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1.
Oncol Lett ; 22(5): 805, 2021 Nov.
Article En | MEDLINE | ID: mdl-34630712

MicroRNAs (miRs) modulate the expression of target genes in the signal pathway on transcriptome level. The present study investigated the 'epigenetic-based miRNA (epi-miRNA)-mRNA' regulatory network of miR-34b, miR-34c, miR-148a, miR-152, miR-200a and miR-200b epi-miRNAs and their target genes, DNA methyltransferase (DNMT1, 3a and 3b), phosphate and tensin homolog (PTEN) and NK3 Homeobox 1 (NKX3.1), in prostate cancer (PCa) using reverse transcription-quantitative PCR. The expression level of NKX3.1 were not significantly different between the PCa, Met-PCa and control groups. However, in the PCa and Met-PCa groups, the expression level of DNMT1 was upregulated, while DNMT3a, DNMT3b and PTEN were downregulated. Overexpression of DNMT1 (~5 and ~6-fold increase in the PCa and Met-PCa groups respectively) was accompanied by a decreased expression in PTEN, indicating a potential negative association. Both groups indicated that a high level of DNMT1 is associated with the aggressiveness of cancer, and there is a a directly proportional relationship between this gene and PSA, GS and TNM staging. A significant ~2 to ~5-fold decrease in the expression levels of DNMT3a and DNMT3b was found in both groups. In the PCa group, significant associations were identified between miR-34b and DNMT1/DNMT3b; between miR-34c/miR-148a and all target genes; between miR-152 and DNMT1/DNMT3b and PTEN; and between miR-200a/b and DNMT1. In the Met-PCa group, miR-148a, miR-152 and miR-200b exhibited a significant association with all target genes. A significant negative association was identified between PTEN and DNMT1 in the Met-PCa group. It was also revealed that that miR-148a, miR-152 and miR-200b increased the expression of DNMT1 and suppressed PTEN. Furthermore, the 'epi-miRNA-mRNA' bidirectional feedback loop was emphasised and the methylation pattern in PCa anti-cancer therapeutics was highlighted.

2.
Vaccine ; 39(15): 2041-2047, 2021 04 08.
Article En | MEDLINE | ID: mdl-33741188

PURPOSE: In Turkey, pneumococcal conjugate vaccine (PCV) was introduced to the national immunization program as PCV7 in 2008, and was replaced with PCV13 in 2011. The aim of the study was to demonstrate the pneumococcal carriage rate and the serotype distribution in healthy children under 5 years in Turkey who were vaccinated with PCV13. METHODS: We conducted a cross-sectional study including the collection of questionnaire data and nasopharyngeal (NP) specimens among children aged <5 years from five centers from March 2019 to March 2020. Pneumococcal isolates were identified using optochin sensitivity and bile solubility. Serotyping was performed using a latex agglutination kit and Quellung reaction. RESULTS: NP swab samples were collected from 580 healthy children. The observed overall carriage rate was 17.8%. None of the hypothesised predictors of S. pneumoniae carriage, except maternal education level was statistically significant (p = 0.017). High maternal education level appeared to decrease the risk (lower vs. higher maternal education OR: 1.992 [95% CI; 1.089-3.643], p = 0.025). The overall NP S. pneumoniae carriage prevalence for the PCV13-vaccinated children was 17.8% (103/580). The most common serotypes detected were serotype 15B (n = 10, 9.7%), serotype 23F (n = 9, 8.7%), serotype 23A (n = 9, 8.7%), serotype 11A (n = 7, 6.7%), serotype 19F (n = 5, 4.8%) and serotype 15F (n = 5, 4.8%). Of the isolates, 28 (27.2%) were in PCV13 vaccine strains (VSs), and 75 (72.8%) strains were non-VS. The serotype coverage rate was 27.2% for PCV13. CONCLUSION: The overall S. pneumoniae carriage rate was higher than in earlier studies from Turkey. Post-vaccine era studies from around the world have reported a decrease in VS serotypes and a 'serotype replacement' to non-VS serotypes, as we determined in our study.


