Influence of uridine diphosphate-glucuronosyltransferases (1A9) polymorphisms on mycophenolic acid pharmacokinetics in patients with renal transplant.

BACKGROUND: There are differences in pharmacokinetic of mycophenolic acid among individuals. The UGT1A9 enzyme is of special interest since it is the main enzyme involved in the glucuronidation of MPA. Single nucleotide polymorphisms in the UGT1A9 gene may be responsible for individual differences in the pharmacokinetics of MPA. The aim of this study was to explain MPA pharmacokinetics in UGT1A9 1399 C > T polymorphisms in Turkish renal transplant patients. PATIENTS AND METHODS: One hundred and twenty-five living-donor transplant recipients and 100 healthy control subjects underwent UGT1A9 1399 C > T genotyping using polymerase chain reaction-restriction fragment length polymorphism. Concentrations of MPA were determined with Cloned Enzyme Donor Immunoassay (CEDIA). Besides that, all the patients were monitored for acute rejection and graft function during the study period. RESULTS: The UGT1A9 1399 C > T CC, CT, and TT genotype frequencies among patients were, respectively, 68.0%, 23.2%, and 8.8%. The CC, CT, and TT genotype frequencies among controls were, respectively, 63.0%, 23.0%, and 14.0%. There was no significant difference between patients and controls (p = .480, p = .999, p = .286, respectively). At first month, respectively, through blood concentrations of MPA were significantly higher in UGT1A9 1399 C > T TT carriers than in CT and CC carriers (p = .046). The doses for these patients were lower at first month (p = .021). Acute rejection episodes were not associated with the CC vs CT or TT genotypes (p = .064). CONCLUSIONS: Our results demonstrated a correlation between the UGT1A9 1399 C > T polymorphism and MPA pharmacokinetics among renal transplant patients. Determination of UGT1A9 polymorphism may help to achieve target of MPA blood concentrations.

Genetic association of interleukin-2, interleukin-4, interleukin-6, transforming growth factor-ß, tumour necrosis factor-α and blood concentrations of calcineurin inhibitors in Turkish renal transplant patients.

Cytokines are essential for the control of the immune response as most of the immunosuppressive drugs target cytokine production or their action. The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are immunosuppressive drugs widely used after renal transplantation to prevent allograft rejection. They are characterized by large interindividual variability in their pharmacokinetics; therefore, monitoring their blood concentrations is important to predict their optimal dosage following transplantation. Calcineurin inhibitors inhibit the phosphatase activity of calcineurin, thereby suppressing the production of other cytokines such as transforming growth factor (TGF-ß), tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-2, and IL-4. The aim of this study was to investigate the relationship between polymorphisms of cytokines and blood concentrations of CNIs in renal transplant patients. The study included 53 CsA-treated renal transplant patients and 37 tacrolimus-treated renal transplant patients. Cytokine polymorphisms were analysed using polymerase chain reaction (PCR) sequence-specific primers with the cytokine CTS-PCR-sequence-specific primers Tray Kit; University of Heidelberg. Blood concentrations of CNIs were determined with Cloned Enzyme Donor Immunoassay (CEDIA) method. Patients with TC genotype of TGF-ß at codon 10 had lower CsA blood concentrations than the TT and CC genotypes (P = 0.005) at 1 month in CsA treatment group. The ratio of blood concentration/dose of CsA for patients with TGF-ß1-codon 10 TC genotype was lower than for patients with TT, CC genotypes, and the dose given to these patients was higher in the first month (P = 0.046). The ratio of blood concentration/dose of CsA for patients with IL-2-330 GG genotype was higher than for patients with GT, TT genotypes, and the dose given to these patients was lower at first month and sixth months (P = 0.043, P = 0.035 respectively). The tacrolimus blood concentrations were significantly higher in patients with the genotype GG of IL-2-330 (P = 0.012) at the third month. Patients who had the TC genotype TGF-ß codon 10 had lower CsA blood concentrations and this group had higher acute rejection (P = 0.033). These results suggest that the genotyping for TGF-ß-codon 10, IL-2-330 and IL-6-174 polymorphisms may help individualized immunosuppressive dosage regiments.

