scholarly journals Energetic dysfunction in sepsis: a narrative review

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sebastien Preau ◽  
Dominique Vodovar ◽  
Boris Jung ◽  
Steve Lancel ◽  
Lara Zafrani ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Organ Dysfunction ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Substrate Utilization ◽  
Future Research ◽  
Targeted Treatments ◽  
Organ Specific ◽  
Future Research Directions ◽  
Poor Outcomes

Abstract Background Growing evidence associates organ dysfunction(s) with impaired metabolism in sepsis. Recent research has increased our understanding of the role of substrate utilization and mitochondrial dysfunction in the pathophysiology of sepsis-related organ dysfunction. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions. Main text Sepsis is characterized by systemic and organ-specific changes in metabolism. Alterations of oxygen consumption, increased levels of circulating substrates, impaired glucose and lipid oxidation, and mitochondrial dysfunction are all associated with organ dysfunction and poor outcomes in both animal models and patients. The pathophysiological relevance of bioenergetics and metabolism in the specific examples of sepsis-related immunodeficiency, cerebral dysfunction, cardiomyopathy, acute kidney injury and diaphragmatic failure is also described. Conclusions Recent understandings in substrate utilization and mitochondrial dysfunction may pave the way for new diagnostic and therapeutic approaches. These findings could help physicians to identify distinct subgroups of sepsis and to develop personalized treatment strategies. Implications for their use as bioenergetic targets to identify metabolism- and mitochondria-targeted treatments need to be evaluated in future studies.

scholarly journals Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

2021 ◽  
Vol 22 (9) ◽  
pp. 4646
Author(s):  
Alexey A. Tinkov ◽  
Monica M. B. Paoliello ◽  
Aksana N. Mazilina ◽  
Anatoly V. Skalny ◽  
Airton C. Martins ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Synaptic Dysfunction ◽  
Future Research ◽  
Protective Mechanism ◽  
Autophagic Flux ◽  
Future Research Directions ◽  
The Impact

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity.

scholarly journals Mechanical challenges and cytoskeletal impairments in focal segmental glomerulosclerosis

2018 ◽  
Vol 314 (5) ◽  
pp. F921-F925 ◽  
Author(s):  
Di Feng ◽  
Clark DuMontier ◽  
Martin R. Pollak
Keyword(s):  
Blood Flow ◽  
Focal Segmental Glomerulosclerosis ◽  
Kidney Injury ◽  
Future Research ◽  
Disease States ◽  
Filtration Barrier ◽  
Segmental Glomerulosclerosis ◽  
The Face ◽  
Foot Process ◽  
Future Research Directions

Focal segmental glomerulosclerosis (FSGS) is a histologically defined form of kidney injury typically mediated by podocyte dysfunction. Podocytes rely on their intricate actin-based cytoskeleton to maintain the glomerular filtration barrier in the face of mechanical challenges resulting from pulsatile blood flow and filtration of this blood flow. This review summarizes the mechanical challenges faced by podocytes in the form of stretch and shear stress, both of which may play a role in the progression of podocyte dysfunction and detachment. It also reviews how podocytes respond to these mechanical challenges in dynamic fashion through rearranging their cytoskeleton, triggering various biochemical pathways, and, in some disease states, altering their morphology in the form of foot process effacement. Furthermore, this review highlights the growing body of evidence identifying several mutations of important cytoskeleton proteins as causes of FSGS. Lastly, it synthesizes the above evidence to show that a better understanding of how these mutations leave podocytes vulnerable to the mechanical challenges they face is essential to better understanding the mechanisms by which they lead to disease. The review concludes with future research directions to fill this gap and some novel techniques with which to pursue these directions.

Hyperthermia Exacerbates Ischaemic Brain Injury

2009 ◽  
Vol 4 (4) ◽  
pp. 274-284 ◽  
Author(s):  
C. X. Wang ◽  
A. Stroink ◽  
J. M. Casto ◽  
K. Kattner
Keyword(s):  
Brain Injury ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Future Research ◽  
Preclinical Studies ◽  
Stroke Patients ◽  
Research Directions ◽  
Ischaemic Brain ◽  
Future Research Directions ◽  
Ischaemic Brain Injury

Hyperthermia frequently occurs in stroke patients. Hyperthermia negatively correlates with clinical outcome and adversely effects treatment regiments otherwise successful under normothermic conditions. Preclinical studies also demonstrate that hyperthermia converts salvageable penumbra to ischaemic infarct. The present article reviews the knowledge accumulated from both clinical and preclinical studies about hyperthermia and ischaemic brain injury, examines current treatment strategies and discusses future research directions.

scholarly journals Involvement of Mitochondrial Disorders in Septic Cardiomyopathy

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Arthur Durand ◽  
Thibault Duburcq ◽  
Thibault Dekeyser ◽  
Remi Neviere ◽  
Michael Howsam ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cardiac Dysfunction ◽  
Host Response ◽  
Therapeutic Strategies ◽  
Future Research ◽  
Septic Cardiomyopathy ◽  
Research Directions ◽  
Life Threatening ◽  
Future Research Directions

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It remains a leading cause of death worldwide, despite the development of various therapeutic strategies. Cardiac dysfunction, also referred to as septic cardiomyopathy, is a frequent and well-described complication of sepsis and associated with worse clinical outcomes. Recent research has increased our understanding of the role of mitochondrial dysfunction in the pathophysiology of septic cardiomyopathy. The purpose of this review is to present this evidence as a coherent whole and to highlight future research directions.

