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Raymond J Malapero, Michael P Zaccagnino, Ethan Y Brovman, Alan David Kaye, Richard D Urman
Etomidate is an imidazole derivative that possesses important sedative properties employed in anesthesia practice, however, etomidate has a number of well-know side effects which limit its use in certain subpopulations and over long periods of time, mostly related to dose-dependent adrenal suppression. This review focuses on novel etomidate derivatives with an emphasis on pharmacological properties which afford improved safety profile and potentially desirable clinical effects. The pharmacology and clinical investigation of some of these etomidate derivatives, e...
October 2017: Journal of Anaesthesiology, Clinical Pharmacology
Junli Jiang, Bin Wang, Zhaoqiong Zhu, Jun Yang, Jin Liu, Wensheng Zhang
BACKGROUND: Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia...
2017: PeerJ
Jun Yang, Yi Kang, Bin Wang, Linghui Yang, Jin Liu, Wensheng Zhang
Owing to rapid generation in body, the metabolites of etomidate softdrug are able to accumulate in either the brain or periphery and subsequently affect the recovery from anaesthesia or cause corticosteroid suppression. This study was designed to investigate the ability of two etomidate analogues (ET-26, ET-42) with inactive metabolites to provide anaesthesia with lesser corticosteroid suppression. The 50% effective dose (ED50 ) of ET-26, ET-42, Etomidate, MOC-ET (an etomidate softdrug) and CPMM (an improved etomidate softdrug) required to induce anaesthesia intravenously in Beagle dogs were 1...
March 1, 2017: European Journal of Pharmaceutical Sciences
Ervin Pejo, Xiaojuan Zhou, S Shaukat Husain, Douglas E Raines
BACKGROUND: Etomidate potently suppresses adrenocortical steroid synthesis with potentially deleterious consequences by binding to 11β-hydroxylase and inhibiting its function. The authors hypothesized that other sedative-hypnotics currently in clinical use or under development (or their metabolites) might bind to the same site at clinically relevant concentrations. The authors tested this hypothesis by defining etomidate's affinity for this site and the potencies with which other sedative-hypnotics (and their metabolites) inhibit etomidate binding...
November 2016: Anesthesiology
Ervin Pejo, Jifeng Liu, Xiangjie Lin, Douglas E Raines
BACKGROUND: Methoxycarbonyl etomidate (MOC-etomidate) and cyclopropyl methoxycarbonyl metomidate (CPMM) are rapidly metabolized "soft" etomidate analogs. CPMM's duration of hypnotic effect is context insensitive, whereas MOC-etomidate's is not. In this study, we tested the hypothesis that CPMM's effect is context insensitive because, unlike MOC-etomidate, its metabolite fails to reach physiologically important concentrations in vivo even with prolonged continuous infusion. METHODS: We compared the potencies with which MOC-etomidate and CPMM activate α1(L264T)β3γ2 γ-aminobutyric acid type A receptors and induce loss-of-righting reflexes (i...
April 2016: Anesthesia and Analgesia
F Londono, B Uytterhaegen, R Kassel, R Vanraemdonck, A Beck, B Comet, A Runge, P Segers
OBJECTIVE: The aim was to test the technical feasibility of a set up combining tonometry and ultrasound, designated as Continuous Physiological and Medical Monitoring (CPMM), for cardiovascular assessment on humans and to evaluate the ability to assess physiological changes induced by artificial gravity in the short arm human centrifuge (SAHC, Verhaert, Belgium) for detecting and preventing potential disorders induced by weightlessness. DESIGN AND METHOD: The project was developed under an European Space Agency (ESA) contract (4000101988/10/NL/EM) and with its support, by the company Verhaert in consortium with the Institute for Space Medicine and Physiology (MEDES) and Ghent University...
June 2015: Journal of Hypertension
Peter Santer, Ervin Pejo, Yan Feng, Wei Chao, Douglas E Raines
BACKGROUND: Cyclopropyl-methoxycarbonyl metomidate (CPMM) is a rapidly metabolized etomidate analog that is currently in clinical trials. The goal of this study is to assess CPMM's potential value as an anesthetic agent for use in patients with sepsis by defining its actions in an acute inflammatory model of sepsis. METHODS: Escherichia coli lipopolysaccharide (1 mg/kg) was injected intravenously into Sprague-Dawley rats. Thirty minutes later, CPMM, etomidate, or vehicle (n = 8 per group) was infused for 1 h...
