Improvement of survival after hematopoietic stem cell transplantation and trends at a pediatric transplantation center; a three-decade journey.

BACKGROUND: Advances in stem cell transplantation have resulted in improved outcomes. METHODS: This is a retrospective study aimed to analyze changes in patient profile, transplantation, graft characteristics, and outcome among 241 pediatric patients who received stem cell transplantation in a single center between 1993 and 2019. RESULTS: In the 2010-2019, compared with the 1993-2009 period, a significantly higher 5-year overall survival (60% vs. 44%, p = .022) and an event-free survival (53% vs. 34%, p = .025) were observed. Cumulative incidence of deaths due to relapse or progression between the 1993-2009 and 2010-2019 periods were 33% and 26% respectively (p = .66). Cumulative incidence of non-relapse mortality was significantly higher during the 1993-2009 period compared with the 2010-2019 period for malignant diseases (57.7% vs. 28.3%, p = .007). The overall survival from acute graft-versus-host disease between 1993 and 2009 was 11% versus 46% between 2010 and 2019 (p = .0001). The overall survival from infection in both eras did not show any difference (p = .41). CONCLUSIONS: Development in transplantation technology has led to a decrease in non-relapse mortality and better control of graft-versus-host disease. However, relapse and infection remained as major causes of death. Studies evaluating institutional trends in patients undergoing HSCT and analyzing their mortality profile, can improve the management of patients, leading to a reduction in transplant-related problems.

Nimotuzumab-vinorelbine combination therapy versus other regimens in the treatment of pediatric diffuse intrinsic pontine glioma.

PURPOSE: Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18 years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens. METHODS: After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed. RESULTS: The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12 months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12 months in all patients (n = 40), and it was 16, 10, and 11 months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16 months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4 months. CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.

Associations between neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and prognosis in patients with neuroblastoma.

OBJECTIVES: Recent studies have shown that the neutrophil-to-lymphocyte ratio (NLR) is a new inflammatory marker that is effective in determining the prognosis of many solid tumors, chemotherapy responses, survival, and their recurrence rate. Therefore, we performed a retrospective study to investigate the effect of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio (PLR) on risk factors and prognosis in these patients. MATERIALS AND METHODS: In this study, 246 pediatric patients with neuroblastoma who were diagnosed, treated, and followed up during 2000-2021 in Division of Pediatric Oncology, Çukurova University Faculty of Medicine, were included. Required information of patients was obtained from archive files, Mergentech hospital program, and E-pulse system. RESULTS: Median value for NLR was found to be 1.06, for PLR it was found as 92. The relationship of NLR values with age, stage, risk group, and Shimada was found to be statistically significant with p < .001, vanillylmandelic acid (VMA) (p = .006) also depicted the significant value. Likewise, the relationship of PLR values with age (p < .001), stage (p = .022), Shimada (p = .004), and N-Myc amplification (p = .039) was found to be statistically significant as well. Survival analysis showed that no statistically significant difference was observed among the higher and lower values of NLR. Survival rates were noticed to be higher in the lower values of NLR (10-year overall survival [OS] 55% vs. 49%, 10-year event-free survival (EFS) 54% vs. 43%), albeit nonsignificant. CONCLUSION: Pretreatment evaluation of NLR and PLR values in patients with neuroblastoma may be instructive in respect of prognosis and risk group.

Contributions of Chemical Content and Biological Activity to Plant Taxonomy Based on the Four Allium L. Taxa (Sect. Cupanioscordum - Amaryllidaceae).

