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BMC Psychiatry Mar 2021Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency...
BACKGROUND
Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency ward and the ICU. OP compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a unusual case of OP poisoning (OPP) in which prolonged apnea ensued in a patient of severe depression following MECT (modified electroconvulsive therapy) in which suxamethonium was used as muscle relaxant, in whom we were cautious of the side-effect of prior organophosphorus poisoning. Since the cases of OPP are very high worldwide, a thorough knowledge of the interaction of the action of the drug and the receptors on which it acts takes pride of place. This article highlights the nuances in the field of psychiatry and anaesthesia in diagnosis and management of prolonged apnea after ECT.
CASE PRESENTATION
A 53/F patient consumed OP 38 days prior to MECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of < 0.3 mg/kg, the patient remained apneic for 3 h. Suxamethionum apnea was managed with elective ventilation. After recovery, patient had no residual effect. Subsequently her pseudocholinesterase levels were done which were found to be very low.
CONCLUSION
This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure. In strong suspects dibucaine number and fluoride number also needs to be estimated.
Topics: Apnea; Electroconvulsive Therapy; Female; Humans; Neuromuscular Depolarizing Agents; Organophosphate Poisoning; Poisoning; Succinylcholine
PubMed: 33691646
DOI: 10.1186/s12888-021-03150-0 -
Molecules (Basel, Switzerland) Aug 2022In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic...
In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02-5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0-108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5-7.7% and 1.5-8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.
Topics: Anesthetics, Local; Chromatography, High Pressure Liquid; Humans; Magnetic Phenomena; Nanotubes, Carbon; Solid Phase Extraction
PubMed: 36080279
DOI: 10.3390/molecules27175509 -
Evidence-based Complementary and... 2022Alzheimer's disease (AD) is the most common type of dementia, and the abnormal hyperphosphorylation of the tau protein is the main component of its pathogenesis. Calpain...
Alzheimer's disease (AD) is the most common type of dementia, and the abnormal hyperphosphorylation of the tau protein is the main component of its pathogenesis. Calpain was found to be abnormally activated in neurofibrillary tangles (NFTs) in a previous report. Cornel iridoid glycosides (CIG) have been reported to reduce the hyperphosphorylation of tau protein. Nevertheless, the role of calpain in the reduction tau hyperphosphorylation by CIG remains unclear. In the present study, we investigated the effect of CIG on calpain activity through in vitro and in vivo experiments. Western blotting results suggested that CIG decreased the phosphorylation of tau at Ser 404 and Ser 262 sites in P301S mice. Moreover, CIG inhibited the activity of calpain and glycogen synthase kinase 3 (GSK-3) and enhanced the activity of protein phosphatase 2A (PP2A) both in vivo and in vitro. CIG also inhibited the activation of PP2A and reduced the GSK-3 activity caused by the calpain activator dibucaine. In addition, the main components of CIG, morroniside and loganin, play an equivalent role in reducing calpain activity, as the effect of their combined use is equivalent to that of CIG. The abovementioned findings revealed that CIG improved PP2A activity and reduced GSK-3 activity by adjusting the activity of calpain 1, leading to a reduction in the phosphorylation of tau. This study highlights the remarkable therapeutic potential of CIG for managing AD.
PubMed: 35096120
DOI: 10.1155/2022/9213046 -
European Journal of Hospital Pharmacy :... Jul 2016This work aimed to evaluate the quality of non-sterile formulations compounded at Centro Hospitalar Cova da Beira (Covilhã, Portugal) immediately after preparation and...
OBJECTIVES
This work aimed to evaluate the quality of non-sterile formulations compounded at Centro Hospitalar Cova da Beira (Covilhã, Portugal) immediately after preparation and up to the defined 'beyond-use date'.
METHODS
Microbiological quality control tests were performed in accordance with monograph 5.1.4 of the European Pharmacopoeia 8.0. Samples of compounded products were collected from January to December 2014 after preparation and were analysed immediately and reanalysed after storage under the established conditions, for each preparation.
