2,4-Dinitrophenol: 'diet' drug death following major trauma.
Ontology highlight
ABSTRACT:
SUBMITTER: Freeman N
PROVIDER: S-EPMC8131886 | biostudies-literature | 2021 Jan-Jun
REPOSITORIES: biostudies-literature
Publications
2,4-Dinitrophenol: 'diet' drug death following major trauma.
Freeman N N Moir D D Lowis E E Tam E E
Anaesthesia reports 20210101 1
There has been a resurgence in the illicit use of 2,4-dinitrophenol by people wishing to achieve rapid weight loss. Despite its availability, the drug is banned for human consumption as it is toxic and can have fatal consequences. We present the case of a 23-year-old man who regularly consumed 2,4-dinitrophenol to generate fat loss without apparent ill effect. He was involved in a high-speed road traffic collision and sustained limb-threatening injuries. The combination of emergency surgery, tra ...[more]
Similar Datasets
Project description:Rhodococcus (opacus) erythropolis HL PM-1 grows on 2,4,6-trinitrophenol or 2,4-dinitrophenol (2,4-DNP) as a sole nitrogen source. The NADPH-dependent F(420) reductase (NDFR; encoded by npdG) and the hydride transferase II (HTII; encoded by npdI) of the strain were previously shown to convert both nitrophenols to their respective hydride Meisenheimer complexes. In the present study, npdG and npdI were amplified from six 2,4-DNP degrading Rhodococcus spp. The genes showed sequence similarities of 86 to 99% to the respective npd genes of strain HL PM-1. Heterologous expression of the npdG and npdI genes showed that they were involved in 2,4-DNP degradation. Sequence analyses of both the NDFRs and the HTIIs revealed conserved domains which may be involved in binding of NADPH or F(420). Phylogenetic analyses of the NDFRs showed that they represent a new group in the family of F(420)-dependent NADPH reductases. Phylogenetic analyses of the HTIIs revealed that they form an additional group in the family of F(420)-dependent glucose-6-phosphate dehydrogenases and F(420)-dependent N(5),N(10)-methylenetetrahydromethanopterin reductases. Thus, the NDFRs and the HTIIs may each represent a novel group of F(420)-dependent enzymes involved in catabolism.
| S-EPMC154519 | biostudies-literature
Project description:IntroductionEvidence-based recommendations can be made with respect to many aspects of the acute management of the bleeding trauma patient, which when implemented may lead to improved patient outcomes.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing guidelines for the management of bleeding following severe injury. Recommendations were formulated using a nominal group process and the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) hierarchy of evidence and were based on a systematic review of published literature.ResultsKey recommendations include the following: The time elapsed between injury and operation should be minimised for patients in need of urgent surgical bleeding control, and patients presenting with haemorrhagic shock and an identified source of bleeding should undergo immediate surgical bleeding control unless initial resuscitation measures are successful. A damage control surgical approach is essential in the severely injured patient. Pelvic ring disruptions should be closed and stabilised, followed by appropriate angiographic embolisation or surgical bleeding control, including packing. Patients presenting with haemorrhagic shock and an unidentified source of bleeding should undergo immediate further assessment as appropriate using focused sonography, computed tomography, serum lactate, and/or base deficit measurements. This guideline also reviews appropriate physiological targets and suggested use and dosing of blood products, pharmacological agents, and coagulation factor replacement in the bleeding trauma patient.ConclusionA multidisciplinary approach to the management of the bleeding trauma patient will help create circumstances in which optimal care can be provided. By their very nature, these guidelines reflect the current state-of-the-art and will need to be updated and revised as important new evidence becomes available.
| S-EPMC2151863 | biostudies-literature
Project description:1. The effect of dinitrophenol on the metabolism of glucose labelled with (14)C and tritium by epididymal fat-pad segments from fed rats was studied. Dinitrophenol at concentrations of 0.1-0.3mm: (a) had little effect on glucose utilization; (b) depressed synthesis of fatty acids and greatly increased that of lactate; (c) increased the T/(14)C ratio in fatty acids synthesized from [U-(14)C,3-T]glucose and decreased that in fatty acids synthesized from [U-(14)C,4-T]glucose; (d) abolished randomization of (14)C from [6-(14)C]glucose in lactate. 2. Dinitrophenol stimulated oxidation of pyruvate and greatly inhibited the oxidation of lactate. It inhibited lipogenesis from pyruvate and lactate. 3. From the isotope data it was calculated that: (a) dinitrophenol stimulates oxidation via the tricarboxylic acid cycle three- to six-fold; (b) dinitrophenol depresses markedly the operation of the pentose cycle; (c) in the presence of dinitrophenol, NADPH formed in the pentose cycle provides all the hydrogen equivalents for fatty acid reduction, whereas, in its absence, NADPH provides 50-70% of the hydrogen equivalents; (d) in the presence of dinitrophenol, there is an excess of ATP produced in the cytoplasm, which flows into the mitochondria. A reverse flow operates in the absence of dinitrophenol. 4. A balance of formation and utilization of reduced nicotinamide nucleotides in the cytoplasm was established. With dinitrophenol there is some excess of NADH. There are indications that this excess may be transferred into mitochondria in the form of malate. 5. Our results are interpreted to indicate the absence from adipose tissue of the alpha-glycerophosphate shuttle for transferring reducing equivalents from the cytoplasm to mitochondria. 6. The effects of dinitrophenol are accounted for in terms of decreased ATP concentrations in the cells, leading to marked decrease in pyruvate carboxylation in the mitochondria and depression of fatty acid synthesis in the cytoplasm.
