A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed ...that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.
The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for ...the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.
Background/Aim. The prognostic impact of complete atrioventricular (AV) block on the long-term prognosis of patients with ST-elevation myocardial infarction (STEMI) has not been fully determined. The ...aim of the study was to analyze the incidence and prognostic impact of complete AV block on in-hospital mortality (IHM) and 6-year mortality in STEMI patients treated with primary percutaneous coronary intervention. Methods. The study included 3,044 consecutive STEMI patients. Results. Complete AV block was registered only on admission in 144 (4.73%) patients; 125 (86.8%) patients with complete AV block had inferior infarction. A temporary pacemaker was implanted in 72 (50%) patients with complete AV block. No patient under-went permanent pacemaker implantation. IHM was significantly higher in patients with complete AV block than in patients without complete A V b lock: 1 7.9% v s. 3 .6%, respectively, p < 0.001. In patients with heart block and inferior infarction, IHM was 13%, whereas IHM was 53% in patients with heart block and anterior infarction. When we analyzed patients discharged alive from the hospital, we also found a significantly higher long-term (6-year) mortality rate in those with complete AV block vs. patients without AV block: 7.8% vs. 3.4%, respectively, p < 0.001. Complete AV block was an independent predictor for IHM and 6-year mortality: IHM odds ratio (OR) 2.94 95%, confidence interval (CI) 1.23?5.22; 6-year mortality hazard ratio (HR) 1.61, 95%, CI 1.10?2.37. When subanalysis was performed in patients with inferior STEMI, complete AV block was an independent predictor of IHM and 6 -year mortality, while in patients with anterior STEMI, complete AV block was an independent predictor of IHM. Conclusion. In analyzed STEMI patients, complete AV block was transitory and was registered only on hospital admission. Although transitory, complete AV block remained a strong independent predictor of IHM and long-term mortality.
Sepsis is a life-threatening condition caused by the dysregulated and overwhelming response to infection, accompanied by an exaggerated pro-inflammatory state and lipid metabolism disturbance leading ...to sequential organ failure. Meldonium is an anti-ischemic and anti-inflammatory agent which negatively interferes with lipid metabolism by shifting energy production from fatty acid oxidation to glycolysis, as a less oxygen-demanding pathway. Thus, we investigated the effects of a four-week meldonium pre-treatment on faecal-induced sepsis in Sprague-Dawley male rats. Surprisingly, under septic conditions, meldonium increased animal mortality rate compared with the meldonium non-treated group. However, analysis of the tissue oxidative status did not provide support for the detrimental effects of meldonium, nor did the analysis of the tissue inflammatory status showing anti-inflammatory, anti-apoptotic, and anti-necrotic effects of meldonium. After performing tissue lipidomic analysis, we concluded that the potential cause of the meldonium harmful effect is to be found in the overall decreased lipid metabolism. The present study underlines the importance of uninterrupted energy production in sepsis, closely drawing attention to the possible harmful effects of lipid-mobilization impairment caused by certain therapeutics. This could lead to the much-needed revision of the existing guidelines in the clinical treatment of sepsis while paving the way for discovering new therapeutic approaches.
Estrogen signaling plays an important role in pituitary development and function. In sensitive rat or mice strains of both sexes, estrogen treatments promote lactotropic cell proliferation and induce ...the formation of pituitary adenomas (dominantly prolactin or growth-hormone-secreting ones). In male patients receiving estrogen, treatment does not necessarily result in pituitary hyperplasia, hyperprolactinemia or adenoma development. In this review, we comprehensively analyze the mechanisms of estrogen action upon their application in male animal models comparing it with available data in human subjects. Sex-specific molecular targets of estrogen action in lactotropic (PRL) cells are highlighted in the context of their proliferative and secretory activity. In addition, putative effects of estradiol on the cellular/tumor microenvironment and the contribution of postnatal pituitary progenitor/stem cells and transdifferentiation processes to prolactinoma development have been analyzed. Finally, estrogen-induced morphological and hormone-secreting changes in pituitary thyrotropic (TSH) and adrenocorticotropic (ACTH) cells are discussed, as well as the putative role of the thyroid and/or glucocorticoid hormones in prolactinoma development, based on the current scarce literature.
Hyperglycemia has detrimental effect on ischemic myocardium, but the impact of acute hyperglycemia on the myocardium in asymptomatic diabetic patients has not been fully elucidated. Thus, this ...follow-up study was aimed to investigate the effects and reversibility of acute hyperglycemia on regional contractile function of left ventricle (LV) in diabetic patients without cardiovascular disease.
The two-dimensional speckle tracking echocardiography (2D-STE), including multilayer strain analysis, was used for evaluation of global and regional LV function in asymptomatic, normotensive patients with uncomplicated diabetes, with acute hyperglycemia ( ≥ 11.1 mmol/l) (Group A, n = 67), or with optimal metabolic control (fasting plasma glucose < 7 mmol/l and HbA1c < 7%) (Group B, n = 20), while 20 healthy individuals served as controls (Group C). In group A, after 72 h of i.v. continuous insulin treatment (at the time euglycemia was achieved) (second examination) and after 3 months following acute hyperglycemia (third examination) 2D-STE was repeated.
