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1.
Int J Mol Sci ; 25(12)2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38928095

RESUMEN

Hypertension is a highly prevalent population-level disease that represents an important risk factor for several cardiovascular complications and occupies a leading position in mortality statistics. Antihypertensive therapy includes a wide variety of drugs. Additionally, the potential antihypertensive and cardioprotective effects of several phytotherapy products have been evaluated, as these could also be a valuable therapeutic option for the prevention, improvement or treatment of hypertension and its complications. The present review includes an evaluation of the cardioprotective and antihypertensive effects of garlic, Aloe vera, green tea, Ginkgo biloba, berberine, ginseng, Nigella sativa, Apium graveolens, thyme, cinnamon and ginger, and their possible interactions with antihypertensive drugs. A literature search was undertaken via the PubMed, Google Scholar, Embase and Cochrane databases. Research articles, systematic reviews and meta-analyses published between 2010 and 2023, in the English, Hungarian, and Romanian languages were selected.


Asunto(s)
Antihipertensivos , Humanos , Antihipertensivos/uso terapéutico , Antihipertensivos/farmacología , Hipertensión/tratamiento farmacológico , Interacciones de Hierba-Droga , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Fitoterapia/métodos , Animales , Plantas Medicinales/química , Enfermedades Cardiovasculares/tratamiento farmacológico
2.
Int J Mol Sci ; 24(16)2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37628963

RESUMEN

The course of COVID-19 is highly dependent on the associated cardiometabolic comorbidities of the patient, which worsen the prognosis of coronavirus infection, mainly due to systemic inflammation, endothelium dysfunction, and thrombosis. A search on the recent medical literature was performed in five languages, using the PubMed, Embase, Cochrane, and Google Scholar databases, for the review of data regarding the management of patients with a high risk for severe COVID-19, focusing on the associated coagulopathy. Special features of COVID-19 management are presented, based on the underlying conditions (obesity, diabetes mellitus, and cardiovascular diseases), emphasizing the necessity of a modern, holistic approach to thromboembolic states. The latest findings regarding the most efficient therapeutic approaches are included in the article, offering guidance for medical professionals in severe, complicated cases of SARS-CoV-2 infection. We can conclude that severe COVID-19 is closely related to vascular inflammation and intense cytokine release leading to hemostasis disorders. Overweight, hyperglycemia, cardiovascular diseases, and old age are important risk factors for severe outcomes of coronavirus infection, involving a hypercoagulable state. Early diagnosis and proper therapy in complicated SARS-CoV-2-infected cases could reduce mortality and the need for intensive care during hospitalization in patients with cardiometabolic comorbidities.


Asunto(s)
Trastornos de la Coagulación Sanguínea , COVID-19 , Enfermedades Cardiovasculares , Enfermedades Vasculares , Humanos , COVID-19/complicaciones , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/terapia , SARS-CoV-2 , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/terapia , Inflamación/terapia
3.
Int J Mol Sci ; 24(5)2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36901751

RESUMEN

Chronic inflammation and endothelium dysfunction are present in diabetic patients. COVID-19 has a high mortality rate in association with diabetes, partially due to the development of thromboembolic events in the context of coronavirus infection. The purpose of this review is to present the most important underlying pathomechanisms in the development of COVID-19-related coagulopathy in diabetic patients. The methodology consisted of data collection and synthesis from the recent scientific literature by accessing different databases (Cochrane, PubMed, Embase). The main results are the comprehensive and detailed presentation of the very complex interrelations between different factors and pathways involved in the development of arteriopathy and thrombosis in COVID-19-infected diabetic patients. Several genetic and metabolic factors influence the course of COVID-19 within the background of diabetes mellitus. Extensive knowledge of the underlying pathomechanisms of SARS-CoV-2-related vasculopathy and coagulopathy in diabetic subjects contributes to a better understanding of the manifestations in this highly vulnerable group of patients; thus, they can benefit from a modern, more efficient approach regarding diagnostic and therapeutic management.


