Cigdem Kaspar

Effect of double growth factor release on cartilage tissue engineering

The effects of double release of insulin‐like growth factor I (IGF‐I) and growth factor β1 (TGF–β1) from nanoparticles on the growth of bone marrow mesenchymal stem cells and their differentiation into cartilage cells were studied on PLGA scaffolds. The release was achieved by using nanoparticles of poly(lactic acid‐co‐glycolic acid) (PLGA) and poly(N‐isopropylacrylamide) (PNIPAM) carrying IGF‐I and TGF–β1, respectively. On tissue culture polystyrene (TCPS), TGF‐β1 released from PNIPAM nanoparticles was found to have a significant effect on proliferation, while IGF‐I encouraged differentiation, as shown by collagen type II deposition. The study was then conducted on macroporous (pore size 200–400 µm) PLGA scaffolds. It was observed that the combination of IGF‐I and TGF‐β1 yielded better results in terms of collagen type II and aggrecan expression than GF‐free and single GF‐containing applications. It thus appears that gradual release of a combination of growth factors from nanoparticles could make a significant contribution to the quality of the engineered cartilage tissue. Copyright

Impact of Genetic Factors (CYP2C9, VKORC1 and CYP4F2) on Warfarin Dose Requirement in the Turkish Population

Warfarin has a narrow therapeutic index and displays marked person‐to‐person variation in dose requirement. Functional polymorphisms at candidate genes can therefore offer utility as biomarkers to individualize warfarin treatment. The main objective of this study was to determine whether and to what extent variability in warfarin dose requirements was determined by polymorphisms in CYP2C9, VKORC1, CYP4F2 (rs2108622) and EPHX1 (rs2292566) in the Turkish population. Patients (n = 107) who had stable doses and international normalized ratio (INRs) at their last three consecutive visits were registered. Their demographic factors, concurrent medications, warfarin‐related bleedings or thromboembolisms, smoking, alcohol intake and weekly green vegetable consumption were recorded. From a blood sample, DNA was isolated and genotyped by real‐time PCR for polymorphisms of CYP2C9, VKORC1, CYP4F2 and EPHX1. A regression analysis was used to determine the independent effects of genetic and non‐genetic factors on warfarin dose optimization. In our study, in addition to age, genetic variants of CYP2C9, VKORC1 and CYP4F2 were found to be significant predictor variables for the maintenance dose for warfarin, explaining 39.3% of dose variability. VKORC1 and CYP2C9 genotypes remain predictor variables of the warfarin dose, and we first found that CYP4F2 (rs2108622) contributes to dose variability in the Turkish population as well. These observations may be of benefit to future translation research with a view to global personalized medicine in regions hitherto understudied such as the Turkish population so as to rationalize initial warfarin dose and reduce the burden of frequent INR measurements.

The importance of the length of uterine cavity, the position of the tip of the inner catheter and the distance between the fundal endometrial surface and the air bubbles as determinants of the pregnancy rate in IVF cycles.

OBJECTIVE To evaluate the relationship between the pregnancy rate (PR) and the positioning of the intrauterine catheter at embryo transfer (ET) under transabdominal ultrasound (US) guidance in in vitro fertilization (IVF) cycles. STUDY DESIGN Prospective data analysis of 281 consecutive US-guided fresh ETs performed by a single physician at Yeditepe University Hospital IVF Center, Istanbul, Turkey, after controlled ovarian hyperstimulation between April 2012 and March 2013. The length of the uterine cavity (A), the distance between the fundal endometrial surface and the tip of inner catheter (B), the distance between the fundal endometrial surface and the air bubbles (C), and the pregnancy rates (PRs) were recorded. RESULTS The mean age of the patients was 33.25±5.5 years. Of all transfers, 115 (40.9%) resulted in a clinical pregnancy. With regard to distance (C), the clinical intrauterine pregnancy rates were 65.2%, 32.2% and 2.6% in the <10mm, 10-20mm, and 20mm distance groups, respectively. The PR was dramatically reduced in cases with >10mm between the fundal endometrial surface and the air bubbles, although this did not reach statistical significance. Between those patients who conceived and those who did not, there was no significant difference in terms of the distance between the fundal endometrial surface and the tip of inner catheter, the ratio of A/B or the ratio of B/C. CONCLUSIONS The final position of the air bubble used as an identifier of the position of the embryo at ET can be determinative for PR, although it cannot be predicted. Clinical pregnancy rates appeared higher in cases with air bubbles closer to the fundus and the optimal position of the air bubble seems to be a distance of <10mm from the fundal endometrial surface. It could be advisable to monitor the final position of air bubble at ET for identifying PR. In addition, the depth of uterine cavity may be considered to indirectly be important factor as it affects ET depth. The optimal distance between the fundal endometrial surface and the tip of inner catheter is 1.5-2cm. Further well-designed randomized controlled trials are required to optimize ET technique in the future.