Pneumococcal Infections , Streptococcus pneumoniae , Carrier State/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Nasopharynx , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Serogroup , Turkey/epidemiology
3.
Gene ; 758: 144963, 2020 Oct 20.
Article En | MEDLINE | ID: mdl-32683077

Abnormal expression of enzymes involved in epigenetic mechanisms, such as DNA methyl transferases, can trigger large chaos in cellular gene expression networks and eventually lead to cancer progression. In our study, which is a pioneer in the literature that clinicopathologically evaluates the expression of 30 epi-miRNAs in prostate cancer (PCa), we investigated which of the new miRNA class epi-miRNAs could be an effective biomarker in the diagnosis and progression of PCa. In this study, the expression levels of 30 epi-miRNAs in whole blood samples from 25 control, 25 PCa and 40 metastatic PCa patients were investigated by the Quantitative Real-Time PCR method. Then, promoter methylation levels of 11 epi-miRNAs, whose expression levels were found to be significantly higher, were examined by methylation-specific qPCR method. The correlations between miRNA expression levels and clinicopathological parameters (Gleason Score (GS), PSA levels, TNM Staging) in different stages of PCa groups as well as disease-specific expression levels were examined. We found a hypomethylation in the promoter regions of miRNAs that showed a direct proportional increase with PSA levels (miR-34b/c, miR-148a, miR-152), GS's (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-148a, miR- 152, miR-185-5p) and T staging (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-140, miR-148a, miR-152, miR-185-5p) (p < 0.05). When miR-200a/b was evaluated according to clinicopathological parameters, it acted as an onco-miR in local/local advanced PCa and as a tumor-suppressor-miR in metastatic stage. This study is novel in the sense that our findings draw attention to the important role of miRNAs as diagnostic and prognostic biomarkers in PCa.


DNA Methylation/genetics , Gene Expression Regulation, Neoplastic/genetics , MicroRNAs/genetics , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/genetics , Biomarkers, Tumor/genetics , Epigenesis, Genetic/genetics , Humans , Male , Neoplasm Grading , Prognosis , Promoter Regions, Genetic/genetics , Prostate-Specific Antigen/blood , Prostatic Neoplasms/pathology
4.
J Chemother ; 32(4): 213-216, 2020 Jul.
Article En | MEDLINE | ID: mdl-32028863

Neisseria meningitidis (N. meningitidis) is regarded as the leading cause of bacterial meningitis in many regions of the world. The empiric antimicrobial treatment is mainly based on antimicrobial resistance and patient characteristics. We aimed to analyze susceptibility patterns of N. meningitidis strains isolated in Turkey. Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0-18 years of age) bacterial meningitis cases between 2013 and 2018 were studied. Five isolates (8.7%) displayed resistance to penicillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All isolates were cefotaxime and rifampin susceptible. The data shows appropriateness of third-generation cephalosporins in empirical use for meningococcal infections in children. Since Turkey is located in a transition zone geographically, surveillance reports are very crucial.


Anti-Bacterial Agents/therapeutic use , Meningitis, Meningococcal/drug therapy , Meningitis, Meningococcal/epidemiology , Neisseria meningitidis/isolation & purification , Penicillin Resistance/drug effects , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Microbial Sensitivity Tests , Turkey/epidemiology
5.
Arch. argent. pediatr ; 117(2): 155-157, abr. 2019. ilus
Article En, Es | LILACS, BINACIS | ID: biblio-1001173

El Streptococcus pneumoniae es la causa más frecuente de una neumonía complicada. La neumonía neumocócica necrosante (NNN) constituye una complicación rara y relacionada con el serotipo. Los serotipos 1, 3, 14, 15, 19A y 33 fueron los más frecuentemente informados en los niños con NNN antes de la inmunización. A pesar de la práctica extendida de la vacunación, el S. pneumoniae sigue siendo la causa de las enfermedades invasivas. Aquí se informa el caso de un niño que había recibido el esquema completo con la vacuna neumocócica conjugada de 13 serotipos (VCN13) diagnosticado con NNN del serotipo 3. La progresión de la enfermedad invasiva por S. pneumoniae debe considerarse a pesar de la inmunización completa.


Streptococcus pneumoniae is the most common cause of complicated pneumonia. Pneumococcal necrotizing pneumonia (PNP) is a rare and serotype related complication. Serotypes 1, 3, 14, 15, 19A and 33 were the most reported serotypes in children with PNP before immunization. Despite widespread vaccination, S. pneumoniae is still cause of invasive diseases. We reported a child, fully immunized with 13-valent conjugated pneumococcal vaccine (PCV13) who was diagnosed PNP due to serotype 3. Breakthrough invasive infection caused by S. pneumoniae must be considered in mind despite fully vaccination.


Humans , Male , Infant , Streptococcus pneumoniae , Child , Immunization , Pneumonia, Necrotizing
6.
Arch Argent Pediatr ; 117(2): e155-e157, 2019 04 01.
Article En, Es | MEDLINE | ID: mdl-30869496

Streptococcus pneumoniae is the most common cause of complicated pneumonia. Pneumococcal necrotizing pneumonia (PNP) is a rare and serotype related complication. Serotypes 1, 3, 14, 15, 19A and 33 were the most reported serotypes in children with PNP before immunization. Despite widespread vaccination, S. pneumoniae is still cause of invasive diseases. We reported a child, fully immunized with 13-valent conjugated pneumococcal vaccine (PCV13) who was diagnosed PNP due to serotype 3. Breakthrough invasive infection caused by S. pneumoniae must be considered in mind despite fully vaccination.


El Streptococcus pneumoniae es la causa más frecuente de una neumonía complicada. La neumonía neumocócica necrosante (NNN) constituye una complicación rara y relacionada con el serotipo. Los serotipos 1, 3, 14, 15, 19A y 33 fueron los más frecuentemente informados en los niños con NNN antes de la inmunización. A pesar de la práctica extendida de la vacunación, el S. pneumoniae sigue siendo la causa de las enfermedades invasivas. Aquí se informa el caso de un niño que había recibido el esquema completo con la vacuna neumocócica conjugada de 13 serotipos (VCN13) diagnosticado con NNN del serotipo 3. La progresión de la enfermedad invasiva por S. pneumoniae debe considerarse a pesar de la inmunización completa.


Pneumococcal Vaccines/administration & dosage , Pneumonia, Necrotizing/diagnosis , Pneumonia, Pneumococcal/diagnosis , Streptococcus pneumoniae/isolation & purification , Humans , Infant , Male , Pneumonia, Necrotizing/microbiology , Pneumonia, Pneumococcal/microbiology , Serogroup , Streptococcus pneumoniae/classification
7.
Hum Vaccin Immunother ; 13(8): 1892-1894, 2017 08 03.
Article En | MEDLINE | ID: mdl-28574743

Invasive pneumococcal infections among children are a serious public health problem in many countries, including Turkey. Pneumococcal conjugate vaccine has been included in Turkey's National Immunization Programme since 2009. We report the first two pediatric cases of invasive pneumococcal infection due to non-vaccine serotype 15A after pneumococcal conjugate vaccine implementation in Turkey. It is essential to monitor the countries' own local seroepidemiologic data for detecting selective pressure of non-vaccine serotypes of S. pneumonia.


Immunization Programs , Pneumococcal Infections/epidemiology , Pneumococcal Infections/microbiology , Pneumococcal Vaccines/administration & dosage , Seroepidemiologic Studies , Streptococcus pneumoniae/classification , Adolescent , Heptavalent Pneumococcal Conjugate Vaccine/administration & dosage , Heptavalent Pneumococcal Conjugate Vaccine/adverse effects , Humans , Male , Pneumococcal Infections/complications , Pneumococcal Infections/diagnosis , Pneumococcal Vaccines/adverse effects , Serogroup , Serotyping , Streptococcus pneumoniae/pathogenicity , Turkey/epidemiology , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/adverse effects
8.
Hum Vaccin Immunother ; 13(5): 1182-1189, 2017 05 04.
Article En | MEDLINE | ID: mdl-28140784

