Amanda Thimmesch

Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung

Oxygen (O2) is life essential but as a drug has a maximum positive biological benefit and accompanying toxicity effects. Oxygen is therapeutic for treatment of hypoxemia and hypoxia associated with many pathological processes. Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation.

Traumatic Brain Injury and Mitochondrial Dysfunction

Abstract:Traumatic brain injury (TBI) is a major cause of death and disability in the United States and causes mitochondrial damage leading to impaired brain function. The purpose of this review is to (1) describe TBI processes and manifestations, (2) examine the mitochondrial alterations after TBI, specifically increased reactive oxygen species production, decreased bioenergetics and apoptosis and (3) current TBI treatments. There are various degrees of severity of TBI, yet all affect mitochondrial function. Currently, health care professionals use various methods to assess TBI severity—from brain imaging to serum biomarkers. The major cause of TBI-associated brain damage is secondary injury, which is mainly from mitochondrial injury dysfunction. Mitochondrial injury leads to oxidative stress and subsequent apoptosis and decreased cellular energy production. These brain cellular alterations impair neurologic functions, which are observed in individuals with TBI. The complex mitochondrial dysfunction after TBI requires treatment that specifically addresses the secondary injury. There are numerous therapies being used, including (1) hypothermia, (2) hyperbaric oxygen, (3) exercise and (4) antioxidants. Researchers are exploring novel approaches to prevent, diagnose and treat TBI focusing on maintaining mitochondrial function.

Flow cytometry and laser scanning cytometry, a comparison of techniques

ObjectiveFlow and laser scanning cytometry are used extensively in research and clinical settings. These techniques provide clinicians and scientists information about cell functioning in a variety of health and disease states. An in-depth knowledge and understanding of cytometry techniques can enhance interpretation of current research findings. Our goal with this review is to reacquaint clinicians and scientists with information concerning differences between flow and laser scanning cytometry by comparing their capabilities and applications.MethodsA Pubmed abstract search was conducted for articles on research, reviews and current texts relating to origins and use of flow and laser scanning cytometry. Attention was given to studies describing application of these techniques in the clinical setting.ResultsBoth techniques exploit interactions between the physical properties of light. Data are immediately and automatically acquired; they are distinctly different. Flow cytometry provides valuable rapid information about a wide variety of cellular or particle characteristics. This technique does not provide the scanned high resolution image analysis needed for investigators to localize areas of interest within the cell for quantification. Flow cytometry requires that the sample contain a large amount disaggregated, single, suspended cells. Laser scanning cytometry is slide-based and does not require as large of a sample. The tissue sample is affixed to a slide allowing repeated sample analyses. These cytometry techniques are used in the clinical setting to understand pathophysiological derangements associated with many diseases; cardiovascular disease, diabetes, acute lung injury, hemorrhagic shock, surgery, cancer and Alzheimer’s disease.ConclusionsUnderstanding the dif- ferences between FCM and LSCM can assist investigators in planning and design of their research or clinical testing. Researchers and clinicians optimize these technique capa- bilities with the cellular characteristics they wish to measure delineating molecular and cellular events occurring in health and disease. Discovery of mechanisms in cells using FCM and LSCM provide evidence needed to guide future treatment and interventions.

Systems biology in critical-care nursing.

Systems biology applies advances in technology and new fields of study including genomics, transcriptomics, proteomics, and metabolomics to the development of new treatments and approaches of care for the critically ill and injured patient. An understanding of systems biology enhances a nurses ability to implement evidence-based practice and to educate patients and families on novel testing and therapies. Systems biology is an integrated and holistic view of humans in relationship with the environment. Biomarkers are used to measure the presence and severity of disease and are rapidly expanding in systems biology endeavors. A systems biology approach using predictive, preventive, and participatory involvement is being utilized in a plethora of conditions of critical illness and injury including sepsis, cancer, pulmonary disease, and traumatic injuries.

Effects of ubiquinol with fluid resuscitation following haemorrhagic shock on rat lungs, diaphragm, heart and kidneys

What is the central question of this study? What are the effects of administering ubiquinol (reduced form of co‐enzyme Q10) following haemorrhagic shock on leucocyte mitochondrial superoxide, diaphragmatic hydrogen peroxide concentration and apoptosis in the lungs, diaphragm, heart and kidneys? What is the main finding and its importance? The administration of ubiquinol attenuated damage to the lungs, diaphragm, heart and kidneys following haemorrhagic shock and fluid resuscitation. Leucocyte mitochondrial superoxide was reduced, while hydrogen peroxide and apoptosis in the diaphragm decreased, as did apoptosis in the lungs, heart and kidneys. These findings suggest that ubiquinol could be a potential antioxidant used to reduce the reperfusion injury following haemorrhagic shock.

