Vefik Arica

Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats

Aim: Oxidative stress has been implicated as a potential responsible mechanism in the pathogenesis of vancomycin (VCM)-induced renal toxicity. Therefore, we aimed to investigate the protective effect of thymoquinone (TQ) against VCM-induced nephrotoxicity by tissue oxidant/antioxidant parameters and histological changes in rats. Materials and methods: Wistar albino rats were randomly separated into four groups consisting of seven rats per group. The groups had normal saline (control group), VCM, VCM and TQ and TQ, respectively. VCM was injected intraperitoneally at a dose of 200 mg/kg and continued at 12-h intervals for 7 days. TQ was injected intraperitoneally at a dose of 10 mg/kg and continued at 24 h intervals for 8 days. Animals were killed and blood samples were analyzed for the levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Kidney specimens were analyzed for levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as for histopathological changes. Results: We found that the levels of serum BUN, Cr and kidney tissue MDA were increased in the VCM group. Activities of SOD and GSH-Px in kidney tissue were decreased. TQ administration ameliorated significantly these changes. Conclusion: These results indicate that the TQ produces a protective mechanism against VCM-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.

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.

Ceftriaxone ameliorates cyclosporine A-induced oxidative nephrotoxicity in rat.

A growing body of evidence now suggested that cyclosporine A (CycA)‐induced nephrotoxicity is a crucial clinical problem and oxidative stress is importantly responsible for its toxicity. Ceftriaxone induced antioxidant effect in brain and neuronal tissues against oxidative damage although its antioxidant potential effect on kidney has not been clarified. The aim of this study was to evaluate whether ceftriaxone protects CycA‐induced oxidative stress kidney injury in rats. Twenty‐four rats were equally divided into four groups. First group was used as control. Ceftriaxone (200 mg/kg) and CycA (15 mg/kg) were administrated to second and third groups for 10 days, respectively. The ceftriaxone and CycA combination was given to rats constituting the fourth group for 10 days. Lipid peroxidation (LP), urea nitrogen and lactate dehydrogenase (LDH) levels were higher in CycA group than in control and ceftriaxone groups although LP, urea nitrogen and LDH levels were lower in ceftriaxone + CycA group than in control and ceftriaxone groups. Glutathione peroxidase and catalase activities were lower in CycA group than in control whereas their activities were increased in control and ceftriaxone groups. Superoxide dismutase activity did not change by the treatments. Ceftriaxone administration recovered also CycA‐induced atrophy, vacuolization and exfoliations of tubular epithelium and glomerular collapse in histopathological evaluation of kidney. In conclusion, we observed that ceftriaxone is beneficial on CycA‐induced oxidative stress in kidney of rats by modulating oxidative and antioxidant system. Copyright

Frequency of MEFV gene mutations in Hatay province, Mediterranean region of Turkey and report of a novel missense mutation (I247V)

In the present study, 1000 patients with clinical suspicion of FMF were retrospectively reviewed to determine the spectrum of MEFV gene mutations by using DNA sequence analysis between September, 2008 and April, 2012. Sixteen different mutations and 55 different genotypes were detected in 618 of 1000 patients. Among 16 different mutations, R202Q (21.35%) was the most frequently observed mutation; followed by E148Q (8.85%), M694V (7.95%), M680I (2.40%), V726A (1.85%), M694I (0.95%), A744S (0.80%), R761H (0.55%), P283L (0.35%), K695R (0.20%), E230K (0.15%), L110P (0.10%), I247V (0.05%), G196W (0.05%) and G304R (0.05%). In the present study, a novel missense mutation (I247V) and a silent variant (G150G) were identified in the MEFV gene. On the other hand, P238L, G632A and G304R mutations are the first cases reported from Turkey. Our results indicated that MEFV mutations are highly heterogeneous in our study population as in other regions of Turkey and mutation screening techniques such as PCR-RFLP, amplification refractory mutation system or reverse hybridization do not adequately detect uncommon or novel mutations. Therefore, it was proven that sequence analysis of the MEFV gene could be useful for detection of rare or unknown mutations.