The serogroup epidemiology of invasive meningococcal disease (IMD), which varies considerably by geographic region and immunization schedule, changes continuously. Meningococcal carriage data are crucial for assessing IMD epidemiology and designing f potential vaccination strategies. Meningococcal seroepidemiology in Turkey differs from that in other countries: serogroups W and B are the predominant strains for IMD during childhood, whereas no serogroup C cases were identified over the last 10 y and no adolescent peak for IMD was found. There is a lack of data on meningococcal carriage that represents the whole population. The aims of this multicenter study (12 cities in Turkey) were to evaluate the prevalence of Neisseria meningitidis carriage, the serogroup distribution and the related risk factors (educational status, living in a dormitory or student house, being a household contact with Hajj pilgrims, smoking, completion of military service, attending bars/clubs) in 1518 adolescents and young adults aged 10-24 y. The presence of N. meningitidis DNA was tested, and a serogroup analysis was performed using polymerase chain reaction. The overall meningococcal carriage rate was 6.3% (n = 96) in the study population. A serogroup distribution of the 96 N. meningitidis strains isolated from the nasopharyngeal specimens revealed serogroup A in 5 specimens (5.2%), serogroup B in 9 specimens (9.4%), serogroup W in 64 specimens (66.6%), and serogroup Y in 4 specimens (4.2%); 14 were classified as non-grouped (14.4%). No serogroup C cases were detected. The nasopharyngeal meningococcal carriage rate was 5% in the 10-14 age group, 6.4% in the 15-17 age-group, and 4.7% in the 18-20 age group; the highest carriage rate was found in the 21-24 age group (9.1%), which was significantly higher than those of the other age groups (p < 0.05). The highest carriage rate was found in 17-year-old adolescents (11%). The carriage rate was higher among the participants who had had close contact with Hajj/Umrah pilgrims (p < 0.01) or a history of upper respiratory tract infections over the past 3 months (p < 0.05). The nasopharyngeal carriage rate was 6.3% among adolescents and young adults in Turkey and was similar to the recent rates observed in the same age groups in other countries. The most prevalent serogroup was W, and no serogroup C cases were found. In conclusion, the present study found that meningococcal carriage reaches its peak level by age 17, the highest carriage rate was found in 21 - to 24 - year-olds and the majority of the carriage cases were due to serogroup W. Adolescents and young adult carriers seem to be a potential reservoir for the disease, and further immunization strategies, including adolescent immunization, may play a role in the control of IMD.


Carrier State/epidemiology , Carrier State/microbiology , Meningococcal Infections/epidemiology , Neisseria meningitidis/isolation & purification , Serogroup , Adolescent , Carrier State/immunology , Child , DNA, Bacterial , Humans , Male , Meningococcal Infections/immunology , Meningococcal Infections/microbiology , Nasopharynx/microbiology , Neisseria meningitidis/classification , Neisseria meningitidis/genetics , Neisseria meningitidis/immunology , Polymerase Chain Reaction , Prevalence , Risk Factors , Seroepidemiologic Studies , Turkey/epidemiology , Vaccination , Young Adult
9.
J. pediatr. (Rio J.) ; 92(4): 414-420, July-Aug. 2016. tab, graf
Article En | LILACS | ID: lil-792583

Abstract Objective The potential role of procalcitonin (PCT) in the diagnosis of catheter-related bloodstream infection (CRBSIs) is still unclear and requires further research. The diagnostic value of serum PCT for the diagnosis of CRBSI in children is evaluated here. Method This study was conducted between October 2013 and November 2014, and included patients with suspected CRBSI from 1 month to 18 years of age who were febrile, with no focus of infection, and had a central venous catheter. Levels of PCT and other serum markers were measured, and their utility as CRBSI markers was assessed. Additionally, the clinical performance of a new, automated, rapid, and quantitative assay for the detection of PCT was tested. Results Among the 49 patients, 24 were diagnosed with CRBSI. The PCT-Kryptor and PCT-RTA values were significantly higher in proven CRBSI compared to those in unproven CRBSI (p = 0.03 and p = 0.03, respectively). There were no differences in white blood cell count and C-reactive protein (CRP) levels between proven CRBSI and unproven CRBSI. Among the 24 patients with CRBSI, CRP was significantly higher among those with Gram-negative bacterial infection than in those with Gram-positive bacterial infections. PCT-Kryptor was also significantly higher among patients with Gram-negative bacterial infection than in those with Gram-positive bacterial infections (p = 0.01 and p = 0.02, respectively). Conclusions The authors suggest that PCT could be a helpful rapid diagnostic marker in children with suspected CRBSIs.


