Kidney damage in burn disease. Part 2. Biochemical markers (literature review)

Recently discovered specific markers open up new possibilities for the diagnosis of acute kidney injury (AKI) in burn disease in order to optimize the treatment of such patients. Early diagnosis with the involvement of biomarkers prevents the sudden death of burn patients and allows predicting the course of the pathological condition. There are several characteristics that an “ideal” AKI biomarker should conform to: being non-invasive, locally specific, highly sensitive, being a stable molecule at different temperatures and pH values, having the ability to rapidly increase in response to kidney injury (quantify it), remaining at high levels during the episode and decreasing during the recovery period. There is a difference between the biomarkers that can be freely filtered in the glomerulus, so any increase in their plasma concentration (due to damage to other renal tissues) can lead to a high concentration of indicators in the urine (loss of specificity), and high-molecular-weight markers that are not freely filtered and therefore are more specific when measured in urine. Renal function in burn patients is usually determined by blood and urine tests, as biopsy can cause iatrogenic damage and is not commonly used in this cohort. After the onset of AKI, the level of biomarkers remains elevated for a certain period. None of the described indicators is monospecific for AKI; this makes estimating the time of AKI quite difficult. It has been proven that the combination of three biomarkers at two different time points in adults and the combination of two indicators at two time intervals in children allows to increase the reliability of determining AKI up to 0.78. Нещодавно виявлені специфічні маркери відкривають нові можливості для діагностики гострого пошкодження нирок (ГПН) при опіковій хворобі з метою оптимізації лікування таких хворих. Рання діагностика із залученням біомаркерів запобігає раптовій смерті опікових пацієнтів і дозволяє прогнозувати перебіг патологічного стану. Існує кілька характеристик, яким повинен відповідати «ідеальний» біомаркер ГПН: бути неінвазивним, локально специфічним, високочутливим, бути стабільною молекулою при різних температурах і pH, мати здатність швидко підвищуватися у відповідь на ураження нирок (кількісно його відображати), залишатися на високих рівнях протягом усього епізоду та знижуватися в період відновлення. Існує різниця між біомаркерами, що можуть вільно фільтруватися в клубочках, тому будь-яке збільшення їх концентрації в плазмі (внаслідок пошкодження інших ниркових тканин) може призвести до високої концентрації індикаторів у сечі (втрачається специфічність), і високомолекулярними маркерами, які не фільтруються вільно і тому є більш специфічними при вимірюванні в сечі. Функцію нирок у пацієнтів з опіками, як правило, визначають за показниками крові та сечі, оскільки біопсія може спричинити ятрогенне пошкодження та зазвичай у цій когорті не використовується. Після виникнення ГПН рівень біомаркерів залишається підвищеним протягом певного часу. Жоден з описаних індикаторів не є моноспецифічним для ГПН. Це робить оцінку часу перебігу ГПН досить складною. Доведено, що комбінації трьох біомаркерів у двох різних часових точках у дорослих та поєднання двох індикаторів у двох часових проміжках у дітей здатні збільшити достовірність визначення ГПН до 0,78

Kidney damage in burn disease. Part 2. Biochemical markers (literature review)

Recently discovered specific markers open up new possibilities for the diagnosis of acute kidney injury (AKI) in burn disease in order to optimize the treatment of such patients. Early diagnosis with the involvement of biomarkers prevents the sudden death of burn patients and allows predicting the course of the pathological condition. There are several characteristics that an “ideal” AKI biomarker should conform to: being non-invasive, locally specific, highly sensitive, being a stable molecule at different temperatures and pH values, having the ability to rapidly increase in response to kidney injury (quantify it), remaining at high levels during the episode and decreasing during the recovery period. There is a difference between the biomarkers that can be freely filtered in the glomerulus, so any increase in their plasma concentration (due to damage to other renal tissues) can lead to a high concentration of indicators in the urine (loss of specificity), and high-molecular-weight markers that are not freely filtered and therefore are more specific when measured in urine. Renal function in burn patients is usually determined by blood and urine tests, as biopsy can cause iatrogenic damage and is not commonly used in this cohort. After the onset of AKI, the level of biomarkers remains elevated for a certain period. None of the described indicators is monospecific for AKI; this makes estimating the time of AKI quite difficult. It has been proven that the combination of three biomarkers at two different time points in adults and the combination of two indicators at two time intervals in children allows to increase the reliability of determining AKI up to 0.7

Specific Etiologies Associated With the Multiple Organ Dysfunction Syndrome in Children: Part 2

To describe a number of conditions and therapies associated with multiple organ dysfunction syndrome (MODS) presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development MODS Workshop (March 26–27, 2015). In addition, the relationship between burn injuries and MODS is also included although it was not discussed at the Workshop

Montelukast: much more than an antiasthma drug

Montelukast (MK), a selective leukotriene D4 receptor antagonist, is used mainly to reduce eosinophilic inflammation in asthmatic patients. The primary objective of this mini-review is to describe novel additional targets for MK besides the lung and to highlight its antioxidant potential. Literature published between 2002 and 2013 was reviewed for significant antioxidant and anti-inflammatory properties of MK in various experimental models of inflammation rather than that in the airways of asthmatics. Evidence suggests the potential use of MK in many inflammatory diseases rather than asthma therapy

Outcomes of Resistance Exercise Training in Adults with Acute Burn Injury

Decreased quality-of-life and impairments in physical function, muscle strength and muscle volume are known complications of a burn injury. As such, rehabilitation is an important aspect of the burn care journey. Rehabilitation of burn injury is currently hampered by a lack of tools to reliably measure muscle strength and lower limb function, as well as an incomplete understanding of the effect of resistance training after a burn injury. Specifically, there is currently no data on the safety or efficacy of resistance training immediately after a burn injury. The series of studies presented in this thesis aimed to: 1) systematically review the current literature and evaluate the usefulness of resistance training during recovery from burn injury, 2) determine the ability of the Lower Limb Functional Index-10 to assess lower limb function after a burn injury, 3) determine the reliability and validity of hand held dynamometry to measure strength in people with an acute burn injury, and 4) evaluate the effect of an individually prescribed resistance training programme on quality-of-life, physical function, muscle strength, muscle volume and biochemical markers of inflammation in people with an acute burn injury. The novel findings from this thesis include: 1) estimates of effectiveness of resistance training in burn injury are based on low quality data and no data is available on acute injury rehabilitation 2) lower limb function can be reliably assessed using the Lower Limb Functional Index-10 after a lower limb burn injury, 3) hand held dynamometry is a reliable and valid assessment of muscle strength in burn injuries up to 40% total burn surface area, 4) resistance training commenced within 72-hours of burn injury improves quality-of-life, upper limb function and blood markers of inflammation compared to sham resistance training, and, 5) resistance training for acute burn injuries appears to be a safe and feasible practice

Branched Chain Amino Acids and Risk of Type 2 Diabetes Mellitus: A Literature Review

INTRODUCTION Type 2 diabetes mellitus (T2DM) is recognized as a major public health problem in the modern world, with its prevalence increasing each year. Consistently poor lifestyle habits — namely, nutritional excess coupled with sedentary behavior — are the leading causes of obesity, which in turn leverages the gradual desensitization of cells to insulin, followed by the onset of insulin resistance (IR) and the subsequent development of T2DM. Countless studies and ongoing research have confirmed that nutrition plays a definitive role in contributing to the development and onset of T2DM. However, in recent years, there has been increasing controversy surrounding the role that branched-chain amino acids (BCAAs) may play in influencing IR and the development of T2DM. AIM To review existing literature regarding both the purportedly harmful and beneficial roles and impacts of BCAAs on metabolic health, in order to better understand the contradictory nature of BCAAs and their effects on IR and T2DM. METHODS Relevant research, review articles and epidemiological studies spanning the time frame from 2004 to 2020 were collected, analyzed and summarized with the goal of underscoring and delineating the conflicting roles of BCAAs. RESULTS Evidence of beneficial effects of BCAAs includes enhanced muscle protein synthesis, more efficient glucose homeostasis, increased satiety, better body composition and improved body weight regulation. Evidence of harmful effects of BCAAs includes elevated fasting concentrations of circulating BCAAs correlating with an increased risk of IR and T2DM in human and rodent models. DISCUSSION In spite of the various studies that have been undertaken to shed further light on BCAAs, it still remains unclear whether they are simply markers of metabolic disturbances that ultimately lead to the development of T2DM, or if they are, at least in part, the actual cause of metabolic disturbances leading to T2DM. The general consensus amongst the scientific community is that more research is needed on this topic

Markers for sepsis diagnosis in the forensic setting: state of the art.

Reliable diagnoses of sepsis remain challenging in forensic pathology routine despite improved methods of sample collection and extensive biochemical and immunohistochemical investigations. Macroscopic findings may be elusive and have an infectious or non-infectious origin. Blood culture results can be difficult to interpret due to postmortem contamination or bacterial translocation. Lastly, peripheral and cardiac blood may be unavailable during autopsy. Procalcitonin, C-reactive protein, and interleukin-6 can be measured in biological fluids collected during autopsy and may be used as in clinical practice for diagnostic purposes. However, concentrations of these parameters may be increased due to etiologies other than bacterial infections, indicating that a combination of biomarkers could more effectively discriminate non-infectious from infectious inflammations. In this article, we propose a review of the literature pertaining to the diagnostic performance of classical and novel biomarkers of inflammation and bacterial infection in the forensic setting

Using Artificial Neural Networks to Predict Disease Associations for Chemicals Present in Burn Pit Emissions

In June of 2015, 27,378 of the 28,000 returning Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans report being exposed to burn pits. According to Barth et al. (2014), 9,660 returning OIF/OEF veterans were diagnosed with respiratory diseases, to include asthma, bronchitis, and sinusitis, thus strengthening the need to develop decision support tools that can be used to understand the relationships between chemical exposure and disease. In this study an Artificial Neural Network (ANN) was used to predict the chemical-disease associations for burn pit constituents. Ten burn pit constituents were tested using varying hidden layers, similar chemical structure relationships, and three Training, Validation, and Testing (TVT) ratios. The ANN predicted misidentification rates of 73% or greater when the hidden layer size varied between 1 and 5. Misidentification rates of 75% or greater were observed for ANN simulations when the TVT ratios ranged from 60/20/20 to 80/10/10. ANN-based screening of chemical groups containing chemicals with benzene rings and chemicals containing hydrocarbon chains produced misidentification rates of 73% or greater, and R2 values of 0.0762 and lower. Hidden Layer size, TVT ratios, and chemical structure had little effect on the model’s performance; additional training data is needed to improve the predictive capability of the ANN. The ANN-based screening of individual burn pit constituents produced several chemicals with R2 values greater than 0.8. These chemicals have been prioritized to further develop predictive ANN models for human health force support, resulting in the first research screening burn pit constituents with an ANN, and the first to prioritize burn pit emissions for future testing

Dexmedetomidine on the interplay of IL-6 and STAT3 pathways in adrenal gland damage-induced scalding burns in rats

Scalding burns are a common form of thermal injury that often leads to systemic complications. Pro-inflammatory cytokines like interleukin-6 (IL-6) and the activation of signal transducer and activator of transcription 3 (STAT3) pathways have been linked to the pathophysiology of organ damage caused by burns. This study aimed to investigate the potential therapeutic effects of dexmedetomidine, an alpha 2-adrenergic receptor agonist with anti-inflammatory properties, on the interplay of IL-6 and STAT3 pathways in adrenal gland damage following scalding burns in rats. Twenty-eight rats were divided randomly into four groups. Rats in group 1 (n=7, control) were given only 0.9% intraperitoneal (i.p.) NaCl. Rats in group 2 (n=7, DEX) were exposed to 25 degrees C water for 17 s on day 1 and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days; for rats in group 3 (n=7, Burn), boiling water of 94 degrees C was applied inside for 17 s. Rats in group 4 (n=7, Burn+DEX) were exposed to 94 degrees C water for 17 s and received 100 mcg/kg/day dexmedetomidine i.p. for 3 days. Adrenal gland tissues were histopathological examined, and STAT3, IL-6, and TUNEL staining were performed using immunohistochemically. Our results revealed that scalding burns increased IL-6 and STAT3 expression in the adrenal glands of rats. Histological analysis demonstrated that dexmedetomidine administration ameliorated adrenal gland damage and reduced inflammatory cell infiltration. Our findings suggest that dexmedetomidine protects the adrenal glands in scalding burns. This protection appears to be mediated, at least in part, by its modulation of IL-6 and STAT3 pathways