pretreatment of hepatocytes with amiodarone abolished the protective effect of lovastatin.CONCLUSION: We suggest that the observed cytoprotective effect was due to interactions between lovastatin,CCl4 and amiodarone at a metabolic level.

  4. Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.

    Science.gov (United States)

    Chhabra, Resham; Grabrucker, Andreas M; Veratti, Patrizia; Belletti, Daniela; Boeckers, Tobias M; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara

    2014-08-25

    Polymeric nanoparticles (NPs) offer a promising approach for therapeutic intracellular delivery of proteins, conventionally hampered by short half-lives, instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic internalization leading to NPs content's release within lysosomes. To overcome lysosomal degradation and achieve NPs and/or loaded proteins release into cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid organization within the polymeric matrix. Experiments on NIH cells and rat primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover, after internalization, NPs are able to transiently destabilize the integrity of lysosomes in which they are taken up, speeding their escape and favoring cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as promising carriers for intracellular protein delivery.

  5. Comparison of amiodarone vs magnesium sulphate in the prevention of atrial fibrillation after coronary artery bypass grafting surgery

    International Nuclear Information System (INIS)

    Background: Atrial fibrillation (AF) is common in patients after coronary artery bypass grafting (CABG) and can result in increased morbidity and mortality, increased length of hospital stay, and increased cost. In this study we compared the efficacy of amiodarone versus magnesium sulphate in the prophylaxis of post-CABG atrial fibrillation. Objective: This study was carried out to assess the efficacy of amiodarone in comparison to magnesium sulphate in the prevention of atrial fibrillation after coronary artery bypass grafting. Study Design: Randomized controlled trials. Place and duration of study: The study was carried out at Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi from July 2010 to December 2011 Patients and Methods: Total 240 patients were included in the study and randomly divided in two groups of 120 each using random number table. Patients in Group A (Amiodarone group) were given a loading dose of amiodarone 5 mg/Kg after induction of anesthesia which was then continued as infusion at 5 micro gm/Kg/minute on first postoperative day. This was followed by an oral dose of 600 mg/day postoperatively for 5 days. Those in Group B (Magnesium Sulphate group) received 2 g of magnesium sulphate in 100 ml of isotonic 0.9% solution intravenously over 1 hour at following times: preoperatively, immediately following the operation, and on postoperative days 1, 2, and 3. Results: Thirteen patients (10.8%) developed AF in Amiodarone group, compared to 31 patients (25.8%) in magnesium sulphate group. The results proved amiodarone to be more effective than magnesium sulphate in preventing post-CABG AF (p<0.001). Thirty one patients who developed AF postoperatively in the magnesium group were treated with amiodarone, and all patients recovered normal sinus rhythm. In the amiodarone prophylaxis group, 9 patients regained sinus rhythm in 6 - 8 hours, while for 4 remaining patients cardioversion was attempted out of which 2

  6. Histopathological and Biochemical Toxic Effect of Amiodarone on Thyroid Gland in Albino Rat

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    Ola A. El Sayed*, Safaa E. Gawish

    2007-12-01

    Full Text Available Backgrounds: Amiodarone AMD (Cordarone was a benzofuran derivative, used in management of angina and refractory ventricular arrhythmia. Its effect on the thyroid gland structure and function was investigated in this study. Material and Methods: Fifty adult male albino rats were used and divided into three groups. The first group was consisted of 10 rats which served as control, received distilled water orally (1ml. The second group was consisted of 20 rats used as therapeutic dose treated group, received 40 mg/Kg b. w. of amiodarone while the third group was consisted of 20 rats used as a toxic dose treated group which received 60 mg/Kg b. w. of amiodarone orally daily for three months. Body weight of animals was determined. Serum concentration of tri-iodothyonine (T3, thyroxine (T4, thyrotrophin (TSH, interleukin 6 (IL6, tumour marker P53 and tissue residue for amiodarone in plasma, fat, liver, lung, thyroid gland and heart was determined. Results: Specimens from thyroid gland were taken and prepared for light and electron microscope examination. Highly significant decrease in body weight (P<0.001 were observed in both therapeutic and toxic doses treated groups in comparison to the control one. A very highly significant increase (P<0.001 of serum (T4 & T3 with Concomitant suppression of (TSH (P<0.001. Serum levels of IL6 and P53 showed also a very highly significant increase (P<0.001. Amiodarone concentration in plasma, fat, liver, lung, thyroid gland and heart showed significant increase in therapeutic dose treated group and highly significant increase in toxic dose treated group. Histopathological examination of thyroid gland of therapeutic dose treated group by light microscope showed marked evidence of thyotoxicosis in the form of microcystic follicular changes and peripheral scalloping, cellular degeneration with scanty cytoplasm and vesicular nuclei appeared. These changes became more severe in toxic dose treated group in the form of

  7. Correlation of Biomicroscopic Findings with Confocal Microscopy in Eyes with Amiodarone-Induced Cornea Verticillata

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    Emine Kaya

    2014-01-01

    Full Text Available Objectives: To investigate the correlation between biomicroscopic and confocal microscopic findings in eyes with amiodarone-induced cornea verticillata. Materials and Methods: Sixteen eyes of 8 patients with amiodarone-induced cornea verticillata were evaluated. Eyes with keratopathy were staged according to Orlando slit-lamp microscopy classification. Confocal laser-scanning microscopy was performed by Rostock cornea modulated to HRT II (Heidelberg Engineering GmbH, Heidelberg, Germany, and staging was done according to Falke’s classification that is based on the degree of epithelial basal cell deposit accumulation. The relation between biomicroscopic staging and corneal involvement detected on confocal microscopy was assessed by Spearman correlation analysis. Results: The mean age of the 8 patients (5 male, 3 female was 63.1±7.2 (50 to 69 years. The mean duration of drug treatment was 12.1±11.8 (3 to 36 months, and the mean drug treatment dose was 312.5±223.2 (100 to 800 mg/day. At the time of examination, 50% of the patients had already given up the treatment at a mean of 29.5±15.8 (6 to 40 months ago, whereas the other 50% were still on amiodarone therapy. Hyper-reflecting deposits were observed in the basal epithelium, anterior-, mid-and deep-stroma, and in the endothelium on confocal microscopic examination. Correlation was detected between biomicroscopic and confocal microscopic stages (r=0.770, p<0.001. Frequency of detecting deposits in the stroma and endothelium was found to be increasing as the biomicroscopic stage increased (r=0.844; p<0.001 and r=0.551; p<0.01, respectively. Conclusion: In amiodarone-induced cornea verticillata, correlated results were detected between biomicroscopic and confocal microscopic staging. Therefore, in clinics where confocal microscopy is not available, biomicroscopic staging can be used as a guiding parameter in eyes with amiodarone-induced cornea verticillata. (Turk J Ophthalmol 2014; 44: 63-67

  8. Mexiletine as an adjunctive therapy to amiodarone reduces the frequency of ventricular tachyarrhythmia events in patients with an implantable defibrillator.

    Science.gov (United States)

    Gao, Dongsheng; Van Herendael, Hugo; Alshengeiti, Lamia; Dorian, Paul; Mangat, Iqwal; Korley, Victoria; Ahmad, Kamran; Golovchiner, Gregory; Aves, Theresa; Pinter, Arnold

    2013-08-01

    The most effective pharmacological management of frequent ventricular tachyarrhythmia events in patients with an implantable defibrillator who failed or did not tolerate amiodarone is unknown. The aim of this retrospective cohort study was to assess the efficacy and tolerability of mexiletine in such patients. The patients served as self-controls. The number of treated ventricular tachyarrhythmia episodes (primary outcome); mortality, shocks from the defibrillator, and electrical storm events (secondary outcomes) during mexiletine therapy was compared with a matched duration of observation just before initiating mexiletine in 29 patients who were treated with a median dose of 300 mg/d of mexiletine and were followed for a median of 12 months. None of the patients had to stop mexiletine due to side effect. There was a significant reduction in the incidence of ventricular tachycardia/fibrillation episodes (median 2 vs. 12 events, P = 0.001) and shocks (median 0 vs. 2 events, P = 0.003) in the first 3 months of treatment, but long-term efficacy was only observed among patients who continued amiodarone therapy. In conclusion, mexiletine, when added to amiodarone in case of amiodarone inefficacy, reduces ventricular tachycardia/fibrillation events and appropriate therapies in patients with an implantable cardioverter defibrillator. A randomized trial should validate the efficacy and safety of mexiletine as an adjunctive therapy to amiodarone. PMID:23609328

  9. Trastornos tiroideos por amiodarona The effects of amiodarone on the thyroid

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    M. Toni

    2009-12-01

    (59% vs 41%, lo que puede estar justificado por ser Navarra una comunidad con déficit de yodo. Es necesario el seguimiento de la función tiroidea durante al menos 2-3 años después del inicio del tratamiento con amiodarona.Background. Amiodarone is a drug widely used for the treatment of arrhythmias. In 16% of amiodarone-treated patients it causes changes in the thyroid function. The aim of this study was to determine the importance of amiodarone-induced thyroid dysfunction in the population of Navarre, studied between 2001 and 2007. Methods. We present a retrospective study that considers the characteristics of 182 amiodarone-treated patients with thyroid dysfunction who had been referred to our Institute. We determined a series of biochemical and instrumental investigations (measurement of thyrotrophin, free thyroid hormones and thyroid autoantibodies; thyroid sonography and thyroid scintigraphy uptake. Results. Screening of the thyroid function, recommended before starting amiodarone treatment, was carried out in only 20.9 % of the patients. Forty-one percent of patients developed amiodarone induced hypothyroidism; in 76% of them the drug was withdrawn. Hypothyroidism appears after 21 (± 12 months of amiodarone treatment. Forty-eight point six developed permanent hypothyroidism. This group of patients had higher serum levels of TSH (thyrotropin and were treated for less time with amiodarone. Fifty-nine percent of patients developed amiodarone induced thyrotoxicosis; 59.4 % were diagnosed with thyrotoxicosis (AIT type 1, 30.6% AIT type 2 and the remaining 10 % were diagnosed with mixed thyrotoxicosis. Thyrotoxicosis appears after 29.5 (± 17 months of amiodarone treatment. The serum levels of free thyroxine were significantly higher in the AIT type 2 than in the AIT type1. All patients were treated with antithyroid drugs and/or corticoids. Some patients were admitted to hospital due to the severity of their illness. Conclusions. In our study, amiodarone induced

  10. Microscopia confocal in vivo nos depósitos corneanos por amiodarona In vivo confocal microscopy in amiodarone corneal deposits

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    Gustavo Victor

    2007-02-01

    Full Text Available OBJETIVO: Descrever os achados da microscopia confocal in vivo em pacientes nos diversos estágios de ceratopatia induzida por amiodarona, e correlacionar o estadiamento biomicroscópico com o estadiamento confocal. MÉTODOS: Vinte olhos de 10 pacientes (6 homens e 4 mulheres em tratamento com amiodarona, que apresentavam ceratopatia induzida pela droga, foram selecionados para o estudo, com a microscopia confocal (MC. RESULTADOS: A média de idade foi 58 ± 6,2 anos (50-66 anos e o tempo de uso da droga foi de 6 ± 3,2 anos (2-11 anos. Todos pacientes tinham acuidade visual com correção melhor ou igual a 20/40. A biomicroscopia evidenciou ceratopatia por amiodarona: dois pacientes no estágio 1, quatro no estágio 2 e quatro no estágio 3. Todas as córneas apresentaram inclusões intracelulares brilhantes e de alta refletividade na camada epitelial basal. A partir dos estágios 2 e 3, foram encontrados microdepósitos em todas camadas corneanas. Foram observados afilamento e aumento da tortuosidade dos nervos corneanos nos estágios 2 e 3 da ceratopatia. A contagem endotelial média foi de 2.524 ± 150,3 células/mm². CONCLUSÃO: O epitélio basal foi o mais acometido nos diferentes estágios da ceratopatia. Nos pacientes do estágio 1 a biomicroscopia, os microdepósitos subepiteliais são restritos ao epitélio superficial e basal, ao passo que nos pacientes dos estágios 2 e 3, os microdepósitos afetam todas camadas corneanas. À medida que a ceratopatia avança, os nervos corneanos ficam mais afilados e tortuosos.PURPOSE: To describe in vivo confocal microscopy findings in patients with different stages of amiodarone-induced keratopathy, and correlate biomicroscopy stages with confocal stages. METHODS: Twenty eyes of 10 patients (6 men and 4 women, who receive treatment with amiodarone were selected for the study with confocal microscopy (MC. RESULTS: The average age was 58 ± 6.2 years (50-66 years and time of use of the drug was 6

  11. Intracellular Bacteria in Protozoa

    Science.gov (United States)

    Görtz, Hans-Dieter; Brigge, Theo

    Intracellular bacteria in humans are typically detrimental, and such infections are regarded by the patients as accidental and abnormal. In protozoa it seems obvious that many bacteria have coevolved with their hosts and are well adapted to the intracellular way of life. Manifold interactions between hosts and intracellular bacteria are found, and examples of antibacterial resistance of unknown mechanisms are observed. The wide diversity of intracellular bacteria in protozoa has become particularly obvious since they have begun to be classified by molecular techniques. Some of the bacteria are closely related to pathogens; others are responsible for the production of toxins.

  12. Analysis of destabilizing factors effect on hybrid reflector antenna radiation

    OpenAIRE

    Smorodin, G. N.; Braude, V. B.

    1995-01-01

    The paper deals with the effect of various destabilizing factors including manufacture inaccuracy on a hybrid reflector antenna (HRA) radiation pattern. Antenna designed for the airport precision approach radar (PAR) is considered as an example of HRA. Antenna uses a reflector 2.8*3.3 m cut of hyperboloid and an offset cylindrical phased array containing about seven hundred transmission-type waveguide phase shifters. The array is fed by a monopulse four-waveguide horn and is operated by a ste...

  13. Catastrophic destabilization of tunnel under rocks slipping in faultage

    Institute of Scientific and Technical Information of China (English)

    LIU Hai-qing; WANG Xue-qing; YUAN Jing

    2008-01-01

    The model of catastrophic destabilization of tunnel under rock slipping in fault zone based on catastrophic theory and the potential function of fault movement were presented. On the basis of the results above, through Taylor series expansion of the equation of equilibrium surface, its standard form was obtained. Analysis show that catastrophic destabilization of tunnel will occur only when stiffness ratio between elastic sector and strain weakening sector of soft rocks was larger than or equal to 1. On the other hand,sliding behavior and evolution path of fault were directly affected by exogenous process,and it was a major extraneous factor which leads to catastrophic destabilization of tunnel.In the condition of system catastrophe could be generated, if external forces vary from smaller to larger, firstly, fault sticks or creeps, and secondly, when external force equal to or larger than critical value, fault turns to slip suddenly. Inverse, if external forces vary from larger to smaller, fault smoothly slips firstly, when external force equal to or smaller than critical value, and fault turns to stick or creep suddenly.

  14. Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

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    Helene Hartwig

    Full Text Available Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

  15. Alternative methods of local amiodarone delivery for atrial fibrillation prevention in patients after coronary artery bypass grafting

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    Bockeria L.A.

    2016-03-01

    Some anti-inflammatory agents have shown good results in postoperative AF prevention, including such as non-steroidal anti-inflammatory drugs, Colchicine, glucocorticoids and statins. The method of using of epicardial patches with antyarrhythmic drugs is limited with short drug exposition duration time. Epicardial application of the adhesive hydrogel with amiodarone is less invasive, safe, technically simple and effective method of atrial fibrillation prevention. The results of preclinical and known clinical trials have shown the possibility of this method using for AF prevention with lower risk of systemic and local adverse effects of amiodarone in comparison with oral and systemic use.

  16. Dysfunction of the thyroid gland during amiodarone therapy: a study of 297 cases

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    Czarnywojtek A

    2016-04-01

    Full Text Available Agata Czarnywojtek,1,2,* Maria Teresa Płazińska,3,* Małgorzata Zgorzalewicz-Stachowiak,4 Kosma Woliński,1 Adam Stangierski,1 Izabela Miechowicz,5 Joanna Waligórska-Stachura,1 Paweł Gut,1 Leszek Królicki,3 Maja Zioncheck,6 Marek Ruchała1 1Department of Endocrinology, Metabolism and Internal Medicine, 2Department of Pharmacology, Poznan University of Medical Sciences, Poznan, 3Nuclear Medicine Department, Medical University of Warsaw, Warsaw, 4Department of Health Prophylaxis, Laboratory of Medical Electrodiagnostics, 5Department of Computer Science and Statistics, 6Poznan University of Medical Sciences, Poznan, Poland *These authors contributed equally to this work Aim: This study aims to explore and compare the efficacy of radioiodine treatment (RIT in hyperthyroid and euthyroid patients who have been treated with amiodarone (AM in the past or are currently undergoing AM treatment. Clinical observation of a group of patients with amiodarone-induced hypothyroidism during a 12-month follow-up period was used for comparison.Design: This was a observational, two-centered study. Patients were assessed at baseline and at 2 months, 6 months, 8 months, and 12 months after RIT.Patients: Group A: At baseline (61 males [M] and 17 females [F], mean age 50±19 years, there were 78 euthyroid patients with cardiac arrhythmias, who were treated with AM and developed amiodarone-induced thyrotoxicosis, and currently require retreatment with AM. Group B: Hyperthyroid patients (92 M and 26 F, mean age 72±11.8 years after AM therapy in the past. Group C: Hyperthyroid patients (66 M and 13 F, mean age 63.9±13.2 years currently treated by AM. Group D: Hypothyroid patients (6 M and 16 F, mean age 61.4±10.4 years after AM therapy. The patients from Groups A, B, and C were retreated with AM after ~3–6 weeks of RIT.Results: In Group A, after 12 months of RIT therapy, recurrent thyrotoxicosis was observed in six (7.7% cases, and persistent

  17. Protective Effect of Wenxin Granula on Heart from Myocardial Infarction through Regulating Intracellular Ca2+

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-xue; YANG Bao-feng; LI Xue-lian; CHU Wen-feng; CAI Rui-jun; SHI Yong-fang; XU Chao-qian; SHAN Hong-li; WANG Xing-yang; LU Yan-jie

    2011-01-01

    Objective To assess the anti-arrhythmic activity and cardioprotective effects of Wenxin Granula, a traditional Chinese formula (consisting of Salviae Miltiorrhizae Radix, Polygonati Rhizoma, Notoginseng Radix et Rhizoma, Nardostachyos Radix et Rhizoma, Angelicae Sinensis Radix, and Succinum), on heart in ischemic-induced myocardial infarction (MI) rats and compare with those of Amiodarone which have been demonstrated in clinic. Methods Rats were randomly divided into Sham-operated (control), Ml + Amiodarone [5 mg/(kg·d)] (MI), and MI + Wenxin Granula [10 mg/(kg·d)] groups and left anterior descending coronary artery was occluded in each group. After left anterior descending for 12 h, standard lead Ⅱ of administration electrocardiogram was recorded in order to analyze the occurrence of arrhythmia. After one month, the size of the infarct area of heart was evaluated by TTC staining method and haemodynamic function was assessed to detect the heart function. Laser scanning confocal microscope and the technique of patch clamp were used to detect the intracellular Ca2+ ([Ca2+]j) and L-type calcium current (ICa-L), respectively. Results Both Wenxin Granula [10 mg/(kg·d)] and Amiodarone [5 mg/(kg·d)] could markedly decrease the incidence of arrhythmia in heart of rats which were subjected to ischemic injury. After one month, Wenxin Granula could significantly decrease mortality to 22.22% and reduce the infarct area (P < 0.05), but Amiodarone did not. The mechanism may involve that Wenxin Granula attenuated [Ca2+]j decreasing in MI rats. Additionally, Wenxin Granula could obviously ameliorate the impaired heart function of MI rats by decreasing the elevated left ventricular end-diastolic pressure and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period. On the other hand, electrophysiological experiment results revealed that Wenxin Granula administration one month later also increased the

  18. Amiodarona y disfunción tiroidea Amiodarone and thyroid dysfunction

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    Leonardo F. L. Rizzo

    2012-02-01

    Full Text Available La amiodarona es un análogo estructural de la hormona tiroidea, y algunas de sus propiedades antiarrítmicas como así también su toxicidad son atribuibles a su interacción con los receptores nucleares de las hormonas tiroideas. Por ser muy lipofílica, la amiodarona se concentra en muchos tejidos y se elimina, por consecuencia, muy lentamente. Se emplea preferentemente para el tratamiento de arritmias graves tales como fibrilación y taquicardia ventriculares. Otras indicaciones incluyen la fibrilación auricular y el aleteo, la insuficiencia cardíaca congestiva grave, la prevención de la fibrilación auricular recurrente y situaciones de emergencia médica como la prevención de muerte súbita cardiaca¹. Nuestro objetivo es proporcionar un enfoque actualizado sobre la amiodarona y su influencia sobre la fisiología tiroidea y discutir y analizar en profundidad sus potenciales efectos adversos como el hipotiroidismo y la tirotoxicosis.Amiodarone is a structural analogue of thyroid hormone, and some of its anti-arrhythmic actions and toxicity are attributable to its interaction with nuclear receptors of thyroid hormones. Being highly lipophilic, amiodarone is concentrated in many tissues and is eliminated, consequently, very slowly. It is preferably employed to manage life-threatening arrhythmias, including ventricular fibrillation and unstable ventricular tachycardia. Other indications include atrial fibrillation and flutter, severe congestive heart failure, prevention of atrial fibrillation recurrence, and even in emergency medical situations to prevent sudden cardiac death. The aim of this review is to provide an updated approach on amiodarone and its influence on thyroid physiology and to discuss and analyze in depth its potential and not infrequent thyroidal adverse effects such as hypothyroidism and thyrotoxicosis.

  19. Effects of amiodarone therapy on thyroid iodine content as measured by x-ray fluorescence

    Energy Technology Data Exchange (ETDEWEB)

    Fragu, P.; Schlumberger, M.; Davy, J.M.; Slama, M.; Berdeaux, A.

    1988-04-01

    Thyroid iodine content (TIC) was measured by x-ray fluorescence in 68 patients who had received amiodarone treatment for varying intervals (1 g/week for 1-120 months). Thirty-six patients were euthyroid; the mean TIC of the patients (n = 15), who had been treated for less than 12 months was 30 +/- 19 (+/- SD) mg, twice the normal mean value (14.6 +/- 5.0 mg), and it was 39 +/- 17 mg in those (n = 16) who had been treated for 12-60 months and 29 +/- 6 mg in those (n = 5) who had been treated longer (greater than 60 months). Nineteen patients were hyperthyroid and had elevated TIC values. Of them, 6 patients had a goiter; their TIC (50 +/- 19 mg) was not significantly different from that of the hyperthyroid patients with no goiter (55 +/- 29 mg), but they became hyperthyroid more rapidly. Thirteen patients were hypothyroid; none had TIC values above the normal range, and it was below 2.5 mg in 5 patients. A sequential study was undertaken in 11 euthyroid patients who had no detectable antithyroid antibodies. TIC did not increase during treatment in 2 patients; both developed hypothyroidism, which was transient in 1 despite continuation of amiodarone treatment. The TIC initially increased during amiodarone treatment in the other 9 patients, leveling off at the end of the first year. The TIC rose well above the upper limit of the normal range in 4 patients, of whom 2 became hyperthyroid during the second year of treatment. TIC remained within the normal range in the other 5 patients, of whom 3 became hypothyroid after 12-24 months of treatment (1 subclinical, 2 overt). Although the TIC was significantly higher in the patients with hyperthyroidism than in the patients who remained euthyroid, the TIC test cannot be used to predict the occurrence of hyperthyroidism.

  20. Cardiac arrest provoked by itraconazole and amiodarone interaction: a case report

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    Betrosian Alex

    2011-07-01

    Full Text Available Abstract Introduction Azoles, and specifically itraconazole, are often prescribed for the treatment of fungal diseases or empirically for persistent sepsis in patients who are neutropenic or in intensive care. Occasional cardiovascular adverse events have been associated with itraconazole use, and are usually attributed to the interaction of itraconazole with cisapride, terfenadine or digoxin. Its interaction with amiodarone has not been previously described. Case presentation A 65-year-old Caucasian man was admitted to the Intensive Care Unit at our facility for an extensive ischemic stroke associated with atrial fibrillation. Due to rapid ventricular response he was started on intravenous amiodarone and few days later itraconazole was also prescribed for presumed candidemia. After receiving the first dose our patient became profoundly hypotensive but responded rapidly to fluids and adrenaline. Then, two months later, itraconazole was again prescribed for confirmed fungemia. After receiving the first dose via a central venous catheter our patient became hypotensive and subsequently arrested. He was resuscitated successfully, and as no other cause was identified the arrest was attributed to septic shock and his antifungal treatment was changed to caspofungin. When sensitivity test results became available, antifungal treatment was down-staged to itraconazole and immediately after drug administration our patient suffered another arrest and was once again resuscitated successfully. This time the arrest was related to itraconazole, which was discontinued, and from then on our patient remained stable until his discharge to our neurology ward. Conclusions Itraconazole and amiodarone coadministration can lead to serious cardiovascular adverse events in patients who are critically ill. Intensivists, pharmacists and medical physicians should be aware of the interaction of these two commonly used drugs.

  1. Role of Pre-incision, Intravenous Prophylactic Amiodarone to Control Arrhythmias in Patients with Rheumatic Valvular Heart Disease undergoing Mitral Valve Replacement

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect of intra-operative single intra venous dose of amiodarone on post operative cardiac arrhythmias in patients undergoing valvular heart surgery. Study Design: Randomized controlled trials. Place and Duration of surgery: This study was performed at Armed forces Institute of Cardiology Rawalpindi from Jan 01, 2011 to Dec 31, 2011. Patients and Methods: In this study 80 patients with rheumatic valvular heart disease and undergoing elective mitral valve replacement were randomly divided into two groups. Group I, n = 40 (Amiodarone group) was given single intravenous dose of amiodarone (5 mg/kg in 100 ml of saline over 30 min) before sternotomy incision. Group II, n = 40(control / placebo group) was given 100 ml of saline over 30 min. Result: In the amiodarone group, after removal of aortic cross clamp 75% patients had sinus rhythm compared to 47.5% in control group. p=0.045. Similarly 15% had AF, 5% JR and 5% VT/VF in amiodarone group in contrast to 32.5% with AF, 12.5% JR and 7.5% Vt/VF in control group. (p=0.045). Response to cardioversion was positive in 75% of the patients requiring shocks in amiodarone group as against 43.75% in the control group. (p=0.044). Conclusion: A single intravenous bolus dose of amiodarone is effective in decreasing the incidence of cardiac arrhythmias after mitral valve replacement in patients with rheumatic MVD. (author)

  2. A CASE REPORT OF AMIODARONE INDUCED MYOPATHY IN A PATIENT OF VENTRICULAR ARRHYTHMIA

    Directory of Open Access Journals (Sweden)

    Rajat

    2014-09-01

    Full Text Available Myopathies are disorders with structural changes or functional impairment of muscle. Voluntary muscle is subject to a range of hereditary and acquired disorders affecting either its structure, or the biochemical processes which convert the chemical energy derived from cell metabolism into mechanical energy in a controlled manner. These disorders present in a limited number of ways, most commonly a symmetrical weakness of the large, power-generating proximal muscles. Drug induced myopathy comes under acquired causes of myopathy. Here we shall be presenting a case of Amiodarone induced myopathy in a 40 years old male patient of ventricular arrhythmia. We shall also discuss the further management of this presentation.

  3. Effect of Aronia melanocarpa fruit juice on amiodarone-induced pneumotoxicity in rats

    OpenAIRE

    Valcheva-Kuzmanova, Stefka; Stavreva, Galya; Dancheva, Violeta; Terziev, Ljudmil; Atanasova, Milena; Stoyanova, Angelina; Dimitrova, Anelia; Shopova, Veneta

    2014-01-01

    Background: The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in biologically active polyphenols. Objective: We studied the protective effect of A. melanocarpa fruit juice (AMFJ) in a model of amiodarone (AD)-induced pneumotoxicity in rats. Materials and Methods: AD was instilled intratracheally on days 0 and 2 (6.25 mg/kg). AMFJ (5 mL/kg and 10 mL/kg) was given orally from day 1 to days 2, 4, 9, and 10 to rats, which were sacrificed respectively on days 3, 5, 10, and 28 when...

  4. Effect of single intraoperative dose of amiodarone in patients with rheumatic valvular heart disease and atrial fibrillation undergoing valve replacement surgery

    Directory of Open Access Journals (Sweden)

    Selvaraj Thiruvenkadam

    2009-01-01

    Full Text Available Maintenance of sinus rhythm (SR is superior to rate control in atrial fibrillation (AF. In order to achieve SR, we administered single-dose intravenous amiodarone intraoperatively and evaluated its effect on conversion of rheumatic AF to SR in patients undergoing valvular heart surgery. Patients were randomly assigned to amiodarone ( n = 42 or control ( n = 40 group in a double blind manner. The amiodarone group received amiodarone (3 mg/kg intravenously prior to the institution of cardiopulmonary bypass and the control group received the same volume of normal saline. In the amiodarone group, the initial rhythm after the release of aortic cross clamp was noted to be AF in 14.3% ( n = 6 and remained so in 9.5% ( n = 4 of patients till the end of surgery. In the control group, the rhythm soon after the release of aortic cross clamp was AF in 37.5% ( n = 15 ( p = 0.035 and remained so in 32.5% ( n = 13 of patients till the end of surgery ( p = 0.01. At the end of first post-operative day 21.4% ( n = 9 of patients in amiodarone group and 55% ( n = 22 of patients in control group were in AF ( p = 0.002. The requirement of cardioversion/defibrillation was 1.5 (±0.54 in amiodarone group and 2.26 (±0.73 in the control group ( p = 0.014, and the energy needed was 22.5 (±8.86 joules in the amiodarone group and 40.53 (±16.5 in the control group ( p = 0.008. A single intraoperative dose of intravenous amiodarone increased the conversion rate of AF to normal sinus rhythm, reduced the need and energy required for cardioversion/defibrillation and reduced the recurrence of AF within one day.

  5. Unfolding Ubiquitin by force: water mediated H-bond destabilization

    Directory of Open Access Journals (Sweden)

    Germán Pabón

    2012-12-01

    Full Text Available Using the “pull and wait” (PNW simulation protocol at 300 K, we studied the unfolding by force of an ubiquitin molecule. PNW was implemented in the CHARMM program using an integration time step of 1 fs and a uniform dielectric constant of 1. The ubiquitin molecule, initially solvated, was put under mechanical stress, exerting forces from different directions. The rupture of five hydrogen bonds between parallel strands β1 and β5 takes place during the extension from 13 to 15 Å, defines a mechanical barrier for unfolding and dominates the point of maximum unfolding force. The simulations described here show that given adequate time, a small applied force can destabilize those five H-bonds relative to the bonds that can be created to water molecules; allowing the formation of stable H-bonds between a single water molecule and the donor and acceptor groups of the interstrand H-bonds. Thus, simulations run with PNW show that the force is not responsible for “ripping apart” the backbone H-bonds; it merely destabilizes them making them less stable than the H-bonds they can make with water. Additional simulations show that the force necessary to destabilize the H-bonds and allow them to be replaced by H-bonds to water molecules depends strongly on the pulling direction. By using a simulation protocol that allows equilibration at each extension we have been able to observe the details of the events leading to the unfolding of ubiquitin by mechanical force.

  6. Trapped particle destabilization of the internal kink mode

    Energy Technology Data Exchange (ETDEWEB)

    White, R.B.; Chen, L.; Romanelli, F.; Hay, R.

    1984-06-01

    The internal kink mode is destabilized by trapped high energy particles, leading to a new branch of the internal kink dispersion relation with a real frequency near the average trapped particle precession frequency and a growth rate of the same magnitude. This trapped particle branch of the dispersion relation is investigated numerically for a variety of particle distributions. Mode growth rate and frequency are found as a function of plasma ..beta.., density, and trapped particle energy and distribution. The high energy trapped particle sources considered are neutral beam injection, ion cyclotron heating, and fusion alpha particles. Relevance for various plasma heating schemes is discussed.

  7. Geometrical destabilization of heavy scalar fields during inflation

    CERN Document Server

    Renaux-Petel, Sébastien

    2015-01-01

    We show the existence of a general mechanism by which heavy scalar fields can be destabilized during inflation. It relies on the fact that the effective mass of fluctuations orthogonal to the inflationary direction contains a contribution proportional to the curvature tensor of the field space metric, and that it can render the entropic fluctuations tachyonic. We describe a simple and rather universal setup in which apparently benign higher-order operators trigger this instability. This phenomenon can prematurely end inflation and have important observational consequences, sometimes excluding models that would otherwise perfectly fit the data. More generally, it modifies the interpretation of cosmological constraints in terms of fundamental physics.

  8. Comparative Study of Nifekalant Versus Amiodarone for Shock-Resistant Ventricular Fibrillation in Out-of-Hospital Cardiopulmonary Arrest Patients

    NARCIS (Netherlands)

    M. Amino; K. Yoshioka; T. Opthof; S. Morita; S. Uemura; K. Tamura; T. Fukushima; S. Higami; H. Otsuka; K. Akieda; M. Shima; D. Fujibayashi; T. Hashida; S. Inokuchi; I. Kodama; T. Tanabe

    2010-01-01

    Background: In Japan, intravenous nifekalant ( NIF) was often used for direct current cardioversion-resistant ventricular fibrillation (VF), until the use of intravenous amiodarone (AMD) was approved in 2007. The defibrillatory efficacy of NIF and AMD has thus far not been compared for resuscitation

  9. Efficacy of i.v. amiodarone in converting rapid atrial fibrillation and flutter to sinus rhythm in intensive care patients.

    Science.gov (United States)

    Faniel, R; Schoenfeld, P

    1983-03-01

    Twenty-six consecutive patients (14 males, 12 females--mean age 66.6) were admitted to an intensive care unit (ICU) because of a rapid ventricular response to atrial fibrillation (RAF). Fourteen of them had been unsuccessfully treated by drugs (other than amiodarone) and/or DC shock before admission. A loading dose of i.v. amiodarone was administered (repeated boluses of 3 mg/kg in 3 min, or 30 min-infusions of 5 to 7.5 mg/kg), followed by continuous infusion, in order to reach a maximal total dosage of 1500 mg in 24 h. This treatment was considered efficacious if a reversion to stable sinus rhythm (SSR) occurred within 24 h and was maintained for more than 48 h. This was achieved in 21 out of 26 patients (80.8%). The mean time between the administration of therapy and the occurrence of SSR was 171 min. The total dose of amiodarone delivered to effect SSR was 6.9 +/- 2.3 mg/kg. No adverse reactions were encountered during the bolus injection but we recommend that continuous infusion be carried out through a central venous catheter to avoid phlebitis. The administration of 7 mg/kg of intravenous amiodarone delivered in 30 min proved a safe and successful first choice of management in atrial fibrillation with a rapid ventricular response. PMID:6861767

  10. COMPARATIVE EFFICACY OF AMIODARONE AND BISOPROLOL IN TREATMENT OF VENTRICULAR PREMATURE BEATS IN PATIENTS WITH METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    V. M. Provotorov

    2016-01-01

    Full Text Available Aim. Comparative study of amiodarone and bisoprolol efficacy in patients with ventricular arrhythmia and metabolic syndrome.Methods. 146 patients with the AHA/NHLBI 2005 metabolic syndrome and symptomatic ventricular arrhythmia were included in the study. 52 patients received regular oral amiodarone (200 mg daily, 5 days a week therapy, 55 patients received bisoprolol (10 mg daily treatment and 39 patients did not receive any antiarrhythmic therapy (control group. Treatment efficacy was evaluated by Holter monitoring (before start and after 1, 3, 6, 9, 12 months of therapy.Results. Significant efficacy advantage of bisoprolol vs this of amiodarone was observed in 12 months of therapy (50.0% of effectively treated patients vs 17.3%, p=0.02. Significant difference in a number of patients ceased therapy because of antiarrhythmic effect loss was also revealed (20.0% vs 46.1%, p=0.004. A number of patients stopped therapy because of side effects was comparable in the both groups. Patient age younger than 42 years old in combination with a number of ventricular premature beats morphology less than 4 allowed predicting effective antiarrhythmic treatment for both drugs with sensitivity of 70.3% and specificity of 65.0%.Conclusion. Bisoprolol have an advantage (versus amiodarone within 9-12 month therapy in patients with ventricular premature beats and metabolic syndrome. Drug refractoriness and side effects monitoring is necessary.

  11. A Comparative Study on the Effect of Amiodarone and Metaprolol for Prevention of Arrythmias after Open Heart Surgery

    Directory of Open Access Journals (Sweden)

    Nayeem‑ul‑hassan

    2013-03-01

    Full Text Available Objectives: The aim of this study was to compare the effect of amiodarone and metaprolol in prevention of atrial fibrillation in patients, following open heart surgery. Methods: This prospective study was carried out between May 2008 to Nov. 2010, and comprised a total of 50 patients with normal preoperative sinus rhythm undergoing open heart surgery using cardio pulmonary bypass. Results: Mean age of patients was 47+2.7 years, of which 60% who developed atrial fibrillation aged from 51 to 60 years. Most patients (62% were in NYHA Class III. Patients who received amiodarone showed significant improvement in LVEF compared to those treated with Metaprolol. Amiodarone treated group exhibited lesser incidence and short-lasting atrial fibrillation, lower ventricular rate, shorter hospitalization, and lesser cost of care than those in metaprolol group. Conclusions: The present study showed that amiodarone was more efficient in controlling post-operative atrial fibrillation as compared to metaprolol. However, a larger randomized controlled trial is needed to corroborate the result of this study.

  12. Total Thyroidectomy for Amiodarone-induced Thyrotoxicosis in the Hyperthyroid State.

    Science.gov (United States)

    Kaderli, R M; Fahrner, R; Christ, E R; Stettler, C; Fuhrer, J; Martinelli, M; Vogt, A; Seiler, C A

    2016-01-01

    Amiodarone is a potent antiarrhythmic agent, indicated for the treatment of refractory arrhythmias, which may lead to thyrotoxicosis. In these patients, thyroidectomy is a valid therapeutic option. Antithyroid therapy in the immediate preoperative setting and the subsequently accepted minimal delay until thyroidectomy have not been clearly defined yet. The aim of the present study was to show, that total thyroidectomy under general anaesthesia in patients with amiodarone-induced thyrotoxicosis (AIT) is safe without necessarily obtaining an euthyroid state preoperatively.We conducted a retrospective cohort study of prospectively gathered data on 11 patients undergoing total thyroidectomy under general anaesthesia between January 2008 and December 2013 for AIT at our University Hospital.All patients were preoperatively treated with carbimazole, steroids and β-receptor antagonists. Additionally, 3 patients received potassium perchlorate and in one patient carbimazole was changed to propylthiouracil. Plasmapheresis was performed in 3 patients. Only one patient was euthyroid at the time of operation. There were no significant intra- and postoperative complications, especially no signs of thyroid storm. One patient could postoperatively be removed from the cardiac transplant waiting list due to improved cardiac function.Improvements in the interdisciplinary surgical management for AIT between cardiologists, endocrinologists, anaesthetists and endocrine surgeons provide the basis of safe total thyroidectomy under general anaesthesia in hyperthyroid state. Early surgery without long delay for medical antithyroid treatment (with its potential negative side effects) is recommended. PMID:26575117

  13. Amiodarone-induced pulmonary toxicity. Immunoallergologic tests and bronchoalveolar lavage phospholipid content.

    Science.gov (United States)

    Nicolet-Chatelain, G; Prevost, M C; Escamilla, R; Migueres, J

    1991-02-01

    Amiodarone (A) is a widely-used antiarrhythmic drug. Pulmonary toxicity is the most serious adverse effect with an estimated mortality of 1 to 33 percent. In order to determine an element helpful for diagnosis, we examined four patients with amiodarone-induced pulmonary toxicity, three patients treated with A, without evidence of pulmonary toxicity but with a main underlying pulmonary disease, and four healthy volunteers. Daily and cumulative doses or duration of treatment were similar in the first two groups. Pulmonary function tests (spirometry, CO-diffusing capacity, arterial blood gases), roentgenographic examinations, pulmonary biopsies or immunoallergologic tests (skin reaction, lymphoblastic transformation test and human basophile degranulation test) did not provide any discriminatory element. In APT+, we observed an increased cellularity of the bronchoalveolar lavage. Neither the differential cell count nor the presence of foamy macrophages were distinguishable between APT+ and APT-. The phospholipid composition of BAL fluid showed a decreased total phospholipid and phospholipid/protein ratio in all patients compared to normal subjects. These changes reflect more the severity of pulmonary disease than the specificity of the causative agent. However, we observed that the unique PL which decreases in APT- and remains normal in APT+ is phosphatidyl-serine + phosphatidylinositol (PS + PI). This has to be confirmed and should be evaluated at different stages of the disease to determine an eventual specific element. We conclude that there are no data currently available to establish the diagnosis of APT except perhaps for the analysis of BAL PL content.

  14. Bacterial lipopolysaccharide promotes destabilization of lung surfactant-like films.

    Science.gov (United States)

    Cañadas, Olga; Keough, Kevin M W; Casals, Cristina

    2011-01-01

    The airspaces are lined with a dipalmitoylphosphatidylcholine (DPPC)-rich film called pulmonary surfactant, which is named for its ability to maintain normal respiratory mechanics by reducing surface tension at the air-liquid interface. Inhaled airborne particles containing bacterial lipopolysaccharide (LPS) may incorporate into the surfactant monolayer. In this study, we evaluated the effect of smooth LPS (S-LPS), containing the entire core oligosaccharide region and the O-antigen, on the biophysical properties of lung surfactant-like films composed of either DPPC or DPPC/palmitoyloleoylphosphatidylglycerol (POPG)/palmitic acid (PA) (28:9:5.6, w/w/w). Our results show that low amounts of S-LPS fluidized DPPC monolayers, as demonstrated by fluorescence microscopy and changes in the compressibility modulus. This promoted early collapse and prevented the attainment of high surface pressures. These destabilizing effects could not be relieved by repeated compression-expansion cycles. Similar effects were observed with surfactant-like films composed of DPPC/POPG/PA. On the other hand, the interaction of SP-A, a surfactant membrane-associated alveolar protein that also binds to LPS, with surfactant-like films containing S-LPS increased monolayer destabilization due to the extraction of lipid molecules from the monolayer, leading to the dissolution of monolayer material in the aqueous subphase. This suggests that SP-A may act as an LPS scavenger. PMID:21190662

  15. Destabilization of confined granular packings due to fluid flow

    Science.gov (United States)

    Monloubou, Martin; Sandnes, Bjørnar

    2016-04-01

    Fluid flow through granular materials can cause fluidization when fluid drag exceeds the frictional stress within the packing. Fluid driven failure of granular packings is observed in both natural and engineered settings, e.g. soil liquefaction and flowback of proppants during hydraulic fracturing operations. We study experimentally the destabilization and flow of an unconsolidated granular packing subjected to a point source fluid withdrawal using a model system consisting of a vertical Hele-Shaw cell containing a water-grain mixture. The fluid is withdrawn from the cell at a constant rate, and the emerging flow patterns are imaged in time-lapse mode. Using Particle Image Velocimetry (PIV), we show that the granular flow gets localized in a narrow channel down the center of the cell, and adopts a Gaussian velocity profile similar to those observed in dry grain flows in silos. We investigate the effects of the experimental parameters (flow rate, grain size, grain shape, fluid viscosity) on the packing destabilization, and identify the physical mechanisms responsible for the observed complex flow behaviour.

  16. Nutrient flows between ecosystems can destabilize simple food chains.

    Science.gov (United States)

    Marleau, Justin N; Guichard, Frédéric; Mallard, François; Loreau, Michel

    2010-09-01

    Dispersal of organisms has large effects on the dynamics and stability of populations and communities. However, current metacommunity theory largely ignores how the flows of limiting nutrients across ecosystems can influence communities. We studied a meta-ecosystem model where two autotroph-consumer communities are spatially coupled through the diffusion of the limiting nutrient. We analyzed regional and local stability, as well as spatial and temporal synchrony to elucidate the impacts of nutrient recycling and diffusion on trophic dynamics. We show that nutrient diffusion is capable of inducing asynchronous local destabilization of biotic compartments through a diffusion-induced spatiotemporal bifurcation. Nutrient recycling interacts with nutrient diffusion and influences the susceptibility of the meta-ecosystem to diffusion-induced instabilities. This interaction between nutrient recycling and transport is further shown to depend on ecosystem enrichment. It more generally emphasizes the importance of meta-ecosystem theory for predicting species persistence and distribution in managed ecosystems. PMID:20600133

  17. Constraining interacting dark energy models with flux destabilization

    CERN Document Server

    Horvat, Raul

    2007-01-01

    A destabilization in the transfer energy flux from the vacuum to radiation, for two vacuum decay laws relevant to the dark energy problem, is analyzed using the Landau-Lifshitz fluctuation hydrodynamic theory. Assuming thermal (or near thermal) equilibrium between the vacuum and radiation, at the earliest epoch of the Universe expansion, we show that the law due to renormalization-group running of the cosmological constant term, with parameters chosen not to spoil the primordial nucleosynthesis scenario, does soon drive the flux to fluctuate beyond its statistical average value thereby distorting the cosmic background radiation spectrum beyond observational limits. While the law coming from the saturated holographic dark energy does not lead the flux to wildly fluctuate, a more realistic non--saturated form shows again such anomalous behavior.

  18. Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA)

    Science.gov (United States)

    Doval, H C; Nul, D R; Grancelli, H O; Perrone, S V; Bortman, G R; Curiel, R

    1994-08-20

    In severe heart failure many deaths are sudden and are presumed to be due to ventricular arrhythmias. The GESICA trial evaluated the effect of low-dose amiodarone on two-year mortality in patients with severe heart failure. Our prospective multicentre trial included 516 patients on optimal standard treatment for heart failure. Patients were randomised to 300 mg/day amiodarone (260) or to standard treatment (256). Intention-to-treat analysis showed 87 deaths in the amiodarone group (33.5%) compared with 106 in the control group (41.4%) (risk reduction 28%; 95% CI 4%-45%; log rank test p = 0.024). There were reductions in both sudden death (risk reduction 27%; p = 0.16) and death due to progressive heart failure (risk reduction 23%; p = 0.16). Fewer patients in the amiodarone group died or were admitted to hospital due to worsening heart failure (119 versus 149 in the control group; risk reduction 31%; 95% CI 13-46%; p = 0.0024). The decrease in mortality and hospital admission was present in all subgroups examined and independent of the presence of non-sustained ventricular tachycardia. Side-effects were reported in 17 patients (6.1%); amiodarone was withdrawn in 12. Low-dose amiodarone proved to be an effective and reliable treatment, reducing mortality and hospital admission in patients with severe heart failure independently of the presence of complex ventricular arrhythmias.

  19. Twenty-four hour radioactive iodine uptake in 35 patients with amiodarone associated thyrotoxicosis

    Energy Technology Data Exchange (ETDEWEB)

    Martino, E.; Aghini-Lombardi, F.; Lippi, F.; Baschieri, L.; Safran, M.; Braverman, L.E.; Pinchera, A.

    1985-12-01

    Amiodarone associated thyrotoxicosis (AAT) occurs in approximately 10% of patients treated with this iodine rich drug in areas of mild iodine deficiency. The thyroid radioactive iodine uptake (RAIU) is usually undetectable or very low in iodine-induced thyrotoxicosis. In the present study, 35 patients with AAT were evaluated. Twelve patients had no thyroid abnormalities by physical exam and all had 24-hr RAIU less than or equal to 4%. In contrast, nine of 11 patients with AAT and diffuse goiters and eight of 12 patients with AAT and nodular goiters had RAIU values greater than 8%. In patients with AAT and goiter it appears possible that the thyroid fails to adapt normally to the excess iodide load, resulting in an inappropriately high RAIU in the presence of excess plasma iodine.

  20. Concurrent Chagas’ disease and borderline disseminated cutaneous leishmaniasis: The role of amiodarone as an antitrypanosomatidae drug

    Directory of Open Access Journals (Sweden)

    Alberto E Paniz-Mondolfi

    2008-06-01

    Full Text Available Alberto E Paniz-Mondolfi1,4, Alexandra M Pérez-Álvarez1, Oscar Reyes-Jaimes2, Gustavo Socorro1, Olga Zerpa3, Denisa Slova4, Juan L Concepción51Laboratorio de Estudio de Antígenos, Instituto de Biomedicina, “Hospital José Gregório Hernández”, Instituto Venezolano de los Seguros Sociales, Caracas, Venezuela; 2Departamento de Dermopatología, Instituto de Biomedicina, 3Sección de Leishmaniasis, Instituto de Biomedicina, Caracas, Venezuela; 4Department of Pathology and Laboratory Medicine, St. Luke’s – Roosevelt - Beth Israel Medical Center, University Hospital of Columbia University College of Physicians and Surgeons, New York, USA; 5Laboratorio de Enzimología de Parásitos, Facultad de Ciencias, Universidad de Los Andes, Mérida, VenezuelaAbstract: The occurrence of mixed infections of Trypanosoma cruzi and Leishmania spp. is becoming a common feature in Central and South America due to overlapping endemic areas. Unfortunately, the possibilities for treating flagellated kinetoplastid infections are still very limited and most of the available drugs exhibit severe side effects. Although the development of new drugs for Leishmania has markedly improved in the last years, the tendency is still to employ antimonial compounds. On the other hand, treatment for Chagas’ disease is only available for the acute phase with no effective therapeutical options for chronic stage disease. The following case report substantiates the recently discovered effect of amiodarone as a nonconventional antiparasitic drug, particularly against Leishmania, breaching a new perspective in the therapeutic management of these important infectious parasitic diseases.Keywords: Chagas’ disease, leishmaniasis, chemotherapy, amiodarone

  1. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2016-02-01

    Full Text Available Rasmus Rivinius,1 Matthias Helmschrott,1 Arjang Ruhparwar,2 Bastian Schmack,2 Christian Erbel,1 Christian A Gleissner,1 Mohammadreza Akhavanpoor,1 Lutz Frankenstein,1 Fabrice F Darche,1 Patrick A Schweizer,1 Dierk Thomas,1 Philipp Ehlermann,1 Tom Bruckner,3 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology and Pneumology, 2Department of Cardiac Surgery, Heidelberg University Hospital, 3Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: Amiodarone is a frequently used antiarrhythmic drug in patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been controversially discussed, with divergent results regarding morbidity and mortality after heart transplantation (HTX.Aim: The aim of this study was to investigate the effects of long-term use of amiodarone before HTX on early post-transplant atrial fibrillation (AF and mortality after HTX.Methods: Five hundred and thirty patients (age ≥18 years receiving HTX between June 1989 and December 2012 were included in this retrospective single-center study. Patients with long-term use of amiodarone before HTX (≥1 year were compared to those without long-term use (none or <1 year of amiodarone. Primary outcomes were early post-transplant AF and mortality after HTX. The Kaplan–Meier estimator using log-rank tests was applied for freedom from early post-transplant AF and survival.Results: Of the 530 patients, 74 (14.0% received long-term amiodarone therapy, with a mean duration of 32.3±26.3 months. Mean daily dose was 223.0±75.0 mg. Indications included AF, Wolff–Parkinson–White syndrome, ventricular tachycardia, and ventricular fibrillation. Patients with long-term use of amiodarone before HTX had significantly lower rates of early post-transplant AF (P=0.0105. Further, Kaplan–Meier analysis of freedom from early post-transplant AF showed significantly lower rates of AF in this

  2. Involvement of Protein Phosphatases in the Destabilization of Methamphetamine-Associated Contextual Memory

    Science.gov (United States)

    Yu, Yang-Jung; Huang, Chien-Hsuan; Chang, Chih-Hua; Gean, Po-Wu

    2016-01-01

    Destabilization refers to a memory that becomes unstable when reactivated and is susceptible to disruption by amnestic agents. Here we delineated the cellular mechanism underlying the destabilization of drug memory. Mice were conditioned with methamphetamine (MeAM) for 3 d, and drug memory was assessed with a conditioned place preference (CPP)…

  3. Measurements of intracellular calcium

    International Nuclear Information System (INIS)

    Intracellular calcium concentration ([Ca2+]i) has been measured in cultured cells by using Fura-2 load cells and a computer-controlled Perkin Elmer LS-5B spectrofluorometer. Increased [Ca2+]i in cells exposed to extracellular bilirubin was observed both with and without extracellular calcium. However, the increase was considerable larger with extracellular calcium. The enhancement of [Ca2+]i became smaller with decreasing bilirubin/BSA (bovine serum albumine) ratio. 5 refs., 5 figs

  4. Fingertip contact suppresses the destabilizing influence of leg muscle vibration

    Science.gov (United States)

    Lackner, J. R.; Rabin, E.; DiZio, P.

    2000-01-01

    Touch of the hand with a stationary surface at nonmechanically supportive force levels (physiotherapy vibrator (120 Hz) was applied approximately 5 cm above the malleolous to stimulate the peroneus longus and brevis tendons. Touch conditions involved contact of the right index finger with a laterally positioned surface ( 0.05) from each other and both had significantly less mean sway amplitude of head and of center of pressure than the other conditions (P < 0.01). In experiment 2, eight subjects stood heel-to-toe under touch and no-touch conditions involving 40-s duration trials of peroneus tendon vibration at different duty cycles: 1-, 2-, 3-, and 4-s ON and OFF periods. The vibrator was attached to the subject's leg and remotely activated. In the no-touch conditions, subjects showed periodic postural disruptions contingent on the duty cycle and mirror image rebounds with the offset of vibration. In the touch conditions, subjects were much less disrupted and showed compensations occurring within 500 ms of vibration onset and mirror image rebounds with vibration offset. Subjects were able to suppress almost completely the destabilizing influence of the vibration in the 3- and 4-s duty cycle trials. These experiments show that haptic contact of the hand with a stable surface can suppress abnormal proprioceptive and motor signals in leg muscles.

  5. Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

    Institute of Scientific and Technical Information of China (English)

    Shanshan Kong; Xinrong Du; Chao Peng; Yiming Wu; Huirong Li; Xi Jin; Ling Hou

    2013-01-01

    Cytoplasmic dynein 1 is fundamentally important for transporting a variety of essential cargoes along microtubules within eukaryotic cells.However,in mammals,few mutants are available for studying the effects of defects in dynein-controlled processes in the context of the whole organism.Here,we deleted mouse Dlic1 gene encoding DLIC1,a subunit of the dynein complex.Dlic1-/-mice are viable,but display severe photoreceptor degeneration.Ablation of Dlic1 results in ectopic accumulation of outer segment (OS) proteins,and impairs OS growth and ciliogenesis of photoreceptors by interfering with Rabll-vesicle trafficking and blocking efficient OS protein transport from Golgi to the basal body.Our studies show that Dlic1 deficiency partially blocks vesicle export from endoplasmic reticulum (ER),but seems not to affect vesicle transport from the ER to Golgi.Further mechanistic study reveals that lack of Dlic1 destabilizes dynein subunits and alters the normal subcellular distribution of dynein in photoreceptors,probably due to the impaired transport function of dynein.Our results demonstrate that Dlic1 plays important roles in ciliogenesis and protein transport to the OS,and is required for photoreceptor development and survival.The Dlic1-/-mice also provide a new mouse model to study human retinal degeneration.

  6. New viewpoint of clinical treatment of amiodarone%胺碘酮临床治疗的新观点

    Institute of Scientific and Technical Information of China (English)

    朱彩玲

    2015-01-01

    Amiodarone is widely used in clinical.It has an important role in the treatment of arrhythmia and anti angina pectoris and so on.It has good treatment effect,at the same time,amiodarone also has more adverse reactions,which should arouse the attention of clinicians.In this paper,the author briefly introduces the new viewpoint of clinical treatment of amiodarone,to provide study for clinical.%胺碘酮在临床有着广泛的应用,其在治疗心律失常和抗心绞痛等方面有着重要的作用.在发挥较好治疗作用的同时,胺碘酮也有着较多的不良反应,应引起临床医生的注意.本文简要介绍胺碘酮临床治疗的新观点,为临床提供依据.

  7. Destabilization of a Heterogeneous Rate-and-State Interface

    Science.gov (United States)

    Dublanchet, P.

    2014-12-01

    Among all the physics-based earthquake theories, rate-and-state friction has been one of the most successful in explaining several features of the earthquake cycle. This indicates that the laboratory derived friction laws, although deduced from experiments on centimeter to meter scale rock samples, could also be used to model the behavior of kilometer scale heterogeneous fault systems where earthquakes occur. However, the question of whether the behavior of complex faults could be described with an effective rate-and-state friction law remains poorly addressed. In this framework, the study presented here focuses on fault zones experiencing both aseismic slip and earthquakes, such as the San-Andreas fault. These heterogeneous systems could be approximated by a planar rate-and-state frictional fault between elastic solids, coupling unstable velocity weakening patches and stable velocity strengthening areas (figure). The seismicity generated by such systems is computed numerically, and we show that the different regimes of activity obtained (swarms, major unstable events, continuous activity, regular events) are separated by an effective a-b friction parameter obtained as the spatial average of the steady-state a-b parameter. In order to further investigate what are the relevant effective friction parameters controlling the mechanical behavior of heterogeneous a-b faults, we analyze the transition between the regime of regular activity and the more unstable regime where accelerating swarms develop towards major failures destabilizing the entire fault. We compare in detail the nucleation process of a such major instabilities, to the acceleration of slip on a homogeneous rate-and-state fault. The similarity in the way the two systems accelerate provides a strong evidence that effective rate-and-state friction parameters control the nucleation on a frictionally heterogeneous structure.

  8. Alpha particle destabilization of the toroidicity-induced Alfven eigenmodes

    International Nuclear Information System (INIS)

    The high frequency, low mode number toroidicity-induced Alfven eigenmodes (TAE) are shown to be driven unstable by the circulating and/or trapped α-particles through the wave-particle resonances. Satisfying the resonance condition requires that the α-particle birth speed vα ≥ vA/2|m-nq|, where vA is the Alfven speed, m is the poloidal model number, and n is the toroidal mode number. To destabilize the TAE modes, the inverse Landau damping associated with the α-particle pressure gradient free energy must overcome the velocity space Landau damping due to both the α-particles and the core electrons and ions. The growth rate was studied analytically with a perturbative formula derived from the quadratic dispersion relation, and numerically with the aid of the NOVA-K code. Stability criteria in terms of the α-particle beta βα, α-particle pressure gradient parameter (ω*/ωA) (ω* is the α-particle diamagnetic drift frequency), and (vα/vA) parameters will be presented for TFTR, CIT, and ITER tokamaks. The volume averaged α-particle beta threshold for TAE instability also depends sensitively on the core electron and ion temperature. Typically the volume averaged α-particle beta threshold is in the order of 10-4. Typical growth rates of the n=1 TAE mode can be in the order of 10-2ωA, where ωA=vA/qR. Other types of global Alfven waves are stable in D-T tokamaks due to toroidal coupling effects

  9. Rhodopsin mutant P23H destabilizes rod photoreceptor disk membranes.

    Directory of Open Access Journals (Sweden)

    Mohammad Haeri

    Full Text Available Mutations in rhodopsin cause retinitis pigmentosa in humans and retinal degeneration in a multitude of other animals. We utilized high-resolution live imaging of the large rod photoreceptors from transgenic frogs (Xenopus to compare the properties of fluorescently tagged rhodopsin, Rho-EGFP, and Rho(P23H-EGFP. The mutant was abnormally distributed both in the inner and outer segments (OS, accumulating in the OS to a concentration of ∼0.1% compared to endogenous opsin. Rho(P23H-EGFP formed dense fluorescent foci, with concentrations of mutant protein up to ten times higher than other regions. Wild-type transgenic Rho-EGFP did not concentrate in OS foci when co-expressed in the same rod with Rho(P23H-EGFP. Outer segment regions containing fluorescent foci were refractory to fluorescence recovery after photobleaching, while foci in the inner segment exhibited recovery kinetics similar to OS regions without foci and Rho-EGFP. The Rho(P23H-EGFP foci were often in older, more distal OS disks. Electron micrographs of OS revealed abnormal disk membranes, with the regular disk bilayers broken into vesiculotubular structures. Furthermore, we observed similar OS disturbances in transgenic mice expressing Rho(P23H, suggesting such structures are a general consequence of mutant expression. Together these results show that mutant opsin disrupts OS disks, destabilizing the outer segment possibly via the formation of aggregates. This may render rods susceptible to mechanical injury or compromise OS function, contributing to photoreceptor loss.

  10. Cognitive Fatigue Destabilizes Economic Decision Making Preferences and Strategies.

    Directory of Open Access Journals (Sweden)

    O'Dhaniel A Mullette-Gillman

    Full Text Available It is common for individuals to engage in taxing cognitive activity for prolonged periods of time, resulting in cognitive fatigue that has the potential to produce significant effects in behaviour and decision making. We sought to examine whether cognitive fatigue modulates economic decision making.We employed a between-subject manipulation design, inducing fatigue through 60 to 90 minutes of taxing cognitive engagement against a control group that watched relaxing videos for a matched period of time. Both before and after the manipulation, participants engaged in two economic decision making tasks (one for gains and one for losses. The analyses focused on two areas of economic decision making--preferences and choice strategies. Uncertainty preferences (risk and ambiguity were quantified as premium values, defined as the degree and direction in which participants alter the valuation of the gamble in comparison to the certain option. The strategies that each participant engaged in were quantified through a choice strategy metric, which contrasts the degree to which choice behaviour relies upon available satisficing or maximizing information. We separately examined these metrics for alterations within both the gains and losses domains, through the two choice tasks.The fatigue manipulation resulted in significantly greater levels of reported subjective fatigue, with correspondingly higher levels of reported effort during the cognitively taxing activity. Cognitive fatigue did not alter uncertainty preferences (risk or ambiguity or informational strategies, in either the gains or losses domains. Rather, cognitive fatigue resulted in greater test-retest variability across most of our economic measures. These results indicate that cognitive fatigue destabilizes economic decision making, resulting in inconsistent preferences and informational strategies that may significantly reduce decision quality.