Resumo Objetivo O possível papel da procalcitonina (PCT) no diagnóstico de infecções de corrente sanguínea relacionadas a cateter (ICSRCs) ainda não está claro e precisa ser mais pesquisado. O valor diagnóstico da PCT sérica para o diagnóstico de ICSRC em crianças é avaliado neste estudo. Método Este estudo foi feito entre outubro de 2013 e novembro de 2014 e incluiu pacientes com suspeita de ICSRC de um mês a 18 anos que estavam febris, não tinham foco de infecção e tinham cateter venoso central. Foram medidos os níveis de PCT e de outros marcadores séricos, cuja utilidade como marcadores de ICSRC foi avaliada. Adicionalmente, foi testado o desempenho clínico de um novo ensaio quantitativo automatizado e rápido para a detecção de PCT. Resultados Dentre 49 pacientes, 24 foram diagnosticados com ICSRC. Os valores de PCT-Kryptor e PCT-RTA foram significativamente maiores em ICSRCs comprovadas do que em ICSRCs não comprovadas (p = 0,03 e p = 0,03, respectivamente). Não houve diferença na contagem de glóbulos brancos e nos níveis de proteína C reativa (PCR) entre ICSRCs comprovadas e ICSRCs não comprovadas. Dentre os 24 pacientes com ICSRC, a PCR era significativamente maior entre aqueles com infecção bacteriana gram-negativa do que naqueles com infecção bacteriana gram-positiva. O PCT-Kryptor também foi significativamente maior entre pacientes com infecção por bactérias gram-negativas do que naqueles com infecção por bactérias gram-positivas (p = 0,01 e p = 0,02, respectivamente). Conclusões Sugerimos que a PCT pode ser um marcador de diagnóstico rápido útil em crianças com suspeita de ICSRCs.


Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Calcitonin/blood , Bacteremia/diagnosis , Bacteremia/blood , Catheter-Related Infections/diagnosis , Catheter-Related Infections/blood , Reference Values , C-Reactive Protein/analysis , Immunoassay , Biomarkers/blood , Reproducibility of Results , Sensitivity and Specificity , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/blood , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/blood , Statistics, Nonparametric , Leukocyte Count
10.
J Pediatr (Rio J) ; 92(4): 414-20, 2016.
Article En | MEDLINE | ID: mdl-27131015

OBJECTIVE: The potential role of procalcitonin (PCT) in the diagnosis of catheter-related bloodstream infection (CRBSIs) is still unclear and requires further research. The diagnostic value of serum PCT for the diagnosis of CRBSI in children is evaluated here. METHOD: This study was conducted between October 2013 and November 2014, and included patients with suspected CRBSI from 1 month to 18 years of age who were febrile, with no focus of infection, and had a central venous catheter. Levels of PCT and other serum markers were measured, and their utility as CRBSI markers was assessed. Additionally, the clinical performance of a new, automated, rapid, and quantitative assay for the detection of PCT was tested. RESULTS: Among the 49 patients, 24 were diagnosed with CRBSI. The PCT-Kryptor and PCT-RTA values were significantly higher in proven CRBSI compared to those in unproven CRBSI (p=0.03 and p=0.03, respectively). There were no differences in white blood cell count and C-reactive protein (CRP) levels between proven CRBSI and unproven CRBSI. Among the 24 patients with CRBSI, CRP was significantly higher among those with Gram-negative bacterial infection than in those with Gram-positive bacterial infections. PCT-Kryptor was also significantly higher among patients with Gram-negative bacterial infection than in those with Gram-positive bacterial infections (p=0.01 and p=0.02, respectively). CONCLUSIONS: The authors suggest that PCT could be a helpful rapid diagnostic marker in children with suspected CRBSIs.


