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1.
Microb Ecol ; 87(1): 52, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38498218

RESUMEN

The use of algae for industrial, biotechnological, and agricultural purposes is spreading globally. Scenedesmus species can play an essential role in the food industry and agriculture due to their favorable nutrient content and plant-stimulating properties. Previous research and the development of Scenedesmus-based foliar fertilizers raised several questions about the effectiveness of large-scale algal cultivation and the potential effects of algae on associative rhizobacteria. In the microbiological practice applied in agriculture, bacteria from the genus Azospirillum are one of the most studied plant growth-promoting, associative, nitrogen-fixing bacteria. Co-cultivation with Azospirillum species may be a new way of optimizing Scenedesmus culturing, but the functioning of the co-culture system still needs to be fully understood. It is known that Azospirillum brasilense can produce indole-3-acetic acid, which could stimulate algae growth as a plant hormone. However, the effect of microalgae on Azospirillum bacteria is unclear. In this study, we investigated the behavior of Azospirillum brasilense bacteria in the vicinity of Scenedesmus sp. or its supernatant using a microfluidic device consisting of physically separated but chemically coupled microchambers. Following the spatial distribution of bacteria within the device, we detected a positive chemotactic response toward the microalgae culture. To identify the metabolites responsible for this behavior, we tested the chemoeffector potential of citric acid and oxaloacetic acid, which, according to our HPLC analysis, were present in the algae supernatant in 0.074 mg/ml and 0.116 mg/ml concentrations, respectively. We found that oxaloacetic acid acts as a chemoattractant for Azospirillum brasilense.


Asunto(s)
Azospirillum brasilense , Scenedesmus , Scenedesmus/metabolismo , Microfluídica , Ácido Oxaloacético/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Plantas/metabolismo
2.
Semin Thromb Hemost ; 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38016649

RESUMEN

Platelets are essential in maintaining blood homeostasis and regulating several inflammatory processes. They constantly interact with immune cells, have immunoregulatory functions, and can affect, through immunologically active substances, endothelium, leukocytes, and other immune response components. In reverse, inflammatory and immune processes can activate platelets, which might be significant in autoimmune disease progression and arising complications. Thus, considering this interplay, targeting platelet activity may represent a new approach to treatment of autoimmune diseases. This review aims to highlight the role of platelets in the pathogenic mechanisms of the most frequent chronic autoimmune inflammatory diseases to identify gaps in current knowledge and to provide potential new targets for medical interventions.

3.
BMC Biol ; 20(1): 262, 2022 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-36447225

RESUMEN

BACKGROUND: During range expansion in spatially distributed habitats, organisms differ from one another in terms of their patterns of localization versus propagation. To exploit locations or explore the landscape? This is the competition-colonization trade-off, a dichotomy at the core of ecological succession. In bacterial communities, this trade-off is a fundamental mechanism towards understanding spatio-temporal fluxes in microbiome composition. RESULTS: Using microfluidics devices as structured bacterial habitats, we show that, in a synthetic two-species community of motile strains, Escherichia coli is a fugitive species, whereas Pseudomonas aeruginosa is a slower colonizer but superior competitor. We provide evidence highlighting the role of succession and the relevance of this trade-off in the community assembly of bacteria in spatially distributed patchy landscapes. Furthermore, aggregation-dependent priority effects enhance coexistence which is not possible in well-mixed environments. CONCLUSIONS: Our findings underscore the interplay between micron-scale landscape structure and dispersal in shaping biodiversity patterns in microbial ecosystems. Understanding this interplay is key to unleash the technological revolution of microbiome applications.


