Biochemical Markers of Renal Function

Kidney damage can be induced by ischemia, autoimmune diseases, hypertension, allograft rejection, metabolic or genetic disorders, infections or toxins. The influence of these factors could result in acute kidney injury (AKI) defined as an unexpected decrease in urine output or renal function, or encourage the development of chronic kidney disease (CKD). Biomarkers of renal function, measured in urine and serum, are in increasing use in order to estimate the severity and nature of kidney injury, and consequently apply appropriate therapy and improve patient management. The determined values of biomarkers can suggest the potential risk of kidney disease and the type of renal injury, predict the disease progression, as well as be helpful for assessing the response to an applied therapy. Although novel biomarkers are in practical use, serum creatinine, the indicator of glomerular filtration rate is still the most frequently used biomarker of renal function despite its known limitations. In recent decades, numerous studies resulted in discovering urinary and serum proteins that can serve as biomarkers for early and accurate detection of AKI and its development, as well as the identification of CKD. This review gives an overview of the most important renal biomarkers investigated in kidney diseases, classified in following types: functional biomarkers, up-regulated proteins, enzymes, and cycle arrest biomarkers. It describes their properties, physiological roles, and discusses the utility of these molecules in different clinical settings

Deletion of Galectin-3 attenuates acute pancreatitis in mice by affecting activation of innate inflammatory cells

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Acute pancreatitis is characterized by autodigestion of pancreatic cells followed by acute inflammation leading to pathology and death. In experimental acute pancreatitis, pancreatic acinar cells and infiltrating macrophages express Galectin-3 but its role in pathology of this disease is unknown. Therefore, we studied its role using Galectin-3 deficient mice. Deletion of Galectin-3 prolonged the survival of mice, led to attenuation of histopathology, and decreased infiltration of mononuclear cells and neutrophils that express TLR-4, in particular, pro-inflammatory N1 neutrophils. Galectin-3 and TLR-4 are also colocalized on infiltrating cells. Lack of Galectin-3 reduced expression of pro-inflammatory TNF-α and IL-1β in F4/80+CD11c- and CD11c+F4/80− cells. Thus, deletion of Galectin-3 ameliorates acute pancreatitis by attenuating early influx of neutrophils and inflammatory mononuclear cells of innate immunity. These findings provide the basis to consider Galectin-3 as a therapeutic target in acute pancreatitis

Different Sensitivity of Various Brain Structures to Thioacetamide-Induced Lipid Peroxidation

Thioacetamide (TAA) exerts hepatotoxic, neurotoxic and carcinogenic effects. The aim of our study was to investigate the effects of TAA on lipid peroxidation and catalase activity in various rat brain regions. Male Wistar rats were divided into following groups: 1. control, saline-treated; 2. thioacetamide-treated groups, TAA(300) (300 mg/kg), TAA(600) (600 mg/kg) and TAA(900) (900 mg/kg). Daily dose of TAA (300 mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)) and three times (TAA(900)) in consecutive days. Brain samples were collected 24 h after the last dose of TAA and malondialdehyde (MDA) level and catalase activity were determined in cortex, brainstem and hippocampus. MDA level was significantly increased while catalase activity was significantly lower in all brain regions in TAA(900) group in comparison with control group. In TAA(600) MDA level was increased in the brainstem and cortex when compared to control (p LT 0.01). The same dose of TAA(600) mg/kg induced a significant decline in catalase activity in the brainstem and cortex and an increase in its activity in the hippocampus when compared to control (p LT 0.01). In TAA(300) an increase in MDA level was evident only in the brainstem. Catalase activity was significantly higher in the cortex and hippocampus in TAA(300) group in comparison with control (p LT 0.01). Based on these results, it may be concluded that various rat brain regions have different sensitivity to TAA-induced lipid peroxidation with hippocampus being less sensitive than cerebral cortex and brainstem

