Mechanism of hemoglobin-induced protection against endotoxemia in rats: a ferritin-independent pathway

1997 ◽  
Vol 272 (2) ◽  
pp. L268-L275 ◽  
Author(s):  
L. Otterbein ◽  
B. Y. Chin ◽  
S. L. Otterbein ◽  
V. C. Lowe ◽  
H. E. Fessler ◽  
...  

Hemoglobin (Hb) induces heme oxygenase-1 (HO-1), which catalyzes the breakdown of heme to bilirubin, and ferritin. Rats pretreated with Hb have been shown to survive lethal doses of lipopolysaccharide (LPS; see L. Otterbein, S. L. Sylvester, and A. M. Choi. Am. J. Respir. Cell Mol. Biol. 13: 595-601, 1995). The physiological basis of this increased survival and the mechanism(s) involved in the protection against LPS by Hb are unknown. Here we investigated 1) the effects of Hb on the hemodynamic and biochemical parameters of LPS-induced tissue injury and 2) the mechanism(s) by which Hb conferred protection against shock and tissue injury. Hb-treated rats maintained normal mean arterial blood pressure, whereas control rats experienced cardiovascular collapse after a lethal dose of LPS. Hepatic and renal functions, peripheral white blood cells, serum lactate dehydrogenase, and phosphate also remained normal after LPS in Hb-treated rats. Hb also attenuated LPS-induced neutrophil alveolitis and tumor necrosis factor-alpha levels. Pretreatment with both desferoxamine, which, like ferritin, can bind iron, and with exogenous apoferritin failed to protect against LPS. In contrast, treatment with Hb plus desferoxamine, which induced HO-1 but not ferritin, did protect against LPS. Treatment with iron-dextran, which induced ferritin but not HO-1, did not protect against LPS. We conclude that Hb pretreatment reduces the inflammatory and physiological consequences of LPS and that the Hb-induced protection against LPS is dependent on HO-1 and not ferritin induction.

1987 ◽  
Vol 33 (11) ◽  
pp. 2111-2113 ◽  
Author(s):  
G C Moses ◽  
A R Henderson

Abstract We describe a case of a limb-girdle myopathy presenting with myoglobinuria. A partial deficiency of muscle carnitine palmitoyltransferase (EC 2.3.1.21) may also have been present. All "muscle-type" serum enzymes were markedly increased (to between 30- and 400-fold their respective upper reference limits) and creatine kinase (EC 2.7.3.2) isoenzyme 2 (CK-MB) was increased 130-fold but was still less than 2% of the total creatine kinase activity. The isoenzyme pattern of lactate dehydrogenase (EC 1.1.1.27) in serum was "anodic," with isoenzyme 1 greater than isoenzyme 2--an unusual pattern for myopathies. The possible physiological basis for such a finding is discussed.


Praxis medica ◽  
2021 ◽  
Vol 50 (1-2) ◽  
pp. 1-6
Author(s):  
Radojica Stolić ◽  
Dragica Bukumirić ◽  
Milena Jovanović ◽  
Tomislav Nikolić ◽  
Tatjana Labudović ◽  
...  

Introduction. At the very beginning of the Corona virus epidemic there was not enough data on whether hemodialysis patients have a higher risk for Corona virus infection and which factors may affect the severity of clinical picture. Objective. The aim of the study was to determine the significance of the Modified Early Warning Assessment (MEWS) score for the assessment of coronavirus disease exacerbation. Methods. The research was conducted in COVID dialysis, as a retrospective, descriptive-analytical study, at the University Clinical Center Kragujevac, Serbia, which was organized ad-hoc for treatment of SARS-Cov-2 infection positive patients, which are transfered from Center for Hemodialysis "Ćuprija". They were evaluated routine laboratory findings, demographic and gender structure, arterial blood pressure, presence of comorbidities and residual diuresis, duration of dialysis, radiological evaluation of lungs, determination of MEWS score were the parameters that were monitored. The results were monitored on admission and and in the end of treatment. Results. A statistically significant difference was registered in serum lactate dehydrogenase concentration (486 ± 107.62 vs. 423.7 ± 92.4 U/L); p = 0.022 and absolute monocyte count (0.46 ± 0.15 vs. 0.67 ± 0.34 x 103; p = 0.008). The significant increase in MEWS score was also found (b = 0.017; p = 0.030). There was a positive correlation between increase of MEWS score and age (b = 0.027; p = 0.002) and arterial hypertension as a concomitant comorbidity (b = 0.700; p = 0.033). Conclusion. In the observed period, there was a significant increase in the degree of MEWS score of dialysis patients who had SARS-Cov-2 infection.


2016 ◽  
Vol 36 (9) ◽  
pp. 949-966 ◽  
Author(s):  
W Liu ◽  
Z Xu ◽  
H Li ◽  
M Guo ◽  
T Yang ◽  
...  