Garlic and onions are used as food and for medicinal purposes worldwide. Allium L. species are rich in bioactive organosulphur compounds that exhibit many biological activities like anticancer, antimicrobial, antihypertensive, antidiabetic activities. In this study, macro- and micromorphological characteristics of four Allium taxa were examined and the results suggested that A. callimischon subsp. haemostictum was the outgroup to sect. Cupanioscordum. Also, for the genus Allium, which is a taxonomically difficult genus, the hypothesis that chemical content and bioactivity can also be used taxonomically in addition to micro and macromorphological characters has been questioned. The bulb extract was analyzed to determine their volatile compositions and anticancer activities against human breast cancer, human cervical cancer, and rat glioma cells for the first time in the literature. To detect the volatiles, the Head Space-Solid Phase Micro Extraction method was used followed by Gas Chromatography-Mass Spectrometry. The main compounds were found as dimethyl disulfide that (36.9 %, 63.8 %, 81.9 %, 12.2 %) and methyl (methylthio)-methyl disulfide (10.8 %, 6.9 %, 14.9 %, 60.0 %) for A. peroninianum, A. hirtovaginatum and A. callidyction, respectively. Additionally, methyl-trans-propenyl disulfide is detected for A. peroniniaum (36 %). As a result, all extracts have shown significant efficacy against MCF-7 cells depending on applied concentrations. The treatment of MCF-7 cells for 24 h with 10, 50, 200, or 400 µg/mL ethanolic bulb extract of four Allium species resulted in DNA synthesis inhibition. Survival rates for A. peroninianum was 51.3 %, 49.7 %, 42.2 %, 42.0 %, for A. callimischon subsp. haemostictum 62.5 %, 63.0 %, 23.2 %, 22 %, for A. hirtovaginatum 52.9 %, 42.2 %, 42.4 %, 39.9 %, for A. callidyction 51.8 %, 43.2 %, 39.1 %, 31.3 %, for cisplatin 59.6 %, 59.9 %, 50,9 %, 48.2 %, respectively. Moreover, taxonomic evaluation according to biochemical compounds and bioactivities is almost in agreement with that made according to micro and macromorphological characters.

Effects of adropin on learning and memory in rats tested in the Morris water maze.

Adropin is a secreted peptide, which is composed of 43 amino acids and shows an effective role in regulating energy metabolism and insulin resistance. Motor coordination and locomotor activity were improved by adropin in the cerebellum. However, it is not known whether adropin administration has an effect on spatial learning and memory. In this study, we investigated the effect of adropin on spatial learning and memory and characterized the biochemical properties of adropin in the hippocampus. Thirty male Sprague-Dawley rats were randomly divided into two groups as control and adropin groups. The control group received 0.9% NaCl intracerebroventricular for 6 days, while the adropin groups received 1 nmol of adropin dissolved in 0.9% NaCl (for 6 days). The Morris water maze, Y maze, and object location recognition tests were performed to evaluate learning and memory. Also, the locomotor activity tests were measured to assess the motor function. The expression of Akt, phospho-Akt, CREB, phospho-CREB, Erk1/2, phospho-Erk1/2, glycogen synthase kinase 3 ß (GSK3ß), phospho-GSK3ß, brain-derived neurotrophic factor (BDNF), and N-methyl-d-aspartate receptor NR2B subunit were determined in the hippocampal tissues by using western blot. Behavior tests showed that adropin significantly increase spatial memory performance. Meanwhile, the western blot analyses revealed that the phosphorylated form of the Akt and CREB were enhanced with adropin administration in the hippocampus. Also, the expression of BDNF showed an enhancement in adropin group in comparison to the control group. In conclusion, we have shown for the first time that adropin exerts its enhancing effect on spatial memory capacity through Akt/CREB/BDNF signaling pathways.

Total nucleated cell dose in graft is a better prognostic factor for survival in pediatric patients transplanted with bone marrow compared to CD34+, CD3+, or total mononuclear cell count.

BACKGROUND: Most studies investigating the impact of graft composition on transplant-related outcomes have focused on the effect of CD34+ cell dose and reported equivocal results. The aim of this study is to investigate the impact of doses of total nucleated cells (TNCs), total mononuclear cells (TMCs), CD3+, and CD34+ cells on the outcome of children receiving allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: Children and adolescents who underwent allogeneic HSCT for malignant hemato-oncological diseases or nonmalignant diseases in Cukurova University Faculty of Medicine, Pediatric Bone Marrow Transplantation Center between 2010 and 2020 were enrolled in the study. RESULTS: A total of 212 patients receiving allogeneic HSCT (154 bone marrow transplantation; 58 peripheral blood stem cell transplantation) from matched related or unrelated donors were included in the study. Higher TNC doses associated with a superior 5-year event-free survival (EFS; 67.7% vs 44.7%) in the whole group (log-rank P = .027). Overall survival (OS) and EFS of bone marrow-transplanted patients differed significantly according to TNC doses (log-rank P = .041 and .027, respectively). Multivariant analysis for OS revealed a P value of .038 for TNC, Exp(B) = 1.939 (95% CI: [1.038, 3.621]). That for EFS revealed a P value of .025 for TNC, Exp(B) = 1.992 (95% CI: [1.088, 3.647]). There was no relationship between doses of CD34+ cells, CD3+ cells, TMC, TNC, and neutrophil or platelet engraftment. CONCLUSION: Our data suggest that TNC dose is a better prognostic factor for pediatric allogeneic HSCT outcomes than doses of CD34+ cells, CD3+ cells, or TMC in patients transplanted with bone marrow. Future studies analyzing cell subsets and other components in TNC could elaborate the factor(s) accompanying this observed survival advantage.

