Previous reports provided recommendations for familial renal glucosuria diagnosis without complex view on differential diagnosis of glucosuria. The aim of this review was to provide an overview of the causes of glucosuria and to create an evidence-based diagnostic approach for children with glucosuria. We searched the current literature with a focus to identify the possible etiology of glucosuria, gaining insight into the pathophysiology of glucosuria. Urinary glucose is completely reabsorbed in the proximal tubule of kidneys. It only appears in the urine if the plasma glucose concentration exceeds the renal threshold for glucose or in the case of insufficient renal glucose reabsorption. The proteins that provide glucose reabsorption are SGLT2 and SGLT1 - sodium-dependent co-transporters that transport glucose from the lumen into epithelial cells - and GLUT2 - a passive transporter providing facilitative glucose transport from epithelial cells to plasma. Renal glucose reabsorption is affected in case of acquired or inherited complex dysfunction of proximal tubule called Fanconi Syndrome or due to pathogenic variants of genes encoding glucose transporters. Prior to diagnosing any of these, diabetes mellitus must be excluded together with other conditions leading to hyperglycemia. In conclusion, glucosuria is always an abnormal finding. The review provides a simple evidence-based diagnostic approach to navigate the differential diagnosis of glucosuria.

• MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• Fanconiho syndrom diagnóza   komplikace   MeSH
• glukosa * metabolismus   MeSH
• glykosurie * diagnóza   etiologie   MeSH
• lidé MeSH
• přenašeč glukosy typ 2 metabolismus   MeSH
• proximální tubuly ledvin metabolismus   MeSH
• renální glykosurie * diagnóza   etiologie   patofyziologie   MeSH
• transportér 1 pro sodík a glukosu metabolismus   MeSH
• transportér 2 pro sodík a glukózu metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: In a previously published randomised, placebo-controlled trial, 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was shown to be superior to placebo in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). The aim of the current post hoc analyses was to evaluate the cost-effectiveness of CS compared with placebo in a European perspective using individual patient data from this clinical trial. METHODS: Patients with knee OA randomised to CS or placebo were followed up at 1, 3 and 6 months. The algo-functional Lequesne index was used to derive the EuroQol Five-Dimension Five-Level (EQ-5D-5L) score based on a validated formula. The EQ-5D-5L scores at each time point were used to calculate the changes in quality-adjusted life years (QALYs) with the area under the curve method. Costs were assessed using the average price of CS in the countries where the original study took place and where CS is currently marketed. The costs of CS in three countries were then used (i.e. the Czech Republic, Italy and Switzerland). The incremental cost-effectiveness ratio (ICER) threshold for CS to be considered cost-effective was set at 91,870 EUR per QALY (equivalent to the usually recommended threshold of US $100,000). The study used an intention-to-treat population, i.e. patients who received one dose of the study drug, and imputed missing values using the basal observation carried forward method. RESULTS: No significant differences in baseline characteristics were observed between the CS group (N = 199) and the placebo group (N = 205). The mean cost of CS for 6 months of treatment was 194.74 EUR. After 6 months of treatment, CS showed a mean ICER of 33,462 (95% CI 5130-61,794) EUR per QALY gained, indicating cost-effectiveness compared with placebo. The acceptability curve for cost-effectiveness shows that the CS treatment is likely to be cost-effective compared with placebo, with a 93% probability when the ceiling ratio is set at 91,870 EUR per QALY gained. CONCLUSIONS: These results highlight the role of CS as a cost-effective therapeutic option in the management of OA. However, further studies taking into account the use of other healthcare resources are warranted for a more complete understanding.