  11. Effects of Amiodarone on Transmural Dispersion of Ventricular Effective Refractory Periods across Myocardial Layers in the Normal and Hypertrophic Canine Heart

    Institute of Scientific and Technical Information of China (English)

    WANG Lan; L(U) Jiagao; ZHANG Fanzhi; BAI Rong; WANG Lin

    2006-01-01

    The effects of amiodarone on transmural dispersion of ventricular effective refractory periods (ERPs) in the normal and hypertrophic canine heart were investigated in vivo. By using the programmed stimulation protocol, the ERPs of epicardium (Epi), midmyocardium (Mid) and endocardium (Endo) were measured by inserting specially-designed electrodes into the three myocardial layers before and after mainlining of amiodarone. No significant ERPs-dispersion was observed in the three layers before and after mainlining of amiodarone in the normal group. In contrast, ERPs of all the three layers were prolonged in the hypertrophic heart, while the ERPs-dispersion was reduced significantly after mainlining of amiodarone. The ERPs-dispersion was significantly increased in the hypertrophic heart but not in the normal heart using "long-short" and "short-long" interval stimulation technique. It was concluded that (1) the differences in ERPs-dispersion among the three layers were significant in hypertrophic heart, and differences were not significant in normal canine heart;(2) ERPs of each three-myocardial layers were significantly prolonged after using amiodarone, but the ERPs-dispersion decreased in hypertrophic heart and (3) the programmed extrastimulus technique of "long-short" and "short-long" intervals increased the transmural ERPs-dispersion in the hypertrophic heart.

  12. Nanovehicular intracellular delivery systems.

    Science.gov (United States)

    Prokop, Ales; Davidson, Jeffrey M

    2008-09-01

    This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood-brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list "elementary" phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

  13. Low-dose amiodarone for the prevention of atrial fibrillation after coronary artery bypass grafting in patients older than 70 years

    Institute of Scientific and Technical Information of China (English)

    GU Song; SU Pi-xiong; LIU Yan; YAN Jun; ZHANG Xi-tao; WANG Tian-you

    2009-01-01

    Background Atrial fibrillation (AF) is one of the most common arrhythmia after coronary artery bypass grafting (CABG), which not only increases the suffering of the patients, but also prolongs hospital stay and enhances cost of care, especially for patients older than 70 years. This study was designed to evaluate the efficacy and safety of low-dose amiodarone in the prevention of AF after CABG, especially for the elderly.Methods Two hundred and ten senile patients undergoing off-pump CABG were included in this prospective, randomized, double-blind and placebo controlled study. Patients were given 10 mg/kg of amiodarone (low-dose amiodarone group, n=100) or placebo (control group, n=110) daily for 7 days before surgery and followed by 200 mg of amiodarone or placebo daily for 10 days postoperatively.Results Postoperative AF occurred in 16 patients (16%) receiving amiodarone and in 36 (37.7%) patients receiving placebo (P=0.006). AF occurred at (58.13±16.63) hours after CABG in the low-dose amiodarone group and at (45.03±17.40) hours in the control group (P=0.018). The maximum ventricular rate during AF was significantly slower in the low-dose amiodarone group ((121.42±28.91) beats/min) than in the control group ((134.11 ±30.57) beats/min, P=0.036). The duration of AF was (10.92±9.56) hours for the low-dose amiodarone group compared with (14.81 ±10.37) hours for the control group (P=0.002). The postoperative left ventricular ejection fraction (LVEF) was significantly improved in the low-dose amiodarone group (from (59.9 ±10.3)% to (63.4±11.4)%, P=0.001), and significantly higher compared with the control group ((58.5±10.7)%, P=0.002). Both groups had a similar incidence of complication other than rhythm disturbances (12.0% vs 16.4%, P=0.368). The low-dose amiodarone group patients had shorter hospital stays ((11.8±3.2) days vs (13.8±4.7) days, P=0.001) and lower cost of care (RMB (79 115±16 673) Yuan vs RMB (84 997±21 587) Yuan, P=0.031) than that of

  14. Gas hydrate destabilization and methane release events in the Krishna-Godavari Basin, Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Joshi, R.K.; Mazumdar, A.; Peketi, A.; Ramamurty, P.B.; Naik, B.G.; Kocherla, M.; Carvalho, M.A.; Mahalakshmi, P.; Dewangan, P.; Ramana, M.V.

    13C excursions and earlier reports on the occurrence chemosynthetic bivalves and Mo concentration anomaly to the destabilization of the base of gas hydrate stability zone (BGHSZ). Sea level drop and shale tectonics induced focused fluid flow...

  15. A Proteolytic Cascade Controls Lysosome Rupture and Necrotic Cell Death Mediated by Lysosome-Destabilizing Adjuvants

    OpenAIRE

    Jürgen Brojatsch; Heriberto Lima; Alak K Kar; Jacobson, Lee S.; Stefan M Muehlbauer; Kartik Chandran; Felipe Diaz-Griffero

    2014-01-01

    Recent studies have linked necrotic cell death and proteolysis of inflammatory proteins to the adaptive immune response mediated by the lysosome-destabilizing adjuvants, alum and Leu-Leu-OMe (LLOMe). However, the mechanism by which lysosome-destabilizing agents trigger necrosis and proteolysis of inflammatory proteins is poorly understood. The proteasome is a cellular complex that has been shown to regulate both necrotic cell death and proteolysis of inflammatory proteins. We found that the p...

  16. Study of the influence of ascorbyl palmitate and amiodarone in the stability of unilamellar liposomes.

    Science.gov (United States)

    Benedini, Luciano; Antollini, Silvia; Fanani, Maria Laura; Palma, Santiago; Messina, Paula; Schulz, Pablo

    2014-01-01

    Amiodarone (AMI) is a low water-solubility drug, which is very useful in the treatment of severe cardiac disease. Its adverse effects are associated with toxicity in different tissues. Several antioxidants have been shown to reduce, and prevent AMI toxicity. The aim of this work was to develop and characterize Dimyristoylphosphatidylcholine (DMPC) liposomal carriers doped with ascorbyl palmitate (Asc16) as antioxidant, in order to either minimize or avoid the adverse effects produced by AMI. The employment of liposomes would avoid the use of cosolvents in AMI formulations, and Asc16 could minimize the adverse effects of AMI. To evaluate the partition and integration of AMI and Asc16 in lipid membranes, penetration studies into DMPC monolayers were carried out. The disturbance of the liposomes membranes was studied by generalized polarization (GP). The stability of liposomes was evaluated experimentally and by means of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The size particle and zeta potential (ζ) values of the liposomes were used for application in calculations for attractive and repulsive forces in DLVO theory. In experimental conditions all of these vesicles showed stability at time 0, but only DMPC + Asc16 10% + AMI 10% liposomes kept their size stable and ζ during 28 days. These results are encouraging and suggest that such systems could be suitable for AMI delivery formulations. PMID:24650150

  17. Comparative effect of amiodarone and amiodarone combined with other drugs in treatment of atrial fibrillation%胺碘酮与胺碘酮联合用药治疗心房纤颤疗效的比较

    Institute of Scientific and Technical Information of China (English)

    陈士良; 辛卫鹏; 高谊

    2011-01-01

    AIM: To compare the effect of amiodarone alone and amiodarone combined with other drugs in treatment of atrial fibrillation ( AF). METHODS: A total of 119 patients with AF were divided into single drug group ( n = 54) and multiple drug group ( n = 65 ). The single drug group received amiodarone treatment, whereas the multiple drug group received treatment of amiodarone together with glucose-insulin-potassium and diuretics. The recovery rate of AF and the maintenance rate of sinus rhythm were observed and compared after 6 months treatment. RESULTS: A significant increase in the recovery rate (from 80% vs. 94% ) and a significant decrease in the recovery duration of sinus rhythm from (55 ± 19) h to (39 ±15) h were observed in the multiple drug group. The maintenance rate increased from 81% to 95% , left atrial diameter decreased from (46 ±6) mm to (42 ±6) mm and the left ventricular diastolic diameter decreased from (52 ±7) mm to (45 ±6) mm in the multiple drug group. However, these phenomena were not seen in the single drug group. CONCLUSION: Compared with amiodarone alone, amiodarone combined with other drugs significantly increases the recovery rate and the maintenance rate in patients with AF.%目的:观察单纯用药与联合用药对心房纤颤(房颤)治疗效果.方法:选择119例房颤患者随机分为2组:单纯用药组54例,给予静脉胺碘酮150~300 mg后,继之以口服胺碘酮维持;联合用药组65例,使用极化液、硝酸甘油和小剂量利尿剂、胺碘酮,胺碘酮使用的剂量与方法同单纯用药组.观察两组房颤转复率和窦性维持率.结果:联合用药组的房颤转复率较单纯组明显提高(80% vs.94%,P<0.05),复律时间减少[(55±19)vs.(39±15)s,P<0.05],追踪复律半年后的维持率,联合用药组明显高于单纯用药组(81% vs.95%,P<0.05).复查B超显示:联合用药后,左心房内经明显缩小,从[(46±6)mm减少到(42±6)mm,P<0.05],左心

  18. Treatment of Atrial Fibrillation with Amiodarone Combined with Simvastatin and Amiodarone: A Meta-analysis%胺碘酮联合辛伐他汀与单用胺碘酮治疗心房颤动的Meta分析

    Institute of Scientific and Technical Information of China (English)

    易欣; 黎明江

    2012-01-01

    目的 评价胺碘酮联合辛伐他汀与单用胺碘酮治疗心房颤动(房颤)的疗效.方法 计算机检索Cochrane图书馆、EMBASE及万方医学数据库等1990~2011年收录的文献,对其中胺碘酮联合辛伐他汀(试验组)与单用胺碘酮(对照组)治疗房颤的随机对照试验进行Meta分析.结果 共纳入12篇文献954例.经异质性检验发现各研究结果具有同质性(P=1.0,I2=0%),故选择固定效应模型合并进行两组疗效的Meta分析,求得OR=2.98,95%CI(2.21,4.02),对总体效应进行假设检验得Z=7.18,P<0.00001,提示试验组治疗房颤的效果较对照组好.漏斗图分析结果显示两组疗效Meta分析结果存在偏倚的可能性较小.Meta分析结果示两组治疗房颤不良反应发生率比较差异无统计学意义.结论 胺碘酮联合辛伐他汀治疗房颤较单用胺碘酮效果好.%Objective To evaluate the effectiveness of Amiodarone combined with Simvastatin and Amiodarone in treating atrial fibrillation. Methods We retrieved the literature of Cochrane Library, EMBASE and Wangfang medical Databases, etc, which were published during 1990 to 2011. A Meta-analysis was conducted on the outcomes of randomized controlled trials (RCT) of Amiodarone with simvastatin (experimental group) and Amiodarone (control group) in treating atrial fibrillation. Results We included 954 cases of 12 records in the analysis. The test for heterogeneity in all studies showed that various research results were of heterogeneity (P = 1.0,I2 =0% ) , so a fixed effect model of Meta-analysis was conducted. The total odds ratio was 2.95, 95% confidence interval (95% CI) was from 2.21 to 4.02. The test of hypothesis for overall effects: Z =7. 18, P < 0.00001. The results in treatment of atrial fibrillation were better in experimental group than in control group. There was little deflective possibility in Meta-analysis result of treatment effectiveness from infundibular schema in the two groups. Mela

  19. LKB1 destabilizes microtubules in myoblasts and contributes to myoblast differentiation.

    Directory of Open Access Journals (Sweden)

    Isma Mian

    Full Text Available BACKGROUND: Skeletal muscle myoblast differentiation and fusion into multinucleate myotubes is associated with dramatic cytoskeletal changes. We find that microtubules in differentiated myotubes are highly stabilized, but premature microtubule stabilization blocks differentiation. Factors responsible for microtubule destabilization in myoblasts have not been identified. FINDINGS: We find that a transient decrease in microtubule stabilization early during myoblast differentiation precedes the ultimate microtubule stabilization seen in differentiated myotubes. We report a role for the serine-threonine kinase LKB1 in both microtubule destabilization and myoblast differentiation. LKB1 overexpression reduced microtubule elongation in a Nocodazole washout assay, and LKB1 RNAi increased it, showing LKB1 destabilizes microtubule assembly in myoblasts. LKB1 levels and activity increased during myoblast differentiation, along with activation of the known LKB1 substrates AMP-activated protein kinase (AMPK and microtubule affinity regulating kinases (MARKs. LKB1 overexpression accelerated differentiation, whereas RNAi impaired it. CONCLUSIONS: Reduced microtubule stability precedes myoblast differentiation and the associated ultimate microtubule stabilization seen in myotubes. LKB1 plays a positive role in microtubule destabilization in myoblasts and in myoblast differentiation. This work suggests a model by which LKB1-induced microtubule destabilization facilitates the cytoskeletal changes required for differentiation. Transient destabilization of microtubules might be a useful strategy for enhancing and/or synchronizing myoblast differentiation.

  20. EFFICACY AND SAFETY OF SINUS RHYTHM RESTORATION WITH AMIODARONE AND PROPAFENONE IN OUTPATIENTS, ECONOMIC ASPECTS (BASED ON DATA OF N.A. SEMASHKO NORTHERN MEDICAL CLINICAL CENTER

    Directory of Open Access Journals (Sweden)

    T. A. Istomina

    2016-01-01

    Full Text Available Aim. To study efficacy and safey of sinus rhythm restoration with amiodarone and propafenone in outpatients with recurrent atrial fibrillation (AF, and to estimate pharmacoeconomic efficiency of such cardioversion in comparison with hospital treatment.Material and methods. Patients (n=199; aged 59.2±1.36 with paroxysmal (73.9% or persistent (26.1% AF were included into the multicenter prospective study. Follow-up period was 13.14 months (min 1 month, max 36 months. Patients with arrhythmia relapse <48 h received outpatient cardioversion with amiodarone or propafenone orally. Daily outpatient examination, including ECG and blood pressure monitoring every 30-60 min, was carried out to evaluate efficacy of cardioversion and hemodynamics. Phone contact with patients was available. Patients with unstable hemodynamics received cardioversion in hospital. Patients received propafenone in cumulative dose of 600 mg (150-300 mg every hour, and amiodarone 600-800 mg daily. The cost/effectiveness ratio (CER was estimated. This ratio shows the cost of one unit of effect.Results. Outpatient cardioversion with amiodarone was started 24 h earlier (p=0.029 and with propafenone — 4.5 h earlier (p=0.002 than that in hospital. The average dose of amiodarone in ambulatory cardioversion was 1.3 times less (713.7±84,62 mg, p=0.345 than that in hospital cardioversion. Outpatient treatment with amiodarone restored sinus rhythm 8.7 h earlier, and with propafenone - 3.5 h earlier than the same treatments in hospital. Efficiency of hospital cardioversion with amiodarone was 70%, with propafenone - 80%, and efficiency of outpatient cardioversion — 96,1% and 98,4%, respectively. Outpatient treatment did not cause any severe side effects. Expenses for outpatient cardioversion made up 143 724.25 rubles, and for hospital cardioversion — 92 870.47 rubles. Average treatment costs for one patient in hospital was 6 times greater than for an outpatient. Outpatient

  1. Effect of Aronia melanocarpa fruit juice on amiodarone-induced pneumotoxicity in rats

    Science.gov (United States)

    Valcheva-Kuzmanova, Stefka; Stavreva, Galya; Dancheva, Violeta; Terziev, Ljudmil; Atanasova, Milena; Stoyanova, Angelina; Dimitrova, Anelia; Shopova, Veneta

    2014-01-01

    Background: The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in biologically active polyphenols. Objective: We studied the protective effect of A. melanocarpa fruit juice (AMFJ) in a model of amiodarone (AD)-induced pneumotoxicity in rats. Materials and Methods: AD was instilled intratracheally on days 0 and 2 (6.25 mg/kg). AMFJ (5 mL/kg and 10 mL/kg) was given orally from day 1 to days 2, 4, 9, and 10 to rats, which were sacrificed respectively on days 3, 5, 10, and 28 when biochemical, cytological, and immunological assays were performed. Results: AMFJ antagonized AD-induced increase of the lung weight coefficient. In bronchoalveolar lavage fluid, AD increased significantly the protein content, total cell count, polymorphonuclear cells, lymphocytes and the activity of lactate dehydrogenase, acid phosphatase and alkaline phosphatase on days 3 and 5. In AMFJ-treated rats these indices of direct toxic damage did not differ significantly from the control values. In lung tissue, AD induced oxidative stress measured by malondialdehyde content and fibrosis assessed by the hydroxyproline level. AMFJ prevented these effects of AD. In rat serum, AD caused a significant elevation of interleukin IL-6 on days 3 and 5, and a decrease of IL-10 on day 3. In AMFJ-treated rats, these indices of inflammation had values that did not differ significantly from the control ones. Conclusion: AMFJ could have a protective effect against AD-induced pulmonary toxicity as evidenced by the reduced signs of AD-induced direct toxic damage, oxidative stress, inflammation, and fibrosis. PMID:24914278

  2. Effects of Amiodarone and N-Desethylamiodarone on Cardiac Voltage-gated Sodium Channels

    Directory of Open Access Journals (Sweden)

    Mohammad-Reza eGhovanloo

    2016-03-01

    Full Text Available Amiodarone (AMD is a potent antiarrhythmic drug with high efficacy for treating atrial fibrillation and tachycardia. The pharmacologic profile of AMD is complex. AMD possesses biophysical characteristics of all of class I, II, III, and IV agents. Despite its adverse side effects, AMD remains the most commonly prescribed antiarrhythmic drug. AMD was described to prolong the QT interval and can lead to torsades de pointes. Our goal was to study the effects of AMD on peak and late sodium currents (INa,P and INa,L and determine whether these effects change as AMD is metabolized into N-Desethylamiodarone (DES. We hypothesized that AMD and DES block both INa,P and INa,L with similar profiles due to structural similarities. Given the inherent small amounts of INa,L in NaV1.5, we screened AMD and DES against the Long QT-3-causing mutation, ∆KPQ, to better detect any drug-mediated effect on INa,L. Our results show that AMD and DES do not affect WT or ∆KPQ activation; however, both drugs altered the apparent valence of steady-state fast-inactivation. In addition, AMD and DES preferentially block ∆KPQ peak conductance compared to WT. Both compounds significantly increase INa,L and window currents. We conclude that both compounds have pro-arrhythmic effects on NaV1.5, especially ∆KPQ; however, DES seems to have a greater pro-arrhythmic effect than AMD.

  3. Destabilization analysis of overlapping underground chambers induced by blasting vibration with catastrophe theory

    Institute of Scientific and Technical Information of China (English)

    YAN Chang-bin; XU Guo-yuan; ZUO Yu-jun

    2006-01-01

    According to the main characters of overlapping underground chambers, the roof (floor) of two adjacent underground chambers is simplified to the mechanical model that is the beam with build-in ends. And vibration load due to blasting is simplified to harmonic wave. The catastrophic model of double cusp for underground chambers destabilization induced by blasting vibration has been established under the circumstances of considering deadweight of the beam, and the condition of destabilization has been worked out. The critical safety thickness of the roof (floor) of underground chambers has been confirmed according to the destabilization condition. The influence of amplitude and frequency of blasting vibration load on the critical safety thickness has been analyzed, and the quantitative relation between velocity, frequency of blasting vibration and critical safety thickness has been determined. Research results show that the destabilization of underground chambers is not only dependent on the amplitude and frequency of blasting vibration load, but also related to deadweight load and intrinsic attribute. It is accordant to testing results and some related latest research results of blasting seismic effect. With increasing amplitude, the critical safety thickness of underground chambers decreases gradually. And the possibility of underground chambers destabilization increases. When the frequency of blasting vibration is equal to or very close to the frequency of beam, resonance effect will take place in the system. Then the critical safety thickness will turn to zero, underground chambers will be damaged severely, and its loading capacity will lose on the whole.

  4. Lymphocytes with cytotoxic activity induce rapid microtubule axonal destabilization independently and before signs of neuronal death

    Directory of Open Access Journals (Sweden)

    Arundhati Jana

    2013-02-01

    Full Text Available MS (multiple sclerosis is the most prevalent autoimmune disease of the CNS (central nervous system historically characterized as an inflammatory and demyelinating disease. More recently, extensive neuronal pathology has lead to its classification as a neurodegenerative disease as well. While the immune system initiates the autoimmune response it remains unclear how it orchestrates neuronal damage. In our previous studies, using in vitro cultured embryonic neurons, we demonstrated that MBP (myelin basic protein-specific encephalitogenic CD4 T-cells induce early neuronal damage. In an extension of those studies, here we show that polarized CD4 Th1 and Th17 cells as wells as CD8 T-cells and NK (natural killer cells induce microtubule destabilization within neurites in a contact-independent manner. Owing to the cytotoxic potential of these immune cells, we isolated the luminal components of lytic granules and determined that they were sufficient to drive microtubule destabilization. Since lytic granules contain cytolytic proteins, we determined that the induction of microtubule destabilization occurred prior to signs of apoptosis. Furthermore, we determined that microtubule destabilization was largely restricted to axons, sparing dendrites. This study demonstrated that lymphocytes with cytolytic activity have the capacity to directly drive MAD (microtubule axonal destabilization in a bystander manner that is independent of neuronal death.

  5. Pattern destabilization and emotional processing in cognitive therapy for personality disorders

    Directory of Open Access Journals (Sweden)

    Adele M. Hayes

    2015-02-01

    Full Text Available Clinical trials of treatments for personality disorders can provide a medium for studying the process of therapeutic change with particularly entrenched and self-perpetuating systems and might reveal important principles of system transition. We examined the extent to which maladaptive personality patterns were destabilized in a trial of cognitive therapy personality disorders (CT-PD and how destabilization was associated with emotional processing and treatment outcomes. Dynamic systems theory was used as a theoretical framework for studying change. Method: Participants were 27 patients diagnosed with Avoidant or Obsessive Compulsive Personality Disorder, who completed an open trial of CT-PD. Raters coded treatment sessions using a coding system that operationalizes emotional processing, as well as cognitive, affective, behavioral, and somatic components of pathological (negative and more adaptive (positive patterns of functioning. Pattern destabilization (dispersion scores during the early phase of treatment (phase 1: session 1-10 and the schema-focused phase (phase 2: session 11-34 were calculated using a program called GridWare. Results: More pattern destabilization and emotional processing in the schema-focused phase of CT-PD predicted more improvement in personality disorder symptoms and positive pattern strength at the end of treatment, whereas these variables in phase 1 did not predict outcome. Conclusions: In addition to illustrating a quantitative method for studying destabilization and change of patterns of psychopathology, we present findings that are consistent with recent updates of emotional processing theory and with principles from dynamic systems theory.

  6. Efficacy of magnesium-amiodarone step-up scheme in critically ill patients with new-onset atrial fibrillation : a prospective observational study

    NARCIS (Netherlands)

    Sleeswijk, Mengalvio E; Tulleken, Jaap E; Van Noord, Trudeke; Meertens, John H J M; Ligtenberg, Jack J M; Zijlstra, Jan G

    2008-01-01

    Amiodarone is considered a first-choice antiarrhythmic drug in critically ill patients with new-onset atrial fibrillation (AF). However, evidence supporting the use of this potentially toxic drug in critically ill patients is scarce. Magnesium sulphate (MgSO4) has shown to be effective for both rate

  7. Amiodarone use after acute myocardial infarction complicated by heart failure and/or left ventricular dysfunction may be associated with excess mortality

    DEFF Research Database (Denmark)

    Thomas, Kevin L; Al-Khatib, Sana M; Lokhnygina, Yuliya;

    2008-01-01

    BACKGROUND: We sought to assess the association of amiodarone use with mortality during consecutive periods in patients with post-acute myocardial infarction with left ventricular systolic dysfunction and/or HF treated with a contemporary medical regimen. METHODS: This study used data from VALIAN...

  8. No elevation of glutathione S-transferase-a1-1 by amiodarone loading in intensive care unit patients with atrial fibrillation.

    NARCIS (Netherlands)

    Hilkens, M.; Pickkers, P.; Peters, W.H.M.; Hoeven, J.G. van der

    2009-01-01

    Hepatocellular toxicity is a putative side-effect of amiodarone. The hepatic detoxification enzyme glutathione S-transferase-A1-1 (GSTA1-1) is a sensitive indicator of hepatocellular damage. We investigated the occurrence of subclinical liver injury, as measured by plasma GSTA1-1 in intensive care u

  9. Electromagnetic waves destabilized by runaway electrons in near-critical electric fields

    CERN Document Server

    Kómár, A; Fülöp, T

    2013-01-01

    Runaway electron distributions are strongly anisotropic in velocity space. This anisotropy is a source of free energy that may destabilize electromagnetic waves through a resonant interaction between the waves and the energetic electrons. In this work we investigate the high-frequency electromagnetic waves that are destabilized by runaway electron beams when the electric field is close to the critical field for runaway acceleration. Using a runaway electron distribution appropriate for the near-critical case we calculate the linear instability growth rate of these waves and conclude that the obliquely propagating whistler waves are most unstable. We show that the frequencies, wave numbers and propagation angles of the most unstable waves depend strongly on the magnetic field. Taking into account collisional and convective damping of the waves, we determine the number density of runaways that is required to destabilize the waves and show its parametric dependences.

  10. Recent changes to the Gulf Stream causing widespread gas hydrate destabilization.

    Science.gov (United States)

    Phrampus, Benjamin J; Hornbach, Matthew J

    2012-10-25

    The Gulf Stream is an ocean current that modulates climate in the Northern Hemisphere by transporting warm waters from the Gulf of Mexico into the North Atlantic and Arctic oceans. A changing Gulf Stream has the potential to thaw and convert hundreds of gigatonnes of frozen methane hydrate trapped below the sea floor into methane gas, increasing the risk of slope failure and methane release. How the Gulf Stream changes with time and what effect these changes have on methane hydrate stability is unclear. Here, using seismic data combined with thermal models, we show that recent changes in intermediate-depth ocean temperature associated with the Gulf Stream are rapidly destabilizing methane hydrate along a broad swathe of the North American margin. The area of active hydrate destabilization covers at least 10,000 square kilometres of the United States eastern margin, and occurs in a region prone to kilometre-scale slope failures. Previous hypothetical studies postulated that an increase of five degrees Celsius in intermediate-depth ocean temperatures could release enough methane to explain extreme global warming events like the Palaeocene-Eocene thermal maximum (PETM) and trigger widespread ocean acidification. Our analysis suggests that changes in Gulf Stream flow or temperature within the past 5,000 years or so are warming the western North Atlantic margin by up to eight degrees Celsius and are now triggering the destabilization of 2.5 gigatonnes of methane hydrate (about 0.2 per cent of that required to cause the PETM). This destabilization extends along hundreds of kilometres of the margin and may continue for centuries. It is unlikely that the western North Atlantic margin is the only area experiencing changing ocean currents; our estimate of 2.5 gigatonnes of destabilizing methane hydrate may therefore represent only a fraction of the methane hydrate currently destabilizing globally. The transport from ocean to atmosphere of any methane released--and thus its

  11. Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase

    OpenAIRE

    Rasimas, Joseph J.; Dalessio, Paula A.; Ropson, Ira J; Pegg, Anthony E.; Fried, Michael G.

    2004-01-01

    O6-alkylguanine-DNA alkyltransferase (AGT) repairs pro-mutagenic O6-alkylguanine and O4-alkylthymine lesions in DNA. The alkylated form of the protein is not reactivated; instead, it is rapidly ubiquitinated and degraded. Here, we show that alkylation destabilizes the native fold of the protein by 0.5–1.2 kcal/mole and the DNA-binding function by 0.8–1.4 kcal/mole. On this basis, we propose that destabilization of the native conformational ensemble acts as a signal for ubiquitination.

  12. Amiodarone therapy in chronic heart failure and myocardial infarction: a review of the mortality trials with special attention to STAT-CHF and the GESICA trials. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina.

    Science.gov (United States)

    Pinto, J V; Ramani, K; Neelagaru, S; Kown, M; Gheorghiade, M

    1997-01-01

    Amiodarone appears to reduce sudden death in patients with left ventricular dysfunction resulting from an acute MI or a primary dilated cardiomyopathy, particularly if complex ventricular arrhythmias are present. Amiodarone's beneficial effect on mortality in these patients could be unrelated to its antiarrhythmic effects. Multiple factors could account for the improvement in mortality such as the drug's antiischemic effects, neuromodulating effects, its effect on left ventricular function and on heart rate. Moreover, patients with LV dysfunction who have survived an episode of sudden death would potentially benefit from amiodarone therapy. Future trials are needed to determine the precise subsets(s) of patients who would benefit from the drug and the most efficacious dosing regimen for the drug. Based on available data, amiodarone is the only antiarrhythmic agent which has not been shown to increase mortality in patients with chronic heart failure.

  13. 普罗帕酮联合胺碘酮使用对混合性心律失常控制的临床观察%Propafenone Joint Amiodarone Use of Mixed Arrhythmia Controlled Clinical Observation

    Institute of Scientific and Technical Information of China (English)

    连献杰

    2015-01-01

    Objective Observation of propafenone joint amiodarone use and separate use of amiodarone on mixed arrhythmia converting the curative effect of contrast. Methods Wil exist more than two kinds of new 34 cases of arrhythmia patients were randomly divided into into propafenone joint amiodarone group (19 cases) and amiodarone group (15 cases), the selected cases not including slow arrhythmia. Propafenone joint amiodarone group was given propafenone 35~70 mg (5~10 min after injection) intravenous injection, if invalid, 20 min after repeated 1 time, rhythm control give amiodarone after 1 mg/min to the micro pump pumping control; Amiodarone group, give amiodarone 150 mg of diluted intravenous glucose injection (10~15 min after injection), if the invalid 10~15 min after repeated injections, rhythm control give amiodarone after 1 mg/min to the micro pump pumping control. If two groups patients 3 consecutive load intravenous drug can not control the rhythm of the heart, it wil give amiodarone to the micro pump pumping 1 mg/min.Results Propafenone group joint amiodarone amiodarone and converting efficiency were 95% (18/19) and 73% (11/15) (P<0.05); Propafenone joint amiodarone group average converting time (1.2 h), amiodarone group average converting time (3.5 h). Conclusion Propafenone joint amiodarone use on converting mixed arrhythmia in curative effect is better than the separate use of amiodarone.%目的 观察普罗帕酮联合胺碘酮使用与单独使用胺碘酮对混合性心律失常转复的疗效对比.方法 将同时存在有2种以上新发心律失常的患者34例随机分为成普罗帕酮联合胺碘酮组(19例)和胺碘酮组(15例)(此次所选病例不包括缓慢型心律失常).普罗帕酮联合胺碘酮组给予普罗帕酮35~70 mg(5~10 min注完)静脉注射,若无效,20 min后重复1次,心律控制后给予胺碘酮1 mg/min持继微量泵泵入控制;胺碘酮组,给予胺碘酮150 mg以葡萄糖注射液稀释后静脉注射(10~15 min

  14. Comparison of use and role of adrenaline and amiodarone in cardiac arrest:Case of emergency center in Kosovo

    Institute of Scientific and Technical Information of China (English)

    Basri Lenjani; Nehat Baftiu; Ilaz Bunjaku; Kadir Hyseni; Arianit Jakupi

    2013-01-01

    Objective: To investigate application of cardiopulmonary resuscitation (CPR) measures within the golden minutes in Europe. Methods: The collected data belong to the patients with cardiac arrest that have been recorded in patients’ protocol logbook at the Emergency Clinic. During the 2010-2011 in the Emergency Center of the CUCK in Prishtina have been treated a total of 269 patients with cardiac arrest, of whom 159 or 59.1% have been treated in 2010, and 110 patients or 40.9% in 2011. Cardiac arrest cases were present during all days of the week, but most frequently cases have been reported on Monday with 32.0% of cases, and on Friday with 24.5% of cases. All patients with cardiac arrest have been treated with physiological solution. Results: In 245 or 91.1% patients adrenaline has been applied; in 64 or 23.8% amiodarone has been applied; in 12 or 4.5% cases atropine has been applied, 11 or 4.1% of cases were treated with NaHCO3; 7 or 2.6% of cases were treated with lidocaine; and 6 or 2.2% of cases were treated with dopamine. All survivors from cardiac arrest have received appropriate medical assistance within 10 minutes from attack, which implies that if cardiac arrest occurs near an health care institution (with an opportunity to provide the emergent health care) the rate of survival is higher. Conclusions: Anti-arrhythmic drugs as with vasopressors, the evidence that anti-arrhythmic drugs are of benefit in cardiac is limited. No anti-arrhythmic drug given during human cardiac arrest has been shown to increase survival to hospital discharge, although amiodarone has been shown to increase survival to hospital admission after shock-refractory VF/VT. There are no data on the use of amiodarone for shock-refractory VF/VT when single shocks are used. Despite the lack of human long-term outcome data, the balance of evidence is in favour of the use of some anti-arrhythmic drugs for the management of arrhythmias in cardiac arrest.

  15. Stabilization and destabilization effects of the electric field on stochastic precipitate pattern formation

    NARCIS (Netherlands)

    Lagzi, István; Izsák, Ferenc

    2004-01-01

    Stabilization and destabilization effects of an applied electric field on the Liesegang pattern formation in low concentration gradient were studied with numerical model simulations. In the absence of an electric field pattern formation exhibits increasingly stochastic behaviour as the initial conce

  16. Methane seeps, methane hydrate destabilization, and the late Neoproterozoic postglacial cap carbonates

    Institute of Scientific and Technical Information of China (English)

    JIANG Ganqing; SHI Xiaoying; ZHANG Shihong

    2006-01-01

    Methane hydrates constitute the largest pool of readily exchangeable carbon at the Earth's sedimentary carapace and may destabilize, in some cases catastrophically, during times of global-scale warming and/or sea level changes. Given the extreme cold during Neoproterozoic ice ages, the aftermath of such events is perhaps amongst the most likely intervals in Earth history to witness a methane hydrate destabilization event. The coincidence of localized but widespread methane seep-like structures and textures, methane-derived isotopic signal,low sulfate concentration, marine barites, and a prominent, short-lived carbon isotope excursion (δ13C≤-5‰) from the post-Marinoan cap carbonates (~635 Ma) provides strong evidence for a methane hydrate destabilization event during the late Neoproterozoic postglacial warming and transgression. Methane release from hydrates could cause a positive feedback to global warming and oxidation of methane could result in ocean anoxia and fluctuation of atmospheric oxygen, providing an environmental force for the early animal evolution in the latest Neoproterozoic. The issues that remain to be clarified for this event include the trigger of methane hydrate destabilization, the time of initial methane release, the predicted ocean anoxia event and its relationship with the biological innovation, additional geochemical signals in response to methane release, and the regional and global synchrony of cap carbonate precipitation. The Doushantuo cap carbonate in South China provides one of the best examples of its age for a better understanding of these issues.

  17. Molecular mechanisms for the destabilization and restabilization of reactivated spatial memory in the Morris water maze

    Directory of Open Access Journals (Sweden)

    Kim Ryang

    2011-02-01

    Full Text Available Abstract Background Memory retrieval is not a passive process. Recent studies have shown that reactivated memory is destabilized and then restabilized through gene expression-dependent reconsolidation. Molecular studies on the regulation of memory stability after retrieval have focused almost exclusively on fear memory, especially on the restabilization process of the reactivated fear memory. We previously showed that, similarly with fear memories, reactivated spatial memory undergoes reconsolidation in the Morris water maze. However, the underlying molecular mechanisms by which reactivated spatial memory is destabilized and restabilized remain poorly understood. In this study, we investigated the molecular mechanism that regulates the stability of the reactivated spatial memory. Results We first showed that pharmacological inactivation of the N-methyl-D-aspartate glutamate receptor (NMDAR in the hippocampus or genetic inhibition of cAMP-responsible element binding protein (CREB-mediated transcription disrupted reactivated spatial memory. Finally, we showed that pharmacological inhibition of cannabinoid receptor 1 (CB1 and L-type voltage gated calcium channels (LVGCCs in the hippocampus blocked the disruption of the reactivated spatial memory by the inhibition of protein synthesis. Conclusions Our findings indicated that the reactivated spatial memory is destabilized through the activation of CB1 and LVGCCs and then restabilized through the activation of NMDAR- and CREB-mediated transcription. We also suggest that the reactivated spatial memory undergoes destabilization and restabilization in the hippocampus, through similar molecular processes as those for reactivated contextual fear memories, which require CB1 and LVGCCs for destabilization and NMDAR and CREB for restabilization.

  18. Maturation promoting factor destabilization facilitates postovulatory aging-mediated abortive spontaneous egg activation in rat.

    Science.gov (United States)

    Prasad, Shilpa; Koch, Biplob; Chaube, Shail K

    2016-04-01

    The present study was designed to investigate whether destabilization of maturation promoting factor (MPF) leads to postovulatory aging-mediated abortive spontaneous egg activation (SEA). If so, we wished to determine whether changes in Wee-1 as well as Emi2 levels are associated with MPF destabilization during postovulatory aging-mediated abortive SEA in rats eggs aged in vivo. For this purpose, sexually immature female rats were given a single injection (20 IU IM) of pregnant mare serum gonadotropin for 48 h followed by single injection of human chorionic gonadotropin (20 IU). Ovulated eggs were collected after 14, 17, 19 and 21 h post-hCG surge to induce postovulatory aging in vivo. The morphological changes, Wee1, phosphorylation status of cyclin dependent kinase 1(Cdk1), early mitotic inhibitor 2 (Emi2), anaphase promoting complex/cyclosome (APC/C), cyclin B1, mitotic arrest deficient protein (MAD2) levels and Cdk1 activity were analyzed. The increased Wee 1 level triggered phosphorylation of Thr-14/Tyr-15 and dephosphorylation of Thr-161 residues of Cdk1. The decrease of Emi2 level was associated with increased APC/C level and decreased cyclin B1 level. Changes in phosphorylation status of Cdk1 and reduced cyclin B1 level resulted in destabilization of MPF. The destabilized MPF finally led to postovulatory aging-mediated abortive SEA in rat eggs. It was concluded that the increase of Wee 1 but decrease of Emi2 level triggers MPF destabilization and thereby postovulatory aging-mediated abortive SEA in rat eggs. PMID:26991553

  19. Metallochaperones regulate intracellular copper levels.

    Directory of Open Access Journals (Sweden)

    W Lee Pang

    Full Text Available Copper (Cu is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes.

  20. The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone.

    Science.gov (United States)

    Joukar, Siyavash; Dehesh, Mohammad-Moein

    2015-12-01

    Dry stigmas of the Crocus sativus L. (Saffron) are well known in world as a popular flavouring and therapeutic agent. The anxiolytic, antidepressant, anticonvulsant and antiarrhythmic effects of saffron suggest that it may affect the autonomic control of the heart. This study assessed its safety on cardiac sympathovagal balance and heart rate variability in rat. Experimental groups were control, Saf50, Saf100, Saf200 (received saffron at dosages of 50 and 100 and 200 mg/kg/d, orally, respectively) and Amio (received 30 mg/mL/kg/d of amiodarone, orally, for 7 days) groups. On day 8, the frequency domain and time domain indices of animals' electrocardiograms were calculated. The heart rate decreased and RR interval increased in Saf200 and Amio groups (Psaffron not only has no harmful effect on activity of cardiac autonomic nervous system, but it may improve the stability of heart sympathovagal balance in normal rat. PMID:27329172

  1. Combined etiology of anaphylactic cardiogenic shock: Amiodarone, epinephrine, cardioverter defibrillator, left ventricular assist devices and the Kounis syndrome

    Directory of Open Access Journals (Sweden)

    Nicholas G Kounis

    2015-01-01

    Full Text Available Anaphylactic shock is a life-threatening condition which needs detailed and mediculous clinical assessment and thoughtful treatment. Several causes can join forces in order to degranulate mast cells. Amiodarone which is an iodine-containing highly lipophilic benzofuran can induce allergic reactions and anaphylactic shock in sensitized patients. Epinephrine is a life saving drug, but in sulfite allergic patients it should be given with caution due its metabisulfite preservative. Metals covering cardiac defibrillators and pacemakers can act as antigens attached to serum proteins and induce allergic reactions. In anaphylactic shock, myocardial involvement due to vasospasm-induced coronary blood flow reduction manifesting as Kounis syndrome should be always considered. Clinically, combined treatment targeting the primary cause of anaphylaxis together with protection of cardiac tissue seems to be of paramount importance.

  2. A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation

    DEFF Research Database (Denmark)

    Camm, A John; Capucci, Alessandro; Hohnloser, Stefan H;

    2011-01-01

    Objectives This randomized double-blind study compared the efficacy and safety of intravenous vernakalant and amiodarone for the acute conversion of recent-onset atrial fibrillation (AF). Background Intravenous vernakalant has effectively converted recent-onset AF and was well tolerated in placebo...... with 32.8% of amiodarone patients; p = 0.0012). Serious adverse events or events leading to discontinuation of study drug were uncommon. There were no cases of torsades de pointes, ventricular fibrillation, or polymorphic or sustained ventricular tachycardia. Conclusions Vernakalant demonstrated efficacy......-controlled studies. Methods A total of 254 adult patients with AF (3 to 48 h duration) eligible for cardioversion were enrolled in the study. Patients received either a 10-min infusion of vernakalant (3 mg/kg) followed by a 15-min observation period and a second 10-min infusion (2 mg/kg) if still in AF, plus a sham...

  3. Adaptation of the QT interval to heart rate changes in isolated perfused guinea pig heart: influence of amiodarone and D-sotalol.

    Science.gov (United States)

    Padrini, R; Speranza, G; Nollo, G; Bova, S; Piovan, D; Antolini, R; Ferrari, M

    1997-05-01

    The inadequacy of the QT interval to shorten following heart rate increase is a feature of the inherited long QT syndrome and may have a role in the genesis of the typical arrhythmias associated with this syndrome (torsade des pointes). The aim of our study was to evaluate whether drugs that prolong the QT interval, such as amiodarone and D-sotalol, may also impair the ability of the QT interval to adapt to sudden heart rate changes. Experiments were carried out on isolated perfused guinea pig hearts (Langendorff preparation). Driving frequency was changed, in steps, every two minutes (Hz: 2.5-3-2.5-3.75-2.5-5-2.5), while epicardial ECG was continuously recorded on magnetic tape. QT interval was automatically measured by means of a beat-by-beat analysis program. D-sotalol was added to the perfusion medium at a concentration of 4 micrograms ml-1, while amiodarone was administered, before in vitro evaluation, for seven days (50 mg kg-1 per day, intraperitoneally). In control experiments two phases of QT adaptation were identified: an abrupt QT shortening at the first beat after frequency change (QT1), followed by a gradual, exponential QT shortening that reached a new steady state in about 1 min (half life: 13 sec). The electrical restitution curve (the relation between QT1 and the corresponding diastolic interval) had a rate constant of 57 +/- 8 ms. Neither drug changed the slow component of QT adaptation. However, both drugs increased the ability of QT to shorten upon premature stimulation: D-sotalol by increasing the rate constant of the restitution curve and amiodarone by decreasing the y-intercept. Our results indicate that D-sotalol and amiodarone do not impair QT shortening during tachycardia but, on the contrary, they may favour QT adaptation, thus reducing the likelihood of the potentially lethal 'R on T phenomenon'. This may be an additional mechanism by which these drugs can exert their antifibrillatory action.

  4. Destabilization of fast particle stabilized sawteeth in ASDEX Upgrade with electron cyclotron current drive

    DEFF Research Database (Denmark)

    Igochine, V.; Chapman, I.T.; Bobkov, V.;

    2011-01-01

    Upgrade for destabilization of fast particle stabilized sawteeth with electron cyclotron current drive (ECCD). It is shown that moderate ECCD from a single gyrotron is able to destabilize the fast particle stabilized sawteeth. A reduction in sawtooth period by about 40% was achieved in first experiments......It is often observed that large sawteeth trigger the neoclassical tearing mode well below the usual threshold for this instability. At the same time, fast particles in the plasma core stabilize sawteeth and provide these large crashes. The paper presents results of first experiments in ASDEX....... These results show that ECCD can be used as a tool for control of sawteeth also in the presence of fast particles....

  5. Calcium signaling and mitochondrial destabilization in the triggering of the NLRP3 inflammasome.

    Science.gov (United States)

    Horng, Tiffany

    2014-06-01

    The NLRP3 inflammasome is a cytosolic complex that activates Caspase-1, leading to maturation of interleukin-1β (IL-1β) and IL-18 and induction of proinflammatory cell death in sentinel cells of the innate immune system. Diverse stimuli have been shown to activate the NLRP3 inflammasome during infection and metabolic diseases, implicating the pathway in triggering both adaptive and maladaptive inflammation in various clinically important settings. Here I discuss the emerging model that signals associated with mitochondrial destabilization may critically activate the NLRP3 inflammasome. Together with studies indicating an important role for Ca2+ signaling, these findings suggest that many stimuli engage Ca2+ signaling as an intermediate step to trigger mitochondrial destabilization, generating the mitochondrion-associated ligands that activate the NLRP3 inflammasome.

  6. Chaos in temporarily destabilized regular systems with the slow passage effect

    International Nuclear Information System (INIS)

    We provide evidences for chaotic behaviour in temporarily destabilized regular systems. In particular, we focus on time-continuous systems with the slow passage effect. The extreme sensitivity of the slow passage phase enables the existence of long chaotic transients induced by random pulsatile perturbations, thereby evoking chaotic behaviour in an initially regular system. We confirm the chaotic behaviour of the temporarily destabilized system by calculating the largest Lyapunov exponent. Moreover, we show that the newly obtained unstable periodic orbits can be easily controlled with conventional chaos control techniques, thereby guaranteeing a rich diversity of accessible dynamical states that is usually expected only in intrinsically chaotic systems. Additionally, we discuss the biological importance of presented results

  7. Destabilization of fast particle stabilized sawteeth in ASDEX Upgrade with electron cyclotron current drive

    Energy Technology Data Exchange (ETDEWEB)

    Igochine, V; Bobkov, V; Guenter, S; Maraschek, M; Pereversev, G; Reich, M; Stober, J [MPI fuer Plasmaphysik, Euratom-Association, D-85748 Garching (Germany); Chapman, I T [EURATOM/CCFE Association, Culham Science Centre, Abingdon, Oxfordshire OX14 3DB (United Kingdom); Moseev, D, E-mail: valentin.igochine@ipp.mpg.de [EURATOM-Risoe DTU, Risoe National Laboratory for Sustainable Energy, Technical University of Denmark, DK-4000 Roskilde (Denmark)

    2011-02-15

    It is often observed that large sawteeth trigger the neoclassical tearing mode well below the usual threshold for this instability. At the same time, fast particles in the plasma core stabilize sawteeth and provide these large crashes. The paper presents results of first experiments in ASDEX Upgrade for destabilization of fast particle stabilized sawteeth with electron cyclotron current drive (ECCD). It is shown that moderate ECCD from a single gyrotron is able to destabilize the fast particle stabilized sawteeth. A reduction in sawtooth period by about 40% was achieved in first experiments. These results show that ECCD can be used as a tool for control of sawteeth also in the presence of fast particles. (brief communication)

  8. Dispersal-induced destabilization of metapopulations and oscillatory Turing patterns in ecological networks

    Science.gov (United States)

    Hata, Shigefumi; Nakao, Hiroya; Mikhailov, Alexander S.

    2014-01-01

    As shown by Alan Turing in 1952, differential diffusion may destabilize uniform distributions of reacting species and lead to emergence of patterns. While stationary Turing patterns are broadly known, the oscillatory instability, leading to traveling waves in continuous media and sometimes called the wave bifurcation, remains less investigated. Here, we extend the original analysis by Turing to networks and apply it to ecological metapopulations with dispersal connections between habitats. Remarkably, the oscillatory Turing instability does not lead to wave patterns in networks, but to spontaneous development of heterogeneous oscillations and possible extinction of species. We find such oscillatory instabilities for all possible food webs with three predator or prey species, under various assumptions about the mobility of individual species and nonlinear interactions between them. Hence, the oscillatory Turing instability should be generic and must play a fundamental role in metapopulation dynamics, providing a common mechanism for dispersal-induced destabilization of ecosystems.

  9. Rising Arctic Ocean temperatures cause gas hydrate destabilization and ocean acidification

    OpenAIRE

    Biastoch, Arne; Treude, Tina; Rüpke, Lars H.; Riebesell, Ulf; Roth, Christina; Burwicz, Ewa B.; Park, Wonsun; Latif, Mojib; Böning, Claus W.; Madec, Gurvan; Wallmann, Klaus

    2011-01-01

    Formed under low temperature – high pressure conditions vast amounts of methane hydrates are considered to be locked up in sediments of continental margins including the Arctic shelf regions[1-3]. Because the Arctic has warmed considerably during the recent decades and because climate models predict accelerated warming if global greenhouse gas emissions continue to rise [3], it is debated whether shallow Arctic hydrate deposits could be destabilized in the near future[4, 5]. Me...

  10. Erythrocyte membrane protein destabilization versus clinical outcome in 160 Portuguese Hereditary Spherocytosis patients

    OpenAIRE

    Rocha, Susana; Costa, Elísio; Rocha-Pereira, Petronila; Ferreira, Fátima; Cleto, Esmeralda; Barbot, José; Quintanilha, Alexandre; Belo, Luís; Santos-Silva, Alice

    2010-01-01

    Abstract Hereditary Spherocytosis (HS) is a haemolytic anaemia caused by erythrocyte protein membrane defects ? spectrin, ankyrin, band 3 or protein 4.2 ? that lead to membrane destabilization. Ours aims were to evaluate the prevalence of protein deficiencies and the role of membrane proteins or of membrane linked proteins in membrane disturbance and in HS clinical outcome. We studied 215 Portuguese individuals ? 203 from 71 families plus 12 individual unrelated subjects, and found...

  11. Destabilization kinetics of polyvinylpyrrolidone-iodine in a field of low frequency impacts

    Science.gov (United States)

    Fadeev, G. N.; Ermolaeva, V. I.; Boldyrev, V. S.; Sinkevich, V. V.

    2016-09-01

    Experimental results on the destabilization kinetics of compounds with chelate structure (polyvinylpyrrolidone-iodine) in the field of the impact of low-frequency vibrations (from 2 to 45 Hz) are presented. The optimum frequencies at which the process rate is greatest are found for different impact modes. Based on the experimental data, conclusions are drawn as to the effect the energy of low-frequency impacts has on the studied clathrate and chelate structures.

  12. Phosphorylation site analysis of the anti-inflammatory and mRNA destabilizing protein tristetraprolin

    OpenAIRE

    Cao, Heping; Deterding, Leesa J.; Blackshear, Perry J.

    2007-01-01

    Tristetraprolin (TTP) is a member of the CCCH zinc finger proteins and is an anti-inflammatory protein. Mice deficient in TTP develop a profound inflammatory syndrome with erosive arthritis, autoimmunity and myeloid hyperplasia. TTP binds to mRNA AU-rich elements with high affinity for UUAUUUAUU nucleotides and causes destabilization of those mRNA molecules. TTP is phosphorylated extensively in vivo and is a substrate for multiple protein kinases in vitro. A number of approaches have been use...

  13. RNA-destabilizing Factor Tristetraprolin Negatively Regulates NF-κB Signaling*

    OpenAIRE

    Liang, Jian; Lei, Tianhua; Song, Yuting; Yanes, Natalie; Qi, Yongfen; Fu, Mingui

    2009-01-01

    Tristetraprolin (TTP) is a CCCH zinc finger-containing protein that destabilizes mRNA by binding to an AU-rich element. Mice deficient in TTP develop a severe inflammatory syndrome mainly because of overproduction of tumor necrosis factor α. We report here that TTP also negatively regulates NF-κB signaling at the transcriptional corepressor level, by which it may repress inflammatory gene transcription. TTP expression inhibited NF-κB-dependent transcription. However, overexpression of TTP did...

  14. Does herding among Swedish institutional investors stabilize or destabilize stock prices?

    OpenAIRE

    Frosteby, Martin; Iliesiu, Silviu

    2016-01-01

    Empirical findings on herding behavior among institutional investors suggest that those market participants speed up the price adjustment to new information and as such stabilize stock prices. Other findings indicate the opposite, that institutional herds drive stock prices away from fundamental values, and thus destabilize stock prices. This study examines the effect that Swedish institutional investors have on the stock prices on the Stockholm Stock Exchange. More precisely, we analyze the ...

  15. Playing and Passing: Expressions of Identity and the Destabilization of Gender Construction

    OpenAIRE

    Palmore, Kim J.

    2010-01-01

    In this dissertation, I demonstrate that non-traditional gender expression by women has significantly developed and expanded ranges of acceptable gender performance for all people. The gender deviancy these women communicate functions not only to promote gender fluidity but to undermine compliance with constructed images of originality. "Playing and Passing: Expressions of Identity and the Destabilization of Gender Construction" addresses women who resist gender conformity. Notions of how...

  16. Posturographic destabilization in eating disorders in female patients exposed to body image related phobic stimuli.

    Science.gov (United States)

    Forghieri, M; Monzani, D; Mackinnon, A; Ferrari, S; Gherpelli, C; Galeazzi, G M

    2016-08-26

    Human postural control is dependent on the central integration of vestibular, visual and proprioceptive inputs. Psychological states can affect balance control: anxiety, in particular, has been shown to influence balance mediated by visual stimuli. We hypothesized that patients with eating disorders would show postural destabilization when exposed to their image in a mirror and to the image of a fashion model representing their body ideal in comparison to body neutral stimuli. Seventeen females patients attending a day centre for the treatment of eating disorders were administered psychometric measures of body dissatisfaction, anxiety, depression and underwent posturographic measures with their eyes closed, open, watching a neutral stimulus, while exposed to a full length mirror and to an image of a fashion model corresponding to their body image. Results were compared to those obtained by eighteen healthy subjects. Eating disordered patients showed higher levels of body dissatisfaction and higher postural destabilization than controls, but this was limited to the conditions in which they were exposed to their mirror image or a fashion model image. Postural destabilization under these conditions correlated with measures of body dissatisfaction. In eating disordered patients, body related stimuli seem to act as phobic stimuli in the posturographic paradigm used. If confirmed, this has the potential to be developed for diagnostic and therapeutic purposes.

  17. Permafrost in steep bedrock slopes and its temperature-related destabilization following climate change

    Science.gov (United States)

    Gruber, S.; Haeberli, W.

    2007-06-01

    Permafrost in steep bedrock is abundant in many cold-mountain areas, and its degradation can cause slope instability that is unexpected and unprecedented in location, magnitude, frequency, and timing. These phenomena bear consequences for the understanding of landscape evolution, natural hazards, and the safe and sustainable operation of high-mountain infrastructure. Permafrost in steep bedrock is an emerging field of research. Knowledge of rock temperatures, ice content, mechanisms of degradation, and the processes that link warming and destabilization is often fragmental. In this article we provide a review and discussion of existing literature and pinpoint important questions. Ice-filled joints are common in bedrock permafrost and possibly actively widened by ice segregation. Broad evidence of destabilization by warming permafrost exists despite problems of attributing individual events to this phenomenon with certainty. Convex topography such as ridges, spurs, and peaks is often subject to faster and deeper thaw than other areas. Permafrost degradation in steep bedrock can be strongly affected by percolating water in fractures. This degradation by advection is difficult to predict and can lead to quick and deep development of thaw corridors along fractures in permafrost and potentially destabilize much greater volumes of rock than conduction would. Although most research on steep bedrock permafrost originates from the Alps, it will likely gain importance in other geographic regions with mountain permafrost.

  18. Active destabilization of base pairs by a DNA glycosylase wedge initiates damage recognition

    Science.gov (United States)

    Kuznetsov, Nikita A.; Bergonzo, Christina; Campbell, Arthur J.; Li, Haoquan; Mechetin, Grigory V.; de los Santos, Carlos; Grollman, Arthur P.; Fedorova, Olga S.; Zharkov, Dmitry O.; Simmerling, Carlos

    2015-01-01

    Formamidopyrimidine-DNA glycosylase (Fpg) excises 8-oxoguanine (oxoG) from DNA but ignores normal guanine. We combined molecular dynamics simulation and stopped-flow kinetics with fluorescence detection to track the events in the recognition of oxoG by Fpg and its mutants with a key phenylalanine residue, which intercalates next to the damaged base, changed to either alanine (F110A) or fluorescent reporter tryptophan (F110W). Guanine was sampled by Fpg, as evident from the F110W stopped-flow traces, but less extensively than oxoG. The wedgeless F110A enzyme could bend DNA but failed to proceed further in oxoG recognition. Modeling of the base eversion with energy decomposition suggested that the wedge destabilizes the intrahelical base primarily through buckling both surrounding base pairs. Replacement of oxoG with abasic (AP) site rescued the activity, and calculations suggested that wedge insertion is not required for AP site destabilization and eversion. Our results suggest that Fpg, and possibly other DNA glycosylases, convert part of the binding energy into active destabilization of their substrates, using the energy differences between normal and damaged bases for fast substrate discrimination. PMID:25520195

  19. Destabilization mechanism of edge-localized MHD modes by a toroidal rotation in tokamaks

    Science.gov (United States)

    Aiba, Nobuyuki; Furukawa, Masaru; Hirota, Makoto; Tokuda, Shinji

    2009-11-01

    In JT-60U, some experimental results showed that the ELM frequency depends on the toroidal rotation, and the rapid rotation in the counter direction of the plasma current changes from Type-I ELM to Grassy ELM, whose frequency is high and the amplitude is small [1]. Since both Type-I and Grassy ELMs are considered as ideal MHD modes destabilizing near the plasma surface, theoretical and numerical analyses about the toroidal rotation effects on the edge localized MHD mode are important to understand this dependence of the ELM frequency on the toroidal rotation frequency. Our previous works have illustrated that the toroidal rotation with shear can destabilize low/intermediate-n (Rotenberg equation. Particularly, we pay attention to the destabilizing effects of the toroidal rotation shear and the centrifuged force on not only equilibrium but also change of equation of motion. [1] N. Oyama et al., Plasma Phys. Control. Fusion 49, 249 (2007). [2] N. Aiba et al., Nucl. Fusion 49, 065015 (2009).

  20. Posturographic destabilization in eating disorders in female patients exposed to body image related phobic stimuli.

    Science.gov (United States)

    Forghieri, M; Monzani, D; Mackinnon, A; Ferrari, S; Gherpelli, C; Galeazzi, G M

    2016-08-26

    Human postural control is dependent on the central integration of vestibular, visual and proprioceptive inputs. Psychological states can affect balance control: anxiety, in particular, has been shown to influence balance mediated by visual stimuli. We hypothesized that patients with eating disorders would show postural destabilization when exposed to their image in a mirror and to the image of a fashion model representing their body ideal in comparison to body neutral stimuli. Seventeen females patients attending a day centre for the treatment of eating disorders were administered psychometric measures of body dissatisfaction, anxiety, depression and underwent posturographic measures with their eyes closed, open, watching a neutral stimulus, while exposed to a full length mirror and to an image of a fashion model corresponding to their body image. Results were compared to those obtained by eighteen healthy subjects. Eating disordered patients showed higher levels of body dissatisfaction and higher postural destabilization than controls, but this was limited to the conditions in which they were exposed to their mirror image or a fashion model image. Postural destabilization under these conditions correlated with measures of body dissatisfaction. In eating disordered patients, body related stimuli seem to act as phobic stimuli in the posturographic paradigm used. If confirmed, this has the potential to be developed for diagnostic and therapeutic purposes. PMID:27397012

  1. Raman-driven destabilization of mode-locked long cavity fiber lasers: fundamental limitations to energy scalability.

    Science.gov (United States)

    Aguergaray, Claude; Runge, Antoine; Erkintalo, Miro; Broderick, Neil G R

    2013-08-01

    We report on the destabilization of the mode-locking operation of a long cavity fiber laser. We show that the destabilization is accompanied by the abrupt emergence of a strong frequency-downshifted Stokes signal, and simultaneously, we find that the laser output displays characteristics typical of noise-like pulses. We use numerical simulations to illustrate how the Stokes signal grows from stimulated Raman scattering and plays a key role in the destabilization of the laser output. Our results indicate that stimulated Raman scattering may impose an ultimate limit on the energy scalability via cavity lengthening. PMID:23903099

  2. Dynamic destabilization analysis based on AE experiment of deep-seated, steep-inclined and extra-thick coal seam

    Institute of Scientific and Technical Information of China (English)

    Fenhua Ren; Xingping Lai; Meifeng Cai

    2008-01-01

    No. 5 coal seam in Huating Coal Mine is a deep-seated, steep-inclined extra-thick coal seam where excavation disturbance is quite frequent. The maximum and minimum principal stresses differ widely. During mining, dynamical destabilization happens frequently and induce tragedies. Based on the comparison between the acoustic emission (AE) experiment on dynamical destabilization of coal rock and the related in situ testing results, this article provides comprehensive analysis on the regular quantificational AE patterns (energy rate, total events) of coal rock destabilization in complex-variable environment. The comparison parameters include dynamic tension energy rate, deformation resistance to compression, and shear stress.

  3. Palladium-mediated intracellular chemistry

    OpenAIRE

    Rahimi M. Yusop; Unciti-Broceta, Asier; Johansson, Emma M. V.; Rosario M. Sanchez-Martin; Bradley, Mark

    2011-01-01

    Many important intracellular biochemical reactions are modulated by transition metals, typically in the form of metalloproteins. The ability to carry out selective transformations inside a cell would allow researchers to manipulate or interrogate innumerable biological processes. Here, we show that palladium nanoparticles trapped within polystyrene microspheres can enter cells and mediate a variety of Pd-0-catalysed reactions, such as allylcarbamate cleavage and Suzuki-Miyaura cross-coupling....

  4. Stochastic models of intracellular transport

    KAUST Repository

    Bressloff, Paul C.

    2013-01-09

    The interior of a living cell is a crowded, heterogenuous, fluctuating environment. Hence, a major challenge in modeling intracellular transport is to analyze stochastic processes within complex environments. Broadly speaking, there are two basic mechanisms for intracellular transport: passive diffusion and motor-driven active transport. Diffusive transport can be formulated in terms of the motion of an overdamped Brownian particle. On the other hand, active transport requires chemical energy, usually in the form of adenosine triphosphate hydrolysis, and can be direction specific, allowing biomolecules to be transported long distances; this is particularly important in neurons due to their complex geometry. In this review a wide range of analytical methods and models of intracellular transport is presented. In the case of diffusive transport, narrow escape problems, diffusion to a small target, confined and single-file diffusion, homogenization theory, and fractional diffusion are considered. In the case of active transport, Brownian ratchets, random walk models, exclusion processes, random intermittent search processes, quasi-steady-state reduction methods, and mean-field approximations are considered. Applications include receptor trafficking, axonal transport, membrane diffusion, nuclear transport, protein-DNA interactions, virus trafficking, and the self-organization of subcellular structures. © 2013 American Physical Society.

