The telomere length of gastric mucosal samples and peripheral blood lymphocytes in patients who have undergone Billroth II distal gastrectomy.

INTRODUCTION: Telomeres play an important role in maintaining chromosomal integrity. Functional loss of telomeres increases the risk of cancer by causing genomic instability. Telomere length abnormalities have been reported in several precancerous lesions. There is no study that evaluates telomere length in Billroth II distal gastrectomy, which is known as a risk factor for gastric stump carcinogenesis, in the literature. The aim of this study was to assess the relationship between the telomere length of residual gastric mucosal samples, peripheral blood lymphocytes, and other clinicopathological parameters of patients who had undergone Billroth II distal gastrectomy. MATERIAL AND METHODS: There were two groups: a control group (n = 15) and a patient group (n = 15). In all cases, upper gastrointestinal endoscopy was performed, and biopsies were taken during endoscopy. Telomere lengths were measured by qRT-PCR. RESULTS: It was observed that the lengths of the telomeres were shortened as the time of postoperative period increased in the patient group (r = -0.126) (p > 0.05). Also, the lengths of the telomeres were shortened in chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia. CONCLUSIONS: The telomere length was shortened as the time of postoperative period increased in the patient group. The telomeres were also shorter in chronic inflammation, neutrophil activity, intestinal metaplasia, and glandular atrophy, in all of the study groups. Telomere length abnormalities in gastric stump carcinogenesis process may be a guide for early diagnosis and treatment.

Telbivudine attenuates gentamicin-induced kidney injury in rats.

Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P <0.007) and between the LdT and PC groups (P <0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment.

Clinical significance of glucocorticoid receptor expression in premature infants with respiratory distress syndrome.

OBJECTIVE: Previous studies have shown the relationship between lung development and glucocorticoids, but no studies have been conducted to investigate if a relationship exists between respiratory distress syndrome (RDS) and glucocorticoid receptor (GR) expression in preterm babies. We intended to investigate whether low GR expression is a risk factor for RDS. METHODS: Forty-one preterm babies, 24-35 weeks of gestation, were included in the study following informed consent from the parents. The relative gene expression of GRalpha and GRbeta was measured in the peripheral mononuclear cells form cord blood samples. The demographic characteristics of the babies and the diagnosis of RDS were recorded. RESULTS: RDS was more frequent in the group with low GRalpha expression: 12 (60%) in the GRalpha-I group and 6 (28%) in the GRalpha-II group (p = 0.043). Oxygen use with a hood, time to reach full enteral feeds and the duration of neonatal intensive care unit stay was shorter, and nosocomial sepsis episodes and number of erythrocyte transfusions were less in the GRbeta-I group. Higher hospital costs were found in the GRbeta-II group. CONCLUSIONS: Less RDS development, and better clinical follow-up was observed in premature babies with higher GR expression.

Is there any role of epithelial to mesenchymal transition in the pathogenesis of contrast nephropathy?

AIM: Contrast medium-induced nephropathy is one of the major complications of intravenous contrast medium use. But its pathogenesis is unclear. Epithelial mesenchymal transition (EMT) is defined as the transformation of the primer epithelial cells to mesenchymal cells. EMT in tubular cells might cause tubulointerstitial damage. In this study, we investigated whether or not EMT has a role in radiocontrast-induced nephropathy. Radiocontrast medium might be triggering reversible EMT via serum and glucocorticoid-regulated kinase 1 (SGK 1). We investigated the effect of different concentrations of the contrast agent iopromide on human proximal tubule cell (HK-2) culture by measuring the level of SGK1, snail family zinc finger 1 (SNAIL1), connective tissue growth factor (CTGF), and collagen type I alpha 1 (COL1A1). METHODS: We conducted a scratch assay and qPCR. HK-2 cells were cultured in the petri dishes/flasks and starved with serum-free medium. The 40, 20, and 10 mg/mL doses of iopromide were administrated to cells. The scratches were photographed immediately and again at the 20th hour. The levels of gene expression of SGK1, SNAIL1, CTGF, and COL1A1 were measured using the real-time qPCR system at the end of the 24th hour. RESULTS: Iopromide caused the breaking of intercellular connections, the disappearance of the cobblestone appearance of cells, and the migration of cells at the 20th hour in the scratch assay. It also increased the expression of SGK1, SNAIL1, CTGF, and COL1A1 genes. CONCLUSION: Our study concluded that certain important markers of EMT increase in different concentrations of the contrast agent. High osmolality might trigger EMT. The relationship between contrast agent and EMT has not been defined before. Further in vivo and in vitro studies are required.