• MeSH
• analýza nákladové efektivity MeSH
• analýza nákladů a výnosů * MeSH
• artróza kolenních kloubů * farmakoterapie   ekonomika   MeSH
• chondroitinsulfáty * terapeutické užití   ekonomika   MeSH
• kvalitativně upravené roky života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH
• Itálie MeSH
• Švýcarsko MeSH

L eishmaniasis is a prevalent disease that impacts 98 countries and territories, mainly in Africa, Asia, and South America. It can cause substantial illness and death, particularly in its visceral manifestation that can be specifically targeted in the development of medications to combat leishmaniasis. This study has found natural compounds with possible inhibitory activity against APX using a reliable and accurate QSAR model. Despite the severe side effects of current treatments and the absence of an effective vaccination, these compounds show promise as a potential treatment for the disease. Nine hit compounds were found, and subsequent molecular docking was performed. Estradiol cypionate showed the lowest binding energy (- 10.5 kcal/mol), thus showing the strongest binding, and also had the strongest binding affinity, with a ΔGTotal of - 26.31 ± 3.01 kcal/mol, second only to the control molecule. Additionally, three hits viz. cloxacillin-sodium (- 16.57 ± 2.89 kcal/mol), cinchonidine (- 16.04 ± 3.27 kcal/mol), and quinine hydrochloride dihydrate (13.38 ± 1.06 kcal/mol) also showed significant binding affinity. Multiple interactions between drugs and active site residues demonstrated a substantial binding affinity with the target protein. The identified compounds exhibited drug-like effects and were orally bioavailable based on their ADME-toxicology features. Overall, estradiol cypionate, cloxacillin sodium, cinchonidine, and quinine hydrochloride dihydrate all exhibited inhibitory effects on the APX enzyme of Leishmania donovani. These results suggest that further investigation is needed to explore the potential of developing novel anti-leishmaniasis drugs using these compounds.

• MeSH
• antiprotozoální látky * farmakologie   chemie   MeSH
• inhibitory enzymů * farmakologie   chemie   MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• leishmanióza * farmakoterapie   MeSH
• lidé MeSH
• simulace molekulového dockingu MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

L-Aspartate (aspartic acid; C4H7NO4; 2-aminobutanedoic acid) is a non-essential α-amino acid found ubiquitously throughout the body, including in the brain. Aspartate is one of the protein-forming amino acids and the formation of tRNA-aspartate complex is catalysed by aspartyl tRNA synthetase. Free aspartate, which is the main subject of this review, plays key roles in metabolism, as an amino donor and acceptor. It contributes to the synthesis of protein, arginine and nitric oxide, asparagine, N-acetylaspartate and N-methyl-D-aspartate. Its major metabolic role in the brain is recycling reducing equivalents (protons) between the cytoplasm and mitochondrial matrix as part of the malate-aspartate shuttle. L-Aspartate's actions on synaptic receptors, as well as its possible presence in nerve terminals and synaptic vesicles, are, in principle, consistent with a role as an excitatory neurotransmitter. The evidence is far from conclusive and at times controversial. The role of D-aspartate in brain function is even less certain but, it appears that, rather than being a minor neurotransmitter, D-aspartate is more likely to be involved in fine regulation of endocrine and homeostatic processes. Much research remains to be done in this area. The diversity of its functions and chemistry make aspartate a complex molecule to investigate and measure in vivo. Perturbations of aspartate metabolism have been described in a range of neurological deficits, particularly those of white matter. Here, we examine what is known about the various roles of aspartate in brain, its metabolism, transport and compartmentation, its role as a neurotransmitter or a more general signalling molecule, and what is currently known about its role(s) in disease processes.