The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration

Hyperhomocysteinemia is associated with various pathologies including cardiovascular disease, stroke, and cognitive dysfunctions. Systemic administration of homocysteine can trigger seizures in animals, and patients with homocystinuria suffer from epileptic seizures. Available data suggest that homocysteine can be harmful to human cells because of its metabolic conversion to homocysteine thiolactone, a reactive thioester. A number of reports have demonstrated a reduction of Na+/K+-ATPase activity in cerebral ischemia, epilepsy and neurodegeneration possibly associated with excitotoxic mechanisms. The aim of this study was to examine the in vivo effects of d,l-homocysteine and d,l-homocysteine thiolactone on Na+/K+- and Mg2+-ATPase activities in erythrocyte (RBC), brain cortex, hippocampus, and brain stem of adult male rats. Our results demonstrate a moderate inhibition of rat hippocampal Na+/K+-ATPase activity by d,l-homocysteine, which however expressed no effect on the activity of this enzyme in the cortex and brain stem. In contrast,d,l-homocysteine thiolactone strongly inhibited Na+/K+-ATPase activity in cortex, hippocampus and brain stem of rats. RBC Na+/K+-ATPase and Mg2+-ATPase activities were not affected by d,l-homocysteine, while d,l-homocysteine thiolactone inhibited only Na+/K+-ATPase activity. This study results show that homocysteine thiolactone significantly inhibits Na+/K+-ATPase activity in the cortex, hippocampus, and brain stem, which may contribute at least in part to the understanding of excitotoxic and convulsive properties of this substance

Health Predictors of Pain in Elderly—A Serbian Population-Based Study

Objectives: The aim of our study was to evaluate the association of health factors with the presence and different degrees of pain in elderly above 65 years of life. Methods: The population-based study included 3540 individuals above 65 years of age of life from twofold stratified household sample representative for Serbia, during 2013 (the average age 73.9 ± 6.3 years; average Body Mass Index was 26.7 ± 4.4, females 56.8%, living with partner 55.5%, with primary education 55.3%, with poor wealth index 55.8% and from rural settings 46.2%). As health predictors of pain, we analyzed further health parameters: self-perceived general health, long-lasting health problems, diagnosed pulmonary disease, cardiovascular disease, musculoskeletal disease, diabetes, hyperlipidemia, hypertension and other chronic diseases. Pain domain of SF-36 version 2.0 was used for pain assessment. Results: Significant health predictors of pain were: self-perceived general health (OR 2.28), where bad perception of self-perceived general health in our study had greater risk of pain with higher degree of severity; long-lasting health problems (OR 1.60), where elderly with long-lasting health problems had almost twice the risk of moderate degree of pain, and above twice the risk for severe degree of pain; pulmonary disease (OR 1.38); musculoskeletal disease (OR 2.98) and other chronic diseases (OR 1.71). The presence of musculoskeletal disease increases the risk for pain, even more than double in severe versus mild degrees of pain. Conclusion: Bad self-perceived general health, long-lasting health problems, pulmonary, musculoskeletal diseases, cardiovascular disease and other chronic disease were significant health-related predictors of various degrees of pain in elderly

Lipolysis is altered in MHC class I zinc-α2-glycoprotein deficient mice

AbstractNon-conventional major histocompatibility complex class I molecules are involved in a variety of physiological functions, most at the periphery of the immune system per se. Zinc-α2-glycoprotein (ZAG), the sole soluble member of this superfamily has been implicated in cachexia, a poorly understood yet life-threatening, severe wasting syndrome. To further ascertain the role of ZAG in lipid metabolism and perhaps the immune system, we inactivated both ZAG alleles by gene targeting in mice. Subjecting these ZAG deficient animals to standard or lipid rich food regimens led to increased body weight in comparison to identically treated wild-type mice. This phenotype appeared to correlate with a significant decrease in adipocytic lipolysis that could not be rescued by several pharmacological agents including β3-adrenoreceptor agonists. Furthermore, in contrast to previously reported data, ZAG was found to be ubiquitously and constitutively expressed, with an especially high level in the mouse liver. No overt immunological phenotype was identified in these animals

Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients

Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients