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https://www.readbyqxmd.com/read/29142767/could-congenital-insensitivity-to-pain-with-anhidrosis-be-misdiagnosed-as-papillon-lef%C3%A3-vre-syndrome
#1
Mostafa Ibrahim Mostafa, Maha Rashed Abouzaid, Manal Micheal Thomas, Ghada Yousef El-Kamah
Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by early loss of teeth with hyperkeratosis of the palms and soles. Congenital insensitivity to pain with anhidrosis (CIPA) is a disorder of decreased pain sensation, decreased sweating, recurrent infections, and fever. Here, we report a 5-year-old girl born to consanguineous parents with a family history of a similarly affected sibling. The girl presented with early loss of teeth and palmoplantar hyperkeratosis, hence, provisionally diagnosed as PLS...
December 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/29142185/anesthesia-procedure-for-congenital-insensitivity-to-pain-in-a-child-with-anhidrosis-syndrome-a-rare-case
#2
Aykut Urfalioglu, Mahmut Arslan, Yakup Duman, Gökce Gisi, Gözen Oksuz, Hüseyin Yildiz, Hafize Oksuz, Ayşe Balaban
Congenital insensitivity to pain with anhidrosis (CIPA) syndrome is a neuropathy characterized by insensitivity to pain, impaired thermoregulation, anhidrosis, and mental retardation. A 9-year old boy with CIPA syndrome, underwent 2 operations for a calcaneal ulcer. During the first operation standard monitorization was performed. In the second operation, Bispectral Index (BIS) monitoring was added and temperature was monitored with an esophageal probe. In the first operation, in which anesthesia induction was applied with ketamine and midazolam, extremity movements with surgical stimuli were seen...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/29136846/determination-of-bisphenols-with-estrogenic-activity-in-plastic-packaged-baby-food-samples-using-solid-liquid-extraction-and-clean-up-with-dispersive-sorbents-followed-by-gas-chromatography-tandem-mass-spectrometry-analysis
#3
M T García-Córcoles, M Cipa, R Rodríguez-Gómez, A Rivas, F Olea-Serrano, J L Vílchez, A Zafra-Gómez
Bisphenols (BPs) are a family of chemicals with known endocrine disrupting activity. Bisphenol A (BPA) is the most representative prototype of this group of chemicals. Recently, the use of BPA, a prototype of endocrine disruptors, has been reduced and replaced with structural analogs due to its negative effects on both the environment and consumers. In this work, a new method is presented for the determination of seven BPs, with estrogenic activity in ready-to-eat plastic packaged baby foods. The procedure involves the isolation of the analytes using solid-liquid phase extraction with acetonitrile followed by a clean-up step with a mixture of dispersive-SPE sorbents (C18 and PSA) and magnesium sulphate, to reduce matrix effect from proteins, sugars and lipids...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29075324/comparative-characterization-of-all-cellulosomal-cellulases-from-clostridium-thermocellum-reveals-high-diversity-in-endoglucanase-product-formation-essential-for-complex-activity
#4
Benedikt Leis, Claudia Held, Fabian Bergkemper, Katharina Dennemarck, Robert Steinbauer, Alarich Reiter, Matthias Mechelke, Matthias Moerch, Sigrid Graubner, Wolfgang Liebl, Wolfgang H Schwarz, Vladimir V Zverlov
BACKGROUND: Clostridium thermocellum is a paradigm for efficient cellulose degradation and a promising organism for the production of second generation biofuels. It owes its high degradation rate on cellulosic substrates to the presence of supra-molecular cellulase complexes, cellulosomes, which comprise over 70 different single enzymes assembled on protein-backbone molecules of the scaffold protein CipA. RESULTS: Although all 24 single-cellulosomal cellulases were described previously, we present the first comparative catalogue of all these enzymes together with a comprehensive analysis under identical experimental conditions, including enzyme activity, binding characteristics, substrate specificity, and product analysis...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29061979/hipsc-cm-monolayer-maturation-state-determines-drug-responsiveness-in-high-throughput-pro-arrhythmia-screen
#5
André Monteiro da Rocha, Katherine Campbell, Sergey Mironov, Jiang Jiang, Lakshmi Mundada, Guadalupe Guerrero-Serna, José Jalife, Todd J Herron
Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer a novel in vitro platform for pre-clinical cardiotoxicity and pro-arrhythmia screening of drugs in development. To date hiPSC-CMs used for cardiotoxicity testing display an immature, fetal-like cardiomyocyte structural and electrophysiological phenotype which has called into question the applicability of hiPSC-CM findings to the adult heart. The aim of the current work was to determine the effect of cardiomyocyte maturation state on hiPSC-CM drug responsiveness...
