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Feixiong Cheng, James L Murray, Junfei Zhao, Jinsong Sheng, Zhongming Zhao, Donald H Rubin
Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins...
September 2016: PLoS Computational Biology
Mrinalini Srivastava, Swati Sharma, Pratibha Misra
BACKGROUND: Rauwolfia serpentina and Solanum khasianum are well-known medicinally important plants contained important alkaloids in their different parts. Elicitation of these alkaloids is important because of associated pharmaceutical properties. Targeted metabolites were ajmaline and ajmalicine in R. serpentina; solasodine and α-solanine in S. khasianum. OBJECTIVE: Enhancement of secondary metabolites through biotic and abiotic elicitors in hairy root cultures of R...
May 2016: Pharmacognosy Magazine
Sunil Kumar, Awantika Singh, Vikas Bajpai, Mukesh Srivastava, Bhim Pratap Singh, Sanjeev Ojha, Brijesh Kumar
INTRODUCTION: Rauvolfia serpentina is an endangered plant species due to its over-exploitation. It has highly commercial and economic importance due to the presence of bioactive monoterpene indole alkaloids (MIAs) such as ajmaline, yohimbine, ajmalicine, serpentine and reserpine. OBJECTIVE: To develop a validated, rapid, sensitive and selective ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry (UHPLC-QqQLIT -MS/MS) method in the multiple reaction monitoring (MRM) mode for simultaneous determination of bioactive MIAs in ethanolic extract of seven Rauvolfia species and herbal formulations...
September 2016: Phytochemical Analysis: PCA
Thomas Gicquel, Chloé Hugbart, Françoise Le Devehat, Sylvie Lepage, Alain Baert, Renaud Bouvet, Isabelle Morel
Powdered roots of iboga (Tabernanthe iboga) contain ibogaine, an alkaloid that has been used to treat addictions. We report the case of a 30-year-old woman who died after ingesting a powder labeled as Tabernanthe iboga she had bought online. Analysis of the powder revealed the absence of ibogaine but the presence of toxic alkaloids (ajmaline, yohimbine and reserpine) found in Rauvolfia sp. plant species. An original and specific LC-MS/MS method developed to quantify ajmaline, yohimbine and reserpine showed respective concentrations of 109...
September 2016: Forensic Science International
Greg Mellor, Christopher P Nelson, Claire Robb, Hariharan Raju, Yanushi Wijeyeratne, Christian Hengstenberg, Wibke Reinhard, Michael Papadakis, Sanjay Sharma, Nilesh J Samani, Elijah R Behr
BACKGROUND: The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear. METHODS AND RESULTS: We analyzed 12-lead ECGs of 401 first-degree relatives of individuals who had died from SADS. The prevalence of ER patterns was compared with family-clustered controls. ER was more common in SADS family members than in controls (21% versus 8%; odds ratio: 5...
June 2016: Circulation. Arrhythmia and Electrophysiology
N Alessandri, B L Nguyen, F Tufano, R Sergiacomi, F Tersigni, F Urciuoli, S De Angelis, A Dei Giudici
OBJECTIVE: The role of electrophysiology study in Brugada syndrome (BS) sudden cardiac death risk stratification remains controversial and seems to depend on the phenotypic expression of the channelopathy. Ajmaline has a key role in the diagnosis of BS. We observed that programmed electrical stimulation (PES) of the right ventricular outflow tract (RVOT), only when type 1 BS ECG is unmasked by ajmaline administration, induces ventricular arrhythmias. CASE REPORT: We describe a case of ventricular fibrillation induction by PES of the RVOT when type 1 BS ECG is revealed by ajmaline, in a patient with a baseline dynamic intermittent type 1 and 2 BS ECG...
May 2016: European Review for Medical and Pharmacological Sciences
M Cecilia Gonzalez Corcia, Carlo de Asmundis, Gian-Battista Chierchia, Pedro Brugada
Brugada syndrome is an inherited arrhythmogenic disorder, characterised by coved-type ST-segment elevation in the right precordial leads, and is associated with increased risk of sudden death. It is genetically and clinically heterogeneous, presenting typically in the fourth or fifth decade of life. The prevalence of Brugada syndrome in the paediatric population is low compared with the adult population. Interestingly, over the last several years, there has been growing evidence in the literature of onset of the disease during childhood...
