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Öğe Acquired partial lipodystrophy is associated with increased risk for developing metabolic abnormalities(W.B. Saunders, 2015) Akinci B.; Koseoglu F.D.; Onay H.; Yavuz S.; Altay C.; Simsir I.Y.; Ozisik S.; Demir L.; Korkut M.; Yilmaz N.; Ozen S.; Akinci G.; Atik T.; Calan M.; Secil M.; Comlekci A.; Demir T.Objective Acquired partial lipodystrophy (APL) is a rare disorder characterized by progressive selective fat loss. In previous studies, metabolic abnormalities were reported to be relatively rare in APL, whilst they were quite common in other types of lipodystrophy syndromes. Methods In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI. Hepatic steatosis was evaluated by ultrasound, MRI and MR spectroscopy. Patients with diabetes underwent a mix meal stimulated C-peptide/insulin test to investigate pancreatic beta cell functions. Leptin and adiponectin levels were measured. Results Fifteen individuals (71.4%) had at least one metabolic abnormality. Six patients (28.6%) had diabetes, 12 (57.1%) hypertrigylceridemia, 10 (47.6%) low HDL cholesterol, and 11 (52.4%) hepatic steatosis. Steatohepatitis was further confirmed in 2 patients with liver biopsy. Anti-GAD was negative in all APL patients with diabetes. APL patients with diabetes had lower leptin and adiponectin levels compared to patients with type 2 diabetes and healthy controls. However, contrary to what we observed in patients with congenital generalized lipodystrophy (CGL), we did not detect consistently very low leptin levels in APL patients. The mix meal test suggested that APL patients with diabetes had a significant amount of functional pancreatic beta cells, and their diabetes was apparently associated with insulin resistance. Conclusions Our results show that APL is associated with increased risk for developing metabolic abnormalities. We suggest that close long-term follow-up is required to identify and manage metabolic abnormalities in APL. © 2015 Elsevier Inc.Öğe Asthma-chronic obstructive pulmonary disease overlap: Results from a national-multicenter study; [Astım KOAH overlap: Ulusal çok merkezli bir çalışma sonuçları](Ankara University, 2024) Çelik G.E.; Aydin Ö.; Şen E.; Demir T.; Gemicioğlu B.; Kiyan E.; Mungan D.Introduction: Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have a greater disease burden than those with COPD or asthma alone. In this study, it was aimed to determine the prevalence, risk factors, and clinical features of ACO because there are limited national data in Türkiye. Materials and Methods: The study was conducted in a cross-sectional design in nine tertiary-care hospitals. The patients followed with a diagnosis of asthma or COPD for at least one year were enrolled in the study. The frequency of ACO and the characteristics of the patients were evaluated in the asthma and COPD groups. Results: The study included 408 subjects (F/M= 205/203, mean age= 56.24 ± 11.85 years). The overall prevalence of ACO in both groups was 20.8% (n= 85). The frequency was higher in the COPD group than in the asthma group (n= 55; 33.3% vs. n= 22; 9.8%), respectively (p= 0.001). Patients with ACO had similarities to patients with COPD in terms of advanced age, sex, smoking, exposure to biomass during childhood, being born in rural areas, and radio-logic features. Characteristics such as a history of childhood asthma and allergic rhinitis, presence of chronic sinusitis, NSAID hypersensitivity, atopy, and high eosinophil counts were similar to those of patients with asthma (p< 0.001). The annual decline in FEV1 was more prominent in the ACO group (mean=-250 mL) than in the asthma (mean change=-60 mL) and COPD (mean change=-230 mL) groups (p= 0.003). Conclusion: This study showed that ACO was common among patients with asthma and COPD in tertiary care clinics in our country. ACO should be considered in patients with asthma and COPD who exhibit the abovementioned symptoms. © 2024 by Tuberculosis and Thorax.