Global longitudinal strain (GLS) (- 19.6 ± 0.4%) in Group A was significantly lower in comparison to both groups B (- 21.3 ± 0.4%; p < 0.05) and C (- 21.9 ± 0.4%; p < 0.01) at baseline, while we could not detect the differences between groups B and C. Peak systolic longitudinal endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) layer strain were significantly lower in group A at baseline compared to both groups B and C. Deterioration in peak systolic circumferential strain was observed at basal LV level, in all three layers (Endo, Mid and Epi) and in mid-cavity LV level in Epi layer in group A in comparison to group C. Moreover, in group A, after euglycemia was achieved (at second and third examination) GLS, as well as peak longitudinal and circumferential strain remain the same.
Acute hyperglycemia in asymptomatic diabetic patients has significant negative effects on systolic LV myocardial mechanics primarily by reducing GLS and multilayer peak systolic longitudinal and circumferential strain which was not reversible after three months of good glycemic control.
Differences in pathophysiology, clinical presentation, and natural course of ST-elevation myocardial infarction in female patients due to either spontaneous dissection (SCAD-STEMI) or ...atherothrombotic occlusion (type 1 STEMI) have been discussed. Current knowledge on differences in left ventricular myocardial function and infarct size is limited. The aim of this study was to assess baseline clinical characteristics, imaging findings, and therapeutic approach and to compare differences in echocardiographic findings at baseline and 3-month follow-up in patients with SCAD-STEMI and type 1 STEMI.
This was a prospective multicenter study of 32 female patients (18-55 years of age) presenting with either SCAD-STEMI due to left anterior descending coronary artery (LAD) dissection or type 1 STEMI due to atherothrombotic LAD occlusion.
The two groups were similar in age, risk factors, comorbidities, and complications. SCAD-STEMI patients more often had Thrombolysis in Myocardial Infarction 3 flow, while type 1 STEMI patients were more often treated with percutaneous coronary intervention and dual antiplatelet therapy. Baseline mean left ventricular (LV) ejection fraction (LVEF) was similar in the two groups (48.0% vs. 48.6%,
= 0.881), but there was a significant difference at the 3-month follow-up, driven by an improvement in LVEF in SCAD-STEMI compared to type 1 STEMI patients (Δ LVEF 10.1 ± 5.3% vs. 1.8 ± 5.1%,
= 0.002). LV global longitudinal strain was slightly improved in both groups at follow-up; however, the improvement was not significantly different between groups (-4.6 ± 2.9% vs. -2.0 ± 2.8%,
= 0.055).
The results suggest that female patients with SCAD-STEMI are more likely to experience improvement in LV systolic function than type 1 STEMI patients.
Silicosis is a prevalent incurable pneumoconiosis caused by inhalation of silica dust. Study aimed to investigate inflammatory, hematological, and biochemical parameters as additional biomarkers for ...diagnosing or monitoring silicosis.
Research enrolled 14 workers with silicosis and 7 healthy controls (without exposure and silicosis). The serum level of prostaglandin E2, C-reactive protein, fibrinogen, biochemical, and hematological parameters were measured. The receiver operating characteristic curve was used to determine diagnostic sensitivity of each biomarker.
Patients with silicosis have a significantly higher level of prostaglandin E2, erythrocyte, hemoglobin, and hematocrit than patients without silicosis. Prostaglandin E2, hemoglobin, and the erythrocyte count are significant in separating the silicosis cases from healthy controls.
Prostaglandin E2 might be an adjuvant peripheral diagnostic biomarker for silicosis, while hematological parameters (erythrocytes, hemoglobin, and hematocrit) might be prognostic biomarkers.
Nanoparticles (NPs), a distinct class of particles ranging in size from 1 to 100 nm, are one of the most promising technologies of the 21st century, and titanium dioxide NPs (TiO2 NPs) are among the ...most widely produced and used NPs globally. The increased application of TiO2 NPs raises concerns regarding their global safety and risks of exposure. Many animal studies have reported the accumulation of TiO2 NPs in female reproductive organs; however, evidence of the resultant toxicity remains ambiguous. Since the surface area and chemical modifications of NPs can significantly change their cytotoxicity, we aimed to compare the toxic effects of pristine TiO2 powder with surface-modified TiO2 powders with salicylic acid (TiO2/SA) and 5-aminosalicylic acid (TiO2/5-ASA) on the ovaries, oviducts, and uterus on the 14th day following acute oral treatment. The results, based on alterations in food and water intake, body mass, organ-to-body mass ratio, hormonal status, histological features of tissues of interest, and antioxidant parameters, suggest that the modification with 5-ASA can mitigate some of the observed toxic effects of TiO2 powder and encourage future investigations to create NPs that can potentially reduce the harmful effects of TiO2 NPs while preserving their positive impacts.
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