Asunto(s)
Infecciones por Escherichia coli , Microbiota , Humanos , Biodiversidad , Escherichia coli , Pseudomonas aeruginosa
4.
Bratisl Lek Listy ; 124(7): 527-533, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37218480

RESUMEN

INTRODUCTION: Despite known risk factors for developing type 2 diabetes mellitus (T2D), the research community still tries to discover new markers that would widen our diagnostic and therapeutic approach to diabetes. Therefore, research on microRNA (miR) in diabetes thrives. This study aimed to assess the utility of miR-126, miR-146a, and miR-375 as novel diagnostic markers for T2D. METHODS: We examined relative quantities of miR-126, miR-146a, and miR-375 in the serum of patients with established type 2 diabetes mellitus (n = 68) and compared these with a control group (n = 29). We also undertook a ROC analysis of significantly changed miR to examine their use as a diagnostic test. RESULTS: MiR-126 (p < 0.0001) and miR-146a (p = 0.0005) showed a statistically significant reduction in patients with type 2 diabetes mellitus. MiR-126 also proved to be an exceptional diagnostic test in our study cohort, with high sensitivity (91 %) and specificity (97 %). We did not find any difference in our study groups' relative quantities of miR-375. CONCLUSION: The study proved a statistically significant reduction of miR-126 and miR-146a in patients with T2D (Tab. 4, Fig. 6, Ref. 51). Text in PDF www.elis.sk Keywords: microRNA, epigenetics, genomics, type 2 diabetes mellitus, miR-126, miR-146a and miR-375.


Asunto(s)
Diabetes Mellitus Tipo 2 , MicroARNs , Humanos , Diabetes Mellitus Tipo 2/genética , Proyectos Piloto , MicroARNs/genética
5.
Vnitr Lek ; 68(E-4): 4-9, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36220371

RESUMEN

INTRODUCTION: Kidney transplantation is now a routine method used to treat end-stage renal disease. About 10 % of kidney transplant patients are patients with autosomal dominant polycystic kidney disease (ADPKD). After successful kidney transplantation, recurrent urinary tract infections also occur in initially asymptomatic patients. MATERIAL AND METHODS: The group included 320 patients after kidney transplantation. We compared patients with ADPKD versus patients without ADPKD in terms of the presence of recurrent urinary tract infections. THE RESULTS: The incidence of recurrent urinary tract infections (rIMCs) was 18% in patients without ADPKD and 48% in patients without ADPKD. Nephrectomy after kidney transplantation due to recurrent urinary tract infections eliminated this infectious complication (in 86% of patients). CONCLUSION: Kidney transplant patients with ADPKD have a significantly higher incidence of recurrent urinary tract infections. Removal of polycystic kidneys is a suitable solution if the infection persists.


Asunto(s)
Trasplante de Riñón , Enfermedades Renales Poliquísticas , Riñón Poliquístico Autosómico Dominante , Infecciones Urinarias , Humanos , Trasplante de Riñón/efectos adversos , Nefrectomía/métodos , Enfermedades Renales Poliquísticas/complicaciones , Enfermedades Renales Poliquísticas/cirugía , Riñón Poliquístico Autosómico Dominante/complicaciones , Riñón Poliquístico Autosómico Dominante/cirugía , Estudios Retrospectivos , Infecciones Urinarias/complicaciones , Infecciones Urinarias/epidemiología
6.
J Cardiovasc Pharmacol ; 78(1): e122-e127, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-34173805

