Lactate Dehydrogenase Research Articles

Ethnic disparities in clinical severity of COVID-19 as predictor of long COVID

Abstract Background Recent studies from Europe have shown a higher incidence of long COVID among ethnic minorities compared to the majority population. Little is known of these disparities, but they might be related to factors such as COVID-19 disease severity, barriers in access to health and individual factors such as working and living conditions. This study will elucidate possible predictors of long COVID related to COVID-19 disease severity in an ethnic diverse hospitalised cohort. Methods A retrospective cohort study of 1648 patients admitted with COVID-19 at three hospitals in Copenhagen, Denmark, between 1st February 2020 and 31st May 2022. Clinical data was extracted from health care records, and subsequently linked to data from Statistics Denmark on long COVID diagnosis (ICD-10 “DB948A”) as well as migration status. Results 1361 patients were discharged alive and of those, 113 (8,3%) patients got a long COVID diagnosis. Preliminary analyses show no excess risk of getting a long COVID diagnosis as a migrant compared to patients of Danish origin (RR = 1,20, p = 0,35). Some ethnic disparities are seen in disease severity among all patients discharged alive. Patients with migrant background were admitted to the hospital later (6,8 vs 5,6 days, p < 0,0001), and at a greater risk of needing high flow oxygen administration upon admission (RR = 1,46, p = 0,0012) compared to patients of Danish origin. Furthermore, a higher degree of systemic inflammation is seen among migrants with regards to lactate dehydrogenase (LDH) compared to patients of Danish origin (349,7 vs 317,2 U/L, p = 0,0014). No significant differences in c-reactive protein (CRP) levels (92,8 vs 85,9 mg/L, p = 0,11). Conclusions Preliminary analyses indicates possible ethnic disparities in COVID-19 disease severity among patients discharged alive possibly playing a role as predictors of long COVID. Low health literacy or language barriers might partly explain this. Further analyses are needed. Key messages • In preliminary analyses of 1381 patients previously admitted with COVID-19, we find no excess risk of a long COVID diagnosis (DB 948B) among patients with migrant background. • Preliminary analyses show some ethnic disparities in COVID-19 disease severity that might act as possible predictors of long COVID.

Clinical characteristics of megaloblastic anemia with pancytopenia

ABSTRACT Objectives In this study, we aimed to explore the clinical characteristics of patients with megaloblastic anemia and pancytopenia. Methods Data on patient characteristics, laboratory examinations, clinical manifestations, and associated diseases were collected from Changzhou Hospital of Traditional Chinese Medicine. The participants were divided into two groups according to routine blood test results: megaloblastic anemia patients with pancytopenia (Group A) and megaloblastic anemia patients with simple anemia (Group B). Results The number of patients with fever and bleeding in Group A was much higher than that in Group B. Inpatient days and hospitalization costs in Group A were higher than those in Group B. White blood cell count, red blood cell count, haemoglobin level, and platelet count in Group A were lower than those in Group B. There were no significant differences in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and serum levels of lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), vitamin B12, folic acid, and ferritin between the two groups. The incidence of associated diseases, particularly pulmonary infections, was significantly higher in Group A than in Group B. There was no significant difference in the degree of bone marrow hyperplasia between the two groups. Conclusion Patients with pancytopenia and megaloblastic anemia often developed infection and bleeding, which caused more severe anemia, higher hospitalization costs, and longer inpatient days. Early diagnosis and active treatment are required to reduce patient complications and costs.

Explainable machine learning and multi-modal data for predicting readmission in patients with heart failure