Clinical Impact of KIR2DS3 and KIR2DL3 Genes in Neuroblastoma Patients.

OBJECTIVE: Neuroblastoma is a common fatal tumor of childhood. Natural killer (NK) cells can exert direct cytotoxicity on tumor cells. The killer immunoglobulin-like receptor (KIR) family of NK cell receptors is involved in activation/inhibition of NK cells. In the KIR gene cluster, six of them (3DS1, 2DS1-5) encode receptors triggering activation, while seven of them (3DL1-3, 2DL1-3, 2DL5) encode receptors triggering inhibition. We aimed to assess the distribution of genetic polymorphisms of KIRs on the clinical course of neuroblastoma and provide guidance on potential therapeutic options. METHODS: Our study group included 50 neuroblastoma patients and 100 healthy children as controls. Twenty-eight patients were boys, and twenty-two were girls; median age was 36 months. Fourteen patients had stage 1, 2, 3, or 4S disease, and 36 patients had stage 4 disease. Isolated DNA from the peripheral blood was amplified for sequence-specific oligonucleotide probe analysis of 16 KIR genes. The Fisher's exact test was used to evaluate the variation of KIR gene distribution. RESULTS: All patients had a lower frequency of KIR2DS3 compared to the control group (p = 0.005). Evaluation of individual KIR genes/genotypes in patients with early stages (stage 1, 2, 3, and 4S) versus stage 4 disease revealed that the frequency of KIR2DS3 was increased in early stages (p = 0.023). Inhibitory KIR2DL3 was increased in the patient group compared to controls (p = 0.038). Furthermore, the frequency of KIR2DL3 was higher in stage 4 neuroblastoma patients compared to the patients with early stages (p = 0.023). CONCLUSION: Our data suggest a role for KIR2DS3 and KIR2DL3 in development of neuroblastoma. Thus, modulation of KIR2SD3 and/or KIR2DL3 expression or function might present a novel therapeutic strategy for neuroblastoma.

Protective mechanism of Syringic acid in an experimental model of Parkinson's disease.

6-Hydroxydopamine (6-OHDA) is a widely used chemical to model Parkinson's disease (PD) in rats. Syringic acid (SA) is a polyphenolic compound which has antioxidant and anti-inflammatory properties. The present study aimed to evaluate the neuroprotective role of SA in a rat model of 6-OHDA-induced PD. Parkinson's disease was created by injection of 6-OHDA into the medial forebrain bundle via stereotaxic surgery. Syringic acid was administered daily by oral gavage, before or after surgery. All groups were tested for locomotor activity, rotarod performance and catatony. Dopamine levels in SN were determined by an optimized multiple reaction monitoring method using ultra-fast liquid chromatography coupled with tandem mass spectrometry (MS/MS). The immunoreactivities for tyrosine hydroxylase (TH) and inducible nitric oxide synthase (iNOS) were detected by immunohistochemistry in frozen substantia nigra (SN) sections. Nitrite/nitrate levels, iNOS protein, total oxidant (TOS) and total antioxidant (TAS) status were assayed in SN tissue by standard kits. Motor dysfunction, impaired nigral dopamine release, increased iNOS expression and elevated nitrite/nitrate levels induced by 6-OHDA were significantly restored by SA treatment. Syringic acid significantly improved the loss of nigral TH-positive cells, while increasing TAS capacity and reducing TOS capacity in SN of PD rats. These data conclude that SA is a potential therapeutic agent for the treatment of 6-OHDA-induced rat model of PD. Syringic acid reduced the progression of PD via its neuroprotective, antioxidant and anti-inflammatory effects.

The effect of chronic neuropeptide-S treatment on non-motor parameters in experimental model of Parkinson's disease.