Mercury (Hg) represents a ubiquitous environmental heavy metal that could lead to severe toxic effects in a variety of organs usually at a low level. The present study focused on the liver oxidative stress, one of the most important roles playing in Hg hepatotoxicity, by evaluation of different concentrations of mercuric chloride (HgCl2) administration. Moreover, the protective potential of curcumin against Hg hepatotoxic effects was also investigated. Eighty-four rats were randomly divided into six groups for a three-days experiment: control, dimethyl sulfoxide control, HgCl2 treatment (0.6, 1.2, and 2.4 mg kg−1 day−1), and curcumin pretreatment (100 mg kg−1 day−1) groups. Exposure of HgCl2 resulted in acute dose-dependent hepatotoxic effects. Administration of 2.4 mg kg−1 HgCl2 significantly elevated total Hg, nonprotein sulfhydryl, reactive oxygen species formation, malondialdehyde, apoptosis levels, serum lactate dehydrogenase, and alanine transaminase activities, with an impairment of superoxide dismutase and glutathione peroxidase in the liver. Moreover, HgCl2 treatment activated nuclear factor-E2-related factor 2-antioxidant response element (Nrf2-ARE) signaling pathway in further investigation, with a significant upregulation of Nrf2, heme oxygenase-1, and γ-glutamylcysteine synthetase heavy subunit expression, relative to control. Pretreatment with curcumin obviously prevented HgCl2-induced liver oxidative stress, which may be due to its free radical scavenging or Nrf2-ARE pathway-inducing properties. Taking together these data suggest that curcumin counteracts HgCl2 hepatotoxicity through antagonizing liver oxidative stress.


2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maurizio Bartolucci ◽  
Matteo Benelli ◽  
Margherita Betti ◽  
Sara Bicchi ◽  
Luca Fedeli ◽  
...  

AbstractTriage is crucial for patient’s management and estimation of the required intensive care unit (ICU) beds is fundamental for health systems during the COVID-19 pandemic. We assessed whether chest computed tomography (CT) of COVID-19 pneumonia has an incremental role in predicting patient’s admission to ICU. We performed volumetric and texture analysis of the areas of the affected lung in CT of 115 outpatients with COVID-19 infection presenting to the emergency room with dyspnea and unresponsive hypoxyemia. Admission blood laboratory including lymphocyte count, serum lactate dehydrogenase, D-dimer and C-reactive protein and the ratio between the arterial partial pressure of oxygen and inspired oxygen were collected. By calculating the areas under the receiver-operating characteristic curves (AUC), we compared the performance of blood laboratory-arterial gas analyses features alone and combined with the CT features in two hybrid models (Hybrid radiological and Hybrid radiomics)for predicting ICU admission. Following a machine learning approach, 63 patients were allocated to the training and 52 to the validation set. Twenty-nine (25%) of patients were admitted to ICU. The Hybrid radiological model comprising the lung %consolidation performed significantly (p = 0.04) better in predicting ICU admission in the validation (AUC = 0.82; 95% confidence interval 0.73–0.97) set than the blood laboratory-arterial gas analyses features alone (AUC = 0.71; 95% confidence interval 0.56–0.86). A risk calculator for ICU admission was derived and is available at: https://github.com/cgplab/covidapp. The volume of the consolidated lung in CT of patients with COVID-19 pneumonia has a mild but significant incremental value in predicting ICU admission.


2020 ◽  
Vol 09 (04) ◽  
pp. 191-194
Author(s):  
Ravi Chandran ◽  
Siva Prasad Kuruva ◽  
Rachana Chennamaneni ◽  
Stalin Bala ◽  
Meher Lakshmi Konatam ◽  
...  

Abstract Introduction Ewing sarcoma (ES) is more common in children and relatively rare in adults. Adult ES has poor prognosis than children. Treatment approaches for adults have been extrapolated from pediatric experience. Data on adult ES are very few because of its rarity in adults. The present study was done to analyze the clinical profile and outcome of adult ES. Aims The aim was to study the clinical and pathological treatment and outcomes in adult ES. Subjects and Methods Between 2010 and 2017, a total of 73 ES patients with age more than 18 years were retrospectively analyzed. Survival analysis was done by plotting Kaplan–Meier curves. Results A total of 73 patients were diagnosed with ES during 2010 to 2017. Among them, 43 (58.9%) had localized disease with a median age of 24.5 years. Males were 44 (60.3%) and females were 29 (39.7). Pain (75.3%) was the most common symptom at presentation. Nine patients had incomplete details and were excluded from the analysis. Among 21 (28.8%) patients, the lung (61.9%) was the most common site of metastasis followed by the bone, bone marrow, and brain. The median number of chemotherapy cycles in the localized disease was 14 (range 1–17), and in metastatic disease, it was 4 (range 1–7). Univariate analysis was done with respect to age (< 25 vs. ≥25), gender, elevated or normal serum lactate dehydrogenase level, tumor size (< 8 cm versus ≥8 cm), site (axial versus extremity), and neoadjuvant chemotherapy (NACT) given or not. NACT had a significant impact on overall survival (OS) and the rest had no effect. At a median follow-up of 40 months, the 3-year OS in localized disease was 87.4%. In metastatic disease, the median OS was 13 months with 3-year OS of 26%. Conclusions Outcomes with multimodality therapy in adult ES patients with localized disease are comparable to that of a pediatric cohort. However, metastatic disease has poor survival.


1966 ◽  
Vol 12 (5) ◽  
pp. 308-313 ◽  
Author(s):  
Albert W Opher ◽  
Charles S Collier ◽  
Joseph M Miller

Abstract A convenient electrophoretic procedure for the separation and quantitation of lactate dehydrogenase (LDH) isoenzymes is described. The system uses polyacetate Sepraphore III strips.* The areas of activity are shown by incubation with an LDH substrate combined with tetra-nitro-blue-tetrazolium. The reduction of the latter to the purple formazan is quantitatively related to the enzyme activity. Quantitative determination of the individual colored areas is performed by densitometry.


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