Abstract Background Cardiovascular diseases (CVDs) are among the leading causes of mortality and morbidity globally, with an estimated 1 million hospital admissions for CVD in England in 2019/20, leading to 5.5 million bed days. In addition, patients with CVDs have a notably high rate of hospital readmission, with approximately one in four patients experiencing heart failure (HF) being readmitted within one month of discharge. We explored whether machine learning models trained on electrocardiogram (ECG) and patient electronic health records (EHRs) can support decision-making and risk management and ultimately improve health outcomes for HF patients. Purpose The project aims to develop a machine learning model to predict health outcomes for HF patients. To test the hypothesis, we trained and tested an explainable machine learning model to predict the risk of mortality and hospital readmission rate for HF patients. Methods We used EHR data and tabulated ECG records to train an XGBoost model to predict the risk of 30-day mortality and 30-day hospital readmission for HF patients. EHR data from a cohort of 2,868 patients with their ECG records were used for model development. We extracted a total of 78 features from the ECG data, such as heart rate variability (HRV), P-wave durations, and QT intervals. These ECG features were combined with coded and free-text EHR data (e.g., demographic information, diagnosis, medication history, and lab results) and used as tabular inputs to the XGBoost model. Of the 2,868 patients, an internal set of 574 patients stratified by age, sex, and health outcomes (30-day mortality and 30-day hospital readmission) were held out for testing. Results Among 2,868 HF patients with 10-year follow-up, 1065 patients were reported for mortality or hospital readmission within 30 days of discharge. When the machine learning model was trained on ECG data in addition to EHR data, the model was able to predict patient mortality and hospital readmission rate in the test set with an area under the curve (AUC) of 0.91 and 0.70, respectively. For mortality prediction, the model achieved a sensitivity and specificity of 0.81 and 0.82, respectively, when employing an operating point with minimum difference between the sensitivity and specificity. When the threshold was adjusted to favor sensitivity at 0.91, the model specificity decreased to 0.74. The machine learning model also identified high sensitive troponin levels, QT dispersion, and lactate dehydrogenase levels as features of high importance for predicting the outcomes for HF patients. Conclusions Our developed machine learning model was able to predict mortality and readmission risks in HF patients using multi-modal data. Upon further validation, the machine learning model has the potential to be tested for supporting clinical decision-making and risk management for HF patients.ROC CurveFeature Importance

COMPREENDENDO A INTERSEÇÃO ENTRE HIV/AIDS E PNEUMONIA: UMA ANÁLISE ABRANGENTE DA LITERATURA

INTRODUCTION: The relationship between HIV/AIDS and pneumonia is complex and multifaceted. Individuals infected with HIV have a significantly higher risk of developing pneumonia, caused by both bacterial and viral agents, due to immune suppression from the virus. OBJECTIVE: To identify in the literature the relationship between HIV/AIDS and pneumonia in the context of nursing care. MATERIALS AND METHODS: This is an integrative literature review conducted in the MEDLINE, LILACS, and BDENF databases, using the descriptors: “HIV seropositivity,” “Pneumonia,” and “nursing care.” The descriptors were combined using the boolean operator AND, covering the period from 2018 to 2024. RESULTS: The study found that HIV-positive patients tend to experience a subacute progression of Pneumocystis jirovecii pneumonia (PCP), while immunocompromised patients without HIV face rapid progression, with a higher risk of respiratory failure and mortality. CT scans showed ground-glass opacities and elevated lactate dehydrogenase levels. Non-HIV patients had longer treatment delays and higher hospitalization and mortality rates. Lymphopenia, steroid use, and pneumothorax were associated with 60-day mortality. The incidence of bacterial pneumonia in people living with HIV decreased, linked to improved CD4 counts. Children with HIV showed higher mortality from coronavirus-related pneumonia. CONCLUSIONS: Future research should expand epidemiological surveillance, explore new therapies, and investigate co-infections in at-risk groups, particularly children. Additionally, strengthening public health policies and promoting prevention education are essential to improve clinical outcomes in vulnerable populations.

Neuropeptide FF Promotes Neuronal Survival and Enhances Synaptic Protein Expression Following Ischemic Injury.

This study explores the neuroprotective effects of neuropeptide FF (NPFF, FLFQPQRFamide) in the context of ischemic injury. Based on transcriptomic analysis in stroke models treated with 5-Aza-dC and task-specific training, we identified significant gene expression changes, particularly involving NPFF. To further explore NPFF's role in promoting neuronal recovery, recombinant NPFF protein (rNPFF) was used in primary mixed cortical cultures subjected to oxygen-glucose deprivation and reoxygenation. Our results demonstrated that rNPFF significantly reduced lactate dehydrogenase release, indicating decreased cellular damage. It also significantly increased the expression of TUJ1 and MAP2, markers of neuronal survival and dendritic integrity. Additionally, rNPFF significantly upregulated key synaptic proteins, including GAP43, PSD95, and synaptophysin, which are essential for synaptic repair and plasticity. Post-injury rNPFF treatment led to a significant upregulation of pro-brain-derived neurotrophic factor (BDNF) and mature BDNF, which play critical roles in neuronal survival, growth, and synaptic plasticity. Moreover, rNPFF activated the protein kinase Cε isoform, Sirtuin 1, and peroxisome proliferator-activated receptor gamma pathways, which are crucial for regulating cellular stress responses, synaptic plasticity, and energy homeostasis, further promoting neuronal survival and recovery. These findings suggest that rNPFF may play a pivotal role in enhancing neuronal survival and synaptic plasticity after ischemic injury, highlighting its potential as a therapeutic target for stroke recovery.