October 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021091/an-evaluation-of-multiple-algorithms-for-the-measurement-of-the-heart-rate-corrected-jtpeak-interval
#6
Jean-Philippe Couderc, Shiyang Ma, Alex Page, Connor Besaw, Jean Xia, W Brian Chiu, Johan de Bie, Jose Vicente, Martino Vaglio, Fabio Badilini, Saeed Babaeizadeh, Cheng-Hao Simon Chien, Mathias Baumert
Interest in the effects of drugs on the heart rate-corrected JTpeak (JTpc) interval from the body-surface ECG has spawned an increasing number of scientific investigations in the field of regulatory sciences, and more specifically in the context of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. We conducted a novel initiative to evaluate the role of automatic JTpc measurement technologies by comparing their ability to distinguish multi- from single-channel blocking drugs. A set of 5232 ECGs was shared by the FDA (through the Telemetric and Holter ECG Warehouse) with 3 ECG device companies (AMPS, Mortara, and Philips)...
September 1, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28986934/mechanistic-model-informed-proarrhythmic-risk-assessment-of-drugs-review-of-the-cipa-initiative-and-design-of-a-prospective-clinical-validation-study
#7
Jose Vicente, Robbert Zusterzeel, Lars Johannesen, Jay Mason, Philip Sager, Vikram Patel, Murali K Matta, Zhihua Li, Jiang Liu, Christine Garnett, Norman Stockbridge, Issam Zineh, David G Strauss
The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a mechanistic-based assessment of proarrhythmic risk of drugs. CiPA proposes to assess a drug's effect on multiple ion channels and integrate the effects in a computer model of the human cardiomyocyte to predict proarrhythmic risk. Unanticipated or missed effects will be assessed with human stem cell derived cardiomyocytes and electrocardiogram (ECG) analysis in early phase 1 clinical trials. This paper provides an overview of CiPA and the rationale and design of the CiPA phase 1 ECG validation clinical trial, which involves assessing an additional ECG biomarker (J-Tpeak) for QT prolonging drugs...
October 7, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28981924/-mutation-analysis-of-ntrk1-gene-in-a-family-affected-with-congenital-insensitivity-to-pain-with-anhidrosis
#8
Bingxiao Li, Zhanhui Zhang, Xia Wu, Wenchao Chen, Jianling Chen, Qian Lyu, Guosheng Liu
OBJECTIVE: To screen for mutations of NTRK1 gene in a Chinese family affected with congenital insensitivity to pain with anhidrosis (CIPA). METHODS: Genomic DNA was extracted from the proband and her family members. All of the 17 exons and intron-exon boundaries of the NTRK1 gene were analyzed by direct Sanger sequencing. For the deletional mutation, the PCR products were subjected to T-A cloning and sequencing to verify the mutation. RESULTS: NTRK1 gene analysis revealed that proband has carried a c...
October 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28971611/nerve-growth-factor-inhibitor-with-novel-binding-domain-demonstrates-nanomolar-efficacy-in-both-cell-based-and-cell-free-assay-systems
#9
Allison E Kennedy, Corey A Laamanen, Mitchell S Ross, Rahul Vohra, Douglas R Boreham, John A Scott, Gregory M Ross
Nerve growth factor (NGF), a member of the neurotrophin family, is known to regulate the development and survival of a select population of neurons through the binding and activation of the TrkA receptor. Elevated levels of NGF have been associated with painful pathologies such as diabetic neuropathy and fibromyalgia. However, completely inhibiting the NGF signal could hold significant side effects, such as those observed in a genetic condition called congenital insensitivity to pain and anhidrosis (CIPA). Previous methods of screening for NGF-inhibitors used labeling techniques which have the potential to alter molecular interactions...