Is Serum Caveolin-1 a Useful Biomarker for Progression in Patients with Colorectal Cancer?.

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer diagnosed in males and the second in females. Survival is strongly related to stage at diagnosis. There is an urgent need to find a noninvasive biomarker that can be commonly applied for screening diagnosis, early detection of recurrence, and monitoring of metastatic CRC. Protein caveolin-1 (CAV-1) has been known to be expressed abnormally in colon cancer and appears to contribute to aberrant signaling and protein trafficking. There are controversial results regarding the role of CAV-1 in cancer. We hypothesized that levels of CAV-1 in serum of patients with CRC might be important to estimate the progression of the disease. Therefore, the purpose of this study is to investigate whether serum CAV-1 might be used as a factor determining progression of CRC. METHODS: A total of 61 patients with CRC (26 male, 35 female) and 46 controls (38 male, 8 female) were enrolled. Serum CAV-1 levels were measured by ELISA. The relationship between CAV-1 and progression-free survival (PFS) was analyzed with use of receiver operating characteristic (ROC) and Kaplan-Meier analysis. Results were given as median (95% CI). Mann-Whitney test was used for the comparison of groups. RESULTS: CAV-1 levels were found to be 11.5 ng/mL (10.4-12.9) in CRC and 11.9 ng/mL (10.7-14.4) in controls (p = 0.465). The serum CAV-1 levels in CRC patients with disease progression and without progression were respectively 10.0 ng/mL (8.5-11.3) and 12.2 ng/mL (11.1-14.8) (p = 0.023). In ROC analysis, if CAV-1 levels are equal or lesser than 10.73 ng/mL, it might show presence of progression with a sensitivity 73.3% and specificity 66.7% in patients with CRC (area under the ROC curve (AUC) = 0.697, p = 0.005). The mean PFS time was found to be 29.7 months (19.8-39.7, 95% CI for the mean) in patients who have CAV-1 level ≤ 10.73 ng/mL and 61.9 months (44.2-79.6) in patients who have CAV-1 level > 10.73 ng/mL [hazard ratios (HR) with 95% CI = 3.49 (1.26 - 9.68) (p = 0.017)]. CONCLUSIONS: Our results strongly suggest that CAV-1 levels might be used as a marker to determine progression of CRC. When considered in combination with other biomarkers of CRC, CAV-1 is clinically informative and instructive.

Assessment of different folic acid supplementation doses for low-birth-weight infants.

AIM: The adequacy of 50 mcg folic acid supplementation given to low-birth-weight babies was investigated. The folate levels of the mothers and infants, and breastmilk, and the optimum dose for folic acid supplementation were also investigated. MATERIAL AND METHODS: After obtaining blood from 141 low-birth-weight infants on the 1st day of life for serum and red cell folate levels, the infants were randomly allocated into three groups according to the folic acid supplement dose. Forty-six infants were given 25 µg/d folic acid, 39 were given 50 µg/d folic acid, and 44 were given 75 µg/d folic acid. Folic acid could not be given to 12 infants. Follow-up blood samples were obtained at the end of folic acid supplementation. Maternal samples for red cell and serum folate levels and breast milk folate levels were obtained within the first 48 hours and the samples for measuring breastmilk folate level were obtained on the 3rd day postnatally. The feeding modes of the infants, maternal folic acid intake, and details of neonate intensive care unit course were recorded. RESULTS: The mean birth weight and gestational age of the infants were found as 1788.2±478.4 g and 33.5±2.9 weeks, respectively. The mean serum and red cell folate levels on admission were found as 21.2±12.2 ng/mL and 922.7±460.7 ng/mL, respectively. The mean maternal serum and red cell folate levels and the mean breast milk folate levels were found as 12.3±7.5 ng/mL, 845.5±301.4 ng/mL, and 30.6±33.0 ng/m, respectively. The breast milk folate levels of mothers who were supplemented with folic acid during pregnancy were significantly higher compared with mothers who were not supplemented with folic acid (p<0.001). Infants who were supplemented with folic acid had higher follow-up serum folate levels compared with the basal level in all groups, but there was no statistically significant difference between the groups. CONCLUSION: This study showed that the folic acid doses of 25, 50, and 75 µcg/d affected serum folate levels similarly. We can conclude that the dose of 25 µcg/d is adequate for low-birth-weight infants.