August 2015: Anesthesiology
Francesco Di Nardo, Carla E Cogo, Emanuela Faelli, Micaela Morettini, Laura Burattini, Piero Ruggeri
A C-peptide-based assessment of β-cell function was performed here in the Zucker fatty rat, a suitable animal model of human metabolic syndrome. To this aim, a 90-min intravenous glucose tolerance test (IVGTT) was performed in seven Zucker fatty rats (ZFR), 7-to-9 week-old, and seven age-matched Zucker lean rats (ZLR). The minimal model of C-peptide (CPMM), originally introduced for humans, was adapted to Zucker rats and then applied to interpret IVGTT data. For a comprehensive evaluation of glucose tolerance in ZFR, CPMM was applied in combination with the minimal model of glucose kinetics (GKMM)...
2015: PloS One
Jason A Campagna, Kevin Pojasek, David Grayzel, John Randle, Douglas E Raines
BACKGROUND: Cyclopropyl-methoxycarbonyl metomidate (CPMM, also known as ABP-700) is a second-generation "soft" (i.e., metabolically labile) etomidate analogue. The purpose of this study was to characterize CPMM's pharmacology in beagle dogs in preparation for potential first in human phase 1 clinical trials. METHODS: CPMM's and etomidate's hypnotic activity and duration of action were assessed using loss of righting reflex and anesthesia score assays in three or four dogs...
December 2014: Anesthesiology
Hanneke E Zwikker, Bart J van den Bemt, Johanna E Vriezekolk, Cornelia H van den Ende, Sandra van Dulmen
OBJECTIVES: Several cross-sectional studies suggest that psychosocial factors are associated with non-adherence to chronic preventive maintenance medication (CPMM); however, results from longitudinal associations have not yet been systematically summarized. Therefore, the objective of this study was to systematically synthesize evidence of longitudinal associations between psychosocial predictors and CPMM non-adherence. MATERIALS AND METHODS: PUBMED, EMBASE, CINAHL, and PsychINFO databases were searched for studies meeting our inclusion criteria...
2014: Patient Preference and Adherence
Rile Ge, Ervin Pejo, Hilary Gallin, Spencer Jeffrey, Joseph F Cotten, Douglas E Raines
BACKGROUND: Cyclopropyl-methoxycarbonyl metomidate (CPMM) is a "soft" etomidate analogue currently being developed as a propofol alternative for anesthetic induction and maintenance. METHODS: We compared the potencies of CPMM and propofol by assessing their abilities to directly activate α1(L264T)β3γ2 gamma-aminobutyric acid type A (GABAA) receptors and induce loss of righting reflexes in tadpoles. We also measured the rates of encephalographic recovery in rats after CPMM and propofol infusions ranging in duration from 5 to 120 minutes...
March 2014: Anesthesia and Analgesia
Mahasweta Das, Chunyan Wang, Raminder Bedi, Shyam S Mohapatra, Subhra Mohapatra
Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats...
October 2014: Nanomedicine: Nanotechnology, Biology, and Medicine
Rile Ge, Ervin Pejo, Joseph F Cotten, Douglas E Raines
INTRODUCTION: Etomidate is no longer administered as a continuous infusion for anesthetic maintenance or sedation, because it results in profound and persistent suppression of adrenocortical steroid synthesis with potentially lethal consequences in critically ill patients. We hypothesized that rapidly metabolized soft analogues of etomidate could be developed that do not produce persistent adrenocortical dysfunction even after prolonged continuous infusion. We hope that such agents might also provide more rapid and predictable anesthetic emergence...
2013: Critical Care: the Official Journal of the Critical Care Forum
Rile Ge, Ervin Pejo, S Shaukat Husain, Joseph F Cotten, Douglas E Raines
BACKGROUND: Methoxycarbonyl etomidate is the prototypical soft etomidate analog. Because it has relatively low potency and is extremely rapidly metabolized, large quantities must be infused to maintain hypnosis. Consequently with prolonged infusion, metabolite reaches sufficient concentrations to delay recovery. Dimethyl-methoxycarbonyl metomidate (DMMM) and cyclopropyl-methoxycarbonyl metomidate (CPMM) are methoxycarbonyl etomidate analogs with higher potencies and slower clearance. Because of these properties, we hypothesized that dosing would be lower and electroencephalographic and hypnotic recoveries would be faster - and less context-sensitive - with DMMM or CPMM versus methoxycarbonyl etomidate or etomidate...