October 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28941245/nonclinical-cardiovascularsafety-of-pitolisant-comparing-ich-s7b-and-cipa-initiative-studies
#10
Xavier Ligneau, Rashmi R Shah, Isabelle Berrebi-Bertrand, Gary R Mirams, Philippe Robert, Laurent Landais, Pierre Maison-Blanche, Jean-François Faivre, Jeanne-Marie Lecomte, Jean-Charles Schwartz
PURPOSE: We evaluated the concordance of results from two sets of nonclinical cardiovascular safety studies on pitolisant. METHODS: Nonclinical studies envisaged both in the ICH S7B guideline and Comprehensive in vitroProarrhythmia Assay (CiPA) initiative were undertaken. CiPA-initiative studies included in vitro ion channels and stem cell-derived human ventricular myocyte studies as well asin silico modelling of results to simulate human ventricular electrophysiology...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28928044/electrocardiographic-biomarkers-to-confirm-drug-s-electrophysiological-effects-used-for-proarrhythmic-risk-prediction-under-cipa
#11
Jose Vicente, Meisam Hosseini, Lars Johannesen, David G Strauss
The ECG plays a critical role in the thorough QT study. This clinical study is part of the assessment of proarrhythmic potential of drugs under the current regulatory paradigm. While the current paradigm has been successful in preventing drugs with unexpected QT prolongation or torsade risk from reaching the market, the focus on QT prolongation has likely resulted in potentially beneficial compounds with minimal torsade risk being dropped from development. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is developing and validating a new mechanistic-based paradigm for cardiac safety evaluation of drugs...
August 9, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28919218/cardiologist-s-point-of-view-novel-ecg-biomarkers-and-in-silico-models-for-proarrhythmic-risk-prediction-are-we-ready
#12
Jay W Mason
The CiPA initiative is well underway, but in its early stages. Are we ready for it? There are several issues that bear on the success of this multidisciplinary effort related to (1) the final testing paradigm that will result, (2) the way in which discrepancies in test methods will be handled, (3) commercialization of the testing methods, (4) quantitative understanding of arrhythmia risk of the 6 non-hERG channels being tested, (5) validity of the CiPA drug list, and (6) ultimate clinical validation.
August 15, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28915745/non-local-effects-of-point-mutations-on-the-stability-of-a-protein-module
#13
Mateusz Chwastyk, Andrés M Vera, Albert Galera-Prat, Melissabye Gunnoo, Damien Thompson, Mariano Carrión-Vázquez, Marek Cieplak
We combine experimental and theoretical methods to assess the effect of a set of point mutations on c7A, a highly mechanostable type I cohesin module from scaffoldin CipA from Clostridium thermocellum. We propose a novel robust and computationally expedient theoretical method to determine the effects of point mutations on protein structure and stability. We use all-atom simulations to predict structural shifts with respect to the native protein and then analyze the mutants using a coarse-grained model. We examine transitions in contacts between residues and find that changes in the contact map usually involve a non-local component that can extend up to 50 Å...
September 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28880155/identification-of-ion-currents-components-generating-field-potential-recorded-in-mea-from-hipsc-cm
#14
Fabien Raphel, Muriel Boulakia, Nejib Zemzemi, Yves Coudiere, Jean-Michel Guillon, Philippe Zitoun, Jean-Frederic Gerbeau
Multi Electrodes Arrays (MEAs) combined with cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) can enable high- or medium-throughput drug screening in safety pharmacology. This technology has recently attracted a lot of attention, in particular from an international initiative named CiPA. But it is currently limited by the difficulty to analyze the measured signals. We propose a strategy to analyze the signals acquired by the MEA and to automatically deduce the channels affected by the drug...
September 4, 2017: IEEE Transactions on Bio-medical Engineering
https://www.readbyqxmd.com/read/28878692/optimization-of-an-in-silico-cardiac-cell-model-for-proarrhythmia-risk-assessment
#15
Sara Dutta, Kelly C Chang, Kylie A Beattie, Jiansong Sheng, Phu N Tran, Wendy W Wu, Min Wu, David G Strauss, Thomas Colatsky, Zhihua Li
Drug-induced Torsade-de-Pointes (TdP) has been responsible for the withdrawal of many drugs from the market and is therefore of major concern to global regulatory agencies and the pharmaceutical industry. The Comprehensive in vitro Proarrhythmia Assay (CiPA) was proposed to improve prediction of TdP risk, using in silico models and in vitro multi-channel pharmacology data as integral parts of this initiative. Previously, we reported that combining dynamic interactions between drugs and the rapid delayed rectifier potassium current (IKr) with multi-channel pharmacology is important for TdP risk classification, and we modified the original O'Hara Rudy ventricular cell mathematical model to include a Markov model of IKr to represent dynamic drug-IKr interactions (IKr-dynamic ORd model)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28686863/the-evolving-roles-of-human-ipsc-derived-cardiomyocytes-in-drug-safety-and-discovery
#16
Gary Gintant, Bernard Fermini, Norman Stockbridge, David Strauss
Nonclinical studies of drug effects with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide new possibilities for evaluating drug safety and efficacy. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm provides lessons from the cardiac field that also apply to drug studies with other stem cell-based assays.
