BACKGROUND: Following the broad application of new analytical methods, more and more pathophysiological processes in previously unknown diseases have been elucidated. The spectrum of clinical presentation of rare inherited metabolic diseases (IMDs) is broad and ranges from single organ involvement to multisystemic diseases. With the aim of overcoming the limited knowledge about the natural course, current diagnostic and therapeutic approaches, the project has established the first unified patient registry for IMDs that fully meets the requirements of the European Infrastructure for Rare Diseases (ERDRI). RESULTS: In collaboration with the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), the Unified European registry for Inherited Metabolic Diseases (U-IMD) was established to collect patient data as an observational, non-interventional natural history study. Following the recommendations of the ERDRI the U-IMD registry uses common data elements to define the IMDs, report the clinical phenotype, describe the biochemical markers and to capture the drug treatment. Until today, more than 1100 IMD patients have been registered. CONCLUSION: The U-IMD registry is the first observational, non-interventional patient registry that encompasses all known IMDs. Full semantic interoperability for other registries has been achieved, as demonstrated by the use of a minimum common core data set for equivalent description of metabolic patients in U-IMD and in the patient registry of the European Rare Kidney Disease Reference Network (ERKNet). In conclusion, the U-IMD registry will contribute to a better understanding of the long-term course of IMDs and improved patients care by understanding the natural disease course and by enabling an optimization of diagnostic and therapeutic strategies.

• Klíčová slova
• ERDRI, European infrastructure for rare diseases, European reference network for rare hereditary metabolic disorders, Inherited metabolic diseases, MetabERN, U-IMD, Unified european registry for inherited metabolic diseases,
• MeSH
• lidé MeSH
• metabolické nemoci * genetika   MeSH
• registrace MeSH
• vzácné nemoci genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.

• Klíčová slova
• berberine, cardiovascular diseases, metabolic diseases, targets, therapeutics,
• MeSH
• berberin farmakologie   terapeutické užití   MeSH
• kardiovaskulární nemoci farmakoterapie   MeSH
• kardiovaskulární systém účinky léků   MeSH
• lidé MeSH
• metabolické nemoci farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• berberin MeSH

Background: Women with gestational diabetes (GDM) have an increased risk of metabolic syndrome (MS) after delivery. MS could precede gravidity. The aims of this study were (i) to detect the prevalence of MS in women at the time of GDM diagnosis, (ii) to detect the prevalence of MS in the subgroup of GDM patients with any form of impaired glucose tolerance after delivery (PGI), and (iii) to determine whether GDM women with MS have a higher risk of peripartal adverse outcomes. Methods: A cross-sectional observational study comprised n = 455 women with GDM. International Diabetes Federation (IDF) criteria for MS definition were modified to the pregnancy situation. Results: MS was detected in 22.6% of GDM patients in those with PGI 40%. The presence of MS in GDM patients was associated with two peripartal outcomes: higher incidence of pathologic Apgar score and macrosomia (p = 0.01 resp. p = 0.0004, chi-square). Conclusions: The presence of MS in GDM patients is a statistically significant risk factor (p = 0.04 chi-square) for PGI. A strong clinical implication of our findings might be to include MS diagnostics within GDM screening using modified MS criteria in the second trimester of pregnancy.

• Klíčová slova
• gestational diabetes mellitus, metabolic syndrome, oral glucose tolerance test, postpartum glucose intolerance, pregnancy,
• Publikační typ
• časopisecké články MeSH

External quality assurance (EQA) is crucial to monitor and improve the quality of biochemical genetic testing. ERNDIM (www.erndim.org), established in 1994, aims at reliable and standardized procedures for diagnosis, treatment and monitoring of inherited metabolic disease (IMD) by providing EQA schemes and educational activities. Currently, ERNDIM provides 16 different EQA schemes including quantitative schemes for various metabolite groups, and interpretive schemes such as diagnostic proficiency testing (DPT). DPT schemes focus on the ability of laboratories to correctly identify and interpret abnormalities in authentic urine samples across a wide range of IMDs. In the DPT schemes, six samples each year are distributed together with clinical information. Laboratories choose and perform the tests needed to reach a diagnosis. Data were collected on 345 samples, distributed to up to 105 laboratories worldwide. Diagnostic proficiency (the % of total points possible for all participating laboratories within a scheme for analysis and interpretation) ranged widely: amino acid disorders (n = 20), range 33%-100%, mean 84%; organic acid disorders (n = 35), range 14%-100%, mean 84%; lysosomal storage disorders (n = 13), range 20%-97%, mean 73%; purine/pyrimidine disorders (n = 9), range 37%-100%, mean 70%; miscellaneous disorders (n = 8), range 17%-100%, mean 65%; no IMD, range 65%-95%, mean 85%. When a sample with the same disorder was distributed in a subsequent survey, performance improved in 75 cases with no improvement seen in 32, suggesting overall improvement of performance. ERNDIM diagnostic proficiency testing is a valuable activity which can help to assess laboratory performance, identify methodological/technical challenges, be informative during quality audits and contribute to a better clinical appreciation of diagnostic uncertainty.

