Jaspers’s Struggle for the Idea of the University

The aim of the study presented here is to show that Jasper’s idea of university is intended to present a defence of philosophical life of a university against its reduction to a merely utilitarian concept. Jaspers follows up on the enlightened role of philosophy within university education and develops it in the conditions of the dark twentieth century. He views philosophical life as a precondition for preserving university as a place of a close bond between science and humanity, which turned out to be much needed at a time of the rise of Nazism in Germany. The study shows the crucial importance of philosophy, science and education in Jaspers' thought for the preservation of a free university. This study shows, within a historical context, the restoration of university in democratic conditions after the end of the Nazi Era.Celem prezentowanego tu studium jest pokazanie, że Jaspersowska koncepcja uniwersytetu ma na celu obronę filozoficznego życia uniwersytetu przed jego redukcją do koncepcji czysto utylitarnej. Jaspers kontynuuje oświeceniową rolę filozofii w ramach edukacji uniwersyteckiej i rozwija ją w warunkach mrocznego XX wieku. Postrzega życie filozoficzne jako warunek zachowania uniwersytetu jako miejsca ścisłej więzi między nauką a ludzkością, która okazała się bardzo potrzebna w czasach wzrostu nazizmu w Niemczech. Studium pokazuje kluczowe znaczenie filozofii, nauki i edukacji w myśli Jaspersa dla zachowania wolnego uniwersytetu. Studium to ukazuje, w kontekście historycznym, odbudowę uniwersytetu w warunkach demokratycznych po zakończeniu ery nazistowskiej

Incretin-Based Therapies Role in COVID-19 Era: Evolving Insights

The current coronavirus disease 2019 (COVID-19) pandemic has led the scientific community to breach new frontiers in the understanding of human physiology and disease pathogenesis. It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection. Diabetes is associated with increased COVID-19 severity and mortality, and accumulating evidence suggests that IBTs may favorably alter the clinical course of SARS-CoV-2 infection due to their inherent mechanisms of action. Further research into prognostic variables associated with various antidiabetic treatment regimens, and in particular the IBT, in patients with T2DM affected by the COVID-19 pandemic is therefore warranted

Concomitant iGlarLixi and Sodium-Glucose Co-transporter-2 Inhibitor Therapy in Adults with Type 2 Diabetes: LixiLan-G Trial and Real-World Evidence Results

Introduction: iGlarLixi, the once-daily fixed-ratio combination of insulin glargine 100 U/ml and lixisenatide, robustly improves glycaemic control in adults with type 2 diabetes irrespective of previous treatment [oral antihyperglycaemic drugs (OADs), basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs)]. Sodium-glucose co-transporter-2 inhibitors (SGLT2is) are a recommended treatment option for people with type 2 diabetes with cardiovascular disease, kidney disease and/or heart failure because of their cardio- and renoprotective benefits. Herein, we assessed the effects of concomitant iGlarLixi and SGLT2i therapy. Methods: We conducted subgroup analyses according to SGLT2i use in: (1) adults with suboptimally controlled type 2 diabetes on GLP-1 RAs and OADs switching to iGlarLixi in the 26-week LixiLan-G randomised controlled trial (RCT; NCT02787551) and (2) adults switching to or adding iGlarLixi in a 6-month, retrospective real-world evidence (RWE) observational study using data from the US Optum-Humedica electronic medical records database. Changes in HbA1c and hypoglycaemia prevalence and event rates were assessed. Results: There were no major differences in baseline characteristics for those who initiated iGlarLixi while already using SGLT2i (n = 346) and those initiating iGlarLixi without concomitant SGLT2i therapy (n = 1285). HbA1c reductions from baseline to time of assessment and hypoglycaemia prevalence and event rates were similar for iGlarLixi users regardless of SGLT2i therapy. Conclusion: Evidence from an RCT and an RWE analysis supports the efficacy/effectiveness and safety of iGlarLixi when used concomitantly with SGLT2i. Trial Registration: NCT02787551

Measurement of HNE-protein adducts in human plasma and serum by ELISA-Comparison of two primary antibodies