July 6, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28634147/csahi-study-2-validation-of-multi-electrode-array-systems-mea60-2100-for-prediction-of-drug-induced-proarrhythmia-using-human-ips-cell-derived-cardiomyocytes-assessment-of-reference-compounds-and-comparison-with-non-clinical-studies-and-clinical-information
#17
Yumiko Nozaki, Yayoi Honda, Hitoshi Watanabe, Shota Saiki, Kiyotaka Koyabu, Tetsuji Itoh, Chiho Nagasawa, Chiaki Nakamori, Chiaki Nakayama, Hiroshi Iwasaki, Shinobu Suzuki, Kohji Tanaka, Etsushi Takahashi, Kaori Miyamoto, Kaoru Morimura, Atsuhiro Yamanishi, Hiroko Endo, Junko Shinozaki, Hisashi Nogawa, Tadahiro Shinozawa, Fumiyo Saito, Takeshi Kunimatsu
With the aim of reconsidering ICH S7B and E14 guidelines, a new in vitro assay system has been subjected to worldwide validation to establish a better prediction platform for potential drug-induced QT prolongation and the consequent TdP in clinical practice. In Japan, CSAHi HEART team has been working on hiPS-CMs in the MEA (hiPS-CMs/MEA) under a standardized protocol and found no inter-facility or lot-to-lot variability for proarrhythmic risk assessment of 7 reference compounds. In this study, we evaluated the responses of hiPS-CMs/MEA to another 31 reference compounds associated with cardiac toxicities, and gene expression to further clarify the electrophysiological characteristics over the course of culture period...
June 17, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28546047/an-impedance-based-approach-using-human-ipsc-derived-cardiomyocytes-significantly-improves-in-vitro-prediction-of-in-vivo-cardiotox-liabilities
#18
Bryan Koci, Gregory Luerman, Anika Duenbostell, Ralf Kettenhofen, Heribert Bohlen, Luke Coyle, Brian Knight, Warren Ku, Walter Volberg, Joseph R Woska, Martha P Brown
Current in vitro approaches to cardiac safety testing typically focus on mechanistic ion channel testing to predict in vivo proarrhythmic potential. Outside of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, structural and functional cardiotoxicity related to chronic dosing effects are of great concern as these effects can impact compound attrition. Development and implementation of an in vitro cardiotoxicity screening platform that effectively identifies these liabilities early in the discovery process should reduce costly attrition and decrease preclinical development time...
August 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28467230/ethnic-identity-negotiation-among-sami-youth-living-in-a-majority-sami-community-in-norway
#19
Kristine Nystad, Anna Rita Spein, Asta Mitkija Balto, Benedicte Ingstad
BACKGROUND: This study was part of the international research project "Circumpolar Indigenous Pathways to Adulthood" (CIPA). OBJECTIVES: To explore ethnic identity negotiation, an unexplored theme, among indigenous North Sami youth living in a majority Sami community context in Arctic Norway. METHODS: A qualitative design was followed using open-ended, in-depth interviews conducted in 2010 with 22 Sami adolescents aged 13-19 years, all reporting Sami self-identification...
2017: International Journal of Circumpolar Health
https://www.readbyqxmd.com/read/28461240/safety-pharmacology-methods-and-models-in-an-evolving-regulatory-environment
#20
EDITORIAL
Michael K Pugsley, Tessa de Korte, Simon Authier, Hai Huang, Michael V Accardi, Michael J Curtis
This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2016 Safety Pharmacology Society (SPS), Canadian Society of Pharmacology and Therapeutics (CSPT), and Japanese Safety Pharmacology Society (JSPS) joint meeting held in Vancouver, B.C., Canada. This issue of JPTM continues the tradition of providing a publication summary of articles primarily presented at the joint meeting with direct bearing on the discipline of SP...
April 29, 2017: Journal of Pharmacological and Toxicological Methods
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