RESUMEN

ABSTRACT: Patients with atrial fibrillation (AF) on long-term direct oral anticoagulants (DOACs) may be at higher risk of bleeding because of higher anti-Xa or anti-IIa levels. However, there is no postmarketing study investigating these DOAC plasma levels at the time of bleeding. The aim of this study was to evaluate DOAC levels at the time of a bleeding emergency. We analyzed 5440 patients examined at our Emergency Department in from April 1, 2019, to September 30, 2019. During this period, we prospective identified 105 consecutive patients with bleeding while on long-term antithrombotic therapy; 49 patients had AF on DOACs. We compared DOAC levels in patients who bled against a control sample of 55 patients who tolerated long-term high dose DOAC therapy without any emergency. Samples of these patients were tested with drug-specific anti-Xa chromogenic analysis (rivaroxaban and apixaban) and with Hemoclot Thrombin Inhibitor assay (dabigatran). Dabigatran-treated patients who bled had significantly higher anti-IIa levels when compared with trough (261.4 ± 163.7 vs. 85.4 ± 57.2 ng/mL, P < 0.001) and peak samples of controls (261.4 ± 163.7 vs. 138.8 ± 78.7 ng/mL, P < 0.05). Similarly, there were significantly higher anti-Xa levels in rivaroxaban-treated and apixaban-treated patients with bleeding compared with trough control samples (rivaroxaban: 245.9 ± 150.2 vs. 52.5 ± 36.4 ng/mL, P <0.001 and apixaban: 311.8 ± 142.5 vs. 119.9 ± 81.7 ng/mL, P < 0.001), as well as in apixaban-treated patients when compared with peak control samples (311.8 ± 142.5 vs. 210.9 ± 88.7 ng/mL, P < 0.05). Finally, rivaroxaban anti-Xa levels in patients who bled tended to be higher compared with peak control samples (245.9 ± 150.2 vs. 177.6 ± 38.6 ng/mL, P = 0.13). This observational study showed a significant difference in anti-IIa and anti-Xa plasma levels in patients with AF with bleeding complications compared with those who tolerated long-term high-dose DOAC therapy without bleeding complications.


Asunto(s)
Antitrombinas/efectos adversos , Antitrombinas/sangre , Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/sangre , Hemorragia/inducido químicamente , Anciano , Anciano de 80 o más Años , Antitrombinas/administración & dosificación , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Estudios de Casos y Controles , Dabigatrán/efectos adversos , Dabigatrán/sangre , Monitoreo de Drogas , Inhibidores del Factor Xa/administración & dosificación , Femenino , Hemorragia/sangre , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Pirazoles/efectos adversos , Pirazoles/sangre , Piridonas/efectos adversos , Piridonas/sangre , Rivaroxabán/efectos adversos , Rivaroxabán/sangre , Factores de Tiempo , Resultado del Tratamiento
7.
Am J Ther ; 29(2): e212-e218, 2021 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-35389573

RESUMEN

BACKGROUND: Apixaban, a direct inhibitor of activated coagulation factor X (FXaI), is being frequently selected for treatment and prevention of venous thromboembolism (VTE). Several reports about possible use of oral FXaI in patients with cancer-associated VTE (CA-VTE) have been published recently. AREAS OF UNCERTAINTY: The efficacy/safety profile of oral FXaI anticoagulation in patients with CA-VTE seems promising; however, several problems remain unanswered. The pharmacologic profile of apixaban could prefer this agent for the treatment of CA-VTE. DATA SOURCES: Currently available medical literature was searched and reviewed to summarize data regarding the use of apixaban for the prevention and treatment of cancer-associated VTE. RESULTS: Apixaban therapy in patients with cancer and VTE is expected to increase as clinicians gain more experience and reassurance with data from real-world studies that are generally promising. Several studies demonstrated that apixaban exhibits noninferiority to warfarin and low molecular weight heparin in preventing recurrent thrombosis in cancer-associated VTE. Nevertheless, there are still concerns regarding the bleeding associated with apixaban therapy, and regarding the optimal management of these bleeding emergencies. THERAPEUTIC OPINION: Although currently available evidence confirms the noninferiority of apixaban for reduction of the risk of recurrent VTE in patients with cancer; there are still concerns regarding the safety, especially in selected subpopulations of these patients.


Asunto(s)
Neoplasias , Tromboembolia Venosa , Anticoagulantes/efectos adversos , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Pirazoles/efectos adversos , Piridonas/efectos adversos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
8.
J Cardiovasc Pharmacol ; 75(4): 333-335, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31895873