| S-EPMC1187562 | biostudies-other
Project description:Background2,4-Dinitrophenol (2,4-DNP) is an effective but highly dangerous fat burner, not licensed for human consumption. Death cases reported for 2,4-DNP overdose, particularly among young adults, have raised concerns about the ineffective regulatory control, lack of education and risks associated with impurity, and the unknown concentration of 2,4-DNP purchased on the Internet.MethodsUsing a sequential mixed method design and based on a hypothetical scenario as if 2,4-DNP was a licensed pharmaceutical drug, first we conducted a qualitative study to explore what product attributes people consider when buying a weight-loss aid. Focus group interviews with six females and three males (mean age = 21.6 ± 1.8 years) were audiorecorded, transcribed verbatim, and subjected to thematic analysis. Sixteen attributes were identified for the Best-Worst Scale (BWS) in the quantitative survey with 106 participants (64% female, mean age = 27.1 ± 11.9 years), focusing on 2,4-DNP. Demographics, weight satisfaction, and risk for eating disorder data were collected.ResultsIn contrast to experienced users such as bodybuilders, our study participants approached 2,4-DNP cautiously. Attributes of 2,4-DNP as a hypothetical weight-loss drug comprised a range of desirable and avoidable features. Of the 16 selected attributes, BWS suggested that long-term side effects were the most and branding was the least important attribute. Effectiveness and short-term side effects were also essential. Those in the >25 year group showed least concerns for legality. Neutral BWS scores for cost, treatment, degree of lifestyle changes required, and specificity required for the hypothetical weight-loss drug to be effective were likely caused by disagreement about their importance among the participants, not indifference.ConclusionWith advances in research, 2,4-DNP as a pharmaceutical drug in the future for treating neurodegenerative diseases and potentially for weight loss is not inconceivable. Caution is warranted for interpreting the BWS scores. Owing to the difference in what data represent at individual vs. population levels, with pooled data, the method correctly identifies attributes by which most people are satisfied but misrepresents attributes that are individually very important but not universally agreed. Whilst this may be an advantage in marketing applications, it limits the utility of BWS as a research tool.
| S-EPMC5919945 | biostudies-literature
Project description:IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsThis guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.
| S-EPMC2887168 | biostudies-literature
Project description:Mitochondrial uncoupler 2,4-dinitrophenol (2,4-DNP) is a promising antidiabetic and antiobesity agent. Its clinical use is limited by a narrow dynamic range and accumulation in non-target sensitive organs, which results in whole-body toxicity. A liposomal formulation could enable the mentioned drawbacks to be overcome and simplify the liver-targeted delivery and sustained release of 2,4-DNP. We synthesized 2,4-DNP esters with carboxylic acids of various lipophilic degrees using carboxylic acid chloride and then loaded them into liposomes. We demonstrated the effective increase in the entrapment of 2,4-DNP into liposomes when esters were used. Here, we examined the dependence of the sustained release of 2,4-DNP from liposomes on the lipid composition and LogPoct of the ester. We posit that the optimal chain length of the ester should be close to the palmitic acid and the lipid membrane should be composed of phospholipids with a certain phase transition point depending on the desired release rate. The increased effect of the ATP synthesis inhibition of the liposomal forms of caproic and palmitic acid esters compared to free molecules in liver hepatocytes was demonstrated. The liposomes' stability could well be responsible for this result. This work demonstrates promising possibilities for the liver-targeted delivery of the 2,4-DNP esters with carboxylic acids loaded into liposomes for ATP synthesis inhibition.