• Klíčová slova
• ERNDIM, diagnostic testing, external quality assurance, inborn error of metabolism, inherited metabolic disease, proficiency,
• MeSH
• diagnostické techniky a postupy MeSH
• laboratoře MeSH
• lidé MeSH
• lyzozomální nemoci z ukládání * MeSH
• metabolické nemoci * diagnóza   genetika   moč   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In addition to the main groups of inherited metabolic diseases, including mitochondrial, peroxisomal and lysosomal defects, organic acidurias, porphyrias, defects of amino acids, saccharides and fatty acids metabolism, disorders of transport and utilisation of microelements have also been recognized. Recent findings concerning hereditary hemochromatosis (iron), Wilson and Menkes diseases (copper), molybdenum cofactor deficiency (molybdenum), defects of cobalamine synthesis (cobalt) and acrodermatitis enteropathica (zinc) are reviewed.

• MeSH
• kobalt metabolismus   MeSH
• lidé MeSH
• měď metabolismus   MeSH
• molybden metabolismus   MeSH
• poruchy metabolismu železa diagnóza   genetika   terapie   MeSH
• vrozené poruchy metabolismu kovů * diagnóza   genetika   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• kobalt MeSH
• měď MeSH
• molybden MeSH

The incidence and the burden of cardiovascular disease (CVD), coronary heart disease (CHD), type 2 diabetes mellitus (T2DM), and the metabolic syndrome are greatly increasing in our societies. Together, they account for 31% of all deaths worldwide. This chapter focuses on the role of two revolutionary discoveries that are changing the future of medicine, induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 technology, in the study, and the cure of cardiovascular and metabolic diseases.We summarize the state-of-the-art knowledge about the possibility of editing iPSC genome for therapeutic applications without hampering their pluripotency and differentiation, using CRISPR/Cas technology, in the field of cardiovascular and metabolic diseases.

• Klíčová slova
• Cardiovascular, Epigenetics, Gene editing, Induced pluripotent stem cells (iPSC), Metabolism,
• MeSH
• diabetes mellitus 2. typu * genetika   terapie   MeSH
• editace genu MeSH
• indukované pluripotentní kmenové buňky * MeSH
• kardiovaskulární systém * MeSH
• lidé MeSH
• metabolické nemoci * genetika   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The spectrum of cardiorenal and metabolic diseases comprises many disorders, including obesity, type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), dyslipidemias, hypertension, and associated comorbidities such as pulmonary diseases and metabolism dysfunction-associated steatotic liver disease and metabolism dysfunction-associated steatohepatitis (MASLD and MASH, respectively, formerly known as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis [NAFLD and NASH]). Because cardiorenal and metabolic diseases share pathophysiologic pathways, two or more are often present in the same individual. Findings from recent outcome trials have demonstrated benefits of various treatments across a range of conditions, suggesting a need for practice recommendations that will guide clinicians to better manage complex conditions involving diabetes, cardiorenal, and/or metabolic (DCRM) diseases. To meet this need, we formed an international volunteer task force comprising leading cardiologists, nephrologists, endocrinologists, and primary care physicians to develop the DCRM 2.0 Practice Recommendations, an updated and expanded revision of a previously published multispecialty consensus on the comprehensive management of persons living with DCRM. The recommendations are presented as 22 separate graphics covering the essentials of management to improve general health, control cardiorenal risk factors, and manage cardiorenal and metabolic comorbidities, leading to improved patient outcomes.