Pre-diagnostic trajectory of pediatric hemophagocytic lymphohistiocytosis: observations from hematological and hepatic parameters.

Understanding the early features and characteristics of hemophagocytic lymphohistiocytosis (HLH) is essential for identifying high-risk individuals and also providing valuable pathological insights. This study aims to investigate the characteristics and trends of blood and hepatic parameters before an HLH diagnosis was established. Longitudinal hematological and hepatic test results from pediatric patients with HLH and an age- and sex-matched control group were analyzed. According to the length of time between hospital admission and the establishment of the HLH diagnosis, the HLH cases were divided into early-onset (≤ 7 days) and late-onset (> 7days) groups. Among the 229 pediatric HLH patients, the length of time between hospital admission and the establishment of an HLH diagnosis ranged from 0 to 41 days (median = 4 days). Over 80% of pediatric HLH patients presented abnormal laboratory results for aspartate aminotransferase (AST), triglycerides, lactate dehydrogenase (LDH), and hemoglobin at admission. The abnormal rates in the initial platelet count, neutrophil count, and fibrinogen tests were 67.3%, 48.3%, and 52.2%, respectively. The initial test results for AST, alanine aminotransferase (ALT), LDH, serum sodium, and albumin showed AUCs > 80% for discriminating early-onset HLH. For the discrimination of late-onset HLH, the performance of initial test results was poor. To conclude, abnormalities in AST, triglycerides, LDH, and hemoglobin are early presentations of pediatric HLH; platelet, neutrophil, and fibrinogen levels may become abnormal at a relatively late stage of the HLH disease trajectory; and the initial test results for AST, ALT, LDH, serum sodium, and albumin can be used to identify suspected early-onset HLH.

Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice.

Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen (APAP). However, the role of the complement inhibitor C2-FH in APAP-induced liver injury remains unclear. To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement activation. A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury. C2-FH was administered through intraperitoneal injection 30 minutes after APAP treatment. We detected the effects of C2-FH on liver function, inflammatory response and complement activation. Additionally, RNA-sequencing (RNA-Seq) analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver injury. C2-FH inhibited the increase in serum alanine aminotransferase activity, aspartate aminotransferase activity and lactate dehydrogenase, and reduced liver tissue necrosis caused by APAP. Moreover, it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver injury. RNA-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver injury. C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.

Enzymological Effects of Lead Acetate Exposure in Various Organs of Oreochromis mossambicus (Peters 1852)

The various enzymological effects of heavy metal Lead acetate (Pb(C2H3O2)2) exposed to fingerlings of Oreochromis mossambicus was analyzed in this study. The 30 days old fingerlings of O. mossambicus were exposed to sub lethal dose 3.80ppm of 96 hrs. LC50 of Pb(C2H3O2)2 for 21 and 28 days, various organs (liver, gill, kidney and muscle tissue) were removed from control and treated fishes and were used for various enzymological effect: Succinate dehydrogenase (SDH), Lactate dehydrogenase (LDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Acid phosphatase (ACP) and Alkaline phosphatase ALP). The observed data were subjected into various statistical analysis by using IBM-SPSS version 26. Among the two different exposure periods 21 and 28 days which compared with control fingerlings organs, the various enzymological effects were drastically suffered (Treated fish enzymological levels were inversely proportionate towards the control groups of fish species) by 28 days of exposure periods. Pb(C2H3O2)2 exposed to fingerlings which tested on various organs at 28 days interval periods for assessing of SDH, LDH, AST, ALT, ACP and ALP of various organs of treated fish: Liver: 12.02, 55.75, 58.24, 125.27,12.26, 11.82 µ moles of phenol liberated/ mg of protein; Gill: 10.80, 33.75, 28.73, 28.11, 7.80, 8.63 µ moles of phenol liberated/ mg of protein; Kidney: 12.18, 46.33, 44.78, 75.40, 6.27, 10.38 µ moles of phenol liberated/ mg of protein and Muscle: 11.72, 32.44, 32.76, 44.20, 3.72, 7.20 µ moles of phenol liberated/ mg of protein were recorded on tissue of treated fish. The enzymological effect of Pb(C2H3O2)2 exposed towards O. mossambicus which observed various health defects on organism exposed to a particular toxicant. It may give sufficient information about heavy metal contamination on aquatic organism and would help us to propose policies to protect the ecosystem.