Effects of erdosteine on cyclosporin-A-induced nephrotoxicity

Aim: In cyclosporin-A (CsA)-induced toxicity, oxidative stress has been implicated as a potential responsible mechanism. Therefore, we aimed to investigate the protective role of erdosteine against CsA-induced nephrotoxicity in terms of tissue oxidant/antioxidant parameters and light microscopy in rats. Materials and methods: Wistar albino rats were randomly separated into four groups. Group 1 rats treated with sodium chloride served as the control, group 2 rats were treated with CsA, group 3 with CsA plus erdosteine, and group 4 with erdosteine alone. Animals were killed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (Cr), uric acid (UA), total protein (TP), and albumin (ALB) levels. Kidney sections were analyzed for malondialdehyde (MDA) and nitric oxide (NO) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, as well as for histopathological changes. Results: In the CsA group, MDA, GSH-Px, BUN, and Cr levels were increased. The TP and ALB levels were decreased. These changes had been improved by erdosteine administration. Other biochemical parameters did not show any significant change. Conclusion: These results indicate that erdosteine produces a protective mechanism against CsA-induced nephrotoxicity and suggest a role of oxidative stress in pathogenesis.

N-Acetylcysteine prevents doxorubucine-induced cardiotoxicity in rats

This study is designed to observe the effects of N-acetylcysteine (NAC) on doxorubucine-induced cardiac toxicity in rats both histologically and biochemically. Totally 32 rats divided equally into four groups were studied. The first group received only 200 mg/kg NAC intraperitoneal (i.p.) once every 24 h for 5 days (group 1); the second group received 20 mg/kg doxorubucine (DOX) i.p. single dose plus NAC 200 mg/kg i.p. once every 24 h for 5 days (group 2); the third group received DOX 20 mg/kg DOX i.p. single dose (group 3) and the fourth group, which is also the control group, received saline (group 4). Following 24 h of the final dose, blood samples were drawn from a portal vein and heart tissue were obtained. Tissue thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) levels were highest in the DOX group. In the DOX-treated rats, serum TBARS, NO, aspartate transaminase, lactate dehydrogenase and creatine kinase levels were highest when compared with other groups. Except for serum superoxide dismutase levels, all other parameters differed significantly between the DOX plus NAC group and the DOX group. In the DOX plus NAC group, general architecture was preserved better than the DOX group and myofibril loss was minimal compared with the DOX group. NAC demonstrated, both biochemically and histologically, to be effective in the prevention of DOX-induced cardiotoxicity in rat models. Evaluation of NAC’s effect on DOX toxicity warrants further clinical trials on cancer patients.

Determination of hearing levels in patients with Familial Mediterranean Fever

OBJECTIVE Familial Mediterranean Fever is the most common congenital, periodic fever condition that affects over 100,000 people worldwide. In the literature, there is limited number of studies about hearing levels in children with Familial Mediterranean Fever. In the present study, we aimed to investigate hearing levels and cochlear functions by using Distortion product Otoacoustic Emission and High Frequency Audiometry (250-20,000 Hz) in pediatric patients with Familial Mediterranean Fever. METHODS The study included 62 children with Familial Mediterranean Fever and 27 healthy children with similar age and gender. After otoscopic examination, both groups underwent audiological evaluation including High Frequency Audiometry (250-20,000 Hz) and Distortion product Otoacoustic Emissions. The results obtained were assessed among groups. In addition, these results were compared regarding colchicine use, age at the onset of disease and duration of the diseases in the Familial Mediterranean Fever group. RESULTS Of the Familial Mediterranean Fever patients, 93.5% were on colchicine therapy and mean duration of colchicine use was 19.9 ± 13.9 months. The mean age at diagnosis was 6.57 ± 2.86 years (min-max: 2-14) and mean duration of disease was 23 ± 17 months (min-max: 6-84). Pure tone audiometry values, and hearing levels between 9000 and 20,000 Hz were similar and within normal range in both groups. The Distortion product Otoacoustic Emissions responses at the frequencies of 1020, 2040, 3000, 4080 and 5040 Hz were similar for both groups. CONCLUSION To the best of our knowledge, this is the first study evaluating hearing levels at the frequencies of 18k Hz and 20k Hz in children with Familial Mediterranean Fever in the literature. In children with Familial Mediterranean Fever, Pure tone audiometry values, hearing values obtained at all frequencies from 250 to 20,000 Hz, and Distortion product Otoacoustic Emissions levels were within normal range. Furthermore, hearing levels were found to be similar to those in healthy children.