Prevalence of Burnout among Canadian Radiologists and Radiology Trainees

2018 ◽  
Vol 69 (4) ◽  
pp. 367-372 ◽  
Author(s):  
Nanxi Zha ◽  
Michael N. Patlas ◽  
Nick Neuheimer ◽  
Richard Duszak
Keyword(s):  
Emotional Exhaustion ◽  
Treatment Strategies ◽  
Maslach Burnout Inventory ◽  
Personal Accomplishment ◽  
Future Research ◽  
Survey Period ◽  
Research Directions ◽  
Canadian Association ◽  
Future Research Directions ◽  
E Mail

Purpose Physician burnout is on the rise compared to the average population, and radiology burnout rates are ranked high compared to other specialties. We aim to assess radiologist and radiology trainee burnout in Canada. Methods A survey using the abbreviated 7-item Maslach Burnout Inventory that characterizes burnout symptoms into personal accomplishment, emotional exhaustion, and depersonalization was sent to all eligible members of the Canadian Association of Radiologists in January 2018. The anonymous survey was hosted on SurveyMonkey for 1 month. A reminder e-mail was sent halfway through the survey period. Results Overall, 262 of 1401 invited radiology trainees and radiologists completed the survey (response rate 18.7%). With regards to personal accomplishment, we observed that (1) burnout in this domain improved with increased years worked and (2) milder symptoms were observed in community radiologists compared with their academic counterparts. In comparison with other studies of radiologist burnout, we found mild burnout symptoms in personal accomplishment, but severe symptoms in the burnout domains of both emotional exhaustion and depersonalization. Conclusions Canadian radiologists and radiology trainees reported above average burnout symptoms with regard to both emotional exhaustion and depersonalization. Future research directions include exploring etiologies of burnout and implementation of treatment strategies based on these identified problem areas.

scholarly journals Nanomedicine for Cystic Fibrosis

2019 ◽  
Vol 24 (2) ◽  
pp. 169-180 ◽  
Author(s):  
Victor Ong ◽  
Vincent Mei ◽  
Lin Cao ◽  
Kiana Lee ◽  
Eun Ji Chung
Keyword(s):  
Cystic Fibrosis ◽  
Bacterial Infections ◽  
Treatment Strategies ◽  
Future Research ◽  
Drug Penetration ◽  
Research Directions ◽  
Site Of Action ◽  
Difficulty Breathing ◽  
Future Research Directions ◽  
Lung Infections

Cystic fibrosis is a genetic disease affecting more than 70,000 people worldwide. Caused by a mutation in the CFTR gene, cystic fibrosis can result in difficulty breathing, widespread bacterial infections, edema, malnutrition, pancreatitis, and death. Current drug-based treatments struggle to reach the site of action due to the thick mucus, and only manage symptoms such as blocked airways, lung infections, and limited ability to digest food. Nanotechnology opens up possibilities for improved treatment strategies by focusing on drug penetration through the mucus lining, eliminating resulting bacterial infections, and targeting the underlying genetic cause of the disease. In this review, we present recent nanoparticle developments for cystic fibrosis, challenges in nanomedicine therapeutics, and future research directions in gene editing and nonviral vectors for gene delivery.

scholarly journals Intracranial Bleeding After Reperfusion Therapy in Acute Ischemic Stroke

2021 ◽  
Vol 11 ◽  
Author(s):  
Guillaume Charbonnier ◽  
Louise Bonnet ◽  
Alessandra Biondi ◽  
Thierry Moulin
Keyword(s):  
Intracranial Hemorrhage ◽  
Intravenous Thrombolysis ◽  
Reperfusion Therapy ◽  
Future Research ◽  
Risk Markers ◽  
Research Directions ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Natural Tendency ◽  
Future Research Directions ◽  
Poor Outcomes

Intracranial hemorrhage is one of the most feared complications following brain infarct. Ischemic tissues have a natural tendency to bleed. Moreover, the first recanalization trials using intravenous thrombolysis have shown an increase in mild to severe intracranial hemorrhage. Symptomatic intracerebral hemorrhage is strongly associated with poor outcomes and is an important factor in recanalization decisions. Stroke physicians have to weigh the potential benefit of recanalization therapies, first, with different risks of intracranial hemorrhage described in randomized controlled trials, and second with numerous risk markers that have been found to be associated with intracranial hemorrhage in retrospective series. These decisions have become quite complex with different intravenous thrombolytics and mechanical thrombectomy. This review aims to outline some elements of the pathophysiological mechanisms and classifications, describe most of the risk factors identified for each reperfusion therapy, and finally suggest future research directions that could help physicians dealing with these complications.