Matching-adjusted indirect comparison of Acalabrutinib versus Ibrutinib in relapsed/refractory mantle cell lymphoma

ABSTRACT Objective In the absence of head-to-head clinical trials, matching-adjusted indirect comparison (MAIC) was used to compare 2 Bruton tyrosine kinase inhibitors (BTKis) approved for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL). This analysis compares the efficacy and safety of acalabrutinib versus ibrutinib using a more mature dataset than a previously published MAIC. Methods Individual patient data from 122 patients treated with acalabrutinib in a phase 2 study were weighted to match aggregate baseline characteristics of patients pooled from 3 separate trials of ibrutinib. Patients were matched on Eastern Cooperative Oncology Group performance status, simplified Mantle Cell Lymphoma International Prognostic Index, lactate dehydrogenase, prior lines of therapy, tumor burden, and blastoid histology. Outcomes assessed included progression-free survival (PFS), overall survival (OS), and adverse events. Results After matching, differences in PFS between acalabrutinib (median 17.8 months) and ibrutinib (median 12.8 months) were not statistically significant (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.74–1.15; P = 0.48). Similarly, after matching, OS differences between acalabrutinib (median 36.5 months) and ibrutinib (median 27.9 months) did not reach statistical significance (HR, 0.87; 95% CI, 0.64–1.17; P = 0.35). Acalabrutinib was associated with an improved safety profile compared with ibrutinib, with statistically significantly lower rates of grade ≥3 atrial fibrillation and thrombocytopenia. Conclusions This comparison of 2 BTKis used in the treatment of R/R MCL showed that PFS and OS risk was not statistically different between the treatments; however, acalabrutinib had an improved safety profile compared with ibrutinib.

Risk factors for in-hospital mortality in older patients with acute respiratory distress syndrome due to COVID-19: a retrospective cohort study

BackgroundAdvancing age is associated with an increase in mortality among patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed to determine risk factors for in-hospital mortality in patients over 60 years old with COVID-19-related ARDS (C-ARDS).MethodsThis was an observational, analytical, retrospective study conducted on a cohort that included all patients aged 60 years or older diagnosed with COVID-ARDSwho were admitted to a high-complexity hospital in Bogotá, Colombia, between March 2020 and July 2021.ResultsA total of 1563 patients were included in the analysis, with a median age of 73 years (interquartile range [IQR]: 67–80) and 811 deaths (51.8%). Independent risk factors for in-hospital mortality were identified as follows: patients aged 71–80 [OR 1.87 (95% CI 1.33–2.64)], age > 80 [OR 8.74 (95% CI 5.34–14.31)], lactate dehydrogenase (LDH) [OR 1.009 (95% CI 1.003–1.0015)], severe C-ARDS [OR 2.16 (95% CI 1.50–3.11)], use of invasive mechanical ventilation (IMV) [OR 12.94 (95% CI 9.52–17.60)], and use of steroids [OR 1.49 (95% CI 1.09–2.03)]. In patients over 80 years of age (n = 388), the primary risk factor associated with in-hospital mortality was the use of IMV (n = 76) [OR 6.26 (95% CI 2.67–14.69)], resulting in an in-hospital mortality rate of 89.4% (n = 68) when this therapy was implemented.ConclusionsThe primary risk factors for in-hospital mortality in patients older than 60 years were age, the use of IMV, the severity of C-ARDS, use of steroids and elevated LDH values. Among patients older than 80 years, the main risk factor for in-hospital mortality was the use of IMV. In cases of C-ARDS in older patients, the decision to initiate IMV should always be individualized; therefore, the use of alternative oxygen delivery systems as the first-line approach can be considered.