RESUMEN

BACKGROUND: Several studies demonstrated that proton pump inhibitors (PPIs) co-administrated with dabigatran in patients with atrial fibrillation (AF) decreased dabigatran trough and peak plasma levels. However, it is still unknown whether this interaction is reversible or not, and whether the withdrawal of PPI would lead to normalization of dabigatran plasma levels. AIM OF STUDY: The aim of this study was to determine the effect of PPI withdrawal on dabigatran plasma levels in patients with AF. METHODS: This pilot prospective study enrolled 23 AF patients on long-term dabigatran and PPI therapy (omeprazole 20 mg twice daily or pantoprazole 40 mg once daily). Dabigatran trough and peak levels (ng/mL) were tested on PPI and after a 2-week period of PPI withdrawal with Hemoclot Thrombin Inhibitor Assay. RESULTS: The analysis of dabigatran plasma levels demonstrated significant elevation in trough dabigatran levels after 2 weeks of PPI withdrawal (97.2 ± 79.7 vs. 163.8 ± 105.5 ng/mL; P < 0.05). Moreover, significantly higher peak dabigatran levels were observed after 2 weeks of PPI withdrawal (142.4 ± 102.8 vs. 255 ± 129.5 ng/mL; P ≤ 0.001). CONCLUSIONS: This study showed that a 2-week period of PPI withdrawal lead to a significant increase in dabigatran trough and peak plasma levels in patients with AF.


Asunto(s)
Antitrombinas/sangre , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/sangre , Omeprazol/administración & dosificación , Pantoprazol/administración & dosificación , Inhibidores de la Bomba de Protones/administración & dosificación , Anciano , Anciano de 80 o más Años , Antitrombinas/administración & dosificación , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Dabigatrán/administración & dosificación , Esquema de Medicación , Interacciones Farmacológicas , Monitoreo de Drogas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/efectos adversos , Pantoprazol/efectos adversos , Proyectos Piloto , Estudios Prospectivos , Inhibidores de la Bomba de Protones/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
9.
Vnitr Lek ; 66(6): 28-34, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33380150

RESUMEN

Patients with less severe glycated haemoglobin (HbA1c) targets may find it difficult to achieve the target values of lipid parameters treatment at high cardiovascular risk. We have been monitoring the correlation between levels of triglycerides (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) with glycosylated haemoglobin (HbA1c) by IFCC method (method of testing according to the International Federation of Clinical Chemistry and Laboratory Medicine) and by DCCT method (Diabetes Control and Complication Trial) as well as body mass index (BMI) at the time of diagnosis of the disease, that could help identify patients with an increased risk of cardiovascular disease. In the cohort study we were monitoring outpatients with newly diagnosed type 2 diabetes mellitus during a 5 year period. Patients (117 men, 83 women), aged from 30 to 92 years were conducted sampling blood glucose, HbA1c (IFCC/DCCT), HDL, LDL, TG. At baseline, the patients height, weight, waist circumference, calculated BMI and blood pressure were measured. Waist circumference was measured in the horizontal plane in the middle of the distance between the upper edge of the iliac crest and the lower edge of the last rib in the breath. Our study did not exclude patients taking statin or fibrate. The high HbA1c values increased the risk of elevating LDL-cholesterol levels and TAG levels in the whole group (p = 0.012) and (p = 0.017), and the high BMI values increased the risk of lowering HDL-cholesterol levels in the female population (p = 0.010). The results of our study stratify the increased risk of atherogenicity in these groups. HbA1c is a direct marker of elevated LDL and TAG, and indirect marker for coronary artery disease risk assessment.


Asunto(s)
Diabetes Mellitus Tipo 2 , Adulto , Anciano , Anciano de 80 o más Años , Glucemia , HDL-Colesterol , Estudios de Cohortes , Femenino , Hemoglobina Glucada , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos
10.
Vnitr Lek ; 66(8): 39-46, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33740859

RESUMEN

Heparin-induced thrombocytopenia (HIT) is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low-molecular weight heparin. Some patients with HIT develop serious thrombotic complications like limb ischemia and gangrene, while others may not develop such complications. Current laboratory diagnostic tools incur significant time delays before confirming HIT, therefore upon clinical suspicion, treatment of HIT should start immediately. In this review, the authors highlight heparin-induced thrombocytopenias risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment.