Pediatric neurobrucellosis associated with hydrocephalus

Brucellosis is an infectious disease, frequently encountered in developing countries. It may involve multiple organ systems of the human body. However, neurobrucellosis is a rare complication of brucellosis. The most frequent events of cranial involvement are meningitis and meningoencephalitis. In the present case, a 10-year-old girl was referred to our clinic with fever, headache, nausea, and vomiting. The patient’s blood and cerebrospinal fluid cultures were found positive for brucellosis. Communicating hydrocephalus was also present in the cranial computed tomography as a complication of neurobrucellosis. The patient was successfully treated by external ventricular drainage and triple antibiotic therapy. There was no need to insert a ventriculo-peritoneal shunt.

Mean platelet volume can predict cerebrovascular events in patients with Sickle Cell Anemia

Objective: The purpose of this study was to determine the impact of mean platelet volume (MPV) on the frequency and severity of vaso-occlusive and cerebrovascular events in patients with sickle cell anemia (SCA). Methods: The 238 cases diagnosed with SCA were evaluated retrospectively with respect to the occurrence of painful crisis for the previous year. The incidence, severity and type of the vaso-occlusive crises of the patients with SCA between March 2010 and March 2011 were recorded. The last MPV values in patients who were free of erythrocyte transfusion for the last three months and who had no current vaso-occlusive crises were evaluated. All the patients were grouped according to the frequency of the crises for the previous year preceding the data collection. Group 1: 1 to 3 crises, Group 2: 4 to 5 and Group 3: 6 or more crises annually. Results: In accordance with the results obtained during the evaluation of the cases diagnosed with sickle-cell anemia, MPV value was found to be significantly higher in patients with cerebrovascular events. Also MPV values increased with increasing incidence of the crises (r=0.297) (p=0.001). Conclusion: One of the contributing factors for this clinical heterogeneity may be related to the MPV values in patients with sickle cell anemia. The higher MPV values may be an early predictor of future cerebrovascular events in patients with sickle cell anemia and may require close follow-up and additional measures.

The scintigraphic evaluation and genetic correlation of joint involvements in pediatric patients with familial Mediterranean fever.

Purpose: We aimed to evaluate the articular involvements in pediatric patients with familial Mediterranean fever (FMF) with joint symptoms by bone scintigraphy and to correlate the involved joints with the gene mutations. Materials and methods: A total of 41 newly diagnosed patients in pediatric age group (28 girls and 13 boys; mean age 9.14 ± 2.91 years) with joint involvement symptoms were included in this study. Scintigraphic images were obtained at 5th min (blood pool or early phase) and starting at 3 h (late phase) after (after tracer injection) intravenous administration of technetium-99m (99mTc)-methylendiphosphonate (MDP). Genomic DNA was isolated from leukocytes using standard salting out procedure. The sequencing data were analyzed. Results: Of the 41 patients, arthritis was found in 21 (51.2%) patients. Of the 21 patients, there was single joint involvement in 15 (71.4%) patients and multiple joint involvement in six (28.6%) patients. The mean age of patients with joint involvement (8 ± 2.3 years) were considerably lower than the patients without joint involvement (10.35 ± 3.04 years), and this was statistically significant (p = 0.008). The most commonly involved joints were ankles and knees. Multiple joint involvements were most frequently observed in the M694V and M694I gene mutations (16.7%). Conclusions: We use and recommend the bone scintigraphy in patients with FMF to determine the presence and distribution of arthritis, since bone scintigraphy is inexpensive, noninvasive, easy-to-use, and also is more sensitive in the diagnosis and distribution of arthritis than conventional radiological methods and clinical examination.