Myocardial energetics and ubiquinol in diastolic heart failure

Diastolic heart failure, or heart failure with preserved ejection fraction, is a leading cause of morbidity and mortality. There are no current therapies effective in improving outcomes for these patients. The aim of this article is to review the literature and examine the role of coenzyme Q10 in heart failure with preserved ejection fraction related to mitochondrial synthesis of adenosine triphosphate and reactive oxygen species production. The study results reflect that myocardial energetics alters in diastolic heart failure and that there is defective energy metabolism and increased oxidative stress. Studies are emerging to evaluate coenzyme Q10 , particularly ubiquinol, as a supplemental treatment for heart-failure patients. In diastolic heart-failure patients, clinicians are beginning to use supplemental therapies to improve patient outcomes, and one promising complementary treatment to improve left ventricular diastolic function is ubiquinol. Additional studies are needed using large-scale randomized models to confirm if ubiquinol would be beneficial. Since ubiquinol is an antioxidant and is required for adenosine triphosphate production, clinicians and health scientists should be aware of the potential role of this supplement in the treatment of diastolic heart failure.

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over‐the‐counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra‐arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline‐TBI, (2) ubiquinol 30 minutes before TBI (UB‐PreTBI), or (3) ubiquinol 30 minutes after TBI (UB‐PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C‐terminal hydrolase‐L1 (UCH‐L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury‐induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.

The Use of Antioxidants in the Treatment of Traumatic Brain Injury

AIMS The aim of this study was to discuss secondary traumatic brain injury, the mitochondria and the use of antioxidants as a treatment. BACKGROUND One of the leading causes of death globally is traumatic brain injury, affecting individuals in all demographics. Traumatic brain injury is produced by an external blunt force or penetration resulting in alterations in brain function or pathology. Often, with a traumatic brain injury, secondary injury causes additional damage to the brain tissue that can have further impact on recovery and the quality of life. Secondary injury occurs when metabolic and physiologic processes alter after initial injury and includes increased release of toxic free radicals that cause damage to adjacent tissues and can eventually lead to neuronal necrosis. Although antioxidants in the tissues can reduce free radical damage, the magnitude of increased free radicals overwhelms the bodys reduced defence mechanisms. Supplementing the bodys natural supply of antioxidants, such as coenzyme Q10, can attenuate oxidative damage caused by reactive oxygen species. DESIGN Discussion paper. DATA SOURCES Research literature published from 2011-2016 in PubMed, CINAHL and Cochrane. IMPLICATIONS FOR NURSING Prompt and accurate assessment of patients with traumatic brain injury by nurses is important to ensure optimal recovery and reduced lasting disability. Thus, it is imperative that nurses be knowledgeable about the secondary injury that occurs after a traumatic brain injury and aware of possible antioxidant treatments. CONCLUSION The use of antioxidants has potential to reduce the magnitude of secondary injury in patients who experience a traumatic brain injury.

Impaired Myocardial Bioenergetics in HFpEF and the Role of Antioxidants

Heart failure with preserved ejection fraction (HFpEF) is a significant cardiovascular condition for more than 50% of patients with heart failure. Currently, there is no effective treatment to decrease morbidity and mortality rates associated with HFpEF because of its pathophysiological heterogeneity. Recent evidence shows that deficiency in myocardial bioenergetics is one of the key pathophysiological factors contributing to diastolic dysfunction in HFpEF. Another known mechanism for HFpEF is an overproduction of free radicals, specifically reactive oxygen species. To reduce free radical formation, antioxidants are often used. This article is a summative review of the recent relevant literature that addresses cardiac bioenergetics, deficiency in myocardial bioenergetics, and increased reactive oxygen species associated with HFpEF and the promising potential use of antioxidants in managing this condition.

The Ongoing Controversy: Crystalloids Versus Colloids.

There is still much debate over the optimal fluid to use for resuscitation. Different studies have indicated either crystalloid or colloid is the ideal intravenous solution to administer, based on mortality or various physiological parameters. Older studies found differences between crystalloids and colloids. However, with the evolving science of fluid administration, more recent studies have shown no differences in patient outcomes. This review article will provide an overview of these substances and discuss the advantages, disadvantages, and implications for giving crystalloids and colloids in clinical practice.