Antimetastatic effect of fluvastatin on breast and hepatocellular carcinoma cells in relation to SGK1 and NDRG1 genes.

Metastasis occurs due to migration of the cells from primary tumor toward other tissues by gaining invasive properties. Since metastatic invasion shows a strong resistance against conventional cancer treatments, the studies on this issue have been focused. Within this context, inhibition of migration and determination of the relationships at the gene level will contribute to treatment of metastatic cancer cases. We have aimed to demonstrate the impact of TGF-ß1 and fluvastatin on human breast cancer (MCF-7) and human hepatocellular carcinoma (Hep3B) cell cultures via Real-Time Cell Analyzer (RTCA) and to test the expression levels of some genes (NDRG1, SGK1, TWIST1, AMPKA2) and to compare their gene expression levels according to RTCA results. Both of cell series were applied TGF-ß1 and combinations of TGF-ß1/fluvastatin. Primer and probes were synthesized using Universal Probe Library (UPL, Roche) software, and expression levels of genes were tested via qPCR using the device LightCycler 480 II (Roche). Consequently, fluvastatin dose-dependently inhibited migration induced by TGF-ß1 in both groups. This inhibition was accompanied by low level of SGK1 messenger RNA (mRNA) and high levels of NDRG1 and AMPKA2 mRNA. Thus, we conclude that fluvastatin plays an important role in reducing resistance to chemotherapeutics and preventing metastasis.

The Evaluation of Serum Pentraxin-3 and High-Sensitivity C-Reactive Protein Levels in Patients with Acute Attack of COPD.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by the release of inflammatory mediators. The aim of this study was to compare serum levels of pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute exacerbations of COPD with those of a healthy control group. METHODS: The study included 107 men and 19 women, with mean age of 66.5 (32 - 87) years who were diagnosed with acute COPD exacerbations and 48 healthy individuals as a control group. The serum PTX3 and hs-CRP levels were measured and pulmonary function tests were performed. RESULTS: The mean serum level of the hs-CRP was 39.56 mg/L (10.10 - 262), and it was higher in the COPD group than in the control group (p < 0.0001). The hs-CRP levels increased in accordance with the severity of the COPD (p < 0.0001). The serum PTX3 level was 0.52 pcg/dL (0.42 - 0.56) in acute exacerbations. There was a correlation between the PTX3 levels and the pulmonary function tests, including FEV1, FVC, and FEV1/FVC (r = 0.317, p < 0.001; r = 0.385, p < 0.0001, and r = 0.248, p = 0.001, respectively). CONCLUSIONS: The short pentraxin hs-CRP is elevated in COPD patients with acute exacerbations and correlates with the severity of the disease compared with the long pentraxin PTX3. These results support the idea that hs-CRP can be used as an earlier determinant of inflammation in COPD acute exacerbations and that PTX3 cannot be used as a marker of acute exacerbation and disease severity.

The anticancer effects of desferrioxamine on human breast adenocarcinoma and hepatocellular carcinoma cells.

N-myc downstream-regulated gene 1 (NDRG1) is defined as metastasis suppressor and can be downregulated in many types of cancers, and reported to be an indication of tumor progression in hepatocellular carcinomas. Several in-vivo and in-vitro studies have demonstrated that iron chelators such as Desferrioxamine (DFO) and 1-10 Phenanthroline (PHEN) are effective antitumor agents. It is suggested that these chelators deliver their antitumor activity by acting on the NDRG1 gene expression. It remains unclear why NDRG1 gene expression affects the tumors differently, or becomes affected differently. We consider that this different effect might be caused by variants. Based on this information, we developed specific primers and probes for NDRG1 mRNA variants using bioinformatics analysis, and investigated how DFO and PHEN affected the dynamics of NDRG1 variant on the cell lines of Human Breast Adenocarcinoma (MCF-7) and Hepatocellular Carcinoma (HepG2) that demonstrate opposite action for the relationship NDRG1-metastasis. We administrated various doses of DFO and PHEN into the cells to monitor cell vitality and proliferation with Real time Cell Analyzer. We analyzed the gene expression levels of study groups with Quantitative RT-PCR as well as relative gene expression. Variants of NDRG1 mRNA were transcriptionally regulated after HepG2 and MCF-7 cells were treated by iron chelators, resulting in domination of NDRG1 mRNA Variant 1 (V1) in the HepG2 calls and domination of NDRG1 mRNA Variant 2 (V2) in the MCF-7 cells. Anti-proliferative and cytotoxic effects were observed in the MCF-7 cells whereas an increased proliferation was present in the HepG2 cells.