Asunto(s)
Trastornos de la Coagulación Sanguínea , COVID-19 , Diabetes Mellitus Tipo 2 , Tromboembolia , Humanos , SARS-CoV-2 , Inflamación
4.
Pak J Pharm Sci ; 36(5): 1399-1405, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37869915

RESUMEN

Oxidative stress enhances cardiovascular risk. Metformin decreases intestinal absorption of vitamin B12. Our objective was the evaluation of type 2 diabetics focusing on differences due to their treatment. A prospective study on 224 type 2 diabetics was realized between 2015-2018 in Targu Mures, Romania, divided into 2 subgroups (metformin vs. other therapy - 2nd/3rd generation sulfonylureas, insulin, dietary regimen -, followed for at least one year) and non-diabetic controls (n=25) for oxidative stress level comparison. Serum homocysteine (HC), vitamin B12 were determined by chemiluminescence (Immulite One). Lipid peroxidation was assessed by serum malondialdehyde (MDA) measurement (HPLC). Biochemical tests, minerals, cystatin C, high-sensitivity C reactive protein (hs-CRP) were measured on Konelab20Xti, glycated hemoglobin on Nycocard Reader. GraphPad InStat-3 was used for statistics. Negative correlation occured between serum vitamin B12 and HC, this vitamin's level was significantly lower and serum zinc was significantly higher in patients on metformin. Hyperhomocysteinemia was present in 87% of the subjects, 46% had zinc deficiency and 41% elevated hs-CRP. Serum cystatin C showed positive correlation with creatinine. Serum MDA was significantly higher in diabetics compared to control patients. Elevated hs-CRP and homocysteine represent raised cardiovascular risk. Intense oxidative stress, vitamin, mineral deficiencies are frequent in diabetic subjects.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/uso terapéutico , Hipoglucemiantes/uso terapéutico , Cistatina C , Proteína C-Reactiva , Estudios Prospectivos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/inducido químicamente , Factores de Riesgo , Vitamina B 12 , Factores de Riesgo de Enfermedad Cardiaca , Vitaminas , Homocisteína , Zinc
5.
J Allergy Clin Immunol ; 148(1): 164-172.e9, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33098856

RESUMEN

BACKGROUND: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. OBJECTIVE: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). METHODS: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. RESULTS: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. CONCLUSION: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.


Asunto(s)
Angioedemas Hereditarios/tratamiento farmacológico , Pirazoles/administración & dosificación , Administración Oral , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Calicreína Plasmática/administración & dosificación , Estudios Prospectivos , Resultado del Tratamiento
6.
Allergy ; 76(6): 1789-1799, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33247955

RESUMEN

BACKGROUND: With no approved treatments in Japan for the prevention of hereditary angioedema (HAE) attacks, there is a significant unmet need for long-term prophylactic therapies for Japanese patients with HAE. Berotralstat (BCX7353) is an oral, once-daily, highly selective inhibitor of plasma kallikrein in development for prophylaxis of angioedema attacks in HAE patients. METHODS: APeX-J is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, 3-part trial conducted in Japan (University Hospital Medical Information Network identifier, UMIN000034869; ClinicalTrials.gov identifier, NCT03873116). Patients with a clinical diagnosis of type 1 or 2 HAE underwent a prospective run-in period of 56 days to determine eligibility, allowing enrollment of those with ≥2 expert-confirmed angioedema attacks. Patients were randomly assigned (1:1:1) and stratified by baseline attack rate (≥2 vs. <2 expert-confirmed attacks/month between screening and randomization) to receive once-daily berotralstat 110 mg, berotralstat 150 mg, or placebo. The primary endpoint was the rate of expert-confirmed angioedema attacks during dosing in the 24-week treatment period. RESULTS: Nineteen patients were randomized to receive once-daily berotralstat 110 mg (n = 6), berotralstat 150 mg (n = 7), or placebo (n = 6). Treatment with berotralstat 150 mg significantly reduced HAE attacks relative to placebo (1.11 vs. 2.18 attacks/month, p = .003). The most frequently reported treatment-emergent adverse events (TEAEs) in berotralstat-treated patients (n = 13) were nasopharyngitis (n = 4, 31%), abdominal pain, cough, diarrhea, and pyrexia (n = 2 each, 15%). CONCLUSIONS: Orally administered, once-daily berotralstat 150 mg significantly reduced the frequency of HAE attacks and was safe and well tolerated, supporting its use as a prophylactic therapy in patients with type 1 or 2 HAE in Japan.


Asunto(s)
Angioedemas Hereditarios , Angioedemas Hereditarios/diagnóstico , Angioedemas Hereditarios/tratamiento farmacológico , Angioedemas Hereditarios/epidemiología , Proteína Inhibidora del Complemento C1/efectos adversos , Humanos , Japón/epidemiología , Estudios Prospectivos , Pirazoles
7.
Acta Vet Hung ; 68(3): 318-322, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-33136067

RESUMEN

Three electrosurgical tissue-sealing devices (EnSeal ETSDRC-01, LigaSure LS1500 and Thunderbeat TB-0535PC) were compared regarding sealing time (ST), maximum working temperature (WTmax) and the total (MTZtotal) as well as the collateral microscopic thermal injury zone (MTZcollat) using laparoscopic handpieces 5 mm in diameter on four types of tissue (liver, mesentery, cross striated muscle and spleen) in an in vivo porcine model. LigaSure had the lowest mean ST in spleen, mesentery, muscle and liver, followed by Thunderbeat and EnSeal with significant differences between all types of tissues and devices. The significantly lowest mean WTmax was obtained for EnSeal in mesentery, muscle and liver. LigaSure and EnSeal operated at the lowest temperature in spleen without a significant difference between them. Thunderbeat produced significantly higher temperature peaks in all cases. The lowest mean MTZtotal was caused by LigaSure and EnSeal in spleen, mesentery and muscle without significant differences between them, followed by the significantly higher values of Thunderbeat. Nevertheless, Thunderbeat produced the significantly lowest mean MTZtotal in the liver. EnSeal produced the lowest mean MTZcollat in the liver, followed by LigaSure and Thunderbeat showing significant differences. EnSeal and LigaSure produced the lowest mean MTZcollat in the spleen, mesentery and muscle without significant differences between them, followed by the significantly higher values of Thunderbeat. Based on the results of this study, Thunderbeat seems to be more invasive to tissue integrity (even without the activation of the ultrasonic scissor function) than EnSeal or LigaSure, that operate at lower temperatures and were found to cause negligible collateral thermal damage.


Asunto(s)
Electrocirugia/veterinaria , Laparoscopía/veterinaria , Sus scrofa/cirugía , Animales , Electrocirugia/instrumentación , Laparoscopía/instrumentación , Hígado/cirugía , Mesenterio/cirugía , Modelos Animales , Músculo Estriado/cirugía , Bazo/cirugía
8.
Nucleic Acids Res ; 45(1): 311-326, 2017 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-27913727

RESUMEN

The functional relevance of the inverted repeat structure (IR/DR) in a subgroup of the Tc1/mariner superfamily of transposons has been enigmatic. In contrast to mariner transposition, where a topological filter suppresses single-ended reactions, the IR/DR orchestrates a regulatory mechanism to enforce synapsis of the transposon ends before cleavage by the transposase occurs. This ordered assembly process shepherds primary transposase binding to the inner 12DRs (where cleavage does not occur), followed by capture of the 12DR of the other transposon end. This extra layer of regulation suppresses aberrant, potentially genotoxic recombination activities, and the mobilization of internally deleted copies in the IR/DR subgroup, including Sleeping Beauty (SB). In contrast, internally deleted sequences (MITEs) are preferred substrates of mariner transposition, and this process is associated with the emergence of Hsmar1-derived miRNA genes in the human genome. Translating IR/DR regulation to in vitro evolution yielded an SB transposon version with optimized substrate recognition (pT4). The ends of SB transposons excised by a K248A excision+/integration- transposase variant are processed by hairpin resolution, representing a link between phylogenetically, and mechanistically different recombination reactions, such as V(D)J recombination and transposition. Such variants generated by random mutation might stabilize transposon-host interactions or prepare the transposon for a horizontal transfer.