Preparation, optimization, and evaluation of ligand-tethered atovaquone-proguanil-loaded nanoparticles for malaria treatment

This work focused on improving antimalarial therapy through the development and characterization of Atovaquone-Proguanil-loaded nanoparticles employing a 32 factorial design. The nanoparticles were prepared from combinations of Poly(lactic-co-glycolic acid) (PLGA) and Eudragit L100 polymers and different concentrations of PVA (polyvinyl alcohol). Based on the results obtained the formulations were characterized for the particle size, zeta potential, encapsulation efficiency, and percent drug release. Among the nine formulations, F5 proved to be the most favorable in the biophysical parameters with a particle size of 176.3 nm, a zeta potential of −33.5 mV, and an encapsulation efficiency of 86% was found in the present investigation. Experimental dissolution profile analysis indicated that F5 had a slow and controlled-release profile where approximately 92.5%. Besides, cytotoxicity studies employing MTT, LDH (lactate dehydrogenase), and Trypan blue reduction test also supported the biocompatibility of nanoparticles and F5 had the highest cell viability (96%) with the least LDH release of 4%. In stability studies conducted for six months, F5 was found to remain stable regarding physicochemical characteristics and drug release profile at different temperature conditions such as room temperature, 4 °C, and 45 °C. The use of folic acid-functionalized nanoparticles is more effective, according to parasitemia, survival rate, and weight loss in mice treated with the nanoparticles. This is because functionalized nanoparticles could be used to enhance anti-malarial therapies.

Increased Lipocalin 2 detected by RNA sequencing regulates apoptosis and ferroptosis in COPD

BackgroundChronic obstructive pulmonary disease (COPD) is a complex respiratory condition influenced by environmental and genetic factors. Using next-generation sequencing, we aimed to identify dysregulated genes and potential therapeutic targets for COPD.MethodsPeripheral blood leukocyte RNA profiles from COPD patients and healthy controls were analyzed using next-generation sequencing. Key genes involved in COPD pathogenesis were identified through protein–protein interaction network analysis. In vitro, bronchial epithelial cells treated with cigarette smoke extract (CSE) were used to study the effects on gene expression, cell viability, apoptosis, and ferroptosis. Additionally, Lipocalin 2 (LCN2) inhibition experiments were conducted to elucidate its role in COPD-related cellular processes.ResultsAnalysis of RNA profiles revealed consistent downregulation of 17 genes and upregulation of 21 genes across all COPD groups. Among these, Cathelicidin Antimicrobial Peptide(CAMP), Defensin Alpha 4(DEFA4), Neutrophil Elastase(ELANE), LCN2 and Lactotransferrin(LTF) were identified as potentially important players in COPD pathogenesis. Particularly, LCN2 exhibited a close association with COPD and was found to be involved in cellular processes. In vitro experiments demonstrated that CSE treatment significantly increased LCN2 expression in bronchial epithelial cells in a concentration-dependent manner. Moreover, CSE-induced apoptosis and ferroptosis were observed, along with alterations in cell viability, Glutathione content, Fe2 + accumulation, ROS: Reactive Oxygen Species and Malondialdehyde levels, Lactate Dehydrogenase(LDH) release and Glutathione Peroxidase 4(GPX4) expression. Inhibition of LCN2 expression partially reversed these effects, indicating the pivotal role of LCN2 in COPD-related cellular processes.ConclusionOur study identified six candidate genes: CAMP, DEFA4, ELANE, LCN2, and LTF were upregulated, HSPA1B was downregulated. Notably, LCN2 emerges as a significant biomarker in COPD pathogenesis, exerting its effects by promoting apoptosis and ferroptosis in bronchial epithelial cells.

Prognostic potential of standard laboratory parameters in patients with metastatic renal cell cancer receiving first-line immunotherapy

Through their involvement in cancer metabolism, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) reflect the tumor burden and thus could have a prognostic potential for patients treated with immune checkpoint inhibitors (CPI). Therefore, this study investigated the prognostic potential of these parameters in a real-world cohort of patients with metastatic renal cell cancer (mRCC) under first-line CPI-based therapy. The retrospective study cohort included 82 mRCC patients treated with CPI-based first-line therapy between 2019 and 2023. Progression-free survival (PFS), overall survival (OS) and response rates were evaluated according to baseline levels and early dynamic changes of ALAT, ASAT, GGT and LDH. Multivariate Cox proportional hazard regression models were generated to identify independent prognosticators for PFS and OS. High baseline levels and non-normalized kinetics of ALAT, ASAT, GGT and LDH were significantly associated with shorter PFS and OS (p < 0.05), which was also reflected by lower response rates. Combining the four parameters at baseline into a 4-Risk-Score resulted in an enhanced prognostic power, as indicated by a higher C-index of 0.693 for OS compared to the individual parameters (≤ 0.663). Patients with all four risk factors present showed the worst PFS and OS. Overall, baseline levels and early kinetics of the four parameters as well as the 4-Risk-Score were identified as independent prognosticators for PFS and OS by multivariate analysis. As standard laboratory parameters, ALAT, ASAT, GGT and LDH are cost-effective and could be easily used either alone or in combination for therapy monitoring of CPI-treated mRCC patients.

The Synergistic Effect of Intradialytic Concurrent Training and Melatonin Supplementation on Oxidative Stress and Inflammation in Hemodialysis Patients: A Double-Blind Randomized Controlled Trial

Background: This study aimed to investigate the effects of intradialytic concurrent (resistance–endurance) training combined with melatonin (MEL) supplementation on oxidative stress, inflammation, and cellular damage in hemodialysis (HD) patients. Methods: Thirty-two HD patients were randomly assigned to three groups: Exercise (EX)-MEL, EX-Placebo (PLA), and Control (C)-PLA. Participants in the EX-MEL and EX-PLA groups underwent 12 weeks of concurrent training. Before nocturnal sleep, they ingested either 3 mg of MEL (EX-MEL) or a placebo (EX-PLA and C-PLA). Blood samples were collected at baseline and after 12 weeks of intervention to assess lipid peroxidation [malondialdehyde (MDA)], antioxidant biomarkers [ferric-reducing antioxidant power (FRAP), reduced glutathione (GSH), total thiol (THIOL)], total bilirubin (TBIL), uric acid (UA), biomarkers of muscle and liver damage [aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), creatine kinase (CK), lactate dehydrogenase (LDH), and Gamma-glutamyltransferase (Gamma-GT)], and inflammation [C-reactive protein (CRP)]. Results: EX-MEL demonstrated a decrease in MDA (p &lt; 0.05) and CRP (p &lt; 0.05), and an increase in FRAP (p &lt; 0.05) pre- and post-training. Both EX-MEL and EX-PLA showed an increase in GSH (p &lt; 0.001, and p &lt; 0.05, respectively) and THIOL (p &lt; 0.01, and p &lt; 0.05, respectively) pre- and post-training. No significant changes were observed in TBIL, UA, ASAT, ALAT, CK, LDH, or Gamma-GT pre- and post-training across all groups. Conclusion: Concurrent training combined with MEL supplementation enhances oxidant–antioxidant balance and reduces inflammation in HD patients more effectively than intradialytic concurrent training alone.

Diagnostic accuracy of bone marrow blood evaluation in haemophagocytic lymphohistiocytosis paediatric patients.

Haemophagocytic lymphohistiocytosis (HLH) is a rare and serious immunological syndrome that involves a strong activation of cytotoxic T lymphocytes and macrophages. HLH determines a cytokine-mediated tissue injury with a contemporary multi-organ failure and a high fatality rate. A retrospective study was performed considering the medical records of paediatric patients who underwent a bone marrow aspirate for suspect HLH. The biomarkers evaluated were among those included in the HLH-2004. Lactate dehydrogenase (LD) was also evaluated. Haemophagocytosis was evaluated in bone marrow blood smear slides. Enrolled were 11 patients included in the HLH group and 8 patients as controls. Haemoglobin and fibrinogen resulted lower in HLH patients than in controls, while blood triglycerides, serum ferritin and LD resulted increased. Blood triglycerides and fibrinogen discriminated HLH cases perfectly, with a sensitivity and specificity of 100%. Ferritin had a sensitivity of 100% and a specificity of 83% (cut off ≥3,721µg/L) and LD of 73% and of 100% (the cut off ≥1,903U/L). Haemoglobin was found to have a sensitivity of 75% and a specificity of 100% (cut off ≤ 96g/L). Total haemophagocytes cell counts were not different between patients and controls. Only the increased number of phagocytized nucleated red blood cells (NRBC) was found to be significantly increased in the patients. Erythrocytes phagocytosis (≥4/1,000 cells) only tended towards significance. The blood biomarkers showed better diagnostic performance than the morphological evaluation. Among the different cell lineages engulfed by haemophagocytes, the best diagnostic performance was obtained by phagocytosed mature erythrocytes and immature nucleated erythrocytes.