AIM: Besides motor impairment, non-motor symptoms including cognitive decline, anxiety, and depression are observed in Parkinson's Disease (PD). The aim of this study was to investigate whether chronic administration of central neuropeptide-S (NPS) improves non-motor symptoms in 6-hydroxydopamine (6-OHDA)-induced parkinsonian rats. MATERIAL AND METHODS: Experimental PD was utilized by unilateral stereotaxic injection of the 6-OHDA into the medial forebrain bundle (MFB), while the sham-operated animals underwent the same surgical procedures. NPS (1 nmol) or vehicle was daily administered through an intracerebroventricular (icv) cannula for 7 days. Radial arm maze (RAM) test was used to evaluate the working memory; whereas, elevated plus maze (EPM) test and sucrose preference test were used to monitor the anxiety and depression status, respectively. The levels of dopamine, glutamic acid, and glutamine was determined in harvested striatal and hippocampal tissue samples. The immunoreactivities for tyrosine hydroxylase (TH) was determined using immunohistochemistry. RESULTS: In the RAM test, the 6-OHDA-induced increases in the reference and working memory errors were reduced by the central NPS administration. The decreased sucrose preference in the parkinsonian rats was increased by centrally administered NPS. The levels of dopamine levels in striatum and hippocampus were decreased in the parkinsonian rats, however, they were not altered by the centrally administered NPS. Additionally, NPS treatment significantly attenuated the 6-OHDA-induced loss of TH neuronal number. CONCLUSION: Consequently, NPS appears to be a therapeutic candidate for the treatment of non-motor complications of PD.

Neuropeptide-S affects cognitive impairment and depression-like behavior on MPTP induced experimental mouse model of Parkinson's disease

Background/aim: The present study proposes to investigate the effect of neuropeptide­S (NPS) on cognitive functions and depression-like behavior of MPTP-induced experimental model of Parkinson's disease (PD). Materials and methods: Three-month-old C57BL/6 mice were randomly divided into three groups as; Control, Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and MPTP + NPS 0.1 nmol (received intraperitoneal injection of MPTP and intracerebroventricular injection of NPS, 0.1 nmol for seven days). The radial arm maze and pole tests were carried out, and the levels of tyrosine hydroxylase (TH) were determined using western blotting. A mass spectrometer was used to measure the levels of dopamine, glutamic acid, and glutamine. Results: The T-turn and time to descend enhanced in MPTP group, while these parameters were decreased by NPS treatment. In the MPTP group, the number of working memory errors (WME) and reference memory errors (RME) increased, whereas NPS administration decreased both parameters. Sucrose preference decreased in the MPTP group while increasing in the NPS group. MPTP injection significantly reduced dopamine, glutamic acid, and glutamine levels. NPS treatment restored the MPTP-induced reduction in glutamine and glutamic acid levels. Conclusion: NPS may be involved in the future treatment of cognitive impairments and depression-like behaviors in PD.

The Role of Anti-Neutrophil Antibodies in the Etiologic Classification of Childhood Neutropenia: A Cross-Sectional Study in a Tertiary Center.

Infections, drugs, malignancies, immunodeficiency, and autoimmunity may cause neutropenia. In primary autoimmune neutropenia, anti-neutrophil antibodies (ANeuA) bind to membrane antigens of neutrophils, which give rise to peripheral destruction of neutrophils. However, it is not always easy to detect these antibodies. This study aims to investigate the etiology of neutropenia, and at the same time to evaluate the immune mechanisms by ANeuA testing using granulocyte indirect immunofluorescence test. In our study, 310 neutropenic patients who were between 3 months and 18 years of age were evaluated. ANeuA screening tests were performed in 108 neutropenic patients (group 1), and these patients were divided into 2 subgroups as persistent neutropenia (group 1P, n=12) and recovered neutropenia (group 1R, n=96). Besides, a control group in the same age range was formed, consisting of 39 non-neutropenic children (group 2). ANeuA serum levels were also checked in these groups, and no statistically significant difference could be found between groups 1 and 2, or between groups 1P and 1R, regarding ANeuA levels. As a conclusion, our study was the first comprehensive research in Turkey investigating the large-scale etiology of neutropenia. Moreover, while ANeuA screening tests did not provide sufficient insight for immune neutropenia, we argue that it is not necessary for routine use and that further research in the etiology of neutropenia is required.

Syrian and Turkish children with cancer: a comparison on survival and associated factors.