RESULTS
In the test period, 392 preparations were analysed, corresponding to 24 different formulations (8 intermediate preparations, 11 oral solutions/suspensions and 5 topical preparations). All preparations were in accordance with the pharmacopoeia specifications immediately after preparation. However, for the formulations 'prednisolone oral solution (5 mg/mL)' and 'nitroglycerine and cinchocaine ointment (0.25%/0.5%)', the microbial counts of some batches exceeded the defined limits after storage up to the beyond-use date.
CONCLUSIONS
These results show that the compounding practices implemented at this pharmacy department are able to ensure the microbiological quality of compounded products. This microbiological quality control methodology also allowed identification of the need to replace formulations shown not to be stable throughout the storage period. On the basis of these results, a monthly routine of microbiological control of a random sample of compounded medicines was established in order to ensure their quality and safety for use.
PubMed: 31156854
DOI: 10.1136/ejhpharm-2015-000769 -
Biochimica Et Biophysica Acta Mar 2015Interactions of two local anesthetics, dibucaine and tetracaine have been studied with phospholipid vesicles containing cholesterol and/or monosialogangliosides (GM1)...
Interactions of two local anesthetics, dibucaine and tetracaine have been studied with phospholipid vesicles containing cholesterol and/or monosialogangliosides (GM1) using fluorescence spectroscopy. The fluorescence intensity of tetracaine showed a marked increase with the increasing molar ratio of the phospholipid to tetracaine, while that of dibucaine showed opposite effects. Steady state anisotropy and the wavelength of maximum emission (λmax) decreased with the increasing phospholipids to tetracaine ratio. The extent of such changes in anisotropy and λmax in the presence and absence of two important components of neuronal membranes, cholesterol and GM1 indicated differential membrane localization of the two local anesthetics. To understand the intercellular mode of action of local anesthetics, we have also studied the interactions of dibucaine and tetracaine with brain spectrin which indicate differential spectrin interactions with similar binding strength. Thermodynamic parameters associated with such binding reveal that binding is favored by entropy. Tetracaine brings about distinct structural changes in spectrin compared to dibucaine, as reflected in the tryptophan mean lifetime and far-UV CD spectra. Tetracaine also exhibits a detergent-like property inducing concentration dependent decrease in spectrin anisotropy, further indicating structural changes in brain spectrin with probable implications in its anesthetic potential.
Topics: Algorithms; Anesthetics, Local; Animals; Brain; Cell Membrane; Cholesterol; Circular Dichroism; Dibucaine; G(M1) Ganglioside; Kinetics; Membrane Lipids; Models, Chemical; Models, Molecular; Phospholipids; Protein Binding; Sheep; Spectrin; Spectrometry, Fluorescence; Tetracaine; Thermodynamics
PubMed: 25482358
DOI: 10.1016/j.bbamem.2014.11.022 -
Korean Journal of Family Medicine Sep 2019It has been reported that in 62.5% of cases of incurable cancer pain, the complaint is due to myofascial pain syndrome. Trigger point injections using dibucaine...
BACKGROUND
It has been reported that in 62.5% of cases of incurable cancer pain, the complaint is due to myofascial pain syndrome. Trigger point injections using dibucaine hydrochloride help patients with such cancer pain. This study evaluated the efficacy of trigger point injections for alleviating pain in patients with advanced cancer.
METHODS
Twenty patients with advanced cancer who had a life expectancy of 6 months or less and had been diagnosed with myofascial pain syndrome were treated with trigger point injections. Prior to treatment, a Visual Analog Scale (VAS) was used to measure the resting pain level and discomfort upon application of pressure on the site of pain. These values were compared with last treatment measurements.
RESULTS
The mean pre-treatment VAS scores for pain at rest and upon application of pressure on the pain site were 7.3 and 9.0, respectively. These scores decreased significantly to 1.95 and 3.2, respectively, after the treatment (P<0.05).
CONCLUSION
Trigger point injection is an alternative and effective pain control modality for advanced cancer patients with myofascial pain syndrome.
PubMed: 31487973
DOI: 10.4082/kjfm.18.0065 -
Evidence-based Complementary and... 2021Linn. (CQ) is a medicinal plant with good evidence for the treatment of hemorrhoids, listed in the Thai National List of Herbal Products in the oral dosage form. (Wall...
