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Öğe Altered immune response in organic acidemia(Wiley, 2022) Altun, İlayda; Kıykım, Ayça; Zubarioğlu, Tanyel; Bürtecene, Nihan; Hopurcuoglu, Duhan; Topcu, Birol; Zeybek, Ayşe Çiğdem AktuğluBackground Most patients with organic acidemia suffer from recurrent infections. Although neutropenia has been reported in multiple studies, other components of the immune system have not been evaluated thoroughly. This study was conducted to assess the immune status of patients with organic acidemia (OA). Methods Thirty-three patients with OA who were followed up in Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Nutrition and Metabolism Department and a total of 32 age- and sex-matched healthy controls were enrolled to the study. The demographic and clinical data were recorded retrospectively from patient files. Complete blood counts, immunoglobulins, and lymphocyte immunophenotyping were recorded prospectively in a symptom- (infection-) free period. Results Of the 33 patients enrolled to the study, 21 (88%) were diagnosed with methylmalonic acidemia, 10 (33%) with propionic acidemia, and two (6.6%) with isovaleric acidemia. The mean age of the patients with OA and healthy subjects were 5.89 +/- 4.11 years and 5.34 +/- 4.36, respectively (P = 0.602). Twenty-nine (88%) of the patients had experienced frequent hospital admission, 13 (39%) were admitted to pediatric intensive care unit, and 18 (55%) suffered from sepsis. Naive helper T cells and recent thymic emigrants were significantly lower in OAs (P < 0.001). Various defects in humoral immunity have also been documented including memory B cells and immunoglobulins. Conclusions Patients with OAs may show adaptive immune defects rendering them susceptible to infections. Metabolic reprogramming based on nutritional modifications may be a promising therapeutic option in the future.Öğe Effect of Atypical Antipsychotic Usage at Therapeutic Doses on Daytime Sleepiness(2023) Alan, Meltem; Yuksel, Tugba Nurcan; Topcu, BirolThe aim of this study is to determine the effect of using atypical antipsychotic drug usage at therapeutic doses on daytime sleepiness. One hundred twenty volunteers who met the inclusion-exclusion criteria were divided into two equal groups. Group 1: patient group (60 patients volunteers used atypical antipsychotic in therapeutic doses and hospitalized in the psychiatry clinic of Tekirdağ Namık Kemal University Hospital and Group 2: control group (60 control volunteers). Socio-demographic and Clinical Information Form consist of 14 questions was administration all volunteers. Also, Epworth Sleepiness Scale which is a survey that determines the degree of sleepiness in eight different situations during the day was administered to all volunteers. Atypical antipsychotic drug usage at therapeutic doses significantly increased patients’ daytime sleepiness compared to the control group. Among the atypical antipsychotic drugs usage in therapeutic dose, the drug that caused the most daytime sleepiness was clozapine. Also, using of atypical antipsychotic drugs in therapeutic doses markedly decreased patients’ life quality compared to the control group. Atypical antipsychotic drug usage at therapeutic doses could cause daytime sleepiness and reduce patients’ quality of life.Öğe Effects of Tranexamic Acid on Acute Lung Injury in Rats Exposed to Aortic Ischemia-Reperfusion(Wiley, 2023) Ozcan, Betul; Deger, Ecem Busra; Mengi, Murat; Oznur, Meltem; Celikkol, Aliye; Topcu, Birol; Guner, Ibrahim[Abstract Not Available]Öğe Investigation of Pneumococcus, Influenza, Covid-19 Vaccination Rates and Affecting Factors in Patients Aged 65 and Over(Duzce Univ, Fac Medicine, 2024) Donmez, Aslihan Celik; Guzel, Eda Celik; Topcu, BirolObjective: This study was planned to determine the vaccination rates and related factors with Pneumococcal, Influenza and Covid-19 vaccines in adults aged 65 and over who applied to the Family Medicine Outpatient Clinic. Methods: The sample of the descriptive study consisted of 200 volunteer adult patients aged 65 and over who applied to the Family Medicine outpatient clinic between May and October 2021. AThe data were collected by applying a face-to-face interview with descriptive features. Results: The mean age of the participants was 71.21 +/- 5.97 years. Influenza vaccination rate of all participants in the last 1 year was 24.50%, Pneumococcal vaccination rate in the last 5 years was 42%, and Covid-19 vaccination rate was 86%. In our study, having a chronic disease was the factor that increased the rate of influenza vaccination, it was determined that the factor determining the pneumococcal vaccination rate was affected by the habit of going to the family doctor regularly (p<0.05). Individuals who did not receive the Covid-19 vaccine stated that they did not have the vaccine because they were afraid of the side effects of the vaccine and did not find the vaccine safe. Conclusions: Our study revealed that adult vaccination rates are low and they do not have enough information about their vaccinations. Health professionals, especially family physicians, have important duties to determine the factors affecting the level of knowledge about immunization in adults, to increase awareness and to make preventive medicine reach more people.