  5. 胺碘酮联用缬沙坦治疗阵发性房颤临床观察%Effect of amiodarone combined with valsartan in treating paroxysmal atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    王会玖; 王智斌; 杨迅

    2011-01-01

    目的 观察口服胺碘酮联合应用血管紧张素Ⅱ受体拮抗剂(ARB)缬沙坦在阵发性心房颤动(简称房颤)复律后维持窦律的疗效及对左心房功能的影响.方法 将68例阵发性房颤患者分为单纯口服胺碘酮组(对照组,34例)和胺碘酮加缬沙坦组(治疗组,34例),疗效观察12个月.结果 共66例完成治疗,随访12个月,治疗1、3个月后两组左心房内径比较差异无统计学意义,但6、12个月后两组差异有统计学意义(P<0.05),窦性心律维持6、12个月后比较差异有统计学意义(P<0.05).结论 胺碘酮与缬沙坦联合治疗阵发性房颤维持窦性心律的疗效优于单用胺碘酮,并能延缓左心房扩大.%Objective To investigate the efficacy of amiodarone combined with angiotensin Ⅱ receptor antagonist(ARB)valsartan on paroxysmal atrial fibrillation and left atrial function.Methods A total of 68 patients with paroxysmal atrial fibrillation were randomly divided into two groups:simple amiodarone group(control group,34 cases),amiodarone + valsartan group(stydy group,34 cases),they were treated for 12 months,following-up for 12 months.Results Totally 66 cases completed the treatment.The left atrium in simple amiodarone group was significantly higher than that in amiodarone + valsartan group 6-12 months after treatment(P < 0.05); the maintenance rates of 6 months,12 months of sinus rhythm in amiodarone + valsartan group were significantly higher than those in simple amiodarone group(P < 0.05).Conclusions Amiodarone combined with valsartan can reverse expansion of left atrium,and is more effective for transfer and maintain sinus rhythm compared with simple amiodarone treatment in patients with paroxysmal atrial fibrillation.

  6. DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences

    Directory of Open Access Journals (Sweden)

    Gaëlle Lenglet

    2010-01-01

    Full Text Available DNA targeting drugs represent a large proportion of the actual anticancer drug pharmacopeia, both in terms of drug brands and prescription volumes. Small DNA-interacting molecules share the ability of certain proteins to change the DNA helix's overall organization and geometrical orientation via tilt, roll, twist, slip, and flip effects. In this ocean of DNA-interacting compounds, most stabilize both DNA strands and very few display helix-destabilizing properties. These types of DNA-destabilizing effect are observed with certain mono- or bis-intercalators and DNA alkylating agents (some of which have been or are being developed as cancer drugs. The formation of locally destabilized DNA portions could interfere with protein/DNA recognition and potentially affect several crucial cellular processes, such as DNA repair, replication, and transcription. The present paper describes the molecular basis of DNA destabilization, the cellular impact on protein recognition, and DNA repair processes and the latter's relationships with antitumour efficacy.

  7. Intracardiac intracellular angiotensin system in diabetes.

    NARCIS (Netherlands)

    Kumar, R.; Yong, Q.C.; Thomas, C.M.G.; Baker, K.M.

    2012-01-01

    The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appea

  8. Preparation of liposomal amiodarone and investigation of its cardiomyocyte-targeting ability in cardiac radiofrequency ablation rat model

    Directory of Open Access Journals (Sweden)

    Zhuge Y

    2016-05-01

    Full Text Available Ying Zhuge,1,* Zhi-Feng Zheng,1,* Mu-Qing Xie,2 Lin Li,2 Fang Wang,1 Feng Gao2,3 1Department of Cardiology, Shanghai First People’s Hospital of Nanjing Medical University, 2Department of Pharmaceutics, School of Pharmacy, 3Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: The objective of this study was to develop an amiodarone hydrochloride (ADHC-loaded liposome (ADHC-L formulation and investigate its potential for cardiomyocyte targeting after cardiac radiofrequency ablation (CA in vivo. The ADHC-L was prepared by thin-film method combined with ultrasonication and extrusion. The preparation process was optimized by Box–Behnken design with encapsulation efficiency as the main evaluation index. The optimum formulation was quantitatively obtained with a diameter of 99.9±0.4 nm, a zeta potential of 35.1±10.9 mV, and an encapsulation efficiency of 99.5%±13.3%. Transmission electron microscopy showed that the liposomes were spherical particles with integrated bilayers and well dispersed with high colloidal stability. Pharmacokinetic studies were investigated in rats after intravenous administration, which revealed that compared with free ADHC treatment, ADHC-L treatment showed a 5.1-fold increase in the area under the plasma drug concentration–time curve over a period of 24 hours (AUC0–24 h and an 8.5-fold increase in mean residence time, suggesting that ADHC-L could facilitate drug release in a more stable and sustained manner while increasing the circulation time of ADHC, especially in the blood. Biodistribution studies of ADHC-L demonstrated that ADHC concentration in the heart was 4.1 times higher after ADHC-L treatment in CA rat model compared with ADHC-L sham-operated treatment at 20 minutes postinjection. Fluorescence imaging studies further proved that the heart

  9. Gravity-induced encapsulation of liquids by destabilization of granular rafts

    Science.gov (United States)

    Abkarian, Manouk; Protière, Suzie; Aristoff, Jeffrey M.; Stone, Howard A.

    2013-05-01

    Droplets and bubbles coated by a protective armour of particles find numerous applications in encapsulation, stabilization of emulsions and foams, and flotation techniques. Here we study the role of a body force, such as in flotation, as a means of continuous encapsulation by particles. We use dense particles, which self-assemble into rafts, at oil-water interfaces. We show that these rafts can be spontaneously or controllably destabilized into armoured oil-in-water droplets, which highlights a possible role for common granular materials in environmental remediation. We further present a method for continuous production and discuss the generalization of our approach towards colloidal scales.

  10. Observations and considerations on destabilizing active rock glaciers in the European Alps

    OpenAIRE

    Roer, I.; Haeberli, W.; M. Avian; Kaufmann, V.; R. Delaloye; Lambiel, C; A. Kääb

    2008-01-01

    In many high mountain regions, warming of perennially frozen ground in both coarse debris and rock walls has a major influence on slope stability. In this context, indications of destabilizing active rock glaciers, such as high horizontal velocities (up to 4 ma-1), front advance rates of up to 4 ma-1, and development of crevasse-like cracks (up to 14 m deep), have been documented and monitored in the Alps for a few years. Beside the limited knowledge of rock glacier dynamics, our principle hy...

  11. Mephisto - Research equipment for the study of solid/liquid interface destabilization in metal alloys

    Science.gov (United States)

    Favier, J. J.; Malmejac, Y.; Praizey, J. P.; Cambon, G.; Barillot, R.; Changeart, F. J.

    1982-09-01

    Preliminary results of a feasiblity study of space apparatus intended for solid/liquid destabilization in metal alloys, the Mephisto project, are presented. The phenomena that Mephisto will observe, the parameters it will measure, and the scientific studies that it will perform are stated. A general description is given of the instrument, its experimental tubes, and the experiment process. The environmental and thermal constraints, electrical characteristics, and the characteristics of the different signals are outlined. Finally, the requirements of the payload interfaces on which the equipment will be mounted are set forth, including mechanical/geometrical interfaces, thermal interfaces, and electrical interfaces.

  12. Dendrimers destabilize proteins in a generation-dependent manner involving electrostatic interactions

    DEFF Research Database (Denmark)

    Gichm, Lise; Christensen, Casper; Boas, Ulrik;

    2008-01-01

    . Destabilization is markedly generation-dependent and is most pronounced for generation 3, which is also the most efficient at precipitating insulin. This suggests that proteins can interact with both dendrimer sui-face and interior. The pH-dependence reveals that interactions are mainly mediated by electrostatics......, but their mode of action is unclear. We show that poly(propylene imine) dendrimers based on di-aminobutane (DAB) and modified with guanidinium surface groups reduce insulin thermostability and solubility considerably at microgram per microliter concentrations, while urea-modified groups have hardly any effect...

  13. Destabilizing Effects of Pore-Scale Disorder on Capillary Invasion in Partially-Wettable Porous Media

    CERN Document Server

    Holtzman, Ran

    2016-01-01

    We present a systematic, quantitative assessment of the impact of pore size disorder and its interplay with flow rates and the wettability on immiscible fluid displacement. Pore-scale simulations and micromodel experiments show that increasing disorder destabilizes the displacement, reducing the its efficiency and increasing the fluid-fluid interfacial area, by enhancing trapping at low rates, and fingering at high rates. Lowering disorder enhances the effect of the underlying lattice. Increasing wettability of the invading fluid (contact angle) stabilizes the invasion, smoothing the interface and inhibiting trapping--effects which are suppressed at low disorder and high rates.

  14. Substrate Phosphorylation and Feedback Regulation in JFK-promoted p53 Destabilization*

    OpenAIRE

    Sun, Luyang; SHI, LEI; Wang, Feng; Huangyang, Peiwei; Si, Wenzhe; Yang, Jie; Yao, Zhi; Shang, Yongfeng

    2010-01-01

    The p53 tumor suppressor plays a central role in integrating cellular responses to various stresses. Tight regulation of p53 is thus essential for the maintenance of genome integrity and normal cell proliferation. Previously, we reported that JFK, the only Kelch domain-containing F-box protein in human, promotes ubiquitination and degradation of p53 and that unlike the other E3 ligases for p53, all of which possess an intrinsic ubiquitin ligase activity, JFK destabilizes p53 through the assem...

  15. Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone: A case report

    Institute of Scientific and Technical Information of China (English)

    Hiroki Oikawa; Kazuyuki Suzuki; Tomoyuki Masuda; Chihaya Maesawa; Ryo Sato; Kanta Oikawa; Hiroyuki Yamada; Seizo Oriso; Sadahide Ono; Akiko Yashima-Abo; Koji Kotani

    2005-01-01

    The anti-arrhythmic agent amiodarone (AD) is associated with numerous adverse effects, but serious liver disease is rare. The improved safety of administration of daily low doses of AD has already been established and this regimen is used for long-term medication. Nevertheless,asymptomatic continuous liver injury by AD may increase the risk of step-wise progression of non-alcoholic fatty liver disease. We present an autopsy case of AD-induced liver cirrhosis in a patient who had been treated with a low dose of AD (200 mg/d) daily for 84 mo. The patient was a 85-year-old male with a history of ischemic heart disease.Seven years after initiation of treatment with AD, he was admitted with cardiac congestion. The total dose of AD was 528 g. Mild elevation of serum aminotransferase and hepatomegaly were present. Liver biopsy specimens revealed cirrhosis, and under electron microscopy numerous lysosomes with electron-dense, whorled, lamellar inclusions characteristic of a secondary phospholipidosis were observed. Initially, withdrawal of AD led to a slight improvement of serum aminotransferase levels, but unfortunately his general condition deteriorated and he died from complications of pneumonia and renal failure.Long-term administration of daily low doses of AD carries the risk of progression to irreversible liver injury. Therefore,periodic examination of liver function and/or liver biopsy is required for the management of patients receiving long-term treatment with AD.

  16. 120例胺碘酮不良反应分析%Analysis of 120 amiodarone adverse reactions

    Institute of Scientific and Technical Information of China (English)

    彭庚; 谢文燕; 刘东亮; 董艳彩

    2015-01-01

    Objective To investigate adverse drug reaction (ADR) caused by amiodarone, in order to provide reference for clinical safety and rational drug use.Methods There were 120 patients with adverse drug reaction cases caused by amiodarone. Statistical analysis was made on their age, gender, underlying disease, administration route, drug dosage, history and clinical manifestation of adverse reactions.Results Among 120 patients with amiodarone ADR, there were 77 male (64.17%) and 43 female (35.83%). There were 83 cases over 60-year-old (69.17%). 107 cases had circulation system disease as mainly underlying disease (89.17%). 101 cases had arrhythmia as administration reason (84.17%), among them atrial fibrillation was the main cause with 56 cases (46.67%). There were 2 administration routes, as oral administration in 27 cases (22.50%) and intravenous administration in 93 cases (77.50%). Among reports of 120 ADR cases, there were 100 cases with normal ADR(83.33%), and 20 cases with severe ADR (16.67%). Main clinical manifestations included hepatic damage, phlebitis, anaphylactoid reaction, lung damage, hypotension, arrhythmia, and thyroid dysfunction. After measures of dose decrease and drug withdrawal, there were 35 cured cases (29.17%), 76 improved cases (63.33%), 8 cases with sequelae (6.67%), and 1 death case (0.83%).Conclusion As a safe antiarrhythmic agent in clinical application, amiodarone still provides various ADR manifestations. Close monitoring on ADR in clinical work is necessary for reducing incidence of severe adverse reactions.%目的:探讨胺碘酮所致不良反应(ADR)的发生情况,为临床安全、合理用药提供参考。方法120例胺碘酮所致不良反应患者,对其年龄、性别、基础疾病、用药途径、用药剂量、不良反应史、不良反应的临床表现等进行统计分析。结果120例胺碘酮ADR患者中,男77例(64.17%),女43例(35.83%),发生在60岁以上病例83例(69.17%);原患疾病以

  17. 胺碘酮与西地兰控制快速心房颤动的疗效观察%Clinical effect of Amiodarone and Cedilanid in the patients with rapid atrial fibrilation

    Institute of Scientific and Technical Information of China (English)

    廖祖发

    2013-01-01

    Objective: Observe clinical effect of Amiodarone and Cedilanid in the patients with rapid atrial fibrilation.Methods: 70 patients with rapid atrial fibrilation patients were randomly divided into two groups,35 cases in each group, amiodarone and Cedilanid was used respectively in two groups.Result: atrial fibrilation cardioversion success rate of Amiodarone group (74.3%) was significantly higher than Cedilanid group (48.6%), the cardioversion successful time on amiodarone group (6.3± 1.4h) was significantly shorter than Cedilanid group(9.7 ± 3.5h), the difference was statisticaly significant. Conclusion: Intravenous bolus amiodarone in clinical efficacy to control rapid ventricular rate of AF significantly better than Cedilanid. Conclusion: Intravenous bolus amiodarone in clinical efficacy to control rapid ventricular rate of atrial fibrilation significantly better than Cedilanid.%  目的:观察胺碘酮与西地兰在控制快速心房颤动心室率上的临床疗效。方法:将70例快速房颤患者随机分组,每组35例,分别行胺碘酮和西地兰治疗。结果:胺碘酮组的房颤转复成功率(74.3%)显著高于西地兰组(48.6%),转复成功时间上,胺碘酮组(6.3±1.4h)明显短于西地兰组(9.7±3.5h),差异具有统计意义。结论:静脉推注胺碘酮在控制快速房颤心室率的临床疗效上显著优于西地兰。

  18. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells.

    Science.gov (United States)

    Zhou, Yunfei; Tozzi, Federico; Chen, Jinyu; Fan, Fan; Xia, Ling; Wang, Jinrong; Gao, Guang; Zhang, Aijun; Xia, Xuefeng; Brasher, Heather; Widger, William; Ellis, Lee M; Weihua, Zhang

    2012-01-01

    Altered metabolism in cancer cells is suspected to contribute to chemoresistance, but the precise mechanisms are unclear. Here, we show that intracellular ATP levels are a core determinant in the development of acquired cross-drug resistance of human colon cancer cells that harbor different genetic backgrounds. Drug-resistant cells were characterized by defective mitochondrial ATP production, elevated aerobic glycolysis, higher absolute levels of intracellular ATP, and enhanced HIF-1α-mediated signaling. Interestingly, direct delivery of ATP into cross-chemoresistant cells destabilized HIF-1α and inhibited glycolysis. Thus, drug-resistant cells exhibit a greater "ATP debt" defined as the extra amount of ATP needed to maintain homeostasis of survival pathways under genotoxic stress. Direct delivery of ATP was sufficient to render drug-sensitive cells drug resistant. Conversely, depleting ATP by cell treatment with an inhibitor of glycolysis, 3-bromopyruvate, was sufficient to sensitize cells cross-resistant to multiple chemotherapeutic drugs. In revealing that intracellular ATP levels are a core determinant of chemoresistance in colon cancer cells, our findings may offer a foundation for new improvements to colon cancer treatment. PMID:22084398

  19. Spontaneous Protein Adsorption on Graphene Oxide Nanosheets Allowing Efficient Intracellular Vaccine Protein Delivery.

    Science.gov (United States)

    Li, Hui; Fierens, Kaat; Zhang, Zhiyue; Vanparijs, Nane; Schuijs, Martijn J; Van Steendam, Katleen; Feiner Gracia, Natàlia; De Rycke, Riet; De Beer, Thomas; De Beuckelaer, Ans; De Koker, Stefaan; Deforce, Dieter; Albertazzi, Lorenzo; Grooten, Johan; Lambrecht, Bart N; De Geest, Bruno G

    2016-01-20

    Nanomaterials hold potential of altering the interaction between therapeutic molecules and target cells or tissues. High aspect ratio nanomaterials in particular have been reported to possess unprecedented properties and are intensively investigated for their interaction with biological systems. Graphene oxide (GOx) is a water-soluble graphene derivative that combines high aspect ratio dimension with functional groups that can be exploited for bioconjugation. Here, we demonstrate that GOx nanosheets can spontaneously adsorb proteins by a combination of interactions. This property is then explored for intracellular protein vaccine delivery, in view of the potential of GOx nanosheets to destabilize lipid membranes such as those of intracellular vesicles. Using a series of in vitro experiments, we show that GOx nanosheet adsorbed proteins are efficiently internalized by dendritic cells (DCs: the most potent class of antigen presenting cells of the immune system) and promote antigen cross-presentation to CD8 T cells. The latter is a hallmark in the induction of potent cellular antigen-specific immune responses against intracellular pathogens and cancer. PMID:26694764

  20. Genome Destabilizing Mutator Alleles Drive Specific Mutational Trajectories in Saccharomyces cerevisiae

    Science.gov (United States)

    Stirling, Peter C.; Shen, Yaoqing; Corbett, Richard; Jones, Steven J. M.; Hieter, Philip

    2014-01-01

    In addition to environmental factors and intrinsic variations in base substitution rates, specific genome-destabilizing mutations can shape the mutational trajectory of genomes. How specific alleles influence the nature and position of accumulated mutations in a genomic context is largely unknown. Understanding the impact of genome-destabilizing alleles is particularly relevant to cancer genomes where biased mutational signatures are identifiable. We first created a more complete picture of cellular pathways that impact mutation rate using a primary screen to identify essential Saccharomyces cerevisiae gene mutations that cause mutator phenotypes. Drawing primarily on new alleles identified in this resource, we measure the impact of diverse mutator alleles on mutation patterns directly by whole-genome sequencing of 68 mutation-accumulation strains derived from wild-type and 11 parental mutator genotypes. The accumulated mutations differ across mutator strains, displaying base-substitution biases, allele-specific mutation hotspots, and break-associated mutation clustering. For example, in mutants of POLα and the Cdc13–Stn1–Ten1 complex, we find a distinct subtelomeric bias for mutations that we show is independent of the target sequence. Together our data suggest that specific genome-instability mutations are sufficient to drive discrete mutational signatures, some of which share properties with mutation patterns seen in tumors. Thus, in a population of cells, genome-instability mutations could influence clonal evolution by establishing discrete mutational trajectories for genomes. PMID:24336748

  1. Formation of asphaltene deposits from crude oil destabilized by addition of propane

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.; Creek, J. [Chevron Energy Technology Co., Houston, TX (United States); Fan, T.; Buckley, J. [New Mexico Inst. of Mining and Technology, NM (United States)

    2008-07-01

    As oil development moves into deeper water and deeper wells, it is increasingly important to predict the formation of asphaltene deposits. The first step toward predicting deposition is knowing the asphaltene stability as a function of temperature, pressure, and composition. Flocculated asphaltenes can segregate under the influence of gravity in low energy environments. The challenge lies in understanding the deposits that form on pipe walls in producing wells. This paper reported on a continuing study of arterial deposition from destabilized crude oils in stainless steel capillary tubing as a function of several variables, including the molecular size of the paraffinic precipitating agent. The initial studies revealed that destabilization of asphaltenes from a given crude oil with higher molecular weight precipitants produced a larger volume of asphaltene enriched deposit compared to a lower molecular weight precipitant with the same crude oil. Liquid n-paraffins precipitants from n-pentane to n-pentadecane were used in the initial studies. The data was then used to forecast precipitation with solution gas at different pressures and temperatures. In this present study, the range of paraffinic precipitants was extended to include propane for a comparative evaluation to determine the driving force for asphaltene precipitation in reservoir fluids.

  2. Clinical observation of amiodarone in the treatment of atrial fibril ation%胺碘酮在心房颤动治疗中的疗效观察

    Institute of Scientific and Technical Information of China (English)

    陈思光

    2013-01-01

    Objective Comparative Study on efficacy of amiodarone and digitalis drug treatment of atrial fibril ation to control ventricular rate.Methods October 2009 to October 2011, 110 cases of hospitalization of patients with atrial fibril ation in hospital medicine as a research object,The patients were randomly divided into 2 groups,Amiodarone group 54 cases,Digitalis group of 56 cases, Intravenous administration.Results Amiodarone group the total effective rate was 85.2%(46/54),Digitalis group, the total effective rate was 57.1%(32/56),Two groups of patients with total efficiency,Statistical y significant difference(P<0.05).Conclusion Intravenous bolus of amiodarone in the treatment of atrial fibril ation effective than digitalis drugs,Superior to digitalis drugs in the control of ventricular rate.%目的对比研究胺碘酮与洋地黄类药物治疗房颤控制心室率的疗效。方法以2009年10月至2011年10月在本院内科住院110例房颤患者为研究对象,患者随机分成2组,胺碘酮组54例,洋地黄组56例,分别静脉给药胺碘酮和毛花苷C。结果胺碘酮组的总有效率为85.2%(46/54),洋地黄组的总有效率为57.1%(32/56),两组患者的总有效率比较,差异具有统计学意义(P<0.05)。结论静脉推注胺碘酮治疗房颤的疗效优于洋地黄类药物,在控制心室率方面也优于洋地黄类药物。

  3. Quantitation of Flecainide, Mexiletine, Propafenone, and Amiodarone in Serum or Plasma Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

    Science.gov (United States)

    Slawson, Matthew H; Johnson-Davis, Kamisha L

    2016-01-01

    Flecainide, mexiletine, propafenone, and amiodarone are antiarrhythmic drugs that are used primarily in the treatment of cardiac arrhythmias. The monitoring of the use of these drugs has applications in therapeutic drug monitoring and overdose situations. LC-MS/MS is used to analyze plasma/serum extracts with loxapine as the internal standard to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix matched calibration curve is used for quantitation. PMID:26660169

  4. The amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) opens large-conductance Ca2+-activated K+ channels and relaxes vascular smooth muscle.

    Science.gov (United States)

    Gessner, Guido; Heller, Regine; Hoshi, Toshinori; Heinemann, Stefan H

    2007-01-26

    2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) has been developed to retain the antiarrhythmic properties of the parent molecule amiodarone but to eliminate its undesired side effects. In patch-clamp experiments, KB130015 activated large-conductance, Ca2+-activated BK(Ca) channels formed by hSlo1 (alpha) subunits in HEK 293 cells. Channels were reversibly activated by shifting the open-probability/voltage (P(o)/V) relationship by about -60 mV in 3 muM intracellular free Ca2+ ([Ca2+]in). No effect on the single-channel conductance was observed. KB130015-mediated activation of BK(Ca) channels was half-maximal at 20 microM with a Hill coefficient of 2.8. BK(Ca) activation by KB130015 did not require the presence of Ca2+ and still occurred with saturating (100 microM) [Ca2+]in. Effects of the prototypic BK(Ca) activator NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one) and those of KB130015 were not additive suggesting that both activators may at least partially share a common mechanism of action. KB130015-mediated activation was observed also for BK(Ca) channels from insects and for human BK(Ca) channels with already profoundly left-shifted voltage-dependence. In contrast, human intermediate conductance Ca2+-activated channels were inhibited by KB130015. Using segments of porcine pulmonary arteries, KB130015 induced endothelium-independent vasorelaxation, half-maximal at 43 microM KB130015. Relaxation was inhibited by 1 mM tetraethylammonium, suggesting that KB130015 can activate vascular smooth muscle type BK(Ca) channels under physiological conditions. Interestingly, the shift in the P(o)/V relationship was considerably stronger (-90 mV in 3 microM [Ca2+]in) for BK(Ca) channels containing Slo-beta1 subunits. Thus, KB130015 belongs to a novel class of BK(Ca) channel openers that exert an effect depending on the subunit composition of the channel complex.

  5. Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of acetaminophen and amiodarone.

    Science.gov (United States)

    Prill, Sebastian; Bavli, Danny; Levy, Gahl; Ezra, Elishai; Schmälzlin, Elmar; Jaeger, Magnus S; Schwarz, Michael; Duschl, Claus; Cohen, Merav; Nahmias, Yaakov

    2016-05-01

    Prediction of drug-induced toxicity is complicated by the failure of animal models to extrapolate human response, especially during assessment of repeated dose toxicity for cosmetic or chronic drug treatments. In this work, we present a 3D microreactor capable of maintaining metabolically active HepG2/C3A spheroids for over 28 days in vitro under stable oxygen gradients mimicking the in vivo microenvironment. Mitochondrial respiration was monitored using two-frequency phase modulation of phosphorescent microprobes embedded in the tissue. Phase modulation is focus independent and unaffected by cell death or migration. This sensitive measurement of oxygen dynamics revealed important information on the drug mechanism of action and transient subthreshold effects. Specifically, exposure to antiarrhythmic agent, amiodarone, showed that both respiration and the time to onset of mitochondrial damage were dose dependent showing a TC50 of 425 μm. Analysis showed significant induction of both phospholipidosis and microvesicular steatosis during long-term exposure. Importantly, exposure to widely used analgesic, acetaminophen, caused an immediate, reversible, dose-dependent loss of oxygen uptake followed by a slow, irreversible, dose-independent death, with a TC50 of 12.3 mM. Transient loss of mitochondrial respiration was also detected below the threshold of acetaminophen toxicity. The phenomenon was repeated in HeLa cells that lack CYP2E1 and 3A4, and was blocked by preincubation with ascorbate and TMPD. These results mark the importance of tracing toxicity effects over time, suggesting a NAPQI-independent targeting of mitochondrial complex III might be responsible for acetaminophen toxicity in extrahepatic tissues. PMID:26041127

  6. Model steatogenic compounds (amiodarone, valproic acid, and tetracycline alter lipid metabolism by different mechanisms in mouse liver slices.

    Directory of Open Access Journals (Sweden)

    Ewa Szalowska

    Full Text Available Although drug induced steatosis represents a mild type of hepatotoxicity it can progress into more severe non-alcoholic steatohepatitis. Current models used for safety assessment in drug development and chemical risk assessment do not accurately predict steatosis in humans. Therefore, new models need to be developed to screen compounds for steatogenic properties. We have studied the usefulness of mouse precision-cut liver slices (PCLS as an alternative to animal testing to gain more insight into the mechanisms involved in the steatogenesis. To this end, PCLS were incubated 24 h with the model steatogenic compounds: amiodarone (AMI, valproic acid (VA, and tetracycline (TET. Transcriptome analysis using DNA microarrays was used to identify genes and processes affected by these compounds. AMI and VA upregulated lipid metabolism, whereas processes associated with extracellular matrix remodelling and inflammation were downregulated. TET downregulated mitochondrial functions, lipid metabolism, and fibrosis. Furthermore, on the basis of the transcriptomics data it was hypothesized that all three compounds affect peroxisome proliferator activated-receptor (PPAR signaling. Application of PPAR reporter assays classified AMI and VA as PPARγ and triple PPARα/(β/δ/γ agonist, respectively, whereas TET had no effect on any of the PPARs. Some of the differentially expressed genes were considered as potential candidate biomarkers to identify PPAR agonists (i.e. AMI and VA or compounds impairing mitochondrial functions (i.e. TET. Finally, comparison of our findings with publicly available transcriptomics data showed that a number of processes altered in the mouse PCLS was also affected in mouse livers and human primary hepatocytes exposed to known PPAR agonists. Thus mouse PCLS are a valuable model to identify early mechanisms of action of compounds altering lipid metabolism.

  7. Aryl radical involvement in amiodarone-induced pulmonary toxicity: Investigation of protection by spin-trapping nitrones

    International Nuclear Information System (INIS)

    Amiodarone (AM), an antidysrrhythmic drug, can produce serious adverse effects, including potentially fatal AM-induced pulmonary toxicity (AIPT). AM-induced cytotoxicity and pulmonary fibrosis are well recognized, but poorly understood mechanistically. The hypothesis of aryl radical involvement in AM toxicity was tested in non-biological and biological systems. Photolysis of anaerobic aqueous solutions of AM, or N-desethylamiodarone (DEA) resulted in the formation of an aryl radical, as determined by spin-trapping and electron paramagnetic resonance (EPR) spectroscopy experiments. The non-iodinated AM analogue, didesiodoamiodarone (DDIA), did not form aryl radicals under identical conditions. The toxic susceptibility of human lung epithelioid HPL1A cells to AM, DEA, and DDIA showed time- and concentration-dependence. DEA had a more rapid and potent toxic effect (LC50 = 8 μM) than AM (LC50 = 146 μM), whereas DDIA cytotoxicity was intermediate (LC50 = 26 μM) suggesting a minor contribution of the iodine atoms. Incubation of human lung epithelial cells with the spin-trapping nitrones α-phenyl-N-t-butylnitrone (PBN, 10 mM) or α-(4-pyridyl N-oxide)-N-t-butylnitrone (POBN, 5.0 mM) did not significantly protect against AM, DEA, or DDIA cytotoxicity. Intratracheal administration of AM to hamsters produced pulmonary fibrosis at day 21, which was not prevented by 4 days of treatment with 150 mg/kg/day PBN or 164 mg/kg/day POBN. However, the body weight loss in AM-treated animals was counteracted by PBN. These results suggest that, although AM can generate an aryl radical photochemically, its in vivo formation may not be a major contributor to AM toxicity, and that spin-trapping reagents do not halt the onset of AM toxicity

  8. Endoscopic autofluorescence micro-spectroimaging of alveoli: comparative spectral analysis of amiodarone-induced pneumonitis patients and healthy smokers

    Science.gov (United States)

    Bourg-Heckly, G.; Vever-Bizet, C.; Blondel, W.; Salaün, M.; Thiberville, L.

    2011-03-01

    Fibered confocal fluorescence microscopy (FCFM) with spectroscopic analysis capability was used during bronchoscopy, at 488nm excitation, to record autofluorescence images and associated emission spectra of the alveoli of 5 healthy smoking volunteers and 7 non-smoking amiodarone-induced pneumonitis (AIP) patients. Alveolar fluorescent cellular infiltration was observed in both groups. Our objective was to assess the potential of spectroscopy in differentiating these two groups. Methods: We previously demonstrated that in healthy smokers alveolar elastin backbone and tobacco tar contained in macrophages contribute to the observed signal. Each normalized spectrum was modeled as a linear combination of 3 components: Sexp(λ) = Ce.Se(λ)+Ct.St(λ)+CG.SG(λ), Ce, Ct and CG are amplitude coefficients. Se(λ) and St(λ) are respectively the normalized elastin and tobacco tar emission spectra measured experimentally and SG(λ) a gaussian spectrum with tunable width and central wavelength. Levenbergt-Marquardt algorithm determined the optimal set of coefficients. Results: AIP patient autofluorescence spectra can be uniquely modelized by the linear combination of the elastin spectrum (Ce = 0.61) and of a gaussian spectrum (center wavelength 550nm, width 40nm); the tobacco tar spectrum coefficient Ct is found to be zero. For healthy smoking volunteers, only two spectral components were considered: the tobacco tar component (Ct = 1,03) and the elastin component (Ce = 0). Conclusion: Spectral analysis is able to distinguish cellular infiltrated images from AIP patients and healthy smoking volunteers. It appears as a powerful complementary tool for FCFM.

  9. The mass media destabilizes the cultural homogenous regime in Axelrod's model

    International Nuclear Information System (INIS)

    An important feature of Axelrod's model for culture dissemination or social influence is the emergence of many multicultural absorbing states, despite the fact that the local rules that specify the agents interactions are explicitly designed to decrease the cultural differences between agents. Here we re-examine the problem of introducing an external, global interaction-the mass media-in the rules of Axelrod's model: in addition to their nearest neighbors, each agent has a certain probability p to interact with a virtual neighbor whose cultural features are fixed from the outset. Most surprisingly, this apparently homogenizing effect actually increases the cultural diversity of the population. We show that, contrary to previous claims in the literature, even a vanishingly small value of p is sufficient to destabilize the homogeneous regime for very large lattice sizes.

  10. Four-Rod Stabilization of Severely Destabilized Lumbar Spine Caused by Metastatic Tumor

    Directory of Open Access Journals (Sweden)

    Isao Shibuya

    2013-01-01

    Full Text Available We report a case of a 67-year-old female with severely destabilized lumbar spine caused by metastatic malignant tumor. The primary lesion was a thyroid follicular adenocarcinoma. Complete destruction of the L3, L4, and L5 vertebrae had resulted in severe instability, which left the patient with severe back pain and bed-ridden. Since the vertebrae were so severely damaged at 3 levels, 4 rods were used to stabilize the spine. Following stabilization, the pain was alleviated and the patient’s quality of life improved. We introduce here the 4-rod technique to stabilize the spine over 3 vertebral levels following severe destruction by metastatic tumor.

  11. Engineering FKBP-Based Destabilizing Domains to Build Sophisticated Protein Regulation Systems.

    Directory of Open Access Journals (Sweden)

    Wenlin An

    Full Text Available Targeting protein stability with small molecules has emerged as an effective tool to control protein abundance in a fast, scalable and reversible manner. The technique involves tagging a protein of interest (POI with a destabilizing domain (DD specifically controlled by a small molecule. The successful construction of such fusion proteins may, however, be limited by functional interference of the DD epitope with electrostatic interactions required for full biological function of proteins. Another drawback of this approach is the remaining endogenous protein. Here, we combined the Cre-LoxP system with an advanced DD and generated a protein regulation system in which the loss of an endogenous protein, in our case the tumor suppressor PTEN, can be coupled directly with a conditionally fine-tunable DD-PTEN. This new system will consolidate and extend the use of DD-technology to control protein function precisely in living cells and animal models.

  12. Phosphorylation of ARD1 by IKKβ contributes to its destabilization and degradation

    International Nuclear Information System (INIS)

    IκB kinase β (IKKβ), a major kinase downstream of various proinflammatory signals, mediates multiple cellular functions through phosphorylation and regulation of its substrates. On the basis of protein sequence analysis, we identified arrest-defective protein 1 (ARD1), a protein involved in apoptosis and cell proliferation processes in many human cancer cells, as a new IKKβ substrate. We provided evidence showing that ARD1 is indeed a bona fide substrate of IKKβ. IKKβ physically associated with ARD1 and phosphorylated it at Ser209. Phosphorylation by IKKβ destabilized ARD1 and induced its proteasome-mediated degradation. Impaired growth suppression was observed in ARD1 phosphorylation-mimic mutant (S209E)-transfected cells as compared with ARD1 non-phosphorylatable mutant (S209A)-transfected cells. Our findings of molecular interactions between ARD1 and IKKβ may enable further understanding of the upstream regulation mechanisms of ARD1 and of the diverse functions of IKKβ.

  13. Non-resonant destabilization of (1/1) internal kink mode by suprathermal electron pressure

    Energy Technology Data Exchange (ETDEWEB)

    Delgado-Aparicio, L.; Gates, D. A.; Gorelenkov, N.; Scott, S.; Bertelli, N.; Wilson, R. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); Sugiyama, L. [MIT - Laboratory of Nuclear Science, Cambridge, Massachusetts 02139 (United States); Shiraiwa, S.; Irby, J.; Granetz, R.; Parker, R.; Baek, S. G.; Faust, I.; Wallace, G.; Mumgaard, R.; Gao, C.; Greenwald, M.; Hubbard, A.; Hughes, J.; Marmar, E. [MIT - Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); and others

    2015-05-15

    New experimental observations are reported on the structure and dynamics of short-lived periodic (1, 1) “fishbone”-like oscillations that appear during radio frequency heating and current-drive experiments in tokamak plasmas. For the first time, measurements can directly relate changes in the high energy electrons to the mode onset, saturation, and damping. In the relatively high collisionality of Alcator C-Mod with lower hybrid current drive, the instability appears to be destabilized by the non-resonant suprathermal electron pressure—rather than by wave-particle resonance, rotates toroidally with the plasma and grows independently of the (1, 1) sawtooth crash driven by the thermal plasma pressure.

  14. EFFECTS OF AMIODARONE, CYCLOSPORINE-A, AND PSC-833 ON THE CYTOTOXICITY OF MITOXANTRONE, DOXORUBICIN, AND VINCRISTINE IN NON-P-GLYCOPROTEIN HUMAN SMALL-CELL LUNG-CANCER CELL-LINES

    NARCIS (Netherlands)

    VANDERGRAAF, WTA; DEVRIES, EGE; TIMMERBOSSCHA, H; MEERSMA, GJ; MESANDER, G; VELLENGA, E; MULDER, NH

    1994-01-01

    The multidrug resistance (MDR) modulators amiodarone (AM), cyclosporin A (CsA), and PSC 833 were tested for their potential to modulate cytotoxicity of doxorubicin (DOX), vincristine (VCR), and mitoxantrone (MX) in a sensitive human small cell lung carcinoma cell line GLC4 in its DOX-resistant non-P

  15. 胺碘酮致甲状腺功能异常的诊治进展%The progress on the diagnosis and treatment of amiodarone-induced thyroid dysfunction

    Institute of Scientific and Technical Information of China (English)

    许宇静; 洪侃

    2011-01-01

    Amiodarone is an effective medication approved for the treatment of cardiac arrhythmias. However, this drug has high iodine content, and this feature plus the intrinsic effects on the body which make amiodarone toxic to the thyroid gland would induce a series of disfunction,even result in overt hypothyroidism or thyrotoxicosis. So far,the diagnosis and treatment of amiodarone-induced hypothyroidism(AIH) is clear and definite, whereas that of amiodarone-inducedthyrotoxicosis(AIT) and the ability to distinguish between the subtypes of the diease have much more challenge. And confirming the subtype of AIT is instructive to the treatment.%胺碘酮是治疗心律失常的常用药物.但由于其富含碘及自身固有的特性,可导致一系列甲状腺功能的紊乱,甚至引发明显的甲状腺功能减退(甲减)或甲状腺功能亢进(甲亢).对于胺碘酮所致甲减(AIH)的诊断和治疗目前比较清晰,但对胺碘酮所致甲亢(AIT)的诊断、鉴别其亚型及治疗有一定的难度.

  16. 冠心病快速心律失常应用胺碘酮治疗的临床效果分析%The Clinical Effect of Coronary Heart Disease Tachyarrhythmia Analysis Amiodarone Therapy

    Institute of Scientific and Technical Information of China (English)

    陈铸雄

    2014-01-01

    Objective Clinical efficacy in patients with coronary heart disease tachyarrhythmia amiodarone therapy. Methods In our hospital from January 2012 to January 2014 were treated 60 cases of coronary heart disease complicated by tachyarrhythmias in patients of all emergency patients were given amiodarone therapy, and efficacy determination. Results The group of 60 patients after amiodarone total effective rate of 90.0%, adverse reactions were mild and no serious adverse events. Conclusions Amiodarone in the treatment of coronary artery disease in patients with tachyarrhythmia safe and effective.%目的:冠心病快速心律失常患者应用胺碘酮治疗的临床疗效。方法选取我院在2012年1月至2014年1月收治的冠心病并发快速心律失常患者60例,对所有患者均急诊给予胺碘酮治疗,并对疗效进行判定。结果本组60例患者经过胺碘酮治疗总有效率达90.0%,不良反应均较轻微,无严重不良反应发生。结论胺碘酮在冠心病快速心律失常患者的治疗中安全、有效。

  17. Research on the Flow Setting Type Infusion Intravenous Amiodarone in Prevention of Phlebitis%流量设定微调式输液器静脉滴注可达龙预防静脉炎的研究

    Institute of Scientific and Technical Information of China (English)

    李兴芳

    2014-01-01

    目的:探讨使用流量设定微调式输液器静脉滴注可达龙预防静脉炎的临床效果。方法将200例需要使用可达龙患者随机分两组, A组100例,B组100例,A组使用流量设定微调式输液器静脉滴注可达龙。B组使用微量注射泵输注可达龙。结果 A组静脉炎发生率明显低于B组对照组。结论使用流量设定微调式输液器静脉滴注可达龙可有效预防静脉炎发生,值得临床推广。%Objective To explore the use of flow set type infusion intravenous amiodarone in prevention of phlebitis curative effect. Methods 200 cases require the use of amiodarone were randomly divided into two groups,100 cases in A group, 100 cases in B group, group A using flow set type infusion intravenous amiodarone, group B using microinjection pump infusion of cordarone. Results in A group, the incidence of phlebitis was significantly lower than the control group. Conclusion using the flow set type infusion intravenous amiodarone may be effective in preventing phlebitis, worthy of clinical application.

  18. 胺碘酮治疗心衰伴心律失常的临床分析%Therapeutic effects of amiodarone on chronic heart failure complicated by arrhythmia

    Institute of Scientific and Technical Information of China (English)

    周兰珠

    2010-01-01

    目的 评价胺碘酮治疗心力衰竭(HF)伴心律失常的疗效.方法 选择心力衰竭合并心律失常患者96例,在抗心衰治疗同时给予口服胺碘酮6周.结果 治疗6周后观察总有效率91.9%.结论 胺碘酮治疗HF伴心律失常安全、有效.%Objective To evaluate the the therapeutic effects of amiodarone on chronic heart failure complicated by arrhythmia. Methods From 2006 to 2008,96 chronic congestive heart failure patients with arrhythmia were enrolled. All patients were given standard medical treatment according to the current practice guidelines with a β-blocker, an angiotensin-converting enzyme(ACE) inhibitor, and diuretics. At the same time,they were also given oral amiodarone for six weeks. Results After 6 weeks' treatment with amiodarone,the total effective therapeutic effects was 91.9 percent. Conclusion For patients with chronic congestive heart failure complicated by with arrhythmia, amiodarone treatment for six weeks is safe and effective.

  19. Treatment of 200 cases with atrial fibrillation by Shensong Yangxin capsules compared with amiodarone%参松养心胶囊对比胺碘酮治疗心房纤颤200例

    Institute of Scientific and Technical Information of China (English)

    马军

    2015-01-01

    目的:对比参松养心胶囊和胺碘酮治疗心房纤颤的疗效和安全性。方法:100例心房纤颤患者随机分为参松养心胶囊组和胺碘酮组。结果:参松养心胶囊组和胺碘酮组治疗心房纤颤总有效率分别为55%、60%,统计学处理无明显差异(P>0.05)。结论:参松养心胶囊和胺碘酮治疗心房纤颤疗效相当,但参松养心胶囊不良反应更少。%Objective:To compare the clinical effects and safety of Shensong Yangxin capsules and amiodarone in the treatment of atrial fibrillation.Methods:100 cases with atrial fibrillation were divided into Shensong Yangxin capsule group and amiodarone group. Results: Shensong Yangxin capsule group and amiodarone group the total effective rate was 55% and 60% respectively in the treatment of atrial fibrillation, statistically no significant difference (P> 0.05).Conclusion:The therapeutic effects of Shensong Yangxin capsule and amiodarone in the treatment of atrial fibrillation are equal,but Shensong Yangxin capsule with less adverse reactions.

  20. Dynamics of intracellular information decoding

    Science.gov (United States)

    Kobayashi, Tetsuya J.; Kamimura, Atsushi

    2011-10-01

    A variety of cellular functions are robust even to substantial intrinsic and extrinsic noise in intracellular reactions and the environment that could be strong enough to impair or limit them. In particular, of substantial importance is cellular decision-making in which a cell chooses a fate or behavior on the basis of information conveyed in noisy external signals. For robust decoding, the crucial step is filtering out the noise inevitably added during information transmission. As a minimal and optimal implementation of such an information decoding process, the autocatalytic phosphorylation and autocatalytic dephosphorylation (aPadP) cycle was recently proposed. Here, we analyze the dynamical properties of the aPadP cycle in detail. We describe the dynamical roles of the stationary and short-term responses in determining the efficiency of information decoding and clarify the optimality of the threshold value of the stationary response and its information-theoretical meaning. Furthermore, we investigate the robustness of the aPadP cycle against the receptor inactivation time and intrinsic noise. Finally, we discuss the relationship among information decoding with information-dependent actions, bet-hedging and network modularity.

  1. Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

    Directory of Open Access Journals (Sweden)

    Tali Gidalevitz

    2009-03-01

    Full Text Available Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles.

  2. Hydrazine borane-induced destabilization of ammonia borane, and vice versa

    Energy Technology Data Exchange (ETDEWEB)

    Petit, Jean-Fabien; Moussa, Georges [IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095 Montpellier (France); Demirci, Umit B., E-mail: umit.demirci@um2.fr [IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095 Montpellier (France); Toche, François; Chiriac, Rodica [Université Lyon 1, CNRS, UMR 5615, Laboratoire des Multimatériaux et Interfaces, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne (France); Miele, Philippe [IEM (Institut Europeen des Membranes), UMR 5635 (CNRS-ENSCM-UM2), Universite Montpellier 2, Place E. Bataillon, F-34095 Montpellier (France)

    2014-08-15

    Graphical abstract: - Highlights: • Hydrazine borane and ammoniaborane (mole ratio 1:1) destabilize each other. • This is characterized by a melting point at ∼30 °C and decomposition into hydrazine. • Also, some hydrogen H{sub 2} is “explosively” liberated at around 90 °C. • The mixture can be however stabilized into a potential hydrogen storage material. • This hydrogen storage material dehydrogenates up to 300 °C to form boron nitride. - Abstract: In the field of solid-state chemical hydrogen storage, ammonia borane NH{sub 3}BH{sub 3} has been widely studied while hydrazine borane N{sub 2}H{sub 4}BH{sub 3} can be considered as a “novel” material. In the present work, we investigated the behaviour of these boranes when mixed together in a mole ratio of 1:1. Hydrazine borane and ammonia borane destabilize each other. Though stable at 20–25 °C, the mixture melts at ∼30 °C and then undergoes significant decomposition, with desorption of hydrogen H{sub 2} and hydrazine N{sub 2}H{sub 4} from 67 °C. This is explained by the fact that the presence of hydrazine borane disrupts the H{sup δ+}⋯H{sup δ−} network of ammonia borane, and vice versa; the mixture is then much less stable than the pristine boranes. The mixture can nevertheless be stabilized (by heat- or vacuum-treatment and thus extraction of evolving hydrogen and hydrazine), making the as-obtained solid a potential chemical hydrogen storage material. Over the range 25–300 °C, it is able to release ca. 11.4 wt% of almost pure H{sub 2}. Furthermore forms boron nitride as the solid residue, at temperatures as low as 300 °C.

  3. Cationic polymethacrylates with covalently linked membrane destabilizing peptides as gene delivery vectors.

    Science.gov (United States)

    Funhoff, Arjen M; van Nostrum, Cornelus F; Lok, Martin C; Kruijtzer, John A W; Crommelin, Daan J A; Hennink, Wim E

    2005-01-01

    A membrane-disrupting peptide derived from the influenza virus was covalently linked to different polymethacrylates (pDMAEMA, pDAMA and the degradable pHPMA-DMAE, monomers depicted in Fig. 1) using N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) as coupling agent to increase the transfection efficiency of polyplexes based on these polymers. It was shown by circular dichroism (CD) measurements that the polymer-conjugated peptide was, as the free peptide, able to undergo a conformational change of a random coil to an alpha helix upon lowering the pH to 5.0. This indicates that the property of the peptide to destabilize the endosomal membrane was preserved after its conjugation to the cationic polymers. In line herewith, a liposome leakage assay revealed that the polymer-bound peptide has comparable activity as the free peptide. The DNA condensing properties of the synthesized polymer-peptide conjugates were studied with dynamic light scattering and zeta-potential measurements, and it was shown that small (100 to 250 nm), positively charged (+15 to +20 mV) particles were formed. In vitro transfection and toxicity was tested in COS-7 cells, and these experiments showed that the polyplexes with grafted peptide had a substantially higher transfection activity than the control polyplexes, while the toxicity remained unchanged. Cellular uptake of the polyplexes was visualized with confocal laser scanning microscopy, and no differences in cellular uptake could be determined between the peptide containing systems and the control formulation. This shows that the increased transfection activity is indeed due to a better endosomal escape of the peptide grafted polyplexes. This study demonstrates that it is possible to covalently conjugate an endosome disruptive peptide to cationic gene delivery polymers with preservation of its membrane destabilization activity, making these conjugates suitable for in vivo DNA delivery. PMID:15588908

  4. Hydrophilic fluorescent nanogel thermometer for intracellular thermometry.

    Science.gov (United States)

    Gota, Chie; Okabe, Kohki; Funatsu, Takashi; Harada, Yoshie; Uchiyama, Seiichi

    2009-03-01

    The first methodology to measure intracellular temperature is described. A highly hydrophilic fluorescent nanogel thermometer developed for this purpose stays in the cytoplasm and emits stronger fluorescence at a higher temperature. Thus, intracellular temperature variations associated with biological processes can be monitored by this novel thermometer with a temperature resolution of better than 0.5 degrees C.

  5. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    NARCIS (Netherlands)

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free calciu

  6. Curative Effect Observation on Amiodarone in the Treatment of Arrhythmia%胺碘酮治疗心律失常的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    李光立; 李玲

    2014-01-01

    Objective:To explore the arrhythmia outcomes in patients treated with amiodarone. Method:49 patients were treated with arrhythmia. Result:34 cases were markedly improved(69.4%),effective in 11 cases (accounting for 22.4%),4 cases were ineffective(8.2%),the total effective rate was 91.8%. Conclusion:Oral application of amiodarone in the treatment of arrhythmia in clinical effect is good,and can significantly improve cardiac arrhythmia patients,high security,small side effects,with the value of clinical application and promotion.%目的:探讨心律失常患者采用胺碘酮治疗的疗效。方法:对49例心律失常患者进行胺碘酮治疗。结果:显效34例(69.4%),有效11例(22.4%),无效4例(8.2%),总有效率为91.8%。结论:口服应用胺碘酮在治疗心律失常方面临床效果好,能够明显改善心律失常患者病情,安全性高,副作用小,具有临床应用与推广的价值。

  7. Amiodarona causa vasodilatação dependente do endotélio em artérias coronárias caninas Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries

    Directory of Open Access Journals (Sweden)

    Alfredo José Rodrigues

    2005-03-01

    Full Text Available OBJETIVO: Avaliar os efeitos vasodilatadores da amiodarona em artérias coronárias caninas empregando soluções de amiodarona dissolvida em polisorbato 80 ou em água. MÉTODOS: Anéis de artéria coronária, com e sem o endotélio íntegro, foram imersos em solução de krebs e conectadas a um transdutor para aferição de força isométrica promovida por contração vascular. As artérias foram expostas a concentrações crescentes de polisorbato 80, amiodarona dissolvida em água, amiodarona dissolvida em polisorbato 80 e uma apresentação comercial da amiodarona (Cordarone®. Os experimentos foram conduzidos na presença e na ausência dos seguintes bloqueadores enzimáticos: apenas indometacina, Nômega-nitro-L-arginina associada à indometacina e apenas Nômega-nitro-L-arginina. RESULTADOS: O polisorbato 80 causou pequeno relaxamento não dependente do endotélio. O Cordarone®, a amiodarona dissolvida em água e em polisorbato 80 promoveram relaxamento dependente do endotélio, que foi de maior magnitude para a amiodarona dissolvida em polisorbato e para o Cordarone®. Apenas a associação de indometacina com a Nômega-nitro-L-arginina foi capaz de abolir o relaxamento dependente do endotélio provocado pela amiodarona dissolvida em polisorbato 80. CONCLUSÃO: Os resultados obtidos indicam que a vasodilatação promovida pela amiodarona em artérias coronárias caninas é causada principalmente pela estimulação da liberação de óxido nítrico e fatores endoteliais relaxantes dependentes das ciclo-oxigenases.OBJECTIVE: To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water. METHODS: Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of

  8. Long-term efficacy and safety of very-low-dose amiodarone treatment for the maintenance of sinus rhythm in patients with chronic atrial fibrillation after successful direct-current cardioversion

    Institute of Scientific and Technical Information of China (English)

    JONG Gwo-ping; CHANG Mu-hsin; CHANG Ting-chuan; CHOU Pesus; FU Chong-yau; TIEN Li-yun; CHEN Chung-yin; MA Tso-chiang

    2006-01-01

    Background Long-term maintenance of sinus rhythm after successful conversion of chronic atrial fibrillation (CAF), often ameliorates patients' symptoms, reduces the risk of ischemic stroke and improves cardiovascular hemodynamics. This prospective study aims to evaluate the long-term efficacy and safety of very low-dose amiodarone (100 mg daily) for the maintenance of sinus rhythm after successful direct-current (DC)cardioversion in patients with CAF and rheumatic heart disease (RHD) post intervention.Methods This study was a randomized prospective trial. One day after successful DC cardioversion (remained normal sinus rhythm) in patients with CAF and RHD post intervention for more than six months and adequate anticoagulation, all were randomly administered either amiodarone 200 mg daily in group A or amiodarone 100mg daily in group B.Results A total of 76 patients (40 men and 36 women) were examined from February 1998 to December 1999.The mean age of the patients was (66±10) years, and the mean follow-up was (67±8) months (range 61 to 84months). Actuarial rates of the maintenance of sinus rhythm were similar in the two groups after 5 years of follow-up. Four patients (11%) in group A but none in group B experienced significant adverse effects that necessitated withdrawal of amiodarone. No death occurred during the study period.Conclusion A very low dose of amiodarone results in adequate long-term efficacy and is safe for maintaining sinus rhythm in patients with CAF and RHD post intervention after successful DC cardioversion.

  9. Curative Effect Observation of Esmolol and Amiodarone in Controlling Rapid Atrial Fibrillation Ventricular Rate%艾司洛尔与胺碘酮控制快速心房颤动心室率的效果观察

    Institute of Scientific and Technical Information of China (English)

    黄金莹; 姚丹林; 李渊

    2016-01-01

    目的:比较急诊静脉注射艾司洛尔、胺碘酮控制快速房颤心室率的疗效及安全性。方法:将115例快速房颤患者随机分为两组,两组分别给予静脉注射胺碘酮和艾司洛尔治疗,比较两组治疗效果。结果:艾司洛尔组心率减慢情况显著优于胺碘酮组,差异有统计学意义(P0.05)。结论:静脉注射艾司洛尔和胺碘酮在控制快速房颤患者心室率方面都同样安全和有效,艾司洛尔较胺碘酮能更快、更有效地控制快速房颤的心室率。%Objective:To evaluate the efficacy and safety of intravenous Esmolol and Amiodarone controlling ventricular rate in the patients with rapid atrial fibrillation.Method:115 patients with rapid atrial fibrillation patients were randomly divided into two groups,two groups were given intravenous injection of amiodarone and esmolol treatment,compared two groups of treatment effect.Result:Esmolol group heart rate was significantly higher than that of amiodarone group,the difference was statistically significant(P0.05).Conclusion:Intravenous Esmolol and Amiodarone in patients with rapid atrial fibrillation ventricular rate are equally safe and effective,Esmolol than Amiodarone can faster,more effective control of rapid atrial fibrillation ventricular rate.

  10. Clinical study on the efficacy and safety of Amiodarone for treating atrial fibrillation in old patients%胺碘酮治疗老年心房纤颤的疗效及安全性观察

    Institute of Scientific and Technical Information of China (English)

    曹丹阳; 曹晶晶; 周冬翠; 武云涛; 陈艳梅; 毕磊

    2011-01-01

    Objective To study the efficacy and safety of Amiodarone for treating atrial fibrillation in old patients. Methods We retrospectively reviewed 40 elderly cases of atrial fibrillation, amiodarone was administered 0.6 g/day initially, then gradually reduced to 0.2 g/day for maintainance, the curative effect and the side effects of amiodarone in treatment of atrial fibrillation was observed. Results The efficiency of amiodarone treatment was 55%, laseris 32.5%, inefficient to 12. 5%. Simultaneous hypothyroidism occurred in 7 cases, thyroid function in hyperthyroidism, pulmonary fibrosis, pigmentation did not happen in all cases. Conclusions Amiodarone for treating atrial fibrillation in old patients is effective and safe.%目的 探讨胺碘酮对老年阵发性房颤治疗的效果和安全性.方法 观察分析40例老年阵发性房颤患者胺碘酮治疗的效果和药物副作用.结果 胺碘酮治疗显效率为55 0%,有效率为32 5%,无效率为12 5%;发生甲状腺功能减退 7例,未发生甲状腺功能亢进、肺纤维化、色素沉着.结论 胺碘酮应用于老年人房颤有效、安全,但需密切观察甲状腺功能和对肺的毒性作用.

  11. The Clinical Analysis of 24 Cases of Patients with Amiodarone Ventricular Tachycardia%胺碘酮室性心动过速24例临床分析

    Institute of Scientific and Technical Information of China (English)

    宋雪莲

    2014-01-01

    目的:探讨静脉注射胺碘酮治疗室性心动过速疗效。方法自2012年2月~2013年12月对24例室性心动过速患者应用胺碘酮临床治疗资料进行分析。结果经治疗室性心动过速成功复律21例,占87.5%。结论室速发生较多者可用胺碘酮,胺碘酮应采取小剂量负荷,胺碘酮治疗较为安全,维持量亦可相应减少,可提高疗效,提高生活质量。%Objective The effect of intravenous amiodarone treatment of ventricular tachycardia to be investigated. Methods Analyzing clinical treatment data selected from 24 cases of patients with ventricular tachycardia who are given intravenous amiodarone treatment from February 2012 to December 2013. Results With intravenous amiodarone treatment, 21 cases of patients with ventricular tachycardia are cured which make up 87.5 percent of the whole. Conclusions The patients with ventricular tachycardia are suggested to take intravenous amiodarone, but with smal amount of dosage;since the intravenous amiodarone treatment is comparative safe, the dosage can be reduced gradual y with improving the effect and quality of life.

  12. 厄贝沙坦联合胺碘酮治疗阵发性房颤的临床疗效%Effects of the irbesartan combined with amiodarone in the treatment of paroxysmal atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    邹丽芳; 张光君; 陈士良

    2012-01-01

    目的 评价胺碘酮联合厄贝沙坦治疗阵发性房颤的临床疗效.方法 78例阵发性房颤的患者随机分为治疗组(胺碘酮+厄贝沙坦)和对照组(胺碘酮),口服给药,疗程均为1年.比较治疗后2组窦性心律维持率和左心房内径的变化.结果 治疗组窦性心率维持率明显高于对照组(P<0.05),左心房内径亦有显著性缩小(P<0.05).结论 胺碘酮联合厄贝沙坦治疗阵发性心房颤动维持窦性心率的疗效优于单用胺碘酮,且能抑制左心房扩大.%Objective To observe clinical efficacy of amiodarone and irbesartan in the treatment of paroxysmal atrial fibrillation. Methods Seventy - eight cases of paroxysmal atrial fibrillation were randomly divided into treatment group ( amiodarone + irbesartan ) and the control group ( single with amiodarone ) . Taking drugs were by orally and the course was a year. Compared the change of sinus rhythm maintenance rate and left atrial diameter after the treatment in two groups. Results Compared with control group, the sinus rhythm maintenance rate in the treatment group was significantly higher than the control group (P < 0. 05 ) , the left atrial diameter in the treatment group also significantly reduced than the control group ( P < 0. 05 ).Conclusion Effects of amiodarone and irbesartan in the treatment of paroxysmal atrial fibrillation to maintain sinus rhythm has better than single amiodarone , and it can inhibit left atrial enlargement.

  13. Intracellular structure and nucleocytoplasmic transport.

    Science.gov (United States)

    Agutter, P S

    1995-01-01

    Intracellular movement of any solute or particle accords with one of two general schemes: either it takes place predominantly in the solution phase or it occurs by dynamic interactions with solid-state structures. If nucleocytoplasmic exchanges of macromolecules and complexes are predominantly solution-phase processes, i.e., if the former ("diffusionist") perspective applies, then the only significant structures in nucleocytoplasmic transport are the pore complexes. However, if such exchanges accord with the latter ("solid-state") perspective, then the roles of the nucleoskeleton and cytoskeleton in nucleocytoplasmic transport are potentially, at least, as important as that of the pore complexes. The role of the nucleoskeleton in mRNA transport is more difficult to evaluate than that of the cytoskeleton because it is less well characterized, and current evidence does not exclude either perspective. However, the balance of evidence favors a solid-state scheme. It is argued that ribosomal subunits are also more likely to migrate by a solid-state rather than a diffusionist mechanism, though the opposite is true of proteins and tRNAs. Moreover, recent data on the effects of viral proteins on intranuclear RNA processing and migration accord with the solid-state perspective. In view of this balance of evidence, three possible solid-state mechanisms for nucleocytoplasmic mRNA transport are described and evaluated. The explanatory advantage of solid-state models is contrasted with the heuristic advantage of diffusion theory, but it is argued that diffusion theory itself, even aided by modern computational techniques and numerical and graphical approaches, cannot account for data describing the movements of materials within the cell. Therefore, the mechanisms envisaged in a diffusionist perspective cannot be confined to diffusion alone, but must include other processes such as bulk fluid flow.

  14. Validation of merocyanine 540 staining as a technique for assessing capacitation-related membrane destabilization of fresh dog sperm

    NARCIS (Netherlands)

    Steckler, D; Stout, T A E; Durandt, C; Nöthling, J O

    2015-01-01

    The aim of this study was to determine whether flow cytometric evaluation of combined merocyanine 540 and Yo-Pro 1 (M540-YP) staining would identify viable dog sperm that had undergone membrane stabilization known to be associated with capacitation in other species, and whether such destabilization

  15. Simulation of Asymmetric Destabilization of Mine-void Rock Masses Using a Large 3D Physical Model

    Science.gov (United States)

    Lai, X. P.; Shan, P. F.; Cao, J. T.; Cui, F.; Sun, H.

    2016-02-01

    When mechanized sub-horizontal section top coal caving (SSTCC) is used as an underground mining method for exploiting extremely steep and thick coal seams (ESTCS), a large-scale surrounding rock caving may be violently created and have the potential to induce asymmetric destabilization from mine voids. In this study, a methodology for assessing the destabilization was developed to simulate the Weihuliang coal mine in the Urumchi coal field, China. Coal-rock mass and geological structure characterization were integrated with rock mechanics testing for assessment of the methodology and factors influencing asymmetric destabilization. The porous rock-like composite material ensured accuracy for building a 3D geological physical model of mechanized SSTCC by combining multi-mean timely track monitoring including acoustic emission, crack optical acquirement, roof separation observation, and close-field photogrammetry. An asymmetric 3D modeling analysis for destabilization characteristics was completed. Data from the simulated hydraulic support and buried pressure sensor provided effective information that was linked with stress-strain relationship of the working face in ESTCS. The results of the 3D physical model experiments combined with hybrid statistical methods were effective for predicting dynamic hazards in ESTCS.