Can long-term bisphosphonate use causes low-energy fractures? A case report.

Bisphosphonates are inorganic pyrophosphate analog which accumulate on the bone surface, cause osteoclast apoptosis, and inhibit bone resorption. The nitrogen-containing bisphosphonates continue to be the drug of choice for the treatment of osteoporosis in both men and women. Although histomorphometric studies including bone biopsies have not shown any evidence of microcracks, recent studies have revealed that potent bisphosphonates are responsible for the oversuppression of bone turnover leading to microdamages, reduced bone strength, and increased fracture risk. There are individual cases reporting atypical femoral fractures and severely suppressed bone turnover along with long-term (≥ 5 years) use of biphosphonates. In this study, we report on a 74-year-old woman with a history of continuous alendronate use for nearly 16 years who presented to the emergency department with right proximal humerus and left femur fracture.

The relationship of the interleukin-6 -174 G>C gene polymorphism with cardiovascular risk factors in Turkish polycystic ovary syndrome patients.

We aimed to evaluate the relationship between 174 promoter region of the interleukin-6 (IL-6) C/G gene polymorphism and high sensitive C-reactive protein (hs-CRP), fibrinogen and carotis intima-media thickness (CIMT), body mass index, homeostatic model assessment (HOMA) insulin resistance index, serum lipid parameters, in polycystic ovary syndrome (PCOS) patients carrying a potential risk for developing cardiovascular disease (CVD). We studied 88 PCOS patients and 119 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. The genotype IL-6 distribution did differ between the control group (CC 10.1%, GC 63.0%, GG 29.6%) and the PCOS patients (CC 5.7%, GC 29.5%, GG 64.8%) (P < 0.001). The frequency of the polymorphic G allele was also no similar for the group with PCOS as for the control group with 79.5% and 58.4% respectively (P < 0.001). Both in PCOS patients and in control group, no statistically significant difference was determined between C/C, G/C and G/G, and blood cholesterol levels, triglyceride levels, high-density lipoprotein levels, low density lipoprotein levels, fasting blood sugar levels, insulin levels, HOMA values, CIMT measurements either on the right or left side, hs-CRP, f-testosterone, fibrinogen and 17 alpha-hydroxy-progesterone levels (P > 0.05). Gene polymorphism of IL-6 -174 G>C is a risk factor for PCOS in Turkish patients, but we found no relationship between the cardiovascular risk factors and IL-6 -174 G>C gene polymorphism in women with PCOS and healthy subjects. Our negative results in risk factors of CVD can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short time of period.

The (-174) G/C polymorphism in the interleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish patients.

INTRODUCTION: Interleukins and cytokines play an important role in the pathogenesis of many cancers.We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in patients with papillary thyroid carcinoma (PTC) and control subjects. MATERIAL AND METHODS: In this study, 42 patients with PTC and 340 healthy controls were included. Peripheral blood samples were taken from control group and patients, and blood samples were preserved at -80 C in tubes containing Na-EDTA. RESULTS: We also found a statistically significant difference between patients with PTC and the control group with respect to IL-6 genotype (p<0.05). IL-6 gene polymorphism in patients with PTC patients did not reveal statistically significant difference between the 2 groups (size of tumor >1 cm and <1 cm), multicentricity, RET-PTC types and capsule invasion (p>0.05).We also did not find a statistically significant difference between patients with PTC and the control group with respect to IL-6-gene allele frequency (p>0.05). DISCUSSION: Our data suggest that the IL-6 G-174 C polymorphism could play a role in thyroid cancer risk, but there is no effective role as a prognostic factor.

The relationship of the apolipoprotein E gene polymorphism Turkish Type 2 diabetic patients with and without nephropathy.