Asunto(s)
Trombocitopenia , Trombosis , Anticoagulantes/efectos adversos , Heparina/efectos adversos , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Trombocitopenia/inducido químicamente
11.
Semin Thromb Hemost ; 45(8): 846-850, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31537027

RESUMEN

Dabigatran etexilate, a direct thrombin inhibitor, is now frequently used for long-term pharmacological prevention of stroke or systemic embolism in patients with atrial fibrillation. However, such long-term dabigatran therapy (DT) significantly increases the risk of upper gastrointestinal (GI) bleeding. This increased risk of gastric bleeds might be reduced with gastroprotective agents, such as proton pump inhibitors (PPIs). PPIs coadministrated with dabigatran reduce the risk of upper GI bleeding in patients on long-term oral DT. Nevertheless, there is heated discussion regarding interactions between PPI and dabigatran that lead to decreases in dabigatran plasma levels. This article reviews up to date data about the risk of gastric bleeding on dabigatran, the impact of PPI on the reduction of gastric bleeding, and the interaction between PPI and dabigatran leading to decreased dabigatran plasma levels.


Asunto(s)
Dabigatrán/uso terapéutico , Hemorragia Gastrointestinal/tratamiento farmacológico , Inhibidores de la Bomba de Protones/uso terapéutico , Dabigatrán/farmacología , Humanos , Inhibidores de la Bomba de Protones/farmacología , Factores de Riesgo
12.
Am J Ther ; 26(3): e308-e313, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-28452843

RESUMEN

BACKGROUND: Proton pump inhibition (PPI) administrated together with dabigatran reduces the risk of gastrointestinal hemorrhage. However, there is a discussion regarding possible PPI-dabigatran interaction that may reduce the efficacy of this therapy. STUDY QUESTION: To determine the impact of concomitant PPI on dabigatran plasma levels in patients with nonvalvular atrial fibrillation (NV-AF). STUDY DESIGN: A pilot prospective study in patients with NV-AF on dabigatran therapy was performed; 31 patients were enrolled. PPI with either omeprazole or pantoprazole was administrated in 19 patients. MEASURES AND OUTCOMES: Blood samples were taken for the assessment of the dabigatran trough and peak levels. Dabigatran concentration was measured with the Hemoclot Thrombin Inhibitor Assay. RESULTS: There were significant differences in dabigatran trough level comparing patients treated with PPI and patients without PPI (58.86 ± 36.76 ng/mL vs. 110.72 ± 88.47 ng/mL, P < 0.05). Similarly, there were significant differences in dabigatran peak level between compared groups (88.0 ± 20.5 ng/mL vs. 174.4 ± 139.64 ng/mL, P < 0.05). CONCLUSIONS: This pilot study demonstrated the interaction between PPI and dabigatran levels in patients with NV-AF.


Asunto(s)
Anticoagulantes/farmacocinética , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/farmacocinética , Hemorragia Gastrointestinal/prevención & control , Inhibidores de la Bomba de Protones/farmacocinética , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Dabigatrán/efectos adversos , Interacciones Farmacológicas , Femenino , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Omeprazol/farmacocinética , Pantoprazol/administración & dosificación , Pantoprazol/farmacocinética , Proyectos Piloto , Estudios Prospectivos , Inhibidores de la Bomba de Protones/administración & dosificación
13.
J Thromb Thrombolysis ; 47(1): 140-145, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30288664

RESUMEN

Proton pump inhibition (PPI) reduces gastrointestinal bleeding on direct oral anticoagulants. However, PPI may affect dabigatran on-treatment levels; and there is no information regarding the effect of PPI on xabans on-treatment activity. Thus, the aim of this study was to determine the impact of PPI on therapeutic anti-Xa activity in rivaroxaban- and apixaban-treated patients with atrial fibrillation (AF). This single-centre pilot prospective study enrolled 77 consecutive xabans-treated patients (42 rivaroxaban-treated and 35 apixaban-treated patients) with AF. PPI was administrated in 44 patients. Trough and peak anti-Xa activity was assessed with factor Xa-calibrated anti-Xa chromogenic analysis. There were no significant differences in trough anti-Xa activity comparing PPI-treated patients and patients without PPI (80.5 ± 66.5 ng/mL in PPI group vs. 71.6 ± 64.1 ng/mL in non-PPI group, p = 0.57, Table 2). Similarly, there were no significant differences in peak anti-Xa activity between compared groups (175.2 ± 102.5 ng/mL in PPI group vs. 202.9 ± 84.1 ng/mL in non-PPI group, p = 0.21). This pilot study did not reveal significant changes in xabans on-treatment anti-Xa activity according the PPI status.


Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/farmacología , Inhibidores de la Bomba de Protones/farmacología , Anticoagulantes/farmacología , Interacciones Farmacológicas , Inhibidores del Factor Xa/uso terapéutico , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/tratamiento farmacológico , Humanos , Proyectos Piloto , Estudios Prospectivos , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Rivaroxabán/uso terapéutico
14.
J Thromb Thrombolysis ; 48(4): 619-622, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31264059

RESUMEN

Very limited but promising experiences with the use of direct factor Xa inhibitors for the treatment of heparin-induced thrombocytopenia (HIT) have been reported. This contribution features our first experience with the use of apixaban (without a pre-treatment with parenteral anticoagulant) to treat a case of HIT which developed in a patient after multiple heart replacement surgery. Apixaban was effective, well tolerated and safe. An apixaban-calibrated chromogenic anti-Xa activity assessment was used to monitor apixaban activity throughout the therapy. Patient continued on apixaban for the prevention of thrombosis in the settings of atrial fibrillation. No ischemic or bleeding events occurred during the clinical follow up and the platelet count was stable. Our experience suggests that apixaban might be effectively used for the treatment of HIT and for the long-term prevention of embolism in patients after multiple valve replacement with biological prostheses and atrial fibrillation.


Asunto(s)
Embolia/prevención & control , Pirazoles/uso terapéutico , Piridonas/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Fibrilación Atrial/etiología , Inhibidores del Factor Xa/uso terapéutico , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Heparina/efectos adversos , Humanos , Trombocitopenia/inducido químicamente , Resultado del Tratamiento
15.
Vnitr Lek ; 65(4): 264-272, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31091945

RESUMEN

Insulin resistance (IR) is defined as insufficient insulin metabolic effect in target tissues, including glucose utilisation in skeletal muscle, suppression of hepatic glucose production and suppression of lipolysis in fat tissue. Primary IR originates as consequence of rare monogenetic defects of insulin receptor or molecules includes to post-receptor insulin signal cascade. Secondary IR originates mainly as a result of metabolic or hormonal changes, most commonly in visceral obesity by multifactorial postreceptor inhibition of insulin signal and it is associated with metabolic syndrome and type 2 diabetes mellitus. It is also present in endocrinopathies with overproduction of contraregulatory insulin hormones (cortisol, growth hormone, catecholamines) and using of some drugs (mainly steroids, immunosuppressive treatment). In practice IR is usually diagnosed by glycemic parameters with confirmation of prediabetic states and type 2 diabetes mellitus. The healthy life style and physical activity associated with weight loss are the most important for type 2 diabetes prevention. According to actual international guidelines metformin is only antidiabetic drug which is possible to use in prediabetic states with high risk of type 2 diabetes development, mainly in obese subjects with BMI > 35 kg/m2, age under 60 years and in women with history of gestational diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Resistencia a la Insulina , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Insulina
16.
J Cardiovasc Pharmacol ; 72(1): 71-76, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29738377

RESUMEN

Proton pump inhibition (PPI) administered together with antiplatelet and anticoagulant agents reduces the risk of gastrointestinal hemorrhage. Several novel antithrombotic agents have been recently introduced for patients with acute coronary syndrome (prasugrel and ticagrelor) or for patients requiring long-term anticoagulation (dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban). In fact, these agents might offer even stronger inhibition of platelets or coagulation compared with older agents; therefore, the need for gastroprotection might be even stronger when these new agents are used for long-term antithrombotic therapy. On the contrary, there are several reports regarding an adverse interaction between PPI and antithrombotic agents connected with a reduction in antithrombotic therapy on-treatment levels, implicating a higher risk of thrombosis. This interaction was demonstrated in clopidogrel-treated patients and more recently also in dabigatran-treated patients. This article discusses a possible novel antithrombotic therapy/PPI interaction leading to higher risk of thrombosis.