Asunto(s)
Reparación del ADN por Unión de Extremidades , Elementos Transponibles de ADN , Reparación del ADN por Recombinación , Transposasas/genética , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Células HeLa , Humanos , Secuencias Invertidas Repetidas , MicroARNs/genética , MicroARNs/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Transposasas/metabolismo , Pez Cebra , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo
9.
Blood ; 128(18): 2206-2217, 2016 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-27554082

RESUMEN

Current protocols for hematopoietic stem/progenitor cell (HSPC) gene therapy, involving the transplantation of ex vivo genetically modified HSPCs are complex and not without risk for the patient. We developed a new approach for in vivo HSPC transduction that does not require myeloablation and transplantation. It involves subcutaneous injections of granulocyte-colony-stimulating factor/AMD3100 to mobilize HSPCs from the bone marrow (BM) into the peripheral blood stream and the IV injection of an integrating, helper-dependent adenovirus (HD-Ad5/35++) vector system. These vectors target CD46, a receptor that is uniformly expressed on HSPCs. We demonstrated in human CD46 transgenic mice and immunodeficient mice with engrafted human CD34+ cells that HSPCs transduced in the periphery home back to the BM where they stably express the transgene. In hCD46 transgenic mice, we showed that our in vivo HSPC transduction approach allows for the stable transduction of primitive HSPCs. Twenty weeks after in vivo transduction, green fluorescent protein (GFP) marking in BM HSPCs (Lin-Sca1+Kit- cells) in most of the mice was in the range of 5% to 10%. The percentage of GFP-expressing primitive HSPCs capable of forming multilineage progenitor colonies (colony-forming units [CFUs]) increased from 4% of all CFUs at week 4 to 16% at week 12, indicating transduction and expansion of long-term surviving HSPCs. Our approach was well tolerated, did not result in significant transduction of nonhematopoietic tissues, and was not associated with genotoxicty. The ability to stably genetically modify HSPCs without the need of myeloablative conditioning is relevant for a broader clinical application of gene therapy.


Asunto(s)
Terapia Genética/métodos , Movilización de Célula Madre Hematopoyética/métodos , Proteína Cofactora de Membrana/biosíntesis , Transducción Genética/métodos , Adenoviridae , Animales , Vectores Genéticos/administración & dosificación , Células Madre Hematopoyéticas , Xenoinjertos , Humanos , Inyecciones Intravenosas , Ratones , Ratones Endogámicos C57BL
10.
World J Microbiol Biotechnol ; 30(9): 2449-58, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24845167

RESUMEN

Laccase-producing fungi were isolated from air, using selective media with a chromogenic substrate to indicate enzyme activity. The best laccase producer strain proved to be a Leptosphaerulina chartarum isolate. Laccase production was investigated in the presence of various inducers in different cultivation conditions. The extracellular laccase was purified for further investigations. SDS-PAGE showed that this laccase is a monomeric protein of 38 kDa molecular weight. The enzyme is active in the pH-range of 3.5-6, with an optimum at pH 3.8. It is active in the 10-60 °C temperature range, with an optimum at 40 °C. After 20 min incubation at temperatures above 70 °C the enzyme lost its activity. Degradation of seven aniline and phenol compounds (2,4-dichlorophenol; 2-methyl-4-chlorophenol; 3-chloroaniline; 4-chloroaniline; 2,6-dimethylaniline; 3,4-dichloroaniline and 3-chloro-4-methylaniline) was investigated, with or without guaiacol (2-methoxyphenol) as mediator molecule. Addition of a mediator to the system significantly increased the degradation levels. These results confirmed that the isolated laccase is able to convert these harmful xenobiotics at in vitro conditions.


Asunto(s)
Ascomicetos/enzimología , Lacasa/metabolismo , Microbiología del Aire , Compuestos de Anilina/metabolismo , Ascomicetos/crecimiento & desarrollo , Ascomicetos/aislamiento & purificación , Biotransformación , Medios de Cultivo/química , Electroforesis en Gel de Poliacrilamida , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Lacasa/química , Lacasa/aislamiento & purificación , Peso Molecular , Fenoles/metabolismo , Temperatura
11.
J Funct Morphol Kinesiol ; 9(3)2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39311251

RESUMEN

The use of virtual reality (VR) in older adults promotes improvements in mobility, strength, and balance. Changes in neuromuscular activation have been found to be associated with these improvements; however, during VR activities, this aspect has not been thoroughly investigated. The aim of this study was to investigate neuromuscular activation among older female adults during VR activities. Sixteen older female adults, with the use of VR, performed dynamic punching movements involving elbow flexion/extension for one minute, and the muscle activation of the bicep brachii was recorded with electromyography (EMG) and normalized to the maximal voluntary isometric contraction of elbow flexion. The one-minute activity was divided into three time phases: 0-10 s, 25-35 s, and 50-60 s. The five highest EMG amplitude values (%) in each phase were selected and averaged. Differences between phases were analyzed using repeated ANOVA (αadj = 0.017). The EMG amplitude for the first phase was 39.1 ± 2.6%, that for the second phase was 44.8 ± 3.0%, and that for the third phase was 49.6 ± 3.1%. Statistically significant differences were found in all phases, with the first phase demonstrating a lower EMG amplitude (%) compared to the second (p = 0.002) and third phases (p = 0.000). The third phase demonstrated a higher EMG amplitude (%) compared to the second phase (p = 0.025). Engagement in VR activities can have significant effects on neuromuscular activation in older female adults, with our findings revealing a significant increase in the EMG amplitude within one minute of commencing a dynamic and challenging activity such as virtual boxing.

12.
J Clin Med ; 13(14)2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39064156

RESUMEN

Objectives: Our study investigated the inverse relationship between cognitive decline (CD) and the presence of documented atrial fibrillation (AFib), ischemic stroke, heart failure, lower extremity peripheral artery disease, and diabetes mellitus. Methods: We conducted a retrospective cross-sectional study between December 2016 and November 2019. A total of 469 patients were enrolled who underwent cognitive evaluation with three cognitive tests (Montreal Cognitive Assessment-MOCA, Mini-Mental State Examination-MMSE, and General Practitioner Assessment of Cognition-GPCOG). We used the standard cut-off values, and the optimal thresholds were obtained from the receiver operating characteristic curves. Results: The standard cut-off level of the MOCA (<26 points) was associated with the presence of AFib (OR: 1.83, 95% CI: 1.11-3.01) and the optimal cut-off level with <23 points with ischemic stroke (OR: 2.64, 95% CI: 1.47-4.74; p = 0.0011). The optimal cut-off value of the MMSE (<28 points) was associated with the presence of ischemic stroke (OR: 3.07, 95% CI: 1.56-6.07; p = 0.0012), AFib (OR: 1.65, 95% CI: 1.05-2.60; p = 0.0287), and peripheral artery disease (OR: 2.72, 95% CI: 1.38-5.36; p = 0.0039). GPCOG < 8 points were associated with ischemic stroke (OR: 2.18, 95% CI: 1.14-4.14; p = 0.0176) and heart failure (OR: 1.49, 95% CI: 1.01-2.21; p = 0.0430). Conclusions: Our research highlighted the broader utility of cognitive assessment. The MOCA and MMSE scores proved to be associated with documented AFib. Higher cognitive test results than the standard threshold for CD of the MMSE, GPCOG, and lower MOCA scores represented risk factors for the presence of previous ischemic stroke.

13.
Sci Rep ; 14(1): 12943, 2024 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839972

RESUMEN

The present study aimed to investigate whether the strength of mental health competencies and the severity of mental disorder symptoms, and their interaction, differ in the strength of their associations with several dimensions of well-being in Hungarian adult psychiatric and non-clinical samples. All respondent in the psychiatric sample (129 patients (44 male, 85 female)) and in the non-clinical community sample (253 adults (43 male, 210 female)) completed the Mental Health Test, six measures of well-being and mental health, and the Symptom Checklist-90-Revised. Including both mental health competencies and mental disorder symptoms in a regression model in both samples can predict patients' well-being even more accurately. Mental health competencies were positively related; mental disorder symptoms were negatively related to subjective well-being. In all models and in both samples, mental health competencies were found to be stronger determinants of well-being than mental disorder symptoms. The interaction of mental health competencies and mental disorder symptoms is no more predictive of well-being in either psychiatric or non-clinical samples than when the effects of each are considered separately. The assessment of mental health competencies has an important predictive value for well-being in the presence of psychopathological symptoms and/or mental disorders.


