Mitochondrial Disease and Anesthesia

2018 ◽  
Author(s):  
Mary A. Felberg
Keyword(s):  
Mitochondrial Disease ◽  
Clinical Symptoms ◽  
Anesthetic Management ◽  
Mitochondrial Diseases ◽  
High Energy ◽  
Postoperative Management ◽  
Anesthetic Agents ◽  
Energy Demands ◽  
Perioperative Fluids

Mitochondrial disease is a genetically, biochemically, and clinically heterogeneous group of disorders that arise from defects in cellular oxidative phosphorylation, most commonly within the electron transport chain. All mitochondrial diseases involve disruption in energy production; clinical symptoms usually manifest in tissues with high energy demands although all organs may be affected. The extent of disease depends not only on the mitochondrial defect but on the numbers of dysfunctional mitochondria present in each tissue. Despite in vitro evidence that almost every anesthetic agent studied has been shown to decrease mitochondrial function, all anesthetic agents have been used safely. Discussion of the implications of mitochondrial disease for anesthetic management includes preoperative preparation, volatile and intravenous anesthetic agents, avoidance of succinylcholine, risk of malignant hyperthermia, perioperative fluids, and postoperative management.

scholarly journals General anesthesia with remimazolam in a patient with mitochondrial encephalomyopathy: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuji Suzuki ◽  
Matsuyuki Doi ◽  
Yoshiki Nakajima
Keyword(s):  
Lactic Acidosis ◽  
General Anesthesia ◽  
Mitochondrial Disease ◽  
Muscle Relaxation ◽  
Anesthetic Management ◽  
Perioperative Period ◽  
Mitochondrial Encephalomyopathy ◽  
Anesthesia Induction ◽  
General Anesthetic ◽  
Anesthetic Agents

Abstract Background Systemic anesthetic management of patients with mitochondrial disease requires careful preoperative preparation to administer adequate anesthesia and address potential disease-related complications. The appropriate general anesthetic agents to use in these patients remain controversial. Case presentation A 54-year-old woman (height, 145 cm; weight, 43 kg) diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes underwent elective cochlear implantation. Infusions of intravenous remimazolam and remifentanil guided by patient state index monitoring were used for anesthesia induction and maintenance. Neither lactic acidosis nor prolonged muscle relaxation occurred in the perioperative period. At the end of surgery, flumazenil was administered to antagonize sedation, which rapidly resulted in consciousness. Conclusions Remimazolam administration and reversal with flumazenil were successfully used for general anesthesia in a patient with mitochondrial disease.

scholarly journals Study of the effect of the introduction of mitochondrial import determinants into the gRNA structure on the activity of the gRNA/SpCas9 complex in vitro

2020 ◽  
Vol 24 (5) ◽  
pp. 512-518
Author(s):  
E. G. Zakirova ◽  
Y. V. Vyatkin ◽  
N. A. Verechshagina ◽  
V. V. Muzyka ◽  
I. O. Mazunin ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Copy Number ◽  
Clinical Symptoms ◽  
Mitochondrial Diseases ◽  
Wild Type ◽  
Therapeutic Approaches ◽  
Mitochondrial Import ◽  
Promising Tool ◽  
First Time

It has long been known that defects in the structure of the mitochondrial genome can cause various neuromuscular and neurodegenerative diseases. Nevertheless, at present there is no effective method for treating mitochondrial diseases. The major problem with the treatment of such diseases is associated with mitochondrial DNA (mtDNA) heteroplasmy. It means that due to a high copy number of the mitochondrial genome, mutant copies of mtDNA coexist with wild-type molecules in the same organelle. The clinical symptoms of mitochondrial diseases and the degree of their manifestation directly depend on the number of mutant mtDNA molecules in the cell. The possible way to reduce adverse effects of the mutation is by shifting the level of heteroplasmy towards the wild-type mtDNA molecules. Using this idea, several gene therapeutic approaches based on TALE and ZF nucleases have been developed for this purpose. However, the construction of protein domains of such systems is rather long and laborious process. Meanwhile, the CRISPR/Cas9 system is fundamentally different from protein systems in that it is easy to use, highly efficiency and has a different mechanism of action. All the characteristics and capabilities of the CRISPR/Cas9 system make it a promising tool in mitochondrial genetic engineering. In this article, we demonstrate for the first time that the modification of gRNA by integration of specific mitochondrial import determinants in the gRNA scaffold does not affect the activity of the gRNA/Cas9 complex in vitro.

