RESUMEN
Stroke is a common multifactorial disease, and the third leading cause of death worldwide, which results in serious long-term mental and physical disability among survivors. The role of affected triglyceride metabolism in the development of ischemic stroke is under extensive investigations. Here, we examined three SNPs, rs12130333 located within the ANGPTL3 locus; rs16996148 residing at the CILP2 gene locus; and rs17321515 at the TRIB1 locus, which were originally reported in association with decreased triglyceride levels; therefore, we investigated their possible protective effect against the development of ischemic stroke. A total of 459 Caucasian stroke patients, stratified as large-vessel, small-vessel, and mixed stroke groups, and 168 control subjects were genotyped using PCR-RFLP methods. As a result, we could not detect any differences in triglyceride or total cholesterol levels in relation to any allelic variants of rs16996148, rs17321515, or rs12130333 SNPs. No correlation was found between the minor alleles rs16996148-T (P = 0.881), rs17321515-G (P = 0.070), or rs12130333-T allele (P = 0.757) and the risk for development of stroke. The data presented here suggest different scale of effect of triglyceride modifier alleles and also their variable susceptibility or protective nature.
Asunto(s)
Angiopoyetinas/genética , Isquemia Encefálica/genética , Proteínas de la Matriz Extracelular/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Polimorfismo de Nucleótido Simple , Proteínas Serina-Treonina Quinasas/genética , Pirofosfatasas/genética , Accidente Cerebrovascular/genética , Triglicéridos/metabolismo , Anciano , Alelos , Proteína 3 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Isquemia Encefálica/fisiopatología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUNDS AND AIMS: The IGR2198a_1 and IGR2096a_1 variants of the IBD5 region were found to be associated with Crohn's disease (CD) in the Hungarian population, while IGR2230a_1 does not seem to confer risk for the disease. In the present study, our aim was to investigate the statistical interaction of these three IBD5 polymorphisms with the +49 A/G substitution within the cytotoxic T lymphocyte antigen-4 (CTLA4) gene, detected previously as neutral gene variant in Hungarian IBD patients. METHODS: A total of 305 unrelated subjects with CD and 310 healthy controls were genotyped with PCR-RFLP methods. RESULTS: In contrast with single gene effects, after genotype stratification, the IGR2198a_1 C and IGR2096a_1 T variants were found to confer susceptibility only in subjects with CTLA4 +49 AA genotype (P = 0.008; OR = 1.86 and P = 0.016; OR = 1.74, respectively), for IGR2230a_1 no such effect on disease risk could be demonstrated. CONCLUSION: Analysis of specific genotype combinations unfolded a possible association between the CTLA4 +49 A/G substitution and two of the observed IBD5 variants with respect to disease risk.
Asunto(s)
Antígeno CTLA-4/genética , Enfermedad de Crohn/genética , Epistasis Genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Humanos , Hungría , Masculino , Factores de RiesgoRESUMEN
We studied cardioprotective as well as Akt and extracellular signal-activated kinase (ERK) activating effect of a Ca(2+) antagonist and a beta-adrenergic receptor blocker during ischemia-reperfusion, and compared these properties of the substances with that of a poly(ADP-ribose) polymerase (PARP) inhibitor used as a positive control throughout the experiments. Langendorff-perfused isolated rat hearts were subjected to 25 min global ischemia followed by 45 min reperfusion, and recovery of energy metabolism as well as functional cardiac parameters were monitored. Although to varying extents, all substances improved recovery of creatine phosphate, ATP, intracellular pH, and reutilization of inorganic phosphate. These favorable changes were accompanied by improved recovery of heart function parameters and reduced infarct size. In addition and again to varying extents, all studied substances decreased oxidative damage (lipid peroxidation and protein oxidation), and activated Akt, glycogen synthase kinase (GSK)-3beta, and ERK1/2. Correlation between cardioprotective and kinase activating effectivity of the compounds proved to be statistically significant. Physiological significance of these kinase activations was established by demonstrating that inhibition of Akt by LY294002 and ERK1/2 by PD98059 compromised the cardioprotective effect of all the substances studied. In conclusion, we demonstrated for the first time that activation of phosphatidylinositol-3-kinase (PI-3K)-Akt and ERK2 pathways significantly contributed to cardioprotective effects of a Ca(2+) antagonist and a beta-adrenergic receptor blocker. Furthermore, we found a strong correlation between cardioprotective and kinase-activating potencies of the substances studied (Verapamil, Metoprolol and two PARP inhibitors), which indicated the potentiality of these kinases as drug-targets in the therapy of ischemic heart disease.
Asunto(s)
Antagonistas Adrenérgicos beta/metabolismo , Bloqueadores de los Canales de Calcio/metabolismo , Cardiotónicos/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Miocardio/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Daño por Reperfusión/metabolismo , Animales , Bencimidazoles/metabolismo , Activación Enzimática , Inhibidores Enzimáticos/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Peroxidación de Lípido , Masculino , Metoprolol/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/patología , Oxidación-Reducción , Fosfatos/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/patología , Transducción de Señal/fisiología , Verapamilo/metabolismoRESUMEN
BACKGROUND: The increasing incidence of bacterial infections in orthopedic surgery might be related to the increasing application of artificial devices. In most cases, bacteria multiply on the surface of implants in biofilms. Poor penetration of antibiotics, frequent necessity of prosthesis removal, chronic processes and financial costs emphasize the significance of preventive measures. METHOD: Adhesion of bacterial strains (two Staphylococcus aureus, two coagulase-negative staphylococci and two Pseudomonas aeruginosa strains isolated from orthopedic patients' wounds) to the surface of a polyethylene cup was investigated using an ultrasonic method. Results were compared to the adhesive ability of three Hungarian standard strains. The effect of antibiotic treatment (cefuroxime, cefotaxime, amoxicillin with clavulanic acid and amikacin) has been examined. RESULTS: The staphylococcal strains showed significantly higher adhesive ability than Pseudomonas strains. Antibiotic treatment significantly reduced the attachment of bacteria. The higher the concentration of the antibiotics, the higher was the decrease in bacterial adhesion. CONCLUSIONS: Antibiotic prophylaxis was proven to be effective against bacterial adhesion, and, if applied at the proper time at the highest tolerable dose, it might prevent the formation of biofilms.
Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Adhesión Bacteriana/efectos de los fármacos , Prótesis e Implantes/microbiología , Biopelículas , Niño , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/etiología , Infecciones por Pseudomonas/prevención & control , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Pseudomonas aeruginosa/fisiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/prevención & control , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/fisiologíaRESUMEN
BACKGROUND: Despite antibiotic prophylaxis and treatment, the incidence of wound infections in orthopedic surgery is significant. Postoperative wound infection is a multifactorial process, which can be modified by several bacterial factors. Cell surface hydrophobicity of bacteria is a very important physicochemical feature, which has a great influence on the ability of bacteria to adhere to the surface of host cells or medical implants. METHODS: In this study, the hydrophobic properties of thirteen bacterial strains (coagulase-negative staphylococci, Staphylococcus aureus and Pseudomonas aeruginosa) isolated from patients with postoperative deep wound infections following orthopedic procedures were determined by the salt aggregation test. Results were compared to the hydrophobicity of three Hungarian standard bacterial strains. The modifying effect of four antibiotics (cefuroxime, cefotaxime, amoxicillin combined with clavulanic acid and amikacin)--applied most often in our Department for prophylaxis and treatment of patients--were analyzed. RESULTS: The cell surface hydrophobicity of certain strains showed considerable changes after antibiotic treatment. These alterations indicated the decrease in hydrophobicity. Supra-inhibitory concentrations (2x minimum inhibitory concentrations, MIC) of the antibiotics were able to induce more frequent alterations in hydrophobicity than sub-inhibitory (0.5x MIC) levels. CONCLUSIONS: Alterations in cell surface hydrophobicity caused by antibiotics can modify the adhesion process and thus the pathogenicity of bacterial strains. These changes should be taken into consideration in the management of proper antibiotic prophylaxis and in the treatment of orthopedic patients.