BACKGROUND
Linn. (CQ) is a medicinal plant with good evidence for the treatment of hemorrhoids, listed in the Thai National List of Herbal Products in the oral dosage form. (Wall ex. DC.) R. K. Jansen. (AP) is a medicinal plant with a local anesthetic effect.
OBJECTIVE
To investigate the potential of rectal suppositories containing CQ and AP extracts to alleviate symptoms of hemorrhoids compared with the commercialized rectal suppository containing hydrocortisone and cinchocaine.
MATERIALS AND METHODS
Hemorrhoid outpatients ( = 105) with different severity grades (I, II, or III) from eight hospitals in northern Thailand were included in this study. Hemorrhoid severity was graded by proctoscopy associated with either anal pain or bleeding related to hemorrhoids or both. The patients were randomly allocated to two groups: CQ-AP group ( = 52) or the commercialized rectal suppository group ( = 53). One suppository was rectally administered twice daily in the morning and at bedtime for seven days. Evaluations were performed by physicians on days 1, 4, and 8 of the study. The primary endpoints were bleeding and prolapse size, while the secondary endpoint was anal pain.
RESULTS
Baseline demographics, lifestyle, constipation, number of prolapses, grade of hemorrhoid severity, and duration of experiencing hemorrhoids were comparable in both groups of patients. The effects of CQ-AP and the commercialized rectal suppository on bleeding, prolapse size, and anal pain were comparable. The patients in both groups were satisfied with both products at comparable levels and stated a preference for further use in the case of hemorrhoids recurrence. In terms of safety, the patients in the commercialized rectal suppository group experienced a higher incidence of adverse events, including anal pain and bleeding.
CONCLUSION
Rectal suppositories containing a combined extract of CQ and AP show potential in alleviating hemorrhoidal symptoms with a good safety profile.
PubMed: 34765003
DOI: 10.1155/2021/5605323 -
PloS One 2015Butyrylcholinesterase (BChE) activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of...
Butyrylcholinesterase (BChE) activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.
Topics: Biological Assay; Butyrylcholinesterase; Butyrylthiocholine; Cholinesterase Inhibitors; Humans; Indicator Dilution Techniques; Pesticides
PubMed: 26444431
DOI: 10.1371/journal.pone.0139480 -
The West Virginia Medical Journal 2016Prolonged paralysis due to a quantitative or qualitative deficiency of pseudocholinesterase activity is an uncommon but known side effect of succinylcholine. We describe...
Prolonged paralysis due to a quantitative or qualitative deficiency of pseudocholinesterase activity is an uncommon but known side effect of succinylcholine. We describe a patient who experienced prolonged paralysis following administration of succinylcholine for general anesthesia and endotracheal intubation for an emergent cesarean section despite laboratory evidence of normal enzyme function. The patient required mechanical ventilation in the intensive care unit for several hours following surgery. The patient was extubated following return of full muscle strength and had a good outcome. The enzyme responsible for the metabolism of succinylcholine, pseudocholinesterase, was determined to be low in quantity in this patient but was functionally normal. This low level, by itself, was unlikely to be solely responsible for the prolonged paralysis. The patient likely had an abnormal pseudocholinesterase enzyme variant that is undetectable by standard laboratory tests.
Topics: Adult; Anesthesia, General; Anesthetics, Local; Butyrylcholinesterase; Cesarean Section; Dibucaine; Emergencies; Female; Humans; Intensive Care Units; Intubation, Intratracheal; Neuromuscular Depolarizing Agents; Obstetric Labor Complications; Paralysis; Pregnancy; Respiration, Artificial; Succinylcholine; Time Factors; Treatment Outcome
PubMed: 27025119
DOI: No ID Found -
PloS One 2014Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in...
Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a "silent" phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 µM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD) simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels.
Topics: Alleles; Apnea; Base Sequence; Biocatalysis; Butyrylcholinesterase; DNA Mutational Analysis; Family Health; Female; Humans; Infant, Newborn; Isoquinolines; Kinetics; Male; Mivacurium; Molecular Dynamics Simulation; Mutation, Missense; Neuromuscular Depolarizing Agents; Pedigree; Succinylcholine
PubMed: 25054547
DOI: 10.1371/journal.pone.0101552