Mehmet Gürbilek

Comparative Effect of Oral Pulse and Intravenous Calcitriol Treatment in Hemodialysis Patients: The Effect on Serum IL-1 and IL-6 Levels and Bone Mineral Density

Introduction: Increased serum levels of bone-resorptive cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6) have been implicated for changes in bone remodeling in hemodialysis patients. In this prospective randomized study, we aimed to compare the effect of oral and intravenous (IV) pulse calcitriol on serum levels of IL-1β and IL-6. Patients and Methods: Twenty-eight hemodialysis patients were included and consecutively randomized to receive either oral (n = 14, M/F = 7/7, mean age 42 ± 15 years) or IV pulse (n = 14, M/F = 6/8, mean age 38 ± 14 years) calcitriol treatment. No difference was found between groups for age, sex distribution, primary renal disease, mean time on hemodialysis and baseline biochemical parameters including serum levels of IL-1β and IL-6. Results: The percent fall of intact parathyroid hormone (iPTH) was significantly less with oral compared to IV calcitriol between 0 and the 3rd month (32 ± 21 vs. 56 ± 28%, p = 0.03). However, the percent fall in iPTH at the 6th month of the therapy was not different in the oral group compared to the IV group (57 ± 22 vs. 73 ± 24%, p = 0.12). The increase in bone mineral densities was higher in the IV group than the oral group. Oral and IV calcitriol caused a significant fall in IL-1β (p = 0.02 and p = 0.03, respectively) and IL-6 levels (p = 0.02 and p < 0.001, respectively) at the 6th month of treatment. The percent fall in serum IL-6 levels at the 6th month was significantly greater in the IV compared to the oral group (61 ± 18 vs. 36 ± 33%, p = 0.04), while the percent changes in serum IL-1β levels were similar. Conclusion: IV calcitriol therapy has a greater suppression of PTH at the 3rd month of the therapy. Despite no difference in serum PTH levels at the 6th month, IV therapy has a greater increase in bone mineral densities and a greater decrease in serum IL-6 levels. These findings suggest IV calcitriol treatment has a superior effect on bone remodeling by influencing the levels of bone-resorptive cytokines as compared to the oral therapy group, beyond its suppressive effect on iPTH.

Enteral glutamine supplementation and dexamethasone attenuate the local intestinal damage in rats with experimental necrotizing enterocolitis

The pathogenesis of necrotizing enterocolitis (NEC) presumptively is due to an inappropriate intestinal epithelial immunologic response of immature gut to luminal stimuli. Glutamine is essential for intestinal crypt cell proliferation and enhances the cellular response to growth factors. We aimed to test the hypothesis that the supplementation of enteral feedings with glutamine may stimulate an immature intestine and decrease the intestinal inflammatory change in NEC. Immediately after birth, the neonatal rats were weighed and randomized into one of four treatment groups. Group 1 consisted of rats whom were breast-fed. Group 2 (NEC group) consisted of neonates whom were fed with a special rodent formula. Rats in groups 3 and 4 were fed in a similar fashion to those in group 2, and glutamine 0.3xa0mg/kg per day and dexamethasone 0.5xa0mg/kg per day were added to their formula, respectively. The neonatal rats were weighed and killed on day 4: the last 4xa0cm of terminal ileum was harvested for morphological studies and detection of nitrite and nitrate levels in tissue. The animals in the NEC group showed various degrees of inflammatory changes similar to clinical NEC. The inflammatory changes of the intestine appeared to be attenuated in both glutamine- and steroid-treated animals compared to those in the NEC group. Only steroid treatment decreased the tissue levels of these nitrogen oxides that were increased in rats in the NEC group. We herein provide evidence that maturational agents such as glutamine and dexametasone can attenuate the local intestinal inflammatory damage in experimental NEC. These findings support the hypothesis that the gut immaturity in premature infants represents a risk factor for NEC.

Serum cardiac troponin-I in active rheumatic carditis.

Objective :The study was performed to investigate the level of serum cardiac troponin I (cTnl), a specific marker for myocardial cell damage, in the acute rheumatic carditis (RC).Methods : Twenty seven consecutive patients with acute RC and 23 healthy children were enrolled.Result: cTnl level in both groups showed no statistical difference (p > 0.05).Conclusion: Serum cTnl level did not gain clinical use.

Cardiac troponin-I in the serum of infants of diabetic mothers.

A transient form of hypertrophic cardiomyopathy has been previously described in infants of diabetic mothers. When it occurs, it is generally benign. The purpose of our study was to establish the extent of injury to the cardiomyocytes in symptomatic and asymptomatic patients with and without hypertrophic cardiomyopathy. Thus, we compared 35 consecutive patients to 20 healthy controls, establishing the significance, if any, of differences in cardiac troponin-I and creatine kinase, including its MB-fraction, and seeking to establish the value of these parameters in the diagnosis of cardiac injury. We also determined to levels of glucose and insulin in the serum, and took note of electrocardiographic and echocardiographic investigations. Values were determined at the 1st and 7th days after admission in the patients, while parameters were measured in the control group only on the first day. We found that the levels of cardiac troponin-I in the serum, known to be a marker for cardiac injury, were significantly elevated in symptomatic patients with life-threatening respiratory or haemodynamic distress. We speculate that transient ventricular hypertrophy is neither the cause nor the consequence of damage to the cardiomyocytes. It would be interesting, nonetheless, to determine the relationship, if any, between cardiomyocytic damage and clinical outcome.

Urinary kidney injury molecule-1 levels in renal stone patients

ObjectiveTo study kidney injury molecule-1 (KIM-1) biomarker levels, indicating renal tubular damage, in patients with kidney stones and in those who underwent minimally invasive method stone treatment.Patients and methodsSixty patients with renal stones between 10 and 20xa0mm were included into the present study. Patients who were divided into three cohorts underwent micropercutaneous nephrolithotomy (microperc), retrograde intrarenal stone surgery (RIRS), and percutaneous nephrolithotomy (PNL). Urine samples were obtained from all participants before, 4xa0h and 14xa0days after the procedure. In all the samples obtained, urinary KIM-1 and creatinine (Cr) levels were measured and KIM-1/Cr ratios (ng/mg creatinine) were calculated.ResultsPreoperative urine KIM-1/Cr ratio was higher than postoperative 14th day. The bigger the renal stone size, the higher was the ratio (correlation coefficient 0.353, pxa0=xa00.006). According to preferred treatment procedure, there was a statistically significant decrease in preoperative and postoperative 4th hour and 14th day urine KIM-1/Cr rates in the RIRS and PNL, yet none in the microperc group (pxa0=xa00.010, pxa0=xa00.001, pxa0=xa00.212, respectively).ConclusionIn renal stone patients, the elevated urine KIM-1/Cr ratio levels increase further according to stone size. KIM-1/Cr ratio is a promising marker might be helpful in monitoring the damage created by stone disease.

Prognostic value of interferon-gamma, interleukin-6, and tumor necrosis factor-alpha in the radiation response of patients diagnosed with locally advanced non-small-cell lung cancer and glioblastoma multiforme

Background/aim: This study aimed to investigate the effect of chemoradiotherapy (CRT) on interferon-gamma (IFN-γ), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), which are critical markers of the clinical radiation response of patients with locally advanced non-small-cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). Materials and methods: Thirty patients who were treated with CRT and 20 healthy controls were prospectively evaluated. Circulating levels of cytokines were measured by enzyme-linked immunosorbent assay procedure. Post-CRT and pre-CRT levels were compared. Results: Post-CRT, TNF-α and IFN-γ levels were significantly lower than pre-CRT levels in the NSCLC and GBM groups, respectively. The statistical analysis did not show any significant difference between the post- and pre-CRT IL-6 levels. However, the pre-CRT IL-6 levels in the GBM group and post-CRT IL-6 levels in the NSCLC group were significantly higher than those of the control group. Conclusion: CRT affected TNF-α levels in NSCLC and IFN-γ levels in GBM, with the levels of both decreasing significantly. The IL-6 levels of the post-CRT NSCLC group were higher than those of the post-CRT GBM group. Irradiation-induced IL-6 may be responsible for tumor regrowth. Therefore, treatment with IL-6 inhibitors could be a potential therapeutic strategy for sensitizing NSCLC to irradiation in the clinic.

Effects of chemoradiotherapy on acute-phase protein levels in glioblastoma multiforme and locally advanced non-small cell lung cancer

Abstract Objective: Chemoradiotherapy (CRT) is a commonly used therapeutic modality. We investigated CRT effects on acute phase reactants (APRs). The aim of this study was to assess possible changes in APR levels during radiotherapy and to determine the usefulness of APRs as prognostic factors in patients with non-small cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). Methods: We prospectively evaluated 30 patients and 30 healthy controls. Plasma levels of APRs were measured. Post-CRT and pre-CRT levels were compared. Survival of patients were also followed up for a period of 3 years. Results: In NSCLC patients, post-CRT albumin, transferrin (Trf), and ceruloplasmin (Cp) levels were significantly lower, and post-CRT ferritin (FER) levels were significantly higher, than their pre-CRT levels. In GBM patients, post-CRT Trf and prealbumin (Prealb) levels were significantly higher than pre-CRT levels. Pre-CRT C-reactive protein (CRP) and FER levels in NSCLC patients and Cp levels in GBM patients were associated with patient survival. Conclusion: This study suggests that APRs may be useful for monitoring response to treatment during CRT in NSCLC and GBM patients. Bearing in mind their accessibility and clinical value, plasma CRP and FER in NSCLC patients and Cp in GBM patients can be considered candidate prognostic factors.

Evaluation of the radioprotective effects of thymoquinone on dynamic thiol-disulphide homeostasis during total-body irradiation in rats

Abstract Ionizing radiation–induced free radicals cause functional and structural harmful effects. Thiol, an important antioxidant, plays a major role in the eradication of reactive oxygen molecules. Thiol/disulphide homeostasis is a marker of oxidative stress. The objective of this study was to assess the potential radioprotective effects of thymoquinone (TQ) on the dynamic thiol/disulphide homeostasis of rats receiving total-body irradiation (IR). Twenty-two rats were divided into three groups to test the radioprotective effectiveness of TQ. The sham control group did not receive TQ or IR. The IR group received only total-body IR. The TQ + IR group received IR plus TQ. Following IR, blood samples were taken. The thiol/disulphide homeostasis parameters were analysed by a newly established method. In the IR group, native thiol and the native thiol/total thiol ratio were significantly decreased (P = 0.003 and P = 0.003, respectively), whereas the disulphide/native thiol and disulphide/total thiol ratios were significantly increased when compared with those of the sham control group (P = 0.003 and P = 0.003, respectively). In the TQ + IR group, the mean disulphide, native thiol and total thiol levels and the disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were not found to be significantly different when compared with those of the sham control group (P > 0.05 for all). Thiol/disulphide homeostasis was found to be disturbed after IR exposure. The results showed that TQ had antioxidant effects and reduced the IR-induced oxidative stress, which was demonstrated through the dynamic thiol/disulphide homeostasis. Thus, the use of TQ before radiation treatment helped protect the rats from oxidant side effects.