Öğe Investigation of the Effect of Farnesol on Biofilm Formation by Candida albicans and Candida parapsilosis Complex Isolates(Ankara Microbiology Soc, 2024) Erdal, Berna; Baylan, Bensu; Batar, Bahadir; Ozturk, Ali; Topcu, BirolThe incidence of infections caused by Candida species has significantly increased over the past three decades. Candida albicans is commonly recognized as the primary causative agent in cases of candidiasis; however, non-albicans Candida species, including Candida parapsilosis, are also frequently defined as pathogens. Treatment -resistant infections arise as a result of biofilm formation, which is one of the effective mechanisms in the pathogenesis of Candida infections. However, the mechanisms of action of farnesol, a quorum sensing (QS) system molecule, on biofilm formation by Candida species remain unclear. This study aimed to demonstrate the changes in the biofilm biomass of C.albicans and C.parapsilosis complex isolates in the presence of farnesol and reveal the expression of the EFG1 and BCR1 genes, which are believed to play a role in the production of QS molecules, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis. C.albicans (n= 91) and C.parapsilosis complex (n= 29) isolates obtained from different clinical samples were included in the study. The minimum inhibitory concentration (MIC) values of farnesol were determined using the broth microdilution method according to the M27 -A3 protocol of the Clinical and Laboratory Standards Institute (CLSI). The biofilm biomass of the isolates was examined without farnesol and at the MIC-0 and MIC-2 concentrations of farnesol. Changes in the expression of the biofilm-associated EFG1 and BCR1 genes were investigated using qRT-PCR. According to the results of the study, the MIC values of farnesol were detected in the range of 1-2 mM in 82.4% (n= 75) of the C.albicans isolates and in the range of 0.5-1 mM in 72.4% (n= 21) of the C.parapsilosis complex isolates. Of the C.albicans isolates, 27 (29.7%) exhibited a strong biofilm formation and 58 (63.7%) demonstrated a weaker biofilm formation, while these rates were 34.4% (n= 10) and 62.1% (n= 18), respectively, for the C.parapsilosis complex isolates. At the MIC-0 and MIC-2 concentrations, farnesol was observed to reduce biofilm biomass among C.albicans (n= 24, 88.9%) and C.parapsilosis complex (n= 8, 80.0%) isolates that formed strong biofilms and observed to increase biofilm biomass among those that formed weak biofilms [60.3% (n= 35) and 55.6% (n= 10), respectively]. On completion of the qRT-PCR analysis supporting the results of the biofilm experiment, it was determined that the expressions of the EFG1 and BCR1 genes decreased at the MIC-0 and MIC-2 concentrations of farnesol among the strong biofilm-forming C.albi- cans and C.parapsilosis complex isolates, but there was an increase in gene expressions among the weak biofilm-forming isolates. In addition to the antifungal effect of farnesol on Candida species, this study provided data on the efficacy of the MIC-0 and MIC-2 concentrations of farnesol against Candida biofilm biomass. Although our results suggest that farnesol can be used as an alternative agent to reduce biofilm formation in Candida infections, they need to be supported by further studies. Moreover, this research has significance as it represents the first study to determine the EFG1 and BCR1 gene expressions among C.parapsilosis complex isolates in the presence of farnesol.Öğe Myxoma Virus Combination Therapy Enhances Lenalidomide and Bortezomib Treatments for Multiple Myeloma(Mdpi, 2024) Yesilaltay, Alpay; Muz, Dilek; Erdal, Berna; Bilgen, Turker; Batar, Bahadir; Turgut, Burhan; Topcu, BirolThis study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.Öğe Serum Neopterin, Biopterin, Tryptophan, and Kynurenine Levels in Patients with Fabry Disease(Galenos Publ House, 2024) Ucar, Tugce; Cansever, Mehmet Serif; Isat, Esra; Zubarioglu, Tanyel; Zeybek, Ayse Cigdem Aktuglu; Topcu, Birol; Seyahi, NurhanBackground: Fabry disease is characterized by the accumulation of globotriaosylceramide. Substrate accumulation in lysosomes is thought to trigger an inflammatory response and is responsible for progressive organ damage through the induction of autoimmunity. The levels of pteridine and kynurenine pathway metabolites increase when immune activation is observed and are employed to monitor several diseases and determine prognosis. Aims: To elucidate the effects of immune activation on the pathophysiology of Fabry disease and to investigate the potential utility of pteridine and kynurenine metabolites. Study design: A prospective case-control study. Methods: In this study, 33 patients with Fabry disease and 33 age-and sex-matched healthy controls were included. Blood pteridine and kynurenine metabolites were studied in both groups. Organ involvement in Fabry disease and its correlation with the pteridine and kynurenine pathways were also investigated. Results: The patients' neopterin and biopterin levels and the tryptophan/kynurenine ratio were statistically higher than those of the healthy control group (p < 0.05). A statistically significant association was found between neopterin levels and hypertrophic cardiomyopathy, cardiac arrhythmias, and GFR values (p = 0.044, p = 0.021, and p = 0.030, respectively), tryptophan and corneal verticillate, hearing loss and tinnitus (p = 0.010, p = 0.009 and p = 0.046, respectively), and kynurenine levels and valvular heart disease (p = 0.020). Conclusion: From the onset of the disease, patients with Fabry disease exhibited elevated levels of inflammation and immune activation. Furthermore, inflammation and immune activation markers can be used as early disease biomarkers.