Öğe Asthma-KOAH overlap syndrome [Astım-KOAH overlap sendromu](Ankara University, 2015) Şen E.; Oğuzülgen K.; Bavbek S.; Günen H.; Kiyan E.; Türktaş H.; Yorgancioğlu A.; Polatli M.; Yildiz F.; Çelik G.; Demir T.; Gemicioğlu B.; Mungan D.; Saryal S.; Sayiner A.; Yildirim N.Asthma and chronic obstructive pulmonary disease (COPD) are common lung diseases characterized by chronic airway inflammation and airway obstruction. Among patient with COPD and asthma; there is a group of patients with an overlap between clinical, functional characteristics and airway inflammation patterns, named “Asthma-COPD Overlap Syndrome” (ACOS). ACOS is a syndrome characterized by reversible but persistant airflow limitation (postbronchodilator FEV1/FVC < 70%) which has some features of both asthma and COPD. ACOS should be suspected in a patient > 40 years, with smoking history, previous asthma diagnosis or history of childhood asthma who has persistant airflow limitation and reversible ariway obstruction (defined by an increase of > %12 of FEV1 pred or increase of FEV1 > 200 mL after inhalation of 400 mcg salbutamol or 1000 mcg terbutaline). The prevalence for ACOS has been reported 11-55% in different case series to date and increases by age and is more frequent in females in different age groups. Patients with ACOS are younger than COPD patients and older than asthma patients. Frequent and severe exacerbations and related hospitalization and emergency room visits are common in ACOS and this causes an impaired quality of life. Current recommendations of guidelines for pharmacologic treatment of ACOS have been composed of a combination with optimal COPD and asthma treatment. Future therapeutic approaches should be based on endotypes. Clinical phenotype and underlying endotype driven clinical studies may be the base of ACOS guidelines. © 2015, Ankara University. All rights reserved.Öğe Bioaffinity immobilization and characterization of ?-galactosidase on aminophenylboronicacid derivatized chitosan and Sepabeads EC-EA(Academic Press, 2018) Demir T.; Önal S.Enzyme immobilization with affinity binding which is based on the specific affinity interactions have an important advantage as; high selectivity. In the present study, chitosan and Sepabeads EC-EA were derivatized with aminophenylboronicacid(APBA) for the affinity immobilization of ?-galactosidase. The influence of various process parameters on immobilization of the enzyme is investigated to get high immobilization yields. Under optimized immobilization conditions, the chitosan and Sepabeads EC-EA immobilized enzymes exhibited activity yield of 89.5% and 72%, respectively. The maximum activities were detected at 40 °C for free and Sepabeads EC-EA immobilized enzyme and 55 °C for chitosan immobilized enzyme. The optimum pH was found as pH 5.0 for free and Sepabeads EC-EA immobilized enzyme and pH 5.5 for chitosan immobilized enzyme. Both immobilized enzymes were very stable at temperature ranged from 4 to 55 °C and also in a pH range of 2.6–7.0. The immobilized ?-galactosidases were also used in the hydrolysis of raffinose. The chitosan and Sepabeads EC-EA immobilized enzymes hydrolysed 55% and 42% of raffinose in 32 h at 50 °C, respectively. The obtained results shed light for the useability of these immobilized enzymes in the hydrolysis of raffinose in food industry and make these immobilized enzymes good candidates for their various biotechnological applications. © 2018 Elsevier LtdÖğe Bioaffinity immobilization and characterization of ?-galactosidase on aminophenylboronicacid derivatized chitosan and Sepabeads EC-EA(Academic Press, 2018) Demir T.; Önal S.Enzyme immobilization with affinity binding which is based on the specific affinity interactions have an important advantage as; high selectivity. In the present study, chitosan and Sepabeads EC-EA were derivatized with aminophenylboronicacid(APBA) for the affinity immobilization of ?-galactosidase. The influence of various process parameters on immobilization of the enzyme is investigated to get high immobilization yields. Under optimized immobilization conditions, the chitosan and Sepabeads EC-EA immobilized enzymes exhibited activity yield of 89.5% and 72%, respectively. The maximum activities were detected at 40 °C for free and Sepabeads EC-EA immobilized enzyme and 55 °C for chitosan immobilized enzyme. The optimum pH was found as pH 5.0 for free and Sepabeads EC-EA immobilized enzyme and pH 5.5 for chitosan immobilized enzyme. Both immobilized enzymes were very stable at temperature ranged from 4 to 55 °C and also in a pH range of 2.6–7.0. The immobilized ?-galactosidases were also used in the hydrolysis of raffinose. The chitosan and Sepabeads EC-EA immobilized enzymes hydrolysed 55% and 42% of raffinose in 32 h at 50 °C, respectively. The obtained results shed light for the useability of these immobilized enzymes in the hydrolysis of raffinose in food industry and make these immobilized enzymes good candidates for their various biotechnological applications. © 2018 Elsevier LtdÖğe Determining residual adipose tissue characteristics with mri in patients with various subtypes of lipodystrophy(AVES İbrahim KARA, 2017) Altay C.; Seçil M.; Demir T.; Atik T.; Akıncı G.; Kutbay N.Ö.; Temeloğlu E.K.; Şimşir I.Y.; Özışık S.; Demir L.; Eren E.; Tuna E.B.; Aytaç H.; Onay H.; Akıncı B.PURPOSE We aimed to investigate residual adipose tissue with whole-body magnetic resonance imaging to differentiate between subtypes of lipodystrophy. METHODS A total of 32 patients (12 with congenital generalized lipodystrophy [CGL], 1 with acquired generalized lipodystrophy [AGL], 12 with familial partial lipodystrophy [FPLD], and 7 with acquired partial lipodystrophy [APL]) were included. RESULTS Despite generalized loss of metabolically active adipose tissue, patients with CGL1 caused by AGPAT2 mutations had a significant amount of residual adipose tissue in the scalp, earlobes, retro-orbital region, and palms and soles. No residual adipose tissue was noted particularly in the head and neck, palms and soles in CGL2 caused by BSCL2 mutations. CGL4 caused by mutations in the PTRF gene was characterized with well-preserved retro-orbital and bone marrow fat in the absence of any visible residual adipose tissue in other areas. No residual adipose tissue was observed in AGL. Despite loss of subcutaneous fat, periarticular adipose tissue was preserved in the lower limbs of patients with FPLD. Retro-orbital adipose tissue was surprisingly preserved in APL, although they lacked head and neck fat. CONCLUSION Lipodystrophies are a heterogeneous group of disorders characterized by generalized or partial loss of adipose tissue, which can be congenital or acquired. Our results suggest that residual adipose tissue characteristics can help distinguish different subtypes of lipodystrophy. © Turkish Society of Radiology 2017.Öğe Familial partial lipodystrophy linked to a novel peroxisome proliferator activator receptor -? (PPARG) mutation, H449L: a comparison of people with this mutation and those with classic codon 482 Lamin A/C (LMNA) mutations(Blackwell Publishing Ltd, 2016) Demir T.; Onay H.; Savage D.B.; Temeloglu E.; Uzum A.K.; Kadioglu P.; Altay C.; Ozen S.; Demir L.; Cavdar U.; Akinci B.Aims: To describe the phenotype associated with a novel heterozygous missense PPARG mutation discovered in a Turkish family and to compare the fat distribution and metabolic characteristics of subjects with the peroxisome proliferator activator receptor -? (PPARG) mutation with those of a cluster of patients with familial partial lipodystrophy with classic codon 482 Lamin A/C (LMNA) mutations. Methods: The study involved four subjects with familial partial lipodystrophy who had a novel PPARG mutation (H449L) and six subjects with classic codon 482 LMNA mutations (R482W). Results: Compared with subjects with LMNA R482W mutation, fat loss was generally less prominent in subjects with the PPARG H449L mutation. Partial fat loss was limited to the extremities, whilst truncal fat mass was preserved. The PPARG H449L mutation was associated with insulin resistance, hypertriglyceridaemia and non-alcoholic fatty liver disease in all affected subjects, but the severity was variable. Three out of four mutation carriers had overt diabetes or impaired glucose tolerance. Pioglitazone therapy in these three individuals resulted in a modest improvement in their metabolic control, and regular menstrual cycles in the two female subjects. Conclusions: We suggest that relatively modest fat loss in patients with PPARG mutations may render the recognition of the syndrome more difficult in routine clinical practice. The PPARG H449L mutation is associated with insulin resistance and metabolic complications, but their severity is variable among the affected subjects. © 2016 Diabetes UKÖğe Increased alkalotolerant and thermostable ribonuclease (RNase) production from alkaliphilic Streptomyces sp. M49-1 by optimizing the growth conditions using response surface methodology(2013) Demir T.; Gübe Ö.; Yücel M.; Hameş-Kocabaş E.E.Total of 171 alkaliphilic actinomycetes were evaluated for extracellular RNase production and Streptomyces sp. M49-1 was selected for further experiments. Fermentation optimization for RNase production was implemented in two steps using response surface methodology with central composite design. In the first step, the effect of independent fermentation variables including temperature, initial pH and process time were investigated. After identification of carbon and nitrogen sources affecting the production by one variable at a time method, concentrations of glucose and yeast extract and also inoculum size were chosen for the second central composite design. A maximum RNase activity was obtained under optimal conditions of 4.14 % glucose concentration, 4.63 % yeast extract concentration, 6.7 × 106 spores as inoculum size for 50 ml medium, 42.9 °C, 91.2 h process time and medium initial pH 9.0. Optimum activity of the enzyme is achieved at pH 11 and temperature 60 °C. The enzyme is highly stable at pH range 9.0-12.0 and at 90 °C after 2 h. Statistical optimization experiments provide 2.25 fold increases in the activity of alkalotolerant and thermostable RNase and shortened the fermentation time compared to that of unoptimized condition. The members of Streptomyces can be promising qualified RNase producer for pharmaceutical industries. © 2013 Springer Science+Business Media Dordrecht.Öğe Koah ve astımda atak [KOAH ve astımda atak](Ankara University, 2015) Yildirim N.; Demir T.; Gemicioğlu B.; Kiyan E.; Oğuzülgen K.; Polatli M.; Saryal S.; Sayiner A.; Yorgancioğlu A.; Bavbek S.; Çelik G.E.; Günen H.; Mungan D.; Şen E.; Türktaş H.; Yildiz F.Chronic obstructive pulmonary disease (COPD) and asthma are airway diseases with acute exacerbations. Natural course of both disease are affected by exacerbations. COPD exacerbations may be caused by infections and other causes; indoor and outdoor pollution, cardiovascular diseases, asthma-COPD overlap syndrome, COPD- obstructive sleep apnea syndrome, pulmonary embolism, gastro-oesophageal reflux, anxiety-depression, pulmonary hypertension. Exposure to triggering factors, viral infections, treatment insufficiency may cause asthma exacerbations. Smoking cessations, prevention of infections, long-acting anticholinergics, long-acting ß2 agonists, inhaled corticosteroids, phosphodiesterase-4 inhibitors, mucolytics, prophilactic antibiotics can be effective on the prevention of COPD exacerbations. Asthma exacerbations may be decreased by the avoidance of allergens, viral infections, occupational exposures, airpollution, treatment of comorbid diseases. Effective treatment of asthma is required to prevent asthma exacerbations. Inhaled steroids and combined treatments are the most effective preventive therapy for exacerbations. Patient education and cooperation is an element of the preventive measures for asthma attacks. Compliance to therapy, inhalation techniques, written asthma plans are required. The essential of COPD and asthma exacerbation treatment is bronchodilator therapy. Steroids are also implemented to the therapy, targeting the inflammation. Specific treatments of the cause (infection, airpollution, pulmonary embolism etc.) should be administered. © 2015, Ankara University. All rights reserved.Öğe An optimization approach to scale up keratinase production byStreptomyces sp. 2M21 by utilizing chicken feather(Elsevier Ltd, 2015) Demir T.; Hameş E.E.; Öncel S.S.; Vardar-Sukan F.The aim of this study was to optimize the culture conditions for keratinase production by a new isolate, Streptomyces sp. 2M21 utilizing chicken feather as an alternative low-cost substrate. Contribution of different independent fermentation variables on keratinase activity was investigated by Plackett-Burman design. Parameters that have the highest contribution were selected for the optimization experiments which were carried out by using response surface methodology (RSM). Relative and mutual effects of fermentation variables on keratinase activity were analyzed with "23 Full Factorial Central Composite Design". Cultivation processes were implemented in 250ml Erlenmeyer flasks containing 50ml medium. Maximum keratinase activity was obtained under optimal conditions of 28°C, 5.0gl-1 chicken feather and 5.5 days of process time. As a result of the optimization studies, a 15 fold increase in keratinase activity was reached compared to the unoptimized conditions. Furthermore, similar results were obtained in the 2l bioreactor under optimized conditions. © 2015 Elsevier Ltd.Öğe Purification of tomato (Lycopersicon esculentum) ?-galactosidase by three-phase partitioning and its characterization(2009) Çalci E.; Demir T.; Biçak Çelem E.; Önal S.Three-phase partitioning (TPP) was used to purify ?-galactosidase from tomato (Lycopersicon esculentum). The technique is a novel separation process used for the extraction and purification of biomolecules. It involves the addition of salt (generally ammonium sulfate) to the crude extract followed by the addition of an organic solvent (generally butanol). The protein appears as an interfacial precipitate between upper organic solvent and lower aqueous phases. The various conditions required for attaining efficient purification of the ?-galactosidase fractions were optimized. Under optimized conditions, it was seen that, 50% of ammonium sulfate saturation with 1:1 ratio of crude extract to t-butanol at pH 4.5 gave 4.3-fold purification with 80% activity yield of ?-galactosidase. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed substantial purification and the molecular weight of ?-galactosidase was nearly found to be as 34 kDa. The purified enzyme was characterized with respect to its activity and stability at various pH and temperature ranges. Optimum pH and temperature were determined at pH 4 and 37 °C, respectively. The enzyme was stable in the range of pH 3-5 and more than 60% of its initial activity was recovered. The ?-galactosidase completely retained nearly about 70% of its initial activity at 40 °C. The kinetic constants; Km and Vmax using p-nitrophenyl-?-d-galactopyranoside (PNPG) as substrate were 1.07 mM and 0.01 U/mg, respectively. TPP is an attractive process for the purification of ?-galactosidase. Crown Copyright © 2009.Öğe Treatment of severe asthma: Expert opinion [Agi{dotless}r asti{dotless}m tedavisi: Uzman görüşü](Ankara University, 2014) Türktaş H.; Bavbek S.; Çelik G.; Demir T.; Gemicioglu B.; Günen H.; Kiyan E.; Mungan D.; Oguzülgen I.K.; Polatli M.; Saryal S.; Sayiner A.; Şen E.; Yildirim N.; Yildiz F.; Yorgancioglu A.Severe asthmatics account 10% of the all asthmatic population. Those asthmatics whose disease is inadequately controlled account for up to half of the cost for asthma, because they have more emergency room visits, more hospital admission and greater absenteeism from work. New therapeutic options were tried in those patients whose asthma was uncontrolled with standart high dose inhaled corticosteroid and long acting beta-2 agonsit combination therapy. In this paper taking into account the conditions of our country, current literature was reviewed and treatment options was discussed and graded recommendations are made for daily clinical practice in patients with severe treatment-refractory asthma.
