Mesut Sancar

Arg753Gln polymorphism of the human Toll-like receptor 2 gene from infection to disease in pediatric tuberculosis

The aim of this study is to examine the occurrence of the Arg753Gln polymorphism of the Toll-like receptor 2 (TLR2) gene in Turkish children with pulmonary and/or extrapulmonary tuberculosis (TB) disease compared with that in healthy children with latent TB infection (LTBI) and to assess the risk of progression from LTBI to active TB disease in children. The Arg753Gln polymorphism of the TLR2 gene was studied in 198 TB patients compared with 200 ethnically and age-matched children with LTBI. The culture confirmed TB patients were more frequently Arg753Gln heterozygous [odds ratio (OR) 5.05, 95% confidence interval (95% CI) 2.61-9.76, p = 0.00], and Gln allele frequency was significantly higher in the patient group (13.86% vs 3.5%, OR 4.40, 95% CI 2.34-8.30, p = 0.00). We also showed that the frequencies of the heterozygous Arg753Gln genotype and the Gln allele were significantly higher in patients with pulmonary TB alone and in patients with definitive pulmonary plus extrapulmonary TB than in children with LTBI. Our data suggest that the Arg753Gln polymorphism of the TLR-2 gene influences the speed of progression from infection to TB disease in children. Further investigations are needed to clarify whether this polymorphism has a strong impact on susceptibility to TB in children.

Probiotic, zinc and lactose‐free formula in children with rotavirus diarrhea: Are they effective?

Background:  The aim of the present study was to evaluate the effectiveness of zinc, probiotic bacteria, and lactose‐free formula and their different combinations in the treatment of rotavirus diarrhea in young children.

Relationship between Toll-Like Receptor 8 Gene Polymorphisms and Pediatric Pulmonary Tuberculosis

Objectives: Genetic variants in Toll-like receptors (TLRs) are considered a potential indicator for host susceptibility to and outcome of several infectious diseases including tuberculosis. The aim of this study was to determine whether −129 C/G and Met1Val polymorphisms of TLR8 were associated with pediatric pulmonary tuberculosis in Turkish population. Methods: The −129 C/G and Met1Val polymorphisms were studied in 124 children with pulmonary tuberculosis compared to 150 age-matched healthy control subjects. Results: We did not identify any statistically significant differences between the patients with TB and control groups with regard to the frequency of genotypes GG or G/(−), CG, and CC or C/(−); and alleles G and C at rs3764879 (p > 0.05). We found a strong association with genotype A/(−) at rs3764880 with susceptibility to pulmonary TB in males (OR 2.87, 95%CI 1.38–5.98, p = 0.007). Conclusions: Our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB in male children. Additional research to verify our results are necessary. Tuberculosis in children presents particularly difficult challenges, but research priorities and advances in pediatric tuberculosis could provide wider insights and opportunities for tuberculosis control.

Ertapenem for the treatment of urinary tract infections caused by extended-spectrum β-lactamase-producing bacteria in children

Abstract Background: Urinary tract infections (UTIs) are a problem frequently encountered by paediatric healthcare providers. Recent data suggest that extended-spectrum β-lactamase (ESBL)-producing bacteria are an emerging cause of UTIs in non-hospitalized patients. We report our experience of ertapenem use in 50 patients with complicated UTIs, mainly pyelonephritis, caused by ESBL-producing organisms. Methods: Fifty patients aged <16 y who had a complicated UTI caused by ESBL-producing organisms and who were treated with ertapenem at our hospital from 1 January 2009 to 31 December 2009, were included in the study. Results: There were 20 (40%) males and 30 (60%) females with a mean ± standard deviation age of 38.6 ± 36.9 months (range 6–156 months). Twenty-eight patients had no urological abnormality. In 40 patients ertapenem was initiated after results of microbiological cultures became available. Ertapenem was initiated empirically for 10 patients known to be colonized with ESBL-producing bacteria. Urine cultures were negative at 3.3 ± 0.7 days (range 2–5 days) after starting ertapenem treatment. The mean duration of ertapenem treatment was 7.8 ± 1.2 days (range 7–14 days). No laboratory or clinical side effects were observed. Conclusions: Ertapenem is promising for the culture-guided treatment of ESBL-producing Gram-negative complicated UTIs. Well-designed prospective studies are needed to define the role of ertapenem in treating complicated paediatric UTIs, especially upper UTIs.

Assessment of medication knowledge and adherence among patients under oral chronic medication treatment in community pharmacy settings

This study aimed to determine whether there is a relationship between the lack of medication knowledge and the self‐reported rates of patient medication adherence.

Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting

OBJECTIVE Two randomized controlled clinical trials have shown that Lactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea. METHODS This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1×10(8)CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded. RESULTS The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15h, 60.4±24.5h [95% CI: 51.0-69.7h] vs. 74.3±15.3h [95% CI: 68.7-79.9h], p<0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79, p<0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted. CONCLUSION L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea.

Adverse drug reactions due to drug-drug interactions with proton pump inhibitors: assessment of systematic reviews with AMSTAR method.