Cure rates of childhood cancer need to be improved in low-income countries and vulnerable populations such as refugees. We aimed to compare the outcome and associated factors in Syrian refugee and Turkish children with cancer treated at our hospital.Files of patients were reviewed for age, tumor type, stage, treatment, compliance to treatment, relapse or progression status, outcomes, secondary malignancy (SM) and treatment-related mortality (TRM). Overall (OS) and event-free survival rates (EFS) were analyzed.105 refugees and 304 Turkish children were treated between January 2012 and January 2019. Median age and median follow-up time were significantly lower in the Syrian group (p=0.046, p<0.001, respectively). Metastatic or advanced-stage disease was significantly more frequent in refugees (p=0.002). Relapse or progression and poor compliance to treatment were more common in refugees (p=0.01, p<0.001, respectively). Rates of OS were 55.7% and 69.7%, EFS were 28.9% and 55.7% in Syrian and Turkish patients. OS and EFS were lower in refugees compared to Turkish patients (p=0.01, p<0.001, respectively). EFS was significantly lower in refugees with poor compliance to treatment (p<0.001). TRM was reported in 12 (8 Syrian, 4 Turkish) patients. SM was detected in 3 (2 Turkish, 1 Syrian) children.Inferior survival rates were detected in Syrian refugee children compared to Turkish children. Besides from cancer-specific factors such as stage and tumor type, a series of barriers in accessing cancer care resulting in poor compliance to treatment might have been responsible from lower survival rates in Syrian children.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

The effect of ingested sulfite on active avoidance in normal and sulfite oxidase-deficient aged rats.

The aim of this study was to investigate the possible toxic effects of sulfite on neurons by measuring active avoidance learning in normal and sulfite oxidase (SOX)-deficient aged rats. Twenty-four months of age Wistar rats were divided into four groups: control (C), sulfite-treated group (S), SOX-deficient group (D) and SOX-deficient + sulfite-treated group (DS). SOX deficiency was established by feeding rats with a low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg/kg) was given by gavage for six weeks. Active avoidance responses were determined by using an automated shuttle box. Hepatic SOX activity was measured to confirm SOX deficiency. The hippocampus was used for determining the activity of cyclooxygenase (COX) and caspase-3 enzymes and the level of prostaglandin E2 (PGE2) and nitrate/nitrite. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with normal rats. Sulfite did not induce impairment of active avoidance learning in SOX-deficient rats and in normal rats compared with their control groups. Sulfite had no effect on the activity of COX and caspase-3 in the hippocampus. Treatment with sulfite did not significantly increase the level of PGE2 and nitrate/nitrite in the hippocampus.

Contribution of ellagic acid on the antioxidant potential of medicinal plant Epilobium hirsutum.

In the present study, the possible role of ellagic acid (EA) on antioxidant potential of Epilobium hirsutum (EH) in rat liver was investigated. Wistar rats were intraperitoneally treated with 37.5 mg/kg of EH and 10 mg/kg of EA for 9 days. Effects of EH and EA on antioxidant [glutathione peroxidase (GPx) and superoxide dismutases (SOD)] and Phase II [NADPH quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs)] enzyme activities, as well as protein and mRNA expressions of those, were investigated. Polyphenolic content of EH was determined by LC-MS/MS analysis. EH and EA injection to rats resulted in a significant increase of NQO1 (3.6-fold and 4.7-fold), GPx (1.45-fold), and SOD (1.34-fold and 1.27-fold) enzyme activities, whereas total GST (46% and 57%) and its isoforms,and GST mu (57% and 72%), and GST theta (60% and 68%) activities were significantly decreased. Western-blot and qRT-PCR analysis showed that NQO1 and GPx protein and mRNA expressions were increased significantly (P < 0.0001), whereas GST mu and GST theta were significantly decreased (P < 0.0001).

The effect of ingested sulfite on visual evoked potentials, lipid peroxidation, and antioxidant status of brain in normal and sulfite oxidase-deficient aged rats.

Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains.

Treatment of Wilms tumor using carboplatin compared to therapy without carboplatin.

BACKGROUND: Wilms tumor (WT) is the most common pediatric malignant primary renal tumor. One of the main drugs used in treatment is actinomycin-D. This was not readily available in Turkey at one time. Carboplatin was used in the primary treatment of WT in order to prevent delays in treatment. The aim of this study is to present the results of patients with WT receiving carboplatin or actinomycin-D therapy. PROCEDURE: Forty-eight consecutive patients with WT treated between July 2005 and December 2011 were included in this retrospective study. The patients were treated according to Turkish Pediatric Oncology Group guidelines. Nineteen patients were treated with actinomycin-D and 29 with carboplatin (500 mg/m(2) /dose). The two groups were then compared in terms of 2- and 4-year overall survival (OS), event-free survival (EFS) and disease-free survival (DFS). RESULTS: Two- and four-year OS rates in the carboplatin group were 90.0% and 90.0%, compared to 100.0% and 88.0%, respectively, in the non-carboplatin group. Two- and four-year EFS levels in the carboplatin group were 92.0% and 88.0%, respectively, compared to 82.0% and 76.0% in the non-carboplatin group. Two-and four-year DFS levels in the carboplatin group were 92.0% and 86.0%, respectively, compared to 77.0% and 77.0% in the non-carboplatin group. CONCLUSIONS: The findings show that the carboplatin can be used as an alternative drug in the primary treatment of WT in the event that actinomycin-D is unavailable or not tolerated.