OBJECTIVE: Apolipoprotein E (ApoE) genetic variation which is a major constituent of plasma lipoproteins causes diabetic nephropathy progress. Chronic kidney disease is associated with increased E2 allele and the decreased E4 allele risk. The aim of this study was to investigate the association between ApoE gene polymorphism in the development of diabetic nephropathy in Type 2 diabetes Turkish patients. RESEARCH DESIGN AND METHODS: The objective of the study is to investigate the influence of ApoE gene polymorphism in the development of diabetic nephropathy in Turkish Type 2 diabetes. The ApoE genotypes were determined retrospectively in 46 patients with nephropathy and 56 without nephropathy and a control group of 35 healthy individuals. Genomic DNA was extracted from peripheral leukocytes of the subjects using the High Pure PCR Template Preparation Kit. For the detection of the presence of the three ApoE E alleles epsilon2, epsilon3, and epsilon4 (codon 112 and 158) were analyzed by the commercial LightCycler ApoE Mutation Detection Kit. RESULTS: No differences in ApoE genotype or the allelic frequencies of epsilon2, epsilon3 or epsilon4 were found between the Type 2 diabetic patient group (with and without nephropathy) and a control group. CONCLUSIONS: We conclude that the ApoE gene polymorphism is not associated with the development of diabetic nephropathy in Turkish Type 2 diabetic patients. Lack of association between ApoE gene polymorphism and Type 2 diabetic nephropathy might be due to ethnic differences.

The relation of adiponectin and tumor necrosis factor alpha levels between endothelial nitric oxide synthase, angiotensin-converting enzyme, transforming growth factor beta, and tumor necrosis factor alpha gene polymorphism in adrenal incidentalomas.

OBJECTIVE: The aim of our study was to demonstrate demographic characteristics, presence of inflammatory markers, distribution of angiotensin-converting enzyme (ACE), tumor necrosis factor (TNF), endothelial nitric oxide synthase (eNOS) genotypes and relations among these parameters in these patients and control subjects. RESEARCH DESIGN AND METHODS: Study samples were collected from 50 patients with adrenal mass and 30 control groups. The eNOS, ACE, TNF-alpha, transforming growth factor (TGF)-beta genes polymorphisms, TNF-alpha, adiponectin levels were analysed in 50 unrelated Turkish patients with a diagnosis of adrenal incidentaloma (AI). RESULTS: There was statistically significant difference between TNF-alpha levels of patient and controls (p=0.048). We have not detected the connection between TGF-beta, TNF-alpha, ACE, eNOS gene polymorphism with serum TNF-alpha and adiponectin levels. In this study, we demonstrated that there were significant differences for ACE genotypes in the patients when compared to the controls (p<0.05). The percentages of the ID, DD, II genotypes for ACE gene polymorphism in the patients group were 30.0, 13.0, 7.0%, respectively. CONCLUSIONS: According to different cases of eNOS, TGF-beta, ACE, and TNF-alpha gene genotypes; no statistical significant difference was found between basal cortisol, ACTH, DHEAS, metanephrine, renin, aldosterone, normetanephrine, 17-hydroxyprogesterone, 1 mg low-dose dexamethasone suppression test-cortisol response and AI size. In this study, I/D genotype was determined to be statistically higher in ACE gene in patients with AI (p=0.014).

Predictive Value of Interleukin 2 and Interleukin 8 on Early Rejection in Living Related Kidney Transplant Recipients.

INTRODUCTION: Early diagnosis of rejection in kidney transplant (KTx) recipients is of paramount importance for long-term graft survival. Cytokines play an important role in rejection via activating T cells. Neutrophil accumulation in the graft indicates cell-mediated rejection. Cellular infiltration is mediated through chemoattractant factors. The aim of this study was to investigate the relationship between graft function and serum levels of interleukin 2 (IL-2) and interleukin 8 (IL-8) in KTx. METHOD: Sixty-five patients undergoing KTx were enrolled in the study. Serum samples of IL-2 and IL-8 were collected the day before the operation, on postoperative days 1 and 7 day, and during the first and third month after the onset of rejection. The enzyme-linked immunosorbent assay method was used to determine the IL-2 and IL-8 values. RESULTS: A total of 9 (13.8%) patients had rejection documented on biopsy samples. Fifty-six patients had stable graft function (SGF). IL-2 and IL-8 values before KTx of both the rejected and SGF patients were not statistically different. Univariate analysis revealed that IL-2 and IL-8 were correlated with rejection (P = .046, P = .015). IL-8 levels were higher in the rejection group compared to the SGF group on the seventh day and first month postoperatively (P = .023, P = .038). The rejection group maintained higher levels of IL-8 for 11 days (range: 7-30) compared to the SGF group (P = .002) and the IL-8 levels correlated with serum creatinine levels (r = 0.621, P = .001). IL-2 levels were higher in the rejection group on days 1 and 7 compared to the SGF group (P = .042, P = .031). IL-2 and IL-8 levels were correlated with low eGFR in the third month in the rejection group (r = 0.421, P = .037; r = 0.518, P = .008). CONCLUSION: Determining the cytokine levels in the early post-KTx period may be helpful in tailoring immunosuppressive regimens in patients with a risk of rejection.

Thrombin-activatable fibrinolysis inhibitor and cardiovascular risk factors in polycystic ovary syndrome.

OBJECTIVE: We aimed to assess circulating thrombin activatable fibrinolysis inhibitor (TAFI) levels and carotid intima-media thickness (CIMT) in PCOS patients and control subjects. In this study we aimed to evaluate the relation between the levels of TAFI and homocysteine, high sensitive CRP (hsCRP), fibrinogen and CIMT in PCOS patients carrying a potential risk for developing CVD and diabetes and compared with age- and body mass index-matched controls. RESEARCH DESIGN AND METHODS: We studied 68 PCOS patients and 26 healthy controls. We conducted an observational study examining noninvasive markers of early CV disease in women with PCOS including structural CIMT. Noninvasive markers of early CVD, CIMT were measured in PCOS patients and control subjects. Metabolic parameters included fasting insulin and glucose levels, lipid and androgen levels, TAFI levels, hsCRP. RESULTS: Fasting glucose levels, prolactin, TSH, Total-cholesterol, LDL-cholesterol, triglyceride, estradiol, DHEA-S and age were similar in the two groups, whereas serum insulin, fibrinogen, hs-CRP, 17-OHP, free-testosterone, total testosterone, HOMA-IR, HDL were significantly elevated in PCOS patients in comparison to control subjects (p<0.05). Plasma TAFI levels were similarly in PCOS patients compared with healthy controls. No difference was observed in the combined IMT among the studied groups. CONCLUSIONS: In our study, no significant difference in lipid parameters was determined between patients with PCOS and healthy controls. In our study, we did not observed any difference in CIMT measurements and TAFI levels between patients with PCOS and healthy controls that can be explained by their low ages and short duration of PCOS.

Oxidative stress markers in young patients with polycystic ovary syndrome, the relationship between insulin resistances.

OBJECTIVE: Polycystic ovary syndrome is a syndrome of ovarian dysfunction. Oxidative stress, inflammation and endothelial cell activation are thought to play concomitant roles in the pathogenesis of the above diseases particularly in the development of atherosclerotic lesions. RESEARCH DESIGN AND METHODS: We studied 58 polycystic ovary syndrome patients and age-matched 25 healthy controls consisting of women that have regular, ovulatory cycles and normal androgen levels. Homeostasis Model Assessment-Insulin Resistance for this study was taken as 1.75 that is the upper level of confidence interval of %95 of the mean of the healthy group. PCOS patients were divided into two groups as for below the cut-off level (<1.75) and above the cut-off level (> or =1.75). hs-CRP, fibrinogen, malondialdehyde, nitric oxide and disulfide level results were compared both in PCOS and control groups. RESULTS: In this study, sensitive CRP was found to be statical significantly higher in polycystic ovary syndrome groups whose Homeostasis Model Assessment-Insulin Resistance were > or =1.75 and <1.75 when compared to the control group. But, no significantly correlation was determined between malondialdehyde, nitric oxide and disulfide levels and CRP elevation. CONCLUSIONS: In our study, because those participants were young and non- obese patients with PCOS, malondialdehyde, nitric oxide and disulfide levels and Carotid Artery Intima-Media Thickness measurements as a pre-indicator of cardiovascular disease were not found to be different from those of the controls.

The prevalence of RET/PTC mutations in papillary thyroid cancers in Turkish population and its relation between tumor histopathology and prognostic factors.

OBJECTIVE: In recent years, thyroid cancer has been at the forefront of molecular pathology as a result of the consequences of the Chernobyl disaster and the recognition of the role of RET/PTC rearrangements in papillary thyroid carcinomas (PTCs). Correlation of RET/PTC expression with clinical outcome is controversial. This study aims to identify the prevalence of RET/PTC oncogene expression in Turkey, and to investigate the correlation between RET/PTC oncogene expression and the known prognostic factors of PTC in 101 patients. METHODS: The RET rearrangements were examined by means of reverse transcriptase-polymerase chain reaction analysis, with primers flanking the chimeric region. Statistical evaluation was performed by using Independent samples t-test, One-sample Chi-square test and Pearson Chi-square or Fisher's Exact Test. RESULTS: RET/PTC was determined positive in 67(66.3%) of totally 101 patients (p<0.001). RET/PTC1 in 32(31.7%), RET/PTC3 in 21(20.8%), RET/PTC1+RET/PTC3 both in 10(9.9%) patients were found to be positive. There was RET/PTC2 positiveness in two patients, RET/PTC2,3 positiveness in one patient, and RET/PTC1,2,3 positiveness in one patient. No statistical difference was found between RET/PTC1 and RET/PTC3. None of genetico-clinical analyses showed any significant association between RET/PTC expression and the clinical and pathological features of the cancers. CONCLUSION: While this prevalence of the RET/PTC is less than RET/PTC frequency seen after Chernobyl in Belarus, its prevalence in our region is also high (66.3%). As a result, no significant correlation was found in between prognosis and RET/PTC frequency.

Comparison of the effects of thoracic and lumbar epidural anaesthesia on induction and maintenance doses of propofol during total i.v. anaesthesia.

BACKGROUND: In this randomized, double-blind study, the effects of thoracic and lumbar epidural anaesthesia on the induction doses (IDs) and maintenance doses (MDs) of propofol during bispectral index (BIS) guided total i.v. anaesthesia were compared. METHODS: Fifty-four patients (three groups, n=18 each) undergoing urological surgery in lumbotomy position were studied in Groups T (Th7-8) and L (L3-4), epidural anaesthesia was performed with initial doses obtaining sensorial block at Th4 (sd 1) followed by 7 ml h(-1) infusion; Group C received no epidural anaesthesia intraoperatively. The ID (BIS <45) and MD (BIS: 40-50) of propofol and recovery (BIS >80) and extubation times were recorded. RESULTS: The volume to obtain a block was significantly lower in Group T than in Group L [10.7 (1.5) vs 14.7 (1.0) ml; P<0.001]. ID was significantly higher in Group C compared with that in Groups T and L [2.16 (0.15) vs 1.33 (0.19) vs 1.46 (0.14) mg kg(-1), respectively; P<0.001] with no significant difference between Groups T and L. For MD, there were significant differences between all groups [3.82 (0.9) vs 5.8 (1.32) vs 9.21 (0.55) mg kg(-1) h(-1) in Groups T, L, and C, respectively; P<0.001]. For recovery and extubation times, Group T

Polymorphism of the interleukin-10 gene in polycystic ovary syndrome.

Interleukin (IL)-10 is a major anti-inflammatory cytokine that has been associated with obesity and type 2 diabetes. We aimed to evaluate the IL-10 gene polymorphisms in polycystic ovary syndrome (PCOS) and control subjects. Ninety-one young women with PCOS and 74 healthy control women were included in our study. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin and IL-10 gene polymorphism genetic analysis and carotid intimae media thickness (CIMT) were measured. The genotype and allele frequencies showed similar ratios between both the control and the patient group. The AA and AG genotypes in IL-10 polymorphism seemed to be relatively high, but statistically no significant difference has been detected in GG genotype. Our results show that IL-10 gene polymorphism of PCOS patients has no effect on inflammatory markers, metabolic parameters (fasting insulin, fasting glucose, HOMA-IR), carotid intimae media thickness and Ferriman- Gallwey scoring. These data will be different in PCOS patients with different ethnical origin.

The relationship of the interleukin-6 -174 G>C gene polymorphism with oxidative stress markers in Turkish polycystic ovary syndrome patients.

OBJECTIVE: Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular (CD) diseases. Cardiovascular risk factors that have been reported include oxidative stress markers [nitric oxide (NO), malondialdehyde (MDA), disulphite (SH)]. We aimed to evaluate the relation between the IL-6 G/C gene polymorphism and oxidative stress markers in polycystic ovary syndrome (PCOS) patients. DESIGN AND PATIENTS: We studied 85 PCOS patients and 115 healthy controls. PCOS was defined by the Rotterdam PCOS consensus criteria. RESULTS: The genotype IL-6 distribution did differ between the control group (CC 9.6%, GC 63.4%, GG 27.0%) and the PCOS patients (CC 4.7%, GC 29.4%, GG 65.9%) (p<0.001). The frequency of the polymorphic G allele was also not similar for the group with PCOS as for the control group with 80.6% and 58.7%, respectively (p<0.001). No statistically significant difference was determined for MDA and NO levels in PCOS patients and control group (p>0.05). Only SH levels were found to be high in favor of patient group (p<0.05). No statistically significant difference was determined between IL-6 G/C gene polymorphism and oxidative stress markers in PCOS patients and in the control group. CONCLUSION: Gene polymorphism of IL-6 -174 G>C is a risk factor for PCOS in Turkish patients. IL-6 gene polymorphisms are not related to NO, MDA, and SH levels in PCOS. Our negative results in risks factors of CV disorders can probably be explained by the fact that metabolic parameters and endothelial systems of patients may not yet be affected in this short period of time.

Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population.

OBJECTIVE: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. RESULTS: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). CONCLUSIONS: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.

Demographic and clinical features of patients with subacute thyroiditis: results of 169 patients from a single university center in Turkey.

BACKGROUND: Turkey is an endemic area for thyroid diseases. The Aegean region is well documented for increased prevalence of thyroid disorders. In this study we investigated the demographic and clinical features of subacute thyroiditis (SAT) patients who had been diagnosed and treated in Ege University. METHODS: The hospital files of patients admitted to the endocrinology clinic of Ege University between January 1987 and December 2001 were retrospectively evaluated. Patients who had been diagnosed as having any thyroid disorder were determined. RESULTS: 176 fulfilled diagnostic criteria for SAT. The majority of patients with SAT were diagnosed as having subacute granulomatous thyroiditis (169/176) (134 females, 35 males, mean age 34.0+/-17.8 yr); 69% of the patients were between 30-50 yr of age. Thyroid pain was present in 97.1% of female patients, and in 100% of male patients. High fever was evident in 78 patients (46.2%). Mean erythrocyte sedimentation rate (ESR) was 43.42+/-39.68 mm/h. Anti-thyroglobulin antibody was positive in 20%, and anti-thyroid peroxydase antibody was positive in 4% of patients. Among patients who were treated with non-steroidal anti-inflammatory drugs (NSAD) 10 female patients (10.6%), and 3 male patients (12%) developed recurrence of the disease. Among patients who were treated with prednisolone 7 female patients (17.5%), and one male patient (10%) developed recurrence. There was no significant difference regarding the recurrence rates between patients who were treated with NSAD and patients who were treated with prednisolone. CONCLUSION: With the exception of ESR, demographic, clinical, laboratory, and imaging findings and prognoses of our patients were comparable to the previous reports.

Fas/Fas ligand gene polymorphism in patients with papillary thyroid cancer in the Turkish population.

OBJECTIVE: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. RESEARCH DESIGN AND METHODS: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. RESULTS: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. CONCLUSIONS: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Comparison of Two Different Inhalation Anesthetics on Grafted Kidney Function in Patients Undergoing Renal Transplantation Surgery: Desflurane or Sevoflurane?

BACKGROUND: Anesthetic management of patients during renal transplantation is vitally important for ensuring proper functioning of kidneys that have undergone ischemia-reperfusion damage. The goal of this prospective study was to compare the effects of 2 different inhalation agents (sevoflurane and desflurane) on grafted kidney function in renal transplantation surgery. METHODS: Sixty-five patients who were scheduled for living donor renal transplantation were enrolled in the study. General anesthesia was performed on all patients. Thirty-five pairs of recipients and donors were anesthetized with sevoflurane (group S) and 30 pairs of recipients and donors were anesthetized with desflurane (group D). Each patient's demographic characteristics, immunologic and clinical data, and hemodynamic parameters were recorded. The estimated glomerular filtration rate was calculated in the preoperative period and on postoperative days 1 and 7. The blood samples were collected before the operation and on postoperative days 1 and 7 for measurement of serum creatinine, neutrophil gelatinase-associated lipocalin, and interleukin 18. RESULTS: There were no significant differences in demographic characteristics or immunologic data between group D and group S. Intraoperative heart rate and mean arterial blood pressure were the same between groups. Creatinine, estimated glomerular filtration rate, neutrophil gelatinase-associated lipocalin, and interleukin 18 values did not differ between groups (P > .05) in the preoperative period and postoperative days 1 and 7. CONCLUSIONS: Sevoflurane and desflurane had no adverse effects on grafted kidney functions according to short-term graft outcomes in patients undergoing living donor renal transplantation.

Influence of Proton Pump Inhibitors on Mycophenolic Acid Pharmacokinetics in Patients With Renal Transplantation and the Relationship With Cytochrome 2C19 Gene Polymorphism.

BACKGROUND: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation. MATERIALS AND METHODS: A total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively. RESULTS: The mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P < .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P < .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P < .05). However, no differences were found according to genotype distribution in all groups (P > .05). CONCLUSION: Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects.

Preprandial repaglinide decreases exogenous insulin requirements and HbA1c levels in type 2 diabetic patients taking intensive insulin treatment.

In this study, we investigated the effects of combining preprandial repaglinide to the insulin therapy for reducing the exogenous insulin requirements and serum HbA(1c) levels in type 2 diabetic patients whose blood glucose levels were previously regulated by multiple dose intensive insulin therapy. Fifty patients with type 2 diabetes who had been initially treated with oral antidiabetic agents without a satisfactory response were included in this study. After adequate glycemic control was achieved with intensive insulin therapy, the patients were divided into two subgroups. The first group continued with intensive insulin therapy. The second group received a combination of multiple insulin injections and oral repaglinide (1.5 mgr tid). The doses of insulin injections were gradually decreased accordingly in the second group. Both groups were followed-up for 3 months. Repaglinide was well tolerated and had no toxicity. A significant reduction regarding exogenous insulin requirements and serum HbA(1c) levels were demonstrated in patients taking preprandial repaglinide (p<0.01). Combining repaglinide to intensive insulin therapy could be a safe and effective alternative to intensive insulin therapy alone for the glycemic control and for reducing exogenous insulin requirements in type 2 diabetic patients.