  16. Effect of Destabilizing Heat Treatment on Solid-State Phase Transformation in High-Chromium Cast Irons

    Science.gov (United States)

    Efremenko, Vasily; Shimizu, Kazumichi; Chabak, Yuliia

    2013-12-01

    This work describes the influence of secondary carbide precipitation at destabilizing heat treatment on kinetics of austenite phase transformation at a subcritical range of temperatures in high-Cr cast irons, alloyed with 4 to 6 wt pct of Mn or by complex Mn-Ni-Mo (Mn-Cu-Mo). The samples were soaked at 1073 K to 1373 K (800 °C to 1100 °C) (destabilization) or at 573 K to 973 K (300 °C to 700 °C) (subcritical treatment); the combination of destabilization and subcritical treatment was also used. The investigation was carried out with application of optical and electron microscopy and bulk hardness measurement. Time-temperature-transformation (TTT) curves of secondary carbide precipitation and pearlite transformation for as-cast austenite and destabilized austenite were built in this work. It was determined that the secondary carbide precipitation significantly inhibited the pearlite transformation rate at 823 K to 973 K (550 °C to 700 °C). The inhibition effect is more evident in cast irons alloyed with complex Mn-Ni-Mo or Mn-Cu-Mo. The possible reasons for transformation decelerating could be austenite chemical composition change (enriching by Ni, Si, and Cu, and depleting by Cr) and stresses induced by secondary carbide precipitation.

  17. Stochastic resonance in an intracellular genetic perceptron

    Science.gov (United States)

    Bates, Russell; Blyuss, Oleg; Zaikin, Alexey

    2014-03-01

    Intracellular genetic networks are more intelligent than was first assumed due to their ability to learn. One of the manifestations of this intelligence is the ability to learn associations of two stimuli within gene-regulating circuitry: Hebbian-type learning within the cellular life. However, gene expression is an intrinsically noisy process; hence, we investigate the effect of intrinsic and extrinsic noise on this kind of intracellular intelligence. We report a stochastic resonance in an intracellular associative genetic perceptron, a noise-induced phenomenon, which manifests itself in noise-induced increase of response in efficiency after the learning event under the conditions of optimal stochasticity.

  18. Visualization of Intracellular Tyrosinase Activity in vitro

    Science.gov (United States)

    Setty, Subba Rao Gangi

    2016-01-01

    Melanocytes produce the melanin pigments in melanosomes and these organelles protect the skin against harmful ultraviolet rays. Tyrosinase is the key cuproenzyme which initiates the pigment synthesis using its substrate amino acid tyrosine or L-DOPA (L-3, 4-dihydroxyphenylalanine). Moreover, the activity of tyrosinase directly correlates to the cellular pigmentation. Defects in tyrosinase transport to melanosomes or mutations in the enzyme or reduced intracellular copper levels results in loss of tyrosinase activity in melanosomes, commonly observed in albinism. Here, we described a method to detect the intracellular activity of tyrosinase in mouse melanocytes. This protocol will visualize the active tyrosinase present in the intracellular vesicles or organelles including melanosomes. PMID:27231711

  19. Inhibition of AmpC beta-lactamase through a destabilizing interaction in the active site

    Energy Technology Data Exchange (ETDEWEB)

    Trehan, I.; Beadle, B.M.; Shoichet, B.K. (NWU)

    2010-03-08

    {beta}-Lactamases hydrolyze {beta}-lactam antibiotics, including penicillins and cephalosporins; these enzymes are the most widespread resistance mechanism to these drugs and pose a growing threat to public health. {beta}-Lactams that contain a bulky 6(7){alpha} substituent, such as imipenem and moxalactam, actually inhibit serine {beta}-lactamases and are widely used for this reason. Although mutant serine {beta}-lactamases have arisen that hydrolyze {beta}-lactamase resistant {beta}-lactams (e.g., ceftazidime) or avoid mechanism-based inhibitors (e.g., clavulanate), mutant serine {beta}-lactamases have not yet arisen in the clinic with imipenemase or moxalactamase activity. Structural and thermodynamic studies suggest that the 6(7){alpha} substituents of these inhibitors form destabilizing contacts within the covalent adduct with the conserved Asn152 in class C {beta}-lactamases (Asn132 in class A {beta}-lactamases). This unfavorable interaction may be crucial to inhibition. To test this destabilization hypothesis, we replaced Asn152 with Ala in the class C {beta}-lactamase AmpC from Escherichia coli and examined the mutant enzyme's thermodynamic stability in complex with imipenem and moxalactam. Consistent with the hypothesis, the Asn152 {yields} Ala substitution relieved 0.44 and 1.10 kcal/mol of strain introduced by imipenem and moxalactam, respectively, relative to the wild-type complexes. However, the kinetic efficiency of AmpC N152A was reduced by 6300-fold relative to that of the wild-type enzyme. To further investigate the inhibitor's interaction with the mutant enzyme, the X-ray crystal structure of moxalactam in complex with N152A was determined to a resolution of 1.83 {angstrom}. Moxalactam in the mutant complex is significantly displaced from its orientation in the wild-type complex; however, moxalactam does not adopt an orientation that would restore competence for hydrolysis. Although Asn152 forces {beta}-lactams with 6(7){alpha

  20. 伊布利特和胺碘酮转复心房扑动及心房颤动的临床观察%Efficacy of ibutilide and amiodarone for termination of atrial fibrillation and flutter

    Institute of Scientific and Technical Information of China (English)

    王磊

    2011-01-01

    目的 观察新一代Ⅲ类抗心律失常药物伊布利特和经典Ⅲ类抗心律失常药物胺碘酮转复心房颤动(房颤)和心房扑动(房扑)的成功率及安全性.方法 选择40 ~ 75岁,持续时间≤90 d的房颤和房扑患者38例,按入院顺序随机分为伊布利特组19例和胺碘酮组19例,伊布利特组体质量≥60 kg者首剂1 mg、体质量<60 kg者首剂0.01 mg/kg,如无效10 min后再给予1 mg或0.01 mg/kg;胺碘酮组首剂150 mg,如无效10 min后再给予150 mg,观察转复率和转复时间,记录不良反应.结果 伊布利特和胺碘酮组4h内转复窦律分别为78.9%和31.5%,24 h内转复窦律分别为84.2%和52.6%,平均转复时间分别为(19±12)min和(48 ±17)min (P<0.01).两组均未发生致命性不良反应.结论 伊布利特与胺碘酮均能终止房颤和房扑,伊布利特转复房颤、房扑的疗效高于胺碘酮,转复时间短于胺碘酮,但须在严格监控下进行.%Objective To investigate the efficacy,safety and tolerance of intravenous ibutilide and amiodarone for conversion of atrial fibrillation( AF) and flutter( AFL) to normal sinus rhythm.Methods Thirty - eight consecutive patients aged 40 - 75 years with AF/AFL were included.The duration of arrhythmia were less than 90 days (ranged from 3 hours to 90 days),and ventricular rate(VR) were more than 60 beats/min.Two groups were assigned randomly.Patients in the ibutilide group( 19 cases) received ibutilide 1 mg if body weight ≥60 kg or 0.01 mg/kg if body weight < 60 kg; Treatment was repeated if atrial fibrillation or flutter was not converted after 10 min of the first dosage.Patients in the amiodarone group( 19 cases) received amiodarone 150 mg,followed by amiodarone 150 mg if atrial fibrillation or flutter persisted after 10 min of the first dosage.Results In 4 hours AF/AFL were converted in 15 of 19 patients(78.9% )in ibutilide group and in 6 of 19 patients(31.5% )in amiodarone group (P < 0.05),and in 24

  1. Clinical Study on Amiodarone in the Treatment of Cardiac Arrhythmia%胺碘酮治疗心律失常的临床研究

    Institute of Scientific and Technical Information of China (English)

    赵明琴

    2016-01-01

    Objective Amiodarone treatment method and its effect for patients with cardiac arrhythmia are to be investigated.MethodsChose 66 patients with cardiac arrhythmia who were treated in hospital from August 2014 to September 2015 and separated them into two groups at random, 37 patients in study group were given Amiodarone treatment, while another 29 patients in control group were given Lidocaine treatment, and then compared treatment effects between two groups.Results Patients’treatment efficacy was 91.89% in study group, which was much higher than 82.76% in control group, thus, treatment efficacy in study group was much better and such a differential had statistic value(P<0.05).Conclusion For patients with cardiac arrhythmia, Amiodarone treatment is quite effective and safe to improve their physical symptom with few side effect.%目的:探究心律失常患者采取胺碘酮治疗的方法和效果。方法选取2014年8月~2015年9月收治的66例心律失常患者进行治疗研究,随机分组,实验组37例患者采取胺碘酮治疗,对照组29例患者选择利多卡因治疗,比较两组患者的治疗效果。结果实验组治疗总有效率为91.89%,对照组治疗总有效率为82.76%,实验组治疗总有效率高于对照组,差异有统计学意义(P<0.05)。结论心律失常患者采取胺碘酮治疗,可改善身体症状,效果显著,不良反应较少,安全性高。

  2. 胺碘酮治疗室性心律失常的临床疗效观察%Effect of amiodarone in the treatment of ventricular arrhythmia

    Institute of Scientific and Technical Information of China (English)

    张育辉

    2015-01-01

    目的:探讨胺碘酮治疗室性心律失常的临床效果。方法:选择观察组40例室性心律失常患者,随机分为观察组和对照组。观察组给予胺碘酮治疗,对照组给予利多卡因治疗,观察两组疗效。结果:观察组显效15例(占75%),有效4例(占20.0%),无效1例(占5.0%);对照组临床效果评定结果:显效9例(占45.0%),有效5例(占25.0%),无效6例(占30.0%);观察组总有效率(95.0%)高于对照组总有效率(70.0%),差异有统计学意义( P<0.05)。结论:胺碘酮治疗室性心律失常疗效显著,值得借鉴。%Objective To explore the clinical effect of amiodarone in treatment of ventricular arrhythmia. Method 40 cases with ven-tricular arrhythmia were selected and randomly divided into observation group and control group. The observation group was treated with amiodarone,the control group was given lidocaine. the curative effect of two groups was observed. Results The effect in observation group:26 cases were significant effect(75%),5 cases were effective(20%),1 cases was invalid(5. 0 %);the effect in control group:9 cases were significant effect(45. 0%),5 cases were effective(25. 0%),6 cases were invalid(30. 0%);the total effective rate in the observa-tion group(95. 0%)was higher than that in the control group(70. 0%),the difference was statistically significant(P<0. 05). Conclu-sion Amiodarone in the treatment of ventricular arrhythmia has significant effect,and which is worth learning.

  3. Adaptor protein complexes and intracellular transport

    OpenAIRE

    2014-01-01

    The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers th...

  4. Entropic (de)stabilization of surface-bound peptides conjugated with polymers

    Science.gov (United States)

    Carmichael, Scott P.; Shell, M. Scott

    2015-12-01

    In many emerging biotechnologies, functional proteins must maintain their native structures on or near interfaces (e.g., tethered peptide arrays, protein coated nanoparticles, and amphiphilic peptide micelles). Because the presence of a surface is known to dramatically alter the thermostability of tethered proteins, strategies to stabilize surface-bound proteins are highly sought. Here, we show that polymer conjugation allows for significant control over the secondary structure and thermostability of a model surface-tethered peptide. We use molecular dynamics simulations to examine the folding behavior of a coarse-grained helical peptide that is conjugated to polymers of various lengths and at various conjugation sites. These polymer variations reveal surprisingly diverse behavior, with some stabilizing and some destabilizing the native helical fold. We show that ideal-chain polymer entropies explain these varied effects and can quantitatively predict shifts in folding temperature. We then develop a generic theoretical model, based on ideal-chain entropies, that predicts critical lengths for conjugated polymers to effect changes in the folding of a surface-bound protein. These results may inform new design strategies for the stabilization of surface-associated proteins important for a range technological applications.

  5. Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Jimcy Platholi

    Full Text Available General anesthetics produce a reversible coma-like state through modulation of excitatory and inhibitory synaptic transmission. Recent evidence suggests that anesthetic exposure can also lead to sustained cognitive dysfunction. However, the subcellular effects of anesthetics on the structure of established synapses are not known. We investigated effects of the widely used volatile anesthetic isoflurane on the structural stability of hippocampal dendritic spines, a postsynaptic structure critical to excitatory synaptic transmission in learning and memory. Exposure to clinical concentrations of isoflurane induced rapid and non-uniform shrinkage and loss of dendritic spines in mature cultured rat hippocampal neurons. Spine shrinkage was associated with a reduction in spine F-actin concentration. Spine loss was prevented by either jasplakinolide or cytochalasin D, drugs that prevent F-actin disassembly. Isoflurane-induced spine shrinkage and loss were reversible upon isoflurane elimination. Thus, isoflurane destabilizes spine F-actin, resulting in changes to dendritic spine morphology and number. These findings support an actin-based mechanism for isoflurane-induced alterations of synaptic structure in the hippocampus. These reversible alterations in dendritic spine structure have important implications for acute anesthetic effects on excitatory synaptic transmission and synaptic stability in the hippocampus, a locus for anesthetic-induced amnesia, and have important implications for anesthetic effects on synaptic plasticity.

  6. The destabilization of the French electricity supply industry nascent competition in an open environment

    International Nuclear Information System (INIS)

    In February 2000 France, compelled by the 1996 European Directive 96/92, undertook a minimal reform of the organisation of its electricity industry, while preserving the boundaries of the incumbent company. The aim of this paper is to analyse the conditions of destabilization of the industrial organisation of the French ESI, by identifying the economic factors of endogenous and exogenous erosion. Firstly, after setting out the main elements of the French reform, which is aimed at making the electricity market contestable, the effectiveness of the ''contestability'' of the French power market is discussed. Secondly in order to test the stability of the new institutional arrangements, an institutional prospect is developed, on the basis of economic factors of instability and resistance, to produce two contrasting scenarios: one in which the particularly French model is retained (limited contestability market scenario); another in which there is movement towards a de-integrated competitive model (contamination by competition scenario). Thirdly the author concludes on the basis of recent elements, that the future would be a mix of these two trajectories which will come within in the progressive integration of the national markets in continental Europe. (A.L.B.)

  7. The destabilization of the French electricity supply industry nascent competition in an open environment

    Energy Technology Data Exchange (ETDEWEB)

    Finon, D

    2001-06-01

    In February 2000 France, compelled by the 1996 European Directive 96/92, undertook a minimal reform of the organisation of its electricity industry, while preserving the boundaries of the incumbent company. The aim of this paper is to analyse the conditions of destabilization of the industrial organisation of the French ESI, by identifying the economic factors of endogenous and exogenous erosion. Firstly, after setting out the main elements of the French reform, which is aimed at making the electricity market contestable, the effectiveness of the ''contestability'' of the French power market is discussed. Secondly in order to test the stability of the new institutional arrangements, an institutional prospect is developed, on the basis of economic factors of instability and resistance, to produce two contrasting scenarios: one in which the particularly French model is retained (limited contestability market scenario); another in which there is movement towards a de-integrated competitive model (contamination by competition scenario). Thirdly the author concludes on the basis of recent elements, that the future would be a mix of these two trajectories which will come within in the progressive integration of the national markets in continental Europe. (A.L.B.)

  8. EDTA-induced Membrane Fluidization and Destabilization: Biophysical Studies on Artificial Lipid Membranes

    Institute of Scientific and Technical Information of China (English)

    Virapong PRACHAYASITTIKUL; Chartchalerm ISARANKURA-NA-AYUDHYA; Tanawut TANTIMONGCOLWAT; Chanin NANTASENAMAT; Hans-Joachim GALLA

    2007-01-01

    The molecular mechanism of ethylenediaminetetraacetic acid (EDTA)-induced membrane destabilization has been studied using a combination of four biophysical techniques on artificial lipid membranes.Data from Langmuir film balance and epifluorescence microscopy revealed the fluidization and expansion effect of EDTA on phase behavior of monolayers of either 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or mixtures of DPPC and metal-chelating lipids, such as Nα,Nα-Bis[carboxymethyl]-Nε-[(dioctadecylamino)succinyl]-L-lysine or 1,2-dioleoyl-sn-glycero-3-[N-(5-amino- 1-carboxypentyl iminodiacetic acid) succinyl]. A plausible explanation could be drawn from the electrostatic interaction between negatively charged groups of EDTA and the positively charged choline head group of DPPC.Intercalation of EDTA into the lipid membrane induced membrane curvature as elucidated by atomic force microscopy. Growth in size and shape of the membrane protrusion was found to be time-dependent upon exposure to EDTA. Further loss of material from the lipid membrane surface was monitored in real time using a quartz crystal microbalance. This indicates membrane restabilization by exclusion of the protrusions from the surface. Loss of lipid components facilitates membrane instability, leading to membrane permeabilization and lysis.

  9. Cortisol and testosterone increase financial risk taking and may destabilize markets

    Science.gov (United States)

    Cueva, Carlos; Roberts, R. Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N.; Herbert, Joe; Rustichini, Aldo

    2015-01-01

    It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders’ financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways. PMID:26135946

  10. Destabilized SMC5/6 complex leads to chromosome breakage syndrome with severe lung disease.

    Science.gov (United States)

    van der Crabben, Saskia N; Hennus, Marije P; McGregor, Grant A; Ritter, Deborah I; Nagamani, Sandesh C S; Wells, Owen S; Harakalova, Magdalena; Chinn, Ivan K; Alt, Aaron; Vondrova, Lucie; Hochstenbach, Ron; van Montfrans, Joris M; Terheggen-Lagro, Suzanne W; van Lieshout, Stef; van Roosmalen, Markus J; Renkens, Ivo; Duran, Karen; Nijman, Isaac J; Kloosterman, Wigard P; Hennekam, Eric; Orange, Jordan S; van Hasselt, Peter M; Wheeler, David A; Palecek, Jan J; Lehmann, Alan R; Oliver, Antony W; Pearl, Laurence H; Plon, Sharon E; Murray, Johanne M; van Haaften, Gijs

    2016-08-01

    The structural maintenance of chromosomes (SMC) family of proteins supports mitotic proliferation, meiosis, and DNA repair to control genomic stability. Impairments in chromosome maintenance are linked to rare chromosome breakage disorders. Here, we have identified a chromosome breakage syndrome associated with severe lung disease in early childhood. Four children from two unrelated kindreds died of severe pulmonary disease during infancy following viral pneumonia with evidence of combined T and B cell immunodeficiency. Whole exome sequencing revealed biallelic missense mutations in the NSMCE3 (also known as NDNL2) gene, which encodes a subunit of the SMC5/6 complex that is essential for DNA damage response and chromosome segregation. The NSMCE3 mutations disrupted interactions within the SMC5/6 complex, leading to destabilization of the complex. Patient cells showed chromosome rearrangements, micronuclei, sensitivity to replication stress and DNA damage, and defective homologous recombination. This work associates missense mutations in NSMCE3 with an autosomal recessive chromosome breakage syndrome that leads to defective T and B cell function and acute respiratory distress syndrome in early childhood. PMID:27427983

  11. Entropic (de)stabilization of surface-bound peptides conjugated with polymers.

    Science.gov (United States)

    Carmichael, Scott P; Shell, M Scott

    2015-12-28

    In many emerging biotechnologies, functional proteins must maintain their native structures on or near interfaces (e.g., tethered peptide arrays, protein coated nanoparticles, and amphiphilic peptide micelles). Because the presence of a surface is known to dramatically alter the thermostability of tethered proteins, strategies to stabilize surface-bound proteins are highly sought. Here, we show that polymer conjugation allows for significant control over the secondary structure and thermostability of a model surface-tethered peptide. We use molecular dynamics simulations to examine the folding behavior of a coarse-grained helical peptide that is conjugated to polymers of various lengths and at various conjugation sites. These polymer variations reveal surprisingly diverse behavior, with some stabilizing and some destabilizing the native helical fold. We show that ideal-chain polymer entropies explain these varied effects and can quantitatively predict shifts in folding temperature. We then develop a generic theoretical model, based on ideal-chain entropies, that predicts critical lengths for conjugated polymers to effect changes in the folding of a surface-bound protein. These results may inform new design strategies for the stabilization of surface-associated proteins important for a range technological applications.

  12. Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.

    Directory of Open Access Journals (Sweden)

    Elisa Dominguez

    Full Text Available Branch retinal vein occlusion (BRVO leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.

  13. Enzyme-responsive destabilization of stabilized plasmid-lipid nanoparticles as an efficient gene delivery.

    Science.gov (United States)

    Song, Su Jeong; Lee, Seulgi; Lee, Yan; Choi, Joon Sig

    2016-08-25

    Stabilized plasmid-lipid particles (SPLPs) have been developed to overcome the low stability issue of cationic liposomes, however, SPLPs that are too stable result in unsatisfactory transfection efficiency. In this article, we prepared enzyme-responsive SPLPs (eSPLPs) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and mPEG-GLFG-K-(C16)2, a PEG lipid with an enzymatically-cleavable linker (glycine-phenylalanine-leucine-glycine, GFLG). eSPLPs were successfully prepared with plasmid DNA (pDNA) encapsulation efficiency of over 80%, using the detergent dialysis method. The PEG shell stabilized eSPLPs and maintained a hydrodynamic diameter of around 200nm. Although typical SPLPs were relatively intact in endosomal condition, the PEG shell of eSPLPs was cleaved following the degradation of the GFLG linker by cathepsin B in the endosome. Then, eSPLPs collapsed and induced endosomal disruption triggering the controlled release of the encapsulated pDNA into cytoplasm. Owing to the enzyme-responsive destabilization, eSPLPs showed a 10 to 100-fold higher transfection efficiency than control SPLPs, which was confirmed using luciferase assay. These results suggest that eSPLPs might be promising candidates for practical use as gene delivery systems, with both stability and high transfection efficiency for future in vivo applications. PMID:27240779

  14. Susceptibility to superhelically driven DNA duplex destabilization: a highly conserved property of yeast replication origins.

    Directory of Open Access Journals (Sweden)

    2005-06-01

    Full Text Available Strand separation is obligatory for several DNA functions, including replication. However, local DNA properties such as A+T content or thermodynamic stability alone do not determine the susceptibility to this transition in vivo. Rather, superhelical stresses provide long-range coupling among the transition behaviors of all base pairs within a topologically constrained domain. We have developed methods to analyze superhelically induced duplex destabilization (SIDD in genomic DNA that take into account both this long-range stress-induced coupling and sequence-dependent local thermodynamic stability. Here we apply this approach to examine the SIDD properties of 39 experimentally well-characterized autonomously replicating DNA sequences (ARS elements, which function as replication origins in the yeast Saccharomyces cerevisiae. We find that these ARS elements have a strikingly increased susceptibility to SIDD relative to their surrounding sequences. On average, these ARS elements require 4.78 kcal/mol less free energy to separate than do their immediately surrounding sequences, making them more than 2,000 times easier to open. Statistical analysis shows that the probability of this strong an association between SIDD sites and ARS elements arising by chance is approximately 4 x 10. This local enhancement of the propensity to separate to single strands under superhelical stress has obvious implications for origin function. SIDD properties also could be used, in conjunction with other known origin attributes, to identify putative replication origins in yeast, and possibly in other metazoan genomes.

  15. SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2

    Science.gov (United States)

    Naudin, Cécile; Sirvent, Audrey; Leroy, Cédric; Larive, Romain; Simon, Valérie; Pannequin, Julie; Bourgaux, Jean-François; Pierre, Josiane; Robert, Bruno; Hollande, Frédéric; Roche, Serge

    2014-01-01

    The adaptor SLAP is a negative regulator of receptor signalling in immune cells but its role in human cancer is ill defined. Here we report that SLAP is abundantly expressed in healthy epithelial intestine but strongly downregulated in 50% of colorectal cancer. SLAP overexpression suppresses cell tumorigenicity and invasiveness while SLAP silencing enhances these transforming properties. Mechanistically, SLAP controls SRC/EPHA2/AKT signalling via destabilization of the SRC substrate and receptor tyrosine kinase EPHA2. This activity is independent from CBL but requires SLAP SH3 interaction with the ubiquitination factor UBE4A and SLAP SH2 interaction with pTyr594-EPHA2. SRC phosphorylates EPHA2 on Tyr594, thus creating a feedback loop that promotes EPHA2 destruction and thereby self-regulates its transforming potential. SLAP silencing enhances SRC oncogenicity and sensitizes colorectal tumour cells to SRC inhibitors. Collectively, these data establish a tumour-suppressive role for SLAP in colorectal cancer and a mechanism of SRC oncogenic induction through stabilization of its cognate substrates.

  16. Cortisol and testosterone increase financial risk taking and may destabilize markets.

    Science.gov (United States)

    Cueva, Carlos; Roberts, R Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N; Herbert, Joe; Rustichini, Aldo

    2015-07-02

    It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders' financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways.

  17. A mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment.

    Directory of Open Access Journals (Sweden)

    Hyo-Jick Choi

    Full Text Available Oral immunization using whole inactivated influenza virus vaccine promises an efficient vaccination strategy. While oral vaccination was hampered by harsh gastric environment, a systematic understanding about vaccine destabilization mechanisms was not performed. Here, we investigated the separate and combined effects of temperature, retention time, pH, and osmotic stress on the stability of influenza vaccine by monitoring the time-dependent morphological change using stopped-flow light scattering. When exposed to osmotic stress, clustering of vaccine particles was enhanced in an acidic medium (pH 2.0 at ≥25°C. Fluorescence spectroscopic studies showed that hyper-osmotic stress at pH 2.0 and 37°C caused a considerable increase in conformational change of antigenic proteins compared to that in acidic iso-osmotic medium. A structural integrity of membrane was destroyed upon exposure to hyper-osmotic stress, leading to irreversible morphological change, as observed by undulation in stopped-flow light scattering intensity and transmission electron microscopy. Consistent with these analyses, hemagglutination activity decreased more significantly with an increasing magnitude of hyper-osmotic stress than in the presence of the hypo- and iso-osmotic stresses. This study shows that the magnitude and direction of the osmotic gradient has a substantial impact on the stability of orally administrated influenza vaccine.

  18. Substrate phosphorylation and feedback regulation in JFK-promoted p53 destabilization.

    Science.gov (United States)

    Sun, Luyang; Shi, Lei; Wang, Feng; Huangyang, Peiwei; Si, Wenzhe; Yang, Jie; Yao, Zhi; Shang, Yongfeng

    2011-02-11

    The p53 tumor suppressor plays a central role in integrating cellular responses to various stresses. Tight regulation of p53 is thus essential for the maintenance of genome integrity and normal cell proliferation. Previously, we reported that JFK, the only Kelch domain-containing F-box protein in human, promotes ubiquitination and degradation of p53 and that unlike the other E3 ligases for p53, all of which possess an intrinsic ubiquitin ligase activity, JFK destabilizes p53 through the assembly of a Skp1-Cul1-F-box complex. Here, we report that the substrate recognition by JFK requires phosphorylation of p53 in its central core region by CSN (COP9 signalosome)-associated kinase. Significantly, inhibition of CSN-associated kinase activity or knockdown of CSN5 impairs JFK-promoted p53 degradation, enhances p53-dependent transcription, and promotes cell growth suppression, G(1) arrest, and apoptosis. Moreover, we showed that JFK is transcriptionally regulated by p53 and forms an auto-regulatory negative feedback loop with p53. These data may shed new light on the functional connection between CSN, Skp1-Cul1-F-box ubiquitin ligase, and p53 and provide a molecular mechanism for the regulation of JFK-promoted p53 degradation.

  19. The Francisella intracellular life cycle: towards molecular mechanisms of intracellular survival and proliferation

    Directory of Open Access Journals (Sweden)

    Audrey eChong

    2010-12-01

    Full Text Available The tularemia-causing bacterium Francisella tularensis is a facultative intracellular organism with a complex intracellular lifecycle that ensures its survival and proliferation in a variety of mammalian cell types, including professional phagocytes. Because this cycle is essential to Francisella pathogenesis and virulence, much research has focused on deciphering the mechanisms of its intracellular survival and replication and characterizing both bacterial and host determinants of the bacterium’s intracellular cycle. Studies of various strains and host cell models have led to the consensual paradigm of Francisella as a cytosolic pathogen, but also to some controversy about its intracellular cycle. In this review, we will detail major findings that have advanced our knowledge of Francisella intracellular survival strategies and also attempt to reconcile discrepancies that exist in our molecular understanding of the Francisella-phagocyte interaction.

  20. 急性心肌梗死急诊诊断与治疗分析%Clinical effect of intravenous injection of amiodarone in treatment of acute heart failure with rapid atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    许敏

    2013-01-01

    目的:分析研究AMI(急性心肌梗死)的临床诊断以及治疗效果。方法抽取近年来在我院收治的80例患有急性心肌梗塞的患者,随机分为实验组和对照组,每组各40例患者,其中实验组对患者采取尿激酶溶栓治疗,对照组对患者采取传统常规治疗。结果实验组患者的临床治疗效果明显优于对照组患者,两组间差异具有统计学意义(P<0.05)。结论采取及时有效的临床干预以及治疗对治疗急性心肌梗塞的患者起到至关重要的作用,具有临床推广价值应用。%Objective To investigate the clinical effect of intravenous injection of amiodarone in the treatment of acute heart failure with rapid atrial fibrillation.Methods A total of 172 patients with acute heart failure and rapid atrial fibrillation who were admitted to our hospital from October 2011 to July 2013 were randomly divided into heart failure and atrial fibrillation group and amiodarone group. The heart failure and atrial fibrillation group received conventional treatment, while the amiodarone group received conventional treatment plus injection of amiodarone. The treatment outcomes of the two groups were compared.Results After 7 d of treatment, the amiodarone group had a significant more improvement in cardiac function, a significantly better heart rate control, and a significantly lower mortality rate, as compared with the heart failure and atrial fibrillation group (P<0.05 for all comparisons). ConclusionConventional treatment plus injection of amiodarone can improve cardiac function and control heart rate in the treatment of heart failure.

  1. Clinical analysis of low-dose amiodarone therapy in the management of ventricular arrhythmias%小剂量胺碘酮治疗室性心律失常56例临床分析

    Institute of Scientific and Technical Information of China (English)

    王珍

    2001-01-01

    Objective:To evaluate the efficacy and safety of low-dose amiodarone therapy in the management of ventricular arrhythmias.Methods:56 patients with symptomatic drug refractory managed with low-dose oral amiodarone therapy over 5-year period was analyzed retrospec tively. Loading dose of amiodarone 800 mg daily for 1 week, 400 mg daily for anoth er week, then, 100-200 mg daily as maintenance daily.Mean treatment duration was 29±8 months.Results:The efficacy of amiodarone was 81% in the management of ventricular arrhymias. The cumulative incidence of amiodarone related adverse effects was 9%. 1 patient had thyroid dysfunction, and 1 developed pulmonary int erstitial fibrosis.Conclusion:The higer efficacy and acceptable side effect profile of low amiodarone therapy in the management of ventricular arrhythmias.%目的:观察小剂量胺碘酮长期治疗室性心律失常的疗效和安全性。方法:回顾性分析了我院5年来收治的经其它药物治疗无效的室性心律失常的患者56例,给以胺碘酮负荷量800 mg/日,一周后400 mg/日,一周后100~200 mg/日维持,平均给药时间29±8月。结果:胺碘酮治疗室性心律失常有效率81%。与胺碘酮有关的副作用累计发生率为9%,引起甲状腺功能异常和肺间质纤维化各1例。结论:小剂量胺碘酮治疗室性心律失常是安全有效的。

  2. Disfunção tireoidiana e conduta dos cardiologistas em pacientes usando amiodarona Thyroid dysfunction and cardiological management in patients receiving amiodarone

    Directory of Open Access Journals (Sweden)

    Anna Gabriela Fuks

    2004-06-01

    Full Text Available OBJETIVO: Determinar a prevalência de disfunção tireoidiana em pacientes usando amiodarona e os possíveis fatores associados. Verificar através de questionário aplicado a cardiologistas, a importância do fármaco causar alterações na função tireoidiana. MÉTODO: Avaliados 56 pacientes em uso crônico (> 3 meses de amiodarona com dosagens séricas de TSH, T4 livre, T3 total e Anti-TPO e definidos como portadores de disfunção tireoidiana (DT pacientes com TSH alterado. RESULTADOS: A prevalência de disfunção tireoidiana foi de 33,9%. Não houve diferença entre este grupo e os pacientes sem disfunção, exceto em relação à prevalência de anti-TPO positivo maior nos pacientes com DT (p=0,02. Hipotireoidismo subclínico foi diagnosticado em 10 (17,9% pacientes e hipotireoidismo clínico em 6 (10,7%. A prevalência de hipertireoidismo subclínico foi de 3,6% e de hipertireoidismo clínico de 1,8%. Anticorpos anti-TPO foram positivos em 5 (8% pacientes (dos quais 4 apresentavam disfunção. Quando comparados aos doentes sem anti-TPO positivo este grupo teve maior prevalência de disfunção (80% vs 29,4%; p=0,04. Verificado que apenas 49,2% dos cardiologistas faziam acompanhamento da função tireoidiana rotineiramente e a prevalência de disfunção referida na experiência da maioria era de 1 a 10%. CONCLUSÃO: A prevalência de disfunção tireoidiana na nossa população foi elevada, mostrando a necessidade de implementação de uma rotina laboratorial. Houve grande divergência entre os cardiologistas em relação ao tipo de acompanhamento utilizado nos pacientes em uso de amiodarona.OBJECTIVE: To determine the prevalence of thyroid dysfunction in patients receiving amiodarone, and the possible associated factors. The study also aimed at assessing the effect of amiodarone on thyroid function through the application of a questionnaire to cardiologists. METHOD: Fifty-six patients chronically (> 3 months receiving amiodarone were

  3. Use of Intravenous Amiodarone in the Treatment of Nifekalant-Resistant Arrhythmia: A Review of 11 Consecutive Cases with Severe Heart Failure

    Directory of Open Access Journals (Sweden)

    Tohru Ujihira

    2011-05-01

    Full Text Available Background: Both nifekalant hydrochloride (NIF, a selective IKr blocker, and intravenous amiodarone (AMD, a multi-channel (including IKr blocking blocker, have been reported to be efficacious for refractory arrhythmias. However, the optimal use of those antiarrhythmic drugs for refractory arrhythmia with severe heart failure has not been established. Intravenous AMD might be effective for arrhythmias refractory to NIF in patients with severe heart failure. Here, we report that intravenous amiodarone was effective in the treatment of nifekalant-resistant in a group of arrhythmia patients with severe heart failure. Methods: Eleven severe heart failure patients who had received intravenous AMD for treatment of NIF-resistant arrhythmias were included in this study, and retrospective analysis was performed. Clinical efficacy (terminative and preventive effects on arrhythmia of intravenous AMD was evaluated. Results: All cases were emergent cases and had depressed left ventricular ejection fraction (30 ± 13%. Clinical arrhythmias were ventricular fibrillation (VF in four patients, ventricular tachycardia (VT in six patients, and atrial fibrillation (AF in one patient. NIF was administered to all patients by intravenous injection. After administration of NIF, VT/VF/AF was terminated in seven of the 10 patients, but a preventive effect was not obtained in any of the patients (NIF-resistance. Intravenous AMD (maintenance dose: 484 ± 166 mg/day was effective both in termination (80% and in prevention (80% of VT/VF events in those patients. It was also effective in termination (80% and prevention (60% of AF events refractory to NIF. During continuous AMD administration, no significant adverse effects or proarrhythmic effects were observed in any of the patients. Five patients died within one month, but there was no arrhythmic deaths. Conclusions: Intravenous AMD was effective in NIF-resistant lethal arrhythmias and was relatively safe in emergent cases

  4. Internal affairs: investigating the Brucella intracellular lifestyle.

    Science.gov (United States)

    von Bargen, Kristine; Gorvel, Jean-Pierre; Salcedo, Suzana P

    2012-05-01

    Bacteria of the genus Brucella are Gram-negative pathogens of several animal species that cause a zoonotic disease in humans known as brucellosis or Malta fever. Within their hosts, brucellae reside within different cell types where they establish a replicative niche and remain protected from the immune response. The aim of this article is to discuss recent advances in the field in the specific context of the Brucella intracellular 'lifestyle'. We initially discuss the different host cell targets and their relevance during infection. As it represents the key to intracellular replication, the focus is then set on the maturation of the Brucella phagosome, with particular emphasis on the Brucella factors that are directly implicated in intracellular trafficking and modulation of host cell signalling pathways. Recent data on the role of the type IV secretion system are discussed, novel effector molecules identified and how some of them impact on trafficking events. Current knowledge on Brucella gene regulation and control of host cell death are summarized, as they directly affect intracellular persistence. Understanding how Brucella molecules interplay with their host cell targets to modulate cellular functions and establish the intracellular niche will help unravel how this pathogen causes disease.

  5. The developmental outcomes of P0-mediated ARGONAUTE destabilization in tomato.

    Science.gov (United States)

    Hendelman, Anat; Kravchik, Michael; Stav, Ran; Zik, Moriyah; Lugassi, Nitsan; Arazi, Tzahi

    2013-01-01

    The plant protein ARGONAUTE1 (AGO1) functions in multiple RNA-silencing pathways, including those of microRNAs, key regulators of growth and development. Genetic analysis of ago1 mutants with informative defects has provided valuable insights into AGO1's biological functions. Tomato encodes two AGO1 homologs (SlAGO1s), but mutants have not been described to date. To analyze SlAGO1s' involvement in development, we confirmed that both undergo decay in the presence of the Polerovirus silencing suppressor P0 and produce a transgenic responder line (OP:P0HA) that, upon transactivation, expresses P0 C-terminally fused to a hemagglutinin (HA) tag (P0HA) and destabilizes SlAGO1s at the site of expression. By crossing OP:P0HA with a battery of driver lines, constitutive as well as organ- and stage-specific SlAGO1 downregulation was induced in the F1 progeny. Activated plants exhibited various developmental phenotypes that partially overlapped with those of Arabidopsis ago1 mutants. Plants that constitutively expressed P0HA had reduced SlAGO1 levels and increased accumulation of miRNA targets, indicating compromised SlAGO1-mediated silencing. Consistent with this, they exhibited pleiotropic morphological defects and their growth was arrested post-germination. Transactivation of P0HA in young leaf and floral organ primordia dramatically modified corresponding organ morphology, including the radialization of leaflets, petals and anthers, suggesting that SlAGO1s' activities are required for normal lateral organ development and polarity. Overall, our results suggest that the OP:P0HA responder line can serve as a valuable tool to suppress SlAGO1 silencing pathways in tomato. The suppression of additional SlAGOs by P0HA and its contribution to the observed phenotypes awaits investigation.

  6. The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

    Directory of Open Access Journals (Sweden)

    Zoega Tomas

    2002-07-01

    Full Text Available Abstract Background A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. Presentation of the hypothesis Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells. This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. Testing the hypothesis Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. Implications of the hypothesis The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments.

  7. Electric field driven destabilization of the insulating state in nominally pure LaMnO3

    International Nuclear Information System (INIS)

    We report an electric field driven destabilization of the insulating state in nominally pure LaMnO3 single crystal with a moderate field which leads to a resistive state transition below 300 K. The transition is between the insulating state in LaMnO3 and a high resistance bad metallic state that has a temperature independent resistivity. The transition occurs at a threshold field (Eth) that shows a steep enhancement on cooling. While at lower temperatures the transition is sharp and involves a large change in resistance, it softens on heating and is eventually absent above 280 K. When the Mn4+ content is increased by Sr substitution up to x = 0.1, the observed transition, although observable in a certain temperature range, softens considerably. This observation has been explained as a bias driven percolation type transition between two co-existing phases, where the majority phase is a charge and orbitally ordered polaronic insulating phase and the minority phase is a bad metallic phase. The mobile fraction f of the bad metallic phase deduced from the experimental data follows an activated kinetics as f = fo(E)exp(−Δ/kBT) with the activation energy Δ ≈ 200 meV, and the pre-factor fo(E) is a strong function of the field that leads to a rapid enhancement of f on application of field, leading to the resistive state transition. We suggest likely scenarios for such co-existing phases in nominally pure LaMnO3 that can lead to the bias driven percolation type transition. (paper)

  8. Negative pressure wound therapy promotes vessel destabilization and maturation at various stages of wound healing and thus influences wound prognosis

    OpenAIRE

    Ma, Zhanjun; SHOU, KANGQUAN; LI, ZONGHUAN; Jian, Chao; QI, BAIWEN; Yu, Aixi

    2016-01-01

    Negative pressure wound therapy (NPWT) has been observed to accelerate the wound healing process in humans through promoting angiogenesis. However, the potential biological effect and relevant molecular mechanisms, including microvessel destabilization, regression and endothelial cell proliferation in the early stage (1–3 days), and the neovascular stabilization and maturation in the later stage (7–15 days), have yet to be fully elucidated. The current study aimed to research the potential ef...

  9. Therapeutic effects of amiodarone combined with metoprolol versus amiodarone alone in treatment of paroxysmal atrial fibrillation%胺腆酮与美托洛尔联合应用与单用胺腆酮治疗阵发性心房纤颤的疗效观察

    Institute of Scientific and Technical Information of China (English)

    杨顺兰

    2015-01-01

    目的:探讨胺腆酮与美托洛尔联合应用与单用胺腆酮治疗阵发性心房纤颤的疗效观察。方法抽取2013年10月-2014年10月于我院就诊的阵发性心房纤颤患者共62例,将患者随机分为观察组(n=31)与常规组(n=31),常规组采用单纯胺碘酮治疗,观察组采用胺腆酮与美托洛尔联合治疗,观察两组患者的治疗效果。结果治疗后,观察组SBP、DBP、HR分别为(138.8±3.1)mmHg、(95.2±8.5)mmHg、(73.4±10.1)次/min,明显低于常规组(151.2±10.1)mmHg、(130.2±10.8)mmHg、(100.2±13.1)次/min,差异具有统计学意义(ta=6.535,tb=14.179,tc=9.021,P均小于0.05);观察组总有效率93.5%,明显高于常规组61.3%,差异具有统计学意义(χ2=7.473,P﹤0.05)。结论采用胺腆酮与美托洛尔联合治疗阵发性心房纤颤效果显著,能有效控制患者的血压及心率,值得临床大力推广。%Objective To investigate the therapeutic effects of amiodarone combined with metoprolol versus amiodarone alone in the treatment of paroxysmal atrial fibrillation. Methods Sixty-two patients with paroxysmal atrial fibrillation who were admitted to our hospital from October 2013 to October 2014 were equally and randomly divided into observation group and conventional group (31 cases for each group). The conventional group was given amiodarone alone, while the observation group was given amiodarone combined with metoprolol. The treatment outcomes of patients in the two groups were observed. Results After treatment, the observation group had significantly lower systolic blood pressure (138.8±3.1mmHg vs 151.2±10.1mmHg, t=6.535, P﹤0.05), diastolic blood pressure (95.2±8.5mmHg vs 130.2±10.8mmHg, t=14.179, P﹤0.05), and heart rate (73.4±10.1beats/min vs 100.2±13.1beats/min, t=9.021, P﹤0.05) than the conventional group. The observation group had a significantly higher overall response rate than the conventional

  10. Hydrogen storage in 2NaBH{sub 4} + MgH{sub 2} mixtures: Destabilization by additives and nanoconfinement

    Energy Technology Data Exchange (ETDEWEB)

    Mulas, G., E-mail: mulas@uniss.it [Dipartimento di Chimica, Universita di Sassari and INSTM, Via Vienna 2, I-07100 Sassari (Italy); Campesi, R. [JRC-IE, Westernduinweg 3, 1755 ZG Petten (Netherlands); Garroni, S.; Napolitano, E. [Dipartimento di Chimica, Universita di Sassari and INSTM, Via Vienna 2, I-07100 Sassari (Italy); Milanese, C. [Pavia H2 Lab, C.S.G.I. and Dipartimento di Chimica, Sezione di Chimica Fisica, Universita di Pavia, Viale Taramelli 16, I-27100 Pavia (Italy); Dolci, F. [JRC-IE, Westernduinweg 3, 1755 ZG Petten (Netherlands); Pellicer, E.; Baro, M.D. [Departament de Fisica, Universitat Autonoma de Barcelona, E-08193 Bellaterra (Spain); Marini, A. [Pavia H2 Lab, C.S.G.I. and Dipartimento di Chimica, Sezione di Chimica Fisica, Universita di Pavia, Viale Taramelli 16, I-27100 Pavia (Italy)

    2012-09-25

    Highlights: Black-Right-Pointing-Pointer Nanoconfinement of 2NaBH{sub 4} + MgH{sub 2} into SBA-15 silica was successful in improving the thermodynamic and kinetic properties of the multi-component system Black-Right-Pointing-Pointer The use of NbF{sub 5} as additive reduced the NaBH{sub 4} decomposition temperature and increased the desorption kinetics. Black-Right-Pointing-Pointer Destabilization of hydrides can be gained by synergic effect of nanoconfinement and use of additive materials. - Abstract: We focus on the H{sub 2} desorption properties of the 2NaBH{sub 4} + MgH{sub 2} system destabilized by different methods. Nanostructured powder mixtures were prepared by ball milling the starting hydrides and nanoconfined reactive composites were obtained by melting infiltration of the hydrides into a Si-based SBA-15 support. NbF{sub 5} was tested as catalyst in both the preparations. Structural characterization by X Ray Diffraction and Transmission Electron Microscopy allowed evaluating the successful synthesis of SBA15 matrix, the microstructural features of ball milled and nanoconfined hydrides as well as the success of infiltration process. The evaluation of the sorption properties, by manometric Sievert-type apparatus and thermal desorption spectroscopy, revealed the efficiency of the hydride destabilization, obtained by the different routes, in decreasing the hydrogen release temperature and improving desorption kinetics.

  11. Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

    Directory of Open Access Journals (Sweden)

    Meehan Maria

    2012-02-01

    Full Text Available Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown. Results As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA, an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. Conclusions PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.

  12. Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

    LENUS (Irish Health Repository)

    Meehan, Maria

    2012-02-05

    Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown. Results As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA\\'s primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. Conclusions PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.

  13. Macrophage defense mechanisms against intracellular bacteria.

    Science.gov (United States)

    Weiss, Günter; Schaible, Ulrich E

    2015-03-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  14. 利多卡因混合制剂湿敷治疗胺碘酮所致静脉炎%Lidocaine mixture wet compress therapy with amiodarone induced phlebitis

    Institute of Scientific and Technical Information of China (English)

    陈秀红

    2012-01-01

      Objective:To investigate the loss and treatment with amiodarone induced phlebitis method. Methods:Using 2%lidocaine, 75%ethanol, dexamethasone, vitamin B12 four kinds of drugs into the mixture wet compress therapy with amiodarone induced phlebitis. 60 patients with amiodarone induced phlebitis were randomly divided into the experimental group 32 cases, 28 cases of the control group. The experimental group used lidocaine mixture wet compress therapy, the control group with 75%alcohol wet compress therapy.Results:in the experimental group were significantly better than the control group, treatment effect.Conclusion:intravenous infusion of amiodarone induced peripheral phlebitis, application of lidocaine mixture wet compress remarkable curative effect, safety and Reliability, no adverse reaction.%  目的:探讨减轻及治疗胺碘酮所致静脉炎的方法。方法:采用2%利多卡因、75%乙醇、地塞米松、维生素B12等四种药物配伍成混合制剂湿敷治疗胺碘酮所致静脉炎。将60例盐酸胺碘酮所致静脉炎患者随机分为实验组32例,对照组28例。实验组用利多卡因混合制剂湿敷治疗,对照组用75%乙醇湿敷治疗。结果:实验组治疗效果显著优于对照组。结论:对于胺碘酮静脉滴注所致的外周静脉炎,应用利多卡因混合制剂湿敷疗效显著,安全可靠,无不良反应。

  15. Clinical Research on Arrhythmia on Metoprolol and Amiodarone Therapy%美托洛尔联合胺碘酮治疗心律失常临床研究

    Institute of Scientific and Technical Information of China (English)

    高春明

    2015-01-01

    目的 分析美托洛尔联合胺碘酮治疗心律失常的效果.方法 选取我院收治的90例心律失常患者作为研究对象,并随机分为45例观察组和45例对照组.对观察组采用美托洛尔和胺碘酮联合疗法,对照组则使用胺碘酮单药疗法,对比两组疗效.结果 经治疗,观察组治疗的总有效率为95.56%,对照组为82.22%,对照组低于观察组,且P<0.05.结论 对心率失常患者采用美托洛尔和胺碘酮联合疗法可有效改善患者心功能水平,促进治疗进程,疗效显著.%Objective Analysis of metoprolol and amiodarone treatment of arrhythmia effect. Methods Select our hospital 90 cases of arrhythmia patients as research subjects, and 45 cases were randomly divided into observation group and 45 patients in the control group. The observation group were metoprolol and amiodarone therapy, the control group amiodarone monotherapy, compared to the two groups. Results After treatment, the observation group total effective rate was 95.56%, 82.22% in the control group, the control group was significantly lower than in the observation group, andP < 0.05. Conclusion Arrhythmia treated withmetoprolol and amiodarone therapy can be effective in improving cardiac function in patients, and promote the process of treatment, a significant effect, can be extended.

  16. Clinical observation of amiodarone in treatment of pulmonary tachyarrhythmia complicated with respiratory failure%胺碘酮治疗呼吸衰竭并快速肺源性心律失常的临床观察

    Institute of Scientific and Technical Information of China (English)

    张淑立; 王毅

    2012-01-01

    Objective To observe the effect of amiodarone in the treatment of pulmonary tachyarrhythmia complicated with respiratory failure. Methods Multifocal atrial tachycardia, atrial fibrillation, atrial flutter and rapid ventricular arrhythmia were observed in 20 patients with acute exacerbation of chronic respiratory failure in our ICU receiving electrocardiography custody. Amiodarone was first injected intravenously followed by infusion pumps, and then orally. Results After amiodarone being administrated, all kinds of arrhythmia in the 19 patients were greatly reduced or disappeared, while only 1 patient with atrial flutter remained. Serious side effect was not detected during the therapy. Conclusions Amiodarone can be used in the patients with pulmonary tachyarrhythmia complicated with respiratory failure safely and effectively.%目的 观察胺碘酮对呼吸衰竭伴快速肺源性心律失常的疗效.方法 20例慢性呼吸衰竭病人,在监护病房持续心电监护,呼吸衰竭急性加重期出现紊乱性房性心律失常、房颤、房扑以及快速室性心律失常,予胺碘酮先静脉推注、静脉泵入,后序贯为口服.结果 用胺碘酮后19例病人各种心律失常明显减少或消失,1例房扑病人无转复.用药过程中未发现明显副作用.结论 胺碘酮对呼吸衰竭伴快速肺源性快速心律失常安全、有效.

  17. 胺碘酮对急性心肌梗死并发室性心动过速的治疗分析%Clinical analysis on intravenous Amiodarone for continuous ventricular tachycardia in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    阎晋华; 齐守罡

    2012-01-01

      目的观察静脉注射胺碘酮治疗急性心肌梗死并发室性心动过速的疗效。方法将30例急性心肌梗死患者分为2组,每组15例,分别给予静脉注射利多卡因、胺碘酮治疗,观察2组临床疗效。结果胺碘酮组15例患者中,13例患者室性心动过速得到控制,对照组有8例患者室性心动过速得到控制,胺碘酮组有效率高于对照组。结论静脉注射胺碘酮治疗急性心肌梗死并发室性心动过速安全有效,可提高急性心肌梗死的抢救成功率。%  Objective To investigate the effect of amiodarone to continuous ventricular tachycardia in patients with acute myocardial infarction.Methods 30 cases of acute myocardial infarction patients were divided into 2 groups, 15 cases in each group, were given intravenous lidocaine, amiodarone treatment, observation of clinical curative effect of 2 sets.Results Among 15 cases in the observation group, 13 patients with ventricular tachycardia were under control, in the control group, 8 patients with ventricular tachycardia got controlled heartbeat, amiodarone group was higher than that of control group.Conclusion Intravenous amiodarone is more effective and safer than lidocaine in treating continuous ventricular tachycardia in patients with AMI.

  18. Discuss the Treatment of Amiodarone Combined With Metoprolol in Coronary Heart Disease in Elderly Patients%胺碘酮联合美托洛尔治疗老年冠心病

    Institute of Scientific and Technical Information of China (English)

    王勇; 李连鑫

    2015-01-01

    目的:探讨胺碘酮联合美托洛尔治疗老年冠心病的临床效果。方法将我院于2013年1月~2014年1月收治的156例老年冠心病患者列为研究对象,将其随机平分,观察组给予常规药物加胺碘酮联合美托洛尔口服;对照组给予常规药物加胺碘酮口服,6个月后对较分析其心绞痛、心律失常的改善情况。结果观察组室性心绞痛、心律失常的治疗有效率均明显大于对照组,差异显著(P<0.05),具有统计学意义。结论胺碘酮联合美托洛尔治疗老年冠心病效果比单用胺碘酮疗效好,差异显著。%ObjectiveDiscuss the clinical effect of Amiodarone combined with metoprolol in Coronary heart disease in elderly.Method Selected 156 cases of coronary heart disease in elderly admitted in our hospital, divided them into two groups. Observation group received conventional drugs and oral amiodarone combined with metoprolol, control group received conventional drugs and oral amiodarone, compared their improvement of angina and arrhythmias six months later.Results Observation group' room angina, arrhythmia treatment effective rate was signiifcantly greater than control group, the difference was signiifcant (P<0.05), with statistical significance.Conclusion Amiodarone combined with metoprolol have a better efifcacy in coronary heart disease in elderly patients..

  19. Clinical investigation on potato external application to prevent amiodarone-induced phlebitis%马铃薯外敷预防胺碘酮注射液致静脉炎的临床研究

    Institute of Scientific and Technical Information of China (English)

    宋美燕; 唐菊素; 翁志英

    2013-01-01

    Objective To investigate the effectiveness of potato slices external application to prevent amiodarone-induced phlebitis.Methods A total of 100 patients treated with intravenous amiodarone were randomly divided into observation group and control group.Fresh potato slices were applied externally to the skin above the venipuncture site during intravenous infusion of amiodarone-in the observation group,while no preventive measures were taken in the control group.Results The incidence and severity of phlebitis in the observation group were significantly decreased compared to those in the control group.Conclusions Potato external application can effectively reduce the occurrence of amiodarone-induced phlebitis.%目的 探讨马铃薯外敷预防胺碘酮注射液致静脉炎的效果.方法 将100例静脉泵入胺碘酮的患者随机分为观察组和对照组各50例.观察组在静脉泵入胺碘酮的同时用新鲜马铃薯外敷静脉穿刺点上方皮肤.对照组不做预防性处理.结果 观察组静脉炎的发生率及严重程度显著低于对照组(P<0.01).结论 使用马铃薯外敷可有效降低胺碘酮注射液所致静脉炎.

  20. 34 Cases of Paroxysmal Atrial Fibrillation Treated with Amiodarone and Syndrome Differentiation and Treatment in Chinese Medicine%胺碘酮结合中医辨证论治治疗阵发性心房纤颤34例

    Institute of Scientific and Technical Information of China (English)

    王浩

    2009-01-01

    目的 研究胺碘酮结合中医辨证论治治疗阵发性心房纤颤的临床疗效.方法 将53例阵发性心房纤颤患者分为对照组和治疗组.对照组19例患者给予胺碘酮治疗,治疗组34例患者在对照组治疗基础上加用中医辨证论治方法治疗.观察两组患者治疗后的临床疗效.结果 治疗组总有效率为91.18%,对照组为68.42%,两组比较有显著性差异(P< 0.05).结论 运用胺碘酮结合中医辨证论治方法治疗心房纤颤,疗效显著优于单用胺碘酮.%Objective To investigate clinical efficacy on paroxysmal atrial fibrillation treated with amiodarone and syndrome differentiation and treatment in Chinese medicine.Methods 53 cases of paroxysmal atrial fibrillation were randomly divided into control group and treatment group.19 cases in control group were treated with amiodarone and 34 cases in treatment group were treated according to syndrome differentiation in Chinese medicine.The clinical efficacy was observed after treatment in two groups.Results The total effective rate was 91.18% in treatment group and 68.42% in control group,demonstrating significant difference in comparison(P<0.05).Conclusion The efficacy of combined therapy of amiodarone and syndrome differentiation and treatment of Chinese medicine is superior significantly to that of simple administration of amiodarone.

  1. Multiplexed imaging of intracellular protein networks.

    Science.gov (United States)

    Grecco, Hernán E; Imtiaz, Sarah; Zamir, Eli

    2016-08-01

    Cellular functions emerge from the collective action of a large number of different proteins. Understanding how these protein networks operate requires monitoring their components in intact cells. Due to intercellular and intracellular molecular variability, it is important to monitor simultaneously multiple components at high spatiotemporal resolution. However, inherent trade-offs narrow the boundaries of achievable multiplexed imaging. Pushing these boundaries is essential for a better understanding of cellular processes. Here the motivations, challenges and approaches for multiplexed imaging of intracellular protein networks are discussed. © 2016 International Society for Advancement of Cytometry. PMID:27183498

  2. Peroxisome is a reservoir of intracellular calcium.

    Science.gov (United States)

    Raychaudhury, Bikramjit; Gupta, Shreedhara; Banerjee, Shouvik; Datta, Salil C

    2006-07-01

    We have examined fura 2-loaded purified peroxisomes under confocal microscope to prove that this mammalian organelle is a store of intracellular calcium pool. Presence of calcium channel and vanadate sensitive Ca(2+)-ATPase in the purified peroxisomal membrane has been demonstrated. We have further observed that machineries to maintain calcium pool in this mammalian organelle are impaired during infection caused by Leishmania donovani. Results reveal that peroxisomes have a merit to play a significant role in the metabolism of intracellular calcium. PMID:16713100

  3. Observation and Nursing Intervention of Amiodarone in the Treatment of Arrhythmia%胺碘酮治疗心率失常的疗效观察和护理干预分析

    Institute of Scientific and Technical Information of China (English)

    王晓荣

    2015-01-01

    目的:探讨使用胺碘酮治疗心率失常的临床效果及护理干预措施。方法回顾性分析入住我院治疗心率失常的62例患者,随机分为两组做比对性分析。结果观察组患者的治疗效果较好,总有效率高于对照组,差异有统计学意义(P<0.05)。结论使用胺腆酮治疗心率失常的临床疗效确切,加以综合护理干预可有效提高胺腆酮的治疗效果,减少并发症的发生。%Objective To investigate the clinical effect and nursing intervention measures of the use of amiodarone in the treatment of arrhythmia. Methods 62 cases of patients with arrhythmia were analyzed in our hospital, were randomly divided into two groups to do a comparison analysis. Results The effect of the observation group was significantly higher than that of the control group, the difference was statistically significant (P<0.05). Conclusion Use of amiodarone in the treatment of arrhythmia clinical curative effect, the comprehensive nursing intervention can effectively improve the therapeutic effect of amiodarone, reduce complications.

  4. The Clinical Research of Amiodarone in the Treatment of Patients With Heart Failure Combined With Arrhythmia%胺碘酮治疗心衰合并心律失常患者的临床研究

    Institute of Scientific and Technical Information of China (English)

    许波

    2015-01-01

    目的:分析胺碘酮治疗心衰合并心律失常的效果。方法选取心衰合并心律失常患者42例,均给予胺碘酮治疗。结果42例患者总有效率95.2%,用药后心功能较用药前明显改善,无严重不良反应,仅2例胃肠道不适,经对症处理后好转。结论胺碘酮治疗心衰合并心律失常效果显著。%Objective To analysis the effect of amiodarone in the treatment of heart failure combined with arrhythmia. Methods 42 cases of patients with heart failure combined with arrhythmia were selected and all patients were given amiodarone treatment. Results After treatment,the total effective rate was 95.2%in 42 cases. The cardiac function of patients were significantly improved than before treatment. There was no serious adverse reaction. Only 2 patients had gastrointestinal discomfort and they were cured after symptomatic treatment. Conclusion The effect of amiodarone in treatment of heart failure combined with arrhythmia is significantly.

  5. 胺碘酮治疗老年冠心病心律不齐的临床疗效观察%Clinical Efficacy of Amiodarone for Elderly Patients With Coronary Heart Disease Combined With Arrhythmia

    Institute of Scientific and Technical Information of China (English)

    张洪莲

    2016-01-01

    Objective To investigate the efficacy of amiodarone in the treatment of CHD combined with Arrhythmia for elderly patients.Methods We divided 80 patients into two groups,the control group used conventional therapy,and observation group used amiodarone treatment.Results The efficiency and incidence of adverse reactions of observation group were significantly better than control group(P<0.05).ConclusionThe effect of of amiodarone in the treatment of CHD combined with Arrhythmia is ideal.%目的:观察胺碘酮治疗老年冠心病心律不齐的效果。方法随机将我院收治的80例冠心病心律不齐老年患者平均分为两组,对照组行常规治疗,观察组行胺碘酮治疗。结果观察组总有效率、不良反应发生率等优于对照组(P<0.05)。结论胺碘酮治疗老年冠心病心律不齐效果理想。

  6. 去乙基胺碘酮--容易被忽视的影响胺碘酮临床使用质量的因素%Desethylamiodarone-an Neglected Factor Affecting the Clinical Use of Amiodarone

    Institute of Scientific and Technical Information of China (English)

    谭蓉; 杨继红; 孙为民

    2014-01-01

    Drugs could affect the activity of CYP450 isoenzyme, which would influence drug safety and efficacy of the substrates of CYP450 isoenzyme. Desethylamiodarone, an in vivo metabolite of amiodarone, not only contributes to its therapeutic effect, at the same time, also plays great role in the side effects of amiodarone by influencing the CYP450 isoenzyme system. Therefore, neglecting the influence factors of desethylamiodarone will affect the safety and efficacy evaluation of amiodarone.%药物可通过CYP450同工酶途径影响其底物药物临床使用的安全性和有效性。胺碘酮体内代谢产物去乙基胺碘酮不仅对其治疗作用贡献较大,同时,对CYP450同工酶系的影响也较为广泛,作用也更强。因此,对胺碘酮临床使用的评估,忽视去乙基胺碘酮的影响因素,将影响胺碘酮临床使用的安全性和有效性。

  7. Destabilization of 2D magnetic current sheets by resonance with bouncing electron - a new theory

    Science.gov (United States)

    Fruit, Gabriel; Louarn, Philippe; Tur, Anatoly

    2016-07-01

    In the general context of understanding the possible destabilization of the magnetotail before a substorm, we propose a kinetic model for electromagnetic instabilities in resonant interaction with trapped bouncing electrons. The geometry is clearly 2D and uses Harris sheet profile. Fruit et al. 2013 already used this model to investigate the possibilities of electrostatic instabilities. Tur et al. 2014 generalizes the model for full electromagnetic perturbations. Starting with a modified Harris sheet as equilibrium state, the linearized gyrokinetic Vlasov equation is solved for electromagnetic fluctuations with period of the order of the electron bounce period (a few seconds). The particle motion is restricted to its first Fourier component along the magnetic field and this allows the complete time integration of the non local perturbed distribution functions. The dispersion relation for electromagnetic modes is finally obtained through the quasi neutrality condition and the Ampere's law for the current density. The present talk will focus on the main results of this theory. The electrostatic version of the model may be applied to the near-Earth environment (8-12 R_{E}) where beta is rather low. It is showed that inclusion of bouncing electron motion may enhance strongly the growth rate of the classical drift wave instability. This model could thus explain the generation of strong parallel electric fields in the ionosphere and the formation of aurora beads with wavelength of a few hundreds of km. In the electromagnetic version, it is found that for mildly stretched current sheet (B_{z} > 0.1 B _{lobes}) undamped modes oscillate at typical electron bounce frequency with wavelength of the order of the plasma sheet thickness. As the stretching of the plasma sheet becomes more intense, the frequency of these normal modes decreases and beyond a certain threshold in B_{z}/B _{lobes}, the mode becomes explosive (pure imaginary frequency) with typical growing rate of a few

  8. Eicosanoid release is increased by membrane destabilization and CFTR inhibition in Calu-3 cells.

    Directory of Open Access Journals (Sweden)

    Florence Borot

    Full Text Available The antiinflammatory protein annexin-1 (ANXA1 and the adaptor S100A10 (p11, inhibit cytosolic phospholipase A2 (cPLA2alpha by direct interaction. Since the latter is responsible for the cleavage of arachidonic acid at membrane phospholipids, all three proteins modulate eicosanoid production. We have previously shown the association of ANXA1 expression with that of CFTR, the multifactorial protein mutated in cystic fibrosis. This could in part account for the abnormal inflammatory status characteristic of this disease. We postulated that CFTR participates in the regulation of eicosanoid release by direct interaction with a complex containing ANXA1, p11 and cPLA2alpha. We first analyzed by plasmon surface resonance the in vitro binding of CFTR to the three proteins. A significant interaction between p11 and the NBD1 domain of CFTR was found. We observed in Calu-3 cells a rapid and partial redistribution of all four proteins in detergent resistant membranes (DRM induced by TNF-alpha. This was concomitant with increased IL-8 synthesis and cPLA2alpha activation, ultimately resulting in eicosanoid (PGE2 and LTB4 overproduction. DRM destabilizing agent methyl-beta-cyclodextrin induced further cPLA2alpha activation and eicosanoid release, but inhibited IL-8 synthesis. We tested in parallel the effect of short exposure of cells to CFTR inhibitors Inh172 and Gly-101. Both inhibitors induced a rapid increase in eicosanoid production. Longer exposure to Inh172 did not increase further eicosanoid release, but inhibited TNF-alpha-induced relocalization to DRM. These results show that (i CFTR may form a complex with cPLA2alpha and ANXA1 via interaction with p11, (ii CFTR inhibition and DRM disruption induce eicosanoid synthesis, and (iii suggest that the putative cPLA2/ANXA1/p11/CFTR complex may participate in the modulation of the TNF-alpha-induced production of eicosanoids, pointing to the importance of membrane composition and CFTR function in the

  9. L-arginine destabilizes oral multi-species biofilm communities developed in human saliva.

    Science.gov (United States)

    Kolderman, Ethan; Bettampadi, Deepti; Samarian, Derek; Dowd, Scot E; Foxman, Betsy; Jakubovics, Nicholas S; Rickard, Alexander H

    2015-01-01

    The amino acid L-arginine inhibits bacterial coaggregation, is involved in cell-cell signaling, and alters bacterial metabolism in a broad range of species present in the human oral cavity. Given the range of effects of L-arginine on bacteria, we hypothesized that L-arginine might alter multi-species oral biofilm development and cause developed multi-species biofilms to disassemble. Because of these potential biofilm-destabilizing effects, we also hypothesized that L-arginine might enhance the efficacy of antimicrobials that normally cannot rapidly penetrate biofilms. A static microplate biofilm system and a controlled-flow microfluidic system were used to develop multi-species oral biofilms derived from pooled unfiltered cell-containing saliva (CCS) in pooled filter-sterilized cell-free saliva (CFS) at 37° C. The addition of pH neutral L-arginine monohydrochloride (LAHCl) to CFS was found to exert negligible antimicrobial effects but significantly altered biofilm architecture in a concentration-dependent manner. Under controlled flow, the biovolume of biofilms (μm(3)/μm(2)) developed in saliva containing 100-500 mM LAHCl were up to two orders of magnitude less than when developed without LAHCI. Culture-independent community analysis demonstrated that 500 mM LAHCl substantially altered biofilm species composition: the proportion of Streptococcus and Veillonella species increased and the proportion of Gram-negative bacteria such as Neisseria and Aggregatibacter species was reduced. Adding LAHCl to pre-formed biofilms also reduced biovolume, presumably by altering cell-cell interactions and causing cell detachment. Furthermore, supplementing 0.01% cetylpyridinium chloride (CPC), an antimicrobial commonly used for the treatment of dental plaque, with 500 mM LAHCl resulted in greater penetration of CPC into the biofilms and significantly greater killing compared to a non-supplemented 0.01% CPC solution. Collectively, this work demonstrates that LAHCl moderates multi

  10. [Magnetic nanoparticles and intracellular delivery of biopolymers].

    Science.gov (United States)

    Kornev, A A; Dubina, M V

    2014-03-01

    The basic methods of intracellular delivery of biopolymers are present in this review. The structure and synthesis of magnetic nanoparticles, their stabilizing surfactants are described. The examples of the interaction of nanoparticles with biopolymers such as nucleic acids and proteins are considered. The final part of the review is devoted to problems physiology and biocompatibility of magnetic nanoparticles.

  11. Stochastic Kinetics of Intracellular Calcium Oscillations

    Institute of Scientific and Technical Information of China (English)

    陈昌胜; 曾仁端

    2003-01-01

    A stochastic model of intracellular calcium oscillations is put forward by taking into account the random opening-closing of Ca2+ channels in endoplasmic reticulum (ER) membrane. The numerical results of the stochastic model show simple and complex calcium oscillations, which accord with the experiment results.

  12. Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis.

    Science.gov (United States)

    Garfoot, Andrew L; Rappleye, Chad A

    2016-02-01

    The fungal pathogen Histoplasma capsulatum causes respiratory and disseminated disease, even in immunocompetent hosts. In contrast to opportunistic pathogens, which are readily controlled by phagocytic cells, H. capsulatum yeasts are able to infect macrophages, survive antimicrobial defenses, and proliferate as an intracellular pathogen. In this review, we discuss some of the molecular mechanisms that enable H. capsulatum yeasts to overcome obstacles to intracellular pathogenesis. H. capsulatum yeasts gain refuge from extracellular obstacles such as antimicrobial lung surfactant proteins by engaging the β-integrin family of phagocytic receptors to promote entry into macrophages. In addition, H. capsulatum yeasts conceal immunostimulatory β-glucans to avoid triggering signaling receptors such as the β-glucan receptor Dectin-1. H. capsulatum yeasts counteract phagocyte-produced reactive oxygen species by expression of oxidative stress defense enzymes including an extracellular superoxide dismutase and an extracellular catalase. Within the phagosome, H. capsulatum yeasts block phagosome acidification, acquire essential metals such as iron and zinc, and utilize de novo biosynthesis pathways to overcome nutritional limitations. These mechanisms explain how H. capsulatum yeasts avoid and negate macrophage defense strategies and establish a hospitable intracellular niche, making H. capsulatum a successful intracellular pathogen of macrophages. PMID:26235362

  13. 胺碘酮与决奈达隆对家兔急性心房颤动作用的比较%Comparsion of the effects of amiodarone and dronedarone on acute atrial fibrillation in rabbits

    Institute of Scientific and Technical Information of China (English)

    李妙龄; 李芳; 顾磊; 唐悦; 刘志强; 梁华; 范新荣; 曾晓荣

    2015-01-01

    Objective To compare the different efficacy of amiodarome and dronedarone in treating acute atrial fibrillation. Methods: Acute atrial fibrillation model was induced by rapid atrial pacing with stimulus frequency of 17Hz. Results The successful rate of atrial fibrillation model was about 40.5%. Amiodarone and dronedarone both significantly decreased the duration and occurrence frequence of atrial fibrillation .Compared with amiodarone, dronedarone produced more potent efficacy for preventing atrial fibrillation. Amiodarone pretreatment was superior to dronedarone pretreatment in preventing atrial fibrillation recurrence. Ventricuiar rate decreased more significantly by dronedarone than by amiodarone. Conclusion In acute atrial fibrillation,amiodarone and dronedarone have similar antiarrhythmic effect with different efficacy.%目的::比较胺碘酮和决奈达隆抗家兔急性心房颤动的作用差异。方法:以17 Hz刺激频率建立心房颤动模型,观察建立模型前后给予胺碘酮和决奈达隆对家兔心房颤动的抑制作用。结果:经心电图分析,家兔急性心房颤动模型成功率为40.5%,模型建立成功后分别给予胺碘酮(5 mg/kg)和决奈达隆(5 mg/kg)均可以明显抑制房颤的持续时间和降低房颤的发作频率;与胺碘酮相比,决奈达隆抑制作用更强(P<0.05);胺碘酮预处理后预防房颤的再发作用强于决奈达隆,决奈达隆心室率抑制作用强于胺碘酮。结论:在急性房颤中,胺碘酮与决奈达隆具有相似的抗心房颤动作用,药物疗效有差异。

  14. 胺碘酮治疗心房颤动23例的临床体会%Clinical Experience of 23 Cases of Atrial Fibrillation Treated with Amiodarone

    Institute of Scientific and Technical Information of China (English)

    赵文霞; 刘成涛

    2015-01-01

    Objective To investigate the amiodarone treatment the clinical curative ef ect of new onset atrial fibril ation.Methods Our hospital from May 2011 to May 2015 were 23 cases of amiodarone treatment for atrial fibril ation patients as the research object. In the strong heart diuresis expansion blood vessel, etc on the basis of routine therapy and amiodarone treatment. Results 23 cases, 13 cases were markedly improved (57%), 7 cases (30%), ef ective invalid in 3 patients (22%), the total ef ective rate was 87%. The group were markedly improved in 1 case because of gastrointestinal symptoms and recur ence after the drug was stopped, take amiodarone after converting. Conclusion Amiodarone compared with other anti-arrhythmic drugs, can more safely and ef ectively control and prevent the occur ence of ventricular ar hythmias, atrial fibril ation and does not af ect heart function.%目的:探讨胺碘酮治疗新发心房纤颤的临床疗效。方法选取本院自2011年5月~2015年5月收治的23例胺碘酮治疗心房房颤动患者作为研究对象。在强心利尿扩血管等常规治疗的基础上采用胺碘酮治疗。结果23例中显效13例(57%),有效7例(30%),无效3例(22%),总有效率87%。其中的显效组中1例因出现胃肠道症状而自行停药后复发,续服胺碘酮后转复。结论胺碘酮与其他抗心律失常药相比,能更安全有效地防治房颤和预防室性心律失常的发生,且不影响心功能。

  15. The clinical effect observation of amiodarone combined with esmolol in rapid paroxysmal atrial fibrillation%胺碘酮联合艾司洛尔治疗快速阵发房颤疗效观察

    Institute of Scientific and Technical Information of China (English)

    黄金莹; 姚丹林

    2016-01-01

    Objective To observe the clinical effect of amiodarone combined with esmolol in rapid paroxysmal atrial fibrillation. Methods 93 cases patients with rapid paroxysmal atrial fibrillation were randomly divided into observation group and control group. Observation group was treated by amiodarone and esmolol. Control group was treated by amiodarone. After treatment,compared the clinical effect and adverse reactions. Results The total efficiency of observation group(91. 5% )was higher than that of control group(80. 4% ),the difference was statistically significant(P 0. 05). Conclu-sion The effect of amiodarone combined with esmolol in rapid paroxysmal atrial fibrillation is better than amiodarone,and without increased adverse events,worthy of promotion.%目的:观察胺碘酮联合艾司洛尔治疗快速阵发房颤的疗效及安全性。方法将93例快速阵发房颤患者随机分为2组,观察组静脉注射胺碘酮联合艾司洛尔治疗,对照组单独静脉注射胺碘酮治疗,比较2组治疗效果和不良反应。结果观察组总有效率为91.5%高于对照组的80.4%,差异有统计学意义(P <0.05)。2组均无严重不良反应发生,且其发生率比较差异无统计学意义(P >0.05)。结论胺碘酮联合艾司洛尔治疗快速阵发房颤的疗效明显优于单独使用胺碘酮患者,且不增加不良反应,值得临床推广。

  16. 胺碘酮联合美托洛尔静注治疗快速心律失常的临床观察%Clinical observation of amiodarone combined with metoprolol injection in the treatment of rapid arrhythmia

    Institute of Scientific and Technical Information of China (English)

    戴志刚

    2014-01-01

    目的:探讨胺碘酮联合美托洛尔静脉注射治疗快速心律失常的临床疗效。方法:2009年1月-2013年8月收治快速心律失常患者60例,对照组给予胺碘酮治疗,研究组给予胺碘酮联合美托洛尔静注治疗。结果:研究组临床治疗效果明显优于对照组,两组差异具有统计学意义(P<0.05);研究组与对照组均未发生严重的不良反应,两组差异不具备统计学意义(P>0.05)。结论:研究胺碘酮联合美托洛尔静脉注射治疗快速心律失常的临床疗效好于单用胺碘酮治疗,安全性、有效性较高,值得在临床治疗中推广使用。%Objective:To investigate the clinical efficacy of amiodarone combined with metoprolol injection in the treatment of rapid arrhythmia.Methods:60 patients with rapid arrhythmia were selected from January 2009 to August 2013.The control group received the treatment of amiodarone,while the research group were treated with amiodarone combined with metoprolol injection therapy.Results:The clinical effect of the treatment group was better than that of the control group,and the difference was statistically significant between two groups(P0.05).Conclusion:The therapeutic effect of amiodarone combined with metoprolol injection is better than single amiodarone in the treatment of rapid arrhythmia.This treatment has high safety,and it also effective,so it worth to be popularized in clinical treatment.

  17. 盐酸胺碘酮治疗儿童难治性持续性心动过速%Treatment of intractable incessant tachycardia in children with Amiodarone

    Institute of Scientific and Technical Information of China (English)

    李筠; 周爱卿; 杨健萍; 朱敏; 张海燕

    2009-01-01

    目的 提高对盐酸胺碘酮治疗儿童难治性持续性心动过速的认识.方法 对2006年1月-2007年12月80例应用盐酸胺碘酮治疗的难治性心动过速患儿的资料进行总结.其中男52例,女38例;年龄1个月~14岁(平均2.5岁).结果 盐酸胺碘酮具有良好的控制心室率的作用,总有效率为90%左右;同时它有不同程度转复窦性心律的作用,房性心动过速67%,阵发性室上性心动过速92%,交界逸搏性心动过速89%、室性心动过速56%;小剂量β受体阻滞剂具有协同盐酸胺碘酮抗心动过速的作用.治疗过程中7例出现低血压,4例出现心动过缓.结论 Ⅲ类抗心律失常药盐酸胺碘酮具有广泛的抗心律失常作用,它对治疗血流动力学相对稳定的小儿难治性持续性心动过速是安全有效的.%Objective To improve the understanding of Amiodarone in the treatment of intractable incessant tachycardia in children. Methods Data of 80 patients with intractable incessant tachycardia treated by Amiodarone were summarized. Among them 52 were male, 38 were female, and average age was 2.5 years old. Results Amiodarone reduced heart rate effectively, with about 90% effective. Simultaneously, it could convert tachycardia into sinus rhythm and succeeded 67% in atrial tachycardia, 92% in paroxysmal supraventricular tachycardia, 89% in junctional ectopic tachycardia, 56% in ventricular tachycardia respectively. Use of small dosage of β-receptor blocker together with Amiodarone showed synergy. Hypotension and bradycardia are the main side effects. Conclusions Too rapid and sustained tachycardia can lead, to hemodynamic disorders and cause heart failure, it requires urgent and adequate treatment. Amiodarone can be used to treat different kinds of intractable incessant tachycardia, and is safe and effective in patients with relatively stable hemodynamis.

  18. Preliminary Observation and Evaluation of the Effect of Small Dose Amiodarone in the Treatment of Amiodarone%心律失常治疗中小剂量胺碘酮治疗的效果初步观察及评估

    Institute of Scientific and Technical Information of China (English)

    桑艳平

    2015-01-01

    目的:探究中小剂量胺碘酮治疗心力衰竭合并心律失常的临床疗效。方法择取我院2013年1月~2015年1月收治的心力衰竭合并心律失常患者50例作为本次的观察对象,并给予胺碘酮进行临床治疗,分析治疗效果。结果治疗有效率达到92.0%(46/50);且仅有2例患者在连续治疗6个月后显示FT3、FT4水平增高,不良反应发生率为4.0%(2/50)。结论对心力衰竭合并心律失常患者给予中小剂量胺碘酮治疗效果好,药物不良反应少,安全性高,可改善患者临床症状。%ObjectiveTo explore the clinical effect of smal dose amiodarone in the treatment of heart failure combined with arrhythmia.MethodsChose my courtyard 50 cases with heart failure combined with arrhythmia in 2013 January to January 2015 as the object.Al patients used amiodarone for clinical treatment,therapeutic effect was analyzed. ResultsThe effective rate of treatment was 92%(46/50),and only 2 patients showed increased FT3 and FT4 levels after 6 months of continuous treatment, the incidence of adverse reactions was 4% (2/50).Conclusion The clinical effect of smal dose of amiodarone in patients with heart failure combined with arrhythmia is significant,with less adverse drug reaction,high safety and can improve the clinical symptoms.

  19. Intracellular labile iron determines H2O2-induced apoptotic signaling via sustained activation of ASK1/JNK-p38 axis.

    Science.gov (United States)

    Mantzaris, M D; Bellou, S; Skiada, V; Kitsati, N; Fotsis, T; Galaris, D

    2016-08-01

    Hydrogen peroxide (H2O2) acts as a second messenger in signal transduction participating in several redox regulated pathways, including cytokine and growth factor stimulated signals. However, the exact molecular mechanisms underlying these processes remain poorly understood and require further investigation. In this work, using Jurkat T lymphoma cells and primary human umbilical vein endothelial cells, it was observed that changes in intracellular "labile iron" were able to modulate signal transduction in H2O2-induced apoptosis. Chelation of intracellular labile iron by desferrioxamine rendered cells resistant to H2O2-induced apoptosis. In order to identify the exact points of iron action, we investigated selected steps in H2O2-mediated apoptotic pathway, focusing on mitogen activated protein kinases (MAPKs) JNK, p38 and ERK. It was observed that spatiotemporal changes in intracellular labile iron, induced by H2O2, influenced the oxidation pattern of the upstream MAP3K ASK1 and promoted the sustained activation of JNK-p38 axis in a defined time-dependent context. Moreover, we indicate that H2O2 induced spatiotemporal changes in intracellular labile iron, at least in part, by triggering the destabilization of lysosomal compartments, promoting a concomitant early response in proteins of iron homeostasis. These results raise the possibility that iron-mediated oxidation of distinct proteins may be implicated in redox signaling processes. Since labile iron can be pharmacologically modified in vivo, it may represent a promising target for therapeutic interventions in related pathological conditions.

  20. Extracellular α-synuclein leads to microtubule destabilization via GSK-3β-dependent Tau phosphorylation in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Magdalena Gąssowska

    Full Text Available α-Synuclein (ASN plays an important role in pathogenesis of Parkinson's disease (PD and other neurodegenerative disorders. Novel and most interesting data showed elevated tauopathy in PD and suggested relationship between ASN and Tau protein. However, the mechanism of ASN-evoked Tau protein modification is not fully elucidated. In this study we investigated the role of extracellular ASN in Tau hyperphosphorylation in rat pheochromocytoma (PC12 cells and the involvement of glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (CDK5 in ASN-dependent Tau modification. Our results indicated that exogenously added ASN increases Tau phosphorylation at Ser396. Accordingly, the GSK-3β inhibitor (SB-216763 prevented ASN-evoked Tau hyperphosphorylation, but the CDK5 inhibitor had no effect. Moreover, western blot analysis showed that ASN affected GSK-3β via increasing of protein level and activation of this enzyme. GSK-3β activity evaluated by its phosphorylation status assay showed that ASN significantly increased the phosphorylation of this enzyme at Tyr216 with parallel decrease in phosphorylation at Ser9, indicative of stimulation of GSK-3β activity. Moreover, the effect of ASN on microtubule (MT destabilization and cell death with simultaneous the involvement of GSK-3β in these processes were analyzed. ASN treatment increased the amount of free tubulin and concomitantly reduced the amount of polymerized tubulin and SB-216763 suppressed these ASN-induced changes in tubulin, indicating that GSK-3β is involved in ASN-evoked MT destabilization. ASN-induced apoptotic processes lead to decrease in PC12 cells viability and SB-216763 protected those cells against ASN-evoked cytotoxicity. Concluding, extracellular ASN is involved in GSK-3β-dependent Tau hyperphosphorylation, which leads to microtubule destabilization. GSK-3β inhibition may be an effective strategy for protecting against ASN-induced cytotoxicity.

  1. Early vessel destabilization mediated by Angiopoietin-2 and subsequent vessel maturation via Angiopoietin-1 induce functional neovasculature after ischemia.

    Directory of Open Access Journals (Sweden)

    Di Qin

    Full Text Available BACKGROUND: We assessed whether Angiopoietin-2 (Ang2, a Tie2 ligand and partial antagonist of Angiopoietin-1 (Ang1, is required for early vessel destabilization during postischemic angiogenesis, when combined with vascular growth factors. METHODS: In vitro, matrigel co-cultures assessed endothelial-cell tube formation and pericyte recruitment after stimulation of VEGF-A, Apelin (APLN, Ang1 with or without Ang2. In a murine hindlimb ischemia model, adeno-associated virus (rAAV, 3×10(12 virusparticles transduction of VEGF-A, APLN and Ang1 with or without Ang2 (continuous or early expression d0-3 was performed intramuscularly (d-14. Femoral artery ligation was performed at d0, followed by laser doppler perfusion meassurements (LDI 7 and 14. At d7 (early timepoint and d14 (late timepoint, histological analysis of capillary/muscle fiber ratio (CMF-R, PECAM-1 and pericyte/capillary ratio (PC-R, NG2 was performed. RESULTS: In vitro, VEGF-A, APLN and Ang1 induced ring formation, but only APLN and Ang1 recruited pericytes. Ang2 did not affect tube formation by APLN, but reduced pericyte recruitment after APLN or Ang1 overexpression. In vivo, rAAV.VEGF-A did not alter LDI-perfusion at d14, consistent with an impaired PC-R despite a rise in CMF-R. rAAV.APLN improved perfusion at d14, with or without continuous Ang2, increasing CMF-R and PC-R. rAAV.Ang1 improved perfusion at d14, when combined with rAAV.Ang2 (d0-3, accompanied by an increased CMF-R and PC-R. CONCLUSION: The combination of early vessel destabilization (Ang2 d0-3 and continuous Ang1 overexpression improves hindlimb perfusion, pointing to the importance of early vessel destabilization and subsequent vessel maturation for enhanced therapeutic neovascularization.

  2. Dynamics of gradient formation by intracellular shuttling

    Energy Technology Data Exchange (ETDEWEB)

    Berezhkovskii, Alexander M. [Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892 (United States); Shvartsman, Stanislav Y. [Department of Chemical and Biological Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544 (United States)

    2015-08-21

    A number of important cellular functions rely on the formation of intracellular protein concentration gradients. Experimental studies discovered a number of mechanisms for the formation of such gradients. One of the mechanisms relies on the intracellular shuttling of a protein that interconverts between the two states with different diffusivities, under the action of two enzymes, one of which is localized to the plasma membrane, whereas the second is uniformly distributed in the cytoplasm. Recent work reported an analytical solution for the steady state gradient in this mechanism, obtained in the framework of a one-dimensional reaction-diffusion model. Here, we study the dynamics in this model and derive analytical expressions for the Laplace transforms of the time-dependent concentration profiles in terms of elementary transcendental functions. Inverting these transforms numerically, one can obtain time-dependent concentration profiles of the two forms of the protein.

  3. Biology and intracellular life of chlamydia

    Directory of Open Access Journals (Sweden)

    Ranin Lazar

    2011-01-01

    Full Text Available Introduction. Chlamydiae are Gram-negative obligate intracellular bacteria. The developmental cycle of Chlamydiae is specific and different from other bacteria. The elementary body is the infectious form of the organism, responsible for attaching to the target host cell and promoting its entry. The reticulate body is the larger, metabolically active form of the organism, synthesizing deoxyribonucleic acid, ribonucleic acid and proteins. The elementary body and reticulate body represent evolutionary adaptations to extracellular and intracellular environments. Intracellular persistence of Chlamydia. Predisposition of Chlamydia to persist within the host cell has been recognized as a major factor in the pathogenesis of chlamydial disease. The persistence implies a long-term association between chlamydiae and their host cell that may not manifest as clinically recognizable disease. The ability of chlamydia to remain within one morphological state for a long time in response to exogenous factors suggests an innate ability of these organisms to persist intracellulary in a unique developmental form. Chlamydiae induce interferon γ and exhibit growth inhibition in their presence. While the high levels of interferon γ completely restrict the development of chlamydia, its low levels induce the development of morphologically aberrant intracellular forms. The persistent forms contain reduced levels of major outer membrane protein but high levels of chlamydial heat shock protein. Conclusion. Immunopathogenesis of chlamydial infection is one of the main focal points of current research into Chlamydia. Chlamydial infections are highly prevalent, usually asymptomatic and associated with serious sequelae. Screening programmes are the most important in the prevention of a long-term sequele.

  4. Paclitaxel Arrests Growth of Intracellular Toxoplasma gondii

    OpenAIRE

    Estes, Randee; Vogel, Nicolas; Mack, Douglas; McLeod, Rima

    1998-01-01

    Addition of paclitaxel (Taxol) at a concentration of 1 μM to Toxoplasma gondii-infected human foreskin fibroblasts arrested parasite multiplication. Division of the T. gondii tachyzoite nucleus was inhibited, leading to syncytium-like parasite structures within the fibroblasts by 24 h after infection and treatment of the cultures. By 4 days after infection and treatment of the cultures with paclitaxel, this inhibition was irreversible, since the arrested intracellular form was incapable of le...

  5. Intracellular serpins, firewalls and tissue necrosis.

    Science.gov (United States)

    Marciniak, Stefan J; Lomas, David A

    2008-02-01

    Luke and colleagues have recently attributed a new role to a member of the serpin superfamily of serine proteinase inhibitors. They have used Caenorhabditis elegans to show that an intracellular serpin is crucial for maintaining lysosomal integrity. We examine the role of this firewall in preventing necrosis and attempt to integrate this with current theories of stress-induced protein degradation. We discuss how mutant serpins cause disease either through polymerization or now, perhaps, by unleashing necrosis. PMID:18215520

  6. Fluorescent nanoparticles for intracellular sensing: A review

    Energy Technology Data Exchange (ETDEWEB)

    Ruedas-Rama, Maria J., E-mail: mjruedas@ugr.esmailto [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Walters, Jamie D. [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, UK CB2 1QT (United Kingdom); Orte, Angel [Department of Physical Chemistry, Faculty of Pharmacy, University of Granada, Campus Cartuja, 18071, Granada (Spain); Hall, Elizabeth A.H., E-mail: lisa.hall@biotech.cam.ac.uk [Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT (United Kingdom)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer Analytical applications of fluorescent nanoparticles (NPs) in intracellular sensing. Black-Right-Pointing-Pointer Critical review on performance of QDots, metal NPs, silica NPs, and polymer NPs. Black-Right-Pointing-Pointer Highlighted potential of fluorescence lifetime imaging microscopy (FLIM). - Abstract: Fluorescent nanoparticles (NPs), including semiconductor NPs (Quantum Dots), metal NPs, silica NPs, polymer NPs, etc., have been a major focus of research and development during the past decade. The fluorescent nanoparticles show unique chemical and optical properties, such as brighter fluorescence, higher photostability and higher biocompatibility, compared to classical fluorescent organic dyes. Moreover, the nanoparticles can also act as multivalent scaffolds for the realization of supramolecular assemblies, since their high surface to volume ratio allow distinct spatial domains to be functionalized, which can provide a versatile synthetic platform for the implementation of different sensing schemes. Their excellent properties make them one of the most useful tools that chemistry has supplied to biomedical research, enabling the intracellular monitoring of many different species for medical and biological purposes. In this review, we focus on the developments and analytical applications of fluorescent nanoparticles in chemical and biological sensing within the intracellular environment. The review also points out the great potential of fluorescent NPs for fluorescence lifetime imaging microscopy (FLIM). Finally, we also give an overview of the current methods for delivering of fluorescent NPs into cells, where critically examine the benefits and liabilities of each strategy.

  7. ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Fumin; Telesco, Shannon E.; Liu, Yingting; Radhakrishnan, Ravi; Lemmon, Mark A. (UPENN); (UPENN-MED)

    2010-06-21

    ErbB3/HER3 is one of four members of the human epidermal growth factor receptor (EGFR/HER) or ErbB receptor tyrosine kinase family. ErbB3 binds neuregulins via its extracellular region and signals primarily by heterodimerizing with ErbB2/HER2/Neu. A recently appreciated role for ErbB3 in resistance of tumor cells to EGFR/ErbB2-targeted therapeutics has made it a focus of attention. However, efforts to inactivate ErbB3 therapeutically in parallel with other ErbB receptors are challenging because its intracellular kinase domain is thought to be an inactive pseudokinase that lacks several key conserved (and catalytically important) residues - including the catalytic base aspartate. We report here that, despite these sequence alterations, ErbB3 retains sufficient kinase activity to robustly trans-autophosphorylate its intracellular region - although it is substantially less active than EGFR and does not phosphorylate exogenous peptides. The ErbB3 kinase domain binds ATP with a K{sub d} of approximately 1.1 {micro}M. We describe a crystal structure of ErbB3 kinase bound to an ATP analogue, which resembles the inactive EGFR and ErbB4 kinase domains (but with a shortened {alpha}C-helix). Whereas mutations that destabilize this configuration activate EGFR and ErbB4 (and promote EGFR-dependent lung cancers), a similar mutation conversely inactivates ErbB3. Using quantum mechanics/molecular mechanics simulations, we delineate a reaction pathway for ErbB3-catalyzed phosphoryl transfer that does not require the conserved catalytic base and can be catalyzed by the 'inactive-like'configuration observed crystallographically. These findings suggest that ErbB3 kinase activity within receptor dimers may be crucial for signaling and could represent an important therapeutic target.

  8. Strategies to improve intracellular drug delivery by targeted liposomes

    NARCIS (Netherlands)

    Fretz, M.M.

    2007-01-01

    Biotechnological advances increased the number of novel macromolecular drugs and new drug targets. The latter are mostly found intracellular. Unfortunately, most of the new macromolecular drugs rely on drug delivery tools for their intracellular delivery because their unfavourable physicochemical pr

  9. Curcumin protects against intracellular amyloid toxicity in rat primary neurons

    OpenAIRE

    Ye, Jelina; Zhang, Yan

    2012-01-01

    To investigate whether curcumin is protective against intracellular amyloid β (Aβ) toxicity, different concentrations of curcumin were applied to with intracellular Aβ in rat primary hippocampal neurons in culture. We find that at low dosages, curcumin effectively inhibits intracellular Aβ toxicity. Reactive oxidative species (ROS) is involved in mediating intracellular Aβ toxicity and possibly curcumin protection. Our results indicate that oxidative stress may mediate cell death induced by i...

  10. Proton-dependent zinc release from intracellular ligands

    OpenAIRE

    Kiedrowski, Lech

    2014-01-01

    In cultured cortical and hippocampal neurons when intracellular pH drops from 6.6 to 6.1, yet unclear intracellular stores release micromolar amounts of Zn2+ into the cytosol. Mitochondria, acidic organelles, and/or intracellular ligands could release this Zn2+. Although exposure to the protonophore FCCP precludes re-loading of the mitochondria and acidic organelles with Zn2+, FCCP failed to compromise the ability of the intracellular stores to repeatedly release Zn2+. There...

  11. Intracellular ethanol accumulation in Saccharomyces cerevisiae during fermentation.

    OpenAIRE

    D'Amore, T; C.J. Panchal; Stewart, G G

    1988-01-01

    An intracellular accumulation of ethanol in Saccharomyces cerevisiae was observed during the early stages of fermentation (3 h). However, after 12 h of fermentation, the intracellular and extracellular ethanol concentrations were similar. Increasing the osmotic pressure of the medium caused an increase in the ratio of intracellular to extracellular ethanol concentrations at 3 h of fermentation. As in the previous case, the intracellular and extracellular ethanol concentrations were similar af...

  12. Destabilization of the 6H-SrIrO3 polymorph through partial substitution of zinc and lithium

    DEFF Research Database (Denmark)

    Bremholm, Martin; K. Kim, Cindi; Hirai, Daigo;

    2012-01-01

    We report on the destabilization of the 6H-SrIrO3 polymorph through partial substitutions of zinc and lithium for iridium to form perovskites. The perovskites crystallize in the orthorhombic space group Pbnm: SrIr1−xZnxO3 is found for 0.25 ≤ x ≤ 0.33, while SrIr1−xLixO3 is found only for x = 0.......25. The Zn and Li ions are randomly distributed in the B-site lattice. Analysis shows that the perovskite stabilization is not driven by changes in average ionic size but rather is due to destabilization of the face-sharing octahedra that are present in 6H-type SrIrO3. Magnetic susceptibility measurements...... show Curie–Weiss behavior, with relatively large temperature independent contributions, and that the iridium atoms have low effective moments, 0.52 to 1.08 μB per Ir. The resistivity of SrIr0.67Zn0.33O3, characterized by Mott variable range hopping type semiconducting behavior, indicates...

  13. A cellular model of memory reconsolidation involves reactivation-induced destabilization and restabilization at the sensorimotor synapse in Aplysia.

    Science.gov (United States)

    Lee, Sue-Hyun; Kwak, Chuljung; Shim, Jaehoon; Kim, Jung-Eun; Choi, Sun-Lim; Kim, Hyoung F; Jang, Deok-Jin; Lee, Jin-A; Lee, Kyungmin; Lee, Chi-Hoon; Lee, Young-Don; Miniaci, Maria Concetta; Bailey, Craig H; Kandel, Eric R; Kaang, Bong-Kiun

    2012-08-28

    The memory reconsolidation hypothesis suggests that a memory trace becomes labile after retrieval and needs to be reconsolidated before it can be stabilized. However, it is unclear from earlier studies whether the same synapses involved in encoding the memory trace are those that are destabilized and restabilized after the synaptic reactivation that accompanies memory retrieval, or whether new and different synapses are recruited. To address this issue, we studied a simple nonassociative form of memory, long-term sensitization of the gill- and siphon-withdrawal reflex in Aplysia, and its cellular analog, long-term facilitation at the sensory-to-motor neuron synapse. We found that after memory retrieval, behavioral long-term sensitization in Aplysia becomes labile via ubiquitin/proteasome-dependent protein degradation and is reconsolidated by means of de novo protein synthesis. In parallel, we found that on the cellular level, long-term facilitation at the sensory-to-motor neuron synapse that mediates long-term sensitization is also destabilized by protein degradation and is restabilized by protein synthesis after synaptic reactivation, a procedure that parallels memory retrieval or retraining evident on the behavioral level. These results provide direct evidence that the same synapses that store the long-term memory trace encoded by changes in the strength of synaptic connections critical for sensitization are disrupted and reconstructed after signal retrieval.

  14. Human Plasma Very Low-Density Lipoproteins Are Stabilized by Electrostatic Interactions and Destabilized by Acidic pH

    Directory of Open Access Journals (Sweden)

    Madhumita Guha

    2011-01-01

    Full Text Available Very low-density lipoproteins (VLDL are precursors of low-density lipoproteins (LDL, or “bad cholesterol”. Factors affecting structural integrity of VLDL are important for their metabolism. To assess the role of electrostatic interactions in VLDL stability, we determined how solvent ionic conditions affect the heat-induced VLDL remodeling. This remodeling involves VLDL fusion, rupture, and fission of apolipoprotein E-containing high-density lipoprotein-(HDL- like particles similar to those formed during VLDL-to-LDL maturation. Circular dichroism and turbidity show that increasing sodium salt concentration in millimolar range reduces VLDL stability and its enthalpic component. Consequently, favorable electrostatic interactions stabilize VLDL. Reduction in pH from 7.4 to 6.0 reduces VLDL stability, with further destabilization detected at pH < 6, which probably results from titration of the N-terminal α-amino groups and free fatty acids. This destabilization is expected to facilitate endosomal degradation of VLDL, promote their coalescence into lipid droplets in atherosclerotic plaques, and affect their potential use as drug carriers.

  15. Dimethyl Sulfoxide Induced Destabilization and Disassembly of Various Structural Variants of Insulin Fibrils Monitored by Vibrational Circular Dichroism.

    Science.gov (United States)

    Zhang, Ge; Babenko, Viktoria; Dzwolak, Wojciech; Keiderling, Timothy A

    2015-12-15

    Dimethyl sulfoxide (DMSO) induced destabilization of insulin fibrils has been previously studied by Fourier transform infrared spectroscopy and interpreted in terms of secondary structural changes. The variation of this process for fibrils with different types of higher-order morphological structures remained unclear. Here, we utilize vibrational circular dichroism (VCD), which has been reported to provide a useful biophysical probe of the supramolecular chirality of amyloid fibrils, to characterize changes in the macroscopic chirality following DMSO-induced disassembly for two types of insulin fibrils formed under different conditions, at different reduced pH values with and without added salt and agitation. We confirm that very high concentrations of DMSO can disaggregate both types of insulin fibrils, which initially maintained a β-sheet conformation and eventually changed their secondary structure to a disordered form. The two types responded to varying concentrations of DMSO, and disaggregation followed different mechanisms. Interconversion of specific insulin fibril morphological types also occurred during the destabilization process as monitored by VCD. With transmission electron microscopy, we were able to correlate the changes in VCD sign patterns to alteration of morphology of the insulin fibrils.

  16. Validation of a direct non-destructive quantitative analysis of amiodarone hydrochloride in Angoron((R)) formulations using FT-Raman spectroscopy.

    Science.gov (United States)

    Orkoula, M G; Kontoyannis, C G; Markopoulou, C K; Koundourellis, J E

    2007-09-15

    Raman spectroscopy was applied for the direct non-destructive analysis of amiodarone hydrochloride (ADH), the active ingredient of the liquid formulation Angoron((R)). The FT-Raman spectra were obtained through the un-broken as-received ampoules of Angoron((R)). Using the most intense vibration of the active pharmaceutical ingredient (API) at 1568cm(-1), a calibration model, based on solutions with known concentrations, was developed. The model was applied to the Raman spectra recorded from three as-purchased commercial formulations of Angoron((R)) having nominal strength of 50mgml(-1) ADH. The average value of the API in these samples was found to be 48.56+/-0.64mgml(-1) while the detection limit of the proposed technique was found to be 2.11mgml(-1). The results were compared to those obtained from the application of HPLC using the methodology described in the European Pharmacopoeia and found to be in excellent agreement. The proposed analytical methodology was also validated by evaluating the linearity of the calibration line as well as its accuracy and precision. The main advantage of Raman spectroscopy over HPLC method during routine analysis is that it is considerably faster and no solvent consuming. Furthermore, Raman spectroscopy is non-destructive for the sample. However, the detection limit for Raman spectroscopy is much higher than the corresponding for the HPLC methodology. PMID:19073025

  17. Mechanisms of amiodarone and valproic acid induced liver steatosis in mouse in vivo act as a template for other hepatotoxicity models.

    Science.gov (United States)

    Vitins, Alexa P; Kienhuis, Anne S; Speksnijder, Ewoud N; Roodbergen, Marianne; Luijten, Mirjam; van der Ven, Leo T M

    2014-08-01

    Liver injury is the leading cause of drug-induced toxicity. For the evaluation of a chemical compound to induce toxicity, in this case steatosis or fatty liver, it is imperative to identify markers reflective of mechanisms and processes induced upon exposure, as these will be the earliest changes reflective of disease. Therefore, an in vivo mouse toxicogenomics study was completed to identify common pathways, nuclear receptor (NR) binding sites, and genes regulated by three known human steatosis-inducing compounds, amiodarone (AMD), valproic acid (VPA), and tetracycline (TET). Over 1, 4, and 11 days of treatment, AMD induced changes in clinical chemistry parameters and histopathology consistent with steatosis. Common processes and NR binding sites involved in lipid, retinol, and drug metabolism were found for AMD and VPA, but not for TET, which showed no response. Interestingly, the pattern of enrichment of these common pathways and NR binding sites over time was unique to each compound. Eleven biomarkers of steatosis were identified as dose responsive and time sensitive to toxicity for AMD and VPA. Finally, this in vivo mouse study was compared to an AMD rat in vivo, an AMD mouse primary hepatocyte, and a VPA human primary hepatocyte study to identify concordance for steatosis. We conclude that concordance is found on the process level independent of species, model or dose*time point. PMID:24535564

  18. Comparison of the Frequency-dependent Effects of Amiodarone on Ventricular Electrophysiology in Congestive Heart Failure Canine Models and Normal Dogs

    Institute of Scientific and Technical Information of China (English)

    Zhou Shuxian; Zhang Yuling; Lei Juan; Wu Wei; Zhang Xuming

    2007-01-01

    Objectives To compare the frequency-dependent effects of amiodarone (Ami) on ventricular electrophysiology in right ventricular rapid pacing-induced congestive heart failure (CHF) canine models.Methods Thirty-two dogs were randomized into four groups: the control group, the Ami group in which the normal dogs were given Ami orally 300 mg a day for 4~5 weeks, the CHF group induced by right ventricular rapid pacing ( 240 pulses. min -1 for 4 ~ 5 weeks), and the group of CHF dogs fed with Ami orally 300 mg a day for 4 ~ 5 weeks. The techniques of electrical stimulation and monophasic action potential (MAP) recording were used in the electrophysiology studies. Results The effects of Ami on ventricular MAP duration(MAPD90) and effective refractory period (VERP)were not frequency-dependent in CHF dogs. There was also no frequency-dependent effect on the increase in the ratio of VERP to MAPD90 (VERP/MAPD90). The prolongation of ventricular conduction time was frequencydependent. Conclusions The frequency-dependent effects of Ami on ventricular electrophysiology in CHF dogs were similar to that in normal dogs.

  19. Methanolic extract of Moringa oleifera leaf and low doses of gamma radiation alleviated amiodarone-induced lung toxicity in albino rats

    Directory of Open Access Journals (Sweden)

    Hasan Hesham F.

    2016-01-01

    Full Text Available This study aimed to evaluate the effects of methanolic extract of Moringa oleifera (MO and/or low doses of gamma radiation (LDR on amiodarone (AMD-induced lung toxicity in rats. AMD administered to female albino rats (100 mg/kg body weight for 10 consecutive days. Rats received methanolic extract of MO (250 mg/kg bwt for 15 successive days and/or were exposed to whole body LDR (0.25Gy on the 1st and 10th days, up to a total dose of 0.5Gy. MO administration induced a significant decrease in serum tumor necrosis factor-alpha (TNF-α and transforming growth factor-beta (TGF-β levels as well as lactate dehydrogenase (LDH activity. Also, the content of malondialdehyde (MDA and hydroxyproline (HYP was significantly decreased in lung tissue. Furthermore, MO significantly increased reduced glutathione (GSH content in lung tissue as compared with AMD. The histopathological investigation of lung tissue revealed the appearance of interstitial pneumonia in rats treated with AMD. The oral administration of MO and/or exposure to LDR reversed the biochemical and histopathological alterations induced by AMD. It can be posited that MO and LDR might have a considerable role in the prevention of lung toxicity induced by AMD.

  20. A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.

    Science.gov (United States)

    Driessen, Marja; Vitins, Alexa P; Pennings, Jeroen L A; Kienhuis, Anne S; Water, Bob van de; van der Ven, Leo T M

    2015-01-22

    The zebrafish embryo (ZFE) is a promising alternative, non-rodent model in toxicology, which has an advantage over the traditionally used models as it contains complete biological complexity and provides a medium to high-throughput setting. Here, we assess how the ZFE compares to the traditionally used models for liver toxicity testing, i.e., in vivo mouse and rat liver, in vitro mouse and rat hepatocytes, and primary human hepatocytes. For this comparison, we analyzed gene expression changes induced by three model compounds for cholestasis, steatosis, and necrosis. The three compounds, cyclosporine A, amiodarone, and acetaminophen, were chosen because of their relevance to human toxicity and these compounds displayed hepatotoxic-specific changes in the mouse in vivo data. Compound induced expression changes in the ZFE model shared similarity with both in vivo and in vitro. Comparison on single gene level revealed the presence of model specific changes and no clear concordance across models. However, concordance was identified on the pathway level. Specifically, the pathway "regulation of metabolism - bile acids regulation of glucose and lipid metabolism via FXR" was affected across all models and compounds. In conclusion, our study with three hepatotoxic model compounds shows that the ZFE model is at least as comparable to traditional models in identifying hepatotoxic activity and has the potential for use as a pre-screen to determine the hepatotoxic potential of compounds.

  1. Curcumin protects against intracellular amyloid toxicity in rat primary neurons

    NARCIS (Netherlands)

    Ye, Jelina; Zhang, Yan

    2012-01-01

    To investigate whether curcumin is protective against intracellular amyloid beta (A beta) toxicity, different concentrations of curcumin were applied to with intracellular A beta in rat primary hippocampal neurons in culture. We find that at low dosages, curcumin effectively inhibits intracellular A

  2. Site-selective probing of cTAR destabilization highlights the necessary plasticity of the HIV-1 nucleocapsid protein to chaperone the first strand transfer

    Science.gov (United States)

    Godet, Julien; Kenfack, Cyril; Przybilla, Frédéric; Richert, Ludovic; Duportail, Guy; Mély, Yves

    2013-01-01

    The HIV-1 nucleocapsid protein (NCp7) is a nucleic acid chaperone required during reverse transcription. During the first strand transfer, NCp7 is thought to destabilize cTAR, the (−)DNA copy of the TAR RNA hairpin, and subsequently direct the TAR/cTAR annealing through the zipping of their destabilized stem ends. To further characterize the destabilizing activity of NCp7, we locally probe the structure and dynamics of cTAR by steady-state and time resolved fluorescence spectroscopy. NC(11–55), a truncated NCp7 version corresponding to its zinc-finger domain, was found to bind all over the sequence and to preferentially destabilize the penultimate double-stranded segment in the lower part of the cTAR stem. This destabilization is achieved through zinc-finger–dependent binding of NC to the G10 and G50 residues. Sequence comparison further revealed that C•A mismatches close to the two G residues were critical for fine tuning the stability of the lower part of the cTAR stem and conferring to G10 and G50 the appropriate mobility and accessibility for specific recognition by NC. Our data also highlight the necessary plasticity of NCp7 to adapt to the sequence and structure variability of cTAR to chaperone its annealing with TAR through a specific pathway. PMID:23511968

  3. Intracellular α-Amylase of Streptococcus mutans

    OpenAIRE

    Simpson, Christine L.; Russell, Roy R. B.

    1998-01-01

    Sequencing upstream of the Streptococcus mutans gene for a CcpA gene homolog, regM, revealed an open reading frame, named amy, with homology to genes encoding α-amylases. The deduced amino acid sequence showed a strong similarity (60% amino acid identity) to the intracellular α-amylase of Streptococcus bovis and, in common with this enzyme, lacked a signal sequence. Amylase activity was found only in S. mutans cell extracts, with no activity detected in culture supernatants. Inactivation of a...

  4. OBSERVATION AND PREVENTION OF PHLEBITIS DURING CONTINUOUSLY INJECTION OF AMIODARONE THROUGH MICRO INFUSION%持续微泵静脉注射可达龙药物的观察与静脉炎防治护理

    Institute of Scientific and Technical Information of China (English)

    向岚; 魏军华; 李雪雁

    2011-01-01

    [目的]加强可达龙用药期间的观察及静脉炎的防治护理.[方法]培养专科护士全面了解药物作用与特殊性,加强用药期间的观察,正确识别副作用、并发症,及时评估血管,采取有效地预防及处置.[结果]减少了用药期间的并发症,提高了药物疗效及工作效率.[结论]专科用药实施严密综合管理,保证了用药期间的安全,减轻了患者痛苦与经济负担.%[Objective] To enforce the nursing observation and prevention of phlebitis during using of amiodurone. [Methods] Effective education and training about the drug effect and specification of amiodarone were given to nurses. The nursing observation during the using of the drug was enforced and the bad effects and complications were correctly identified. The stale of the vein was evaluated and effective prevention measures and treatments were taken in time. [Results] Through these effective nursing measures above, the complications were significantly reduced while the treatment effects of amiodarone and the work efficiency were dramatically improved. [Conclusion] Through rigid integrated management to the nursing during the using of amiodarone, the security can be assured and the agony and economy burden of patients can be relived.

  5. 胺碘酮对心力衰竭并心房颤动病人的疗效观察%Efficacy of amiodarone in heart failure patients with atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    王向阳

    2014-01-01

    目的:就胺碘酮对心力衰竭并心房颤动病人的疗效观察进行探讨。方法选择我院2008年11月到2013年1月所收治的心力衰竭并心房颤动患者50例,随机将所有患者分为2组,分别是治疗组、对照组,。对照组采用常规治疗方法,而治疗组在此基础上增加静脉注射胺碘酮溶液及口服胺碘酮。结果治疗组有效率为96%,对照组有效率为82%,二者存在着较为明显的差异,具有统计学意义(P0.05)。两组患者在治疗后都没有出现肾功能、肝功能损害、恶性心律失常、不可耐受性低血压等严重不良反应。结论胺碘酮对心力衰竭并心房颤动病人的疗效较佳,安全有效,无较为严重的不良反应,可以作为首选治疗药物,值得推广应用。%Objective To investigate the efficacy of amiodarone in heart failure patients with atrial fibrillation. Methods Fifty heart failure patients with atrial fibrillation admitted to our hospital from November 2008 to January 2013 were randomly divided into treatment group and control group. The control group received routine treatment, while the treatment group was intravenously injected with amiodarone solution and orally given amiodarone in addition to the routine treatment. Results The treatment group had a significantly higher response rate than the control group (96% vs 82%, P 0.05). No patients developed severe adverse reactions, such as renal function impairment, liver function impairment, malignant arrhythmia, and intolerable hypotension, after treatment. Conclusion Amiodarone has good efficacy and high safety and does not cause severe adverse reactions in heart failure patients with atrial fibrillation. This therapy can be used as the first choice of medication and holds promise for clinical application.

  6. Analysis of the clinical effect of amiodarone on heart failure complicated with atrial fibrillation%胺碘酮应用于心力衰竭伴发房颤治疗的临床效果分析

    Institute of Scientific and Technical Information of China (English)

    范怀周

    2014-01-01

    Objective To explore clinical effect of amiodarone on heart failure complicated with atrial fibrillation. Methods Selecting 76 patients with heart failure complicated with atrial fibrillation and randomly dividing them into observation group and control group. Two groups were given conventional treatment in the hospital. The observation group was given amiodarone on the basis of conventional treatment, the control group was given acetyl lanatoside, ventricular rate control was observed in two groups. Results The ventricular rate in the observation group and the control group after treatment compared with those in two groups before treatment respectively, the difference was statistically significant(P<0.05);the ventricular rate in the observation group after treatment compared with that in control group before treatment, the difference was statistically significant(P<0.05). Conclusion Amiodarone applied on heart failure complicated with atrial fibrillation has significantly clinical effect and amiodarone may control the ventricular rate of the patients.%目的:探讨胺碘酮应用于心力衰竭伴发房颤治疗的临床效果。方法选择本院76例慢性充血性心力衰竭患者,随机分为观察组和对照组。两组患者均在入院后给予常规治疗。观察组在常规治疗基础上给予胺碘酮治疗,对照组给予乙酰毛花苷治疗。观察两组患者心室率控制情况。结果观察组和对照组治疗后心室率分别与本组治疗前比较,差异有统计学意义(P<0.05);观察组治疗后心室率和对照组治疗后心室率比较,差异有统计学意义(P<0.05)。观察组总有效率高于对照组,差异有统计学意义(P<0.05)。结论胺碘酮应用于心力衰竭伴发房颤治疗的临床效果显著,能够有效控制患者的心室率,值得借鉴。

  7. 胺碘酮致飞行员甲状腺功能异常二例并文献复习%Two cases of pilots with amiodarone-induced thyroid dysfunction and literature review

    Institute of Scientific and Technical Information of China (English)

    杨彩哲; 于亚静; 徐先荣; 郑军; 刘红巾; 付兆君; 崔丽; 关小宏; 王建昌

    2015-01-01

    目的 总结飞行人员因心律失常服用胺碘酮而引起甲状腺功能异常的临床特征、诊断、分型、治疗及预后,为以后类似疾病的诊治及航空医学鉴定提供经验. 方法 通过回顾性分析2例飞行员因心房颤动服用胺碘酮而引起甲状腺功能异常的过程,结合文献复习,总结胺碘酮诱发甲状腺功能异常的临床特征、诊断、分型、治疗及转归. 结果 例1飞行员在服用胺碘酮7个月后停药,停药1个月后出现“低T3综合征”.停药2年后再次服用胺碘酮,1个月后出现碘诱导2型甲状腺毒症;停用胺碘酮3个月,甲状腺功能恢复正常.例2飞行员间断服用胺碘酮9年后诊断为碘诱导甲状腺功能减退,停用胺碘酮,并口服左甲状腺素钠75 μg,1次/d,补充治疗,5个月后甲状腺功能恢复正常.应用左甲状腺素钠2年后停药,甲状腺功能完全恢复正常.两例飞行员鉴定结论为暂时飞行不合格. 结论 飞行人员应用胺碘酮前,应完善相关检查.在治疗过程中、停药后6~9月甚至更长时间内,应定期检查甲状腺功能.对服用胺碘酮的飞行员要定期随访,尤其对既往存在甲状腺疾病和存在危险因素者.胺碘酮所引起的甲状腺功能异常有可能恢复正常.鉴定结论要结合心律失常和甲状腺功能情况综合判断.%Objective To summarize the clinic feature,diagnosis,treatment,and prognosis of amiodarone-induced thyroid dysfunction in the pilots with arrhythmia and gather the experiences on treatment and aviation medical assessment.Methods Retrospective analysis was done on the process of 2 cases with amiodarone induced abnormal thyroid function in pilots with atrial fibrillation and on the literatures to summary the clinic feature,diagnosis,treatment,and prognosis were reviewed.Results Case 1 had taken amiodarone for 7 months and low T3 syndrome was diagnosed 1 month later.Two years later,he took amiodarone again for 1 month and was

  8. 胺碘酮治疗老年冠心病心律不齐的临床研究%Clinical Research on Amiodarone for the Treatment of Senile Coronary Heart Disease and Arrhythmia

    Institute of Scientific and Technical Information of China (English)

    程红伟

    2015-01-01

    目的:研究分析胺碘酮应用于老年冠心病心律不齐患者的临床治疗中所取得的效果。方法选择本院76例冠心病心律不齐老年患者,选择胺碘酮以及普罗帕酮对患者实施分组治疗,对比两组患者的临床疗效。结果采用胺碘酮的观察组总治疗有效率为95.6%,明显优于对照组(采用普罗帕酮)的76.5%,两组患者临床治疗有效率比较存在明显差异,具有统计学意义(P<0.05);观察组患者的不良反应发生率明显低于对照组患者(P<0.05)。结论针对老年冠心病心律不齐患者,采用胺碘酮进行治疗能够取得明显疗效,建议推广应用。%Objective To study the clinical application of amiodarone treatment in elderly patients with coronary heart disease arrhythmia in multi effect has been achieved. Methods 76 cases of elderly patients with coronary heart disease arrhythmia amiodarone and propafenone in our hospital, choice of implementation of grouping treatment of patients, the clinical efficacy were compared between two groups. Results The effective rate of observation group with amiodarone total treatment was 95.6%, significantly better than the control group (using propafenone) 76.5% (P<0.05). Conclusion In elderly coronary heart disease patients with amiodarone for the treatment of arrhythmia, can obtain obvious effect, application suggestions.

  9. 稳心颗粒联合小剂量胺碘酮治疗心律失常50例%Wenxin Granules Combined with Low-Dose Amiodarone in Treating 50 Cases of Arrhythmia

    Institute of Scientific and Technical Information of China (English)

    戴仁森

    2012-01-01

    目的 观察稳心颗粒联合小剂量胺碘酮治疗心律失常的临床疗效及安全性.方法 选择心律失常患者100例,随机分成两组,每组各50例,对照组给予大剂量的胺碘酮治疗,治疗组给予稳心颗粒联合小剂量胺碘酮治疗.疗程均为4周,观察两组临床疗效及不良反应发生情况.结果 临床总有效率和早搏总有效率对照组为80.00%和70.00%,治疗组为92.00%和88.00%;不良反应对照组有9例,治疗组有4例.结论 稳心颗粒联合小剂量胺碘酮治疗心律失常疗效较好、不良反应少,值得临床推广.%Objective To study the clinical efficacy and safety of Wenxin Granules combined low dose amiodarone in the treatment of arrhythmia. Methods 100 patients with arrhythmia were randomly divided into two groups, 50 cases in each group. The control group was treated by large - dose amiodarone, while the treatment group received Wenxin Granules combined low - dose amiodarone. The treatment course in the two groups was 4 weeks. The clinical efficacy and adverse events were observed. Results The clinical total effective rate and the total effective rate of premature beat was 80.00% and 70.00% in the control group, and 92.00% and 88.00% in the treatment group, respectively. The control group had 9 cases of adverse reactions and the treatment group had 4 cases. Conclusion Wenxin Granules combined with low - dose amiodarone has a good effect and less adverse reactions in the treatment of arrhythmia and is worthy of clinically promoted.

  10. Clinical Experience of Amiodarone Combined with Wenxinkeli in Treating New Atrial Fibrillation%胺碘酮联合稳心颗粒治疗新发心房纤颤的临床体会

    Institute of Scientific and Technical Information of China (English)

    李晓渝

    2014-01-01

    Objective To analyze the clinical efficacy of amiodarone combined with Wenxinkeli in treating new atrial fibrillation. Methods A total of 46 patients with new atrial fibrillation in our hospital from April 2O1O to March 2O14 were se-lected,and then they were divided into control group(23 cases)and observation group(23 cases). The control group was treated with amiodarone combined with verapamil,the observation group was treated with amiodarone combined with Wenxinkeli. Clinical efficacy of two groups were compared. Results The total effective rate of the observation group was higher than that of control group,the difference was statistically significant( PAmiodarone combined with Wenxinkeli has significant clinical efficacy in treating new atrial fibrillation,which,can improve patients'physical fitness and quality of life.%目的:探讨胺碘酮联合稳心颗粒治疗新发心房纤颤的临床疗效。方法选取2O1O年4月-2O14年3月于本院接受治疗的新发心房纤颤患者46例作为研究对象。将其分成对照组及观察组,各23例。对照组给予盐酸胺碘酮联合维拉帕米治疗;观察组给予胺碘酮及稳心颗粒的联合治疗。比较两组患者的临床疗效。结果观察组临床治疗的总有效率高于对照组,差异有统计学意义( P

  11. Efifcacy of Amiodarone Combined With Metoprolol Treatment of Coronary Heart Arrhythmia%胺碘酮联合美托洛尔治疗冠心病心律不齐的疗效分析

    Institute of Scientific and Technical Information of China (English)

    赵强; 刘泉

    2015-01-01

    Objective To observe the effect of amiodarone in combination with metoprolol in treatment of patients with coronary heart arrhythmia. Methods Information our hospital’s 106 cases of patients selected from July 2013 to July 2014 with coronary heart arrhythmia were randomly divided into study group and control group , each group had 53 cases. the study group amiodarone used US metoprolol treatment, the control group, only used amiodarone treatment, the clinical effect of two groups were compared. Results Heart rate, blood pressure in the study group were significantly better than the control group (P 0.05). Conclusion The effect of Amiodarone combined with metoprolol in treatment of coronary heart arrhythmia was more signiifcant.%目的:观察胺碘酮联合美托洛尔治疗冠心病心律不齐的疗效。方法资料选取2013年7月~2014年7月本院收治的106例冠心病心律不齐患者,将其随机分为研究组和对照组,每组均为53例,研究组应用胺碘酮联合美托洛尔治疗,对照组仅应用胺碘酮治疗,比较两组的临床疗效。结果研究组的心率、血压改善均明显优于对照组(P<0.05);研究组不良反应发生率7.55%与对照组9.43%比较无明显差异(P>0.05)。结论胺碘酮联合美托洛尔治疗冠心病心律不齐的疗效较为显著。

  12. Clinical application of Amiodarone combined with Irbesartan on treatment in paroxysmal atrial fibrillation patients%胺碘酮联合厄贝沙坦治疗阵发性心房颤动疗效观察

    Institute of Scientific and Technical Information of China (English)

    徐爱琴

    2011-01-01

    Aim To observe the effect of Amiodarone combined with Irbesartan treating paroxysmal atrial fibrillation. Method From May 2008 to May 2010,83 paroxysmal atrial fibrillation patients were enrolled and randonly divided into treatment group and control group. The treatmrent group was treated with Amiodarone and Irbesartan, and the control group only with Amiodarone. All the patients had been observed for 12 months. Results The sinus rhythm maintenance rate in treatment group was higher than that in control group and the atrial diameter decreased remarkably in treatment group than in control group (P < 0.05). Conclusion Irbesartan can inhibit e lectronic and anatomical remodeling of atrial, reduce the recurrence rate of atrial fibrillation, prevent persistence of atrial fibrillation and maintain the sinus rhythm rate more effectively than Amiodarone only,and it can also inhibit the increase of the left atrial diameter.%目的 观察胺碘酮联合厄贝沙坦治疗阵发性房颤的疗效.方法 选择2008年5月~2010年5月期间该院83例阵发性房颤患者,随机分为治疗组(胺碘酮+厄贝沙坦)和对照组(单用胺碘酮),疗程均为一年.结果 治疗组窦性心率维持率明显高于对照组(P<0.05),左房内径亦有显著性缩小(P<0.05).结论 厄贝沙坦具有抑制心房电重构和解剖重构,降低房颤复发率及阻止房颤持续的作用,胺碘酮联合厄贝沙坦治疗阵发性心房颤动维持窦性心率的疗效优于单用胺碘酮,且能抑制左房扩大.