Therapeutic Potentials and Mechanisms of Artemisinin and its Derivatives for Tumorigenesis and Metastasis

2020 ◽  
Vol 20 (5) ◽  
pp. 520-535 ◽  
Author(s):  
Yue Li ◽  
Xiaoyan Zhou ◽  
Jiali Liu ◽  
Xiaohong Yuan ◽  
Qian He
Keyword(s):  
Artemisia Annua ◽  
Treatment Strategies ◽  
Drug Repurposing ◽  
Future Research ◽  
Metastatic Tumors ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Future Research Directions ◽  
Promising Treatment ◽  
Complex Relationships

Background: Tumor recurrence and metastasis are still leading causes of cancer mortality worldwide. The influence of traditional treatment strategies against metastatic tumors may still be limited. To search for novel and powerful agents against tumors has become a major research focus. In this study, Artemisinin (ARM), a natural compound isolated from herbs, Artemisia annua L., proceeding from drug repurposing methods, attracts more attention due to its good efficacy and tolerance in antimalarial practices, as well as newly confirmed anticancer activity. Methods: We have searched and reviewed the literatures about ARM and its derivatives (ARMs) for cancer using keywords "artemisinin" until May 2019. Results: In preclinical studies, ARMs can induce cell cycle arrest and cell death by apoptosis etc., to inhibit the progression of tumors, and suppress EMT and angiogenesis to inhibit the metastasis of tumors. Notably, the complex relationships of ARMs and autophagy are worth exploring. Inspired by the limitations of its antimalarial applications and the mechanical studies of artemisinin and cancer, people are also committed to develop safer and more potent ARM-based modified compounds (ARMs) or combination therapy, such as artemisinin dimers/ trimers, artemisinin-derived hybrids. Some clinical trials support artemisinins as promising candidates for cancer therapy. Conclusion: ARMs show potent therapeutic potentials against carcinoma including metastatic tumors. Novel compounds derived from artemisinin and relevant combination therapies are supposed to be promising treatment strategies for tumors, as the important future research directions.

25c-nbome: Case report and literature review

2017 ◽  
Vol 41 (S1) ◽  
pp. s874-s875
Author(s):  
M. Preve ◽  
S. Casigliani ◽  
L. Tognola ◽  
R. Traber ◽  
R.A. Colombo
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Case Reports ◽  
Kidney Injury ◽  
Drug Market ◽  
Individual Case ◽  
Future Research ◽  
The Internet ◽  
Future Research Directions ◽  
Competing Interest

IntroductionNovel psychoactive drugs (NPS) have rapidly increase in the last years in the drug market as a recreational use. A new group of toxic phenethylamine derivates named NBOMe of 2 C class present have emerged recently, are frequently bought using the internet and have similar effects to other hallucinogenic drugs; however, they may pose larger risks, due to the limited knowledge about them, their relatively low price and availability via the internet. The purpose of this report is to review the clinical evidence for the potential of abuse of NBOMe compounds. We propose a case report and literature review.MethodWe conducted a systematic review of the literature with the principal database (PubMed, Enbase, PsychInfo) and we present a case report.ResultsThe effects of 25C-NBOMe is characterized by hallucination, violent agitation, rhabdomyolysis and kydney injury.Discussion and conclusionEffects from 25C-NBOMe in our case report were similar to previous individual case reports in literature. The clinical features were also similar to effects from other analogues in the class (25I-NBOMe, 25B-NBOMe). In our case, violent agitation (signs of serotonergic stimulation), rhabdomyolysis and kidney injury were observed. Further research is warranted to replicate our clinical and qualitative observations and, in general, quantitative studies in large samples followed up over time are needed. Methodological limitations, clinical implications and suggestions for future research directions are considered.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Acute Kidney Injury and Extrarenal Organ Dysfunction

2012 ◽  
Vol 116 (5) ◽  
pp. 1139-1148 ◽  
Author(s):  
Steven C. Yap ◽  
H. Thomas Lee ◽  
David S. Warner
Keyword(s):  
Acute Kidney Injury ◽  
Organ Dysfunction ◽  
Neutrophil Migration ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Therapeutic Modalities ◽  
Inflammatory Mechanism ◽  
Remote Organ ◽  
Distant Organ ◽  
New Treatment

Acute kidney injury (AKI) is a frequent complication in the intensive care unit with limited therapeutic modalities. Although survival from isolated AKI has improved with recent advancements in renal replacement therapy, mortality from AKI complicated by multiorgan dysfunction has remained unchanged and is estimated to be approximately 50%. Hence, defining and better understanding the pathophysiology of distant organ dysfunction associated with AKI is clinically important because it may lead to new treatment strategies. In animal models, it has become increasingly clear that AKI is not an isolated event but results in remote organ dysfunction involving the heart, lungs, liver, intestines, and brain through an inflammatory mechanism that involves neutrophil migration, cytokine expression, and increased oxidative stress. The purpose of this brief review is to summarize the human and basic science evidence for AKI and its detrimental effects on distant organs.

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