• MeSH
• kyselina asparagová * metabolismus   MeSH
• lidé MeSH
• mozek * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Food hydrocolloids, derived from natural sources such as plants, algae, and microbes, possess bioactive properties that significantly contribute to cardiovascular health. This review focuses on six key hydrocolloids: alginate, astragalus polysaccharides, carrageenan, fucoidan, lunasin, and psyllium, while also considering other important natural hydrocoloids such as short chain fatty acids (SCFAs), plant-derived food hydrocolloids, plant-derived gums, plant-derived mucilages, pectin, modified citrus pectin, inulin, naringenin, chia seeds, gelatine, whey protein, casein, microbial exopolysaccharides and gums, ulvan, and laminarin. Alginate, from brown seaweed, aids in cardiac tissue regeneration and repair. Astragalus polysaccharides, from the Astragalus plant, provide antioxidant, anti-inflammatory, and immunomodulatory benefits. Carrageenan, sourced from red seaweed, supports lipid profile balance and heart health. Fucoidan, another brown seaweed derivative, offers antihypertensive and lipid-lowering effects. Lunasin, a peptide found in soybeans, oats, and barley, is known for its cholesterol-lowering properties and anti-inflammatory effects. Psyllium, rich in soluble fiber, helps lower LDL cholesterol and improve overall cardiovascular function. These hydrocolloids, along with other mentioned compounds, are utilized in drug formulations, cosmetics, processed foods, and dietary supplements, enhancing food texture and stability while delivering health benefits. Upon consumption, they can be absorbed into the bloodstream or metabolized by gut microbiota into bioactive metabolites. This review examines their effects on cardiovascular function, highlighting their mechanisms in regulating vascular tone, blood pressure, vascular inflammation, and cardiac function. It consolidates current research, emphasizing the potential of these hydrocolloids and related compounds in the prevention and management of cardiovascular diseases (CVDs).

• MeSH
• algináty * chemie   farmakologie   MeSH
• karagenan * chemie   farmakologie   MeSH
• kardiovaskulární nemoci * prevence a kontrola   MeSH
• kardiovaskulární systém * účinky léků   MeSH
• koloidy chemie   farmakologie   MeSH
• lidé MeSH
• polysacharidy * chemie   farmakologie   MeSH
• psyllium * chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Diabetes mellitus (DM) is a chronic disease with prevalence increasing worldwide. The aim of this study was to investigate satisfaction with the current method of insulin delivery (INS) amongst patient with type 1 diabetes mellitus (T1DM) using multiple daily injection (MDI) or continuous subcutaneous insulin infusion (CSII). Furthermore, a sub-aim was to test the effect of selected variables on patient satisfaction with MDI or CSII using regression analysis. METHODS: A cross-sectional study carried out in the territory of Moravia in the Czech Republic. A quantitative approach using the Insulin Delivery System Rating Questionnaire (IDSRQ) among 197 respondents with T1DM with INS delivery with MDI or CSII for at least 1 year. Statistical methods used were descriptive statistics, Student's t-tests and regression analysis. RESULTS: Highly significant differences were found between CSII and MDI patients in satisfaction with the current method of INS delivery (p < 0.001), in how the current method of delivery helps patients maintain stable blood glucose values, prevent high blood glucose (p < 0.001), and in overall satisfaction with the current method of INS delivery (p < 0.001). The average overall satisfaction score was 56.19 points for MDI and 62.08 points for CSII. Regression analysis revealed predictors of overall satisfaction on the mean score on how the current method of INS delivery helps MDI patients (p < 0.01). The effect of other selected variables was not confirmed. CONCLUSION: The results of the study showed higher overall satisfaction with the method of INS delivery in CSII patients. The current method of INS delivery does not interfere with daily life and activities in most patients.

• MeSH
• diabetes mellitus 1. typu * farmakoterapie   krev   psychologie   MeSH
• dospělí MeSH
• hypoglykemika * aplikace a dávkování   terapeutické užití   MeSH
• injekce subkutánní MeSH
• inzulin * aplikace a dávkování   terapeutické užití   MeSH
• inzulinové infuzní systémy * MeSH
• krevní glukóza MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• spokojenost pacientů * MeSH
• subkutánní infuze MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving lipid mediator (SPM; resolvins, maresins, and protectins) dysregulation across the ILD spectra, positioning these endogenous molecules as promising therapeutic candidates for modulating maladaptive inflammation and promoting tissue repair. Over the past decade, this paradigm has catalyzed extensive translational research into SPM-based interventions as precision therapeutics for respiratory inflammation. In asthma, they reduce mucus hypersecretion, bronchial hyperreactivity, and airway inflammation, with prenatal SPM exposure potentially lowering offspring disease risk. In COPD, SPMs attenuate amyloid A-driven inflammation, normalizing cytokine/chemokine imbalances and oxidative stress and mitigating COVID-19-associated cytokine storm, enhancing survival. This review synthesizes SPMs' pharmacotherapeutic mechanisms in ILDs and evaluates current preclinical and clinical evidence.

