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American Journal of Physiology. Heart... Oct 2023Cardiovascular regulation of tissue oxygenation is generally viewed as an anti-drop process that prevents tissue oxygen concentration from falling below some minimum. I...
Cardiovascular regulation of tissue oxygenation is generally viewed as an anti-drop process that prevents tissue oxygen concentration from falling below some minimum. I propose that cardiovascular regulation is predominately an anti-rise process designed to downregulate oxygen delivery. This maintains an evolutionarily conserved, reduced intracellular environment to prevent oxidation of redox-sensitive regulatory protein thiols. A number of points support this hypothesis. First, oxygen is the only nutrient with a positive, fourfold diffusion gradient from the environment to systemic tissues, minimizing the likelihood that oxygen delivery is limited. Second, hemoglobin (Hb) retains oxygen unless offloading is absolutely necessary. The allosteric properties of Hb keep oxygen tightly bound until absolutely needed, and the Bohr shift, which favors offloading, is only transient and lost when metabolism is restored. Third, a myoglobin-like Hb (xHb) would offload all of its oxygen and could easily have evolved, but it did not. Fourth, oxygen-sensitive vasoconstrictors and hyperoxic-rarefaction prevent acute and chronic over perfusion. Fifth, Fåhraeus and Fåhraeus-Lindqvist effects reduce capillary hematocrit to minimize microcirculatory oxygen content. Sixth, venous blood remains 75% saturated, wasting 75% of cardiac output were an oxygen reserve not needed. Finally, xHb-containing red blood cells could be considerably smaller and thereby decrease Fåhraeus and Fåhraeus-Lindqvist effects and cardiac load. In summary, the capacity of the cardiovascular system to deliver oxygen to the tissues generally exceeds demand, and although maintenance of an oxygen delivery reserve is important, it is more important to prevent excess oxygen delivery.
Topics: Humans; Microcirculation; Erythrocytes; Heart; Cachexia; Oxygen
PubMed: 37624098
DOI: 10.1152/ajpheart.00449.2023 -
Skeletal Radiology Jan 2024This review illustrates the imaging features of rhabdomyolysis across multiple modalities and in a variety of clinical scenarios. Rhabdomyolysis is the rapid breakdown... (Review)
Review
This review illustrates the imaging features of rhabdomyolysis across multiple modalities and in a variety of clinical scenarios. Rhabdomyolysis is the rapid breakdown of striated muscle following severe or prolonged insult resulting in the release of myocyte constituents into circulation. In turn, patients develop characteristically elevated serum creatine kinase, positive urine myoglobin, and other serum and urine laboratory derangements. While there is a spectrum of clinical symptoms, the classic presentation has been described as muscular pain, weakness, and dark urine. This triad, however, is only seen in about 10% of patients. Thus, when there is a high clinical suspicion, imaging can be valuable in evaluating the extent of muscular involvement, subsequent complications such as myonecrosis and muscular atrophy, and other etiologies or concurrent injuries causing musculoskeletal swelling and pain, especially in the setting of trauma. Sequela of rhabdomyolysis can be limb or life-threatening including compartment syndrome, renal failure, and disseminated intravascular coagulation. MRI, CT, ultrasound, and 18-FDG PET/CT are useful modalities in the evaluation of rhabdomyolysis.
Topics: Humans; Positron Emission Tomography Computed Tomography; Rhabdomyolysis; Muscle, Skeletal; Myalgia; Edema
PubMed: 37318587
DOI: 10.1007/s00256-023-04378-5 -
BMC Nephrology Jul 2023To determine whether continuous venovenous hemodiafiltration (CVVHDF) plus standard medical therapy (SMT) vs. SMT alone prevents rhabdomyolysis (RM)-induced acute kidney...
AIM
To determine whether continuous venovenous hemodiafiltration (CVVHDF) plus standard medical therapy (SMT) vs. SMT alone prevents rhabdomyolysis (RM)-induced acute kidney injury (AKI) and analyze the related health economics.