  13. Application Effect of Amiodarone on Patients With Congestive Heart Failure and Arrhythmias%心力衰竭并心律失常患者胺碘酮的应用效果观察

    Institute of Scientific and Technical Information of China (English)

    雷娜

    2015-01-01

    目的 研究探讨对心力衰竭合并心律失常患者应用胺碘酮的临床疗效.方法 选择我院心内科自2013年1月~2015年1月收治的80例心力衰竭合并心律失常的患者作为研究对象,所有患者均予以胺碘酮进行治疗,对其临床效果进行回顾性分析.结果 经胺碘酮治疗研究患者的总有效率为90.0%,不良反应发生率为8.7%,且心脏功能较治疗前改善(P<0.05),差异具有统计学意义.结论 在临床中应用胺碘酮治疗心力衰竭合并心律失常患者具有有效率高及不良反应率低等优点,并且可显著改善患者的心脏功能.%Objective To investigate the clinical efifcacy in patients with heart failure, arrhythmia amiodarone. Methods Hospital Cardiology from 80 cases of patients with heart failure with cardiac arrhythmia from January 2013 to January 2015 admitted to the study, all patients were to be treated with amiodarone were retrospectively analyzed clinical Results . Results Amiodarone therapy in patients with total effective rate was 90.0% incidence of adverse reactions was 8.7%, and heart function was significantly improved compared with before treatment (P < 0.05), a statistically significant difference. Conclusion The clinical application of amiodarone treatment of heart arrhythmia the patient has high efficiency and low adverse reaction rate, etc., and can significantly improve the patient's cardiac function.

  14. 胺碘酮在心力衰竭合并室性心律失常中的临床应用研究%Clinical Analysis of Amiodarone for Heart Failure Patients of Ventricular Arrhythmia

    Institute of Scientific and Technical Information of China (English)

    齐芳

    2014-01-01

    Objective To investigate the clinical effect of amiodarone on heart failure complicated with ventricular. Methods 80 cases with chronic heart failure complicated with ventricular arrhythmia were selected and randomly divided into observation group and control group. The two groups were given routine anti heart failure treatment,and amiodarone was given to observation group at the same time. The efficacy of the two groups was evaluated. Results The total effective rate, the left ventricular ejection fraction and heart rate in the observation group after treatment compared with those in the control group after treatment, the difference was statistical y significant (P <0.05). Conclusion The curative effect of amiodarone on heart failure complicated with ventricular arrhythmiatreatment is significant,and amiodarone is helpful to improve clinical symptoms and signs.%目的:探讨胺碘酮在心力衰竭合并室性心律失常中的临床应用效果。方法:选取来我院进行治疗的心力衰竭合并室性心律失常患者82例作为研究对象,随机分为观察组和对照组,所有患者均给予常规心力衰竭治疗,此外,观察组患者给予胺碘酮。比较两组患者的治疗效果以及组患者左室射血分数和心率。结果:治疗后观察组患者的总有效率、左室射血分数和心率与观察组相比,差异有统计学意义(P<0.05)。结论:胺碘酮治疗心力衰竭合并室性心律失常疗效显著,值得临床推广。

  15. Effect of Wenxin Particle Combined with Amiodarone on Premature Ventricular Beats%步长稳心颗粒联合胺碘酮治疗室性期前收缩的疗效观察

    Institute of Scientific and Technical Information of China (English)

    郑硕

    2012-01-01

    Objective To evaluate the therapeutic efficacy and safety of Wenxin Particle combined with amiodarone in the treatment of premature ventricular beats.Methods 78 cases with premature ventricular beats were divided into observation group(n=40)and control group(n=38).The observation group was treated with Wenxin Particle and amiodarone,the control group was treated amiodarone with only.The improvement of clinical symptoms and premature ventricular beats and the side effects were observed.Results Total effective rate was 78.94% in control group,92.50% in observation group.There was a significantly statistical difference between two groups(P<0.05).Conclusion Wenxin Particle combined with amiodarone in treating premature ventricular beats can improve the clinical effect and have no obvious side effect,so it is worth being used widely.%目的 观察步长稳心颗粒联合胺碘酮治疗室性期前收缩的临床疗效及安全性.方法 将78例室性期前收缩患者随机分为治疗组和对照组.治疗组40例,予以步长稳心颗粒加胺碘酮治疗;对照组38例,单用胺碘酮治疗.观察两组患者治疗前后临床症状、室性期前收缩改善情况及不良反应.结果 治疗组总有效率92.50%,对照组总有效率78.94%,两组差异有统计学意义(P<0.05).结论 步长稳心颗粒联合胺碘酮治疗室性期前收缩可以显著提高治疗效果,无明显毒副作用,值得临床推广.

  16. 普罗帕酮和胺碘酮治疗阵发性室上性心动过速的临床分析%Clinical analysis of propafenone and amiodarone in the treatment of paroxysmal suproventricular tachycardia

    Institute of Scientific and Technical Information of China (English)

    税小波; 高建军; 邹玉刚; 税朝东; 税朝莲

    2015-01-01

    目的:探讨分别运用普罗帕酮和胺碘酮治疗阵发性室上性心动过速的临床效果。方法:2010年11月-2014年7月收治阵发性室上性心动过速患者64例,随机分为观察组和对照组,各32例。对照组和观察组分别采用普罗帕酮和胺碘酮进行治疗,比较两组的治疗效果。结果:观察组转复时间明显长于对照组,不良反应率明显低于对照组,组间比较差异均具有统计学意义(P<0.05)。观察组临床总有效率(87.50%)同对照组(90.63%)相比差异无统计学意义(P>0.05)。结论:在阵发性室上性心动过速的临床治疗中,普罗帕酮和胺碘酮均有良好的治疗效果,但普罗帕酮起效更快,胺碘酮的安全性更高。%Objective:To explore the clinical effect of propafenone and amiodarone used respectively in the treatment of paroxysmal suproventricular tachycardia.Methods: 64 cases of paroxysmal suproventricular tachycardia were selected from November 2010 to July 2014.They were divided into the observation group and the control group with 32 cases in each.The control group and the observation group were treated with propafenone and amiodarone respectively.We compared the therapeutic effect of the two groups.Results:The converting time of the observation group was obviously higher than that of the control group,and the adverse reaction rate was significantly lower than that of the control group.The differences between the two groups were statistically significant(P0.05).Conclusion:Propafenone and amiodarone in the treatment of paroxysmal suproventricular tachycardia had good treatment effect,but amiodarone had faster effect and higher safety.

  17. Efficacy and safety of small dose of amiodarone in treatment of arrhythmia%小剂量胺碘酮在心律失常治疗中的疗效及安全性

    Institute of Scientific and Technical Information of China (English)

    冯杰

    2015-01-01

    目的:探讨小剂量胺碘酮在心律失常治疗中的疗效和安全性。方法将该院2013年10月—2014年9月医治的54例心律失常患者随机分为常规组与观察组。两组患者在常规治疗基础上分别使用普鲁帕酮与小剂量的胺碘酮进行治疗。比较两组患者不同药物治疗后总有效率和不良反应情况。结果在治疗后,观察组、对照组总有效率分别为88.89%(24/27)、59.26%(16/27),观察组疗效优于对照组(P<0.05);观察组不良反应情况明显低于对照组(P<0.05)。结论使用小剂量胺碘酮治疗室性心律失常,治疗效果明显,安全、有效,值得推广。%Objective To investigate the efficacy and safety of small dose of amiodarone in treatment of arrhythmia. Methods 54 patients with arrhythmia were divided into control group and observation group randomly. Two groups of patients were given propafenone and small dose of amiodarone on the basis of conventional treatment. the clinical efficacy and adverse reactions of propafenone situation with a small dose of amiodarone. Results after treatment, the observation group, the control group total effectiveness respectively is 88.89% (24/27), 59.26% (16/27), the effect of observation group is better than control group (P <0.05); the adverse reactions observed was significantly lower than control group (P < 0.05). Conclusion the use of small dose amiodarone in therapeutic room, arrhythmia, obvious curative effect, safety, effective, worthy of promotion.

  18. Stochastic models of intracellular calcium signals

    International Nuclear Information System (INIS)

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed

  19. Strategies for Intracellular Survival of Burkholderia pseudomallei.

    Science.gov (United States)

    Allwood, Elizabeth M; Devenish, Rodney J; Prescott, Mark; Adler, Ben; Boyce, John D

    2011-01-01

    Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality that is prevalent in tropical regions of the world. A key component of the pathogenesis of melioidosis is the ability of B. pseudomallei to enter, survive, and replicate within mammalian host cells. For non-phagocytic cells, bacterial adhesins have been identified both on the bacterial surface and associated with Type 4 pili. Cell invasion involves components of one or more of the three Type 3 Secretion System clusters, which also mediate, at least in part, the escape of bacteria from the endosome into the cytoplasm, where bacteria move by actin-based motility. The mechanism of actin-based motility is not clearly understood, but appears to differ from characterized mechanisms in other bacterial species. A small proportion of intracellular bacteria is targeted by host cell autophagy, involving direct recruitment of LC3 to endosomes rather than through uptake by canonical autophagosomes. However, the majority of bacterial cells are able to circumvent autophagy and other intracellular defense mechanisms such as the induction of inducible nitric oxide synthase, and then replicate in the cytoplasm and spread to adjacent cells via membrane fusion, resulting in the formation of multi-nucleated giant cells. A potential role for host cell ubiquitin in the autophagic response to bacterial infection has recently been proposed. PMID:22007185

  20. Stochastic models of intracellular calcium signals

    Energy Technology Data Exchange (ETDEWEB)

    Rüdiger, Sten, E-mail: sten.ruediger@physik.hu-berlin.de

    2014-01-10

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

  1. Mechanisms of cellular invasion by intracellular parasites.

    Science.gov (United States)

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  2. Microtubule-Destabilizing Agents: Structural and Mechanistic Insights from the Interaction of Colchicine and Vinblastine with Tubulin

    Science.gov (United States)

    Gigant, B.; Cormier, A.; Dorléans, A.; Ravelli, R. B. G.; Knossow, M.

    Microtubules (MTs) are dynamic structures of the eukaryotic cytoskeleton that, during cell division, form the mitotic spindle. Perturbing them leads to mitotic arrest and ultimately to cell death. Consistently, MTs and their building block, αβ tubulin, are one of the best characterized targets in anti-cancer chemotherapy. Drugs that interfere with MTs either stabilize or destabilize them. The latter class is the subject of this review. These ligands bind to the colchicine site or to the vinca domain, two distinct sites located at a distance from each other on tubulin. Nevertheless the effects of both classes of ligands share a common theme, they prevent the formation of MT specific contacts, therefore triggering their disassembly.

  3. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, Brian S.; Sun, Xiangjie; Chung, Changik [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States); Whittaker, Gary R., E-mail: grw7@cornell.edu [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca NY 14853 (United States); New York Center of Excellence for Influenza Research and Surveillance, University of Rochester Medical Center, Rochester NY 14627 (United States)

    2012-12-05

    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  4. Acquisition of a novel eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site confers intracellular cleavage of an H7N7 influenza virus hemagglutinin

    International Nuclear Information System (INIS)

    A critical feature of highly pathogenic avian influenza viruses (H5N1 and H7N7) is the efficient intracellular cleavage of the hemagglutinin (HA) protein. H7N7 viruses also exist in equine species, and a unique feature of the equine H7N7 HA is the presence of an eleven amino acid insertion directly N-terminal to a tetrabasic cleavage site. Here, we show that three histidine residues within the unique insertion of the equine H7N7 HA are essential for intracellular cleavage. An asparagine residue within the insertion-derived glycosylation site was also found to be essential for intracellular cleavage. The presence of the histidine residues also appear to be involved in triggering fusion, since mutation of the histidine residues resulted in a destabilizing effect. Importantly, the addition of a tetrabasic site and the eleven amino acid insertion conferred efficient intracellular cleavage to the HA of an H7N3 low pathogenicity avian influenza virus. Our studies show that acquisition of the eleven amino acid insertion offers an alternative mechanism for intracellular cleavage of influenza HA.

  5. Thermodynamic Destabilization of Ti-O Solid Solution by H2 and Deoxygenation of Ti Using Mg.

    Science.gov (United States)

    Zhang, Ying; Fang, Zhigang Zak; Sun, Pei; Zhang, Tuoyang; Xia, Yang; Zhou, Chengshang; Huang, Zhe

    2016-06-01

    Reactive metals including Ti, Zr, Hf, and V, among others, have a strong chemical affinity to oxygen, which makes them difficult to produce and costly to use. It is especially challenging to produce pure or metal alloy powders of these elements when extremely low oxygen content is required, because they have high solubility for oxygen, and the solid solution of these metals with oxygen is often more stable thermodynamically than their oxides. We report a novel thermochemical approach to destabilize Ti(O) solid solutions using hydrogen, thus enabling deoxygenation of Ti powder using Mg, which has not been possible before because of the thermodynamic stability of Ti(O) solid solutions relative to MgO. The work on Ti serves as an example for other reactive metals. Both analytical modeling and experimental results show that hydrogen can indeed increase the oxygen potential of Ti-O solid solution alloys; in other words, the stability of Ti-O solid solutions is effectively decreased, thus increasing the thermodynamic driving force for Mg to react with oxygen in Ti. Because hydrogen can be easily removed from Ti by a simple heat treatment, it is used only as a temporary alloying element to destabilize the Ti-O systems. The thermodynamic approach described here is a breakthrough and is applicable to a range of different materials. This work is expected to provide an enabling solution to overcome one of the key scientific and technological hurdles to the additive manufacturing of metals, which is emerging rapidly as the future of the manufacturing industry. PMID:27196140

  6. Destabilization of Heterologous Proteins Mediated by the GSK3β Phosphorylation Domain of the β-Catenin Protein

    Directory of Open Access Journals (Sweden)

    Yuhan Kong

    2013-11-01

    Full Text Available Background and Aims: Wnt/β-catenin signaling plays important roles in development and cellular processes. The hallmark of canonical Wnt signaling activation is the stabilization of β-catenin protein in cytoplasm and/or nucleus. The stability of β-catenin is the key to its biological functions and is controlled by the phosphorylation of its amino-terminal degradation domain. Aberrant activation of β-catenin signaling has been implicated in the development of human cancers. It has been recently suggested that GSK3βmay play an essential role in regulating global protein turnover. Here, we investigate if the GSK3β phosphorylation site-containing degradation domain of β-catenin is sufficient to destabilize heterologous proteins. Methods and Results: We engineer chimeric proteins by fusing β-catenin degradation domain at the N- and/or C-termini of the enhanced green fluorescent protein (eGFP. In both transient and stable expression experiments, the chimeric GFP proteins exhibit a significantly decreased stability, which can be effectively antagonized by lithium and Wnt1. An activating mutation in the destruction domain significantly stabilizes the fusion protein. Furthermore, GSK3 inhibitor SB-216763 effectively increases the GFP signal of the fusion protein. Conversely, the inhibition of Wnt signaling with tankyrase inhibitor XAV939 results in a decrease in GFP signal of the fusion proteins, while these small molecules have no significant effects on the mutant destruction domain-GFP fusion protein. Conclusion: Our findings strongly suggest that the β-catenin degradation domain may be sufficient to destabilize heterologous proteins in Wnt signaling-dependent manner. It is conceivable that the chimeric GFP proteins may be used as a functional reporter to measure the dynamic status of β-catenin signaling, and to identify potential anticancer drugs that target β-catenin signaling.

  7. The MitCHAP-60 disease is due to entropic destabilization of the human mitochondrial Hsp60 oligomer.

    Science.gov (United States)

    Parnas, Avital; Nadler, Michal; Nisemblat, Shahar; Horovitz, Amnon; Mandel, Hanna; Azem, Abdussalam

    2009-10-01

    The 60-kDa heat shock protein (mHsp60) is a vital cellular complex that mediates the folding of many of the mitochondrial proteins. Its function is executed in cooperation with the co-chaperonin, mHsp10, and requires ATP. Recently, the discovery of a new mHsp60-associated neurodegenerative disorder, MitCHAP-60 disease, has been reported. The disease is caused by a point mutation at position 3 (D3G) of the mature mitochondrial Hsp60 protein, which renders it unable to complement the deletion of the homologous bacterial protein in Escherichia coli (Magen, D., Georgopoulos, C., Bross, P., Ang, D., Segev, Y., Goldsher, D., Nemirovski, A., Shahar, E., Ravid, S., Luder, A., Heno, B., Gershoni-Baruch, R., Skorecki, K., and Mandel, H. (2008) Am. J. Hum. Genet. 83, 30-42). The molecular basis of the MitCHAP-60 disease is still unknown. In this study, we present an in vitro structural and functional analysis of the purified wild-type human mHsp60 and the MitCHAP-60 mutant. We show that the D3G mutation leads to destabilization of the mHsp60 oligomer and causes its disassembly at low protein concentrations. We also show that the mutant protein has impaired protein folding and ATPase activities. An additional mutant that lacks the first three amino acids (N-del), including Asp-3, is similarly impaired in refolding activity. Surprisingly, however, this mutant exhibits profound stabilization of its oligomeric structure. These results suggest that the D3G mutation leads to entropic destabilization of the mHsp60 oligomer, which severely impairs its chaperone function, thereby causing the disease.

  8. Thermodynamic Destabilization of Ti-O Solid Solution by H2 and Deoxygenation of Ti Using Mg.

    Science.gov (United States)

    Zhang, Ying; Fang, Zhigang Zak; Sun, Pei; Zhang, Tuoyang; Xia, Yang; Zhou, Chengshang; Huang, Zhe

    2016-06-01

    Reactive metals including Ti, Zr, Hf, and V, among others, have a strong chemical affinity to oxygen, which makes them difficult to produce and costly to use. It is especially challenging to produce pure or metal alloy powders of these elements when extremely low oxygen content is required, because they have high solubility for oxygen, and the solid solution of these metals with oxygen is often more stable thermodynamically than their oxides. We report a novel thermochemical approach to destabilize Ti(O) solid solutions using hydrogen, thus enabling deoxygenation of Ti powder using Mg, which has not been possible before because of the thermodynamic stability of Ti(O) solid solutions relative to MgO. The work on Ti serves as an example for other reactive metals. Both analytical modeling and experimental results show that hydrogen can indeed increase the oxygen potential of Ti-O solid solution alloys; in other words, the stability of Ti-O solid solutions is effectively decreased, thus increasing the thermodynamic driving force for Mg to react with oxygen in Ti. Because hydrogen can be easily removed from Ti by a simple heat treatment, it is used only as a temporary alloying element to destabilize the Ti-O systems. The thermodynamic approach described here is a breakthrough and is applicable to a range of different materials. This work is expected to provide an enabling solution to overcome one of the key scientific and technological hurdles to the additive manufacturing of metals, which is emerging rapidly as the future of the manufacturing industry.

  9. Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation

    Science.gov (United States)

    Robinson, Erik; Kaushal, Sunjay; Alaboson, Justice; Sharma, Sudhish; Belagodu, Amogh; Watkins, Claire; Walker, Brandon; Webster, Gregory; McCarthy, Patrick; Ho, Dean

    2016-02-01

    Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were

  10. The microtubule destabilizing protein stathmin controls the transition from dividing neuronal precursors to postmitotic neurons during adult hippocampal neurogenesis

    NARCIS (Netherlands)

    Boekhoorn, Karin; van Dis, Vera; Goedknegt, Erika; Sobel, André; Lucassen, Paul J; Hoogenraad, Casper C

    2014-01-01

    The hippocampus is one of the two areas in the mammalian brain where adult neurogenesis occurs. Adult neurogenesis is well known to be involved in hippocampal physiological functions as well as pathophysiological conditions. Microtubules (MTs), providing intracellular transport, stability, and trans

  11. Intracellular signalling by C-peptide.

    Science.gov (United States)

    Hills, Claire E; Brunskill, Nigel J

    2008-01-01

    C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na(+)/K(+) ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes. PMID:18382618

  12. Intracellular Signalling by C-Peptide

    Directory of Open Access Journals (Sweden)

    Claire E. Hills

    2008-01-01

    Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

  13. Cytoskeletal network morphology regulates intracellular transport dynamics

    CERN Document Server

    Ando, David; Huang, Kerwyn Casey; Gopinathan, Ajay

    2016-01-01

    Intracellular transport is essential for maintaining proper cellular function in most eukaryotic cells, with perturbations in active transport resulting in several types of disease. Efficient delivery of critical cargos to specific locations is accomplished through a combination of passive diffusion and active transport by molecular motors that ballistically move along a network of cytoskeletal filaments. Although motor-based transport is known to be necessary to overcome cytoplasmic crowding and the limited range of diffusion within reasonable time scales, the topological features of the cytoskeletal network that regulate transport efficiency and robustness have not been established. Using a continuum diffusion model, we observed that the time required for cellular transport was minimized when the network was localized near the nucleus. In simulations that explicitly incorporated network spatial architectures, total filament mass was the primary driver of network transit times. However, filament traps that r...

  14. Intracellular calcium release modulates polycystin-2 trafficking

    Directory of Open Access Journals (Sweden)

    Miyakawa Ayako

    2013-02-01

    Full Text Available Abstract Background Polycystin-2 (PC2, encoded by the gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD, functions as a calcium (Ca2+ permeable ion channel. Considerable controversy remains regarding the subcellular localization and signaling function of PC2 in kidney cells. Methods We investigated the subcellular PC2 localization by immunocytochemistry and confocal microscopy in primary cultures of human and rat proximal tubule cells after stimulating cytosolic Ca2+ signaling. Plasma membrane (PM Ca2+ permeability was evaluated by Fura-2 manganese quenching using time-lapse fluorescence microscopy. Results We demonstrated that PC2 exhibits a dynamic subcellular localization pattern. In unstimulated human or rat proximal tubule cells, PC2 exhibited a cytosolic/reticular distribution. Treatments with agents that in various ways affect the Ca2+ signaling machinery, those being ATP, bradykinin, ionomycin, CPA or thapsigargin, resulted in increased PC2 immunostaining in the PM. Exposing cells to the steroid hormone ouabain, known to trigger Ca2+ oscillations in kidney cells, caused increased PC2 in the PM and increased PM Ca2+ permeability. Intracellular Ca2+ buffering with BAPTA, inositol 1,4,5-trisphosphate receptor (InsP3R inhibition with 2-aminoethoxydiphenyl borate (2-APB or Ca2+/Calmodulin-dependent kinase inhibition with KN-93 completely abolished ouabain-stimulated PC2 translocation to the PM. Conclusions These novel findings demonstrate intracellular Ca2+-dependent PC2 trafficking in human and rat kidney cells, which may provide new insight into cyst formations in ADPKD.

  15. Antibody-Fc receptor interactions in protection against intracellular pathogens.

    Science.gov (United States)

    Joller, Nicole; Weber, Stefan S; Oxenius, Annette

    2011-04-01

    Intracellular pathogen-specific antibodies (Abs) can contribute to host protection by a number of different mechanisms. Ab opsonization of pathogens residing outside a host cell can prevent infection of target cells either via neutralization of the critical surface epitopes required for host cell entry, complement-mediated degradation, or via subsequent intracellular degradation. In the case of intracellular localization, Abs can bind to infected cells and thus mark them for destruction by Fc receptor (FcR)-bearing effector cells. This review focuses on the protective role of Abs against intracellular bacteria and parasites involving FcR interactions that modulate the intracellular trafficking of the pathogen, the ability of FcRs to interfere with the establishment of an intracellular replicative niche and the involvement of FcRs to modulate pathogen-specific T-cell responses. PMID:21413006

  16. Intracellular Environment-Responsive Stabilization of Polymer Vesicles Formed from Head-Tail Type Polycations Composed of a Polyamidoamine Dendron and Poly(L-lysine

    Directory of Open Access Journals (Sweden)

    Kenji Kono

    2013-09-01

    Full Text Available For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine tail (PAMAM dendron-PLL, through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy.

  17. Biosensor Scheme for the Determination of Intracellular Pressure of Erythrocyte

    Directory of Open Access Journals (Sweden)

    Yu.S. Nagornov

    2016-03-01

    Full Text Available The paper presents a scheme of the biosensor for determining the intracellular pressure of erythrocytes. The possibility of measuring of the volume and area of the erythrocyte is provided in a biosensor to determine the value intracellular pressure. In MEMS this creates flow that enters into Coulter capacitive sensor through the rate control system and then in the system of signal transmitting. The definition of erythrocyte volume and calculation of intracellular pressure occur in the computer system.

  18. Amiodarone induced pulmonary interstitial fibrosis and respiratory failure:a case report and literature review%胺碘酮致肺间质纤维化呼吸衰竭1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    吴巧珍; 胡晓蕴; 徐东风; 赵金泉

    2013-01-01

    Objective To intensify the knowledge about amiodarone induced pulmonary interstitial fibrosis,and improve the level of diagnosis and treatment.Methods A retrospective analysis of one case of amiodarone induced pulmonary interstitial fibrosis with literature review was conducted.Results A 60-year-old patient,who received inappropriate high dose of amiodarone (total 30 g) for 50 days due to paroxysmal supraventicuar fachycardia,was admitted to hospital with chief complaint of cough,fatigure and chilly for two days.The symptoms of the patient included short of breath,sychnosphygmia,cyanosis of lip and a nail bed,bilateral moist rales and crackles.Laboratory tests revealed the following levels and values:white blood cell 11.18 × 109/L,neutrophilic granulocyte 0.87,alanine transaminase 70 U/L,albumin 26.3 g/L,total protein 55.9 g/L,C-reactive protein 102.50 mg/L,pH 7.441,PO2 34.80 mm Hg,PCO2 29 mm Hg,SaO268.9 %.CT scan revealed bilateral pulmonary interstitial fibrosis,especially in the right lung.Lung function testing indicated severe mixed ventilation function obstacle and severe decrease in pulmonary diffusion capacity.The diagnosis was amiodarone induced pulmonary interstitial fibrosis with infection and type Ⅰ respiratory failure.After withdrawing the drug,treatments with inhaling oxygen through a face mask,levofloxacin,cefoperazone/sulbactam,vancomycin,fluconazole,corticosteroid and acetylcysteine therapy were implemented,and the results showed clear clinical,functional and radiological improvement.The treatment with corticosteroid and acetylcysteine totally lasted for seven months,and then a seven months follow up was carried out.The results showed the patient had no obvious short of breath after activities,and obvious fibrosis change was not observed in the lung CT images.Conclusions Pulmonary interstitial fibrosis is one of the common adverse reactions of amiodarone.It is recommended that the benefit/risk ratio should be evaluated at the beginning of

  19. 胺碘酮联合β受体阻断药治疗冠脉搭桥术后早期新发房颤%The Effect of Amiodarone and β Blockers on 102 Cases of the Early Arrhythmia after Coronary Artery Bypass Grafting

    Institute of Scientific and Technical Information of China (English)

    陈雪; 唐泓波; 胡大清; 曾宁

    2012-01-01

    [目的]:观察胺碘酮联合β受体阻断药治疗冠状动脉搭桥(CABG)术后早期新发房颤(AF)的效果和不良反应.[方法]:102例CABG术后早期发生快室率房颤患者随机分为对照组48例和治疗组54例,对照组给予胺碘酮注射液静脉泵入,治疗组在对照组基础上加用艾司洛尔注射液或美托洛尔注射液.观察心电监护、心电图及24h动态心电图心率变化,比较两组1周内转复为窦性心律的有效率和不良反应发生率.[结果]:两组有效率分别为79.1%和94.4%,差异有统计学意义(P<0.05).两组不良反应发生率比较,差异无统计学意义(P>0.05).[结论]:胺碘酮联合艾司洛尔或美托洛尔转复CABG术后早期新发房颤效果优于单用胺碘酮.不良反应少,安全性高,值得临床推荐.%Objective:To investigate the effect and side effect of Amiodarone and β blockers on the arrhythmia after Coronary artery bypass grafting( CABG). Methods; 102 AF patients after CABG were randomly divided into two groups; Amiodarone group and Amiodarone and β blockers combined group. There were 48 cases with Amiodarone alone, 54 cases with Amiodarone and β blockers. The heart rale of ambulatory Holter monitor,electrocardiogram ( ECG) and dynamic electrocardiogram were recorded. The effective rate and complication rate of the two groups whose heart rate turned to sinus rhythm in one week were recorded. Results:The effective rate of combined group was superior to the Amiodarone group, 94.4% to 79.1 % (P 0.05). Conclusion: Using combined group on AF patients after CABG can achieve better results comparing to the Amiodarone group. Side effect is low and the combination drug therapy is worth to clinical recommenclation.

  20. Analysis on curative effect of metoprolol combined with amiodarone in patients with congestive heart failure and taehyarrhythmia%胺碘酮联合美托洛尔治疗充血性心力衰竭患者快速型室性心律失常的临床效果分析

    Institute of Scientific and Technical Information of China (English)

    邓志元

    2014-01-01

    目的:观察美托洛尔联合胺碘酮治疗充血性心力衰竭并快速性心律失常的治疗效果。方法:选择慢性心功能不全合并室性心律失常43例。心功能按NYHA分级为Ⅱ~Ⅳ级,随机分为胺碘酮治疗组、胺碘酮+美托洛尔治疗组。结果:胺碘酮+美托洛尔治疗组临床有效率90%(18/20),胺碘酮治疗组的总有效率60.87%(14/23)。2组差异有统计学意义(P<0.05)。结论:联合应用胺碘酮及美托洛尔治疗慢性心功能不全合并室性心律失常疗效明显优于单用胺碘酮或美托洛尔,不良反应无增加。%Objective:To investigate the curative effect of metoprolol combined with amiodarone in patients with congestive heart failure and taehyarrhythmia .Methods:A total of 43 NYHA classⅡ-Ⅳpatients with CHF complicated by ventricular arrhythmia were randomly divided into amiodarone group and amiodarone +metoprolol group .The therapeutic effects were evaluated .Results:The clinical effective rate was 90%(18/20)in amiodarone+metoprolol group,while that was 60.87%(14/23)in amiodarone group,the difference was statisti-cally significant(P<0.05).Conclusion:The combination of amiodarone and metoprolol could produce better effect than amiodarone alone in the treatment of CHF complicated by ventricular arrhythmia .

  1. The treatment effect and relapse prevention of cardioversion of atrial fibrillation with Wenxin granules and amiodarone%稳心颗粒与胺碘酮联合转复心房颤动及预防复发的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张玉榕; 史继利; 贾荣波

    2011-01-01

    目的 观察稳心颗粒联合胺碘酮转复及预防心房颤动复发的疗效.方法 选择慢性心房颤动患者共60例,随机分为稳心颗粒联合胺碘酮组(A组)及单纯胺碘酮组(B组)各30例,所有患者入院后静脉应用胺碘酮24 h同时口服胺碘酮由600 mg/d逐渐减量至200 mg/d维持,另外A组同时给予口服步长稳心颗粒(9 g,3次/d)共4周.观察2组患者4周内转复窦性心律情况及半年内复发情况.结果 第2、3、4周内累积转复窦性心律例数A组显著高于B组(分别是73.3%与43.3%,x2=5.55:83.3%与63.3%,x2=3.07;90.0%与66.7%,x2=4.81;P均<0.05),半年内复发B组有高于A组的趋势.结论 稳心颗粒联合应用胺碘酮转复心房颤动疗效优于单纯应用胺碘酮,并且半年内复发率可能更低.%Objective To observe the treatment effect and relapse prevention of cardioversion of atrial fibrillation with Wenxin granules and amiodarone. Methods Sixty patients of chronic atrial fibrillation were divided randomly into treatment of Wenxin granules and amiodarone group (group A) and treatment of simple amiodarone gorup(group B),Thirty cases in each group. All cases were treated with amiodarone by intravenous drip along with oral amiodarone. Thirty cases in group A were treated with Wenxin granules (9 grams,per day) additionally for 4 weeks. Results Patients in group A resumed normal sinus rhythm significantly higher than that in group B. The increasing relapse tendency of atrial fibrillation was higher in group B within 6 months. Conclusion Drug combination with Wenxin granules and amiodarone has better effect than simple amiodarone in the relapse prevention of cardioversion of atrial fibrillation.

  2. Strategies of Intracellular Pathogens for Obtaining Iron from the Environment

    Directory of Open Access Journals (Sweden)

    Nidia Leon-Sicairos

    2015-01-01

    Full Text Available Most microorganisms are destroyed by the host tissues through processes that usually involve phagocytosis and lysosomal disruption. However, some organisms, called intracellular pathogens, are capable of avoiding destruction by growing inside macrophages or other cells. During infection with intracellular pathogenic microorganisms, the element iron is required by both the host cell and the pathogen that inhabits the host cell. This minireview focuses on how intracellular pathogens use multiple strategies to obtain nutritional iron from the intracellular environment in order to use this element for replication. Additionally, the implications of these mechanisms for iron acquisition in the pathogen-host relationship are discussed.

  3. Catechins and procyanidins of Ginkgo biloba show potent activities towards the inhibition of β-amyloid peptide aggregation and destabilization of preformed fibrils.

    Science.gov (United States)

    Xie, Haiyan; Wang, Jing-Rong; Yau, Lee-Fong; Liu, Yong; Liu, Liang; Han, Quan-Bin; Zhao, Zhongzhen; Jiang, Zhi-Hong

    2014-04-22

    Catechins and procyanidins, together with flavonoid glycosides and terpene trilactones, are three important categories of components in the standard extract of Ginkgo biloba leaves (EGb761). In this research, catechins and proanthocyanidins were found to exist in both the extract of Ginkgo leaves and Ginkgo products. By comparing with reference compounds, six of them were identified as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (-)-epigallocatechin and procyanidins B1 and B3. The activities of these polyphenols in the inhibition of Aβ42 aggregation and the destabilization of preformed fibrils were evaluated using biochemical assays, which showed that all six of the polyphenols, as well as a fraction of the extract of Ginkgo biloba leaves (EGb) containing catechins and procyanidins, exerted potent inhibitory activities towards Aβ42 aggregation and could also destabilize the performed fibrils. Catechins and procyanidins can therefore be regarded as the potent active constituents of EGb761 in terms of their inhibition of Aβ42 aggregation and destabilization of the fibrils. Although quantitative mass spectroscopic analysis revealed that the catechins and procyanidins are only present in low concentrations in EGb761, these components should be studied in greater detail because of their potent inhibitory effects towards Aβ42 aggregation and their ability to destabilize preformed fibrils, especially during the quality control of Ginkgo leaves and the manufacture of Ginkgo products.

  4. Catechins and Procyanidins of Ginkgo biloba Show Potent Activities towards the Inhibition of β-Amyloid Peptide Aggregation and Destabilization of Preformed Fibrils

    Directory of Open Access Journals (Sweden)

    Haiyan Xie

    2014-04-01

    Full Text Available Catechins and procyanidins, together with flavonoid glycosides and terpene trilactones, are three important categories of components in the standard extract of Ginkgo biloba leaves (EGb761. In this research, catechins and proanthocyanidins were found to exist in both the extract of Ginkgo leaves and Ginkgo products. By comparing with reference compounds, six of them were identified as (+-catechin, (−-epicatechin, (−-gallocatechin, (−-epigallocatechin and procyanidins B1 and B3. The activities of these polyphenols in the inhibition of Aβ42 aggregation and the destabilization of preformed fibrils were evaluated using biochemical assays, which showed that all six of the polyphenols, as well as a fraction of the extract of Ginkgo biloba leaves (EGb containing catechins and procyanidins, exerted potent inhibitory activities towards Aβ42 aggregation and could also destabilize the performed fibrils. Catechins and procyanidins can therefore be regarded as the potent active constituents of EGb761 in terms of their inhibition of Aβ42 aggregation and destabilization of the fibrils. Although quantitative mass spectroscopic analysis revealed that the catechins and procyanidins are only present in low concentrations in EGb761, these components should be studied in greater detail because of their potent inhibitory effects towards Aβ42 aggregation and their ability to destabilize preformed fibrils, especially during the quality control of Ginkgo leaves and the manufacture of Ginkgo products.

  5. An appetitive experience after fear memory destabilization attenuates fear retention: involvement GluN2B-NMDA receptors in the Basolateral Amygdala Complex.

    Science.gov (United States)

    Ferrer Monti, Roque I; Giachero, Marcelo; Alfei, Joaquín M; Bueno, Adrián M; Cuadra, Gabriel; Molina, Victor A

    2016-09-01

    It is known that a consolidated memory can return to a labile state and become transiently malleable following reactivation. This instability is followed by a restabilization phase termed reconsolidation. In this work, we explored whether an unrelated appetitive experience (voluntary consumption of diluted sucrose) can affect a contextual fear memory in rats during the reactivation-induced destabilization phase. Our findings show that exposure to an appetitive experience following reactivation can diminish fear retention. This effect persisted after 1 wk. Importantly, it was achieved only under conditions that induced fear memory destabilization. This result could not be explained as a potentiated extinction, because sucrose was unable to promote extinction. Since GluN2B-containing NMDA receptors in the basolateral amygdala complex (BLA) have been implicated in triggering fear memory destabilization, we decided to block pharmacologically these receptors to explore the neurobiological bases of the observed effect. Intra-BLA infusion with ifenprodil, a GluN2B-NMDA antagonist, prevented the fear reduction caused by the appetitive experience. In sum, these results suggest that the expression of a fear memory can be dampened by an unrelated appetitive experience, as long as memory destabilization is achieved during reactivation. Possible mechanisms behind this effect and its clinical implications are discussed.

  6. Intracellular signaling by diffusion: can waves of hydrogen peroxide transmit intracellular information in plant cells?

    DEFF Research Database (Denmark)

    Vestergaard, Christian L.; Flyvbjerg, Henrik; Møller, Ian Max

    2012-01-01

    Amplitude- and frequency-modulated waves of Ca(2+) ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the feasibility of such an intracellular communication system in view...... of the physical and biochemical conditions in plant cells. As model system, we use a H(2)O(2) signal originating at the plasma membrane (PM) and spreading through the cytosol. We consider two maximally simple types of signals, isolated pulses and harmonic oscillations. First we consider the basic limits...... which diffusion-mediated signaling is possible. We show that purely diffusive transmission of intracellular information by H(2)O(2) over a distance of 1 μm (typical distance between organelles, which may function as relay stations) is possible at frequencies well above 1 Hz, which is the highest...

  7. Intracellular signaling by diffusion: can waves of hydrogen peroxide transmit intracellular information in plant cells?

    DEFF Research Database (Denmark)

    Vestergaard, Christian Lyngby; Flyvbjerg, Henrik; Møller, Ian Max

    2012-01-01

    Amplitude- and frequency-modulated waves of Ca2+ ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the feasibility of such an intracellular communication system in view...... of the physical and biochemical conditions in plant cells. As model system, we use a H2O2 signal originating at the plasma membrane (PM) and spreading through the cytosol. We consider two maximally simple types of signals, isolated pulses and harmonic oscillations. First we consider the basic limits...... diffusion-mediated signaling is possible. We show that purely diffusive transmission of intracellular information by H2O2 over a distance of 1 μm (typical distance between organelles, which may function as relay stations) is possible at frequencies well above 1 Hz, which is the highest frequency observed...

  8. 胺碘酮治疗充血性心力衰竭合并心房颤动临床研究%The Clinical Research of Amiodarone Treatment Congestive Heart Failure Merger Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    胡华元; 刘建修; 廖远雄

    2011-01-01

    Objective:The objective of this essay was to observe the clinial research of Amiodarone treatment congestive heart failure merger atrial fibrillation.Methods:180 patients randomly into two groups of comparison group and observation group with 90 members for each respectively.The observation group treated with fundamental Resistance to heart failure treatment like furosemidum,digoxin and oxygen uptake,and at the same time, added up amiodarone with 600mg/d in the first week,400mg/d in the second week and 200mg/d lasted for three months.The comparison group took advantage of cardiac tonic,diuresis and extender vascular medicine regularly.Results:To compare the clinical results of two groups' Amiodarone treatment congestive heart failure merger atrial fibrillation.the total effective rate of the observation group was 92.22%,while that of the comparison group was 81.11%.Their compparative differences entailed the useful meaning of statistics(P <0.05).To compare the improvement situation of their patients'electrocardiogram,the total effective rate of the observation group was 86.67%,while that of the comparison group was 74.44%.Their comparative differences entailed the useful meaning of statistics(P<0.05).Conclusions:Thus we could draw the conclusion that amiodarone possesses the advantages of high curative effect and small side effects in treating the Amiodarone treatment congestive heart failure merger atrial fibrillation.%目的:观察胺碘酮治疗充血性心力衰竭(CHF)合并心房颤动(AF)的临床疗效.方法:随机将入组180例患者随机分为对照组和观察组各90例.观察组予以速尿、地高辛、吸氧等基础抗心衰治疗,同时加用胺碘酮,第1周600mg/d,第2周400mg/d,以后改用200mg/d持续3个月;对照组常规使用强心、利尿、扩血管药.结果:2组CHF合并AF患者临床疗效比较,观察组总有效率为92.22%,对照组总有效率为81.11%,2组比较差异有统计学意义(P<0.05);2组CHF合并AF

  9. Open State Destabilization by Atp Occupancy Is Mechanism Speeding Burst Exit Underlying KATP Channel Inhibition by Atp

    OpenAIRE

    Li, Lehong; Geng, Xuehui; Drain, Peter

    2002-01-01

    The ATP-sensitive potassium (KATP) channel is named after its characteristic inhibition by intracellular ATP. The inhibition is a centerpiece of how the KATP channel sets electrical signaling to the energy state of the cell. In the β cell of the endocrine pancreas, for example, ATP inhibition results from high blood glucose levels and turns on electrical activity leading to insulin release. The underlying gating mechanism (ATP inhibition gating) includes ATP stabilization of closed states, bu...

  10. On the Computing Potential of Intracellular Vesicles.

    Directory of Open Access Journals (Sweden)

    Richard Mayne

    Full Text Available Collision-based computing (CBC is a form of unconventional computing in which travelling localisations represent data and conditional routing of signals determines the output state; collisions between localisations represent logical operations. We investigated patterns of Ca2+-containing vesicle distribution within a live organism, slime mould Physarum polycephalum, with confocal microscopy and observed them colliding regularly. Vesicles travel down cytoskeletal 'circuitry' and their collisions may result in reflection, fusion or annihilation. We demonstrate through experimental observations that naturally-occurring vesicle dynamics may be characterised as a computationally-universal set of Boolean logical operations and present a 'vesicle modification' of the archetypal CBC 'billiard ball model' of computation. We proceed to discuss the viability of intracellular vesicles as an unconventional computing substrate in which we delineate practical considerations for reliable vesicle 'programming' in both in vivo and in vitro vesicle computing architectures and present optimised designs for both single logical gates and combinatorial logic circuits based on cytoskeletal network conformations. The results presented here demonstrate the first characterisation of intracelluar phenomena as collision-based computing and hence the viability of biological substrates for computing.

  11. Duodenal Intracellular Bicarbonate and the 'CF Paradox'

    Directory of Open Access Journals (Sweden)

    Kaunitz JD

    2001-07-01

    Full Text Available HCO(3(- secretion, which is believed to neutralize acid within the mucus gel, is the most studied duodenal defense mechanism. In general, HCO(3(- secretion rate and mucosal injury susceptibility correlate closely. Recent studies suggest that luminal acid can lower intracellular pH (pH(i of duodenal epithelial cells and that HCO(3(- secretion is unchanged during acid stress. Furthermore, peptic ulcers are rare in cystic fibrosis (CF, although, with impaired HCO(3(- secretion, increased ulcer prevalence is predicted, giving rise to the 'CF Paradox'. We thus tested the hypothesis that duodenal epithelial cell protection occurs as the result of pH(i regulation rather than by neutralization of acid by HCO(3(- in the pre-epithelial mucus. Cellular acidification during luminal acid perfusion, and unchanged HCO(3(- secretion during acid stress are inconsistent with pre-epithelial acid neutralization by secreted HCO(3(-. Furthermore, inhibition of HCO(3(- secretion by 5-nitro-2-(3-phenylpropylamino benzoic acid (NPPB despite preservation of pH(i and protection from acid-induced injury further question the pre-epithelial acid neutralization hypothesis. This decoupling of HCO(3(- secretion and injury susceptibility by NPPB (and possibly by CF further suggest that cellular buffering, rather than HCO(3(- exit into the mucus, is of primary importance for duodenal mucosal protection, and may account for the lack of peptic ulceration in CF patients.

  12. Intracellular Shuttle: The Lactate Aerobic Metabolism

    Directory of Open Access Journals (Sweden)

    Rogério Santos de Oliveira Cruz

    2012-01-01

    Full Text Available Lactate is a highly dynamic metabolite that can be used as a fuel by several cells of the human body, particularly during physical exercise. Traditionally, it has been believed that the first step of lactate oxidation occurs in cytosol; however, this idea was recently challenged. A new hypothesis has been presented based on the fact that lactate-to-pyruvate conversion cannot occur in cytosol, because the LDH enzyme characteristics and cytosolic environment do not allow the reaction in this way. Instead, the Intracellular Lactate Shuttle hypothesis states that lactate first enters in mitochondria and only then is metabolized. In several tissues of the human body this idea is well accepted but is quite resistant in skeletal muscle. In this paper, we will present not only the studies which are protagonists in this discussion, but the potential mechanism by which this oxidation occurs and also a link between lactate and mitochondrial proliferation. This new perspective brings some implications and comes to change our understanding of the interaction between the energy systems, because the product of one serves as a substrate for the other.

  13. Intracellular Signals of T Cell Costimulation

    Institute of Scientific and Technical Information of China (English)

    Jianxun Song; Fengyang Tylan Lei; Xiaofang Xiong; Rizwanul Haque

    2008-01-01

    Ligation of T cell receptor (TCR) alone is insufficient to induce full activation of T lymphocytes. Additional ligand-receptor interactions (costimulation) on antigen presenting cells (APCs) and T cells are required. T cell costimulation has been shown to be essential for eliciting efficient T cell responses, involving all phases during T cell development. However, the mechanisms by which costimulation affects the function of T cells still need to be elucidated. In recent years, advances have been made in studies of costimulation as potential therapies in cancer, infectious disease as well as autoimmune disease. In this review, we discussed intracellular costimulation signals that regulate T cell proliferation, cell cycle progression, cytokine production, survival, and memory development. In general, the pathway of phosphoinositide-3 kinase (PBK)/protein kinase B (PKB, also known as Akt)/nuclear factor κB (NF-κB) might be central to many costimulatory effects. Through these pathways, costimulation controls T-cell expansion and proliferation by maintenance of survivin and aurora B expression, and sustains long-term T-cell survival and memory development by regulating the expression of bci-2 family members. Cellular & Molecular Immunology.2008;5(4):239-247.

  14. Modeling HIV-1 intracellular replication: two simulation approaches

    NARCIS (Netherlands)

    N. Zarrabi; E. Mancini; J. Tay; S. Shahand; P.M.A. Sloot

    2010-01-01

    Many mathematical and computational models have been developed to investigate the complexity of HIV dynamics, immune response and drug therapy. However, there are not many models which consider the dynamics of virus intracellular replication at a single level. We propose a model of HIV intracellular

  15. Assessment of Methods for the Intracellular Blockade of GABAA Receptors.

    Science.gov (United States)

    Atherton, Laura A; Burnell, Erica S; Mellor, Jack R

    2016-01-01

    Selective blockade of inhibitory synaptic transmission onto specific neurons is a useful tool for dissecting the excitatory and inhibitory synaptic components of ongoing network activity. To achieve this, intracellular recording with a patch solution capable of blocking GABAA receptors has advantages over other manipulations, such as pharmacological application of GABAergic antagonists or optogenetic inhibition of populations of interneurones, in that the majority of inhibitory transmission is unaffected and hence the remaining network activity preserved. Here, we assess three previously described methods to block inhibition: intracellular application of the molecules picrotoxin, 4,4'-dinitro-stilbene-2,2'-disulphonic acid (DNDS) and 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS). DNDS and picrotoxin were both found to be ineffective at blocking evoked, monosynaptic inhibitory postsynaptic currents (IPSCs) onto mouse CA1 pyramidal cells. An intracellular solution containing DIDS and caesium fluoride, but lacking nucleotides ATP and GTP, was effective at decreasing the amplitude of IPSCs. However, this effect was found to be independent of DIDS, and the absence of intracellular nucleotides, and was instead due to the presence of fluoride ions in this intracellular solution, which also blocked spontaneously occurring IPSCs during hippocampal sharp waves. Critically, intracellular fluoride ions also caused a decrease in both spontaneous and evoked excitatory synaptic currents and precluded the inclusion of nucleotides in the intracellular solution. Therefore, of the methods tested, only fluoride ions were effective for intracellular blockade of IPSCs but this approach has additional cellular effects reducing its selectivity and utility. PMID:27501143

  16. Gravity-destabilized nonwetting phase invasion in macro-heterogeneous porous media: Experimental observations of invasion dynamics and scale analysis

    Energy Technology Data Exchange (ETDEWEB)

    GLASS JR.,ROBERT J.; CONRAD,STEPHEN H.; PEPLINSKI,WILLIAM J.

    1999-02-16

    The authors designed and conducted experiments in a heterogeneous sand pack where gravity-destabilized nonwetting phase invasion (CO{sub 2} and TCE) could be recorded using high resolution light transmission methods. The heterogeneity structure was designed to be reminiscent of fluvial channel lag cut-and-fill architecture and contain a series of capillary barriers. As invasion progressed, nonwetting phase structure developed a series of fingers and pools; behind the growing front they found nonwetting phase saturation to pulsate in certain regions when viscous forces were low. Through a scale analysis, they derive a series of length scales that describe finger diameter, pool height and width, and regions where pulsation occurs within a heterogeneous porous medium. In all cases, they find that the intrinsic pore scale nature of the invasion process and resulting structure must be incorporated into the analysis to explain experimental results. The authors propose a simple macro-scale structural growth model that assembles length scales for sub-structures to delineate nonwetting phase migration from a source into a heterogeneous domain. For such a model applied at the field scale for DNAPL migration, they expect capillary and gravity forces within the complex subsurface lithology to play the primary roles with viscous forces forming a perturbation on the inviscid phase structure.

  17. Destabilization of acrosome and elastase influence mediate the release of secretory phospholipase A2 from human spermatozoa

    Institute of Scientific and Technical Information of China (English)

    Jacqueline Leβig; Uta Reibetanz; Jürgen Arnhold; Hans-Jürgen Glander

    2008-01-01

    Aim: To determine the cellular distribution of secretory phospholipase A2 (sPLA2) in dependence on the acrosomal state and under the action of elastase released under inflammatory processes from leukocytes. Methods: Acrosome reaction of spermatozoa was triggered by calcimycin. Human leukocyte elastase was used to simulate in flammatory conditions. To visualize the distribution of sPLA2 and to determine the acrosomal state, immunofluorescence tech-niques and lectin binding combined with confocal laser scanning fluorescence microscopy and flow cytometry were used. Results: Although sPLA2 was detected at the acrosome and tail regions in intact spermatozoa, it disappearedfrom the head region after triggering the acrosome reaction. This release of sPLA2 was associated with enhanced binding of annexin V-fluoroscein isothiocyanate (FITC) to spermatozoa surfaces, intercalation of ethidium-homodimer L and bnding of FITC-iabelled concanavalin A at the acrosomal region. Spermatozoa from healthy subjects treated with elastase were characterized by release of sPLA2, disturbance of acrosome structure, and loss of vitality. Conclusion:The ability of spermatozoa to release secretory phospholipase A2 is related to the acrosomal state. Premature destabi-lization of the acrosome and loss of sPLA2 can occur during silent inflammations in the male genital tract. The distribution pattern of sPLA2 in intact spermatozoa might be an additional parameter for evaluating sperm quality.

  18. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure.

    Science.gov (United States)

    Banerjee, Saikat; Shi, Heliang; Habte, Habtom H; Qin, Yali; Cho, Michael W

    2016-03-01

    The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; (671)NWFDITNWLWYIK(683)) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. PMID:26803471

  19. Electrostatic transition state stabilization rather than reactant destabilization provides the chemical basis for efficient chorismate mutase catalysis.

    Science.gov (United States)

    Burschowsky, Daniel; van Eerde, André; Ökvist, Mats; Kienhöfer, Alexander; Kast, Peter; Hilvert, Donald; Krengel, Ute

    2014-12-01

    For more than half a century, transition state theory has provided a useful framework for understanding the origins of enzyme catalysis. As proposed by Pauling, enzymes accelerate chemical reactions by binding transition states tighter than substrates, thereby lowering the activation energy compared with that of the corresponding uncatalyzed process. This paradigm has been challenged for chorismate mutase (CM), a well-characterized metabolic enzyme that catalyzes the rearrangement of chorismate to prephenate. Calculations have predicted the decisive factor in CM catalysis to be ground state destabilization rather than transition state stabilization. Using X-ray crystallography, we show, in contrast, that a sluggish variant of Bacillus subtilis CM, in which a cationic active-site arginine was replaced by a neutral citrulline, is a poor catalyst even though it effectively preorganizes chorismate for the reaction. A series of high-resolution molecular snapshots of the reaction coordinate, including the apo enzyme, and complexes with substrate, transition state analog and product, demonstrate that an active site, which is only complementary in shape to a reactive substrate conformer, is insufficient for effective catalysis. Instead, as with other enzymes, electrostatic stabilization of the CM transition state appears to be crucial for achieving high reaction rates.

  20. Imaging and controlling intracellular reactions: Lysosome transport as a function of diameter and the intracellular synthesis of conducting polymers

    Science.gov (United States)

    Payne, Christine

    2014-03-01

    Eukaryotic cells are the ultimate complex environment with intracellular chemical reactions regulated by the local cellular environment. For example, reactants are sequestered into specific organelles to control local concentration and pH, motor proteins transport reactants within the cell, and intracellular vesicles undergo fusion to bring reactants together. Current research in the Payne Lab in the School of Chemistry and Biochemistry at Georgia Tech is aimed at understanding and utilizing this complex environment to control intracellular chemical reactions. This will be illustrated using two examples, intracellular transport as a function of organelle diameter and the intracellular synthesis of conducting polymers. Using single particle tracking fluorescence microscopy, we measured the intracellular transport of lysosomes, membrane-bound organelles, as a function of diameter as they underwent transport in living cells. Both ATP-dependent active transport and diffusion were examined. As expected, diffusion scales with the diameter of the lysosome. However, active transport is unaffected suggesting that motor proteins are insensitive to cytosolic drag. In a second example, we utilize intracellular complexity, specifically the distinct micro-environments of different organelles, to carry out chemical reactions. We show that catalase, found in the peroxisomes of cells, can be used to catalyze the polymerization of the conducting polymer PEDOT:PSS. More importantly, we have found that a range of iron-containing biomolecules are suitable catalysts with different iron-containing biomolecules leading to different polymer properties. These experiments illustrate the advantage of intracellular complexity for the synthesis of novel materials.

  1. A universal strategy for stable intracellular antibodies.

    Science.gov (United States)

    Shaki-Loewenstein, Shelly; Zfania, Rahely; Hyland, Stephen; Wels, Winfried S; Benhar, Itai

    2005-08-01

    The expression of intracellular antibodies (intrabodies) in mammalian cells has provided a powerful tool to manipulate microbial and cellular signalling pathways in a highly precise manner. However, several technical hurdles have thus far restricted their more widespread use. In particular, single-chain antibodies (scFvs) have been reported to fold poorly in the reducing environment of the cytoplasm and as such there has been a reluctance to use scFv-phage libraries as a source of intrabodies unless a preselection step was applied to identify these rare scFvs that could fold properly in the absence of disulfide bonds. Recently, we reported that scFvs can be efficiently expressed within the cytoplasm of bacteria when fused at the C-terminus of the Escherichia coli maltose-binding protein (MBP). Here, we demonstrate that such MBP-scFvs are similarly stabilized when expressed in the mammalian cell cytoplasm as well as other compartments. This was demonstrated by comparing MBP-scFv fusions to the corresponding unfused scFvs that activate a defective beta-galactosidase enzyme, others that neutralize the wild-type beta-galactosidase enzyme, and an antibody that blocks the epidermal growth factor receptor. In all cases, the MBP-scFvs significantly outperformed their unfused counterparts. Our results suggest that fusion of scFvs to MBP, and possibly to other "chaperones in the context of a fusion protein", may provide a universal approach for efficient expression of intrabodies in the mammalian cell cytoplasm. This strategy should allow investigators to bypass much of the in vitro scFv characterization that is often not predictive of in vivo intrabody function and provide a more efficient use of large native and synthetic scFv-phage libraries already in existence to identify intrabodies that will be active in vivo.

  2. Estudo prospectivo dos efeitos da amiodarona na função tiroidiana de pacientes chagásicos em área de deficiência de iodo Prospective study of amiodarone effects on thyroid function of chagasic patients in an iodine deficient area

    Directory of Open Access Journals (Sweden)

    Maria Aparecida Enes de Barros

    1994-09-01

    Full Text Available Com o objetivo de avaliar a junção tiroidiana após uso crônico da amiodarona, em área de deficiência de iodo e endemia chagásica, 24 pacientes foram analisados antes e após três e nove meses de uso da droga. A avaliação constou de exame clínico, dosagem sérica de T4, T3, rT3, TSH, anticorpo antitiroglobulina e TSH 30 minutos após infusão venosa de uma ampola de 200µg de TRH. A captação do iodo radioativo 131 e a cintilografia datiróide foram realizadas antes e aos 9 meses após tratamento. Disfunção tiroidiana ocorreu em 20,8% dos pacientes sendo 12,5% de hipertiroidismo e 8,3% de hipotiroidismo, com anticorpos antitiroglobulina negativos. Captação do iodo radioativo 131 foi positiva em um paciente hipertiroideo com bócio. O diagnóstico de hipertiroidismo foi melhor evidenciado pela resposta reduzida ou bloqueada do TSH ao TRH e não pela concentração do T3 no soro e o de hipotiroidismo pela concentração elevada do TSH. O TSH elevado desde o início do tratamento pode predispor ao aparecimento de bócio. Concluímos que o uso da amiodarona em nossa região deve serjudiciosamente analisado, sendo a função tiroidiana cuidadosamente monitorizada antes e durante o tratamento.In order to evaluate the development of thyroid dysfunction during chronic amiodarone treatment in an area deficient in iodine and endemic for Chagas 'disease, a group of 24patients wasprospectively studied. Clinical examination and measurement of serum T4, T3, rT3, TSH and antithyroglobulin antibodies were performed before and at 3 and 9 months of use of amiodarone. A TSH response 30 minutes after IV injection of 200µg of TRH was also compared to TSH basal levels before and during amiodarone treatment. Thyroid radioative uptake and scan were obtained before and nine months after amiodarone was started. Elevated rT3 concentrations were unexpectedly found in two thirds of the patients before treatment. Thyroid dysfunction developed during

  3. 雷米普利和替米沙坦与胺碘酮联用治疗阵发性心房颤动的临床观察%Clinical observations of ramipril and telmisartan combined with amiodarone in patients with paroxysmal atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    赵美丽; 刘大钧

    2010-01-01

    目的 探讨雷米普利和替米沙坦与小剂量胺碘酮联用对心功能正常的阵发性心房颤动(房颤)维持窦性心律的长期疗效.方法 将180例阵发性房颤患者完全随机分为胺碘酮组(A组,61例)、胺碘酮+雷米普利组(B组,59例)、胺碘酮+替米沙坦组(C组,60例),随访2年,比较3组治疗后6、12、18、24个月的窦性心律维持率以及治疗前、后的左心房内径.结果 治疗12个月后,A组左心房内径大于B、C组(P<0.05),A组窦性心律维持率明显低于B、C组(P<0.05).试验终点时,A组的窦性心律维持率为58.62%,B组为77.78%,C组为78.57%(P<0.05).结论 胺碘酮分别与雷米普利和替米沙坦配伍治疗阵发性房颤维持窦性心律具有相同的疗效,但优于单用胺碘酮,并能抑制左心房的扩大.%Objective To evaluate the clinical efficacy of ramipril and telmisartan combined with amioda-rone on maintenance of sinus rhythm in patients with idiopathic paroxysmal atrial fibrillation(PAF). Methods One hundred and eighty patients with idiopathic PAF were included in the study and randomly divided into three groups: group A (Amiodarone group, n=61) was treated with amiodarone alone; group B (Amiodarone plus Ramipril, n=59) was treated with amiodarone combined with Ramipril;group C(Amiodarone plus telmisartan group,n=60)was trea-ted with amiodarone combined with telmisartan. The left atrial diameter(LAD) was measured with transthoracic echo-cardiogram before and 6,12,18 and 24 month after treatment. The follow-up was up to 2 years and the primary end point of the study was the first recurrence of AF. Results During the 6 months follow-up, there was no difference in LAD among three groups. After 12 months, LAD in group A was significantly larger than that in group B and group C(P<0.05). At the end of 12 months, the sinus rhythm maintenance of group A was lower significantly than that of group B and group C. At the end of the study, the maintenance of sinus rhythm in

  4. Comparison of the efficacy and safety of propafenone and amiodarone in the treatment of paroxysmal supraventricular tachycardia%普罗帕酮和胺碘酮治疗阵发性室上性心动过速疗效与安全性比较

    Institute of Scientific and Technical Information of China (English)

    曾益华; 张世杰; 胡爱民

    2011-01-01

    Objective To evaluate the efficacy and safety of propafenone and amiodarone in the treatment of paroxysmal supraventricular tachycardia(PSVT). Methods Total 86 cases of PSVT were randomly divided into propafenone group and amiodarone group. Propafenone group had intravenously injected 70 mg propafenone. The intravenous injections lasted 5 minutes. Amiodarone group were intravenously infused amiodarone(5-7 mg/kg) (the intravenous infusion lasted 30 minutes). Results The termination rate of PSVT was 93.2% in propafenone group and 88.1% in amiodarone group respectively. Cardioversion time showed as follows: propafenone group(12.4 ±7.8 min) was significantly shorter than amiodarone group (30.7 ± 10.3) min (P < 0.01). Side reaction showed that propafenone group(29.5%) was significantly higher than amiodarone group (11.9%) (P < 0.05). Conclusions The effective cardioversion rates of propafenone and amiodarone in treating PSVT are high in emergency department.Propafenone shows faster effect and higher side effects but better outcome for patients without serious organic heart diseases than Amiodarone which is better for patients with serious organic heart diseases.%目的 比较普罗帕酮和胺碘酮静脉用于急诊转复阵发性室上性心动过速的疗效及不良反应.方法 将急诊阵发性室上性心动过速患者86例完全随机分成普罗帕酮组(44例)和胺碘酮组(42例),普罗帕酮组给予普罗帕酮70 mg静脉注射(5 min注完),若无效,20min后重复1次;胺碘酮组给予胺碘酮5~7 mg/kg加入100 ml 5%葡萄糖或0.9%氯化钠注射液中静脉滴注,30 min滴完,继之以1 mg/min的速度持续静脉滴注.观察2组的治疗效果和不良反应发生情况.结果 普罗帕酮组和胺碘酮组转复有效率分别为93.2%(41/44)和88.1%(37/42)(P>0.05);平均转复时间普罗帕酮组[(12.4±7.8)min]明显短于胺碘酮组[(30.7±10.3)min](P<0.01);不良反应发生率普罗帕酮组为[29.5%(13/44)]明显高

  5. 胺碘酮联合磷酸肌酸钠对心肺复苏后心肌的保护作用%Protective effects of amiodarone combined with creatine phosphate sodium on myocardium after cardiopulmonary resuscitation in rabbits

    Institute of Scientific and Technical Information of China (English)

    王芳; 周雨; 许铁

    2013-01-01

    目的 研究胺碘酮联合磷酸肌酸钠对兔心肺复苏(CPR)后心肌的保护作用.方法 用窒息法制作CPR模型.选取健康日本长耳大白兔40只,随机分为A组(假手术组)、B组(生理盐水组)、C组(胺碘酮组)、D组(磷酸肌酸钠组)、E组(胺碘酮联合磷酸肌酸钠组),每组8只,动态监测HR、MAP及血浆CK、CK-MB含量.复苏后6 h处死兔,光镜下观察心肌组织病理学变化.结果 B组、C组、D组和E组兔的HR、MAP比较差异无统计学意义(P>0.05).与A组比较,CPR后B组、C组、D组和E组兔血浆CK、CK-MB含量均增高,差异有统计学意义(P 0.05). Compared with group A, the levels of plasma CK, CK - MB were significantly higher in group B, group C, group D and group E after CPR (P 0.05). In group B, group C, group D and group E, the levels of plasma CK, CK - MB increased gradually after CPR( P < 0. 05 ). Correlation analysis showed that there was significantly postitive relation between the levels of plasma CK, CK - MB and the time after CPR in group B, group C, group D and group E (P < 0. 05 ) . Results of pathology showed that myocardial injury were more seriously in group B than in group C and group D, and myocardial injury were more seriously in group C and group D than in group E. Conclusion Treatment with amiodarone, creatine phosphate sodium, amiodarone combined with creatine phosphate sodium can alleviate myocardial injury after CPR in rabbits, the protective effects of amiodarone combined with creatine phosphate sodium were the best.

