Cytokine gene polymorphism in denture stomatitis patients: A clinical study.

OBJECTIVE: This clinical study investigated the association between cytokine gene polymorphism and Candida growth in denture stomatitis (DS) patients. SUBJECTS AND METHODS: Saliva and blood samples of 160 complete denture wearers (80 healthy controls and 80 with DS) were collected for mycological and gene polymorphism testing, respectively. Salivary Candida growth and TNF-α, TGF-ß, IL-6, and IL-10 genotypes were investigated. Data were analyzed using Student's t test, Mann-Whitney U test, chi-square analysis, and continuity (yates) correction tests (p < .05). RESULTS: Candida albicans colony counts in saliva were significantly higher in the DS group and in the TNF-α GG genotype (p < .05). TGF-ß TC GG and TGF-ß CC GG haplotypes were significantly higher in DS and control groups, respectively (p < .05). C. albicans colony counts were significantly higher in control group in the TGF-ß TC GG haplotype (p < .05). Candida glabrata colony counts were significantly higher in the DS group than the control group in IL-6 GG genotype (p < .05). The difference between DS types in IL-6 genotypes was significant with lower expression level in DS type 3 than DS type 1 and also type 2 (p ≤ .01). CONCLUSION: The significant differences in some genotypes of the TNF-α, TGF-ß, and IL-6 in DS patients are promising in understanding the host defense in DS.

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.

Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in the Turkish population.

Summary: Background and objective. Many studies have shown associations between HLAB*15:02, HLA-A*31:01 and carbamazepine (CBZ)-induced delayed cutaneous hypersensitivity reactions. The aim of this study is to evaluate a possible association between delayed cutaneous reactions to antiepileptic drugs (AEDs) and certain HLA-A and HLA-B alleles in the Turkish population. Methods. The study consisted of 3 groups: Group I (reactive group) included the patients who had documented delayed cutaneous reactions to any antiepileptic drug. Group II (non-reactive group) included the patients who have been on antiepileptic treatment at least for three months without any adverse reactions. Group III consisted of healthy subjects. The HLA-A and B alleles were analyzed in all groups. Results. Forty patients (29 female) had experienced different hypersensitivity reactions due to AEDs: maculopapular exanthema (26 patients), Stevens-Johnson syndrome (6 patients), drug rash with eosinophilia and systemic symptoms (7 patients), toxic epidermal necrolysis (1 patient). Lamotrigine (11) and CBZ (10) were the most common culprit drugs involved in the reactions. The HLA-B*15:02 was not present in any of the study groups. However, HLA-B*35:02 was found in 4 patients from the reactive group, while it was not observed in non-reactive patients and was detected in only one healthy subject (p = 0.021). Conclusion. Although our preliminary results did not indicate a strong allele association with AED hypersensitivity, HLA-B*35:02 appears to be a candidate allele for MPE / DRESS / DIHSS induced by AED's in Turkish population. Further studies with a larger sample size may result in more comprehensive data about the genetic tendency for AED hypersensitivity in the Turkish population.

Relationship between salivary calprotectin levels and recurrent aphthous stomatitis: A preliminary study.

AIM: Recurrent aphthous stomatitis (RAS) is an inflammatory condition of the oral mucosa. The etiology of RAS remains unclear. Calprotectin is a major cytoplasmic protein contained in granulocytes, monocytes/macrophages and epithelial cells, and its level is increased body fluids in some inflammatory diseases. The aim is to determine the relationship between salivary calprotectin and RAS. MATERIAL AND METHODS: In the cross-sectional study, 67 patients with active lesions of RAS (F/M: 43/24, mean age: 30.27 ± 9.14 years) and 42 healthy controls (HC, F/M: 30/12, 30.54 ± 9.49 years) were included. Calprotectin levels were evaluated in unstimulated whole saliva samples by using the ELISA method in both groups. RESULTS: Salivary calprotectin levels were significantly higher in RAS group (23.72 ± 4.28 mg/L) compared to the HC group (21.59 ± 4.27 mg/L) (P = 0.013). No significant relationship was found between calprotectin levels and age or gender in both groups (P >0.05). CONCLUSION: RAS is a very common inflammatory ulcerative condition of the oral cavity and its etiology is uncertain. Regarded as an inflammatory mechanism, releasing a high level of calprotectin in saliva has been suggested that it may play a role in pathogenesis of RAS.

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.

Quercetin prevents docetaxel-induced testicular damage in rats.

The protective effect of quercetin on docetaxel - an anticancer agent - induced testicular damage in rats was investigated. Thirty-two rats were randomly divided into four groups: group 1 - control, carrier solutions were given; group 2 - quarcetin 20 mg kg(-1)  day(-1) was given orally; group 3 - docetaxel 5 mg kg(-1) was given intraperitoneally as single dose; group 4 - docetaxel and quarcetin were given together. The histopathological changes; the specific biochemical markers, including antioxidants; and the sperm characteristics were evaluated. Docetaxel caused a significant increase in TBARS level and a significant decrease in SOD, GPX, CAT and GSH levels in the testicular tissues compared with the control group, whereas quercetin led to a significant decrease in lipid peroxidation, which was caused by docetaxel, via reducing TBARS level and increasing the levels of SOD, CAT, GPX and GSH. In addition, after docetaxel administration, sperm motility, sperm concentration, testicular and epididymis weights were significantly decreased and abnormal sperm rate and histopathological changes were increased. However, these effects of docetaxel on sperm parameters, histological changes and the tissue weights were eliminated by quercetin treatment. Our results show that the administration of docetaxel induced the testicular damage (oxidative stress, testes tissue damage and sperm parameters), and quercetin prevented docetaxel-induced testicular damage in rats.

Fish oil, contained in eicosapentaenoic acid and docosahexaenoic acid, attenuates testicular and spermatological damage induced by cisplatin in rats.

The aim of this study was to investigate the beneficial effects of the fish oil (FO) supplementation on oxidative stress, sperm characteristics and histological alterations in the male reproductive system of rats against cisplatin (CP) toxicity. The rats were divided randomly into 4 equal groups (control, FO, CP and FO + CP). FO was orally administered at the dose of 1 softgel per rat per day for 14 days and CP was intraperitoneally given at the dose of 7 mg kg(-1) with a single injection. In CP + FO group, they were applicated at the same doses and times. The results showed that CP caused a significant oxidative damage via induction of lipid peroxidation and reduction in the antioxidant defence system potency in the testis tissue. In addition, sperm motility and sperm concentration significantly decreased but the abnormal sperm rate and histopathological testicular damage increased with CP treatment. On the other hand, FO treatment prevented oxidative, histopathological and spermatological effects of CP and reversed side effects of CP. In conclusion, FO supplementation had significant beneficial effects against CP toxicity on male reproductive system and toxic effects of CP can be prevented by FO treatment. Therefore, it appears that fish oil may be useful for the prevention and treatment of cisplatin-induced reproductive system toxicity.

Minor H antigen matches and mismatches are equally distributed among recipients with or without complications after HLA identical sibling renal transplantation.

Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. The International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. The incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n = 36), of which only eight resulted in graft loss. In summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.

16(th) IHIW: immunogenetics of aging.

Ageing is a process characterised by progressive loss of function in multiple different organ systems, such as the nervous, endocrine and immune systems. Current data showing that ageing processes may be associated with alterations in the immune system suggest that some of the genetic determinants of senescence might be polymorphic genes that regulate immune responses. The 'Immunogenetics of Aging' programme was a component introduced in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th and 16th. The aim of this component was to determine the contribution of immune genes to successful ageing and an increased capacity to reach the extreme limits of lifespan. Within the 16th IHIWS, new populations were included, and the number of samples analysed was increased. Analysis was focused on innate immunity genes (KIR and MBL2) and their correlation with CMV serostatus. Collaborative studies suggested that both activating and inhibitory KIR and functionally relevant MBL2 haplotypes are important factors for control of CMV infection in the elderly and therefore for chronic low-grade inflammation. Results showed that these genes might be predictive biomarkers in ageing and longevity. Prevalence of MBL2 haplotypes determining absence of the protein (LYPB, LYQC and HYPD) was observed in elderly people with a higher CMV antibody titre. The high CMV titre was also associated with a decreased frequency of the activatory KIR2DS5 and A1B10 haplotypes in elderly. Due to the role of KIR and low or deficient MBL haplotypes in viral infections, these genetic markers could be considered as indicators of a need for CMV prophylaxis at younger age and therefore increased probability of longer lifespan.

Aminoguanidine prevents testicular damage-induced-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in male rats.

In this study, it was aimed to determinate protective effects of aminoguanidine (AG) against reproductive toxicity caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant. Thirty-two rats were equally divided into four groups; the first group was kept as control and given corn oil as carrier. In second and third groups, TCDD and AG were orally administered at the dose of 2 µg kg(-1) per week and 100 mg kg(-1) per day for 45 days, respectively. In fourth group, TCDD and AG were given together at the same doses. Although TCDD significantly increased the formation of TBARS, it caused a significant decline in the levels of GSH, CAT, GPx and SOD in rats. On the other hand, AG, given together TCDD, reversed TCDD effects on TBARS SOD, GSH, GPx and CAT. In addition, sperm characteristics negatively affected and histopathological deformation occurred with TCDD exposure. However, AG treatment partly prevented these toxic effects of TCDD on spermatological parameters and histopathological changes. In conclusion, TCDD exposure induces testicular damage (oxidative stress, histopathological damage and sperm parameters), and AG treatment reversed TCDD-induced testicular damage in rats. Thus, AG may be useful for the prevention and treatment of TCDD-induced male infertility problems.

NIMA-related kinase 9 regulates the phosphorylation of the essential myosin light chain in the heart.

To adapt to changing hemodynamic demands, regulatory mechanisms modulate actin-myosin-kinetics by calcium-dependent and -independent mechanisms. We investigate the posttranslational modification of human essential myosin light chain (ELC) and identify NIMA-related kinase 9 (NEK9) to interact with ELC. NEK9 is highly expressed in the heart and the interaction with ELC is calcium-dependent. Silencing of NEK9 results in blunting of calcium-dependent ELC-phosphorylation. CRISPR/Cas9-mediated disruption of NEK9 leads to cardiomyopathy in zebrafish. Binding to ELC is mediated via the protein kinase domain of NEK9. A causal relationship between NEK9 activity and ELC-phosphorylation is demonstrated by genetic sensitizing in-vivo. Finally, we observe significantly upregulated ELC-phosphorylation in dilated cardiomyopathy patients and provide a unique map of human ELC-phosphorylation-sites. In summary, NEK9-mediated ELC-phosphorylation is a calcium-dependent regulatory system mediating cardiac contraction and inotropy.

Lycopene prevents experimental priapism against oxidative and nitrosative damage.

The article "Lycopene prevents experimental priapism against oxidative and nitrosative damage, by O. Ciftci, F. Oguz, A. Beytur, F. Polat, R. Altintas, H. Oguzturk, published in Eur Rev Med Pharmacol Sci 2014; 18 (21): 3320-3325-PMID: 25487946" has been withdrawn due to problems concerning authorship. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/8034.

Effectiveness of erdosteine, a second generation mucolytic agent, in children with acute rhinosinusitis: a randomized, placebo controlled, double-blinded clinical study.

AIM: To evaluate whether mucolytic agents have an adjuvant role with antibiotics in the treatment of children with rhinosinusitis. METHODS: Ninety-two children with rhinosinusitis were recruited for this randomized, placebo controlled, double-blinded clinical trial. Mean age was 8.5 +/- 3.2 years. Erdosteine (5-8 mg/kg/day) was administered to 49 children, and 43 children received placebo. Changes in symptoms were recorded with the standard S5 scoring for 14 days. Complete resolution of symptoms on day 14 was considered to be clinical improvement. RESULTS: Eighty-one participants completed the study. Forty-one were in the treatment group and 40 in the placebo group. The average S5 scoring value at the onset of study was 11.0 in treatment group and 12.1 in placebo group. On day 14, mean scores were 3.1 in the treatment group and 2.8 in the placebo group. Complete improvement was 78% in the treatment group and 74.4% in the placebo group. There was no significant difference between the groups. There were no clinically detected serious side effects or complications in both groups. CONCLUSION: Use of erdosteine as a mucolytic agent in children with acute rhinosinusitis does not directly affect the success of treatment.

The frequency of HLA class I and II alleles in Turkish childhood acute leukaemia patients.

In this study, blood samples were taken from 200 patients with childhood acute leukaemias, including acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), and from 100 healthy volunteers (controls). The frequency of the human leucocyte antigen (HLA)-DRB1*04 allele was significantly higher, and the frequencies of the HLA-A23 and HLA-B7 antigens were significantly lower, in patients with ALL compared with controls. Among patients with AML, the frequency of the HLA-B49 antigen and the HLA-DRB1*15 allele were significantly higher, whereas the frequencies of the HLA-A11 and HLA-B38 antigens were significantly lower compared with controls. The frequency of the HLA-DRB1*04 allele was also significantly higher in male patients with ALL and AML, whereas the HLA-DRB1*13 allele was found significantly less frequently in male AML and female ALL patients than in controls. To date, this is the only study to evaluate the associations between HLA molecules and leukaemia in a Turkish population with acute childhood leukaemia.

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.

Panel Reactive Antibody Responses Against Influenza Vaccination in Kidney Transplant Recipients.

INTRODUCTION: Seasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients. MATERIALS AND METHODS: Overall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies. RESULTS: One patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups. CONCLUSION: The influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.

Urinary CXCL9 and CXCL10 Levels and Acute Renal Graft Rejection.

BACKGROUND: Monitoring of chemokines, CXCL9 and CXCL10, in serum may present a non-invasive detection method for rejection. OBJECTIVE: To investigate the relationship between urinary levels of CXCL9 and CXCL10 and graft function following renal transplantation. METHODS: 75 living-related donor renal transplant recipients were studied. Urinary levels of chemokines were collected pre-operatively, on post-operative 1st day, 7th day, 1st month, 3rd month, and at the time of rejection. Chemokines levels were assayed using and enzyme-linked immunosorbent assay. RESULTS: Clinical variables were monitored. 10 (15%) patients had biopsy-proven rejection during the follow-up period. The urinary CXCL9 level in those with rejection was significantly higher than that in those with non-rejection group at the 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.002). The urinary CXCL10 level was also significantly higher in those with rejection compared with non-rejection group at 1st day (p<0.001), 7th day (p<0.001), and at the time of rejection (p=0.001). Serum creatinine level was strongly correlated with the urinary CXCL9 and CXCL10 levels at the time of rejection (r=0.615, p=0.002; and r=0.519, p=0.022, respectively). Among those with T cell-mediated rejections the mean urinary CXCL10 level increased to as high as 258.12 ng/mL. CONCLUSION: Urinary CXCL9 and CXCL10 levels might have a predictive value for T cell-mediated rejection in early post-transplantation period. Measurement of urinary CXCL9 and CXCL10 levels could provide an additional tool for the diagnosis of rejection.

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.

Evaluation of TH17 and TH1 Immune Response Profile in Patients After Renal Transplant.

BACKGROUND: Renal transplantation (RT) is the best treatment option for patients with end-stage renal disease (ESRD) because it improves both quality of life and survival. However, allograft rejection remains the most important barrier to successful transplantation. Underlying immunologic mechanisms should be understood to develop appropriate treatment strategies. METHODS: In this prospective study, we followed renal transplant recipients for 6 months. The study population comprised 50 recipients of renal transplants, and these were divided into 2 groups: 44 patients with stable graft function (SGF) and 6 patients with rejection (RX). Peripheral blood samples were drawn from patients on the pre-RT day, at post-RT day 7, month 1, and month 6, and on the day of rejection for analysis of the percentages of cytokines interleukin (IL) 17 and interferon (IFN) γ with the use of flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The percentages of intracellular IFN-γ were not significant in the group with RX compared with SGF. Levels of intracellular IL-17 obtained at the 6th month after RT were significantly higher in the RX group than in the SGF group. Plasma levels of pre-RT IL-17 were also higher in the RX group; therefore, it may be a predictive biomarker of acute rejection of renal transplants. CONCLUSIONS: The present study provides information about pre-RT and post-RT cytokine profiles of Turkish patients with ESRD. We consider cytokine analysis to be a valuable biomarker panel in the prevention of rejection and in assisting with new treatment strategies for patients undergoing renal transplant.

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.