Bacteremia/blood , Bacteremia/diagnosis , Calcitonin/blood , Catheter-Related Infections/blood , Catheter-Related Infections/diagnosis , Adolescent , Biomarkers/blood , C-Reactive Protein/analysis , Child , Child, Preschool , Female , Gram-Negative Bacterial Infections/blood , Gram-Negative Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/blood , Gram-Positive Bacterial Infections/diagnosis , Humans , Immunoassay , Infant , Infant, Newborn , Leukocyte Count , Male , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Statistics, Nonparametric
11.
J Clin Med Res ; 7(6): 472-8, 2015 Jun.
Article En | MEDLINE | ID: mdl-25883712

BACKGROUND: Clinical diagnosis of diphtheria is often difficult, in particular in countries where the disease is rarely observed, such as Turkey. In 2011, after 12 years of no recorded diphtheria cases in Turkey, a 34-year-old woman was diagnosed with diphtheria; she later died of myocarditis. In this study, we aimed to demonstrate the diagnostic potential of an immunofluorescent antibody method to determine the presence of diphtheria toxin (DT) in the myocardial cells of DT-injected rabbits and the female subject. METHODS: We randomly divided rabbits into two groups: a control group and a DT-injected group. Diphtheria intoxication was simulated in the rabbits by intravenous injection of DT. The myocardium of the rabbits and the female subject were harvested for histopathologic and immunofluorescence examination. A mouse monoclonal anti-DT antibody was used for the immunofluorescent antibody method. RESULTS: The presence of DT in the myocardial cells of both the rabbits and the female subject was visualized using the immunofluorescent method. CONCLUSIONS: Laboratory diagnosis of diphtheria is challenging because of non-toxigenic C. diphtheriae strains and/or the dysfunction of DT. However, visualizing the presence of DT in the myocardial tissue may act as an indicator of biologically active DT. We validated that an immunofluorescent method, which utilizes a monoclonal anti-DT (A-subunit specific) antibody, is a useful diagnostic tool to determine the presence of DT in the myocardium of rabbits and human.

12.
Hum Vaccin Immunother ; 10(9): 2706-12, 2014.
Article En | MEDLINE | ID: mdl-25483487

Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.


Meningitis, Haemophilus/epidemiology , Meningitis, Meningococcal/epidemiology , Meningitis, Pneumococcal/epidemiology , Adolescent , Cerebrospinal Fluid/microbiology , Child , Child, Preschool , DNA, Bacterial/cerebrospinal fluid , Epidemiological Monitoring , Female , Haemophilus influenzae type b/isolation & purification , Humans , Infant , Male , Meningitis, Haemophilus/microbiology , Meningitis, Meningococcal/microbiology , Meningitis, Pneumococcal/microbiology , Multiplex Polymerase Chain Reaction , Neisseria meningitidis/isolation & purification , Prevalence , Prospective Studies , Streptococcus pneumoniae/isolation & purification , Turkey/epidemiology
13.
Oncol Lett ; 7(3): 755-763, 2014 Mar.
Article En | MEDLINE | ID: mdl-24520293

The aim of the present study was to analyze the molecular mechanisms involved in blocking the signaling pathway and the effects of this on the progression of prostate cancer (CaP) cells in vitro. LNCaP human CaP cell line was stimulated with interleukin-6 (IL-6) in the presence/absence of Janus kinase (JAK) 2 (AG490), signal transducer and activator of transcription 3 [(STAT3) S3I-201] inhibitors and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Cytotoxic activity, the activation of phosphorylated (p)-STAT3 protein, caspase (CASP) 3 activity at protein level, vascular endothelial growth factor (VEGF) A, VEGFC, vascular endothelial growth factor receptor 2, STAT3, matrix metalloproteinase-2, myeloid cell leukemia sequence 1 (MCL-1), CASP8 and CASP9 messenger RNA (mRNA) levels were determined. Morphology and apoptosis were confirmed by DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. IL-6 rapidly induced the phosphorylation of STAT3 in a dose- and time-dependent manner with a peak expression at 3 h at a concentration of 25 ng/ml. In addition, AG490 (50 µM) and S3I-201 (300 µM) inhibited STAT3 activation. Western blotting results revealed that p-STAT3 protein expression decreased significantly with AG490 and S3I-201 treatment in LNCaP cells. AG490 and S3I-201 induced the downregulation of VEGFA, MCL-1 and STAT3 and the upregulation of CASP8 and CASP9 mRNA transcription levels. In addition, the inhibitors increased the level of CASP3 protein. Combinations of AG490- and S3I-201-TRAIL did not result in an increase in this effect. Parallel results were found by DAPI staining and TUNEL assay. To the best of our knowledge, this is the first study to investigate the possible clinical use of AG490 or S3I-201, together with the reduced use of chemotherapeutic agents with high cytotoxicity, for their ability to exert an apoptotic effect, targeting the JAK/STAT3 pathway.