  6. 阿托伐他汀钙在胺碘酮转复持续性心房颤动中的作用观察%Treatment with atorvastatin and amiodarone in patients with persistent atrial fibrillation.

    Institute of Scientific and Technical Information of China (English)

    李满生; 王会霞; 石建克; 蔡华; 张晓华; 李新峰; 岳修宇

    2011-01-01

    目的 探讨阿托伐他汀钙联合胺碘酮转复持续性心房颤动(简称房颤)及房颤复律后维持窦性心律的作用及其对血清炎症反应的影响.方法 68例持续性房颤患者,随机分为两组.对照组34例给予胺碘酮,治疗组34例给予胺碘酮和阿托伐他汀钙.两组均连续服药6个月,观察房颤转复后窦性心律维持率及转复前后血清高敏C反应蛋白(hs-CRP)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)变化.结果 治疗组房颤转复率、窦性心律维持率均较对照组高(79.41% vs 61.76%,76.47% vs 55.88%,P均<0.05),对照组治疗前后hs-CRP、IL-6、TNF-α无变化(P>0.05),治疗组治疗后hs-CRP、IL-6、TNF-α明显降低(P<0.05).结论 阿托伐他汀钙可以降低房颤的复发,其机制可能与抗炎作用相关.%Objective To investigate the preventive effective of atorvastatin and amiodarone on recurrence of persistent atrial fibrillation, maintenance rate of sinus rhythm and change of inflammatory factors. Methods Sixty-eight patients with persistent atrial fibrillation were randomly divided into control group (n = 34, treated with amiodarone) and treated group (re =34, treated with amiodarone and atorvastatin). After 6 months follow-up, observe the change of hs-CRP ,IL-6, TNF-a and maintenance rate of sinus rhythm before and after treatment. Results After treatment, sinus rhythm of control group and treated group was 61. 76% vs 79.41 % ( P 0.05), while in treated group which greatly decreased after treatment ( P < 0.05 ). Conclusion Atorvastatin may reduce recurrence of persistent atrial fibrillation, which is related to is anti-inflammation effect.

  7. Amiodarone in treatment of Wolff-Parkinson-White syndrome combined with rapid ar-rhythmia:35 cases%胺碘酮治疗预激综合征合并快速心律失常35例

    Institute of Scientific and Technical Information of China (English)

    王一伟

    2015-01-01

    AIM:To investigate the clinical effect of amiodarone on Wolff-Parkinson-White syndrome (WPW)combined with par-oxysmal supraventricular tachycardia.METHODS:35 cases with WPW combined with paroxysmal supraventricular tachycardia were observed.All 35 patients admitted to our hospital were treated with anti-arrhythmic therapy,and amiodarone was prescribed once sinus rhythm was restored.Clinical efficacy was evaluated.RE-SULTS:Upon treatment,1 6 cases were significantly improved, 1 7 cases were effective and no effect was observed in 2 cases, with total effective rate being 94.29% (33 /35 ).In addition, heart rate was significantly decreased (P <0.01 ).CONCLU-SION:The application of amiodarone in treatment of WPW com-bined with paroxysmal ventricular tachycardia has significant cura-tive effect and is worthy of clinical popularization and application.%目的:探讨胺碘酮对预激综合征(WPW)合并阵发性室上性心动过速的临床疗效.方法:选择我院35例 WPW合并阵发性室上性心动过速患者作为观察对象.所有患者入院后均接受抗心律失常治疗,待到恢复窦性心律后,再给予胺碘酮,最终评价患者临床疗效.结果:治疗后,显效16例,有效17例,无效2例,总有效率高达94.29%(33/35).此外,治疗后患者心率显著降低(P <0.01).结论:应用胺碘酮治疗WPW 合并阵发性室上性心动过速疗效显著,值得临床推广应用.

  8. 普罗帕酮与胺碘酮治疗心房颤动的临床研究%Clinical Study on Propafenone and Amiodarone in Treatment of Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    赵晓慧

    2016-01-01

    Objective Treatment methods and effects of Propafenone and Amiodarone for treatment of atrial fibrilation are to be studied.MethodsChose 70 patients of atrial fibrilation who were treated in hospital from August 2014 to October 2015 and separated them into two groups at random. 38 patients in study group were given Amiodarone treatment,while another 32 patients in control group were given Propafenone treatment,and then compared patients’treatment effects and side-effect incidence between two groups.Results Patients’treatment efficacy in study group was 92.11%,which was much higher than 75.0% in control group,there was a differential between two groups and such a differential had statistic value(P<0.05). Conclusion Amiodarone is much more effective in treatment of patients with atrial fibrilation,it is conducive to relieving patients’ symptoms in short time with few side-effects.%目的:探究心房颤动患者采用普罗帕酮和胺碘酮治疗的方法及效果。方法选取2014年8月~2015年10月收治的70例心房颤动患者进行治疗研究,随机分组,实验组38例患者采取胺碘酮治疗,对照组32例患者采用普罗帕酮治疗,对比两种患者的治疗效果和不良反应。结果实验组患者治疗有效率为92.11%,对照组患者治疗有效率为75.0%,实验组患者治疗效果好,差异有统计学意义(P<0.05)。结论心房颤动患者采用胺碘酮的治疗,其治疗效果优,在短时间内即可缓解身体症状,不良反应较少,安全性高。

  9. A tomografia computadorizada de alta resolução na avaliação da toxicidade pulmonar por amiodarona High-resolution computed tomography of amiodarone pulmonary toxicity

    Directory of Open Access Journals (Sweden)

    Daniela Peixoto Consídera

    2006-04-01

    Full Text Available OBJETIVO: Avaliar as principais alterações identificadas na tomografia computadorizada de alta resolução do tórax em pacientes com toxicidade pulmonar pela amiodarona. MATERIAIS E MÉTODOS: Foram avaliadas dez tomografias computadorizadas de alta resolução de tórax de pacientes com pneumonite pela amiodarona, seis desses pacientes do sexo masculino e quatro do sexo feminino, com idade média de 73,5 anos. RESULTADOS: Os achados tomográficos mais relevantes foram opacidades lineares ou reticulares em seis casos (60%, pequenos nódulos com densidade elevada em seis casos (60%, consolidações densas em três casos (30% e aumento da densidade do parênquima hepático em cinco de oito casos em que havia estudo tomográfico do abdome superior (62,5%. CONCLUSÃO: A tomografia computadorizada de alta resolução é um exame importante na avaliação de pacientes com toxicidade pulmonar pela amiodarona, devendo ser realizada sempre que houver suspeita deste diagnóstico. O achado de espessamento de septos interlobulares associado a lesões com aumento de densidade é altamente sugestivo deste diagnóstico.OBJECTIVE: To evaluate the main findings of chest high-resolution computed tomography in patients with amiodarone pulmonary toxicity. MATERIALS AND METHODS: Ten patients - six male and four female, average age of 73.5 years - with amiodarone-induced pneumonitis have undergone chest high-resolution computed tomography. RESULTS: The most relevant tomographic findings were linear or reticular opacities in six cases (60%, small high density nodules in six cases (60%, dense consolidations in three cases (30% and increased density in the hepatic parenchyma in five of eight cases in which there was a superior abdomen CT scan (62.5%. CONCLUSION: The high-resolution computed tomography is a valuable non-invasive test for evaluating patients with amiodarone pulmonary toxicity and should always be performed when one suspects of the presence of this

  10. Destabilizing Carry Trades

    OpenAIRE

    Plantin, Guillaume; Shin, Hyun Song

    2014-01-01

    We offer a model of currency carry trades in which carry traders generate self-sustained excess returns if they coordinate on supplying excessive capital to a target economy. The interest-rate differential between their funding currency and the target currency is their coordination device. Such self-fulfilling pro table currency trades arise when the central bank of the target economy ignores the impact of carry-trade in flows on domestic asset prices, and responds only to their effect on inf...

  11. Destabilized bioluminescent proteins

    Science.gov (United States)

    Allen, Michael S.; Rakesh, Gupta; Gary, Sayler S.

    2007-07-31

    Purified nucleic acids, vectors and cells containing a gene cassette encoding at least one modified bioluminescent protein, wherein the modification includes the addition of a peptide sequence. The duration of bioluminescence emitted by the modified bioluminescent protein is shorter than the duration of bioluminescence emitted by an unmodified form of the bioluminescent protein.

  12. Destabilizing carry trades

    OpenAIRE

    Guillaume Plantin; Hyun Song Shin

    2015-01-01

    We offer a model of currency carry trades in which carry traders generate self-sustained excess returns if they coordinate on supplying excessive capital to a target economy. The interest-rate differential between their funding currency and the target currency is their coordination device. Such self-fulfilling pro table currency trades arise when the central bank of the target economy ignores the impact of carry-trade in flows on domestic asset prices, and responds only to their effect on inf...

  13. Viscosity Destabilizes Sonoluminescing Bubbles

    NARCIS (Netherlands)

    Toegel, Ruediger; Luther, Stefan; Lohse, Detlef

    2006-01-01

    In single-bubble sonoluminescence (SBSL) microbubbles are trapped in a standing sound wave, typically in water or water-glycerol mixtures. However, in viscous liquids such as glycol, methylformamide, or sulphuric acid it is not possible to trap the bubble in a stable position. This is very peculiar

  14. New perspective in the assessment of total intracellular magnesium

    Directory of Open Access Journals (Sweden)

    Azzurra Sargenti

    2014-01-01

    Full Text Available Magnesium (Mg is essential for biological processes, but its cellular homeostasis has not been thoroughly elucidated, mainly because of the inadequacy of the available techniques to map intracellular Mg distribution. Recently, particular interest has been raised by a new family of fluorescent probes, diaza-18-crown-hydroxyquinoline (DCHQ, that shows remarkably high affinity and specificity for Mg, thus permitting the detection of the total intracellular Mg. The data obtained by fluori- metric and cytofluorimetric assays performed with DCHQ5 are in good agreement with atomic absorption spectroscopy, confirming that DCHQ5 probe allows both qualitative and quantitative determination of total intracellular Mg.

  15. Vesicular demyelination induced by raised intracellular calcium.

    Science.gov (United States)

    Smith, K J; Hall, S M; Schauf, C L

    1985-11-01

    myelin vesiculation. We conclude that vesicular demyelination can be initiated in vital Schwann cells by a raised intracellular Ca2+ concentration. Such demyelination does not necessarily lead to Schwann cell death. The possible relevance of the findings to vesicular demyelinating neuropathies is discussed, and a hypothesis regarding the mechanism of demyelination is advanced. PMID:3003255

  16. Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD.

    Science.gov (United States)

    Eade, Colleen R; Hung, Chien-Che; Bullard, Brian; Gonzalez-Escobedo, Geoffrey; Gunn, John S; Altier, Craig

    2016-08-01

    Salmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

  17. Nutrient/serum starvation derived TRIP-Br3 down-regulation accelerates apoptosis by destabilizing XIAP

    Science.gov (United States)

    Lee, Soonduck; Jeong, Dongjun; Yang, Young; Kim, Keun-Il; Lim, Jong-Seok; Cheon, Chung-Il; Kim, Changjin; Kang, Young-Sook; Lee, Myeong-Sok

    2015-01-01

    TRIP-Br3 and TRIP-Br1 have shown to have important biological functions. However, the function of TRIP-Br3 in tumorigenesis is not well characterized compared to oncogenic TRIP-Br1. Here, we investigated the function of TRIP-Br3 in tumorigenesis by comparing with that of TRIP-Br1. Under nutrient/serum starvation, TRIP-Br3 expression was down-regulated slightly in cancer cells and significantly in normal cells. Unexpectedly, TRIP-Br1 expression was greatly up-regulated in cancer cells but not in normal cells. Moreover, TRIP-Br3 activated autophagy while TRIP-Br1 inactivated it under serum starvation. In spite of different expression and roles of TRIP-Br3 and TRIP-Br1, both of them alleviate cell death by directly binding to and stabilizing XIAP, a potent apoptosis inhibitor, through blocking its ubiquitination. Taken together, we propose that TRIP-Br3 primarily activates the autophagy and suppresses apoptosis in nutrient sufficient condition. However, the prolonged extreme stressful condition of nutrient starvation causes a dramatic decrease of TRIP-Br3, which in turn induces apoptosis by destabilizing XIAP. Up-regulated TRIP-Br1 in cancer cells compensates this effect and delays apoptosis. This can be explained by the competitive alternative binding of TRIP-Br3 and TRIP-Br1 to the BIR2 domain of XIAP. In an extended study, our immunohistochemical analysis revealed a markedly lower level of TRIP-Br3 protein in human carcinoma tissues compared to normal epithelial tissues, implying the role of TRIP-Br3 as a tumor suppressor rather than onco-protein. PMID:25691055

  18. Protein homeostasis disorders of key enzymes of amino acids metabolism: mutation-induced protein kinetic destabilization and new therapeutic strategies.

    Science.gov (United States)

    Pey, Angel L

    2013-12-01

    Many inborn errors of amino acids metabolism are caused by single point mutations affecting the ability of proteins to fold properly (i.e., protein homeostasis), thus leading to enzyme loss-of-function. Mutations may affect protein homeostasis by altering intrinsic physical properties of the polypeptide (folding thermodynamics, and rates of folding/unfolding/misfolding) as well as the interaction of partially folded states with elements of the protein homeostasis network (such as molecular chaperones and proteolytic machineries). Understanding these mutational effects on protein homeostasis is required to develop new therapeutic strategies aimed to target specific features of the mutant polypeptide. Here, I review recent work in three different diseases of protein homeostasis associated to inborn errors of amino acids metabolism: phenylketonuria, inherited homocystinuria and primary hyperoxaluria type I. These three different genetic disorders involve proteins operating in different cell organelles and displaying different structural complexities. Mutations often decrease protein kinetic stability of the native state (i.e., its half-life for irreversible denaturation), which can be studied using simple kinetic models amenable to biophysical and biochemical characterization. Natural ligands and pharmacological chaperones are shown to stabilize mutant enzymes, thus supporting their therapeutic application to overcome protein kinetic destabilization. The role of molecular chaperones in protein folding and misfolding is also discussed as well as their potential pharmacological modulation as promising new therapeutic approaches. Since current available treatments for these diseases are either burdening or only successful in a fraction of patients, alternative treatments must be considered covering studies from protein structure and biophysics to studies in animal models and patients.

  19. Importância da toxicidade pulmonar pela amiodarona no diagnóstico diferencial de paciente com dispnéia em fila para transplante cardíaco The importance of amiodarone pulmonary toxicity in the differential diagnosis of a patient with dyspnea awaiting a heart transplant

    Directory of Open Access Journals (Sweden)

    Christiano Pereira Silva

    2006-09-01

    Full Text Available A amiodarona é um antiarrítmico da classe III, amplamente utilizado em arritmias ventriculares¹. Farmacologicamente é classificado como uma drogra ampifílica catiônica, pelos seus constituintes polares e apolares. Nos últimos anos, a amiodarona obteve destaque pelo seu uso em portadores de disfunção ventricular por qualquer etiologia, em especial a chagásica, quando ocorrem arritmias ventriculares². Entretanto, a despeito de seus benefícios hemodinâmicos e eletrofisiológicos, a amiodarona produz efeitos colaterais relevantes, como coloração azulada da pele, fotossensibilidade, disfunção tireoidiana, depósito corneal, neuropatia periférica, supressão da medula óssea, hepatite, bloqueios cardíacos, pneumonites e outros³. Este relato de caso se propõe a abordar uma de suas mais sérias complicações, a toxicidade pulmonar, aqui especialmente descrita como diagnóstico diferencial em um paciente chagásico que aguardava em fila de transplante cardíaco. Pneumonite por amiodarona constitui-se em um importante diagnóstico diferencial entre os pacientes que se apresentam na sala de emergência com dispnéia, quando estes são portadores de insuficiência cardíaca (IC e estão em uso dessa droga.Amiodarone is a class III antiarrhythmic medication used extensively to treat ventricular arrhythmias¹. It is pharmacologically classified as a cationic amphiphilic drug due to its polar and apolar components. During the past few years, amiodarone has proved to be an effective treatment therapy for patients with ventricular dysfunctions, regardless of the etiology, and in particular ventricular arrhythmia associated with Chagas disease². Nevertheless, despite its hemodynamic and electrophysiological benefits, amiodarone produces serious collateral effects such as a bluish skin discoloration, photosensitivity, thyroid dysfunction, corneal deposit, peripheral neuropathy, bone marrow suppression, hepatitis, heart blocks, pneumonitis

  20. 参松养心胶囊联合胺碘酮治疗充血性心力衰竭伴室性心律失常的疗效及安全性观察%Efficacy and Safety of Shensong Yangxin Capsule Combined with Amiodarone for Treatment of Congestive Heart Failure and Ventricular Arrhythmias

    Institute of Scientific and Technical Information of China (English)

    陈勇; 向琳; 胡玉华; 武万娜

    2011-01-01

    Objective To observe the efficacy and safety of Shensong Yangxin eapsule(SYC) combined with amiodarone for treatment of chronic congestive heart failure(CHF) associated with ventricular arrhythmia(VA). Methods One hundred and sixty-eight patients(pts) with CHF and VA were randomly divided into 3 groupssGroup A (n=52) treated with oral SYC,group B(n=56) treated with oral amiodarone and group C (n = 60) treated with SYC and oral amiodarone for 4 weeks. The efficacy and safety were observed after the clinical treatment. Results After 4 weeks,the total effective rate was 76%, 78% and 86% in group A,group B and group C. The total effective rate in group C was significantly higher than that in group A and group B(P<0. 05). Conclusion SYC was effective as amiodarone hydrochloride for treatment of CHF and VA. SYC combined with amiodarone for treatment of CHF with ventricular arrhythmias was more effective than amiodarone or SYC alone.%目的 观察参松养心胶囊联合胺碘酮治疗慢性充血性心力衰竭(CHF)伴室性心律失常(VA)的疗效及安全性.方法 选择充血性心力衰竭合并室性心律失常患者168例,随机分为A组(52例)、B组(56例)及C组(60例).A组给予参松养心胶囊口服,B组给予胺碘酮口服,C组给予参松养心胶囊与胺碘酮口服.观察用药4周后3组的临床疗效与安全性.结果 治疗4周后总有效率A组76%,B组78%,C组86%,C组显著高于A组和B组(P<0.05).结论 参松养心胶囊治疗慢性心力衰竭室性心律失常与盐酸胺碘酮疗效相当,且副反应小;参松养心胶囊与胺碘酮联用治疗CHF室性心律失常的疗效优于单用胺碘酮或单用参松养心胶囊的疗效,并可明显减少胺碘酮的用量.

  1. Observation of curative effects of Amiodarone on patients with acute coronary syndrome (ACS)and chronic heart failure and ventricular arrythmia%胺碘酮治疗急性冠脉综合征伴心力衰竭的室性心律失常疗效观察

    Institute of Scientific and Technical Information of China (English)

    邹培源; 冯小燕

    2011-01-01

    Objective: To observe the efficacy and safety of Amiodarone in treatment of ventricular arrythmia on acute coronary syndrome (ACS) and chronic heart failure patients and ventricular arrythmia. Methods: On the basis of regular treatment, Amiodarone was used in 52 patients with ACS and chronic heart failure and ventricular arrythmia, intravenous loading does of 3-5 mg/kg of Amiodarone was given within 10-20 min, followed by 0.75-1.50. mg/min infusion. If ventricular arrythmia was uncontrolled, additional bolus of 150 mg could be repeated every other 30 min, and oral Amiodarone 0.2 mg, tid, observation treatment for five days. Results: In 52 patients, 35 cases (67.3%) were significant effective, 11 cases (21.2%) were effective, 6 cases (11.5%) were invalid, the total effective rate was 88.5%. There were no significant changes in the P-R, QRS, QT intervals during iv Amiodarone therapy. Conclusion: Amiodarone can be used effectively and safely to control ventricular arrythmia on ACS with chronic heart failure patients.%目的:观察胺碘酮对急性冠脉综合征(ACS)伴心力衰竭患者室性心律失常的疗效和安全性.方法:对52例ACS伴心力衰竭并发室性心律失常的患者,首剂给予胺碘酮3~5mg/kg静注,10~20min注完,之后给予0.75~1.50mg/min 静滴维持.若心律失常控制不满意,可间隔30 min重复注射胺碘酮150 mg一次,同时口服胺碘酮0.2 mg,tid,治疗5 d.结果:52例患者中,显效35例(67.3%),有效11例(21.2%),无效6例(11.5%),总有效率为88.5%,静脉应用早期对P-R、QRS、QT间期均无影响.结论:胺碘酮对ACS伴心力衰竭的室性心律失常有良好的疗效.

  2. 静脉应用胺碘酮与西地兰对快速阵发性房颤的疗效比较%Comparison of the Clinical Efficacy Between Amiodarone and Cedilanid in the Treatment of Rapid Paroxysmal Atrial Fibrillation with Intravenous Ad-ministration

    Institute of Scientific and Technical Information of China (English)

    李妍

    2014-01-01

    目的:比较静脉推注胺碘酮与西地兰治疗快速阵发性房颤的疗效差异。方法选择92例快速阵发性房颤患者,随机分为胺碘酮组和西地兰组各46例,分别静推胺碘酮和西地兰,观察房颤的转复、心室率变化及不良反应。结果胺碘酮组与西地兰组的治疗有效率分别为82.61%和58.70%,差异有统计学意义(P<0.05)。两组治疗前后心室率下降均差异有统计学意义(P<0.05)。其中胺碘酮组效果更明显,两组比较差异有统计学意义(P<0.05)。结论静脉应用胺碘酮治疗快速阵发性房颤,疗效优于西地兰,不良反应轻,值得推广。%Objective To compare the clinical efficacy between amiodarone and cedilanid in the treatment of rapid paroxysmal a-trial fibrillation with intravenous administration. Methods 92 patients with rapid paroxysmal atrial fibrillation were selected and randomly divided into amiodarone group (n=46) and cedilanid group(n=46), and respectively treated with amiodarone and cedilanid intravenously. The effective rate, change of heart rate and adverse reactions of the two groups were observed. Results The total ef-fective rate was 82.61%in the amiodarone group and 58.70%in the cedilanid group, with a significant difference between the two groups (P<0.05). There was statistically significant difference in heart rate of two groups of patients before and after the treatment (P<0.05). Compared with the cedilanid group, the efficacy of amiodarone group was more obvious and the difference between the two groups was statistically significant (P<0.05). Conclusion Intravenous amiodarone is more effective than cedilanid for rapid paroxysmal artrial fibrillation, with minor side effects. It is worthy of clinical promotion.

  3. 文献对胺碘酮、利多卡因治疗阵发性室性心动过速预后差异的Meta分析%Research Document of Amiodarone, Lidocaine Treatment of Paroxysmal Supraventricular Tachycardia Meta-analysis of Differences in Prognosis

    Institute of Scientific and Technical Information of China (English)

    陈阵; 刘亚凤; 胡念丹; 苏薇薇; 李文强

    2012-01-01

    目的 评价相关文献中关于使用胺碘酮和利多卡因治疗阵发性室性心动过速(paroxysmal ventricular tachycardia,PVT)的预后差异.方法 检索Cochrane图书馆、EMbase、Pubmed及Medline 1996~ 2011年中采用随机对照试验(RCT)中关于使用胺碘酮、利多卡因治疗PVT预后差异的文献,对纳入文献质量进行评价和资料提取,并进行Meta分析.结果 本研究共纳入5篇文献,均表明使用胺碘酮治疗PVT较利多卡因预后好,差异有统计学意义(P<0.05);两药治疗PVT在复律失败人数、死亡人数、药物不良反应等方面比较差异均有统计学意义(P<0.05).结论 使用胺碘酮治疗PVT可降低患者住院次数,且未增加不良反应,故当PVT症状不严重时,胺碘酮可作为治疗的首选.%Objective To evaluate the pertinent literature of amiodarone, lidocaine treatment in the prognosis of paroxysmal ventricular tachycardia ( PVT). Methods The papers from Cochrane Library, EM base, Pubmed were searched, Medline for RCT of paroxysmal ventricular tachycardia treatment using amiodarone or lidocaine was randomly evalvated, an assessment for the methodology after screening and selecting all the papers with the help of the software of Review manager 5.0 was made, and Meta analysis was conducted. Results A total of 5 literatures were included, all of which results showed that amiodarone had a better prognosis than lidocaine, and the difference was significant (P < 0.05 ) ; the number of successful cardio version, adverse reactions and the number of deaths related to the RCT docamented significant differences between the Amiodarone and Lidocaine treatment of PVT (P <0.05). Conclusion The use of PVT Amiodarone treatment can reduce the rate of hospitalization, without increasing the incidence rate of other adverse reactions. Therefore, in minor cases of PVT, Amiodarone can be the preferred treatment method.

  4. Structural fold, conservation and Fe(II) binding of the intracellular domain of prokaryote FeoB

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Kuo-Wei; Chang, Yi-Wei; Eng, Edward T.; Chen, Jai-Hui; Chen, Yi-Chung; Sun, Yuh-Ju; Hsiao, Chwan-Deng; Dong, Gang; Spasov, Krasimir A.; Unger, Vinzenz M.; Huang, Tai-huang (Yale-MED); (Perutz Lab); (AS); (NTHU-Taiwan)

    2010-09-17

    FeoB is a G-protein coupled membrane protein essential for Fe(II) uptake in prokaryotes. Here, we report the crystal structures of the intracellular domain of FeoB (NFeoB) from Klebsiella pneumoniae (KpNFeoB) and Pyrococcus furiosus (PfNFeoB) with and without bound ligands. In the structures, a canonical G-protein domain (G domain) is followed by a helical bundle domain (S-domain), which despite its lack of sequence similarity between species is structurally conserved. In the nucleotide-free state, the G-domain's two switch regions point away from the binding site. This gives rise to an open binding pocket whose shallowness is likely to be responsible for the low nucleotide-binding affinity. Nucleotide binding induced significant conformational changes in the G5 motif which in the case of GMPPNP binding was accompanied by destabilization of the switch I region. In addition to the structural data, we demonstrate that Fe(II)-induced foot printing cleaves the protein close to a putative Fe(II)-binding site at the tip of switch I, and we identify functionally important regions within the S-domain. Moreover, we show that NFeoB exists as a monomer in solution, and that its two constituent domains can undergo large conformational changes. The data show that the S-domain plays important roles in FeoB function.

  5. 金属铝对氧化锆制品的去稳定化行为%Destabilizing Effect of Zirconia Products Caused by Aluminum

    Institute of Scientific and Technical Information of China (English)

    田晓利; 薛群虎; 薛崇勃; 刘宁; 徐伟; 韩艳茹

    2012-01-01

    Thermodynamic analysis on destabilizing effect of zirconia products caused by aluminum is carried on by material Gibbs free energy function, and then the experimental verification was tested by scanning electron microscope ( SEM). The results show that: (1 ) Aluminum reacts with calcium oxide, the stabilizer of zirconia, forming some sheet-like calcium hexaluminate. It results in the stabilizer loss and the volume destabilization of zirconia; (2) Aluminum reacts with magnesium oxide, the stabilizer of zirconia, and form some octahedral magnesia-alumina spinel. It results in the stabilizer loss and the volume destabilization of zirconia; (3) The destabilizing effect of zirconia caused by aluminum can be defined three layers, which are original layer, transition layer and reaction layer.%采用物质吉布斯自南能函数法对金属铝造成氧化锆制品的去稳定化行为进行了热力学分析,并结合扫描电子显微镜(SEM)进行了试验验证.结果表明:(1)含锆质制品中,金属铝易与氧化锆的稳定剂氧化钙发生反应,生成层片状六铝酸钙,造成氧化锆中稳定剂脱溶,体积失稳;(2)金属铝易与氧化锆的稳定剂氧化镁进行反应,生成正八面体的镁铝尖晶石,造成氧化锆中稳定剂脱溶,体积失稳;(3)金属铝对氧化锆制品的去稳定化行为,可界定为原始层、脱溶过渡层和反应层三层.

  6. Polycyclic aromatic hydrocarbon body residues and lysosomal membrane destabilization in mussels exposed to the Dubai Star bunker fuel oil (intermediate fuel oil 380) spill in San Francisco Bay.

    Science.gov (United States)

    Hwang, Hyun-Min; Stanton, Beckye; McBride, Toby; Anderson, Michael J

    2014-05-01

    Following the spill of bunker fuel oil (intermediate fuel oil 380, approximately 1500-3000 L) into San Francisco Bay in October 2009, polycyclic aromatic hydrocarbon (PAH) concentrations in mussels from moderately oiled areas increased up to 87 554 ng/g (dry wt) and, 3 mo later, decreased to concentrations found in mussels collected prior to oiling, with a biological half-life of approximately 16 d. Lysosomal membrane destabilization increased in mussels with higher PAH body burdens.

  7. Comparison on Effect of Amiodarone and Propafenone Treating Paroxysmal Supraventricular Tachycardia%胺碘酮和普罗帕酮治疗阵发性室上性心动过速的效果比较

    Institute of Scientific and Technical Information of China (English)

    赵敏

    2014-01-01

    目的:比较胺碘酮和普罗帕酮治疗阵发性室上性心动过速的疗效。方法将88例阵发性室上性心动过速患者随机分为两组,A 组44例患者给予胺碘酮治疗,B 组44例患者给予普罗帕酮治疗。结果两组复律成功率比较,差异无统计学意义(P >0.05);A 组复律时间长于 B 组,复律时间分布较 B 组差,不良反应发生率低于 B 组,差异均有统计学意义(P <0.05)。结论胺碘酮和普罗帕酮对阵发性室上性心动过速的治疗各有利弊,普罗帕酮见效快、患者耐受差,适用于无严重器质性心脏病及心功能正常者;而胺碘酮见效较慢、不良反应少、适应证广,适用于器质性心脏病及心功能不全患者。%Objective To compare the efficacy of amiodarone and propafenone treating paroxysmal supraventricular tachycardia. Methods 88 cases with paroxysmal supraventricular tachycardia were selected and divided into two groups randomly. The A group for 44 cases were treated with amiodarone, and the B group for 44 cases were treated with propafenone. Results The difference for the successful rate of cardioversion between two groups had no statistical significance(P>0.05). The cardioversion time of A group was longer than that of B group, and the cardioversion time distribution of A group was worse than that of B group, the incidence rate of adverse reactions in A group was lower than that of B group ,which had statistical significance (P<0.05). Conclusion Propafenone and propafenone treating paroxysmal supraventricular tachycardia has advantages and disadvantages. Amiodarone has the advantages that the effect is fast, the patients have poor tolerance and it is applied to the patients with normal cardiac function and without organic heart disease, and amiodarone has the advantages that the effect is slow, there are few adverse reactions, there are wide range of indications, and it is applied to patients with organic heart disease

  8. Roles of autophagy in elimination of intracellular bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Eun-Kyeong eJo

    2013-05-01

    Full Text Available As a fundamental intracellular catabolic process, autophagy is important and required for the elimination of protein aggregates and damaged cytosolic organelles during a variety of stress conditions. Autophagy is now being recognized as an essential component of innate immunity; i.e., the recognition, selective targeting, and elimination of microbes. Because of its crucial roles in the innate immune system, therapeutic targeting of bacteria by means of autophagy activation may prove a useful strategy to combat intracellular infections. However, important questions remain, including which molecules are critical in bacterial targeting by autophagy, and which mechanisms are involved in autophagic clearance of intracellular microbes. In this review, we discuss the roles of antibacterial autophagy in intracellular bacterial infections (Mycobacteria, Salmonella, Shigella, Listeria, and Legionella and present recent evidence in support of molecular mechanisms driving autophagy to target bacteria and eliminate invading pathogens.

  9. Intracellular calcium ions as regulators of renal tubular sodium transport.

    Science.gov (United States)

    Windhager, E; Frindt, G; Yang, J M; Lee, C O

    1986-09-15

    This review addresses the putative role of intracellular calcium ions in the regulation of sodium transport by renal tubules. Cytoplasmic calcium-ion activities in proximal tubules of Necturus are less than 10(-7) M and can be increased by lowering the electrochemical potential gradient for sodium ions across the peritubular cell membrane, or by addition of quinidine or ionomycin to peritubular fluid. Whereas lowering of the peritubular Na concentration increases cytosolic [Ca++] and [H+], ionomycin, a calcium ionophore, raises intracellular [Ca++] without decreasing pHi. The intracellular calcium-ion level is maintained by transport processes in the plasma membrane and membranes of intracellular organelles, as well as by calcium-binding proteins. Calcium ions inhibit net transport of sodium by reducing the rate of sodium entry across the luminal cell membrane. In the collecting tubule this inhibition is caused, at least in part, by an indirect reduction in the activity of the amiloride-sensitive sodium channel. PMID:2430134

  10. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth

    Science.gov (United States)

    Microsporidia comprise a large phylum of obligate intracellular eukaryotes that are fungalrelated parasites responsible for widespread disease, and here we address questions about microsporidia biology and evolution. We sequenced three microsporidian genomes from two species, Nematocida parisii and...

  11. Key Role for Intracellular K+ and Protein Kinases Sat4/Hal4 and Hal5 in the Plasma Membrane Stabilization of Yeast Nutrient Transporters▿

    Science.gov (United States)

    Pérez-Valle, Jorge; Jenkins, Huw; Merchan, Stephanie; Montiel, Vera; Ramos, José; Sharma, Sukesh; Serrano, Ramón; Yenush, Lynne

    2007-01-01

    K+ transport in living cells must be tightly controlled because it affects basic physiological parameters such as turgor, membrane potential, ionic strength, and pH. In yeast, the major high-affinity K+ transporter, Trk1, is inhibited by high intracellular K+ levels and positively regulated by two redundant “halotolerance” protein kinases, Sat4/Hal4 and Hal5. Here we show that these kinases are not required for Trk1 activity; rather, they stabilize the transporter at the plasma membrane under low K+ conditions, preventing its endocytosis and vacuolar degradation. High concentrations (0.2 M) of K+, but not Na+ or sorbitol, transported by undefined low-affinity systems, maintain Trk1 at the plasma membrane in the hal4 hal5 mutant. Other nutrient transporters, such as Can1 (arginine permease), Fur4 (uracil permease), and Hxt1 (low-affinity glucose permease), are also destabilized in the hal4 hal5 mutant under low K+ conditions and, in the case of Can1, are stabilized by high K+ concentrations. Other plasma membrane proteins such as Pma1 (H+-pumping ATPase) and Sur7 (an eisosomal protein) are not regulated by halotolerance kinases or by high K+ levels. This novel regulatory mechanism of nutrient transporters may participate in the quiescence/growth transition and could result from effects of intracellular K+ and halotolerance kinases on membrane trafficking and/or on the transporters themselves. PMID:17548466

  12. Acquisition of an animal gene by microsporidian intracellular parasites

    OpenAIRE

    Selman, Mohammed; Pombert, Jean-François; Solter, Leellen; Farinelli, Laurent; Weiss, Louis M.; Keeling, Patrick; Corradi, Nicolas

    2011-01-01

    Parasites have adapted to their specialised way of life by a number of means, including the acquisition of genes by horizontal gene transfer. These newly acquired genes seem to come from a variety of sources, but seldom from the host, even in the most intimate associations between obligate intracellular parasite and host [1]. Microsporidian intracellular parasites have acquired a handful of genes, mostly from bacteria, that help them take energy from their hosts or protect them from the envir...

  13. In vivo metabolite compartmentalization probed using intracellular GdDTPA

    DEFF Research Database (Denmark)

    Peters, David Alberg; Rowland, Ian

    Fast trans-membrane water exchange enables in- tracellular relaxation enhancement of water by contrast agents in the extracellular space. For me- tabolites not in fast exchange across membranes, intracellular metabolite relaxation enhancement will only occur if the contrast agent and metabolite a...... are in the same compartment. Extracellular contrast has utilized electroporation methods to deliver GdDTPA into the cytosol of rat muscle in vivo in order to probe the intracellular compart- mentalization of MR-visible metabolites....

  14. Ethambutol plasma and intracellular pharmacokinetics: A pharmacogenetic study.

    Science.gov (United States)

    Fatiguso, Giovanna; Allegra, Sarah; Calcagno, Andrea; Baietto, Lorena; Motta, Ilaria; Favata, Fabio; Cusato, Jessica; Bonora, Stefano; Perri, Giovanni Di; D'Avolio, Antonio

    2016-01-30

    We evaluated ethambutol plasma and intracellular pharmacokinetic according to single nucleotide polymorphisms in ABCB1, OATP1B1, PXR, VDR, CYP24A1 and CYP27B1 genes. Mycobacterium tubercolosis infected patients were enrolled. Standard weight-adjusted antitubercular treatment was administered intravenously for 2 weeks and then orally. Allelic discrimination was performed by real-time PCR. Ethambutol plasma and intracellular concentrations were measured by UPLC-MS/MS methods. Twenty-four patients were included. Considering weeks 2 and 4, median plasma Ctrough were 73 ng/mL and 247 ng/mL, intracellular Ctrough were 16,863 ng/mL and 13,535 ng/mL, plasma Cmax were 5627 ng/mL and 2229 ng/mL, intracellular Cmax were 133,830 ng/mL and 78,544 ng/mL. At week 2, ABCB1 3435 CT/TT (p=0.023) and CYP24A1 8620 AG/GG (p=0.030) genotypes for plasma Ctrough, BsmI AA (p=0.036) for intracellular Ctrough and BsmI AA (pethambutol plasma and intracellular concentrations; this may further the potential use of pharmacogenetic for tailoring antitubercular treatment. PMID:26642947

  15. Clinical Analysis of the Treatment of Arrhythmia in Patients with Coronary Heart Disease Combined with the Stability of the Core Particles and Amiodarone%稳心颗粒联合胺碘酮治疗冠心病心律失常疗效分析

    Institute of Scientific and Technical Information of China (English)

    冯宝连

    2016-01-01

    Objective To observe the metacentre grain joint amiodarone treatment of arrhythmia in coronary heart disease clinical curative effect. Methods From October 2009 to October 2009 treatment of 90 cases of patients with arrhythmia in coronary heart disease, were randomly divided into two groups, treatment group 45 cases, on the basis of conventional treatment of oral metacentric particles and amiodarone; Control group 45 cases, on the basis of conventional treatment taking amiodarone, course of six weeks. Look before and after using patients electrocardiogram (ecg) and the improvement of clinical symptoms. Results The curative effect of treatment group is better than that of control group ( < 0.05). Conclusion metacentric particles joint amiodarone has good curative effect of treatment of coronary heart disease (CHD).%目的观察稳心颗粒联合胺碘酮治疗冠心病心律失常的临床疗效.方法选取我院2009年10月~2015年10月治疗的冠心病心律失常患者90例,随机分为两组,治疗组45例,在常规治疗基础上口服稳心颗粒和胺碘酮;对照组45例,在常规治疗基础上服用胺碘酮,疗程6w.观察用药前/后患者心电图及临床症状的改善程度.结果治疗组疗效优于对照组(<0.05).结论稳心颗粒联合胺碘酮治疗冠心病心律失常具有良好的疗效.

  16. Emprego de altas doses de amiodarona via oral na reversão da fibrilação atrial no pós-operatório de cirurgia cardíaca High dose amiodarone for the reversion of atrial fibrillation during the postoperative period of cardiac surgery

    Directory of Open Access Journals (Sweden)

    João Carlos Vieira da Costa Guaragna

    1997-12-01

    Full Text Available OBJETIVO: Relatar a experiência no emprego de altas doses de amiodarona via oral (1800mg/d na reversão da fibrilação atrial (FA em pacientes submetidos à cirurgia cardíaca. MÉTODOS: Analisados, retrospectivamente, 80 pacientes que apresentaram FA no pós operatório de cirurgia cardíaca, constituindo 2 grupos: grupo A com 28 pacientes em uso de amiodarona e grupo B recebendo digital, sendo que este grupo foi subdividido no grupo C com 21 pacientes onde foi associada amiodarona, quando não houvesse reversão da arritmia em 48h. As diferenças foram consideradas significativas para um valor de PPURPOSE: To report our experience using high dose oral amiodarone (1,800mg/day for the reversion of atrial fibrillation to sinus rhythm in patients submitted to cardiac surgery. METHODS: We retrospectively analyzed the records of 80 patients who had atrial fibrillation during the postoperative period after cardiac surgery, initially divided in two groups: group A, 28 patients that used amiodarone, and group B composed of patients receiving digoxin. The latter group was divided further in a third group (C, with 21 patients in which amiodarone was associated with digoxin if there was no reversion of the arrhythmia after 48 hours of treatment. The observed differences were considered significant at P<0.05. RESULTS: Atrial fibrillation occurred in 19.4% of the patients submitted to surgery, predominating in males, 60 to 69 years-old. In group A there was reversion to sinus rhythm in 78.6% of the cases. In group B digoxin succeeded in 60%, and in group C 90% of the patients reverted to sinus rhythm. CONCLUSION: High dose oral amiodarone, alone or combined to digoxin, can be safe and effective for the treatment of atrial fibrillation after cardiac surgery.

  17. The clinical effects of amiodarone combination with atorvastatin in the treatment of heart failure with malignancy arrhythmia in old patients%胺碘酮联用阿托伐他汀治疗老年心衰恶性心律失常观察

    Institute of Scientific and Technical Information of China (English)

    陈晓亮

    2012-01-01

      Objective: To observe the therapeutic effect of amiodarone combination with atorvastatin in the treatment of heart failure with malignancy arrhythmia. Methods: 47 patients were randomly divided into control group and therapy group. 23 patients in control group were treated with amiodarone. 24 patients in therapy group were treated with amiodarone combination with atorvastatin. The curative effects were observed. Results: The two groups both have the therapeutic effects on heart failure with malignancy arrhythmia in old patients. The total effective rate in therapy group was 95.7% which was significantly higher than that in control group (69.6%). Conclusion: Amiodarone combination with atorvastatin was a safety and effective method in the treatment of heart failure with malignancy arrhythmia in old patients.%  目的观察胺碘酮联合阿托伐他汀对老年心力衰竭合并恶性心律失常的治疗效果.方法47例患者随机分为对照组(胺碘酮治疗组)23例和治疗组(阿托伐他汀联合胺碘酮治疗组)24例,观察其疗效.结果两组均对老年心衰恶性心律失常有治疗效果,治疗组总有效率95.7%,显著高于对照组的总有效率69.6%.结论胺碘酮联合阿托伐他汀治疗老年心衰恶性心律失常是安全有效的治疗方法.

  18. Clinical observation of intravenous injection of amiodarone combined with safflower yellow pigment in treatment of tachyarrhythmias%胺碘酮联合红花黄色素静脉注射治疗快速心律失常的临床观察

    Institute of Scientific and Technical Information of China (English)

    高翔

    2012-01-01

    目的 观察胺碘酮联合红花黄色素静脉注射治疗快速心律失常的临床疗效.方法 将95例快速心律失常患者随机分为两组,在常规治疗的基础上,观察组(50例)使用胺碘酮联合红花黄色素,对照组(45例)使用胺碘酮.结果 观察组总有效率88.0%,对照组总有效率71.1%,两组比较,差异有统计学意义(P<0.05).观察组起效时间短于对照组,治疗后心率较对照组慢,差异均有统计学意义.结论 静脉联用胺碘酮与红花黄色素治疗快速心律失常安全且有效.%[ Objective ] To observe the efficacy of intravenous injection of amiodarone combined with safflower yellow pigment in treatment of tachyarrhythmias. [Methods] A total of 95 cases of tachyarrhythmias were divided into 2 groups. Based on the conventional treatment, the observation group( 50 cases ) received amiodarone and safflower yellow pigment treatment, the control group (45 casese) received amiodarone treatment. [Results] The total effective rate in observation group and control group was 88.0% and 71.1% , respectively, the difference was significant(P<0.05). The onset time of observation group was shorter than that of the control group, with slower heart rate in observation group, compared with the control group. [ Conclusion]Intravenous injection of amiodarone combined with safflower yellow pigment is safe and effective in treatment of tachyarrhythmias.

  19. Observation of clinical effect by Shensongyangxin capsule combined with amiodarone in the treatment of arrhythmia%参松养心胶囊与胺碘酮联合治疗心律失常临床治疗效果观察

    Institute of Scientific and Technical Information of China (English)

    张雪玲; 李建绪

    2015-01-01

    Objective To investigate the clinical effect by Shensongyangxin capsule combined with amiodarone in the treatment of arrhythmia.Methods There were 60 patients with arrhythmia as study subjects. They were divided by their willingness into control group and observation group, with 30 cases in each group. The observation group received Shensongyangxin capsule combined with amiodarone for treatment, and the control group received amiodarone. Curative effects and adverse reactions of the two groups were compared.Results The total effective rates of the observation group and control group were respectively 90.0% and 66.7%, and the difference between the two groups had statistical significance (P0.05).Conclusion Combination of Shensongyangxin capsule and amiodarone can improve control effect on arrhythmia, and this method is worthy of promotion and application.%目的:探讨参松养心胶囊与胺碘酮联合治疗心律失常的临床效果。方法60例心律失常患者作为研究对象,根据患者意愿分为对照组和观察组,每组30例。观察组接受参松养心胶囊和胺碘酮治疗,对照组仅接受胺碘酮治疗,比较两组治疗效果及不良反应。结果观察组和对照组总有效率分别为90.0%和66.7%,组间差异具有统计学意义(P0.05)。结论参松养心胶囊与胺碘酮联合用药可提升心律失常控制效果,值得推广使用。

  20. Clinical Observation of Amiodarone Combined With Wenxin Granule in the Treatment of Heart Failure Complicated With Arrhythmia%胺碘酮联合稳心颗粒治疗心衰合并心律失常的临床观察

    Institute of Scientific and Technical Information of China (English)

    高尚

    2015-01-01

    Objective To explore the clinical effect of amiodarone combined with Wenxin Granule in the treatment of heart failure complicated with arrhythmia. Methods 80 cases of patients with heart failure combined with arrhythmia were randomly divided into observation group and control group, respectively treated with amiodarone and amiodarone combined with Wenxin Granule treatment. Results Observation of curative effect, the patient's heart rate, QT interval, LVEF improvement was superior to the control group, the incidence of adverse reaction was lower than the control group (P<0.05). Conclusion Amiodarone combined with Wenxin Granule in the treatment of heart failure complicated with arrythmia curative effect, worthy of clinical application.%目的:探讨胺碘酮联合稳心颗粒治疗心衰合并心律失常的临床效果。方法将80例心衰合并心律失常患者随机分为观察组和对照组,分别给予胺碘酮治疗和胺碘酮联合稳心颗粒治疗。结果观察组疗效、患者心率、QT间期、LVEF改善情况均优于对照组,不良反应发生率明显低于对照组(P<0.05)。结论胺碘酮联合稳心颗粒治疗心衰合并心律失常疗效确切,值得临床应用推广。

  1. Analysis of Clinical Effect on Irbesartan- Amiodarone Combination In Treatment of Chronic Heart Failure With Ventricular Arrhythmia%厄贝沙坦联合胺碘酮治疗慢性心力衰竭合并室性心律失常的临床疗效分析

    Institute of Scientific and Technical Information of China (English)

    刘春英

    2015-01-01

    目的:探究厄贝沙坦联合胺碘酮治疗慢性心力衰竭合并室性心律失常的临床疗效。方法对照组慢性心力衰竭合并室性心律失常患者单纯经胺碘酮治疗,观察组经厄贝沙坦联合胺碘酮治疗。结果观察组治疗后心功能临床总有效率与心律失常临床总有效率为92.1%高于对照组;且心率、射血分数及QT离散度临床指标改善程度均优于对照组,具有统计学差异(P<0.05)。结论厄贝沙坦联合胺碘酮治疗慢性心力衰竭合并心律失常,可改善心功能与心律失常情况。%ObjectiveTo explore the clinical effect on irbesartan- amiodarone combination in treatment of chronic heart failure with ventricular arrhythmia.MethodsThe patients in control group with chronic heart failure with ventricular arrhythmia were simply treated with amiodarone treatment, the patients in observation group were treated with irbesartan- amiodarone combination.ResultsThe total effective rate of cardiac function and clinical arrhythmia was 92.1%. was higher than the control group. The improvement of clinical the heart rate, ejection fraction and QT dispersion degree in observation group were superior to control group signiifcantly (P<0.05).Conclusion The clinical effect on irbesartan- amiodarone combination in treatment of chronic heart failure with ventricular arrhythmia is the improvement of heart function and cardiac arrhythmias.

  2. The Clinic Alapplication Value of Amiodarone in the Treatment of Chronic Heart Failure Complicated With Arrhythmia%胺碘酮治疗慢性心力衰竭并发心律失常的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    姜桂菊

    2015-01-01

    目的:讨论胺碘酮治疗慢性心力衰竭衰并发心律失常的临床应用价值。方法对照组采用抗心衰的治疗,研讨组在此基础上联合应用胺碘酮进行治疗。结果研讨组治疗效果、并发症等方面均优于对照组。结论在常规抗心衰的治疗基础上采用胺碘酮治疗心衰并发心律失常安全、有效。%ObjectiveTo investigate the clinic application value of amiodarone in the treatment of chronic heart failure complicated with arrhythmia. Methods The research group was treated with anti heart failure. The research group based on the combined application of amiodarone for the treatment.Results Research group of the treatment effect, complications were better than those of control group. ConclusionOn the basis of routine anti heart failure treatment on the use of amiodarone in the treatment of heart failure complicated with arrhythmia safe, effective.

  3. Proton-dependent zinc release from intracellular ligands.

    Science.gov (United States)

    Kiedrowski, Lech

    2014-07-01

    In cultured cortical and hippocampal neurons when intracellular pH drops from 6.6 to 6.1, yet unclear intracellular stores release micromolar amounts of Zn(2+) into the cytosol. Mitochondria, acidic organelles, and/or intracellular ligands could release this Zn(2+) . Although exposure to the protonophore FCCP precludes reloading of the mitochondria and acidic organelles with Zn(2+) , FCCP failed to compromise the ability of the intracellular stores to repeatedly release Zn(2+) . Therefore, Zn(2+) -releasing stores were not mitochondria or acidic organelles but rather intracellular Zn(2+) ligands. To test which ligands might be involved, the rate of acid-induced Zn(2+) release from complexes with cysteine, glutathione, histidine, aspartate, glutamate, glycine, and carnosine was investigated; [Zn(2+) ] was monitored in vitro using the ratiometric Zn(2+) -sensitive fluorescent probe FuraZin-1. Carnosine failed to chelate Zn(2+) but did chelate Cu(2+) ; the remaining ligands chelated Zn(2+) and upon acidification were releasing it into the medium. However, when pH was decreasing from 6.6 to 6.1, only zinc-cysteine complexes rapidly accelerated the rate of Zn(2+) release. The zinc-cysteine complexes also released Zn(2+) when a histidine-modifying agent, diethylpyrocarbonate, was applied at pH 7.2. Since the cytosolic zinc-cysteine complexes can contain micromolar amounts of Zn(2+) , these complexes may represent the stores responsible for an acid-induced intracellular Zn(2+) release. This study aimed at identifying intracellular stores which release Zn(2+) when pHi drops from 6.6 to 6.1. It was found that these stores are not mitochondria or acidic organelles, but rather intracellular Zn(2+) ligands. When the pH was decreasing from 6.6 to 6.1, only zinc-cysteine complexes showed a rapid acceleration in the rate of Zn(2+) release. Therefore, the stores responsible for an acid-induced intracellular Zn(2+) release in neurons may be the cytosolic zinc-cysteine complexes

  4. Intracellular Ca-carbonate biomineralization is widespread in cyanobacteria.

    Science.gov (United States)

    Benzerara, Karim; Skouri-Panet, Feriel; Li, Jinhua; Férard, Céline; Gugger, Muriel; Laurent, Thierry; Couradeau, Estelle; Ragon, Marie; Cosmidis, Julie; Menguy, Nicolas; Margaret-Oliver, Isabel; Tavera, Rosaluz; López-García, Purificación; Moreira, David

    2014-07-29

    Cyanobacteria have played a significant role in the formation of past and modern carbonate deposits at the surface of the Earth using a biomineralization process that has been almost systematically considered induced and extracellular. Recently, a deep-branching cyanobacterial species, Candidatus Gloeomargarita lithophora, was reported to form intracellular amorphous Ca-rich carbonates. However, the significance and diversity of the cyanobacteria in which intracellular biomineralization occurs remain unknown. Here, we searched for intracellular Ca-carbonate inclusions in 68 cyanobacterial strains distributed throughout the phylogenetic tree of cyanobacteria. We discovered that diverse unicellular cyanobacterial taxa form intracellular amorphous Ca-carbonates with at least two different distribution patterns, suggesting the existence of at least two distinct mechanisms of biomineralization: (i) one with Ca-carbonate inclusions scattered within the cell cytoplasm such as in Ca. G. lithophora, and (ii) another one observed in strains belonging to the Thermosynechococcus elongatus BP-1 lineage, in which Ca-carbonate inclusions lie at the cell poles. This pattern seems to be linked with the nucleation of the inclusions at the septum of the cells, showing an intricate and original connection between cell division and biomineralization. These findings indicate that intracellular Ca-carbonate biomineralization by cyanobacteria has been overlooked by past studies and open new perspectives on the mechanisms and the evolutionary history of intra- and extracellular Ca-carbonate biomineralization by cyanobacteria.

  5. High-Throughput Intracellular Antimicrobial Susceptibility Testing of Legionella pneumophila

    Science.gov (United States)

    Chiaraviglio, Lucius

    2015-01-01

    Legionella pneumophila is a Gram-negative opportunistic human pathogen that causes a severe pneumonia known as Legionnaires' disease. Notably, in the human host, the organism is believed to replicate solely within an intracellular compartment, predominantly within pulmonary macrophages. Consequently, successful therapy is predicated on antimicrobials penetrating into this intracellular growth niche. However, standard antimicrobial susceptibility testing methods test solely for extracellular growth inhibition. Here, we make use of a high-throughput assay to characterize intracellular growth inhibition activity of known antimicrobials. For select antimicrobials, high-resolution dose-response analysis was then performed to characterize and compare activity levels in both macrophage infection and axenic growth assays. Results support the superiority of several classes of nonpolar antimicrobials in abrogating intracellular growth. Importantly, our assay results show excellent correlations with prior clinical observations of antimicrobial efficacy. Furthermore, we also show the applicability of high-throughput automation to two- and three-dimensional synergy testing. High-resolution isocontour isobolograms provide in vitro support for specific combination antimicrobial therapy. Taken together, findings suggest that high-throughput screening technology may be successfully applied to identify and characterize antimicrobials that target bacterial pathogens that make use of an intracellular growth niche. PMID:26392509

  6. Intracellular calcium levels can regulate Importin-dependent nuclear import

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A., E-mail: David.Jans@monash.edu

    2014-07-18

    Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca{sup 2+} on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 and Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery.

  7. Advances in genetic manipulation of obligate intracellular bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Paul eBeare

    2011-05-01

    Full Text Available Infections by obligate intracellular bacterial pathogens result in significant morbidity and mortality worldwide. These bacteria include Chlamydia spp., which causes millions of cases of sexually transmitted disease and blinding trachoma annually, and members of the α-proteobacterial genera Anaplasma, Ehrlichia, Orientia and Rickettsia, agents of serious human illnesses including epidemic typhus. Coxiella burnetii, the agent of human Q fever, has also been considered a prototypical obligate intracellular bacterium, but recent host cell-free (axenic growth has rescued it from obligatism. The historic genetic intractability of obligate intracellular bacteria has severely limited molecular dissection of their unique lifestyles and virulence factors involved in pathogenesis. Host cell restricted growth is a significant barrier to genetic transformation that can make simple procedures for free-living bacteria, such as cloning, exceedingly difficult. Low transformation efficiency requiring long term culture in host cells to expand small transformant populations is another obstacle. Despite numerous technical limitations, the last decade has witnessed significant gains in genetic manipulation of obligate intracellular bacteria including allelic exchange. Continued development of genetic tools should soon enable routine mutation and complementation strategies for virulence factor discovery and stimulate renewed interest in these refractory pathogens. In this review, we discuss the technical challenges associated with genetic transformation of obligate intracellular bacteria and highlight advances made with individual genera.

  8. Intracellular Neural Recording with Pure Carbon Nanotube Probes.

    Directory of Open Access Journals (Sweden)

    Inho Yoon

    Full Text Available The computational complexity of the brain depends in part on a neuron's capacity to integrate electrochemical information from vast numbers of synaptic inputs. The measurements of synaptic activity that are crucial for mechanistic understanding of brain function are also challenging, because they require intracellular recording methods to detect and resolve millivolt- scale synaptic potentials. Although glass electrodes are widely used for intracellular recordings, novel electrodes with superior mechanical and electrical properties are desirable, because they could extend intracellular recording methods to challenging environments, including long term recordings in freely behaving animals. Carbon nanotubes (CNTs can theoretically deliver this advance, but the difficulty of assembling CNTs has limited their application to a coating layer or assembly on a planar substrate, resulting in electrodes that are more suitable for in vivo extracellular recording or extracellular recording from isolated cells. Here we show that a novel, yet remarkably simple, millimeter-long electrode with a sub-micron tip, fabricated from self-entangled pure CNTs can be used to obtain intracellular and extracellular recordings from vertebrate neurons in vitro and in vivo. This fabrication technology provides a new method for assembling intracellular electrodes from CNTs, affording a promising opportunity to harness nanotechnology for neuroscience applications.

  9. The cystic-fibrosis-associated ΔF508 mutation confers post-transcriptional destabilization on the C. elegans ABC transporter PGP-3

    Directory of Open Access Journals (Sweden)

    Liping He

    2012-11-01

    Membrane proteins make up ∼30% of the proteome. During the early stages of maturation, this class of proteins can experience localized misfolding in distinct cellular compartments, such as the cytoplasm, endoplasmic reticulum (ER lumen and ER membrane. ER quality control (ERQC mechanisms monitor folding and determine whether a membrane protein is appropriately folded or is misfolded and warrants degradation. ERQC plays crucial roles in human diseases, such as cystic fibrosis, in which deletion of a single amino acid (F508 results in the misfolding and degradation of the cystic fibrosis transmembrane conductance regulator (CFTR Cl– channel. We introduced the ΔF508 mutation into Caenorhabditis elegans PGP-3, a 12-transmembrane ABC transporter with 15% identity to CFTR. When expressed in intestinal epithelial cells, PGP-3wt was stable and efficiently trafficked to the apical plasma membrane through a COPII-dependent mechanism. However, PGP-3ΔF508 was post-transcriptionally destabilized, resulting in reduced total and apical membrane protein levels. Genetic or physiological activation of the osmotic stress response pathway, which causes accumulation of the chemical chaperone glycerol, stabilized PGP-3ΔF508. Efficient degradation of PGP-3ΔF508 required the function of several C. elegans ER-associated degradation (ERAD homologs, suggesting that destabilization occurs through an ERAD-type mechanism. Our studies show that the ΔF508 mutation causes post-transcriptional destabilization and degradation of PGP-3 in C. elegans epithelial cells. This model, combined with the power of C. elegans genetics, provides a new opportunity to genetically dissect metazoan ERQC.

  10. Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles.