Cytotoxic effect of fluvastatin on MCF-7 cells possibly through a reduction of the mRNA expression levels of SGK1 and CAV1.

Fluvastatin (FLU) prevents the conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) to mevalonic acid by inhibiting HMG-CoA reductase and decreases cholesterol level. Although the effects of FLU treatment on several cancer types through many mechanisms have been identified, its relationship with unfolded protein response and apoptosis has not been clearly understood. In this recent study, we aimed to investigate the cytotoxic effect of Fluvastatin on MCF-7 cells and define the transcriptional regulation of specific genes during the occurrence of this cytotoxic effect. We administered 0.62, 2.5, 5, and 40 µM FLU on MCF-7 cells singly and in combination with 2-deoxyglucose (2-DG), and we monitored cell viability and proliferation for 48 hours using real-time cell analyzer system (xCELLigence). At the same time, we measured the mRNA expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein, homologous protein (CHOP), caveolin-1 (CAV1), NDRG1 Variant 1 and Variant 2, HMOX1, SGK1, and prostate apoptosis response-4 (PAR4) genes using quantitative real-time polymerase chain reaction (LightCycler 480 II). We accepted GAPDH gene and control groups as the reference gene and calibrator, respectively. We performed relative gene expression analyses of the study groups using the QIAGEN 2009 Relative Expression Software Tool (REST). FLU revealed an antiproliferative and cytotoxic effect on MCF-7 cells, while causing the transcriptional regulation of many genes. Of these genes, the mRNA expressions of CHOP, heme oxygenase 1 (HMOX1), N-myc downstream-regulated gene 1 (NDRG1) V1, and NDRG1 V2 increased. On the other hand, the mRNA expression levels of SGK1 and CAV1 decreased. The antiproliferative effects of FLU may be related to the decreased expression levels of SGK1 and CAV1.

Increased serum heme oxygenase-1 levels as a diagnostic marker of oxidative stress in preeclampsia.

OBJECTIVE: To evaluate the utility of serum biomarkers in the diagnosis of preeclampsia (PE) and also investigate possible correlation with pathogenesis of PE. METHODS: Maternal serum concentrations of heme oxygenase-1 (HO1) and N-myc downstream-regulated gene 1 (NDRG1) were measured at 27-34 weeks of gestation in a case-control study of 33 pregnant women diagnosed with PE and in 43 normotensive pregnant women without proteinuria. The Mann-Whitney U test and Spearman's correlation were used for statistical analysis. RESULTS: The median serum HO1 level was found to be significantly higher in the PE group [76.7 ng/ml (23.4-445.7)] than control group [55.9 ng/ml (3.7-354.3)] (p = 0.006). Positive correlation was found between HO1 levels with presence of PE (r = 0.316, p = 0.005). There was no significant difference in NDRG1 values between the two groups (p = 0.226). CONCLUSIONS: Serum HO1 levels were found to be increased in patients with PE compared with normotensive pregnant women.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers.

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity.

Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M × 10(-5) at 24th hour and 3.93 M × 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M × 10(-3) at 24th hour and 2.85 M × 10(-4) at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.

Increased DNA oxidation (8-OHdG) and protein oxidation (AOPP) by low level electromagnetic field (2.45 GHz) in rat brain and protective effect of garlic.