August 2016: Cardiology in the Young
Paulo Cázares-Flores, Dylan Levac, Vincenzo De Luca
Ajmaline biosynthesis in Rauvolfia serpentina has been one of the most studied monoterpenoid indole alkaloid (MIA) pathways within the plant family Apocynaceae. Detailed molecular and biochemical information on most of the steps involved in the pathway has been generated over the last 30 years. Here we report the identification, molecular cloning and functional expression in Escherichia coli of two R. serpentinacDNAs that are part of a recently discovered γ-tocopherol-like N-methyltransferase (γ-TLMT) family and are involved in indole and side-chain N-methylation of ajmaline...
August 2016: Plant Journal: for Cell and Molecular Biology
Gerd Bürkle, Henry Schäfer, Christoph Marschall, Pedro Brugada, Joachim R Ehrlich
We present a case of a symptomatic patient with Brugada syndrome, who had sustained right ventricular outflow tract tachycardia after pronounced exercise-induced ST segment elevation in V1 and V2. In electrophysiological study he developed right ventricular outflow tract tachycardia provoked by combined infusion of ajmaline and orciprenaline. After ablation no further arrhythmia was provoked by pharmacological stimulation.
February 1, 2016: Canadian Journal of Cardiology
Bieke Dobbels, Dieter De Cleen, Joris Ector
The Brugada syndrome is a genetic disease characterized by an abnormal electrocardiogram (ECG) and an elevated risk of sudden cardiac death. Sodium channel blockers (SCBs), such as ajmaline, are used to unmask the characteristic type 1 Brugada electrocardiographic pattern. We review the literature on the incidence of ventricular arrhythmia (VA) during SCB challenge. We evaluate the clinical and electrocardiographic characteristics of these patients as well as their prognosis. All articles published from January 2000 until August 2015, in which the incidence and predictors of VAs during SCB challenge were reported, are reviewed...
March 3, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Vincent Probst, Stéphanie Chatel, Jean-Baptiste Gourraud, Hervé Le Marec
Brugada syndrome (BrS) is a clinical entity characterised by an incomplete right bundle branch block associated with an ST segment elevation in the right precordial leads and a risk of ventricular arrhythmia and sudden death in the absence of structural abnormalities. Patients with a personal history of sudden death have an annual arrhythmia risk of recurrence as high as 10 %. Similarly, the presence of syncope is consistently associated with an increased arrhythmic risk. This risk can be estimated at about 1...
September 2012: Arrhythmia & Electrophysiology Review
Ojas A Namjoshi, James M Cook
The sarpagine-related macroline and ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the family Apocynaceae. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine-related alkaloids and the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists...
2016: Alkaloids. Chemistry and Biology
Fangrui Wu, Petra Kerčmar, Chenggui Zhang, Joachim Stöckigt
The biosynthetic pathway of the monoterpenoid indole alkaloid ajmaline in the genus Rauvolfia, in particular Rauvolfia serpentina Benth. ex Kurz, is one of the few pathways that have been comprehensively uncovered. Every step in the progress of plant alkaloid biosynthesis research is due to the endeavors of several generations of scientists and the advancement of technologies. The tissue and cell suspension cultures developed in the 1970s by M.H. Zenk enabled the extraction of alkaloids and crude enzymes for use as experimental materials, thus establishing the foundation for further research on enzymatic reaction networks...
2016: Alkaloids. Chemistry and Biology
Anna K M Korte, Lennie Derde, Jeroen van Wijk, David H Tjan
An 18-year-old man suffered a sudden cardiac arrest with ventricular fibrillation and was successfully resuscitated. He had neither a medical nor family history of cardiac disease/sudden death, but was known to have Graves' disease, for which he was treated with radioactive iodine. Recently, block-and-replacement therapy had been discontinued to evaluate thyroid functioning. On admission, thyroid hormone levels were markedly elevated, suggesting thyroid storm due to residual Graves' disease. The patient was treated with propylthiouracil, hydrocortisone and Lugol solution...