    Science.gov (United States)

    Kushiyama, Yasunori; Honjo, Haruo; Niwa, Ryoko; Takanari, Hiroki; Yamazaki, Masatoshi; Takemoto, Yoshio; Sakuma, Ichiro; Kodama, Itsuo; Kamiya, Kaichiro

    2016-09-01

    It has been reported that blockade of the inward rectifier K(+) current (IK1) facilitates termination of ventricular fibrillation. We hypothesized that partial IK1 blockade destabilizes spiral wave (SW) re-entry, leading to its termination. Optical action potential (AP) signals were recorded from left ventricles of Langendorff-perfused rabbit hearts with endocardial cryoablation. The dynamics of SW re-entry were analyzed during ventricular tachycardia (VT), induced by cross-field stimulation. Intercellular electrical coupling in the myocardial tissue was evaluated by the space constant. In separate experiments, AP recordings were made using the microelectrode technique from right ventricular papillary muscles of rabbit hearts. Ba(2+) (10-50 μM) caused a dose-dependent prolongation of VT cycle length and facilitated termination of VT in perfused hearts. Baseline VT was maintained by a stable rotor, where an SW rotated around an I-shaped functional block line (FBL). Ba(2+) at 10 μM prolonged I-shaped FBL and phase-singularity trajectory, whereas Ba(2+) at 50 μM transformed the SW rotation dynamics from a stable linear pattern to unstable circular/cycloidal meandering. The SW destabilization was not accompanied by SW breakup. Under constant pacing, Ba(2+) caused a dose-dependent prolongation of APs, and Ba(2+) at 50 μM decreased conduction velocity. In papillary muscles, Ba(2+) at 50 μM depolarized the resting membrane potential. The space constant was increased by 50 μM Ba(2+) Partial IK1 blockade destabilizes SW rotation dynamics through a combination of prolongation of the wave length, reduction of excitability, and enhancement of electrotonic interactions, which facilitates termination of ventricular tachyarrhythmias. PMID:27422985

  11. Comparison of short-term efficacy and safety between amiodarone and esmolol treatment in elderly patients with acute myocardial infarction complicated with ventricular arrhythmia%胺碘酮与艾司洛尔治疗老年患者急性心肌梗死合并室性心律失常的短期疗效与安全性比较

    Institute of Scientific and Technical Information of China (English)

    邹德玲; 刘兴利; 方悦; 陈艳丽; 耿宁; 庞文跃

    2014-01-01

    目的 比较老年急性心肌梗死(AMI)合并严重室性心律失常患者静脉应用胺碘酮或艾司洛尔48 h内疗效及不良反应,为临床安全用药提供依据. 方法 2009年1月至2013年6月在中国医科大学附属盛京医院心脏内科连续住院治疗的老年AMI合并严重室性心律失常患者纳入研究,分为胺碘酮组与艾司洛尔组.胺碘酮组患者在10 min内静脉注射胺碘酮150 mg+ 5%葡萄糖注射液20 ml后经微量注射泵静脉输注胺碘酮1 mg/min共6h,减量至0.5 mg/min静脉输注24~48 h,之后口服胺碘酮0.2g,3次/d,共7d.艾司洛尔组患者在1 min内静脉注射艾司洛尔注射液0.5 mg/kg后经微量注射泵静脉输注艾司洛尔0.1 mg/(kg·min)共6h,减量至0.05 mg/(kg·min)静脉输注24 ~ 48 h,之后口服美托洛尔25 mg,2次/d,共7d.胺碘酮组和艾司洛尔组静脉应用胺碘酮或艾司洛尔6h后仍有室速发作者,分别加用上述艾司洛尔或胺碘酮治疗方案.比较2组患者治疗48 h内有效率和不良反应发生率. 结果 胺碘酮组和艾司洛尔组48 h内有效率分别为92.1%(35/38)和75.0%(27/36),组间差异有统计学意义(P=0.046);不良反应发生率分别为39.5%(15/38)和19.4%(7/36),组间差异无统计学意义(P =0.060).胺碘酮组2例伴有心力衰竭患者静脉用药24 h后出现急性肝损伤,停药并对症治疗2周后肝功能恢复正常. 结论 静脉应用胺碘酮治疗老年患者AMI合并严重室性心律失常有效率优于艾司洛尔.胺碘酮与艾司洛尔均较安全.高龄AMI且伴心力衰竭者静脉应用胺碘酮时需密切监测肝功能,出现肝损伤需立即停药并给予对症治疗.%Objective To compare the efficacy and safety of intravenous application of amiodarone or esmolol in elderly patients with ventricular arrhythmia following acute myocardial infarction (AMI) within 48 hours,and provide reference for safe use of medication in clinical practice.Methods Elderly hospitalized

  12. Quantifying intracellular hydrogen peroxide perturbations in terms of concentration

    Directory of Open Access Journals (Sweden)

    Beijing K. Huang

    2014-01-01

    Full Text Available Molecular level, mechanistic understanding of the roles of reactive oxygen species (ROS in a variety of pathological conditions is hindered by the difficulties associated with determining the concentration of various ROS species. Here, we present an approach that converts fold-change in the signal from an intracellular sensor of hydrogen peroxide into changes in absolute concentration. The method uses extracellular additions of peroxide and an improved biochemical measurement of the gradient between extracellular and intracellular peroxide concentrations to calibrate the intracellular sensor. By measuring peroxiredoxin activity, we found that this gradient is 650-fold rather than the 7–10-fold that is widely cited. The resulting calibration is important for understanding the mass-action kinetics of complex networks of redox reactions, and it enables meaningful characterization and comparison of outputs from endogenous peroxide generating tools and therapeutics across studies.

  13. Direct determination of the intracellular oxidation state of plutonium.

    Science.gov (United States)

    Gorman-Lewis, Drew; Aryal, Baikuntha P; Paunesku, Tatjana; Vogt, Stefan; Lai, Barry; Woloschak, Gayle E; Jensen, Mark P

    2011-08-15

    Microprobe X-ray absorption near edge structure (μ-XANES) measurements were used to determine directly, for the first time, the oxidation state of intracellular plutonium in individual 0.1-μm(2) areas within single rat pheochromocytoma cells (PC12). The living cells were incubated in vitro for 3 h in the presence of Pu added to the media in different oxidation states (Pu(III), Pu(IV), and Pu(VI)) and in different chemical forms. Regardless of the initial oxidation state or chemical form of Pu presented to the cells, the XANES spectra of the intracellular Pu deposits were always consistent with tetravalent Pu even though the intracellular milieu is generally reducing. PMID:21755934

  14. EFFECT OF TETRACYCLINES ON THE INTRACELLULAR AMINO ACIDS OF MOLDS.

    Science.gov (United States)

    FREEMAN, B A; CIRCO, R

    1963-07-01

    Freeman, Bob A. (University of Chicago, Chicago, Ill.) and Richard Circo. Effect of tetracyclines on the intracellular amino acids of molds. J. Bacteriol. 86:38-44. 1963.-The tetracycline antibiotics were shown to alter the amino acid metabolism of molds whose growth is not markedly affected. Eight molds were grown in the presence of these antiobiotics; four exhibited a general reduction in the concentration of the intracellular amino acids, except for glutamic acid and alanine. In most of these four cultures, the tetracyclines also caused the complete disappearance of arginine, lysine, proline, phenylalanine, and tyrosine from the intracellular amino acid pool. The significance of these observations and the usefulness of the method in the study of the mechanisms of antibiotic action are discussed. PMID:14051820

  15. Impact of the terminal bulges of HIV-1 cTAR DNA on its stability and the destabilizing activity of the nucleocapsid protein NCp7.

    Science.gov (United States)

    Beltz, Hervé; Azoulay, Joel; Bernacchi, Serena; Clamme, Jean-Pierre; Ficheux, Damien; Roques, Bernard; Darlix, Jean-Luc; Mély, Yves

    2003-04-18

    Reverse transcription of HIV-1 genomic RNA to double-stranded DNA by reverse transcriptase (RT) is a critical step in HIV-1 replication. This process relies on two viral proteins, the RT enzyme and nucleocapsid protein NCp7 that has well documented nucleic acid chaperone properties. At the beginning of the linear DNA synthesis, the newly made minus-strand strong-stop DNA ((-)ssDNA) is transferred to the 3'end of the genomic RNA by means of an hybridization reaction between transactivation response element (TAR) RNA and cTAR DNA sequences. Since both TAR sequences exhibit stable hairpin structures, NCp7 needs to destabilize the TAR structures in order to chaperone their hybridization. To further characterize the relationships between TAR stability and NC-mediated destabilization, the role of the A(49) and G(52) bulged residues in cTAR DNA stability was investigated. The stability of cTAR and mutants where one or the two terminal bulges were replaced by base-pairs as well as the NCp7-mediated destabilization of these cTAR sequences were examined. Thermodynamic data indicate that the two bulges cooperatively destabilize cTAR by reducing the stacking interactions between the bases. This causes a free energy change of about 6.4 kcal/mol and seems to be critical for NC activity. Time-resolved fluorescence data of doubly labelled cTAR derivatives suggest that NC-mediated melting of cTAR ends propagates up to the 10C.A(44) mismatch or T(40) bulge. Fluorescence correlation spectroscopy using two-photon excitation was also used to monitor cTAR ends fraying by NC. Results show that NC causes a very significant increase of cTAR ends fraying, probably limited to the terminal base-pair in the case of cTAR mutants. Since the TAR RNA and cTAR DNA bulges or mismatches appear well conserved among all HIV-1 strains, the present data support the notion of a co-evolutionary relationship between TAR and NC activity. PMID:12684000

  16. Impediment of E. coli UvrD by DNA-destabilizing force reveals a strained-inchworm mechanism of DNA unwinding

    OpenAIRE

    Sun, Bo; Wei, Kong-Ji; Zhang, Bo; Zhang, Xing-Hua; Dou, Shuo-Xing; Li, Ming; Xi, Xu Guang

    2008-01-01

    Escherichia coli UvrD is a non-ring-shaped model helicase, displaying a 3′–5′ polarity in DNA unwinding. Using a transverse magnetic tweezer and DNA hairpins, we measured the unwinding kinetics of UvrD at various DNA-destabilizing forces. The multiform patterns of unwinding bursts and the distributions of the off-times favour the mechanism that UvrD unwinds DNA as a dimer. The two subunits of the dimer coordinate to unwind DNA processively. They can jointly switch strands and translocate back...

  17. Intracellular biology and virulence determinants of Francisella tularensis revealed by transcriptional profiling inside macrophages

    OpenAIRE

    Wehrly, Tara D.; Chong, Audrey; Virtaneva, Kimmo; Sturdevant, Dan E.; Child, Robert; Edwards, Jessica A.; Brouwer, Dedeke; Nair, Vinod; Fischer, Elizabeth R.; Wicke, Luke; Curda, Alissa J.; Kupko, John J.; Martens, Craig; Crane, Deborah D.; Bosio, Catharine M.

    2009-01-01

    The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis subsp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages, to characterize its intracellular biology and identify pathogenic determinants based on their intracellular expression profile...

  18. Cadmium induces transcription independently of intracellular calcium mobilization.

    Directory of Open Access Journals (Sweden)

    Brooke E Tvermoes

    Full Text Available BACKGROUND: Exposure to cadmium is associated with human pathologies and altered gene expression. The molecular mechanisms by which cadmium affects transcription remain unclear. It has been proposed that cadmium activates transcription by altering intracellular calcium concentration ([Ca(2+](i and disrupting calcium-mediated intracellular signaling processes. This hypothesis is based on several studies that may be technically problematic; including the use of BAPTA chelators, BAPTA-based fluorescent sensors, and cytotoxic concentrations of metal. METHODOLOGY/PRINCIPAL FINDING: In the present report, the effects of cadmium on [Ca(2+](i under non-cytotoxic and cytotoxic conditions was monitored using the protein-based calcium sensor yellow cameleon (YC3.60, which was stably expressed in HEK293 cells. In HEK293 constitutively expressing YC3.60, this calcium sensor was found to be insensitive to cadmium. Exposing HEK293::YC3.60 cells to non-cytotoxic cadmium concentrations was sufficient to induce transcription of cadmium-responsive genes but did not affect [Ca(2+](i mobilization or increase steady-state mRNA levels of calcium-responsive genes. In contrast, exposure to cytotoxic concentrations of cadmium significantly reduced intracellular calcium stores and altered calcium-responsive gene expression. CONCLUSIONS/SIGNIFICANCE: These data indicate that at low levels, cadmium induces transcription independently of intracellular calcium mobilization. The results also support a model whereby cytotoxic levels of cadmium activate calcium-responsive transcription as a general response to metal-induced intracellular damage and not via a specific mechanism. Thus, the modulation of intracellular calcium may not be a primary mechanism by which cadmium regulates transcription.

  19. 胺碘酮协同卡托普利对老年高血压伴阵发性心房颤动疗效观察%The clinical research of the treatment of Captopril and Amiodarone to elderly hypertensive patients with paroxysmal atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    谢基连; 林小青; 李仕宁

    2009-01-01

    Objective: To evaluate the treatment of Captopril and Amiodarone to cure the elder hypertension and paroxysmal atrial fibrillation. Methods: 70 cases of elderly hypertensive patients with paroxysmal atrial fibrillation were randomly divided into Amiodarone group and combination group (Captopril combined Amiodarone), they were treated of 12 months, the rhythm control of the two groups after treatment 3, 6, 9,12 months and the left atrial diameter after treatment 6, 12 months were calculated. Results: There were significant changes of the blood pressure after treatment in each group, but no significant difference between two groups. The rate of rhythm control of the combination group was significant higher than that of the Amiodarone group after 9 and 12 months treatment. The change of the left atrial diameter was significant between the two groups after 12 months treatment. Conclusion: Captopfil combined with Amiodarone can decrease the blood pressure, inhibit left atrial enlargement and effective in preventing recurrence of atrial fibrillation in elderly hypertensive paroxysmal atrial fibrillation.%目的:观察卡托普利联合胺碘酮治疗老年高血压伴阵发性心房颤动(房颤)患者的疗效.方法:将70例老年高血压伴阵发性房颤患者随机分为胺碘酮组和联合用药组(卡托普利联合胺碘酮),治疗12个月,计算两组治疗后第3、6、9、12个月的窦性心律维持率和治疗前及治疗后第6、12个月的左心房内径.结果:研究期结束后各组内治疗前后血压变化比较具有显著性,但两组间治疗后血压无显著性差异.治疗后9、12个月,联合用药组的窦性心律维持率显著高于胺碘酮组.两组间左心房内径在治疗后12个月时胺碘酮组显著高于联合用药组.结论:卡托普利联合胺碘酮治疗老年高血压伴阵发性房颤,可抑制左房扩大,并有效预防房颤复发.

  20. 炙甘草汤加减配合胺碘酮治疗慢性心力衰竭312例疗效观察%Curative effect observation of Zhi Gan Cao decoction adjusted with amiodarone in the treatment of 312 cases of chronic cardiac failure

    Institute of Scientific and Technical Information of China (English)

    李玉红; 王立娜; 崔骞

    2014-01-01

    目的:观察炙甘草汤加减配合胺碘酮治疗慢性心力衰竭情况。方法:将慢性心力衰竭患者312例按随机数字表法分为观察组160例(炙甘草汤加减配合胺碘酮组)与对照组152例(胺碘酮组)。随访6个月,观察两组总有效率和复发率情况。结果:观察组总有效率98%,复发率10.22%;对照组总有效率82%,复发率32.9%。两者差异有统计学意义(P<0.05)。结论:在预防慢性心力衰竭的复发方面,炙甘草汤加减配合胺碘酮优于单纯应用胺碘酮,值得在临床中推广应用。%Objective:To observe Zhi Gan Cao decoction adjusted with amiodarone in the preventment of recurrence of chronic cardiac failure.Methods:According to random number table method,312 patients with chronic cardiac failure were divided into the observation group in 160 cases(Zhi Gan Cao decoction adjusted with amiodarone group)and the control group in 152 cases(amiodarone group).After 6 months of follow up,the recurrence rates of premature beat in the two groups were observed. Results:In the observation group,the total effective rate was 98%,and the recurrence rate was 10.22%.In the control group, the total effective rate was 82%, and the recurrence rate was 32.9%.The difference was statistically significant(P<0.05).Conclusion:In the preventment of recurrence of chronic cardiac failure,Zhi Gan Cao decoction adjusted with amiodarone is better than the simple application of amiodarone.It is worth of popularization and application in clinical.

  1. 胺碘酮配合中药对慢性心力衰竭并室性早搏的临床干预%Clinical intervention of amiodarone with Traditional Chinese Medicine on chronic heart failure and premature ventricular contractions

    Institute of Scientific and Technical Information of China (English)

    于瑞玲; 宗燕

    2014-01-01

    Objective:T o observe the effect of amiodarone with Traditional Chinese Medicine on prev enting the re currence of chronic h eart failure and p remature ventr icular contractions. Me thods:78 cases with ch ronic heart failur e were randomized into a group given amiodarone with Traditional Chinese Medicine( the treatment group with 40 cases) and a group given amiodarone( the control group with 38 cases) .Followed up for six months, the recurrence r ates of premature w ere observ ed . Results:Th e treatment groups:the t otal effective r ate was 98%, th e re currence ra te w as 10.22%; the control group: the to tal effective rat e was 82%, the re currence rate was 32.9%. The dif ference was st atistically sign ificant ( P<0 .05). C onclusions:In the aspect of prevention of chronic h eart fa ilure and premature ventricular contractions, amiodarone with Traditional Chinese Medicine is better than amiodarone and it is worth y of promotion in clinical applications.%目的:观察中药联合胺碘酮预防慢性心力衰竭并室性早搏复发情况。方法:慢性心力衰竭室性早搏病人78例,随机分为中药联合胺碘酮组(治疗组40例)与胺碘酮组(对照组38例)。随访6个月,观察两组早搏复发率情况。结果:治疗组:总有效率分别为98%,复发率10.22%;对照组:总有效率82%,复发率32.9%。两者有显著性差异(P<0.05)。结论:在预防慢性心力衰竭并室性早搏的复发方面中药联合胺碘酮优于单纯应用胺碘酮,值得在临床中推广应用。

  2. 盐酸胺碘酮联合步长稳心颗粒治疗阵发性快速房颤疗效观察%The Clinical Observation of amiodarone with Wenxinkeli in Treatment of rapid atrial fibrillation in patients with paroxysmal efficacy

    Institute of Scientific and Technical Information of China (English)

    严新美

    2013-01-01

    目的:评价胺碘酮联合步长稳心颗粒治疗阵发性快速房颤的疗效。方法将80例阵发性快速房颤患者随机分为治疗组和对照组,两组均予以吸氧、心电监护、胺碘酮治疗,治疗组加服步长稳心颗粒,共观察6个月。结果观察6个月后,治疗组在有效改善症状、复律时间、及胺碘酮用量方面明显优于对照组,差异有统计学意义(P<0.01)。结论胺碘酮与步长稳心颗粒合用治疗阵发性房颤,能有效改善症状,提高治疗效果且可减少胺碘酮用量,缩短复律时间,有一定的临床应用价值。%Objective Evaluation of amiodarone the joint step Wenxinkeli rapid atrial fibrillation in patients with paroxysmal efficacy. Methods 80 patients with paroxysmal rapid atrial fibrillation were randomly divided into a treatment group and a control group, and both groups are oxygen, ECG, amiodarone,The treatment group took Buchangwenxin particles were observed 6 months. Results Observed after 6 months, the treatment group was effective in improving symptoms, time of cardioversion and amiodarone dosage was significantly better than the control group, the difference was statistically significant (P <0.01). Conclusion the particle combination therapy of paroxysmal atrial fibrillation, amiodarone and Buchangwenxin improve symptoms, improve treatment and reduce amiodarone dosage and shorten the time of cardioversion clinical application value.

  3. Role of intracellular calcium in contraction of internal anal sphincter

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    @@ INTRODUCTION Internal anal sphincter (IAS) is a continuation of the smooth circular muscle layer thickened at the rectum, innervated by vegetative nerve. IAS is a special smooth muscle, which is different from colonic smooth muscle in physiology and pharmaology[1]. It was found that contraction of gastric smooth muscle depends on the influx of extracellular calcium and release of intracellular calcium[2]. In present study, we observed and compared the effects of extra- and intracellular calcium on the contraction of IAS and colonic smooth muscle.

  4. In vitro and ex vivo strategies for intracellular delivery

    Science.gov (United States)

    Stewart, Martin P.; Sharei, Armon; Ding, Xiaoyun; Sahay, Gaurav; Langer, Robert; Jensen, Klavs F.

    2016-10-01

    Intracellular delivery of materials has become a critical component of genome-editing approaches, ex vivo cell-based therapies, and a diversity of fundamental research applications. Limitations of current technologies motivate development of next-generation systems that can deliver a broad variety of cargo to diverse cell types. Here we review in vitro and ex vivo intracellular delivery approaches with a focus on mechanisms, challenges and opportunities. In particular, we emphasize membrane-disruption-based delivery methods and the transformative role of nanotechnology, microfluidics and laboratory-on-chip technology in advancing the field.

  5. Intracellular accumulation of azithromycin by cultured human fibroblasts.

    OpenAIRE

    Gladue, R P; Snider, M E

    1990-01-01

    Azithromycin was shown to achieve high concentrations in human skin fibroblasts. Intracellular penetration occurred rapidly (10 micrograms/mg of cellular protein after 3 h) and then increased progressively over a 3-day period; azithromycin accumulated up to 21 times more than erythromycin (61.1 versus 2.9 micrograms/mg of protein). Uptake was dependent on the extracellular concentration, was inhibited at 4 degrees C, did not occur in nonviable cells, and was reduced by a low pH. Intracellular...

  6. Intracellular pH of acid-tolerant ruminal bacteria.

    OpenAIRE

    Russell, J B

    1991-01-01

    Acid-tolerant ruminal bacteria (Bacteroides ruminicola B1(4), Selenomonas ruminantium HD4, Streptococcus bovis JB1, Megasphaera elsdenii B159, and strain F) allowed their intracellular pH to decline as a function of extracellular pH and did not generate a large pH gradient across the cell membrane until the extracellular pH was low (less than 5.2). This decline in intracellular pH prevented an accumulation of volatile fatty acid anions inside the cells.

  7. FLIPR assays of intracellular calcium in GPCR drug discovery

    DEFF Research Database (Denmark)

    Hansen, Kasper Bø; Bräuner-Osborne, Hans

    2009-01-01

    Fluorescent dyes sensitive to changes in intracellular calcium have become increasingly popular in G protein-coupled receptor (GPCR) drug discovery for several reasons. First of all, the assays using the dyes are easy to perform and are of low cost compared to other assays. Second, most non......-Galpha(q)-coupled GPCRs can be tweaked to modulate intracellular calcium by co-transfection with promiscuous or chimeric/mutated G proteins making the calcium assays broadly applicable in GPCR research. Third, the price of instruments capable of measuring fluorescent-based calcium indicators has become significantly less...

  8. Alta dose de amiodarona em curto período reduz incidência de fibrilação atrial e flutter atrial no pós-operatório de cirurgia de revascularização miocárdica High dose of amiodarone in a short-term period reduces the incidence of postoperative atrial fibrillation and atrial flutter

    Directory of Open Access Journals (Sweden)

    Rafael Vieira Alcalde

    2006-09-01

    Full Text Available OBJETIVOS: Avaliar se a administração de amiodarona, em doses altas e curso rápido, reduz a incidência de fibrilação ou flutter atrial, após cirurgia de revascularização miocárdica e se reduz, também, o tempo de internação hospitalar. MÉTODOS: A amostra se constituiu de 93 pacientes randomizados, em estudo duplo-cego, para receberem amiodarona (46 pacientes ou placebo (47 pacientes. A terapia consistia na aplicação de 600mg de amiodarona, três vezes ao dia, iniciada no mínimo 30 horas e no máximo 56 horas antes da cirurgia. RESULTADOS: Fibrilação ou flutter atrial no pós-operatório ocorreu em 8 dos 46 pacientes no grupo amiodarona (17,4% e em 19 dos 47 pacientes no grupo placebo (40,4% (p=0,027. A dose média de amiodarona foi de 2,8g. Os pacientes do grupo amiodarona ficaram hospitalizados por 8,9±3,1 dias, enquanto a internação dos pacientes do grupo placebo foi de 11,4± 8,7 dias (p=0,07. O tempo de internação foi significativamente prolongado nos pacientes que desenvolveram fibrilação ou flutter atrial após a cirurgia, independente do grupo randomizado. CONCLUSÃO: Esta nova alternativa de administração de amiodarona em alta dose e por um curto período, antes da cirurgia de revascularização miocárdica, reduz a incidência de fibrilação ou flutter atrial no pós-operatório desta cirurgia.OBJECTIVE: To investigate wheter oral amiodarone administered before surgery for a short period in high dose would reduce the incidence of postoperative atrial fibrillation or atrial flutter and reduces the lenght of hospital stay. METHODS: In the double-blind, randomized study, 93 patients were given either oral amiodarone (46 patients or placebo (47 patients. Therapy consisted of 600mg of amiodarone three times a day, started at mininum 30 hours and at maximum 56 hours before surgery. RESULTS: Postoperative atrial fibrillation or atrial flutter occurred in 8 of 46 patients in the amiodarone group (17.4% and 19 of the

  9. The clinical effect of amiodarone versus lidocaine on the myocardial infarction patients complicated with ventricular tachycardia: A Meta-analysis%胺碘酮与利多卡因治疗急性心肌梗死并室性心动过速疗效及安全性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    党松; 王晞; 胡娟; 王鑫

    2012-01-01

    Objective To retrospectively compare the therapeutic effectiveness of amiodarone and lidocaine in the treatment of ventricular arrhythmia after acute myocardial infarction. Methods PubMed, Cochrane, EMBASE, MEDLINE, CNKI, Wanfang data were searched from the time of self-build library to December 2011 for randomized clinical trials( RCT ) of amiodarone vs. Lidocaine on the myocardial infarction patients complicated with ventricular tachycardia. Two investigators independently screened these data. Pooled estimates were calculate with usage of RevMan 5. 0 software. Results Ten trials were included in the analysis ( 1381 patients ). ( 1 )The effective rate in amiodarone group was higher than that in lidocaine group ( RR = 1. 27 , 95% CI 1. 12 ~ 1.44, P =0.0002 ). ( 2 ) Regardless of the effect of other medicines, the side effects of amiodarone was similar as lidocaine ( RR = 0. 79, 95% CI 0. 42 ~ 1. 48, P = 0. 46 ). ( 3 )The mortality rate in amiodarone group was higher than that in lidocaine group ( RR = 0.48, 95% CI 0. 27 ~ 0. 85, P =0.01). Conclusion The results of this Meta-analysis provide strong evidence that preferable effective of amiodarone therapy on the myocardial infarction patients complicated with ventricular arrhythmia, amiodarone can significantly decrease the incidence of ventricular tachycardia without increase the side effects, and decrease the mortality rate.%目的 运用Meta 分析比较胺碘酮和利多卡因对急性心肌梗死合并室性心动过速的疗效.方法 计算机检索PubMed、Cochrane、EMBASE、MEDLINE、中国知网(CNKI)数据库、万方数据库,查找自建库以来至2011年12月公开发表的比较胺碘酮和利多卡因治疗心肌梗死合并室性心动过速临床随机对照试验(RCT),按纳入排除标准进行RCT 的筛选、资料提取和质量评价,使用RevMan 5.0软件进行数据统计学分析.结果 共纳入10项研究、1381例患者.(1)胺碘酮组治疗有效率显著高于利多卡因组(RR=1

  10. Effect of Intravenous Administration of Amiodarone on The Hemodynamics in Rats with Acute Myocardial Ischemic%静脉注射胺碘酮对急性心肌缺血大鼠血流动力学的影响

    Institute of Scientific and Technical Information of China (English)

    徐向钊; 张冬梅; 郎淑慧; 彭亮; 王萌

    2013-01-01

    目的 观察静脉应用胺碘酮对急性心肌缺血大鼠血流动力学的影响.方法 健康雄性SD大鼠40只,体重250~300g,采用随机数字表法,将大鼠随机分为五组:假手术组(S组);缺血再灌注组(I/R组):胺碘酮2.5mg·kg-1+持续泵注组(A1组);胺碘酮5.0mg·kg-1组(A2组),不进行持续泵注;胺碘酮5.0 mg· kg-1组+持续泵注组(A3组)均于缺血前10min静脉注射胺碘酮.分别记录缺血前10min(T0),缺血后30min(T1),再灌注30min(T2),再灌注60min(T3),再灌注120min(T4)大鼠心率(HR),左心室收缩压(LVSP)、左心室终末舒张压(LVEDP)、左心室内压最大上升速率(+dp/dtmax)、左心室内压最大下降率(-dp/dtmax)的变化以及心律失常的分析.结果 各组大鼠在T0时HR、LVSP、LVEDP、+dp/dtmax、-dp/dtmax比较差异无统计学意义(P>0.05);在缺血以后,与S组比较,I/R、A1、A2、A3组大鼠的HR、LVSP、+dp/dtmax、-dp/dtmax降低(P<0.05),LVEDP升高(P<0.05);与I/R组比较,A1、A2、A3组HR、LVSP、+dp/dtmax、-dp/dtmax升高(P<0.05),LVEDP降低(P<0.05);A1组HR、LVSP、+dp/dtmax、-dp/dtmax比A2、A3组降低,LVEDP升高(P<0.05),A3组HR、LVSP、+dp/dtmax、-dp/dtmax比A2组升高,LVEDP降低(P<0.05),组间比较差异有统计学意义(P<0.05).各组大鼠在急性缺血期心律失常的评分显示,I/R、A1、A2、A3组评分均高于S组(P <0.05);A1、A2、A3组评分均低于I/R组(P<0.05);A2、A3组低于A1组,A3组低于A2组,差异均有统计学意义(P<0.05).结论 静脉应用胺碘酮可以改善急性心肌缺血大鼠的血流动力学及减少心律失常的发生率,以5.0mg·kg-1加持续泵注组效果最佳.%Objective To investigate the effect of intravenous administration of amiodarone on the hemodynamics in rats with acute myocardial ischemic. Methods 40 SD rats, weighting 250 ~300g, were randomly divided into 5 groups (n = 8) : sham - operation ( S) , ischemic - reperfusion control group ( I

  11. Clinical Efficacy of Amiodarone Combined With Perindopril in Patients With Paroxysmal Atrial Fibril ation%胺碘酮联合培哚普利治疗阵发性房颤的临床疗效

    Institute of Scientific and Technical Information of China (English)

    孙楠楠

    2014-01-01

    目的:评价胺碘酮联合培哚普利治疗阵发性房颤的临床疗效,指导在治疗阵发性房颤过程中选择合理的药物以减少阵发性房颤的发生,改善患者的预后。方法将57例阵发性房颤随机分为胺碘酮组(A组,n=28)和胺碘酮+培哚普利(B组,n=29),胺碘酮组(A组)包括男16例,女12例,平均年龄58±5.5岁,胺碘酮组(A组)中原发性高血压8例,特发性房颤2例,冠心病7例,风心病5例;胺碘酮+培哚普利(B组)包括男19例,女10例,平均年龄59±6.1岁,胺碘酮+培哚普利(B组)中原发性高血压9例,特发性房颤2例,冠心病6例,风心病7例。胺碘酮组(A组)患者胺碘酮的服用方法为:0.2g,3次/天服药一周,后减至0.2g,2次/天,服药一周,然后0.2g,一次/天,长期维持;胺碘酮+培哚普利(B组)患者在胺碘酮组(A组)治疗用药的基础上加用培哚普利,服用方法为:2mg,一次/天,服药四天,如无低血压,第五天加量至4mg,,一次/天,治疗随访时间为24个月。计算两组治疗后3、6、9、12、18、24月的窦性心律的维持率和治疗前、治疗后6、12、18个月的左心房内径。结果两组治疗前和治疗后6、12个月左心房内径无差别,18个月后有显著差异(P<0.05),治疗后3、6、9个月,A组窦性心律维持率均低于B组,但无显著差异,而治疗12个月后,两组间有显著性差异(P<0.05),治疗结束时A组的窦性心律维持率为61.26%,B组的窦性心律维持率为83.45%。结论胺碘酮联合培哚普利治疗阵发性房颤在维持窦性心律及减少心房颤动发作次数的疗效均优于单用胺碘酮,并能延缓左心房扩大。%Objective To evaluate the clinical effects of amiodarone combined perindopril to treat paroxysmal atrial fibril ation. Methods 57 cases were randomly divided into treated by amiodarone group (group A, n=28) and treated by

  12. Correlation of Cell Strain in Single Osteocytes with Intracellular Calcium, but not Intracellular Nitric Oxide, in Response to Fluid Flow

    OpenAIRE

    Rath, Amber L.; Bonewald, Lynda F.; Ling, Jian; Jiang, Jean X.; VAN DYKE, MARK E.; Nicolella, Daniel P

    2010-01-01

    Osteocytes compose 90–95% of all bone cells and are the mechanosensors of bone. In this study, the strain experienced by individual osteocytes resulting from an applied fluid flow shear stress was quantified and correlated to two biological responses measured in real-time within the same individual osteocytes: 1) the upregulation of intracellular calcium and 2) changes in intracellular nitric oxide. Osteocyte-like MLO-Y4 cells were loaded with Fluo-4 AM and DAR-4M and exposed to uniform lamin...

  13. Load-dependent destabilization of the γ-rotor shaft in FOF1 ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry.

    Science.gov (United States)

    Vahidi, Siavash; Bi, Yumin; Dunn, Stanley D; Konermann, Lars

    2016-03-01

    FoF1 is a membrane-bound molecular motor that uses proton-motive force (PMF) to drive the synthesis of ATP from ADP and Pi. Reverse operation generates PMF via ATP hydrolysis. Catalysis in either direction involves rotation of the γε shaft that connects the α3β3 head and the membrane-anchored cn ring. X-ray crystallography and other techniques have provided insights into the structure and function of FoF1 subcomplexes. However, interrogating the conformational dynamics of intact membrane-bound FoF1 during rotational catalysis has proven to be difficult. Here, we use hydrogen/deuterium exchange mass spectrometry to probe the inner workings of FoF1 in its natural membrane-bound state. A pronounced destabilization of the γ C-terminal helix during hydrolysis-driven rotation was observed. This behavior is attributed to torsional stress in γ, arising from γ⋅⋅⋅α3β3 interactions that cause resistance during γ rotation within the apical bearing. Intriguingly, we find that destabilization of γ occurs only when FoF1 operates against a PMF-induced torque; the effect disappears when PMF is eliminated by an uncoupler. This behavior resembles the properties of automotive engines, where bearings inflict greater forces on the crankshaft when operated under load than during idling. PMID:26884184

  14. Genomic analysis suggests that mRNA destabilization by the microprocessor is specialized for the auto-regulation of Dgcr8.

    Directory of Open Access Journals (Sweden)

    Archana Shenoy

    Full Text Available BACKGROUND: The Microprocessor, containing the RNA binding protein Dgcr8 and RNase III enzyme Drosha, is responsible for processing primary microRNAs to precursor microRNAs. The Microprocessor regulates its own levels by cleaving hairpins in the 5'UTR and coding region of the Dgcr8 mRNA, thereby destabilizing the mature transcript. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether the Microprocessor has a broader role in directly regulating other coding mRNA levels, we integrated results from expression profiling and ultra high-throughput deep sequencing of small RNAs. Expression analysis of mRNAs in wild-type, Dgcr8 knockout, and Dicer knockout mouse embryonic stem (ES cells uncovered mRNAs that were specifically upregulated in the Dgcr8 null background. A number of these transcripts had evolutionarily conserved predicted hairpin targets for the Microprocessor. However, analysis of deep sequencing data of 18 to 200nt small RNAs in mouse ES, HeLa, and HepG2 indicates that exonic sequence reads that map in a pattern consistent with Microprocessor activity are unique to Dgcr8. CONCLUSION/SIGNIFICANCE: We conclude that the Microprocessor's role in directly destabilizing coding mRNAs is likely specifically targeted to Dgcr8 itself, suggesting a specialized cellular mechanism for gene auto-regulation.

  15. Activation of β1-adrenoceptor triggers oxidative stress mediated myocardial membrane destabilization in isoproterenol induced myocardial infarcted rats: 7-hydroxycoumarin and its counter action.

    Science.gov (United States)

    Jagadeesh, Govindan Sangaran; Nagoor Meeran, Mohamed Fizur; Selvaraj, Palanisamy

    2016-04-15

    Activation of β1-adrenoceptor stimulates myocardial membrane destabilization in isoproterenol induced rats. Male albino Wistar rats were pre and co-treated with 7-hydroxycoumarin (16mg/kg body weight) daily for 8 days. Myocardial infarction was induced into rats by the subcutaneous administration of isoproterenol (100mg/kg body weight) at an interval of 24h daily for a period of two days (7th and 8th day). The levels/activities of serum cardiac troponin-T, lactate dehydrogenase and the concentrations of heart lipid peroxidation products were significantly increased and the antioxidant status was significantly decreased in isoproterenol induced rats. Furthermore, the activity of sodium/potassium-dependent adenosine triphosphatase was significantly decreased and the activities of calcium and magnesium-dependent adenosine triphosphatases were significantly increased in the heart of isoproterenol induced myocardial infarcted rats. Isoproterenol induced rats also revealed increased concentrations of sodium and calcium and decreased concentrations of potassium in the heart. 7-hydroxycoumarin pre- and co-treatment showed considerable impact on all biochemical parameters assessed. Also, 7-HC greatly reduced the infarct size of the myocardium. The in vitro study confirmed its potent free radical scavenging activity. Thus, the present study revealed that 7-HC attenuates myocardial membrane destabilization by reinstating the activities/levels of adenosine triphosphatases and minerals in isoproterenol induced rats by inhibiting oxidative stress. These effects are attributed to the membrane stabilizing and free radical scavenging properties of 7-hydroxycoumarin. PMID:26930228

  16. 胺碘酮治疗重度左心衰竭并房颤56例临床报道%Clinical Efficacy of 56 Cases of Amiodarone in Treatment of Severe Left Heart Failure and Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    江波; 江挺

    2015-01-01

    Objective Clinical eficacy of amiodarone in the treatment of severe left heart failure and atrial fibrilation were analyzed and discussed.Methods56 patients in our hospital from March 2012 to March 2014 with severe left heart failure and atrial fibrilation were randomly assigned treatment.Results The observation group treatment eficiency (92.9%) was significantly better than the control group(71.4%). The diference was statisticaly significant,P < 0.05;systolic blood pressure,diastolic and mean arterial pressure and heart rate in the observation group were significantly lower than the control group,and the diference was statisticaly significant,P < 0.05;incidence of adverse reactions in the experimental group was significantly lower than the control group,and the diference was statisticaly significant,P < 0.05.Conclusion Amiodarone in treatment of severe left heart failure and atrial fibrilation is efective and safe.%目的:对胺碘酮治疗重度左心衰竭并房颤的临床疗效进行分析探讨。方法将我院自2012年3月~2014年3月收治的56例重度左心衰竭并房颤患者进行随机分组治疗。结果实验组患者治疗有效率(92.9%)优于对照组患者(71.4%),对比差异,具有统计学意义,P <0.05;实验组患者收缩压、舒张压、平均动脉压及心率均低于对照组,对比差异具有统计学意义,P <0.05;实验组不良反应发生情况低于对照组,对比差异具有统计学意义,P <0.05。结论重度左心衰竭并房颤行胺碘酮治疗,疗效好,安全性高。

  17. Monitoring intracellular oxidative events using dynamic spectral unmixing microscopy

    Science.gov (United States)

    There is increasing interest in using live-cell imaging to monitor not just individual intracellular endpoints, but to investigate the interplay between multiple molecular events as they unfold in real time within the cell. A major impediment to simultaneous acquisition of multip...

  18. CONTRIBUTIONS OF INTRACELLULAR IONS TO Kv CHANNEL VOLTAGE SENSOR DYNAMICS.

    Directory of Open Access Journals (Sweden)

    Samuel eGoodchild

    2012-06-01

    Full Text Available Voltage sensing domains of Kv channels control ionic conductance through coupling of the movement of charged residues in the S4 segment to conformational changes at the cytoplasmic region of the pore domain, that allow K+ ions to flow. Conformational transitions within the voltage sensing domain caused by changes in the applied voltage across the membrane field are coupled to the conducting pore region and the gating of ionic conductance. However, several other factors not directly linked to the voltage dependent movement of charged residues within the voltage sensor impact the dynamics of the voltage sensor, such as inactivation, ionic conductance, intracellular ion identity and block of the channel by intracellular ligands. The effect of intracellular ions on voltage sensor dynamics is of importance in the interpretation of gating current measurements and the physiology of pore/voltage sensor coupling. There is a significant amount of variability in the reported kinetics of voltage sensor deactivation kinetics of Kv channels attributed to different mechanisms such as open state stabilization, immobilization and relaxation processes of the voltage sensor. Here we separate these factors and focus on the causal role that intracellular ions can play in allosterically modulating the dynamics of Kv voltage sensor deactivation kinetics. These considerations are of critical importance in understanding the molecular determinants of the complete channel gating cycle from activation to deactivation.

  19. Novel Waddlia Intracellular Bacterium in Artibeus intermedius Fruit Bats, Mexico.

    Science.gov (United States)

    Pierlé, Sebastián Aguilar; Morales, Cirani Obregón; Martínez, Leonardo Perea; Ceballos, Nidia Aréchiga; Rivero, Juan José Pérez; Díaz, Osvaldo López; Brayton, Kelly A; Setién, Alvaro Aguilar

    2015-12-01

    An intracellular bacterium was isolated from fruit bats (Artibeus intermedius) in Cocoyoc, Mexico. The bacterium caused severe lesions in the lungs and spleens of bats and intracytoplasmic vacuoles in cell cultures. Sequence analyses showed it is related to Waddlia spp. (order Chlamydiales). We propose to call this bacterium Waddlia cocoyoc.

  20. Deciphering the Intracellular Fate of Propionibacterium acnes in Macrophages

    Directory of Open Access Journals (Sweden)

    Natalie Fischer

    2013-01-01

    Full Text Available Propionibacterium acnes is a Gram-positive bacterium that colonizes various niches of the human body, particularly the sebaceous follicles of the skin. Over the last years a role of this common skin bacterium as an opportunistic pathogen has been explored. Persistence of P. acnes in host tissue has been associated with chronic inflammation and disease development, for example, in prostate pathologies. This study investigated the intracellular fate of P. acnes in macrophages after phagocytosis. In a mouse model of P. acnes-induced chronic prostatic inflammation, the bacterium could be detected in prostate-infiltrating macrophages at 2 weeks postinfection. Further studies performed in the human macrophage cell line THP-1 revealed intracellular survival and persistence of P. acnes but no intracellular replication or escape from the host cell. Confocal analyses of phagosome acidification and maturation were performed. Acidification of P. acnes-containing phagosomes was observed at 6 h postinfection but then lost again, indicative of cytosolic escape of P. acnes or intraphagosomal pH neutralization. No colocalization with the lysosomal markers LAMP1 and cathepsin D was observed, implying that the P. acnes-containing phagosome does not fuse with lysosomes. Our findings give first insights into the intracellular fate of P. acnes; its persistency is likely to be important for the development of P. acnes-associated inflammatory diseases.

  1. Intracellular localization of VAMP-1 protein in human neutrophils.

    Science.gov (United States)

    Nabokina, S M

    2001-02-01

    We studied the intracellular localization of vesicle-associated membrane protein VAMP-1 in human neutrophils. VAMP-1 was associated with membranes of gelatinase and specific secretory granules rapidly mobilized during exocytosis. VAMP-1 probably acts as a component of the SNARE complex during exocytosis of gelatinase and specific granules in human neutrophils.

  2. Biomineralization Patterns of Intracellular Carbonatogenesis in Cyanobacteria: Molecular Hypotheses

    Directory of Open Access Journals (Sweden)

    Jinhua Li

    2016-02-01

    Full Text Available The recent discovery of intracellular carbonatogenesis in several cyanobacteria species has challenged the traditional view that this process was extracellular and not controlled. However, a detailed analysis of the size distribution, chemical composition and 3-D-arrangement of carbonates in these cyanobacteria is lacking. Here, we characterized these features in Candidatus Gloeomargarita lithophora C7 and Candidatus Synechococcus calcipolaris G9 by conventional transmission electron microscopy, tomography, ultramicrotomy, and scanning transmission X-ray microscopy (STXM. Both Ca. G. lithophora C7 and Ca. S. calcipolaris G9 formed numerous polyphosphate granules adjacent or engulfing Ca-carbonate inclusions when grown in phosphate-rich solutions. Ca-carbonates were scattered within Ca. G. lithophora C7 cells under these conditions, but sometimes arranged in one or several chains. In contrast, Ca-carbonates formed at cell septa in Ca. S. calcipolaris G9 and were segregated equally between daughter cells after cell division, arranging as distorted disks at cell poles. The size distribution of carbonates evolved from a positively to a negatively skewed distribution as particles grew. Conventional ultramicrotomy did not preserve Ca-carbonates explaining partly why intracellular calcification has been overlooked in the past. All these new observations allow discussing with unprecedented insight some nucleation and growth processes occurring in intracellularly calcifying cyanobacteria with a particular emphasis on the possible involvement of intracellular compartments and cytoskeleton.

  3. Measurement of intracellular oxygen concentration during photodynamic therapy in vitro.

    Science.gov (United States)

    Weston, Mark A; Patterson, Michael S

    2014-01-01

    A technique is introduced that monitors the depletion of intracellular ground state oxygen concentration ([(3)O(2)]) during photodynamic therapy of Mat-LyLu cell monolayers and cell suspensions. The photosensitizer Pd(II) meso-tetra(4-carboxyphenyl)porphine (PdT790) is used to manipulate and indicate intracellular [(3)O(2)] in both of the in vitro models. The Stern-Volmer relationship for PdT790 phosphorescence was characterized in suspensions by flowing nitrogen over the suspension while short pulses of 405 nm light were used to excite the sensitizer. The bleaching of sensitizer and the oxygen consumption rate were also measured during continuous exposure of the cell suspension to the 405 nm laser. Photodynamic therapy (PDT) was conducted in both cell suspensions and in cell monolayers under different treatment conditions while the phosphorescence signal was acquired. The intracellular [(3)O(2)] during PDT was calculated by using the measured Stern-Volmer relationship and correcting for sensitizer photobleaching. In addition, the amount of oxygen that was consumed during the treatments was calculated. It was found that even at large oxygen consumption rates, cells remain well oxygenated during PDT of cell suspensions. For monolayer treatments, it was found that intracellular [(3)O(2)] is rapidly depleted over the course of PDT.

  4. Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms

    DEFF Research Database (Denmark)

    Carlsson, Carl Michael; Bengtson, Per; Cucak, Helena;

    2013-01-01

    these transferrin glycoforms differently after preloading with exogenously added galectin-3. In all, this study provides the first evidence of a functional role for transferrin glycans, in intracellular trafficking after uptake. Moreover, the galectin-3 bound glycoform increased in cancer, suggesting...

  5. Environmental and intracellular regulation of Francisella tularensis ripA

    Directory of Open Access Journals (Sweden)

    Taft-Benz Sharon

    2009-10-01

    Full Text Available Abstract Background Francisella tularensis is a highly virulent, facultative intracellular pathogen and the etiologic agent of the zoonotic disease Tularemia. RipA is a cytoplasmic membrane protein that is conserved among Francisella species and is required for intracellular growth. F. tularensis ripA deletion mutants escape the phagosome of infected cells, but unlike wild type organisms fail to replicate in the host cell cytoplasm. Results Further analysis of ripA with respect to environmental effects on the growth of mutant strains and expression levels revealed that RipA is required for optimal growth at pH 7.5 but not pH 6.5. Using a combination of RT-PCR, ripA-lacZ transcriptional and translational fusions, and a RipA-tetracysteine tag fusion protein we found that both ripA transcription and RipA protein levels were elevated in organisms grown at pH 7.5 as compared to organisms grown at pH 5.5. A number of genes, including iglA, that are required for intracellular growth are regulated by the transcriptional regulators MglA and SspA, and are induced upon infection of host cells. We quantified ripA and iglA expression at different stages of intracellular growth and found that the expression of each increased between 1 and 6 hours post infection. Given the similar intracellular expression patterns of ripA and iglA and that MglA and SspA are positive regulators of iglA we tested the impact of mglA and sspA deletions on ripA and iglA expression. In the deletion mutant strains iglA expression was reduced dramatically as expected, however ripA expression was increased over 2-fold. Conclusion Expression of ripA is required for growth at neutral pH, is pH sensitive, and is responsive to the intracellular environment. The intracellular expression pattern of ripA coincided with iglA, which is positively regulated by MglA and SspA. However, in contrast to their positive impact on iglA expression, MglA and SspA negatively impacted ripA expression in

  6. Single-cell intracellular nano-pH probes†

    Science.gov (United States)

    Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

    2016-01-01

    Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution.

  7. Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Emily R Troemel

    2008-12-01

    Full Text Available For decades the soil nematode Caenorhabditis elegans has been an important model system for biology, but little is known about its natural ecology. Recently, C. elegans has become the focus of studies of innate immunity and several pathogens have been shown to cause lethal intestinal infections in C. elegans. However none of these pathogens has been shown to invade nematode intestinal cells, and no pathogen has been isolated from wild-caught C. elegans. Here we describe an intracellular pathogen isolated from wild-caught C. elegans that we show is a new species of microsporidia. Microsporidia comprise a large class of eukaryotic intracellular parasites that are medically and agriculturally important, but poorly understood. We show that microsporidian infection of the C. elegans intestine proceeds through distinct stages and is transmitted horizontally. Disruption of a conserved cytoskeletal structure in the intestine called the terminal web correlates with the release of microsporidian spores from infected cells, and appears to be part of a novel mechanism by which intracellular pathogens exit from infected cells. Unlike in bacterial intestinal infections, the p38 MAPK and insulin/insulin-like growth factor (IGF signaling pathways do not appear to play substantial roles in resistance to microsporidian infection in C. elegans. We found microsporidia in multiple wild-caught isolates of Caenorhabditis nematodes from diverse geographic locations. These results indicate that microsporidia are common parasites of C. elegans in the wild. In addition, the interaction between C. elegans and its natural microsporidian parasites provides a system in which to dissect intracellular intestinal infection in vivo and insight into the diversity of pathogenic mechanisms used by intracellular microbes.

  8. Modulation of intracellular calcium levels by calcium lactate affects colon cancer cell motility through calcium-dependent calpain.

    Directory of Open Access Journals (Sweden)

    Pasupathi Sundaramoorthy

    Full Text Available Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+ supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa, its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa2+ levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain in a dose-dependent manner. Phosphorylated FAK (p-FAK was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer.

  9. Supramolecular nanoreactors for intracellular singlet-oxygen sensitization

    Science.gov (United States)

    Swaminathan, Subramani; Fowley, Colin; Thapaliya, Ek Raj; McCaughan, Bridgeen; Tang, Sicheng; Fraix, Aurore; Burjor, Captain; Sortino, Salvatore; Callan, John F.; Raymo, Françisco M.

    2015-08-01

    An amphiphilic polymer with multiple decyl and oligo(ethylene glycol) chains attached to a common poly(methacrylate) backbone assembles into nanoscaled particles in aqueous environments. Hydrophobic anthracene and borondipyrromethene (BODIPY) chromophores can be co-encapsulated within the self-assembling nanoparticles and transported across hydrophilic media. The reversible character of the noncovalent bonds, holding the supramolecular containers together, permits the exchange of their components with fast kinetics in aqueous solution. Incubation of cervical cancer (HeLA) cells with a mixture of two sets of nanoparticles, pre-loaded independently with anthracene or BODIPY chromophores, results in guest scrambling first and then transport of co-entrapped species to the intracellular space. Alternatively, incubation of cells with the two sets of nanocarriers in consecutive steps permits the sequential transport of the anthracene and BODIPY chromophores across the plasma membrane and only then allows their co-encapsulation within the same supramolecular containers. Both mechanisms position the two sets of chromophores with complementary spectral overlap in close proximity to enable the efficient transfer of energy intracellularly from the anthracene donors to the BODIPY acceptors. In the presence of iodine substituents on the BODIPY platform, intersystem crossing follows energy transfer. The resulting triplet state can transfer energy further to molecular oxygen with the concomitant production of singlet oxygen to induce cell mortality. Furthermore, the donor can be excited with two near-infrared photons simultaneously to permit the photoinduced generation of singlet oxygen intracellularly under illumination conditions compatible with applications in vivo. Thus, these supramolecular strategies to control the excitation dynamics of multichromophoric assemblies in the intracellular environment can evolve into valuable protocols for photodynamic therapy.An amphiphilic

  10. Effects of undiluted and diluted amiodarone on defibrillation and haemodynamics in a ventricular fibrillation pig model%胺碘酮原液和稀释液对心室颤动转复作用及血流动力学的影响

    Institute of Scientific and Technical Information of China (English)

    武军元; 李春盛; 王胜奇

    2010-01-01

    Objective Amiodarone was diluted to release the side effect of hypotension in clinic, but this maybe unsuitable during cardiopulmonary resuscitation (CPR). This study was designed to observe the effects of undiluted amiodarone, diluted amiodarone, and CPR alone on ventricular fibrillation (VF) in a pig model. Methods VF was induced in 21 pigs. The animals were randomly (random mumber) divided into 3 groups after VF 3 min.① CPR group ( n= 7): standard CPR; ② undiluted amiodarone group ( n= 7): undiluted amiodarone (5 mg/kg)bolus within 3 s, then 20 mL saline flush into the peripheral vein, CPR was started after observed 30 s; ③ diluted amiodarone group ( n = 7): amiodarone was dissolved in 20 mL saline and bolus with 30 s. Defibrillation was attempted at VF 5 min. Results The restoration of spontaneous circulation (ROSC) of CPR and undiluted amiodarone groups were higher than diluted group (85.7% vs. 71.4% vs. 42.9%), but the differences were not significant (all P >0.05). The defibrillation energy and times of CPR group were higher than that of undiluted amiodarone (P= 0.009) and diluted group ( P = 0. 170). The mean arterial pressure of undiluted amiodarone were lower than diluted and CPR groups at ROSC 10 min (all P <0.05), but the differences of undiluted and diluted groups were not significant after ROSC 0.5 h. Conclusions In this study, undiluted amiodaronecan effectively reduced the defibrillation times and energy. Although diluted amiodaronecan release the side effect of hypotension which was transient, it didn't significantly improved cardiac electric activity and delayed to start CPR.%目的 通过猪心室颤动(VF)模型,观察胺碘酮原液、稀释液以及单纯标准CPR对心肺复苏效果的影响.方法 21头北京长白猪,应用程控刺激仪诱导VF,VF 3 min后,将动物随机(随机数字法)分为3组.①单纯CPR组:只进行单纯标准CPR;②胺碘酮原液组:予胺碘酮原液5 mg/kg快速(<3 s)静推,生理盐水20 m

  11. Analysing intracellular deformation of polymer capsules using structured illumination microscopy

    Science.gov (United States)

    Chen, Xi; Cui, Jiwei; Sun, Huanli; Müllner, Markus; Yan, Yan; Noi, Ka Fung; Ping, Yuan; Caruso, Frank

    2016-06-01

    Understanding the behaviour of therapeutic carriers is important in elucidating their mechanism of action and how they are processed inside cells. Herein we examine the intracellular deformation of layer-by-layer assembled polymer capsules using super-resolution structured illumination microscopy (SIM). Spherical- and cylindrical-shaped capsules were studied in three different cell lines, namely HeLa (human epithelial cell line), RAW264.7 (mouse macrophage cell line) and differentiated THP-1 (human monocyte-derived macrophage cell line). We observed that the deformation of capsules was dependent on cell line, but independent of capsule shape. This suggests that the mechanical forces, which induce capsule deformation during cell uptake, vary between cell lines, indicating that the capsules are exposed to higher mechanical forces in HeLa cells, followed by RAW264.7 and then differentiated THP-1 cells. Our study demonstrates the use of super-resolution SIM in analysing intracellular capsule deformation, offering important insights into the cellular processing of drug carriers in cells and providing fundamental knowledge of intracellular mechanobiology. Furthermore, this study may aid in the design of novel drug carriers that are sensitive to deformation for enhanced drug release properties.Understanding the behaviour of therapeutic carriers is important in elucidating their mechanism of action and how they are processed inside cells. Herein we examine the intracellular deformation of layer-by-layer assembled polymer capsules using super-resolution structured illumination microscopy (SIM). Spherical- and cylindrical-shaped capsules were studied in three different cell lines, namely HeLa (human epithelial cell line), RAW264.7 (mouse macrophage cell line) and differentiated THP-1 (human monocyte-derived macrophage cell line). We observed that the deformation of capsules was dependent on cell line, but independent of capsule shape. This suggests that the mechanical forces

  12. 胺碘酮治疗老年充血性心力衰竭伴快速房颤的疗效观察%Efficiency of intravenous amiodarone in congestive heart failure patients with atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    张荣生; 顾翔

    2015-01-01

    ObjectiveTo determine the effect of intravenous amiodarone on the rapid ventricular rate in the patients with atrial fibrillation (AF) and congestive heart failure (CHF).Methods Seventy elderly patients with AF and CHF [ventricular rate>120beats/min, New York Heart Association (NYHA) classⅡ−Ⅳ] hospitalized in theNorthern Jiangsu People’s Hospital from September 2012 to September 2013 were recruited in this study. They were randomized into 2 groups: amiodarone group (n=35, loading dosage of 150mg followed by a dose of 1.5mg/min) anddeslanoside group (n=35, loading dosage of 0.4 or 0.2mg in slow injection, and more 0.2mg should be medicated if no effect occurred in 1h later). The ventricular rate, mean response time, successful cardioversion ratio,brain natriuretic peptide (BNP) level, the adverse effects and follow-up outcomes were recorded after medication.Results The ventricular rate was significantly decreased in 1, 2 and 24h after treatment thanbefore inboth groups (P0.05). In 3 months after discharged from hospital, the ratio of persistent AFafter the medications (amiodarone, metoprorol and digoxin) was 60.0% (21/35) and 82.9% (29/35), respectively, and the rate of adverse effect was 8.6% and 11.4%, respectively, in the 2 groups (P>0.05).Conclusion Amiodarone isof safety, rapid effect andmild adverse effect in treatment of CHF patients with coexisting AF.%目的:观察胺碘酮治疗老年充血性心力衰竭(CHF)伴快速心房纤颤(AF)的疗效。方法选择2012年9月至2013年9月在苏北人民医院住院治疗的老年CHF伴快速AF患者70例,纽约心脏联合会分级(NYHA)Ⅱ~Ⅳ级,心室率≥120次/min;随机分为胺碘酮组和去乙酰毛花苷组,每组各35例。在常规治疗基础上,胺碘酮组首次剂量给予胺碘酮150mg缓慢静注,随后1.5mg/min微量泵维持;去乙酰毛花苷组首次剂量给予去乙酰毛花苷0.4mg或0.2mg缓慢静注,1h后无效者追加0.2mg。观察用药后

  13. 胺碘酮治疗房颤并发静脉炎25例护理体会%The Experience of Nursing for 25 Cases ofP atients with Atrial Fibrillation Complicated Phlebitis with Amiodarone

    Institute of Scientific and Technical Information of China (English)

    安桂香; 王莉

    2011-01-01

    目的:探讨应用胺碘酮注射液治疗快速房颤并发静脉炎的护理方法.方法:加强巡视、按时冲管,并应用微量泵.结果:经及时正确的对症护理,患者静脉炎症状消失,皮温色泽恢复正常.结论:专科护士仔细观察药物疗效和不良反应,及时采取有效的预见性护理,可减轻患者的痛苦.%To investigate the nursing method for patients with atrial fibrillation complicated phlebitis with Amiodarone.Method:Stepped up inspections,washed tube on time to prevent the occurrence of phlebitis, and applied the micro-pump.Result:The symptoms of phlebitis in patients disappeared and the temperature and color of skin came back to normal through timely and correct symptomatic care.Conclusion:The professionl nurses should observe the efficacy and adverse reactions of drugs carefully and take timely and effective nursing care to alleviate the suffering of patients.The best method is to take center intravenous administration.

  14. 乙胺碘肤酮用作甲亢术前准备的临床观察%Clinical Observation of Amiodarone Used in the Preoperative Preperation in Grave's Disease

    Institute of Scientific and Technical Information of China (English)

    曾毅克; 黎绍基; 吕诗寿

    2000-01-01

    目的:初步探讨乙胺碘肤酮(Amiodarone)用于甲亢术前准备的可行性.方法:12名患者非随机分为两组,以使其平均年龄、甲亢的严重程度和甲状腺肿大程度相匹配,分别使用Lugol液和Amiodarone作术前准备,比较两组患者切除的腺体质量(m),术中出血量(V),甲状腺组织的碘含量(mI).结果:Amiodarone组m=(89.81±51.41)g,V=(128.16±30.92)ml,mI=(0.033±0.017)%;Lugol液组m=(81.28±39.81)g,V=(194.97±57.77)ml,mI=(0.034±0.013)%;两组对比在切除腺体质量相当时,Amiodarone组的术中出血量较少(t检验P0.05).结论:乙胺碘肤酮用于甲亢术前准备对甲亢控制良好,能达到常规Lugol液的准备效果,而且口服无刺激,较Lugol液优越.

  15. Intracellular pH Modulates Autophagy and Mitophagy.

    Science.gov (United States)

    Berezhnov, Alexey V; Soutar, Marc P M; Fedotova, Evgeniya I; Frolova, Maria S; Plun-Favreau, Helene; Zinchenko, Valery P; Abramov, Andrey Y

    2016-04-15

    The specific autophagic elimination of mitochondria (mitophagy) plays the role of quality control for this organelle. Deregulation of mitophagy leads to an increased number of damaged mitochondria and triggers cell death. The deterioration of mitophagy has been hypothesized to underlie the pathogenesis of several neurodegenerative diseases, most notably Parkinson disease. Although some of the biochemical and molecular mechanisms of mitochondrial quality control are described in detail, physiological or pathological triggers of mitophagy are still not fully characterized. Here we show that the induction of mitophagy by the mitochondrial uncoupler FCCP is independent of the effect of mitochondrial membrane potential but dependent on acidification of the cytosol by FCCP. The ionophore nigericin also reduces cytosolic pH and induces PINK1/PARKIN-dependent and -independent mitophagy. The increase of intracellular pH with monensin suppresses the effects of FCCP and nigericin on mitochondrial degradation. Thus, a change in intracellular pH is a regulator of mitochondrial quality control. PMID:26893374

  16. Intracellular Delivery of Nanoparticles with Cell Penetrating Peptides.

    Science.gov (United States)

    Salzano, Giuseppina; Torchilin, Vladimir P

    2015-01-01

    The functionalization of nanoparticles (NPs) with cell penetrating peptides (CPPs) constitutes a breakthrough for the intracellular delivery of therapeutic and diagnostic payloads. In late 1998, a significant cellular uptake of a small protein from the HIV-1 virus, namely TAT peptide (TATp), was observed. Thereafter, research began on design of similarly acting peptides, and the coupling of NPs with these novel CPPs. Here, we describe recent methods used to modify the surface of NPs with CPPs and the in vitro and in vivo effects of such functionalization on the intracellular delivery of various cargos. In particular, we highlight recent advances aimed at reducing the non-selectivity of CPPs and the prevention of their enzymatic cleavage en route to target tissues. PMID:26202282

  17. Monitoring the intracellular calcium response to a dynamic hypertonic environment

    Science.gov (United States)

    Huang, Xiaowen; Yue, Wanqing; Liu, Dandan; Yue, Jianbo; Li, Jiaqian; Sun, Dong; Yang, Mengsu; Wang, Zuankai

    2016-03-01

    The profiling of physiological response of cells to external stimuli at the single cell level is of importance. Traditional approaches to study cell responses are often limited by ensemble measurement, which is challenging to reveal the complex single cell behaviors under a dynamic environment. Here we report the development of a simple microfluidic device to investigate intracellular calcium response to dynamic hypertonic conditions at the single cell level in real-time. Interestingly, a dramatic elevation in the intracellular calcium signaling is found in both suspension cells (human leukemic cell line, HL-60) and adherent cells (lung cancer cell line, A549), which is ascribed to the exposure of cells to the hydrodynamic stress. We also demonstrate that the calcium response exhibits distinct single cell heterogeneity as well as cell-type-dependent responses to the same stimuli. Our study opens up a new tool for tracking cellular activity at the single cell level in real time for high throughput drug screening.

  18. An Intracellular Calcium Oscillations Model Including Mitochondrial Calcium Cycling

    Institute of Scientific and Technical Information of China (English)