Asunto(s)
Anticoagulantes/efectos adversos , Fibrinolíticos/efectos adversos , Hemorragia Gastrointestinal/prevención & control , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Antagonistas del Receptor Purinérgico P2Y/efectos adversos , Trombosis/inducido químicamente , Trombosis/prevención & control , Toma de Decisiones Clínicas , Interacciones Farmacológicas , Hemorragia Gastrointestinal/inducido químicamente , Humanos , Medición de Riesgo , Factores de Riesgo
17.
Vnitr Lek ; 64(4): 405-426, 2018.
Artículo en Checo | MEDLINE | ID: mdl-29791176

RESUMEN

Type 2 diabetes mellitus is a heterogeneous medical condition involving multiple pathophysiological mechanisms. Its successful treatment requires an individualized approach and frequently combined therapy with utilizing its effect on multiple levels. Current possibilities enable the employment of such procedures to an incomparably greater extent than before. The effects of different classes of oral antidiabetic drugs on the reduction of glycemia and HbA1c is mutually comparable. However differences are observed in the proportions of patients who met the required criteria, regarding the increase in weight, incidence of hypoglycemia as well as the effect on cardiovascular, renal or oncologic morbidity and mortality, and severity of specific adverse effects, potential risks and contraindications. The presented text provides the reader with the information about the Consensual therapeutic algorithm for the treatment of type 2 diabetes mellitus in compliance with SPC, the ADA/EASD amended indicative limitations and recommendations, formulated by the Committee of the Slovak Diabetes Society.Key words: biguanides - gliflozins - gliptins - glitazones - GLP-1-receptor agonists - insulin - sulfonylurea.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Hipoglucemiantes , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hemoglobina Glucada , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Eslovaquia , Compuestos de Sulfonilurea/uso terapéutico
18.
Photosynth Res ; 132(2): 127-134, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27709414

RESUMEN

Specific inhibitory reactions of herbicides with photosynthetic reaction centers bound to working electrodes were monitored in a conventional electrochemical cell and a newly designed microfluidic electrochemical flow cell. In both cases, the bacterial reaction centers were bound to a transparent conductive metal oxide, indium-tin-oxide, electrode through carbon nanotubes. In the conventional cell, photocurrent densities of up to a few µA/cm2 could be measured routinely. The photocurrent could be blocked by the photosynthetic inhibitor terbutryn (I 50 = 0.38 ± 0.14 µM) and o-phenanthroline (I 50 = 63.9 ± 12.2 µM). The microfluidic flow cell device enabled us to reduce the sample volume and to simplify the electrode arrangement. The useful area of the electrodes remained the same (ca. 2 cm2), similar to the classical electrochemical cell; however, the size of the cell was reduced considerably. The microfluidic flow control enabled us monitoring in real time the binding/unbinding of the inhibitor and cofactor molecules at the secondary quinone site.


Asunto(s)
Técnicas Biosensibles/métodos , Electroquímica/instrumentación , Herbicidas , Fotosíntesis/fisiología
19.
Brain Behav Immun ; 64: 220-231, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28432035