Mitigating effects of agmatine on myocardial infarction in rats subjected to isoproterenol.

Isoproterenol (ISO) usage is limited by its potential for cardiotoxicity. We sought to investigate the potential of agmatine in mitigating ISO-induced cardiotoxicity. Agmatine (100mg/kg/day) was intraperitoneally administered to Wistar rats for 7days in the presence or absence of cardiotoxicity induced by subcutaneous injection of ISO (85mg/kg) on the sixth and seventh days. ECG parameters, lactate dehydrogenase (LDH), malondialdehyde (MDA), and creatinine phosphokinase (CPK) were investigated. Changes in cardiac tissue were also investigated using H&E staining. The heart weight/body weight ratio increased in ISO-treated rats. In the agmatine + ISO group, the increased heart rate observed in ISO-treated rats was reversed (317.2 ± 10.5 vs 452.2 ± 10.61, P < 0.001). Agmatine ameliorated the change in PR, RR, and ST intervals and the QRS complex, which was reduced by ISO. Treatment with saline, ISO, and agmatine had no significant effect on papillary muscle stimulation (P > 0.05). The administration of agmatine to ISO-receiving group could mitigate several parameters when compared to ISO-receiving group including increasing papillary muscle contraction (0.83 vs 0.71 N/M2 respectively, P < 0.01), decreasing LDH levels (660ng/ml vs 1080ng/ml, respectively, P < 0.05), decreasing CPK levels (377 U/l vs 642 U/l, respectively, P < 0.05) and decreasing MDA levels (20.32µM/l vs 46.83µM/l, P < 0.001). Coadministration of agmatine and ISO is capable of ameliorating ISO cardiotoxicity by antioxidant effects and controlling the hemostasis of calcium in myocytes.

Orange peel ethanolic extract and physical exercise prevent testicular toxicity in streptozocin and high fat diet-induced type 2 diabetes rats via Nrf2/NF-kB signaling: In silico and in vivo studies

BackgroundType 2 diabetes mellitus (T2DM) is a significant health issue affecting the quality of life including male reproductive functions. Orange peel ethanolic extract (OPEE) has been established to have antioxidant properties and has been shown to alleviate diabetic complications. This study determined to establish OPEE effect and physical exercise (EX) in T2DM-induced testicular dysfunction. Materials and methodsThirty male Wistar rats were randomly distributed in five groups as follows: control group (received 1 ml/b.w of normal saline), and groups 2–5 were induced with diabetes, with group 2 left untreated, group 3 received 600 mg/kg b.w OPEE, group 4 was subjected to EX while group 5 was treated with OPEE alongside EX. ResultsOPEE + EX ameliorated T2DM-induced decrease in sperm motility, count, and morphology and increased testicular lactate dehydrogenase, alkaline phosphate, gamma-glutamyl transferase, and lactate. T2DM-induced disruption of gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone and, testosterone was also mitigated by OPEE + EX. In addition, OPEE + EX blunted T2DM-induced increase in oxidative stress, inflammatory, and apoptotic markers and the accompanied decrease in testicular nuclear factor erythroid 2–related factor 2 (Nrf2) and increase in nuclear factor kappa B (NF-κB). Also, OPEE + EX reversed T2DM-induced testicular histology distortion. ConclusionsThe outcome of this study revealed that the combination of OPEE and EX ameliorated T2DM-mediated testicular damage via Nrf2/NF-κB signaling.