Which cut-off value of serum anti-Müllerian hormone level can predict poor ovarian reserve, poor ovarian response to stimulation and in vitro fertilization success? A prospective data analysis

Abstract The aim of our study is to demonstrate which cut-off value of serum anti-Müllerian hormone (AMH) level can predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes. About 311 of 520 women enrolled IVF treatment cycle that meets inclusion criteria were recruited for this prospective data analysis. Data were collected for: age, duration of infertility, basal FSH and AMH level, total dosage of gonadotropins, maximum estradiol levels, duration of stimulations, total number of oocytes retrieved and clinical PR. Mean AMH was 1.76 ± 1.4 ng/ml and mean age was 33.25 ± 5.5 years. Clinical PR was 39.8% (n = 124). AMH was inversely correlated to total dosage of gonadotropins and age, AMH positively had a significant correlation with maximum estradiol levels, duration of stimulations and total number of oocytes retrieved. The patients in both categories of AMH levels, ≤0.5 and ≤1 ng/ml responded poorly to ovarian stimulation, had significantly higher total dosage of gonadotropins used and FSH levels on cycle day 3, lower maximum E2 levels and clinical PR. AMH could be an acceptable screening test in prediction of ovarian reserve, response to ovarian stimulation and PRs. AMH cut-off value ≤1 ng/ml may predict poor ovarian reserve, poor ovarian response to stimulation and IVF outcomes.

Epicardial fat thickness is associated with impaired coronary flow reserve in hemodialysis patients

Cardiovascular disease (CVD) is the main cause of mortality in hemodialysis (HD) patients. Epicardial fat tissue (EFT) is a new risk factor in CVD. The aim of this study was to evaluate the association between EFT and coronary artery flow reserve (CFR), which is an early indicator of endothelial dysfunction in coronary vessels of HD patients. We performed a cross‐sectional study including 71 chronic HD patients and 65 age‐ and sex‐matched healthy controls. Epicardial fat tissue was significantly higher in HD patients when compared to healthy controls (6.53 ± 1.01 mm vs. 5.79 ± 1.06 mm, respectively, P < 0.001). On transthoracic Doppler echocardiography, CFR values were significantly lower in HD patients when compared to healthy controls (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001). Correlation analysis showed CFR values to be inversely correlated with EFT (r = −0.287, P < 0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. Artery flow reserve, age, body mass index and total cholesterol levels were independently correlated with EFT thickness. This study demonstrated that EFT was significantly higher among HD patients compared to healthy controls. In addition, this study was the first to demonstrate an inverse correlation between EFT and CFR in this patient population.

The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

Abstract Purpose: To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Methods: Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p = 0.002) and serum E2 levels on the day of hCG administration (p = 0.010) were significantly higher and duration of stimulations (p = 0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p = 0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Conclusion: Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.

Epicardial fat tissue thickness is correlated with diminished levels of co-enzyme Q10, a major antioxidant molecule among hemodialysis patients

OBJECTIVES Accelerated atherosclerosis is the major cause of mortality in patients on chronic maintenance hemodialysis (HD). Epicardial fat tissue (EFT) is a new risk factor in cardiovascular disease (CVD). The aim of this study was to evaluate the relation between plasma coenzyme Q10 levels (Co-Q10) which is a potent physiologic antioxidant and EFT thickness in HD patients. DESIGN AND METHODS Seventy one chronic HD patients and 65 age and sex matched healthy individuals were included in the study. Plasma Co-Q10 levels were performed by high-performance liquid chromatography (HPLC) measurements. EFT was measured by transthoracic echocardiograpy (TTE) performed with a VIVID 7 instrument. RESULTS Plasma Co-Q10 levels (1.36±0.43 vs 2.53±0.55, p<0.001) were significantly lower in HD patients compared to controls. EFT was significantly increased in HD patients compared to healthy controls (6.53±1.01 vs. 5.79±1.06 mm respectively, p<0.001). Correlation analysis showed that plasma Co-Q10 levels were inversely correlated with EFT (r=-0.263, p<0.05). Multiple linear regression analysis was used to define independent determinants of EFT in HD patients. According to linear regression analysis, age, BMI, total cholesterol and Co-Q10 levels were found to be independent predictors of EFT (adjusted r(2)=0.38, p<0.001). CONCLUSION This study demonstrated that EFT thickness was significantly higher among HD patients compared to healthy controls. In addition; this study was the first to demonstrate an inverse correlation between EFT thickness and Co-Q10 levels in this patient population.