RESUMEN

Cerebral pericytes are mural cells embedded in the basement membrane of capillaries. Increasing evidence suggests that they play important role in controlling neurovascular functions, i.e. cerebral blood flow, angiogenesis and permeability of the blood-brain barrier. These cells can also influence neuroinflammation which is highly regulated by the innate immune system. Therefore, we systematically tested the pattern recognition receptor expression of brain pericytes. We detected expression of NOD1, NOD2, NLRC5, NLRP1-3, NLRP5, NLRP9, NLRP10 and NLRX mRNA in non-treated cells. Among the ten known human TLRs, TLR2, TLR4, TLR5, TLR6 and TLR10 were found to be expressed. Inflammatory mediators induced the expression of NLRA, NLRC4 and TLR9 and increased the levels of NOD2, TLR2, inflammasome-forming caspases and inflammasome-cleaved interleukins. Oxidative stress, on the other hand, upregulated expression of TLR10 and NLRP9. Activation of selected pattern recognition receptors can lead to inflammasome assembly and caspase-dependent secretion of IL-1ß. TNF-α and IFN-γ increased the levels of pro-IL-1ß and pro-caspase-1 proteins; however, no canonical activation of NLRP1, NLRP2, NLRP3 or NLRC4 inflammasomes could be observed in human brain vascular pericytes. On the other hand, we could demonstrate secretion of active IL-1ß in response to non-canonical inflammasome activation, i.e. intracellular LPS or infection with E. coli bacteria. Our in vitro results indicate that pericytes might have an important regulatory role in neuroinflammation.


Asunto(s)
Encéfalo/metabolismo , Inflamasomas/metabolismo , Pericitos/metabolismo , Receptores de Reconocimiento de Patrones/metabolismo , Células Cultivadas , Regulación de la Expresión Génica , Humanos , Interleucina-1beta/metabolismo , Transducción de Señal
20.
Am J Ther ; 24(2): e162-e166, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27415979

RESUMEN

BACKGROUND: Proton pump inhibition (PPI) administrated together with adenosine diphosphate (ADP) receptor blockers (ADPRB) significantly reduces the risk of gastrointestinal bleeding. Nevertheless, there is a heated discussion about an interaction between PPI and ADPRB that leads to high on-treatment platelet reactivity (HTPR). STUDY QUESTION: Is there a relationship between pantoprazole PPI and HTPR on ADPRB therapy in patients with acute ST-elevation myocardial infarction (STEMI). METHODS: Single center pilot study in patients with acute STEMI was performed. This study enrolled totally 87 patients (34 clopidogrel-treated and 53 new ADPRB-treated patients). Pantoprazole was administrated in 33 patients. HTPR was detected with ADP-induced light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation analysis. Samples were taken before coronary angiography (sample 1) and on the next day after the procedure (sample 2). RESULTS: No significant differences were found in pantoprazole-treated patients and patients without PPI neither in sample 1 (59.2 ± 29.5% vs. 54.9 ± 22.7%, P = 0.49) nor in sample 2 (43.8 ± 27.2% vs. 37.0 ± 22.9%, P = 0.30). Similarly, there were no significant differences in the platelet reactivity index of vasodilator-stimulated phosphoprotein phosphorylation in both samples (sample 1: 53.3 ± 29.8% vs. 65.0 ± 20.5%, P = 0.11; sample 2: 30.8 ± 27.1% vs. 40.6 ± 27.5%, P = 0.19). A comparison of clopidogrel and new ADP receptor blockers in patients on pantoprazole PPI did not reveal significant differences in on-treatment platelet reactivity. CONCLUSIONS: This study did not reveal interaction between pantoprazole and ADPRB in patients with acute STEMI.


Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/farmacología , Plaquetas/efectos de los fármacos , Moléculas de Adhesión Celular/efectos de los fármacos , Proteínas de Microfilamentos/efectos de los fármacos , Fosfoproteínas/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de la Bomba de Protones/farmacología , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Infarto del Miocardio con Elevación del ST/terapia , Adenosina/análogos & derivados , Adenosina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Moléculas de Adhesión Celular/metabolismo , Clopidogrel , Angiografía Coronaria , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Proteínas de Microfilamentos/metabolismo , Persona de Mediana Edad , Pantoprazol , Intervención Coronaria Percutánea , Fosfoproteínas/metabolismo , Fosforilación/efectos de los fármacos , Proyectos Piloto , Clorhidrato de Prasugrel/uso terapéutico , Estudios Prospectivos , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico
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