14.
Turk J Pediatr ; 56(6): 618-25, 2014.
Article En | MEDLINE | ID: mdl-26388592

Vancomycin-resistant enterococci (VRE) have become a major concern in medical practice. Asymptomatic VRE colonization of the gastrointestinal tract may lead to infection. In this study, which included patients who stayed in our hospital between 2006 and 2011, we looked at the cases of 342 patients with VRE colonization and 19 patients with VRE infection. Vancomycin and carbapenem exposure and intestinal disorders were significantly more common in patients with VRE infection than in those with VRE colonization (p=0.02/0.04/0.04 respectively). Secondary immune deficiency was significantly more common in VRE-colonized patients than in VRE-infected patients (p=0.03). VRE colonization time was significantly related with young age, presence of intravenous catheter, presence of mechanical ventilation, length of hospital stay, length of hospitalization before and after VRE isolation, length of ICU stay before and after VRE isolation, total ICU stay, antibiotic exposure within 3 months, hospitalization (in our hospital) within 3 months, and having a site of infection other than VRE (p=0.01/ 0.01/ 0.04/ <0.001/0.02/ <0.001/ 0.002/ 0.006/ 0.002/ 0.004/ 0.01/ 0.002, respectively). Overall mortality and sepsis was more common in the VRE-infected group than in the VRE-colonized group. Taking into consideration limiting antibiotic usage in potential cases and screening for patients at risk could be beneficial in terms of limiting VRE infection and colonization.


Enterococcus/isolation & purification , Gram-Positive Bacterial Infections/drug therapy , Vancomycin Resistance , Vancomycin/therapeutic use , Adolescent , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Enterococcus/drug effects , Female , Follow-Up Studies , Gram-Positive Bacterial Infections/microbiology , Humans , Infant , Infant, Newborn , Length of Stay/trends , Male , Risk Factors , Time Factors
15.
Clin Vaccine Immunol ; 20(7): 972-6, 2013 Jul.
Article En | MEDLINE | ID: mdl-23637041

Streptococcus pneumoniae is the most common etiological cause of complicated pneumonia, including empyema. In this study, we investigated the serotypes of S. pneumoniae that cause empyema in children. One hundred fifty-six children who were diagnosed with pneumonia complicated with empyema in 13 hospitals in seven geographic regions of Turkey between 2010 and 2012 were included in this study. Pleural fluid samples were collected by thoracentesis and tested for 14 serotypes/serogroups using a Bio-Plex multiplex antigen detection assay. The serotypes of S. pneumoniae were specified in 33 of 156 samples. The mean age ± the standard deviation of the 33 patients was 6.17 ± 3.54 years (range, 0.6 to 15 years). All of the children were unvaccinated according to the vaccination reports. Eighteen of the children were male, and 15 were female. The serotypes of the non-7-valent pneumococcal conjugated vaccine (non-PCV-7), serotype 1, serotype 5, and serotype 3, were detected in eight (14.5%), seven (12.7%), and five (9.1%) of the samples, respectively. Serotypes 1 and 5 were codetected in two samples. The remaining non-PCV-7 serotypes were 8 (n = 3), 18 (n = 1), 19A (n = 1), and 7F/A (n = 1). PCV-7 serotypes 6B, 9V, 14, 19F, and 23F were detected in nine (16.3%) of the samples. The potential serotype coverages of PCV-7, PCV-10, and PCV-13 were 16.3%, 45.4%, and 60%, respectively. Pediatric parapneumonic empyema continues to be an important health problem despite the introduction of conjugated pneumococcal vaccines. Active surveillance studies are needed to monitor the change in S. pneumoniae serotypes that cause empyema in order to have a better selection of pneumococcal vaccines.