November 2012: Anesthesiology
Roberto Burattini, Micaela Morettini, Francesco Di Nardo, Massimo Boemi
Based on glucose kinetics minimal model (GKMM) interpretation of frequently sampled intravenous glucose tolerance test (FSIGTT), the aim was to broaden the characterization of insulin-mediated glucose disposal in hypertension by aid of a dynamic insulin sensitivity index, S(D)(I), and the related efficiency, η = S(D)(I) / S(I), of the metabolic system to convert the maximal individual response capacity, measured by S (I), into an effective insulin control on glucose. The C-peptide minimal model (CPMM) was used to interpret the role of β-cell function...
July 2011: Medical & Biological Engineering & Computing
M S Tivers, E J Commerford, M R Owen
OBJECTIVES: The objective of this study was to evaluate the effects of fabella-tibial suture (FTS) on long-term outcome in dogs with cranial cruciate ligament (CCL) insufficiency and concurrent medial meniscal tear (MMT) that were managed by an open, caudal pole medial meniscectomy (CPMM). METHODS: A retrospective review was performed of the clinical records of dogs treated for CCL insufficiency with concurrent MMT by open CPMM, with or without the non-random addition of a nylon FTS according to surgeon preference, during the period of 2001 to 2004...
2009: Veterinary and Comparative Orthopaedics and Traumatology: V.C.O.T
Edmund G Lowrie, Ming Teng, Nancy L Lew, Eduardo J Lacson, J M Lazarus, William F Owen
BACKGROUND: Consensus processes using the clinical literature as the primary source for information generally drive projects to draft clinical practice guidelines (CPGs). Most such literature citations describe special projects that are not part of an organized quality management initiative, and the publication/review/consensus process tends to be long. This project describes an initiative to develop and explore a flexible and dedicated data-driven paradigm for deciding new CPGs that could be rapidly responsive to changing medical knowledge and practice...
January 1, 2003: Hemodialysis International
Albert Rosenberger, Manu Sharma, Bertram Müller-Myhsok, Thomas Gasser, Heike Bickeböller
BACKGROUND: Genome wide linkage scans have often been successful in the identification of genetic regions containing susceptibility genes for a disease. Meta analysis is used to synthesize information and can even deliver evidence for findings missed by original studies. If researchers are not contributing their data, extracting valid information from publications is technically challenging, but worth the effort. We propose an approach to include data extracted from published figures of genome wide linkage scans...
2007: BMC Genetics
Kadir Kizilkaya, Robert J Tempelman
We propose a general Bayesian approach to heteroskedastic error modeling for generalized linear mixed models (GLMM) in which linked functions of conditional means and residual variances are specified as separate linear combinations of fixed and random effects. We focus on the linear mixed model (LMM) analysis of birth weight (BW) and the cumulative probit mixed model (CPMM) analysis of calving ease (CE). The deviance information criterion (DIC) was demonstrated to be useful in correctly choosing between homoskedastic and heteroskedastic error GLMM for both traits when data was generated according to a mixed model specification for both location parameters and residual variances...
January 2005: Genetics, Selection, Evolution: GSE
Dyi-Sheng Chang, Chih-Lung Lin, Ann-Shung Lieu, Chi-Yun Cheng, Shu-Chuan Wu, Mei-Hsiang Hung, Joon-Khim Loh, Tai-Hong Kuo, Shen-Long Howng, Shiuh-Lin Hwang
Increasing evidence implies the existence of a visceral pain pathway in the dorsal column of the spinal cord. Limited midline myelotomy has been used to treat intractable pelvic cancer pain. However, no obvious evidence has been provided that high cervical punctate midline myelotomy (CPMM) relieves visceral pain originating from the abdomen. This study was designed to examine the pain relief effect of CPMM in a mouse model of visceral pain. Thirty-six Institute of Cancer Research (ICR) mice were divided into three groups: Group 1, healthy controls; Group 2, treated with CPMM at C1 and C2; and Group 3, a sham group that underwent laminectomy at C1 and C2 without CPMM...
April 2003: Kaohsiung Journal of Medical Sciences
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