2015: BMJ Case Reports
Marcus Geissler, Marie Burghard, Jascha Volk, Agata Staniek, Heribert Warzecha
Based on findings described herein, we contend that the reduction of vomilenine en route to antiarrhythmic ajmaline in planta might proceed via an alternative, novel sequence of biosynthetic steps. In the genus Rauvolfia, monoterpenoid indole alkaloids (MIAs) are formed via complex biosynthetic sequences. Despite the wealth of information about the biochemistry and molecular genetics underlying these processes, many reaction steps involving oxygenases and oxidoreductases are still elusive. Here, we describe molecular cloning and characterization of three cinnamyl alcohol dehydrogenase (CAD)-like reductases from Rauvolfia serpentina cell culture and R...
March 2016: Planta
Giulio Conte, Francois Regoli, Tiziano Moccetti, Angelo Auricchio
No abstract text is available yet for this article.
May 14, 2016: European Heart Journal
Judith N Ten Sande, Ruben Coronel, Chantal E Conrath, Antoine H G Driessen, Joris R de Groot, Hanno L Tan, Koonlawee Nademanee, Arthur A M Wilde, Jacques M T de Bakker, Pascal F H M van Dessel
BACKGROUND: Brugada syndrome (BrS) is characterized by a typical ECG pattern. We aimed to determine the pathophysiologic basis of the ST-segment in the BrS-ECG with data from various epicardial and endocardial right ventricular activation mapping procedures in 6 BrS patients and in 5 non-BrS controls. METHODS AND RESULTS: In 7 patients (2 BrS and 5 controls) with atrial fibrillation, an epicardial 8×6 electrode grid (interelectrode distance 1 mm) was placed epicardially on the right ventricular outflow tract (RVOT) before video-assisted thoracoscopic surgical pulmonary vein isolation...
December 2015: Circulation. Arrhythmia and Electrophysiology
Satyanarayanaraju Sagi, Bharathi Avula, Yan-Hong Wang, Ikhlas A Khan
A new UHPLC-UV method has been developed for the simultaneous analysis of seven alkaloids [ajmaline (1), yohimbine (2), corynanthine (3), ajmalicine (4), serpentine (5), serpentinine (6), and reserpine (7)] from the root samples of Rauwolfia serpentina (L.) Benth. ex Kurz. The chromatographic separation was achieved using a reversed phase C18 column with a mobile phase of water and acetonitrile, both containing 0.05% formic acid. The seven compounds were completely separated within 8 min at a flow rate of 0...
January 2016: Analytical and Bioanalytical Chemistry
K Jeevaratnam, L Guzadhur, Y M Goh, A A Grace, C L-H Huang
Normal cardiac excitation involves orderly conduction of electrical activation and recovery dependent upon surface membrane, voltage-gated, sodium (Na(+) ) channel α-subunits (Nav 1.5). We summarize experimental studies of physiological and clinical consequences of loss-of-function Na(+) channel mutations. Of these conditions, Brugada syndrome (BrS) and progressive cardiac conduction defect (PCCD) are associated with sudden, often fatal, ventricular tachycardia (VT) or fibrillation. Mouse Scn5a(+/-) hearts replicate important clinical phenotypes modelling these human conditions...
February 2016: Acta Physiologica
Gaurav Raj Dwivedi, Shikha Gupta, Anupam Maurya, Shubhandra Tripathi, Ashok Sharma, Mahendra P Darokar, Santosh K Srivastava
Antibacterial and synergy potential of naturally occurring indole alkaloids (IA): 10-methoxy tetrahydroalstonine (1), isoreserpiline (2), 10 and 11 demethoxyreserpiline (3), reserpiline (4), serpentine (5), ajmaline (6), ajmalicine (7), yohimbine (8), and α-yohimbine (9) was evaluated using microbroth dilution assay. Further, α-yohimbine (9) was chemically transformed into six semisynthetic derivatives (9A-9F), and their antibacterial and synergy potential in combination with nalidixic acid (NAL) against E...
December 2015: Chemical Biology & Drug Design
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