Empyema/epidemiology , Empyema/microbiology , Pneumonia, Pneumococcal/complications , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/isolation & purification , Adolescent , Child , Child, Preschool , Female , Hospitals , Humans , Infant , Male , Pneumococcal Vaccines/immunology , Prospective Studies , Serotyping , Streptococcus pneumoniae/immunology , Turkey/epidemiology
16.
J Med Virol ; 84(8): 1242-7, 2012 Aug.
Article En | MEDLINE | ID: mdl-22711352

The age-specific human papillomavirus (HPV) seroprevalence and HPV type distribution in women with normal cervical cytology were studied. Cervical smear samples obtained using liquid-based smears from 582 clinically healthy women aged between 15 and 68 years from five centers from four different regions of Turkey, were studied between February 2010 and January 2011. Overall, 530 of the women with normal cytology were included and the samples were analyzed for the presence of HPV by AmpliTaq. Positive samples were typed further for 37 different HPV genotypes by a line blot assay. HPV was positive in 17.9% of the women. HPV prevalence was highest in the age group of 25-29 years (31.8%), and decreased with increasing age. HPV 16 was the most common type (3.6%) followed by type 6 (2.6%) and type 45 (2.2%). Types 11 and 18 were rare (0.6% and 0.4%, respectively). Among the risk factors, number of sexual partners and parity were positively correlated with HPV positivity. In the present study, a large number of sex partners and high parity increased the risk for HPV infection. The age-specific distribution of HPV in women with normal Pap smears did not show a U-shaped curve in contrast to European countries and the USA.


Papanicolaou Test , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Uterine Cervical Diseases/epidemiology , Vaginal Smears , Adolescent , Adult , Aged , Cervix Uteri/virology , DNA, Viral/analysis , Female , Humans , Middle Aged , Papillomaviridae/classification , Papillomavirus Infections/virology , Prevalence , Risk Factors , Sexual Partners , Turkey/epidemiology , Uterine Cervical Diseases/virology , Young Adult
17.
Am J Infect Control ; 36(6): 453-7, 2008 Aug.
Article En | MEDLINE | ID: mdl-18675153

Three clusters of Chryseobacterium meningosepticum infections in a tertiary health center in July 2006 and January 2007 involving 8 newborns and 5 older children were investigated. The index patient was from the neonatal intensive care unit, and the older patients were from other pediatric wards. Cultures were obtained from the environment and from health care workers' hands as part of an outbreak investigation. C meningosepticum was isolated from hand cultures obtained from a senior resident and from environmental cultures obtained from powdered infant formula, an electrical button, a computer keyboard, phone, a doorknob, and an Ambu bag. Antibiogram typing and enterobacterial repetitive intergenic consensus sequence polymerase chain reaction indicated that all of the isolates were epidemiologically related. Nine patients improved on antimicrobial treatment, and 4 premature infants died after the infection. C meningosepticum is a well-known etiologic agent for nosocomial infections involving newborns and immunocompromised patients. Wet and dry environmental surfaces and equipment may act as a source or play a role in disseminating the microorganism. Outbreaks may be controlled with strong emphasis on infection control measures.


Chryseobacterium/classification , Chryseobacterium/isolation & purification , Cross Infection/epidemiology , Disease Outbreaks , Flavobacteriaceae Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cluster Analysis , Cross Infection/drug therapy , DNA Fingerprinting , DNA, Bacterial/genetics , Environmental Microbiology , Female , Flavobacteriaceae Infections/drug therapy , Genotype , Hand/microbiology , Health Personnel , Hospital Units , Humans , Infant , Infant, Newborn , Male , Microbial Sensitivity Tests , Random Amplified Polymorphic DNA Technique , Turkey/epidemiology
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