Behavioral and biochemical effects of environmental concentrations of caffeine in zebrafish after long-term exposure

Caffeine (CAF) is widely detected in aquatic environments, serving as an indicator of anthropogenic contamination. Its high consumption, and persistence raise environmental concerns. This study was to evaluate the chronic effects in terms of growth rate, weight, behavior, and biochemical parameters of environmental concentrations of CAF on adult zebrafish. Adult zebrafish were exposed, for 30 d, to 0, 0.5, 1.5, and 300 µg L−1 CAF, with behavior (feeding latency, exploration, aggression, sociability, sound response) and biochemical endpoints (acetylcholinesterase (AChE), lactate dehydrogenase (LDH), and cortisol levels) assessed at the end of the exposure. CAF 0.5 µg L−1 increased feeding latency time, while 300 µg L−1 reduced growth and weight. Exposure to CAF affect fish behavior in terms of vertical exploration, aggressiveness, shoaling, and sound responses although were concentration specific. All concentrations tested increased social behavior, with fish swimming closer to the shoal. At a biochemical level, CAF exposed showed reduced AChE activity, while LDH activity, and cortisol levels increased at 300 µg L−1. Low concentrations of CAF caused neurotoxicity in zebrafish which may compromise their feeding behavior, and social interactions in the wild. These changes suggest potential ecological impacts of chronic exposure to CAF, such as impaired feeding and stress responses.

Evaluation of protective potency of coconut oil-based probiotic against antibiotic-induced compromised gastrointestinal attributes and associated complications in Swiss albino mice

Background: Antibiotic-induced gastrointestinal toxicity is a major concern globally. The gut-organ axis has been explicitly studied, and hence, any damage to the gut ecosystem directly or indirectly manifests into compromised multi-organ functions. Therefore, the present study was designed to explore the protective potency of coconut oil-probiotic (C-PRO) against antibiotic-induced compromised gastrointestinal attributes and associated complications. Methods: Animals were divided into 5 groups (n=6). Normal saline was given to the control group; the antibiotic cocktail was given to the antibiotic group. In the treatment group, low and high doses of C-PRO were given post-antibiotic treatment. In the per se group, only a high dose of C-PRO was given. After 28 days, animals were studied for neurobehavioral parameters and scarified. Blood and organs were collected and stored for histopathological, immune histochemical, and biochemical analysis. Results: Antibiotic treatment reduced body weight, increased oxidative stress, and caused histopathological damage to the stomach, duodenum, colon, brain, heart, liver, lungs, kidney, spleen, and testis. It also altered biochemical parameters such as lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), albumin, creatinine, urea, uric acid, and blood urea nitrogen (BUN). Additionally, Antibiotic exposure in mice exhibited depressive-like behaviour and declined cognitive function. The treatment with a low dose of C-PROs showed negligible protective effect, whereas a high dose of C-PRO effectively reversed the structural, biochemical, and neurobehavioral attributes toward normal. Conclusions: We conclude that the synergistic effect of coconut oil and probiotics, which have potent antioxidant and anti-inflammatory effects, might be responsible for multidimensional protective effects against compromised gastrointestinal attributes and associated complications.

New tumor markers for testicular cancer - in the here and now and in the future

Germ cell tumors of the testis are the most common tumor entities in young men. Since the introduction of platinum-based chemotherapy in the 1970s, most patients can be cured despite the aggressiveness of germ cell tumors. Optimal serum tumor markers are required for diagnostics, therapy monitoring and aftercare, and these are subject to high requirements. The conventional testicular tumor markers human chorionic gonadotropin (hCG), alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) only meet these requirements with insufficient sensitivity (30-70%). The markers investigated in recent decades, such as PLAP, CEA and NSE, have not become established. Currently, miRNA-371 is being researched in particular. Reliable findings are available for initial staging with significantly better specificities of miRNA-371 compared to conventional tumor markers. Further prospective studies are being conducted for other possible clinical applications, such as follow-up care, therapy monitoring or residual tumors, in order to investigate the revolutionary potential of miRNA-371 in these areas as well. Research is also currently being conducted on circulating tumor cells (CTCs) and cell-free DNA (cfNA) in various areas of application. With regard to germ cell tumors of the testis, however, these analyses are still in their infancy, but it is hoped that this will provide a further sufficient opportunity to use serum tumor markers.