| S-EPMC9268429 | biostudies-literature
Project description:BackgroundFemoral shaft fractures are common in major trauma. Early definitive fixation, within 24 hours, is feasible in most patients and is associated with improved outcomes. Nonetheless, variability might exist between trauma centers in timeliness of fixation. Such variability could impact outcomes and would therefore represent a target for quality improvement. We evaluated variability in delayed fixation (≥24 hours) between trauma centers participating in the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) and measured the resultant association with important clinical outcomes at the hospital level.Methods and findingsA retrospective cohort study was performed using data derived from the ACS TQIP database. Adults with severe injury who underwent definitive fixation of a femoral shaft fracture at a level I or II trauma center participating in ACS TQIP (2012-2015) were included. Patient baseline and injury characteristics that might affect timing of fixation were considered. A hierarchical logistic regression model was used to identify predictors of delayed fixation. Hospital variability in delayed fixation was measured using 2 approaches. First, the random effects output of the hierarchical model was used to identify outlier hospitals where the odds of delayed fixation were significantly higher or lower than average. Second, the median odds ratio (MOR) was calculated to quantify heterogeneity in delayed fixation between hospitals. Finally, complications (pulmonary embolism, deep vein thrombosis, acute respiratory distress syndrome, pneumonia, decubitus ulcer, and death) and hospital length of stay were compared across quartiles of risk-adjusted delayed fixation. We identified 17,993 patients who underwent definitive fixation at 216 trauma centers. The median injury severity score (ISS) was 13 (interquartile range [IQR] 9-22). Median time to fixation was 15 hours (IQR 7-24 hours) and delayed fixation was performed in 26% of patients. After adjusting for patient characteristics, 57 hospitals (26%) were identified as outliers, reflecting significant practice variation unexplained by patient case mix. The MOR was 1.84, reflecting heterogeneity in delayed fixation across centers. Compared to hospitals in the lowest quartile of delayed fixation, patients treated at hospitals in the highest quartile of delayed fixation suffered 2-fold higher rates of pulmonary embolism (2.6% versus 1.3%; rate ratio [RR] 2.0; 95% CI 1.2-3.2; P = 0.005) and required greater length of stay (7 versus 6 days; RR 1.15; 95% CI 1.1-1.19; P < 0.001). There was no significant difference with respect to mortality (1.3% versus 0.8%; RR 1.6; 95% CI 1.0-2.8; P = 0.066). The main limitations of this study include the inability to classify fractures by severity, challenges related to the heterogeneity of the study population, and the potential for residual confounding due to unmeasured factors.ConclusionsIn this large cohort study of 216 trauma centers, significant practice variability was observed in delayed fixation of femoral shaft fractures, which could not be explained by differences in patient case mix. Patients treated at centers where delayed fixation was most common were at significantly greater risk of pulmonary embolism and required longer hospital stay. Trauma centers should strive to minimize delays in fixation, and quality improvement initiatives should emphasize this recommendation in best practice guidelines.
| S-EPMC5497944 | biostudies-literature
Project description:INTRODUCTION: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. METHODS: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. RESULTS: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. CONCLUSIONS: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.
| S-EPMC4056078 | biostudies-other
Project description:Trauma-induced coagulopathy (TIC) is present soon after injury and is associated with increased transfusion requirements and worse outcomes. The pathophysiological mechanisms, which result in the widespread derangements of hemostasis following major trauma hemorrhage, are as yet not fully defined. Profound activation of fibrinolytic pathways and fibrinogen depletion appear to be fundamental processes in the development of TIC and offer potential therapeutic targets. Collaborative and multi-disciplinary scientific study is thus a research priority in order to characterize the primary drivers of TIC and develop targeted and efficacious treatment strategies.
| S-EPMC4075417 | biostudies-other
Project description:MarR is the dedicated autorepressor of the marRAB operon found in seven genera of the Enterobacteraceae. The MarA transcriptional regulator directly activates numerous genes involved in multidrug resistance and other environmental responses. MarR is inactivated by certain phenolic ligands, such as salicylate, by an unknown mechanism. Our recent work has shown that several amino acid residues of Escherichia coli MarR affecting ligand binding are located between the dimerization and DNA-binding domains. To further characterize the ligand-binding region of MarR, we have now examined 7 point mutants generated by random mutagenesis and 11 site-directed alanine replacement mutants for inactivation by three ligands: salicylate, 2,4-dinitrophenol, and plumbagin. Inactivation of MarR was quantitated in intact cells by loss of MarR-mediated repression of a chromosomal mar-lacZ transcriptional fusion. The results showed that most of the residues important for ligand effectiveness lay in the ?1 and ?2 helices of MarR, between the putative DNA-binding domain and the dimerization domain of MarR, reinforcing our earlier findings. Moreover, the three ligands had different, but overlapping, sets of residues impacting their effects on MarR.
| S-EPMC3947609 | biostudies-literature