PURPOSE: To investigate the oxidative damage and protective effect of garlic on rats exposed to low level of electromagnetic fields (EMF) at 2.45 GHz Microwave radiation (MWR). METHODS: Thirty-six Wistar rats were divided into three groups. Group I was the control group and not exposed to EMF. Group II and III were exposed to low level EMF (3.68 ± 0.36 V/m) at 2.45 GHz MWR for 1 hour/day for 30 consecutive days. Daily 500 mg/kg garlic was given to Group III during the study period. At the end of the study, thiobarbituric acid reactive substances (TBARS), advanced oxidation protein products (AOPP) and 8-hydroxydeoxyguanosine (8-OHdG) levels were investigated in brain tissue and blood samples. RESULTS: Exposure to low level of EMF increased 8-OHdG level in both plasma and brain tissue whereas it increased AOPP level only in plasma. Garlic prevented the increase of 8-OHdG level in brain tissue and plasma AOPP levels. CONCLUSIONS: It may be concluded that low level EMF at 2.45 GHz MWR increases the DNA damage in both brain tissues and plasma of the rats whereas it increases protein oxidation only in plasma. It may also be argued that the use of garlic decreases these effects.

Effect of free creatine therapy on cisplatin-induced renal damage.

Abstract Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n=20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin+creatine monohydrate (n=20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n=20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p<0.05). In group II, there was a slight decrease in body weight at same days (p=0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p<0.05). Although creatine significantly reversed kidney functions and pathological findings, this improvement was not sufficient to reach normal control group's results at days 7 and 30. In conclusion, the present study demonstrates that creatine administration is a promising adjuvant protective drug for reducing nephrotoxic effect of cisplatin.

Do iron chelators increase the antiproliferative effect of trichostatin A through a glucose-regulated protein 78 mediated mechanism?

Histone deacetylase (HDAC) inhibitors, such as trichostatin A (TSA), and iron chelators, including deferoxamine (DFO) and phenanthroline (PHEN), appear to have anticancer effects. We hypothesized that the HDAC inhibitors and iron chelators would be synergistic with their effect on breast cancer cell line MCF7, because the HDAC inhibitors increase glucose-regulated protein 78 (Grp78) and the iron chelators reduce its expression. Although the administration of TSA alone resulted in a dose-related decrease in the cell index, it did not have an antiproliferative effect except the 62.5 and 500 nM of TSA. However, all doses of TSA produced a cytotoxic effect from the initial hours when combined with 150 µM of DFO and 25 µM of PHEN. DFO and PHEN downregulated Grp78, Grp94, and MRP1 expressions and upregulated CHOP and HO-1 expressions. TSA upregulated all the genes in various rates when used alone but resulted in decreased expression levels when combined with DFO and PHEN. Increased HDAC-1 levels in the Grp78 promoter region indicated that DFO and PHEN either promoted binding of HDAC-1 to this region or inhibited its detachment. We determined that the reduction of increased Grp78, Grp94, HO-1, and MRP1 expressions, which appears to inhibit the chemotherapeutic effect of TSA, through the combination with DFO or PHEN will contribute to the anticancer effect.

Effects of circulating endothelial progenitor cells, serum vascular endothelial growth factor and hypogammaglobulinemia in Perthes disease.

OBJECTIVE: The aim of this study was to investigate Legg-Calvé-Perthes disease (PD) pathogenesis by comparing absolute circulating endothelial progenitor cell (EPC) counts, serum levels of vascular endothelial growth factor-A (VEGF-A) and immunoglobulins between PD patients and controls. METHODS: The study included 28 PD cases (mean age: 8 ± 3.8) and 25 healthy age-matched control subjects. EPC, serum VEGF-A and immunoglobulin levels were measured in peripheral blood samples. Comparisons and correlation analysis were performed. RESULTS: In the PD group, 17 subjects were in the fragmentation stage and 11 in the healing stage. Four patients had bilateral disease and 14 had hypogammaglobulinemia. Median EPC count of the PD group was 80 and was significantly higher than those of the control group (p=0.011). No significant difference was determined in serum VEGF-A levels (p=0.354). EPC count were inversely correlated with serum IgG levels of the PD group (r=0.403, p=0.03). Absolute EPC count was also significantly higher in the fragmentation stage than in the healing stage and were also greater in bilaterally affected than in unilaterally affected patients. Circulating EPC count was correlated to the serum VEGF-A levels in patients with fragmentation stage of PD (r=0.605, p=0.01) and in those with hypogammaglobulinemia (r=0.599, p=0.001). CONCLUSION: High EPC count at the fragmentation stage of PD and relatively higher counts in bilateral disease suggest that EPC may be a valuable marker in the diagnosis and follow-up of PD. Additional studies are needed to explain the strong correlation between EPC and serum VEGF-A level in the fragmentation stage and in the presence of hypogammaglobulinemia.