Asunto(s)
Trastornos Mentales , Salud Mental , Humanos , Masculino , Femenino , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Adulto , Persona de Mediana Edad , Anciano , Competencia Mental/psicología , Hungría , Adulto Joven , Encuestas y Cuestionarios
14.
Front Public Health ; 12: 1385089, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39346594

RESUMEN

Background: The impact of cardiovascular diseases on cognition raises important research questions. The study aimed to investigate the relationship between demographic data, cardiovascular diseases, kidney disease and depressive symptoms on cognition. Methods: A cross-sectional study of patients with cardiovascular diseases was performed. The Montreal Cognitive Assessment (MoCA) was applied for cognitive evaluation. Based on MoCA three groups were defined: preserved cognition, mild, and advanced cognitive dysfunction (CD). Data were analyzed using Cronbach alpha (Cα) and McDonald's ω (Mω) for internal consistency. The Chi-square test, Cramer's V test, and correlation analyses were also applied. Results: Of 628 patients, 55.2% had mild CD, and the mean age was 67.95 (SD 9.53) years. Cα and Mω were 0.7, indicating good internal consistency. We found a moderate positive correlation between depression and the severity of CD (r = 0.25, p = 0.0001). A weak association between CD and female gender (p = 0.016), atrial fibrillation (p = 0.03), stroke (p = 0.009), and a moderate association for age group (p < 0.0001), education level (p < 0.0001), smoking (p < 0.0001), and renal dysfunction (p < 0.0001) was found. Age ≥ 70 years, eGFR 30-59 mL/min/1.73m2 significantly increased the likelihood for mild and advanced CD, while smoking and > 9 classes decreased it. Female gender, history of atrial fibrillation, and stroke significantly increased the likelihood of advanced CD. Conclusion: Mild CD was the most common in patients with cardiovascular diseases. Older age, lower education, being a non-smoker, and renal dysfunction were risk factors for both mild and advanced CD. Female gender, previous diagnosis of atrial fibrillation, and stroke are risk factors for advanced CD.


Asunto(s)
Enfermedades Cardiovasculares , Disfunción Cognitiva , Depresión , Humanos , Femenino , Masculino , Anciano , Estudios Transversales , Factores de Riesgo , Persona de Mediana Edad , Depresión/epidemiología
15.
Sci Rep ; 14(1): 15740, 2024 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977862

RESUMEN

Genome replication is frequently impeded by highly stable DNA secondary structures, including G-quadruplex (G4) DNA, that can hinder the progression of the replication fork. Human WRNIP1 (Werner helicase Interacting Protein 1) associates with various components of the replication machinery and plays a crucial role in genome maintenance processes. However, its detailed function is still not fully understood. Here we show that human WRNIP1 interacts with G4 structures and provide evidence for its contribution to G4 processing. The absence of WRNIP1 results in elevated levels of G4 structures, DNA damage and chromosome aberrations following treatment with PhenDC3, a G4-stabilizing ligand. Additionally, we establish a functional and physical relationship between WRNIP1 and the PIF1 helicase in G4 processing. In summary, our results suggest that WRNIP1 aids genome replication and maintenance by regulating G4 processing and this activity relies on Pif1 DNA helicase.