METHODS
This retrospective cohort study involved 9 RM patients without AKI, coronary heart disease, or chronic kidney disease treated with CVVHDF plus SMT (CVVHDF + SMT group). Nine matched RM patients without AKI treated with SMT only served as controls (SMT group). Baseline characteristics, biochemical indexes, renal survival data, and health economic data were compared between groups. In the CVVHDF + SMT group, biochemical data were compared at different time points.
RESULTS
At 2 and 7 days after admission, serum biochemical indices (e.g., myoglobin, creatine kinase, creatinine, and blood urea nitrogen) did not differ between the groups. Total (P = 0.011) and daily hospitalization costs (P = 0.002) were higher in the CVVHDF + SMT group than in the SMT group. After 53 months of follow-up, no patient developed increased serum creatinine, except for 1 CVVHDF + SMT-group patient who died of acute myocardial infarction. In the CVVHDF + SMT group, myoglobin levels significantly differed before and after the first CVVHDF treatment (P = 0.008), and serum myoglobin, serum creatinine, and blood urea nitrogen decreased significantly at different time points after CVVHDF.
CONCLUSIONS
Although CVVHDF facilitated myoglobin elimination, its addition to SMT did not improve biochemical indices like serum myoglobin, serum creatine kinase, creatinine, blood urea nitrogen, and lactate dehydrogenase or the long-term renal prognosis. Despite similar hospitalization durations, both total and daily hospitalization costs were higher in the CVVHDF + SMT group.
Topics: Humans; Hemodiafiltration; Continuous Renal Replacement Therapy; Creatinine; Retrospective Studies; Myoglobin; Acute Kidney Injury; Rhabdomyolysis; Creatine Kinase
PubMed: 37468857
DOI: 10.1186/s12882-023-03242-x -
Cells Sep 2023Brown adipose tissue (BAT) plays an important role in energy homeostasis by generating heat from chemical energy via uncoupled oxidative phosphorylation. Besides its... (Review)
Review
Brown adipose tissue (BAT) plays an important role in energy homeostasis by generating heat from chemical energy via uncoupled oxidative phosphorylation. Besides its high mitochondrial content and its exclusive expression of the uncoupling protein 1, another key feature of BAT is the high expression of myoglobin (MB), a heme-containing protein that typically binds oxygen, thereby facilitating the diffusion of the gas from cell membranes to mitochondria of muscle cells. In addition, MB also modulates nitric oxide (NO•) pools and can bind C16 and C18 fatty acids, which indicates a role in lipid metabolism. Recent studies in humans and mice implicated MB present in BAT in the regulation of lipid droplet morphology and fatty acid shuttling and composition, as well as mitochondrial oxidative metabolism. These functions suggest that MB plays an essential role in BAT energy metabolism and thermogenesis. In this review, we will discuss in detail the possible physiological roles played by MB in BAT thermogenesis along with the potential underlying molecular mechanisms and focus on the question of how BAT-MB expression is regulated and, in turn, how this globin regulates mitochondrial, lipid, and NO• metabolism. Finally, we present potential MB-mediated approaches to augment energy metabolism, which ultimately could help tackle different metabolic disorders.
Topics: Humans; Animals; Mice; Myoglobin; Adiposity; Obesity; Adipose Tissue, Brown; Cell Membrane; Fatty Acids
PubMed: 37759463
DOI: 10.3390/cells12182240 -
Journal of Clinical Medicine Dec 2023Unexpected filter clotting is a major problem in continuous renal replacement therapy (CRRT). Reduced solute clearance is observed prior to filter clotting. This...
Unexpected filter clotting is a major problem in continuous renal replacement therapy (CRRT). Reduced solute clearance is observed prior to filter clotting. This single-center, retrospective, observational study aimed to determine whether reduced solute clearance of low- and medium-molecular-weight molecules in CRRT can predict filter clotting. Solute clearances of urea and myoglobin (Mb) were measured at 24 h after initiation of continuous hemodiafiltration (CHDF). Clearance per flow (CL/F) was calculated. The primary outcome was clotting of the filter in the subsequent 24 h, and 775 CHDF treatments conducted on 230 patients for at least 24 consecutive hours in our ICU were analyzed. Filter clotting was observed in 127 treatments involving 39 patients. Urea and Mb CL/F at 24 h were significantly lower in the patients who experienced clotting. Further analysis was limited to the first CHDF treatment of each patient to adjust for confounding factors. Multivariate logistic regression analysis revealed that both urea CL/F < 94% and Mb CL/F < 64% were significant predictors of clotting within the next 24 h. Lower urea and Mb CL/F measured at 24 h after CRRT initiation were associated with filter clotting in the next 24 h. Further study is necessary to ascertain whether measurement of urea and MB CL/F will help with avoiding unexpected filter clotting.