Mitochondrial Disease

2018 ◽  
Author(s):  
Ajay D’Mello
Keyword(s):  
Mitochondrial Disease ◽  
Surgical Stress ◽  
Anesthetic Management ◽  
Metabolic Stress ◽  
Mitochondrial Respiratory Chain ◽  
Endocrine Disorders ◽  
Anesthetic Techniques ◽  
Diverse Range ◽  
Cellular Processes ◽  
Anesthetic Agents

Mitochondrial disease is now considered to be an important cause for a diverse range of neurological, muscular, cardiac and endocrine disorders. Initially thought to be a rare group of disorders, it is now increasingly common for children with mitochondrial disease to present for a surgical procedure. While the mitochondrial respiratory chain is the essential finally common pathway for aerobic metabolism, mitochondria also play a role in a several important cellular processes. A variety of anesthetic techniques have been successfully used for this group of patients. However, the possibility of complications due to inhibition of mitochondrial function by anesthetic agents and surgical stress is a worry for the physician managing these patients. Anesthetic management focuses on disease symptoms at presentation, maintaining normoglycemia, while preventing further metabolic stress and complications that worsen lactic acidosis.

scholarly journals Modelling of BCS1L-related human mitochondrial disease in Drosophila melanogaster

2021 ◽  
Author(s):  
Michele Brischigliaro ◽  
Elena Frigo ◽  
Samantha Corrà ◽  
Cristiano De Pittà ◽  
Ildikò Szabò ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Mitochondrial Disease ◽  
Clinical Symptoms ◽  
Genetic Manipulation ◽  
Chain Complex ◽  
Mitochondrial Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Complex Iii ◽  
Mitochondrial Respiratory Chain Complex

AbstractMutations in BCS1L are the most frequent cause of human mitochondrial disease linked to complex III deficiency. Different forms of BCS1L-related diseases and more than 20 pathogenic alleles have been reported to date. Clinical symptoms are highly heterogenous, and multisystem involvement is often present, with liver and brain being the most frequently affected organs. BCS1L encodes a mitochondrial AAA + -family member with essential roles in the latest steps in the biogenesis of mitochondrial respiratory chain complex III. Since Bcs1 has been investigated mostly in yeast and mammals, its function in invertebrates remains largely unknown. Here, we describe the phenotypical, biochemical and metabolic consequences of Bcs1 genetic manipulation in Drosophila melanogaster. Our data demonstrate the fundamental role of Bcs1 in complex III biogenesis in invertebrates and provide novel, reliable models for BCS1L-related human mitochondrial diseases. These models recapitulate several features of the human disorders, collectively pointing to a crucial role of Bcs1 and, in turn, of complex III, in development, organismal fitness and physiology of several tissues.

Anesthesia for rabbits submitted to experimental surgeries: Report of a series of eight anesthesias

2020 ◽  
pp. 151-158
Author(s):  
Rafael Antonio Caldart Bedin ◽  
Maisa Schultz ◽  
Antonio Bedin
Keyword(s):  
Muscle Relaxation ◽  
Anesthetic Management ◽  
Laboratory Animals ◽  
Average Weight ◽  
Anesthetic Induction ◽  
Anesthetic Agents ◽  
Reasonable Degree ◽  
Bioethical Debate ◽  
Precordial Stethoscope