Asunto(s)
ADN Helicasas , Replicación del ADN , G-Cuádruplex , Humanos , ADN Helicasas/metabolismo , Daño del ADN , Aberraciones Cromosómicas , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , ATPasas Asociadas con Actividades Celulares Diversas/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética
16.
Crit Care Med ; 41(11): e344-51, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23949471

RESUMEN

OBJECTIVE: Cardiogenic shock often leads to splanchnic macro- and microcirculatory complications, and these events are linked to local and systemic inflammatory activation. Our aim was to investigate the consequences of complement C5a antagonist treatment on the early circulatory and inflammatory changes in a clinically relevant large animal model of cardiac tamponade. DESIGN AND SETTING: A randomized, controlled in vivo animal study in a university research laboratory. SUBJECTS: Anesthetized, ventilated, and thoracotomized Vietnamese mini pigs (24 ± 3 kg). INTERVENTIONS: Group 1 (n = 6) served as sham-operated control. In group 2 (n = 7), cardiac tamponade was induced for 60 minutes by the administration of intrapericardial fluid, while the mean arterial pressure was kept in the interval 40 to 45 mm Hg. Group 3 (n = 6) was treated with a complement C5a antagonist compound (the peptide acetyl-peptide-A, 4 mg/kg) after 45 minutes of tamponade. MEASUREMENTS AND MAIN RESULTS: The macrohemodynamics, including the superior mesenteric artery flow, was monitored; the average red blood cell velocity in the small intestinal mucosa was determined by an intravital orthogonal polarization imaging technique. The whole blood superoxide production, the plasma level of high-mobility group box protein-1 and big-endothelin and the small intestinal myeloperoxidase activity were measured. One hundred eighty minutes after the relief of tamponade, the mean arterial pressure was decreased, while the plasma levels of superoxide, high-mobility group box protein-1, and big-endothelin, and the intestinal myeloperoxidase activity were increased. The administration of acetyl-peptide-A normalized the mean arterial pressure and preserved the cardiac output, while the superior mesenteric artery flow and mucosal average red blood cell velocity were increased significantly, and the plasma superoxide, high-mobility group box protein-1, big-endothelin, and intestinal myeloperoxidase levels were reduced. CONCLUSIONS: These results provide evidence that blockade of the C5a effects significantly influences the acute splanchnic macro- and microhemodynamic complications and decreases the potentially harmful inflammatory consequences of experimental cardiogenic shock.


Asunto(s)
Taponamiento Cardíaco/terapia , Complemento C5a/antagonistas & inhibidores , Péptidos/farmacología , Animales , Taponamiento Cardíaco/fisiopatología , Modelos Animales de Enfermedad , Endotelina-1/metabolismo , Femenino , Proteína HMGB1/metabolismo , Hemodinámica , Histamina/sangre , Mucosa Intestinal/irrigación sanguínea , Masculino , Microcirculación , Distribución Aleatoria , Superóxidos/metabolismo , Porcinos
17.
Curr Microbiol ; 66(3): 243-50, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23143288

RESUMEN

In this study, more than 150 bacteria showing antagonistic properties against bacterial and fungal pathogens of the tomato plant were isolated and characterized. The most efficient agents against these phytopathogenic microorganisms belong to the genus Bacillus: the best biocontrol isolates were representatives of Bacillus subtilis, B. mojavensis and B. amyloliquefaciens species. They intensively produced fengycin or/and surfactin depsipeptide antibiotics and also proved to be excellent protease secretors. It was proved, that the selected strains were able to use ethylenethiourea (ETU) as sole nitrogen source. These antagonistic and ETU-degrading Bacillus strains can be applied as biocontrol and also as bioremediation agents.


Asunto(s)
Antibiosis , Bacillus/aislamiento & purificación , Bacillus/metabolismo , Etilenotiourea/metabolismo , Antibacterianos/biosíntesis , Bacillus/clasificación , Bacillus/genética , Biodegradación Ambiental , Girasa de ADN/genética , Hongos/metabolismo , Solanum lycopersicum/microbiología , Datos de Secuencia Molecular , ARN Ribosómico 16S , Rizosfera , Microbiología del Suelo
18.
Mol Membr Biol ; 29(7): 274-89, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22583025