There is increasing evidence that non-enzymatic post-translational protein modifications might play key roles in various diseases. These protein modifications can be caused by free radicals generated during oxidative stress or by their products generated during lipid peroxidation. 4-Hydroxynonenal (HNE), a major biomarker of oxidative stress and lipid peroxidation, has been recognized as important molecule in pathology as well as in physiology of living organisms. Therefore, its detection and quantification can be considered as valuable tool for evaluating various pathophysiological conditions.The HNE-protein adduct ELISA is a method to detect HNE bound to proteins, which is considered as the most likely form of HNE occurrence in living systems. Since the earlier described ELISA has been validated for cell lysates and the antibody used for detection of HNE-protein adducts is non-commercial, the aim of this work was to adapt the ELISA to a commercial antibody and to apply it in the analysis of human plasma samples.After modification and validation of the protocol for both antibodies, samples of two groups were analyzed: apparently healthy obese (n=62) and non-obese controls (n=15). Although the detected absolute values of HNE-protein adducts were different, depending on the antibody used, both ELISA methods showed significantly higher values of HNE-protein adducts in the obese group

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Vysetreni kozni mikrocirkulace laser-Dopplerem pri diabetes mellitus a pri deficitu rustoveho hormonu.

Very important result obtained in current study is the finding of statistically significant negative inverse relationship between parameters of diabetes control and the microvascular reactivity and the fact that no relationship was observed between microvascular function and diabetes duration. Unsatisfactory diabetes control is thus probably one of the most important factors contributing to diabetic angiopathy. Good diabetes control is necessary for the prevention of serious vascular complications without respect to the duration of the disease. The combination of examinations of biochemical markers of endothelial dysfunction and microvascular reactivity by laser-Doppler fluxmetry can be easy and non-invasive method for diagnostic of early microangiopathic changes in diabetic patients. It is not well known in what order are appearing changes in microvascular bed detectable by laser-Doppler and endothelial dysfunction or morphologic changes in vessel wall. Further research will be necessary to resolve the time consequence of these disorders and its information value especially with respect to the risk of vessel complications. The results of this research support the hypothesis that the system of IGF-I and its binding proteins contributes to the development of vessel impairment in Type 1 diabetic patients. The elevated concentration of free-IGF-I in Type 1 diabetes has probably promoting effect while IGFBP-1 plays protective role in the vascular damage. In patient with growth hormone deficiency without therapy the microvascular reactivity is significantly decreased in comparison to healthy persons. It is known that during growth hormone therapy the reactivity of large vessels improves and the regression of atherosclerotic changes occurs. In our study we have proved that during therapy the microvascular reactivity is completely normalized. The effect of growth hormone substitution is probably complex and one of the most important ways it improves microvascular function is its stimulation of NO-synthase. The studies using laser-Doppler fluxmetry in Type 1 diabetic patients and in patients with growth hormone deficiency were performed for the first time in Czech republic. They show the possible implementation of laser-Doppler in diabetology and endocrinology. The resulkt gained in this research are not only comparable with results of similar studies performed abroad, but they bring also new findings and especially the results of the studies of the influence of growth hormone and of the IGF-I system on microvascular function measured by lasser Doppler are quite unique.Summary in EnglishAvailable from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Nektere imunologicke aspekty u diabetes mellitus 1. typu a pridruzenych autoimunit.

Type 1 diabetes mellitus is an autoimmune disease and can be associated with other autoimmune endocrine disorders and also with autoimmune impairment of a non-endocrine tissue. In this work we studied specific antibodies against islet antigens - glutamic acid decarboxylase, protein thyrosine phosphatase IA-2?, against thyroid autoantigens - thyroid microsomal peroxidase, thyroglobulin, autoantigens of small bowel - endomysial autoantibodies, tissue transglutaminase autoantibodies, antibodies against gliadin in class IgA (AGA-IgA) and IgG (AGA-IgG), and adrenal cortex antibodies in a cohort of Type 1 diabetic patients. The autoantibodies were detected with special regard to the clinical status and with the aim to detect subclinically associated autoimmune thyroid disease, celiac disease and Addison's disease.Parts of the text in English.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome. ----- RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. ----- RESULTS: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. ----- CONCLUSION: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome