Is There a Long-Term Risk for Donors With Heterozygous MEFV Mutation After Kidney Donation?

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal-recessive autoinflammatory disorder manifested severely by systemic amyloidosis. It has been hypothesized that heterozygous carriers may also have susceptibility to certain symptoms or even diseases. Because the living kidney donors of patients with FMF are generally relatives of the kidney recipients, there is a high possibility that the donors will have a heterozygous mutation of the FMF gene. The goal of this study was to investigate the long-term kidney function of donors who are carriers of the Mediterranean fever (MEFV) gene. METHODS: The medium- to long-term outcomes of 12 asymptomatic donors were compared with MEFV gene carriers and 24 non-FMF recipients' donors. RESULTS: Heterozygous carriers and the control group were similar with respect to age, sex, and follow-up period. The preoperative estimated glomerular filtration rate and 24-hour urine proteinuria levels were similar in the MEFV carrier and control groups. Four years after the donation, both groups had similar estimated glomerular filtration rates, but the change in 24-hour urine protein was statistically higher in the MEFV carrier group, and no significant change was observed in the control group (P = .004). At the end of the follow-up period, neither overt proteinuria nor kidney failure was seen in either group. CONCLUSIONS: This study showed that the medium- to long-term results of the kidney donors who are carriers of the MEFV gene seem to be safe. However, there was more of a tendency for an increase in proteinuria in the MEFV gene carriers compared with control subjects, which necessitated further long-term care for these donors.

Average Tacrolimus Trough Level in the First Month After Transplantation May Predict Acute Rejection.

BACKGROUND: Although tacrolimus is one of the essential drugs used for the prevention of rejection in kidney recipients, target trough levels are not well established. In this study, we aimed to investigate the association between average tacrolimus trough levels (TTLs) of the first month after transplantation and biopsy-proven acute rejection (BPAR) during the first 12 months after transplant. METHODS: A total of 274 patients who underwent kidney-alone transplantation between 2002 and 2014 were enrolled in the study. Average TTLs of the first month were assessed by means of receiver operating characteristic (ROC) curve analysis to discriminate patients with and those without BPAR. Univariate and multivariate Cox proportional hazards models were used to determine the effect of average TTLs of the first month on BPAR. RESULTS: According to ROC curve analysis, the highest area under the curve (AUC) was obtained from 8 ng/mL (AUC = 0.73 ± 0.11; 95% confidence interval [CI], 0.62-0.84). Forty-two (31.8%) of the 132 patients with average TTLs <8 ng/mL and 13 (9.1%) of 142 patients with ≥8 ng/mL had BPAR during the first 12 months after transplant (P < .001). In univariable analysis, average TTLs of the first month <8 ng/mL were associated with higher risk of BPAR (P < .001), and the significance remained in Cox multivariable analysis (hazard ratio, 2.79; 95% CI, 1.76-3.82; P = .001). No significant differences were observed in the glomerular filtration rate, cytomegalovirus, BK viremia, or BK nephropathy between groups at post-transplant month 12. CONCLUSIONS: Keeping the average TTLs of the first month after transplantation at ≥8 ng/mL not only prevents BPAR occurrence but also minimizes the toxic effects of the use of a single-trough level.

Evaluation of cytotoxic and genotoxic effects of Benodanil by using Allium and Micronucleus assays.

The aim of this study was to evaluate the potential cytotoxic effects of Benodanil fungicide by employing both mitotic index (MI) and mitotic phases on the root meristem cells of Allium cepa and genotoxic effects by using in vitro micronucleus assay (MN) in human peripheral blood lymphocyte. In the Allium root growth inhibition test, the EC50 value was first determined as 25 ppm. Then, 2 × EC50 value (50 ppm), EC50 value (25 ppm), and 1/2 × EC50 value (12.5 ppm) were tested with different treatment periods (24, 48, and 72 h). Both negative and positive controls were also used in parallel experiments. We obtained that mitotic index and prophase index decreased when compared with the control in all concentrations. In the micronucleus assay, lymphocytes were treated with various concentrations (250, 500, 750, and 1000 µg/ml) of Benodanil for 24 and 48 h. The results showed that Benodanil did not induce MN frequency in all concentrations of both treatment periods. Additionally, it was determined that this pesticide decreased nuclear division index (NDI) significantly. It was concluded that Benodanil has a cytotoxic effects depending on decreasing of MI and NDI.

Urgency Priority in Kidney Transplantation: Experience in Turkey.

BACKGROUND: In Turkey, according to the directions of National Organ and Tissue Transplant Coordination System, a system has been established since 2008 of urgency priority for kidney transplantation in cases with imminent lack of access for either hemodialysis or peritoneal dialysis. In this study, we compared patient and graft outcomes between patients on the national waiting list having urgency priority for kidney transplantation (UKT) and those having the other kidney from the same deceased donor (control group). METHODS: We examined retrospective data of patients, who underwent transplantation under urgency priority allocation in Turkey from 2010 to 2014 and compared that group with other patients receiving kidney transplants from the same deceased donors (control group). Then we compared these patients for early and long-term patient and graft outcomes. RESULTS: Forty-seven patients had UKT, and 40 patients received transplants from the same deceased donors. Mean follow-up of patients after transplantation was 18 ± 12 months. Eight patients with UKT and 4 patients in the control group lost their grafts. At follow-up, 7 patients died in the UKT group, and 4 patients died in the control group. Patient survival in the UKT group was 90% at 1 year and 83% at 2 years, and in the control group was 93% at 1 year and 84% at 2 years (P = .384). Graft survival was 87% at 1 year and 81% at 2 years in UKT, and 91% at both 1 and 2 years in the control group (P = .260). CONCLUSIONS: Although patients with UKT showed lower graft and patient survivals than the control group, the difference was statistically nonsignificant. UKT can be an obligatory treatment model for patients with lack of vascular or peritoneal access for dialysis.

Pregnancy After Kidney Transplantation: Outcomes, Tacrolimus Doses, and Trough Levels.

Although pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications, it can be successful in properly selected patients. It is well known that pregnancy can induce changes in the plasma concentrations of some drugs; however, there has been very limited information about tacrolimus pharmacokinetics during pregnancy. In this study, we evaluated the tacrolimus doses, blood levels, and the outcomes of pregnancies in kidney allograft recipients. From 2004 to 2014, we found 16 pregnancies in 12 kidney allograft recipients at our center. We reviewed the files and data reports including fetal outcomes, graft function, complications, tacrolimus trough levels, and doses. We analyzed the tacrolimus trough levels and doses before pregnancy, during pregnancy (monthly), and in the postpartum period. Throughout the pregnancy, we aimed to achieve tacrolimus trough levels between 4 and 7 ng/mL. All patients were on triple immunosuppression, including tacrolimus, azathioprine, and prednisolone. In total, 11 of 16 (68.7%) pregnancies were successful, with a mean weight gain of 12.5 ± 1.66 kg. One patient developed gestational diabetes mellitus and 2 had preeclampsia. Although 5 of 11 babies were found to have low birth weight, 4 of these were premature. Two patients lost their grafts, 1 due to acute rejection and the second due to progression of chronic allograft dysfunction. We have shown that tacrolimus doses need to be significantly increased to keep appropriate trough levels during pregnancy (the doses: before, 3.20 ± 0.9 mg/day; first trimester, 5.03 ± 1.5; second trimester, 6.50 ± 1.8; third trimester, 7.30 ± 2.3; post-partum, 3.5 ± 0.9). In conclusion, the dose of tacrolimus needs to be increased to provide safe and stable tacrolimus trough levels during pregnancy. Although pregnancy can be successful in most cases, it should be kept in mind that there is an increased risk of maternal and fetal complications, including allograft loss, low birth weight, spontaneous abortus, and preeclampsia.

Assessment of cytotoxic and genotoxic potential of pyracarbolid by Allium test and micronucleus assay.

The present study evaluates the cytotoxic and genotoxic potential of pyracarbolid using both micronuleus (MN) assay, in human lymphocytes, and Allium cepa assay, in the root meristem cells. In Allium test, EC50 value was determined in order to selecting the test concentrations for the assay and the root tips were treated with 25 ppm (EC50/2), 50 ppm (EC50) and 100 ppm (EC50 × 2) concentrations of pyracarbolid. One percent of dimethyl sulphoxide (DMSO) and methyl methane sulfonate (MMS) were used as negative and positive controls, respectively. In the micronucleus assay, the cultures were treated with four concentrations (250, 500, 750 and 1000 µg/ml) of pyracarbolid for 24 and 48 h, negative and positive controls were also used in the experiment parallely. The results showed that mitotic index (MI) significantly reduced with increasing the pyracarbolid concentration at each exposure time. It was also obtained that prophase and metaphase index decreased significantly in all concentration at each exposure time. Anaphase index decreased as well and results were found to be statistically significant, except 24 h. A significant increase was observed in MN frequency in all concentrations and both treatment periods when compared with the controls. Pyracarbolid also caused a significant reduction in the cytokinesis block proliferation index (CBPI) in all concentration and both exposure time.

Potential cytotoxic effect of Anilofos by using Allium cepa assay.

Cytogenetic effects of Anilofos which was widely used in agriculture, was evaluated in Allium cepa root meristematic cells. In the Allium root growth inhibition test EC50 value was determined 50 ppm and 1/2× EC50 (25 ppm), EC50 (50 ppm) and 2 × EC50 (100 ppm) concentrations of Anilofos were applied to onion roots. A negative and positive control were used in the experiment in parallel. According to results mitotic index decreased with increasing the Anilofos concentrations in all application groups and each exposure time, while disturbed anaphase-telophase, choromosome laggard(s), stickiness and anaphase bridge(s) were observed. In anaphase-telophase cells, c-metaphase, disturbed nucleus and binuclear cells were observed in other anomalies. The results were also analyzed statistically by using Dunnett t test (2-tailed) and all concentrations of Anilofos were found significant.

Micronucleus assay in human lymphocytes after exposure to alloxydim sodium herbicide in vitro.

This study evaluates the cytotoxic and genotoxic potential of alloxydim sodium using micronucleus (MN) assay, in human peripheral lymphocytes. MN assay was used to investigate the genotoxic effects of alloxydim sodium in human peripheral lymphocytes treated with 250, 500, 750, 1,000 µg/ml concentrations of alloxydim sodium for 24 and 48 h. Solvent, negative and positive controls were also used in the experiments in parallel. The obtained results were evaluated in statistical analyses by using Dunnett-t test (two sided) and p < 0.05 was accepted as significant. Alloxydim sodium significantly increased the MN formation compared with the negative control, at both 750 and 1,000 µg/ml concentrations and treatment periods. We also evaluated the nuclear division index (NDI) for cytotoxicity of this pesticide in the experiment, and finally observed a significant decrease of the NDI values at all concentrations of alloxydim sodium and at both treatment periods.

Urinary angiotensinogen level is correlated with proteinuria in renal transplant recipients.

OBJECTIVE: Along with immunologic mechanisms, intrarenal renin-angiotensin system (RAS) activation has been suggested to play a role in the development and progression of chronic allograft injury. In various glomerular diseases, urinary angiotensinogen (AGT) level is a good indicator for the activation of intrarenal RAS. In this study, we aimed to investigate the parameters associated with urinary AGT level in patients with kidney transplantation. METHODS: Seventy renal transplant patients with stable graft function (≥ 6 months after transplantation, serum creatinine level <2 mg/dL) and 21 healthy volunteers were included in the study. Patients were taking standard triple immunosuppressive treatment. Demographic characteristics of patients and healthy volunteers, drug use, and 24-hour ambulatory blood pressure measurements were recorded. Morning second urine and fasting blood samples were taken from all participants. Serum biochemical markers and urine Na, K, uric acid, creatinine, and protein levels were measured. Urinary AGT levels were determined by enzyme-linked immunosorbent assay. RESULTS: Mean systolic and diastolic blood pressures in patients with renal transplantation were higher than in healthy volunteers. Both urinary AGT-urinary creatinine ratio (UAGT/UCr) and urinary protein-urinary creatinine ratio (UPro/UCr) were higher in kidney transplant patients than in healthy volunteers (P < .01; P < .0001; respectively). In patients with renal transplantation, UAGT/UCr was positively correlated with UPro/UCr and negatively correlated with estimated glomerular filtration rate (eGFR) (r = 0.738; P = .01; and r = -0.397; P = .01; respectively). There was no correlation between UAGT/UCr and other study parameters, including bood pressure levels. CONCLUSIONS: Our findings indicate that high urinary excretion of AGT is associated with proteinuria and lower eGFR in kidney transplant recipients without overt chronic allograft injury. These preliminary results encourage us to design a long-term longitudinal analysis using urinary AGT along with multiple markers to obtain early diagnosis and to predict the prognosis of chronic allograft dysfunction.

Evaluation of antibacterial, antioxidant and DNA protective capacity of Chenopodium album's ethanolic leaf extract.

We have investigated the antibacterial effects of Chenopodium album's ethanolic leaf extract (CAE) on all the Gram (+) and Gram (-) microorganisms and evaluated the protective effects of CAE on both yeast and human mononuclear leukocytes' genomic DNA upon oxidative shock. Antibacterial activity was recorded on Bacillus subtilis with 13 mm of inhibition zone. Total oxidative status (TOS) and the total antioxidative status (TAS) levels were determined to evaluate the antioxidant activity of CAE. Results indicated that there was a good correlation between dose of CAE and TAS levels. We also observed that CAE protect the DNA of both yeast and mononuclear leukocytes against the damaging effect of hydrogen peroxide. The comet assay, applied on both Saccharomyces cerevisiae BY4741 (MATa his3Δ1 leu2Δ0 met15Δ0 ura3Δ0) and human leukocytes, results suggested that there was statistically significant correlation between CAE dilutions and antigenotoxic activity.

Accurate course and relationships of the intraorbital part of the ophthalmic artery in the sagittal plane.

INTRODUCTION: Knowledge of variations in the course and distribution of the intraorbital part of ophthalmic artery (OA) is necessary for the diagnosis and treatment of anterior cranial and orbital disorders. MATERIAL: 38 human cadaver dissections to demonstrate the microsurgical anatomy of the intraorbital part of the OA were studied in three stages, considering its neighbourhood with the optic nerve in the sagittal plane. RESULTS: The first part of the OA was located on the inferolateral aspect of the optic nerve in 89.47%. The diameter and the length of the first part of the OA were 1.69+/-0.34 mm and 7.58+/-0.89 mm. 73.68% of the cases crossed the optic nerve superiorly, and 26.31% inferiorly. The diameter and length of the second part of the OA were as 1.52+/-0.29 mm and 4.12+/-0.85 mm. The diameter and length of the third part of the OA were 1.07+/-0.18 mm and 4.12+/-0.85 mm. The first branch of the intraorbital part of the OA was the central retinal artery in 26.31% of the specimens. CONCLUSION: A better understanding of the vascular anatomy of the orbit should allow for the modification of surgical techniques to reduce bleeding during biopsy or excision of orbital structures.

Distal variations of the neurovascular pedicle of the serratus anterior muscle as a flap.

The serratus anterior muscle has recently been suggested as a versatile and reliable flap for reconstruction of complex craniofacial and neck lesions, extremity and sacroiliac region injuries, as well as intrathoracic and extrathoracic reconstruction procedures. The muscle has been used as a microvascular flap or a pedicled transfer and has been transferred in combination with other muscles, bones, and skin. We performed 15 dissections of adult axilla regions that were examined under x3.5 loupe magnification to collect anatomic data regarding the neurovascular pedicle of the serratus anterior muscle. The serratus muscle and fascia were found to have a dual blood supply, with the upper part supplied by the lateral thoracic artery and the lower part by terminal branches of the thoracodorsal artery. The lateral thoracic artery was noted to supply the upper four slips but it extended into the lower serratus anterior muscle in two cases. Seven branching patterns were found in the lower serratus anterior muscle. In type I, the only branch of serrati proceeded over the long thoracic nerve. Type II had the only branch of serrati proceeding under the long thoracic nerve. In type III, double branches of serrati proceeded over the long thoracic nerve; while in type IV branches of serrati ran with a double branch under the long thoracic nerve. In type V, three serrati branches proceeded over the long thoracic nerve. Type VI serrati branches were branches of thoracodorsalis, which was hypoplastic, and the supply was maintained from the lateral thoracic artery. In type VII, one serrati branch ran over the long thoracic nerve. There was no connection between the branches of serrati and the branches of the lateral thoracic artery. The length of the long thoracic nerve, the number of motor axons and the vascular network in anatomic proximity to this nerve make it an expendable but powerful source of reconstructions of head, neck, chest wall and extremity defects. Results of this study provide an anatomic framework to improve current reconstructive or aesthetic procedures on the serratus anterior neurovascular structures.