• MeSH
• chronická obstrukční plicní nemoc farmakoterapie   metabolismus   MeSH
• COVID-19 metabolismus   MeSH
• kyseliny dokosahexaenové terapeutické užití   metabolismus   MeSH
• lidé MeSH
• plicní nemoci * farmakoterapie   metabolismus   MeSH
• SARS-CoV-2 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Trvalá antikoagulační terapie u pacientů v chronickém hemodialyzačním programu přináší řadu klinických a farmakologických výzev. Fibrilace síní, často komplikovaná nerovnováhou mezi pro- a antikoagulačními mechanismy, vyžaduje individuální přístup s ohledem na vysoké riziko krvácivých komplikací a trombembolismu. V posledních letech přibývá důkazů o použití přímých perorálních antikoagulancií (DOAC) u této populace na úkor warfarinu, jehož podávání nebylo prokázáno jako efektivní, a je navíc spojeno se zvýšeným rizikem krvácení a negativním vlivem na kalcium-fosfátový metabolismus. Tato práce se zaměřuje na zhodnocení současných možností antikoagulace s důrazem na nefrologické a koagulační aspekty, včetně přehodnocení zastaralých režimů a potenciální aplikace moderních přístupů.

Long-term anticoagulation therapy in patients on chronic hemodialysis presents a few clinical and pharmacological challenges. Atrial fibrillation, often complicated by an imbalance between pro- and anticoagulant factors, requires an individualized approach considering the high risk of bleeding complications and thromboembolism. In recent years, we have an increasing evidence for the use of direct oral anticoagulants (DOAC) in this population at the expense of warfarin The administration of warfarin has not been proven to be effective and is also associated with an increased risk of bleeding and a negative effect on calcium-phosphate metabolism. This work focuses on the evaluation of current anticoagulation options with an emphasis on nephrological and coagulation aspects, including a re-evaluation of outdated regimens and the potential application of modern approaches

• Klíčová slova
• apixaban,
• MeSH
• chronická renální insuficience * komplikace   terapie   MeSH
• dialýza ledvin MeSH
• fibrilace síní * farmakoterapie   MeSH
• heparin nízkomolekulární aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• pyrazoly terapeutické užití   MeSH
• rizikové faktory MeSH
• tromboembolie farmakoterapie   prevence a kontrola   MeSH
• warfarin terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Objev inzulinu v roce 1921 znamenal revoluci v léčbě diabetes mellitus. Od počátečních intravenózních aplikací inzulinu se léčba přesunula k subkutánním injekcím a následně k využití inzulinových per. Významný pokrok přinesly inzulinové pumpy, které umožňují kontinuální subkutánní podávání inzulinu a tím napodobení fyziologické sekrece. Propojení inzulinových pump s kontinuální monitorací glukózy vedlo k vývoji hybridních uzavřených smyček. Tyto systémy využívají algoritmy pro automatickou úpravu dávek inzulinu na základě aktuálních a predikovaných hodnot glykemie. Výsledkem je zlepšení glykemické kontroly, snížení variability glykemie a snížení rizika jak hypoglykemických, tak hyperglykemických epizod.