ABSTRACT Introduction: Many systematic reviews resulted in claims on drug-drug interactions (DDIs) with proton pump inhibitors (PPIs). Such a large number begs for consensus on the clinical significance of findings. Areas covered: We critically evaluated the safety of PPI use with respect to DDIs with a meta-review of systematic reviews published between 1978 and 2015. We assessed the evidence by their reliability, repeatability, transparency, and objectivity according to the Assessment of Multiple Systematic Reviews (AMSTAR) criteria. Expert opinion: Clinicians must assess risks for each PPI for certain comorbid conditions. DDIs don’t substantiate class effect for PPIs; each PPI could induce unique DDIs. Concomitant use of PPIs with thienopyridines (e.g. clopidogrel) could be justified in patients without strong affinity to cytochrome CYP2C19 and with high risk of bleeding (e.g. patients with prior upper gastrointestinal bleeding, Helicobacter pylori infection, advanced age, steroid treatment, and nonsteroidal anti-inflammatory drug use). DDIs could occur in an AIDS subpopulation treated with highly active antiretroviral therapy (HAART). DDIs exist for cancer patients undergoing targeted therapy. Hypomagnesemia could increase in the setting of advanced age and polypharmacy. Omeprazole poses high risks owing to its pharmacokinetic DDI profile. Future systematic reviews should incorporate these additional risks for better clinical guidance

Comparison of the protective effects of various antiulcer agents alone or in combination on indomethacin-induced gastric ulcers in rats.

The aim of this study which was structured with the objective of determination of the optimum protective therapy against the long term NSAID therapy-induced ulcers was to compare the gastro-protective effects of various antiulcer drugs (ranitidine, omeprazole, bismuth and misoprostol) alone or in combination with each other in different doses on indomethacin-induced gastric ulcers in rats. In this experimental study the protective effect of misoprostol (100 μg/kg/day and 10 μg/kg/day i.g.), omeprazole (5 mg/kg/day and 1.5 mg/kg/day i.p.), ranitidine (40 mg/kg/day and 10 mg/kg/day i.p.), bismuth (70 mg/kg/day and 15 mg/kg/day i.g.), combinations of misoprostol (10 μg/kg/day i.g.) plus omeprazole (1.5mg/kg/day i.p.) and misoprostol (10 μg/kg/day i.g.) plus ranitidine (10 mg/kg/day i.p.) are investigated on indomethacin (50 mg/kg/day s.c.) induced gastric ulcers. Half an hour before indomethacin administration, each group received the above treatment regimens for 5 days. After 5-day treatment, the rats were sacrificed and histopathological and hematological examinations were performed. The following regimens were found to be effective in the prevention of indomethacin-induced gastric lesions: 100 μg/kg misoprostol, 10 μg/kg misoprostol, 5mg/kg omeprazole, combination of 10 μg/kg misoprostol plus 1.5 mg/kg omeprazole and 10 μg/kg misoprostol plus 10 mg/kg ranitidine. The prevention rates achieved by these treatments were 71.4%, 50%, 47.6%, 52.4% and 50%, respectively. As a result of this study, misoprostol and omeprazol were found to be effective in protection against NSAID-induced gastric problems; while, ranitidine and bismuth were not. Also, the combinations of these agents were not found to have additive or synergistic effects.

Protective effect of ferulic acid on cisplatin induced nephrotoxicity in rats

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels (p<0.05). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals (p<0.05). All parameters showed improvement in groups treated with ferulic acid (p<0.05). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.

Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea.

Evidence from the literature has shown that Saccharomyces boulardii provides a clinically significant benefit in the treatment of acute infectious diarrhoea in children. In this multicentre, randomised, prospective, controlled, single blind clinical trial performed in children with acute watery diarrhoea, we aimed to evaluate the impact of S. boulardii CNCM I-745 in hospitalised children, in children requiring emergency care unit (ECU) stay and in outpatient settings. The primary endpoint was the duration of diarrhoea (in hours). Secondary outcome measures were duration of hospitalisation and diarrhoea at the 3(rd) day of intervention. In the whole study group (363 children), the duration of diarrhoea was approximately 24 h shorter in the S. boulardii group (75.4±33.1 vs 99.8±32.5 h, P<0.001). The effect of S. boulardii (diarrhoea-free children) was observed starting at 48 h. After 72 h, only 27.3% of the children receiving probiotic still had watery diarrhoea, in contrast to 48.5% in the control group (P<0.001). The duration of diarrhoea was significantly reduced in the probiotic group in hospital, ECU and outpatient settings (P<0.001, P<0.01 and P<0.001, respectively). The percentage of diarrhoea-free children was significantly larger after 48 and 72 h in all settings. The mean length of hospital stay was shorter with more than 36 h difference in the S. boulardii group (4.60±1.72 vs 6.12±1.71 days, P<0.001). The mean length of ECU stay was shorter with more than 19 h difference in the probiotic group (1.20±0.4 vs 2.0±0.3 days, P<0.001). No adverse effects related to the probiotic were noted. Because treatment can shorten the duration of diarrhoea and reduce the length of ECU and hospital stay, there is likely a social and economic benefit of S. boulardii CNCM I-745 in adjunction to oral rehydration solution in acute infectious gastroenteritis in children.