RESUMEN

The in vitro culture of cells offers an extremely valuable method for probing biochemical questions and many commonly-used protocols are available. For mammalian cells a source of lipid is usually provided in the serum component. In this study we examined the question as to whether the nature of the lipid could become limiting at high cell densities and, therefore, prospectively influence the metabolism and physiology of the cells themselves. When B16 mouse melanoma cells were cultured, we noted a marked decrease in the proportions of n-3 and n-6 polyunsaturated fatty acids (PUFAs) with increasing cell density. This was despite considerable quantities of these PUFAs still remaining in the culture medium and seemed to reflect the preferential uptake of unesterified PUFA rather than other lipid classes from the media. The reduction in B16 total PUFA was reflected in changes in about 70% of the molecular species of membrane phosphoglycerides which were analysed by mass spectrometry. The importance of this finding lies in the need for n-3 and n-6 PUFA in mammalian cells (which cannot synthesize their own). Although the cholesterol content of cells was unchanged the amount of cholesterol enrichment in membrane rafts (as assessed by fluorescence) was severely decreased, simultaneous with a reduced heat shock response following exposure to 42°C. These data emphasize the pivotal role of nutrient supply (in this case for PUFAs) in modifying responses to stress and highlight the need for the careful control of culture conditions when assessing cellular responses in vitro.


Asunto(s)
Ácidos Grasos Insaturados/farmacología , Glicerofosfolípidos/metabolismo , Respuesta al Choque Térmico/efectos de los fármacos , Melanoma/metabolismo , Animales , Línea Celular Tumoral , Medios de Cultivo/farmacología , Ácidos Grasos Insaturados/metabolismo , Calor , Melanoma/patología , Ratones
19.
J Pers Med ; 13(3)2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36983669

RESUMEN

International trends indicate that celiac disease (CeD) is becoming more common, while the clinical presentation of CeD tends to change. We aimed to investigate factors associated with the clinical presentation of CeD. We reviewed all CeD cases diagnosed at our tertiary center, University of Pécs (Hungary), between 1992 and 2019. We collected data of verified CeD patients on clinical presentations (classified by the Oslo Classification), the age at and calendar year of diagnosis, and sex, serology and histology at diagnosis. To assess the associations of baseline variables with clinical presentations, we applied univariate and multivariate (binary logistic regression) statistics. A total of 738 CeD patients were eligible for inclusion. In the univariate analysis, patients with classical CeD were more common in the latest calendar period (p < 0.001) and tended to be older (p = 0.056), but we failed to observe a significant association between the clinical presentation and sex, serology or histology at diagnosis. In the multivariate analysis, only age at diagnosis and calendar year were independently associated with clinical presentations (OR = 1.02, CI: 1.01-1.04 and OR = 0.93, CI: 0.89-0.98, respectively). Our findings confirmed that classical CeD is independently associated with age at diagnosis and calendar year of diagnosis of CeD, whereas other parameters were not significantly associated with clinical presentations.

20.
Life (Basel) ; 13(2)2023 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-36836668

RESUMEN

(1) Background: Cognitive dysfunction is a major concern in hypertensive patients. Lifestyle habits and nutrition influence laboratory parameters, with an impact on clinical course. The objective of the study was to evaluate nutrition and lifestyle habits in hypertensive patients with/without cognitive dysfunction and establish correlations to laboratory parameters. MATERIAL AND METHODS: 50 patients admitted to the Cardiovascular Rehabilitation Clinic in Târgu Mureș were enrolled in this study between March-June 2021. We evaluated their cognitive function, and they filled in a questionnaire about lifestyle and nutrition. Biochemical blood tests were performed using a Konelab Prime 60i analyzer. IBM-SPSS22 and GraphPad InStat3 were used for statistics. RESULTS: Mean age of hypertensive patients (n = 50) was 70.42 ± 4.82 (SD) years, half of them had cognitive dysfunction. Zinc deficiency was present in 74% of the subjects. The subgroup with cognitive dysfunction had significantly higher BMI (p = 0.009) and microalbuminuria (p = 0.0479), as well as significantly lower magnesium intake (p = 0.032) and cholesterol intake (p = 0.022), compared to those with normal cognitive status. CONCLUSIONS: Nutrition is in a close relationship with laboratory parameters; significant differences (microalbuminuria, cholesterol intake, BMI, etc.) are present between hypertensive patients with/without cognitive dysfunction. A healthy diet is important for the maintenance of metabolic balance, the achievement of optimal body weight, and the prevention of complications.

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