Serum coenzyme Q10 levels are associated with coronary flow reserve in hemodialysis patients

Accelerated atherosclerosis is the major cause of mortality in patients on chronic hemodialysis (HD). The aim of this study was to evaluate the relation between coenzyme Q10 (CoQ10) levels and coronary flow reserve (CFR) in HD patients as an indicator of atherosclerosis. Seventy‐one chronic HD patients and 65 age‐ and sex‐matched healthy individuals were included in the study. Plasma CoQ10 levels were performed by high‐performance liquid chromatography measurements. CFR was assessed by transthoracic Doppler echocardiography. Serum CoQ10 levels (1.36 ± 0.43 vs. 2.53 ± 0.55, P < 0.001) and CFR values (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001) were significantly lower in HD patients compared with controls. There was a significant positive correlation between CFR and serum levels of CoQ10 (r = 0.669, P < 0.001). A linear regression analysis showed that serum levels of CoQ10 were still significantly and positively correlated with CFR (regression coefficient = 0.235, P < 0.001). Our data have demonstrated that HD patients exhibit decreased plasma CoQ10 levels and CFR values. The study also showed for the first time that serum CoQ10 levels independently predict CFR in HD patients.

Ultrasound/Laparoscopic Camera-Guided Transversus Abdominis Plane Block for Renal Transplant Donors: A Randomized Controlled Trial.

BACKGROUND The most common treatment modality for postoperative pain relief following laparoscopic surgery is multimodal, using nonsteroidal antiinflammatory drugs (NSAID), opioids, and infiltration of local anesthetics. Because NSAIDs are nephrotoxic, local infiltration does not relieve deep tissue pain, and opioids have an adverse effects profile including pruritus, nausea, vomiting, oversedation, apnea, and decreased gastrointestinal motility. Therefore, the use of a regional analgesic technique can lead to an improved quality of recovery. The aim of this prospective, randomized, placebo-controlled study was to evaluate the effect of TAP block on postoperative verbal analog scale (VAS) scores and total morphine requirements in the first 24 hours after laparoscopic live donor nephrectomy. MATERIAL AND METHODS After obtaining approval from the hospital ethics committee and written informed consent from the patients, 49 ASA I-II patients undergoing laparoscopic donor nephrectomy, aged 18 years or over, were included in this prospective, randomized, controlled study. In this clinical trial patients were divided into 2 groups: TAP block group (group T) and placebo group (group P). The demographic variables, pain scores, morphine consumption, level of sedation, presence of postoperative nausea, vomiting, pruritus, and average length of postoperative stay were reviewed. RESULTS The pain scores were significantly lower after TAP block with bupivacaine at most but not all time points. Patients receiving the TAP block with bupivacaine required less morphine up to 24 hours after surgery compared with the saline group. CONCLUSIONS USG-guided TAP block as part of a balanced analgesia regimen is of benefit in reducing postoperative pain and morphine consumption after laparoscopic donor nephrectomy.

Association between FAS and FASL genetic variants and risk of primary brain tumor.

The purpose of this study was to investigate whether functional polymorphisms of apoptosis pathway genes FAS and FASL are associated with the development of primary brain tumors. The study constituted 83 patients with primary brain tumor and 108 healthy individuals. In the present case-control study, the primary brain tumors were divided into two groups: gliomas and meningiomas. Evaluation of FAS -1377 G/A and FASL -844 T/C gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To confirm the genotyping, results were examined by DNA sequencing method. Our results were analyzed by SPSS. The frequency of the FAS -1377 AA genotype was significantly lower in meningioma and glioma patients compared to controls (p = 0.023; p = 0.001, respectively). Multivariate logistic regression analysis revealed that FAS -1377 AA genotype was associated with decreased risk of meningioma and glioma (OR = 0.092, 95% CI: 0.012–0.719, p = 0.023 for meningiomas; OR = 0.056, 95% CI: 0.007–0.428, p = 0.006 for gliomas). However, there was no significant differences in FASL -844 T/C genotype frequencies between patients with primary brain tumors and controls (p > 0.05). In this study, combined genotypes were evaluated for association with primary brain tumors. Combined genotype analysis showed that the frequencies of AATC and AACC were significantly lower in glioma patients in comparison with those of controls (p = 0.023; p = 0.022, respectively). This study provides the first evidence that FAS -1377 AA genotype may have a protective effect on the developing primary brain tumor in a Turkish population.