Comparison of predictive powers of S100B and cell-free plasma DNA values in intensive care unit patients with intracranial hemorrhage.

PURPOSE: To investigate predictive powers of S100B and cell-free DNA (cfDNA) levels in patients in the intensive care unit (ICU) who have with intracranial hemorrhage (ICH) for prognosis. METHODS: Ninety-nine patients diagnosed with ICH were included in the study. The blood samples were drawn on the day of admittance to ICU and again on the third day. Duration of stay in the ICU and mortality were recorded. RESULTS: A positive correlation was determined between the values of S100B and cfDNA from both the analysis and the Acute Physiology and Chronic Health Evaluation II scores. For all patients, there was a positive correlation between the duration of stay in the ICU and the values of S100B and cfDNA on the third day. The levels of both S100B and cfDNA in patients who died in the ICU were significantly higher than of those who survived on the day of admittance. CONCLUSIONS: Both S100B and cfDNA values can be used as markers to predict the prognosis of ICU patients with ICH. However, S100B is more powerful for predicting the prognosis.

Helicobacter pylori eradication increases telomere length in gastric mucosa.

BACKGROUND/AIMS: Our purpose in this study was to analyze telomere length and telomerase activity before and after eradication treatment in gastric mucosa in patients positive for H. pylori. METHODOLOGY: There were two groups: a control group (n=17) and a study group (n=21). For H. pylori eradication, the patients were administrated proton pump inhibitor (PPI) + clarithromycin + amoxicillin or PPI + metronidazole + tetracycline + bismuth for 14 days. Telomere length was analyzed with RT-PCR and telomerase activity with PCR-ELISA on biopsy specimens from the antrum. The result p<0.05 was considered significant. RESULTS: Prior to eradication, there was no significant difference between telomere lengths of the patient and control groups (2481.2±1823 and 2958.9±1345.7 bp, p=0.11, respectively). The telomere length of the study group became longer after eradication (before 2481.2±1823bp, after 3766.3±1608.8bp, p=0.01). Telomerase activity was not detected in either the patient or the control group. CONCLUSIONS: An increase in telomere length was observed with H. pylori eradication. This finding may indicate the importance of H. pylori eradication to avoid the development of gastric cancer.

Is vitamin d deficiency a risk factor for respiratory distress syndrome?

BACKGROUND: Previous studies have shown the relationship between in utero lung development and vitamin D [25(OH)D], but there have been no studies to investigate whether vitamin D deficiency is a risk factor for respiratory distress syndrome (RDS) in preterm babies. OBJECTIVES: In this study, we investigated if 25(OH)D deficiency is a risk factor for RDS. METHODS: One hundred fifty-two preterm newborns, born at 29 - 35 weeks gestational age, were included in the study following informed consent from the parents. Peripheral blood samples were collected within the first 24 hours of life and 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry. Demographic characteristics of the babies and the diagnosis of RDS were recorded. RESULTS: In 64 % of preterm infants, 25(OH)D levels were compatible with severe deficiency (≤ 10 ng/mL), 33 % with moderate deficiency (10 - 20 ng/mL), and 3 % with mild deficiency (20 - 30 ng/mL). In none of the babies was a normal 25(OH)D level observed. Serum 25(OH)D levels were not correlated with gestational age. Respiratory distress syndrome was more common in preterm babies with severe (28 %) compared to mild-moderate 25(OH)D deficiency (14 %) (p < 0.05). CONCLUSIONS: None of the preterm infants in this study had normal vitamin D level, which underlined the burden of vitamin D deficiency in pregnant women and their offspring. RDS was more common in severely vitamin D-deficient preterms. Determination of vitamin D status of the mothers and appropriate supplementation might be a valuable strategy to reduce RDS, in addition to antenatal steroids. Besides, since vitamin D is a regulatory factor in many organs during fetal development, long-term effects of in utero vitamin D deficiency warrant further studies.