Anesthesia for laboratory animals is a matter of biomedical concern and one of the most present dilemmas in the current bioethical debate. The use of anesthetic agents in experimental surgery aims at analgesia and restraining the animal, in order to achieve a reasonable degree of muscle relaxation and to produce sufficient analgesia. This practice requires the use of protocols for the administration of safe and efficient doses. Eight New Zealand rabbits were submitted to laparotomies demonstrating the surgical technique discipline of the local medical course. For pre-anesthetic medication, acepromazine 1 mg.kg-1 associated with ketamine 15 mg.kg-1 was used subcutaneously. Anesthesia was maintained with isoflurane and oxygen under a laryngeal mask in a Mapleson D anesthesia system and under spontaneous breathing. Hydration was performed with 10 ml.kg-1 saline every hour. A thermal mattress was used. Precordial stethoscope, pulse oximetry and clinical parameters were used for monitoring. For euthanasia, ketamine 10 mg.kg-1 associated with potassium chloride 19.1% 1 ml.kg-1 was used intravenously. The average weight of the rabbits was 2721.25 ± 275.01 grams and the duration of the anesthetic procedure was 120 ± 87 minutes. Discussion. In long-term anesthesia, such as laparotomies, the use of pre-anesthetic medication and then anesthetic induction by the combination of agents is recommended. However, anesthetic management requires monitoring to prevent insufficient or excessive doses from occurring.

scholarly journals In vitro testing of explanted shunt valves in hydrocephalic patients with suspected valve malfunction

2021 ◽  
Author(s):  
Christoph Bettag ◽  
Christian von der Brelie ◽  
Florian Baptist Freimann ◽  
Ulrich-Wilhelm Thomale ◽  
Veit Rohde ◽  
...  
Keyword(s):  
Flow Rate ◽  
Clinical Symptoms ◽  
Obstructive Hydrocephalus ◽  
Flow Characteristics ◽  
Normal Pressure ◽  
Diagnostic Tools ◽  
Programmable Valve ◽  
Significant Difference ◽  
Valve Malfunction

AbstractDiagnosis of symptomatic valve malfunction in hydrocephalic patients treated with VP-Shunt (VPS) might be difficult. Clinical symptoms such as headache or nausea are nonspecific, hence cerebrospinal fluid (CSF) over- or underdrainage can only be suspected but not proven. Knowledge concerning valve malfunction is still limited. We aim to provide data on the flow characteristics of explanted shunt valves in patients with suspected valve malfunction. An in vitro shunt laboratory setup was used to analyze the explanted valves under conditions similar to those in an implanted VPS. The differential pressure (DP) of the valve was adjusted stepwise to 20, 10, 6, and 4 cmH2O. The flow rate of the explanted and the regular flow rate of an identical reference valve were evaluated at the respective DPs. Twelve valves of different types (Codman CertasPlus valve n = 3, Miethke Shuntassistant valve n = 4, Codman Hakim programmable valve n = 3, DP component of Miethke proGAV 2.0 valve n = 2) from eight hydrocephalic patients (four male), in whom valve malfunction was assumed between 2016 and 2017, were replaced with a new valve. Four patients suffered from idiopathic normal pressure (iNPH), three patients from malresorptive and one patient from obstructive hydrocephalus. Post-hoc analysis revealed a significant difference (p < 0.001) of the flow rate between each explanted valve and their corresponding reference valve, at each DP. In all patients, significant alterations of flow rates were demonstrated, verifying a valve malfunction, which could not be objectified by the diagnostic tools used in the clinical routine. In cases with obscure clinical VPS insufficiency, valve deficiency should be considered.

scholarly journals Ovaries of Chrysanthemum Irradiated with High-Energy Photons and High-Energy Electrons Can Regenerate Plants with Novel Traits

Agronomy ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1111
Author(s):  
Natalia Miler ◽  
Iwona Jedrzejczyk ◽  
Seweryn Jakubowski ◽  
Janusz Winiecki
Keyword(s):  
Total Dose ◽  
In Vitro Regeneration ◽  
High Energy ◽  
Mutation Breeding ◽  
Chrysanthemum Morifolium ◽  
Physical Factors ◽  
Strong Impact ◽  
Breeding Method ◽  
High Energy Electrons

Classical mutation breeding using physical factors is a common breeding method for ornamental crops. The aim of our study was to examine the utility of ovaries excised from irradiated inflorescences of Chrysanthemum × morifolium (Ramat.) as explants for breeding purposes. We studied the in vitro regeneration capacity of the ovaries of two chrysanthemum cultivars: ‘Profesor Jerzy’ and ‘Karolina’ preceded by irradiation with high-energy photons (total dose 5, 10 and 15 Gy) and high-energy electrons (total dose 10 Gy). Growth and inflorescence parameters of greenhouse acclimatized regenerants were recorded, and ploidy level was estimated with flow cytometry. The strong impact of genotype on regeneration efficiency was recorded—cultivar ‘Karolina’ produced only 7 viable shoots, while ‘Profesor Jerzy’ produced totally 428 shoots. With an increase of irradiation dose, the regeneration decreased, the least responsive were explants irradiated with 15 Gy high-energy photons and 10 Gy high-energy electrons. Regenerants of ‘Profesor Jerzy’ obtained from these explants possessed shorter stem and flowered later. The highest number of stable, color and shape inflorescence variations were obtained from explants treated with 10 Gy high-energy photons. Variations of inflorescences were predominantly changes of shape—from full to semi-full. New color phenotypes were dark yellow, light yellow and pinkish, among them only the dark yellow phenotype remained stable during second year cultivation. None of the regenerants were haploid. The application of ovaries irradiated within the whole inflorescence of chrysanthemum can be successfully applied in the breeding programs, provided the mother cultivar regenerate in vitro efficiently.

scholarly journals The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 489
Author(s):  
Hilary Y. Liu ◽  
Jenna R. Gale ◽  
Ian J. Reynolds ◽  
John H. Weiss ◽  
Elias Aizenman
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Neuronal Damage ◽  
Mitochondrial Fission ◽  
Permeability Transition ◽  
High Energy ◽  
Atp Depletion ◽  
Ros Generation ◽  
Cellular Functions ◽  
Calcium Deregulation ◽  
Energy Demands

Zinc is a highly abundant cation in the brain, essential for cellular functions, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential (MMP), leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and excitotoxic calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting.

scholarly journals Processing Methodologies of Wet Microalga Biomass Toward Oil Separation: An Overview

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 641
Author(s):  
Vânia Pôjo ◽  
Tânia Tavares ◽  
Francisco Xavier Malcata
Keyword(s):  
Food System ◽  
Lipid Extraction ◽  
High Energy ◽  
Economic Feasibility ◽  
Alternative Source ◽  
Microalgal Biomass ◽  
Energy Demands ◽  
Chemical Profiles ◽  
System Sustainability ◽  
Industrial Level

One of the main goals of Mankind is to ensure food system sustainability—including management of land, soil, water, and biodiversity. Microalgae accordingly appear as an innovative and scalable alternative source in view of the richness of their chemical profiles. In what concerns lipids in particular, microalgae can synthesize and accumulate significant amounts of fatty acids, a great fraction of which are polyunsaturated; this makes them excellent candidates within the framework of production and exploitation of lipids by various industrial and health sectors, either as bulk products or fine chemicals. Conventional lipid extraction methodologies require previous dehydration of microalgal biomass, which hampers economic feasibility due to the high energy demands thereof. Therefore, extraction of lipids directly from wet biomass would be a plus in this endeavor. Supporting processes and methodologies are still limited, and most approaches are empirical in nature—so a deeper mechanistic elucidation is a must, in order to facilitate rational optimization of the extraction processes. Besides circumventing the current high energy demands by dehydration, an ideal extraction method should be selective, sustainable, efficient, harmless, and feasible for upscale to industrial level. This review presents and discusses several pretreatments incurred in lipid extraction from wet microalga biomass, namely recent developments and integrated processes. Unfortunately, most such developments have been proven at bench-scale only—so demonstration in large facilities is still needed to confirm whether they can turn into competitive alternatives.

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