RESUMEN
OBJECTIVE: Denture base materials are susceptible to fungal adhesion, which is an important etiological issue in the pathogenesis of denture stomatitis. The purpose of this in vitro study was to evaluate the antifungal activity and cytotoxicity of denture base material containing silver microparticles. MATERIALS AND METHODS: The polymethyl methacrylate (PMMA) denture base material was used, and silver microparticles were added to the polymer powder in different concentrations by volume (0%, 0.25%, 0.5%, and 1%). Their antifungal activity against Candida albicans was assessed in terms of colony-forming units. PMMA disc specimens containing silver microparticles were eluted with culture medium for 1, 2, and 5 days. The cytotoxicity of the eluates to cultured L929 mouse fibroblast cells was evaluated using a real-time cell analysis (RTCA) system and the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. RESULTS: The antifungal effect against C. albicans increased with the percentage of silver microparticles (P < 0.05). For both tests, both RTCA and the MTT assay, no time- or silver-dependent cytotoxicity of PMMA denture base material containing silver microparticles was observed. CONCLUSIONS: PMMA denture base material containing silver microparticles have antifungal activity and no cytotoxic effect.
Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Bases para Dentadura , Polimetil Metacrilato/farmacología , Plata/farmacología , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
In this study we looked at smokers with and without chronic obstructive pulmonary disease (COPD) patients in order to evaluate the incidence of 4977 base pair (bp) mtDNA (mtDNA4977) deletion and mtDNA copy number in sputum cells and in peripheral blood leukocytes (PBLs) in relation to mitochondrial function and oxidative stress status. Twenty-five COPD patients who were current smokers, 22 smokers and 23 healthy nonsmokers (for only PBLs studies) participated in this study. The 4977-bp deletion was detected in all examined samples within 40 cyles of PCR amplification, using a quantitative real time PCR. The frequency of the mtDNA4977 was significantly higher in the sputum cells of patients with COPD compared to smokers without COPD (p < 0.0001). This difference was not observed in PBLs. Levels of cellular oxidative stress were significantly higher in the sputum cells of subjects with COPD than in the smoker group. However, mtDNA copy number, mitochondrial membrane potential (ΔΨm) and cellular ATP levels in PBLs and sputum cells were not significantly different between the studied groups. The Pearson analysis revealed no correlations between the accumulation of mtDNA4977, and intracellular ATP content and ΔΨm values of the sputum cells, although there was a positive correlation between the increase in the percentage of deleted mtDNA4977 and the levels of cellular oxidative stress in COPD patients (r = 0.80, p < 0.0001). Our studies may suggest that the accumulation of mtDNA4977 in the sputum cells of smokers with COPD does not seem to have an important impact on mitochondrial dysfunction in relation to ATP production and ΔΨm when compared to those of healthy smokers.
Asunto(s)
Adenosina Trifosfato/análisis , Fumar Cigarrillos , Genoma Mitocondrial , Enfermedad Pulmonar Obstructiva Crónica/genética , Eliminación de Secuencia , Esputo/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Fumadores , Esputo/metabolismoRESUMEN
The Behçet's disease (BD)-associated human leukocyte antigen (HLA) allele, HLA-B*51 (B*51), encodes a ligand for a pair of allelic killer immunoglobulin-like receptors (KIR) present on cytotoxic cells-KIR3DL1, which inhibits their cytotoxicity, and KIR3DS1, which activates their cytotoxic activity. We tested whether KIR-regulated mechanisms contribute to BD by testing for association of KIR3DL1/KIR3DS1 genotypes with disease in 1799 BD patients and 1710 healthy controls from Turkey, as well as in different subsets of individuals with HLA-type-defined ligands for the KIR3D receptors. HLA types were imputed from single nucleotide polymorphism genotypes determined with the Immunochip. The presence of inhibitory KIR3DL1 or activating KIR3DS1 alleles did not differ significantly between cases and controls (KIR3DL1: 92.9% vs 93.4%, Pdominant=0.55; KIR3DS1: 42.7% vs 41.0%, Pdominant=0.29). The KIR3DL1/KIR3DS1 alleles were also present at similar frequencies among cases and controls bearing HLA-B with a Bw4 motif; HLA-B with a Bw4 motif with isoleucine at position 80; and HLA-B*51. Our results suggest that pathogenic mechanisms associated with HLA-B*51 do not primarily involve differential interactions with KIR3DL1 and KIR3DS1 receptors. However, due to the complexity of this locus (that is, sequence variation and copy number variation), we cannot exclude a role for other types of KIR variation in the pathogenesis of BD.
Asunto(s)
Síndrome de Behçet/genética , Polimorfismo de Nucleótido Simple , Receptores KIR3DL1/genética , Receptores KIR3DS1/genética , Genotipo , Antígenos HLA/genética , HumanosRESUMEN
Proton pump inhibitors (PPI) metabolism and pharmacokinetics are regulated by cytochrome P450 enzymes in the liver. Cytochrome P450 2C19 (CYP2C19) polymorphism plays an import role in the metabolism of PPIs. The three possible genotypes for CYP2C19 each has a distinct effect on the pharmacodynamics of PPIs. Homozygote extensive metabolizers (HomEM) are the most frequent genotype and have two wild-types (non-mutant) (*1/*1) alleles. HomEM is associated with increased enzyme activity, which increases the rate of PPI metabolism. Intragastric pH, which is required for eradication, is lowest in HomEM. In HomEMs, an insufficient increase in intragastric pH results in decreased anti-Helicobacter pylori (HP) efficacy of the antibiotics and, therefore, lower eradication rates. We determined whether the HP eradication rate would increase after high-dose PPI treatment of extensive PPI metabolizers who had been treated unsuccessfully with a standard PPI dose. In our report, increasing the PPI dosage in patients with genotype polymorphisms may be effective on eradication rates. Eradication rates are directly affected by CYP2C19 polymorphisms, and eradication treatments should be planned considering such genotypic polymorphisms. Hence, CYP2C19 genotyping prior to treatment may facilitate determination of the optimum PPI dose to improve the therapeutic outcome. However, further researches are required to confirm this hypothesis.
Asunto(s)
Helicobacter pylori/efectos de los fármacos , Inhibidores de la Bomba de Protones/administración & dosificación , Citocromo P-450 CYP2C19/genética , Genotipo , Infecciones por Helicobacter/tratamiento farmacológico , HumanosRESUMEN
OBJECTIVE: Cytochrome P450 2C19 (CYP2C19) polymorphisms play an important role in the metabolism of proton pump inhibitors. Rabeprazole is primarily metabolized via non-enzymatic pathways. In this study, we determined whether rabeprazole- and pantoprazole-based eradication treatments were influenced by CYP2C19 polymorphisms. PATIENTS AND METHODS: A total of 200 patients infected with Helicobacter pylori were treated with either 40 mg of pantoprazole or 20 mg of rabeprazole plus 500 mg of clarithromycin, 1000 mg of amoxicillin twice daily for 2 weeks. CYP2C19 genotype status was determined by Polymerase Chain Reaction (PCR)-restriction-fragment-length polymorphism. The genotypes of cytochrome P450 2C19 were classified as homozigote extensive metabolizer (HomEM), heterozigote metabolizer (HetEM) and poor metabolizer (PM). The CYP2C19 genotype of all patients, the effectiveness of the treatment, the effect of the genotypic polymorphism on the treatment were assessed. RESULTS: The frequencies of HotEM, HetEM, PM were 78%, 19.5% and 2.5%, respectively. 48% (n = 96) of the patients received treatment with rabeprazole and 52% (n = 104) with pantoprazole. The eradication rate was 64.7% for HomEM, 79.4% for HetEM, 100% for PM (p = 0.06). In HetEM, PM, are considered as a single group, the eradication rates were higher in patients with the HetEM and PM (HetEM+PM) genotypes than in those with the wild-type genotype (81.8 vs. 64.7% p = 0.031). Among the patients treated with rabeprazole, the eradication rates were significantly lower in those with the HomEM genotype than in those with the HetEM+PM genotypes (60% vs. 85.7% p = 0.023). CONCLUSIONS: The genotypic polymorphism is effective on the rate of eradication. Eradication treatment rate with rabeprazole is influenced by CYP2C19 genotype.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Citocromo P-450 CYP2C19/genética , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/genética , Polimorfismo de Longitud del Fragmento de Restricción , Rabeprazol/administración & dosificación , Adolescente , Adulto , Anciano , Amoxicilina/administración & dosificación , Claritromicina/administración & dosificación , Quimioterapia Combinada , Femenino , Genotipo , Helicobacter pylori/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificación , Pantoprazol , Inhibidores de la Bomba de Protones/administración & dosificación , Adulto JovenRESUMEN
OBJECTIVE: Familial Mediterranean fever (FMF), an autosomal recessively inherited autoinflammatory disorder, is caused by missense mutations in the pyrin-encoding MEFV gene. The MEFV mutations can be detected in the majority of FMF patients, but there is an important proportion of patients with the FMF phenotype who carry a single or no coding region mutation. This study aimed to investigate the promoter region and 3'-UTR polymorphisms of the MEFV gene in a group of FMF patients with no coding region mutations, to identify variations with a possible role in the regulation of MEFV expression. METHODS: The study group consisted of 289 patients with FMF and 103 ethnically-matched healthy individuals of Turkish origin. All individuals were first genotyped for the five most commonly observed mutations (M694V, M680I, V726A, E148Q and M694I). Then, the coding regions of the MEFV gene in patients carrying none of the 5 mutations were amplified and screened using single-stranded conformation polymorphism and DNA sequencing. After the exclusion of patients with mutations in exons, the promoter and 3'-UTR regions of the MEFV gene were investigated in the remainder. For the haplotype analysis, all study groups were genotyped for two of the 3'-UTR single nucleotide polymorphisms (SNP). RESULTS: Genotyping for five mutations revealed 186 patients (64.4%) with two mutations, 61 patients (21.1%) with one mutation, and 42 patients (14.5%) with no mutation. The carrier rate for healthy controls was found to be 10%. After screening all 10 exons in the patients with none of the 5 mutations, we identified 36 patients (12.5%) who had no coding region mutations. Analysis of the 3'-UTR region in these patients showed two Alu repeats (AluSx and AluSq), which were located in the 3'-UTR of the reference mRNA sequence. Sequencing of the 3'-UTR of the MEFV gene showed several SNPs that were clustered in 2 haplotypes. When we genotyped all study groups for two of the 3'-UTR SNPs (rs2741918 and rs450021), we observed a significant increase in the frequency of heterozygotes for the 3'-UTR haplotypes in the FMF patients with no coding region polymorphisms compared to the healthy controls (75% versus 48.5%, p=0.006, OR=3.2, 95% CI 1.4-7.4). CONCLUSION: This study showed a group of 3'-UTR polymorphisms in the MEFV gene that are clustered in two haplotypes. In addition, a genetic association was observed between 3'-UTR polymorphisms and the FMF patients with no coding region mutations. These findings may suggest a role for 3'-UTR sequences in the regulation of MEFV expression.
Asunto(s)
Regiones no Traducidas 3'/genética , Proteínas del Citoesqueleto/genética , Fiebre Mediterránea Familiar/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Elementos Alu/genética , Estudios de Casos y Controles , Haplotipos , Humanos , Regiones Promotoras Genéticas/genética , PirinaRESUMEN
CONTEXT: Effects of erythropoietin on parathyroid cell function has not been studied before. OBJECTIVE: We aimed to demonstrate whether erythropoietin receptor present in parathyroid cells. DESIGN: The specimens of normal parathyroid gland, parathyroid adenoma and hyperplasia were retrieved from our pathology archives. The sections were stained immunohistochemically. Quantitative gene expression study was performed for erythropoietin and erythropoietin receptor. RESULTS: Erythropoietin receptors were detected by immunohistochemical staining and by its gene expression. Its density was higher in normal parathyroid, followed by parathyroid adenoma and hyperplasia. CONCLUSION: Erythropoietin receptor is present in normal parathyroid, parathyroid adenoma, and hyperplasia.
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Adenoma/metabolismo , Glándulas Paratiroides/metabolismo , Neoplasias de las Paratiroides/metabolismo , Receptores de Eritropoyetina/metabolismo , Adenoma/patología , Eritropoyetina/genética , Eritropoyetina/metabolismo , Regulación de la Expresión Génica , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Glándulas Paratiroides/patología , Neoplasias de las Paratiroides/patología , Receptores de Eritropoyetina/genéticaRESUMEN
Facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant disorder, represents the third most common human muscular dystrophy. The FSHD disease locus, at chromosome 4q35, is associated with large contractions of the polymorphic repeat sequence array D4Z4. In addition to FSHD disease association with large D4Z4 deletions, a biased interaction with a specific 4qter subtelomeric sequence has been described in patients. Two distinct 4qter subtelomeres, defined as types 4qA and 4qB, have been identified and shown to be equally prevalent in the Caucasian population. In almost all 4q35-linked patients with FSHD, however, disease expression only occurs when large D4Z4 deletions are located on 4qA-defined 4qter subtelomeres. Conversely, large D4Z4 repeat contractions situated on 4qB-defined subtelomeres either are not disease-causing or exhibit a greatly reduced disease penetrance. This study was initiated to confirm this direct FSHD disease association data by measuring the frequency of type 4qA-defined and 4qB-defined subtelomeric sequences in a large cohort of 164 unrelated patients with FSHD from Turkey and the UK, all known to have large D4Z4 deletions. An almost complete association was found between large D4Z4 repeat array deletions located on 4qA-defined 4qter subtelomeres and disease expression in our large FSHD patient cohort. The observed failure of probes 4qA and 4qB to hybridise to two patient-derived DNA samples confirms the presence of an additional rare type of 4qter subtelomeric sequence in humans.
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Cromosomas Humanos Par 4/genética , Repeticiones de Minisatélite , Distrofia Muscular Facioescapulohumeral/genética , Eliminación de Secuencia , Australia , Cromosomas Humanos Par 4/ultraestructura , Estudios de Cohortes , ADN Complementario/genética , Electroforesis en Gel de Campo Pulsado , Genes Dominantes , Humanos , Sondas de Oligonucleótidos , Penetrancia , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Turquía , Reino UnidoRESUMEN
In one couple investigated because of recurrent abortions, the female was found to have an unusual translocation between the long arm of the telomeric region of chromosome 12 and the long arm of the chromosome 14 at band q11. We studied ten additional members of the family who were under the risk of the same chromosomal rearrangement, and four of them were found to be carriers. The diagnosis of this translocation was determined using different banding techniques and FISH. The karyotype was found to be 45,XX,t(12;14)(qtel;q11).
Asunto(s)
Cromosomas Humanos Par 12 , Cromosomas Humanos Par 14 , Translocación Genética , Aborto Habitual/genética , Adulto , Femenino , Humanos , Cariotipificación , Masculino , Linaje , Embarazo , TelómeroRESUMEN
Common variable immune deficiency (CVID) is characterized by low immunoglobulin levels and recurrent infections in patients with a period of normal immune function several years after birth. It is associated with diarrhea, malabsorption, bronchiectasis, and lymphoreticular malignancies. Radiation-induced chromosome instability may contribute to the high degree of susceptibility to neoplasia. Peripheral blood lymphocyte cultures were obtained from six patients with CVID and the healthy control group matched by age and sex. The groups did not differ in the frequency of spontaneous chromosome aberrations. After exposure to X-ray radiation, mitotic indices were found to be significantly low and incidence of chromosomal alterations were high in the CVID group. We conclude that chromosomes of cells from patients with CVID are significantly more radiosensitive than those of controls. Thus these patients must be protected from unnecessary X-ray examinations and in case of radiosensitive tumour, the dose of irradiation should be carefully monitored.