• MeSH
• diabetes mellitus 2. typu terapie   MeSH
• lidé MeSH
• metabolické nemoci * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH

BACKGROUND AND AIMS: Glucocorticoids and the GR serve as an essential molecular mediator of stress and different physiologic processes. This review summarizes main findings from studies on the role of the GC/GR signaling in the modulation of genes for nutrient processing by the different organs involved in metabolic diseases. METHODS: Descriptive review of relevant papers known to the author was conducted. RESULTS: Several high-throughput screenings in the past 15 years have identified potential GR DNA-binding regions in different cell types with genes that are annotated to be important for the control of metabolism. Transcriptional regulation of these GC-responsive genes provides links between the hypothalamic-pituitary-adrenal axis (HPA) and systemic energy homeostasis in both physiological and pathophysiological states. Future studies must reconsider the use of agonist, the utilization of animal models of stress and metabolic disorders, and validation in humans. CONCLUSION: This review recapitulates the significant role of the GC/GR signaling in molecular metabolic control and metabolic disorders. Potential future research focus and optimizations have also been identified.

• Klíčová slova
• Glucocorticoid receptor, Glucocorticoids, Metabolic disorders, Metabolism,
• MeSH
• fyziologický stres * MeSH
• glukokortikoidy metabolismus   MeSH
• lidé MeSH
• metabolické nemoci etiologie   metabolismus   patologie   MeSH
• signální transdukce * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glukokortikoidy MeSH

BACKGROUND: Allium sativum L., or garlic, is one of the most studied plants worldwide within the field of traditional medicine. Current interests lie in the potential use of garlic as a preventive measure and adjuvant treatment for viral infections, e.g., SARS-CoV-2. Even though it cannot be presented as a single treatment, its beneficial effects are beyond doubt. The World Health Organization has deemed it an essential part of any balanced diet with immunomodulatory properties. OBJECTIVE: The aim of the study was to review the literature on the effects of garlic compounds and preparations on immunomodulation and viral infection management, with emphasis on SARS-CoV- -2. METHODS: Exhaustive literature search has been carried out on electronic databases. CONCLUSION: Garlic is a fundamental part of a well-balanced diet which helps maintain general good health. The reported information regarding garlic's ability to beneficially modulate inflammation and the immune system is encouraging. Nonetheless, more efforts must be made to understand the actual medicinal properties and mechanisms of action of the compounds found in this plant to inhibit or diminish viral infections, particularly SARS-CoV-2. Based on our findings, we propose a series of innovative strategies to achieve such a challenge in the near future.

• Klíčová slova
• Antiviral agents, Chronic diseases, Coronavirus infection, Garlic, Immunomodulation agents, Metabolic diseases,
• MeSH
• česnek * MeSH
• farmakoterapie COVID-19 * MeSH
• imunomodulace MeSH
• lidé MeSH
• metabolické nemoci * MeSH
• rostlinné extrakty farmakologie   MeSH
• SARS-CoV-2 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• rostlinné extrakty MeSH

Bilirubin belongs to a phylogenetically old superfamily of tetrapyrrolic compounds, which have multiple biological functions. Although for decades bilirubin was believed to be only a waste product of the heme catabolic pathway at best, and a potentially toxic compound at worst; recent data has convincingly demonstrated that mildly elevated serum bilirubin levels are strongly associated with a lower prevalence of oxidative stress-mediated diseases. Indeed, serum bilirubin has been consistently shown to be negatively correlated to cardiovascular diseases (CVD), as well as to CVD-related diseases and risk factors such as arterial hypertension, diabetes mellitus, metabolic syndrome, and obesity. In addition, the clinical data are strongly supported by evidence arising from both in vitro and in vivo experimental studies. This data not only shows the protective effects of bilirubin per se; but additionally, of other products of the heme catabolic pathway such as biliverdin and carbon monoxide, as well as its key enzymes (heme oxygenase and biliverdin reductase); thus, further underlining the biological impacts of this pathway. In this review, detailed information on the experimental and clinical evidence between the heme catabolic pathway and CVD, and those related diseases such as diabetes, metabolic syndrome, and obesity is provided. All of these pathological conditions represent an important threat to human civilization, being the major killers in developed countries, with a steadily increasing prevalence. Thus, it is extremely important to search for novel markers of these diseases, as well as for novel therapeutic modalities to reverse this unfavorable situation. The heme catabolic pathway seems to fulfill the criteria for both diagnostic purposes as well as for potential therapeutical interventions.

• Klíčová slova
• UGT1A1, bilirubin, biliverdin, biliverdin reductase, cardiovascular diseases, diabetes, heme oxygenase, metabolic syndrome,
• Publikační typ
• časopisecké články MeSH