The discovery of insulin in 1921 revolutionized the treatment of diabetes mellitus. From initial intravenous applications, treatment progressed to subcutaneous injections and subsequently to the use of insulin pens. Insulin pumps represented a significant advancement, enabling continuous subcutaneous insulin infusion and thus mimicking physiological secretion. The combination of insulin pumps with continuous glucose monitoring has led to the development of hybrid closed-loop systems. These systems utilize algorithms to automatically adjust insulin doses based on current and predicted glucose levels. The result is improved glycemic control, reduced glycemic variability, and decreased risk of both hypoglycemic and hyperglycemic episodes.

• MeSH
• diabetes mellitus 1. typu farmakoterapie   krev   prevence a kontrola   MeSH
• diabetes mellitus farmakoterapie   prevence a kontrola   MeSH
• hyperglykemie krev   prevence a kontrola   MeSH
• hypoglykemie krev   prevence a kontrola   MeSH
• inzulin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• inzulinové infuzní systémy * MeSH
• kontinuální monitorování glukózy metody   přístrojové vybavení   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Chronické onemocnění ledvin (chronic kidney disesase, CKD) je spojeno se zvýšenou morbiditou a mortalitou, zejména z kardiovaskulárních (KV) příčin, a to zejména u osob s diabetes mellitus (DM). Již přítomnost DM zvyšuje KV riziko a potencuje riziko CKD. Proto má vedle kontroly glykemie klinický význam i prevence a léčba CKD, která má zpomalit její progresi. Významný nefroprotektivní účinek nových antidiabetik, konkrétně inhibitorů sodíko-glukózového kotransportéru 2 (sodium-glucose cotransporter 2, SGLT2) a agonistů receptoru pro glukagonu podobný peptid 1 (glucagon-like peptide 1 receptor agonist, GLP-1 RA), byl prokázán vedle jejich účinku na snížení koncentrace glukózy ve velkých KV studiích. Léčba inhibitory SGLT2 podobně jako GLP-1 RA je spojena s nižším rizikem poklesu glomerulární filtrace (glomerular filtration rate, GFR) v průběhu času jak u diabetické, tak nediabetické populace. Podle současných doporučení se inhibitory SGLT2 a/nebo GLP-1 RA doporučují osobám s DM, které mají chronické onemocnění ledvin a/nebo zvýšené KV riziko. Nefroprotektivní vlastnosti však nabízejí i další antidiabetika, o nichž bude v tomto přehledu rovněž pojednáno.

Chronic kidney disease (CKD) is associated with increased morbidity and mortality, especially from cardiovascular (CV) causes, and especially in people with diabetes mellitus (DM). Already presence of DM increases CV risk and potentiates the risk of CKD. Therefore, besides glycemic control, prevention and treatment of CKD to slow its progression are of clinical importance. A significant nephroprotective effect of novel antidiabetic drugs, namely sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), has been shown on top of their glucose-lowering effects and was confirmed in cardiovascular outcome trials. Inhibitors SGLT2 treatment, like GLP-1 RA, is associated with a lower risk of glomerular filtration rate (GFR) decline over time in both diabetic and non-diabetic populations. According to current guidelines, inhibitors SGLT2 and/or GLP-1 RA are recommended for people with DM who have CKD and/or increased CV risk. However, other antidiabetic drugs offer nephroprotective properties, which will also be discussed in this review.

• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 farmakologie   terapeutické užití   MeSH
• chronická renální insuficience * diagnóza   mortalita   prevence a kontrola   MeSH
• diabetes mellitus diagnóza   prevence a kontrola   MeSH
• glifloziny farmakologie   terapeutické užití   MeSH
• hypoglykemika * farmakologie   terapeutické užití   MeSH
• inzulin farmakologie   terapeutické užití   MeSH
• komplikace diabetu farmakoterapie   prevence a kontrola   MeSH
• ledviny účinky léků   MeSH
• lidé MeSH
• metformin farmakologie   terapeutické užití   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• sulfonylmočovinové sloučeniny farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH