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Öğe Acute renal failure caused by blunt trauma in a kidney transplant recipient(Medicine Science | International Medical Journal, 2016) Ünal, Bülent; Kayabaş, Üner; Taşkapan, Hülya; Pişkin, Turgut; Baysal, Tamer; Kayhan, BaşakInjuries in renal graft are mostly caused by blunt trauma to the abdomen in any time after transplantation. The response to a trauma depends on the balance between inflammatory and antiinflammatory mediators. Trauma associated renal failure can be confused with acute humoral/cellular rejection in an allograft recipient. Delay in diagnosis and appropriate treatment can cause loss of graft in those patients. A 27-year-old male patient underwent renal transplantation because of unidentified end-stage renal failure. He was admitted to emergency department with abdominal pain on graft region, hematuria and oliguria. He informed that he fell down on his bottom from tabouret in the bath before onset of the complaints. After observing hematoma in renal pelvis of the transplanted kidney by urinary ultrasonography, an ureteral double J stent was applied. The serum creatinine level continuously increased, anuria was observed and creatinine level rose to 7.9 mg/dL. The patient was treated with pulsed doses of methylprednisolone, anti-thymocyte globulin because of acute allograft rejection with preliminary diagnosis. But both radiological findings of renal allograft and the performed immunological tests excluded the diagnosis of renal acute allograft rejection and confirmed the renal kidney failure due to post-traumatic blood clots in the renal pelvis and ureter of the allograft. Then he was discharged with functional graft through applied medical interventions.The application of basic immunophenotyping protocols together with clinical assessment may help to distinguish rejection from the other situations in renal transplant recipient with acute renal failure following blunt trauma.Öğe Analysis of peripheral blood lymphocyte phenotypes and Th1 Th2 cytokines profile in the systemic immune responses ofHelicobacter pylori infected individuals(Microbiology and Immunology, 2008) Kayhan, Başak; Araslı, Mehmet; Eren, Hacı; Aydemir, Selim; Aktaş, ElifH. pylori elicits specific humoral and cellularimmune responsesin themucosalimmune system.However, the type and extent of T lymphocyte response in the systemic immune system is not clear for H. pylori positive patients. In this study, peripheral blood T lymphocyte phenotypes and serum Th1/Th2 based cytokines of 32 H. pylori positive patients were analyzed and compared to those of healthy controls. While αβ TCR+ lymphocytes and their phenotype analysis were not significantly different to those of healthy controls, the percentage of pan γδ TCR+ lymphocytes was up to 2.4 times greater in the H. pylori positive group then in healthy controls. Furthermore, significant increases in IL-10 concentrations in serum samples of H. pylori patients indicated that their immune systems had switched toward a Th2 type immune response. The correlation between phenotype and type of T cell response in the peripheral blood during H. pylori infection is discussed.Öğe Aptamers an in vitro evolution of therapeutic and diagnostic applications in medicine(Disease and Molecular Medicine, 2013) Kayhan, Başak; Kayabaş, ÜnerAptamers are nucleic acid oligomers with distinct conformational shapes that allow binding targets with high affinity and specificity. Selective Evolution of Ligands by Exponential Enrichment (SELEX); an in vitro selection process to develop aptamers, has been invented in 1990. Despite more than 20 years have passed after its discovery, products of SELEX technology are in use in medicine. In this review we discuss why we need aptamers not only in therapeutic but also in diagnostic applications; and also critical points in SELEX technology. Finally; we present the aptamers in use and some patented aptamers awaiting approval.Öğe A bioactive product lipoxin A4 attenuates liver fibrosis in an experimental model by regulating immune response and modulating the expression of regeneration genes(2019) Kurtoğlu, Elçin Latife; Kayhan, Başak; Gül, Mehmet; Kayhan, Burçak; Akdoğan Kayhan, Meral; Karaca, Zeynal Mete; Yeşilada, ElifAbstract: Background/Aims: Lipoxin A4 (LXA4), an anti-inflammatory lipid mediator, regulates leukocyte cellular activity and activates gene transcription. The therapeutic effect of LXA4 on liver fibrosis and its mechanism on the immune system are largely unknown. Because the regenerative capacity of hepatocytes in acute and chronic liver failure models of mouse increases by silencing MKK4, we aimed to investigate the effect of parenteral administration of LXA4 on the genes responsible for regeneration of liver, namely MKK4, MKK7, and ATF2, and visualize the therapeutic effects in an experimental model. Materials and Methods: Fibrosis was induced in mice by administration of thioacetamide (TAA). LXA4 was administered during the last two weeks of fibrosis induction. The fibrosis level was measured by Knodell scoring. The liver function was measured by analyzing serum ALT, AST, and AP levels. Expression levels of genes responsible for liver fibrosis (TGF-?) and cell regeneration (MKK4, MKK7, and ATF2) have been measured by RT-PCR analysis. Inflammatory and anti-inflammatory cytokine levels were measured in serum samples and liver homogenates by Enzyme Linked Immunosorbent Assay (ELISA). Ultrathin sections were examined using a transmission electron microscope and analyzed. Results: We observed significant healing in liver of the LXA4-treated group, histologically. This finding was in parallel with reduction of serum ALT, AST, but not AP levels. TGF-? and MKK4 expressions were significantly reduced in the LXA4-treated group. Administration of LXA4 caused significant elevation of IL-10 in systemic circulation; however, that elevation was not detected in liver homogenates. Nevertheless, significant reductions in TNF-? and IL-17 have been observed. Conclusion: The anti-inflammatory effect of LXA4 maintains the regenerative capacity of liver during fibrosis in an experimental liver fibrosis model. LXA4 may be therapeutically beneficial in liver fibrosis.Öğe Can IL 2R alpha be a valuable marker along with CA 19 9 in the diagnosis of chronic pancreatitis and pancreatic cancer(International journal of biological markers, 2004) Kayhan, Başak; Kayhan, Burçak; Akdoğan, MeralPancreatic cancer is characterized initially by non-specific abdominal symptoms followed by rapid tumor progression. Although chronic pancreatitis is a benign disorder, it can be one of the causative factors of pancreatic cancer. The level of the tumor marker carbohydrate antigen 19-9 (CA 19-9) in pancreatic cancer does not correlate with the stage of the neoplasm. Soluble interleukin 2 receptor (sIL-2R) is a cytokine that shows increased levels during some inflammatory processes and malignant disorders. AIM: Our aim in this study was to investigate whether sIL-2Ralpha levels can be used in association with CA 19-9 in the early diagnosis of pancreatic cancer and chronic pancreatitis. PATIENTS: Serum samples were obtained from the blood of 21 pancreatic cancer patients without distant metastasis who were deemed inoperable, 16 chronic pancreatitis patients and 20 normal volunteers. RESULTS: We did not find any significant differences in CA 19-9 levels between normal controls and patients with chronic pancreatitis. There was a significant difference in the levels between the control group and the pancreatic cancer group (p = 0.003) and between patients with chronic pancreatitis and those with pancreatic cancer (p = 0.004). Although there was no significant difference in sIL-2Ralpha levels between the control group and the patient groups, we found a slight correlation between sIL-2Ralpha and CA 19-9 levels in the pancreatic cancer group (p = 0.003, r = 0.623) and a more marked correlation in the chronic pancreatitis group (p < 0.01, r = 0.751). CONCLUSION: According to our results, sIL-2Ralpha alone is not a good candidate marker in the diagnosis of pancreatic cancer; it can, however, be used in association with CA 19-9 for this purpose.Öğe The combined use of dimethyl sulfoxide with chemotherapeutics on bladder cell culture(Gazi Medical Journal, 2001) Sözen, Sinan; Yaman, Önder; Oğuzülgen, İbrahim; Kayhan, Başak; Tuncel, Aytuğ; Alkibay, Turgut; Bozkırlı, İbrahimÖğe The comparison of the effect of somatostatin and SMS 201 995 on enzyme change following endoscopic retrograde cholangiopancreotography(Gazi MEdical Journal, 1998) Görgül, Ahmet; Kayhan, Burçak; Menteş, Bülent; Kayhan, Başak; Akı, ZeynepÖğe A competitive enzyme linked immunosorbent assay ELISA for determination of human albumin in the nanogram range(Gazi Medical Journal, 1999) Aybay, Cemalettin; İmir, Turgut; Kayhan, BaşakÖğe Dexmedetomidine ameliorates TNBS induced colitis by inducing immunomodulator effect(Journal of Surgical Research, 2013) Erdoğan Kayhan, Gülay; Gül, Mehmet; Kayhan, Başak; Gedik, Ender; Özgül, Ülkü; Kurtoğlu, Elçin Latıfe; Durmuş, Mahmut; Ersoy, Mehmet ÖzcanBackground: Since sedatives are often administered to immune-compromised and critically ill patients, our understanding of immunomodulation by sedation will be critical. Dexmedetomidine, a selective a2-adrenergic receptor agonist, is often used for sedation and analgesia especially in intensive care units. There are conflicting and little data concerning both the effect and the mechanism of dexmedetomidine on immune response. In our study, we aimed to investigate the effect of dexmedetomidine on immune system at two different doses (5 mg.kg 1 and 30 mg.kg 1 ) during inflammatory bowel disease by using an experimental model, which resembles both systemic and local inflammation. Methods: The effect of dexmedetomidine on the course of inflammatory bowel disease was investigated by measuring macroscopic and microscopic parameters. We investigated proinflammatory Th1, Th2, and Th17 cytokine levels in serum samples to analyze systemic immune response. Following this, local immune response was investigated by measuring cytokine levels in the presence of dexmedetomidine in spleen cell culture. Results: Dexmedetomidine administration led to amelioration of all disease associated pathological manifestations. According to our in vitro and in vivo results, dexmedetomidine shows anti-inflammatory effect by increasing IL-4 and IL-10 levels responsible from antiinflammatory response via Th2 pathway. Moreover, we showed for the first time in the study that dexmedetomidine administration reduces IL-23, which is responsible from initiation of inflammatory response via Th17 pathway. Conclusions: Dexmedetomidine can have beneficial effect on preoperative or postoperative inflammatory bowel disease patients in intensive care units by down-regulating inflammatory immune response not only in systemic circulation but also in tissue-specific manner.Öğe Dexmedetomidine improves ultrastructural view of renal damage and biochemical parameters during an experimental inflammatory bowel disease(2018) Karaca, Zeynal Mete; Gül, Mehmet; Kayhan, Başak; Erdoğan Kayhan, GülayAbstract: Abstract Investigation of the effect of Dexmedetomidine (Dex) on inflammatory bowel diseases (IBD) induced renal damage by using an experimental model. IBD frequently cause reduction in renal function and renal failure. Since perioperative anesthesia and postoperative conditions in intensive care can cause acute kidney injury and reduction on renal function; deciding on a sedative and anesthetic agent without side effects would reduce IBD caused renal damage. We investigated histopathological, electron microscopic analyzes and antioxidant effects of Dex on kidney tissue during trinitrobenzene sulfonic acid (TNBS) induced damage in BALB/c mice at two different concentrations of Dex; 5?g/kg and 30?g/kg. Blood samples were collected to analyze creatinine levels. The levels of malondialdehyde (MDA) and activity of antioxidant enzymes glutathione (GSH) and superoxide dismutase (SOD) were measured in tissue homogenates. Histopathological and ultrastructural changes in kidney following TNBS induction were significantly reduced in Dex treatment groups. Administration of Dex significantly reduced creatinine levels. MDA levels were significantly reduced in Dex groups. Administration of Dex brought back GSH level to control level. Administration of Dex significantly 1.48 and 1.96 times increased SOD activity at 5?g/kg and 30 ?g/kg, respectively. Dexmedetomidine treatment may have benefits to prevent IBD induced renal damage.Öğe Diyaliz hastalarında panel reaktif antikor düzeyinin tespiti: iki yöntem ve iki analizin karșılaștırılması(İnönü Üniversitesi Sağlık Bilimleri Dergisi, 2015) Kurtoğlu, Elçin Latife; Şahin, İdris; Taşkapan, Hülya; Yeşilada, Elif; Kayhan, Başakİnsan doku uygunluk antijenleri sınıf-I ve sınıf- II'ye karşı özgül antikorlar (Panel Reaktif Antikor-PRA-) doğum; kan transfüzyonu ve/veya organ transplantasyonu sonrası gelişir. PRA, nakil sonrası graft’in reddinde önemli rol oynamaktadır. Bu nedenle PRA analizi organ bekleyen hastaların takibinde nakil öncesi ve sonrası yapılması zorunlu rutin testlerdendir. PRA testi, tarama ve tanımlama olarak isimlendirilen; iki farklı analiz ile gerçekleştirilmektedir. Tarama PRA varlığının tespitine yönelik kalitatif bir test’tir. Tanımlama ise çoğunlukla donor spesifik antikor tespitinde kullanılan kantitatif bir test’tir. Tanımlama sadece özgül PRA yüzdesini vermekle kalmaz aynı zamanda ölçüm yöntemine de bağlı olarak donor spesifik antikor tespitini de sağlar. PRA ölçümü için kompleman bağımlı sitotoksisite; Enzyme Linked Immunoassay (ELISA), Akım sitometri ve Luminex yöntemleri kullanılmaktadır. Bu çalışmanın amacı, laboratuvarımızda böbrek nakli bekleme listesindeki diyaliz hastaları için yaptığımız rutin PRA analizinde kullanılan ELISA ve Luminex yöntemlerinin tarama ve tanımlama analizlerinde etkinliğini karşılaştırmaktır. Laboratuvarımıza başvuran 154 hastadan yapılan analizlere göre; ELISA ve Luminex PRA tarama sonuçları arasında %85 uyum bulunurken, her iki yöntemle yapılan tanımlama sonuçları arasında ise toplamda %72 uyum saptanmıştır. Aynı yöntemin tarama ve tanımlama sonuçları incelendiğinde; ELISA PRA tarama ve tanımlama sonuçlarının %19 oranında uyumsuzluk gösterdiği belirlenirken, Luminex PRA tarama ve tanımlama sonuçları arasında %2 gibi ELISA sonuçlarına göre daha az bir uyumsuzluk olduğu belirlenmiştir. Sonuç olarak; nakil öncesi rutin PRA analizi için ELISA yöntemi yerine Luminex yönteminin kullanılması; doğru ve hızlı sonuç alınabilmesi bakımından önemlidir.Öğe A DNA aptamer prevents influenza infection by blocking the receptor binding region of the viral hemagglutinin(Journal of Biological Chemistry, 2004) Jeon, Sung Ho; Kayhan, Başak; Benyedidia, Tamar; Arnon, RuthInfluenza A virus infection is a major source of morbidity and mortality worldwide. Current means of control for influenza are based on prophylaxis by vaccines and on treatment by the available specific influenza neuraminidase inhibitor drugs. The approach taken in the present study is to prevent and/or ameliorate influenza infection by site-specific blocking of the viral binding to host cell receptors. We describe a novel oligonucleotide, known also as an aptamer, which has been designed to complement the receptor-binding region of the influenza hemagglutinin molecule. It was constructed by screening a DNA library and processing by the selective evolution of ligands by exponential enrichment (SELEX) procedure. We show that this DNA aptamer is indeed capable of inhibiting the hemagglutinin capacity of the virus, as well as in the prevention of viral infectivity in vitro, in tissue culture. Furthermore, it inhibits viral infection by different influenza strains in an animal model, as manifested by 90 –99% reduction of virus burden in the lungs of treated mice. The mode of action of this aptamer is by blocking the binding of influenza virus to target cell receptors and consequently prevention of the virus invasion into the host cells.Öğe The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis(Immunopharmacology and Immunotoxicology, 2011) Aktunç, Erol; Kayhan, Başak; Araslı, Mehmet; Doğan Gün, Banu; Barut, FigenInflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1α, IL-6, TNF-α), Th1 (IFN-γ, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-α level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.Öğe The effect of diphtheria toxin on nitric oxide induction from RAW264.7 murine macrophages(Turkish journal of medıcal scıences, 1997) Aybay, Cemalettin; Tarhan, Gülnur; İmir, Turgut; Kayhan, Başak: In this study the effect of diphtheria toxin (DT) on nitric oxide (NO) production from RAW 264.7 murine macrophages was investigated. Griess reagent was used to determine NO production by measuring nitrite levels in the culture supernatants. Corynebacterium diphtheriae G12/6 strain-produced DT (Limes flocculation activity and immunodiffusion assays were positive) demonstrated a dosedependent effect on RAW 264.7 macrophages to induce NO production. LNAME, an L-arginine analogue, inhibited NO production from DT-stimulated RAW 264.7 macrophages. At the given concentrations of DT, lipopolysaccharide (LPS or endotoxin)- induced NO production from RAW 264.7 macrophages was also inhibited. RAW 264.7 macrophage cells, incubated with various concentrations of DT for 3 days, were killed by DT in a dose dependent manner. Endotoxin contamination of DT was demonstrated with limulus amoebocyte lysate assay. Polymyxin B, frequently added to neutralize the effects of LPS in vitro, inhibited DT-induced NO production from RAW 264.7 cells. The misleading data concerning NO inducing capacity of DT was seemed to be related to endotoxin contamination. Thus, DT does not seem to be capable of inducing NO production from macrophages.Öğe The effect of exercise induced weight loss on myokines and adipokines in overweight sedentary females steps aerobics vs jogging walking exercises(J Sports Med Phys Fitness, 2016) Düzova, Halil; Güllü, Esin; Çiçek, Güner; Köksal, Burcu; Kayhan, Başak; Güllü, Abdullah; Şahin, İbrahimThe objectives of this study were to verify effects of step-aerobic exercise (SAE) and jogging-walking exercise (JWE) program on myokines and adipokines levels in overweight sedentary females. METHODS:Volunteer subjects (n=25) were assigned to two exercise groups: steps aerobics and jogging-walking. The exercise program given to them was for five days a week and for twelve weeks period. Serum samples were collected from venous blood before and immediately after cardio-respiratory fitness test (CRF) by Bruce protocol and stored at -80 C until they were assayed before 12 weeks exercise program. After 12- weeks training program this procedure was repeated. Serum TNF-α, IL-6, IL-15, IL-17, IL- 18, leptin, resistin and adiponectin levels were assayed by ELISA. RESULTS: Leptin and IL-15 levels were increased whereas resistin levels were decreased after CRF test in JWE training group following 12-weeks exercise program. TNF-α, IL-15 and IL-18 levels were higher and leptin levels were lower in SAE group than JWE group after 12-weeks exercise period. However, both SAE and JWE did not lead to significant change in serum levels of IL-17, IL-6 and adiponectin levels. CONCLUSIONS: What this study has added to existing knowledge that both SAE and JWE may cause weight loss especially in fat mass. But, the effect of SAE and JWE on myokines and adipokines levels may be the different. Further studies are needed to find out clinical importance of these findings.Öğe Effect of mucosal immunomodulation with fed cholera toxin on healing of experimental colonic anastomosis(Diseases of the Colon & Rectum, 2002) Kaplan, Mehmet; Menteş, Bülent; Tatlıcıoğlu, Ertan; Kayhan, Başak; Aybay, CemalettinThe aim of this study was to investigate in rats whether preoperative orogastric administration of low doses of cholera toxin would influence the mechanical strength of experimental colonic anastomosis on the basis of the gut mucosal immunomodulation effect of this antigen. METHODS: The cholera toxin group (n 14) was fed 10 g of cholera toxin in phosphate-buffered saline three times before surgery at 10-day intervals, whereas the controls (n 14) received phosphate-buffered saline only. Twenty-four hours after the last dose of cholera toxin (or placebo in control group), the animals underwent left colonic transection and anastomosis. Seven days after colonic transection-anastomosis, the bursting pressure of the anastomotic segment was recorded in situ. Perianastomotic and extra-anastomotic tissue samples were obtained for measurements of tissue transforming growth factor-beta, interleukin-6, and interferon-gamma levels with enzyme-linked immunosorbent assay. RESULTS: Cholera toxin administration resulted in a significantly higher bursting pressure than in the control group (165.78 12.37 vs. 138.4 7.87 mmHg; P 0.001). Compared with the control group, the heightened mechanical strength of colonic anastomosis provided by cholera toxin was associated with significant increases in the perianastomotic tissue levels of transforming growth factor-beta (199.34 24.85 vs. 70.66 10.63 pg/ml; P 0.001) and interleukin-6 (439.31 95.14 vs. 289.57 96.59 pg/ml; P 0.001), whereas interferongamma was significantly lower (174.04 44.82 vs. 219.00 31.35 pg/ml; P 0.05). This cytokine pattern induced by cholera toxin in the wound milieu was also found to be similar in the extra-anastomotic colon. CONCLUSION: The mechanical strength of uncomplicated experimental colonic anastomosis increased significantly with gut mucosal immunomodulation with repeated low preoperative doses of cholera toxin. This enhanced healing had significant positive correlation with the colonic tissue level of transforming growth factor-beta and inverse correlation with interferon-gamma. If the relevant dose regimen is identified and its safety is assured in humans, gut mucosal immunomodulation might provide an efficient, safe, and inexpensive tool to improve surgical outcome in colorectal surgery, particularly in high-risk situations.Öğe Effects of interactions between various fats and active passive phases on postprandial inflammation in rats(Biological Rhythm Research, 2016) Otlu, Hüsniye Gül; Kayhan, Başak; Güldür, TayfunThe circadian clock controls number of behavioral and physiological processes during daily light/dark cycle including inflammation and vascular injury. However, how reciprocal interaction of dietary fats and light/dark cycle affects postprandial inflammation is currently unknown. To this end, effects of various dietary fats given to rats by gavaging either in light or dark phase on postprandial inflammation were compared. Sunflower oil load activated greater number of inflammatory CD markers in passive phase whereas the butter load in active phase compared to their counter phase. The inflammatory influence of fish oil load appeared to be mostly confined to passive phase. Differences found between the levels of some of the inflammatory markers in active and passive phases of normal fed rats were altered by fat/oil administrations. We conclude that influences of dietary fats/oils on postprandial inflammatory changes might depend not only on their fatty acid compositions but also on their ingestion times.Öğe Effects of reciprocal interactions between various dietary fats and circadian phases on postprandial hyperlipidemia in rats(TAYLOR & FRANCIS LTD, 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND, 2018) Satılmış, Basri; Kayhan, Başak; Güldür, TayfunExpression levels of various intestinal proteins involved in postprandial lipoprotein assembly as well as plasma triglyceride concentration exhibit daily oscillations indicating circadian control. The length of the carbon chain and degree and position of unsaturation of fatty acids influence triglyceride secretion by the enterocytes. To this end, effects of reciprocal interactions of various single fats/oil (olive oil, fish oil or butter) gavaging either in active or passive phase were investigated in rats. Fat/oil gavaged in the active phase of circadian rhythm resulted in higher postprandial serum triglyceride levels compared to that in the passive phase. Moreover, olive oil led to higher MTP activity and apo B-48 gene expression, while fish oil gavaging caused more prominent apo B-48 and MTP gene expression when they were given in the passive phase. The present results indicate that circadian time at which fat or oil gavaged once might exert influence on postprandial lipoprotein synthesis/assembly.Öğe Effects of reciprocal interactions between various dietary fats and circadian phases on postprandial hyperlipidemia in rats(Biological Rhythm Research, 2017) Satılmış, Basri; Kayhan, Başak; Güldür, TayfunExpression levels of various intestinal proteins involved in postprandial lipoprotein assembly as well as plasma triglyceride concentration exhibit daily oscillations indicating circadian control. The length of the carbon chain and degree and position of unsaturation of fatty acids influence triglyceride secretion by the enterocytes. To this end, effects of reciprocal interactions of various single fats/oil (olive oil, fish oil or butter) gavaging either in active or passive phase were investigated in rats. Fat/oil gavaged in the active phase of circadian rhythm resulted in higher postprandial serum triglyceride levels compared to that in the passive phase. Moreover, olive oil led to higher MTP activity and apo B-48 gene expression, while fish oil gavaging caused more prominent apo B-48 and MTP gene expression when they were given in the passive phase. The present results indicate that circadian time at which fat or oil gavaged once might exert influence on postprandial lipoprotein synthesis/assembly.Öğe Fare makrofajlarından nitrik oksit sentezine interferon gamma ve lipopolisakkaritin etkileri(Türkiye Tıp Dergisi, 1999) Tayşi, Bülent; Kayhan, Başak; Aybay, Cemalettin; İmir, TurgutNitrik oksit (NO) makrofajların sitotoksik etkisinin ortaya çıkmasında rol almaktadır. NO’in yapımını nitrik oksit sentaz (NOS) enzimi katalize etmektedir. Sitozolde bulunan bu enzimin, enzimi kodlayan genler, hücre veya organ lokalizasyonlarındaki farklılıklar ve kalsiyum uyarımına verdikleri yanıta göre iki izoformu tanımlanmıştır: 1. Uyarılabilir NOS (inducible NOS-iNOS), 2. Yapısal NOS (constitutional NOS-cNOS). Makrofajlarda iNOS bulunur. Lipopolisakkarit (LPS) ve interferon gamma (IFN-g) iNOS enzimini uyaran maddeler arasındadır. Patojen ajanların IFN-g ile birlikte makrofajların NO salgılanması üzerine sinerjistik etki yapmalarının yüksek düzeylerde üretildiğinde konakçı hücre ve dokularına karşı da zararlı etkileri olabilen NO’in ortamda patojen bir ajan bulunmadıkça üretilmemesi şeklinde bir çeşit düzenleyici mekanizma oluşturduğu düşünülmektedir. Ancak, fare kökenli makrofaj tiplerinin IFN-g ve LPS’in tek başına veya beraber uygulanması durumundaki NO yanıtları, kullanılan hücre tipleri ve araştırma grupları arasında farklılıklar göstermektedir. Bu çalışmada fare makrofaj kökenli RAW 264.7 hücresi kullanılarak IFN-g, LPS ve IFN-g+LPS kombinasyonunun NO sentezi üzerindeki etkileri ve bu etkilerin NG-nitro-L-arjinin-metil ester (L-NAME) ve polimiksin B ile inhibisyonu araştırıldı. Kültür süpernatanlarında NO düzeyi Griess ayıracı ile nitrit düzeyi ölçülerek belirlendi. Sadece IFN-g ile uyarılan hücrelerde doza bağımlı ve LPS uyarımı ile kıyaslanabilir düzeyde NO yanıtının oluştuğu saptandı. IFN-g+LPS kombinasyonu ile uyarılan hücrelerden, tek başına IFN-gveya LPS ile uyarılanlara göre daha fazla NO salgılanmaktadır. IFN-g veya LPS aracılığı ile NO salgılanması L-NAME ile baskılanmaktadır. LPS’nin biyolojik etkilerini inhibe etmek amacıyla in vitro ortamlarda sıkça kullanılan polimiksin B, LPS ile uyarılan hücrelerdeki NO yanıtını inhibe etmenin yanısıra, IFN-g ile uyarılan hücrelerde NO yanıtını da anlamlı düzeyde (p=0.024) baskılamaktadır.
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