PubMed: 38137772
DOI: 10.3390/jcm12247703 -
Journal of Proteomics Jul 2023Metabolites are the final products of metabolism and provide insights into the biochemical balance of tissue systems. A cascade of reactions involving proteins,... (Review)
Review
Metabolites are the final products of metabolism and provide insights into the biochemical balance of tissue systems. A cascade of reactions involving proteins, carbohydrates, and lipids affects meat color, tenderness, and flavor, specifically, metabolites that are key biomolecules in biochemical reactions associated with attainment of acceptable meat quality. Bioinformatics platforms, such as Kyoto Encyclopedia of Genes and Genomes (KEGG) databases and MetaboAnalyst, are utilized to help understanding the role of differentially abundant metabolites and characterizing their roles in cellular function/metabolism. However, the inability to identify all metabolites using a single platform and limited metabolite libraries specifically for meat/food remains a challenge. Therefore, the advances in metabolite separation, easy-to-use data processing, increased resolution of mass-spectrometry, and data analysis will help to make inferences or develop biomarkers related to meat quality. This review discusses how metabolomics can be exploited to characterize meat quality, the challenges, and current trends. SIGNIFICANCE: Metabolites play an important role in attaining consumer-preferred meat quality traits and nutritive value of foods. Visual appearance of fresh foods, such as muscle foods, are utilized by consumers to assess the quality at the retail market before making purchases. Similarly, tenderness and flavor of meats influence eating satisfaction and re-purchase decisions. Inconsistencies in meat quality lead to enormous economic losses to the food industry. For instance, consumers often associate a bright-cherry red color with freshness, and the US beef industry loses $3.74 billion annually due to discoloration during storage. Both pre-and post-harvest factors influence the extent of meat quality changes. Metabolomics offer robust tools to get a snapshot of small molecules such as acids, amino acids, glycolytic- and tricarboxylic acids, fatty acids, and sugars present in post-mortem muscle tissue and their role in meat quality. Further, using bioinformatics platforms enables characterizing the role of differentially present metabolites in meat quality as well as identifying biomarkers for desirable quality traits such as tender meat or color-stable carcasses. Innovative applications of metabolomics can be exploited to elucidate the underpinnings of meat quality and to develop novel strategies to enhance marketability of retail fresh meats.
Topics: Animals; Cattle; Meat; Metabolomics; Computational Biology; Muscles; Red Meat
PubMed: 37207813
DOI: 10.1016/j.jprot.2023.104926 -
Journal of Cachexia, Sarcopenia and... Aug 2023Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as...
BACKGROUND
Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population-based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes.
METHODS
In a population-based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24-h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5-bromo-2'-deoxy-uridine ELISA assay. Myocyte differentiation was assessed using Myh7-stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence-activated cell sorting. RNA sequencing (RNAseq) was used to identify ID-related gene and pathway enrichment in myoblasts and myocytes.
RESULTS
Participants in the lowest age- and sex-specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25-2.10, P < 0.001) or transferrin saturation (OR 1.34, 95% CI 1.03-1.75, P = 0.03) had a significantly higher risk of being in the lowest age- and sex-specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs-CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine-induced ID reduced myoblast proliferation rate (P-trend <0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (-52%, P < 0.001) and tended to reduce mitochondrial oxygen consumption capacity (-28%, P = 0.10). Deferoxamine induced gene expression of cellular atrophy markers Trim63 (+20%, P = 0.002) and Fbxo32 (+27%, P = 0.048), which was reversed by ferric citrate (-31%, P = 0.04 and -26%, P = 0.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in glycolytic energy metabolism, cell cycle regulation and apoptosis; co-treatment with ferric citrate reversed these effects.
CONCLUSIONS
In population-dwelling individuals, ID is related to lower muscle mass, independent of haemoglobin levels and potential confounders. ID impaired myoblast proliferation and aerobic glycolytic capacity, and induced markers of myocyte atrophy and apoptosis. These findings suggest that ID contributes to loss of muscle mass.
Topics: Animals; Female; Male; Mice; Atrophy; Cell Proliferation; Deferoxamine; Ferritins; Independent Living; Iron; Iron Deficiencies; Muscles; Myoblasts, Skeletal; Quality of Life; Transferrins; Humans; Adult
PubMed: 37386912
DOI: 10.1002/jcsm.13277 -
Clinical Nutrition ESPEN Dec 2023The presented review is an updating of Iron metabolism in context of normal physiology and pathological phases. Iron is one of the vital elements in humans and... (Review)
Review
PURPOSE (BACKGROUND)
The presented review is an updating of Iron metabolism in context of normal physiology and pathological phases. Iron is one of the vital elements in humans and associated into proteins as a component of heme (e.g. hemoglobin, myoglobin, cytochromes proteins, myeloperoxidase, nitric oxide synthetases), iron sulfur clusters (e.g. respiratory complexes I-III, coenzyme Q10, mitochondrial aconitase, DNA primase), or other functional groups (e.g. hypoxia inducible factor prolyl hydroxylases). All these entire iron-containing proteins ar e needed for vital cellular and organismal functions together with oxygen transport, mitochondrial respiration, intermediary and xenobiotic metabolism, nucleic acid replication and repair, host defense, and cell signaling.
METHODS (METABOLIC STRATEGIES)
Cells have developed metabolic strategies to import and employ iron safely. Regulatory process of iron uptake, storage, intracellular trafficking and utilization is vital for the maintenance of cellular iron homeostasis. Cellular iron utilization and intracellular iron trafficking pathways are not well established and very little knowledge about this. The predominant organs, which are associated in the metabolism of iron, are intestine, liver, bone marrow and spleen. Iron is conserved, recycled and stored. The reduced bioavailability of iron in humans has developed extremely efficient mechanisms for iron conservation. Prominently, the losses of iron cannot considerably enhance through physiologic mechanisms, even if iron intake and stores become excessive. Loss of iron is balanced or maintained from dietary sources.
RESULTS (OUTCOMES)
Numerous physiological abnormalities are associated with impaired iron metabolism. These abnormalities are appeared in the form of several diseases. There are duodenal ulcer, inflammatory bowel disease, sideroblastic anaemia, congenital dyserythropoietic anemias and low-grade myelodysplastic syndromes. Hereditary hemochromatosis and anaemia are two chronic diseases, which are responsible for disturbing the iron metabolism in various tissues, including the spleen and the intestine. Impairment in hepatic hepcidin synthesis is responsible for chronic liver disease, which is grounding from alcoholism or viral hepatitis. This condition directs to iron overload that can cause further hepatic damage. Iron has important role in several infectious diseases are tuberculosis, malaria trypanosomatid diseases and acquired immunodeficiency syndrome (AIDS). Iron is also associated with Systemic lupus erythematosus [SLE], cancer, Alzheimer's disease (AD) and post-traumatic epilepsy.
CONCLUSION
Recently, numerous research studies are gradually more dedicated in the field of iron metabolism, but a number of burning questions are still waiting for answer. Cellular iron utilization and intracellular iron trafficking pathways are not well established and very little knowledge about this. Increased information of the physiology of iron homeostasis will support considerate of the pathology of iron disorders and also make available the support to advance treatment.
Topics: Humans; Iron; Hemochromatosis; Iron Overload; Homeostasis; Liver Diseases
PubMed: 38057018
DOI: 10.1016/j.clnesp.2023.10.006 -
Frontiers in Cellular and Infection... 2023The gut microbiota plays an important role in human health. In this study, we aimed to investigate whether and how gut microbiota communities are altered in patients...
AIM
The gut microbiota plays an important role in human health. In this study, we aimed to investigate whether and how gut microbiota communities are altered in patients with immune-mediated necrotizing myopathy (IMNM) and provide new ideas to further explore the pathogenesis of IMNM or screen for its clinical therapeutic targets in the future.
METHODS
The gut microbiota collected from 19 IMNM patients and 23 healthy controls (HCs) were examined by using 16S rRNA gene sequencing. Alpha and beta-diversity analyses were applied to examine the bacterial diversity and community structure. Welch's t test was performed to identify the significantly abundant taxa of bacteria between the two groups. Spearman correlation analysis was performed to analyze the correlation between gut microbiota and clinical indicators. A receiver operator characteristic (ROC) curve was used to reflect the sensitivity and specificity of microbial biomarker prediction of IMNM disease. P < 0.05 was considered statistically significant.
RESULTS
Nineteen IMNM patients and 23 HCs were included in the analysis. Among IMNM patients, 94.74% (18/19) of them used glucocorticoids, while 57.89% (11/19) of them used disease-modifying antirheumatic drugs (DMARDs), and the disease was accessed by MITAX (18.26 ± 8.62) and MYOACT (20.68 ± 8.65) scores. Participants in the groups were matched for gender and age. The diversity of the gut microbiota of IMNM patients differed and decreased compared to that of HCs (Chao1, Shannon, and Simpson indexes: p < 0.05). In IMNM patients, the relative abundances of Bacteroides, Roseburia, and Coprococcus were decreased, while that of Lactobacillus and Streptococcus were relatively increased. Furthermore, in IMNM patients, Lactobacillus was positively correlated with the levels of anti-signal recognition particle (SRP) antibodies, anti-Ro52 antibodies, and erythrocyte sedimentation rate (ESR), while Streptococcus was positively correlated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies and C-reactive protein (CRP). Roseburia was negatively correlated with myoglobin (MYO), cardiac troponin T (cTnT), ESR, CRP, and the occurrence of interstitial lung disease (ILD). Bacteroides was negatively correlated with ESR and CRP, and Coprococcus was negatively correlated with ESR. Finally, the prediction model was built using the top five differential genera, which was verified using a ROC curve (area under the curve (AUC): 87%, 95% confidence interval: 73%-100%).
CONCLUSION
We observed a characteristic compositional change in the gut microbiota with an abnormal elevation of Lactobacillus in IMNM patients, which was accompanied by changes in clinical indicators. This suggests that gut microbiota dysbiosis occurs in IMNM patients and is correlated with systemic autoimmune features.
Topics: Gastrointestinal Microbiome; Dysbiosis; Lactobacillus; Humans; Myositis; Autoimmune Diseases; Necrosis; Male; Female; Middle Aged
PubMed: 37692165
DOI: 10.3389/fcimb.2023.1243512 -
Turkish Journal of Emergency Medicine 2023Earthquakes are natural disasters which can destroy the rural and urban infrastructure causing a high toll of injuries and death without advanced notice. We aim to...
Earthquakes are natural disasters which can destroy the rural and urban infrastructure causing a high toll of injuries and death without advanced notice. We aim to review the prehospital medical management of earthquake crush injuries in the field. PubMed was searched using general terms including rhabdomyolysis, crush injury, and earthquake in English language without time restriction. Selected articles were critically evaluated by three experts in disaster medicine, emergency medicine, and critical care. The medical response to earthquakes includes: (1) search and rescue; (2) triage and initial stabilization; (3) definitive care; and (4) evacuation. Long-term, continuous pressure on muscles causes crush injury. Ischemia-reperfusion injury following the relieving of muscle compression may cause metabolic changes and rhabdomyolysis depending on the time of extrication. Sodium and water enter the cell causing cell swelling and hypovolemia, while potassium and myoglobin are released into the circulation. This may cause sudden cardiac arrest, acute extremity compartment syndrome, and acute kidney injury. Recognizing these conditions and treating them timely and properly in the field will save many patients. Majority of emergency physicians who have worked in the field of the recent Kahramanmaraş 2023, Turkey, earthquakes, have acknowledged their lack of knowledge and experience in managing earthquake crush injuries. We hope that this collective review will cover the essential knowledge needed for properly managing seriously crushed injured patients in the earthquake field.
PubMed: 38024191
DOI: 10.4103/tjem.tjem_201_23