Dermatopathic lymphadenitis associated with human papilloma virus infection and verruca vulgaris.

Here we present a pediatric case of human papilloma virus associated with dermatopathic lymphadenitis (DL). A 5-year-old boy presented to the pediatric oncology clinic with swelling of the neck and warts on his lower jaw. His blood chemistry and complete blood count were normal, as was chest x-ray. HIV, EBV, CMV, and parvovirus serologies were negative. The patient was investigated for malignancy and lymphoma but no association was found. Histopathologic examination of the lymph node and the lesion revealed DL and verruca vulgaris, respectively. DL represents a benign form of reactive lymph node hyperplasia and described in patients with HIV and EBV infections. It is a rare entity described in patients with human papilloma virus infection. To our knowledge, this is the first report of DL in a patient with human papilloma virus infection.

The protective effect of hesperidin on methotrexate-induced intestinal epithelial damage in rats: an experimental study.

OBJECTIVE: The purpose of this experimental study was to evaluate the efficacy of hesperidin (HES) in protecting against methotrexate (MTX)-induced intestinal damage using histopathological and immunohistochemical techniques. MATERIALS AND METHODS: Seventy-eight male Wistar albino rats were divided into 4 groups that received (a) saline only (control group), n = 19; (b) HES only, n = 19; (c) MTX only, n = 19, and (d) MTX plus HES, n = 21. On the first day of the study, a single dose of MTX (20 mg/kg) was administered intraperitoneally to group 3 and 4 rats. The HES (200 mg/kg) was administered by gavage for 5 days. For the MTX plus HES group, HES (200 mg/kg) was administered by gavage for 5 days after MTX treatment. Rats were sacrificed on the 2nd, 4th and 6th day of the study. Tissue samples from the jejunum were taken for histopathological and immunohistochemical analysis. RESULTS: On the 4th day, crypt injury in the MTX plus HES group (1.00 ± 0.00) was less than that in the MTX group (2.00 ± 0.89; p < 0.05). The small intestinal damage score was lower in the MTX plus HES group (6.33 ± 0.82) as compared to the MTX group (8.00 ± 2.37). Inducible nitric oxide synthase and interleukin-8 levels were lower in the MTX plus HES group (65 and 25%, respectively) as compared to the corresponding values of the MTX group (80 and 52.5%, respectively). On the 6th day, the Ki-67 proliferation index in the MTX group (45%) was lower than that in the MTX plus HES group (76.67%) and the control group (p < 0.05). The small intestinal damage score was high in the HES group on the 4th day due to increased cellular infiltration. On the 6th day, the Ki-67 proliferation index rose in parallel with the decrease in cellular infiltration and therefore histopathological scoring. The proliferation-enhancing effect of HES also appeared in healthy rats. CONCLUSION: HES seemed to have a protective effect against MTX-induced intestinal injury.

Epilobium hirsutum alters xenobiotic metabolizing CYP1A1, CYP2E1, NQO1 and GPx activities, mRNA and protein levels in rats.

CONTEXT: Natural products have attracted increasing interests due to their use in flavoring, nutrition, cosmetics, pharmacy and medicine. Epilobium hirsutum L. (Onagraceae) is known for its analgesic, antimicrobial, and antiproliferative activity. CYP1A1 and CYP2E1, xenobiotic metabolizing enzymes, serve as a metabolic activation route yielding reactive metabolites that are eliminated by the action of NQO1 and glutathione peroxidase (GPx) enzymes. OBJECTIVE: This study investigated in vivo effects of Epilobium hirsutum (EH) on CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA expressions in liver. MATERIALS AND METHODS: Male Wistar Albino rats were injected with EH at a dose of 37.5 mg/kg i.p. daily for 9 d. CYP2E1, CYP1A1, NQO1 and GPx activities, protein and mRNA levels were determined by enzyme assays, Western blotting and qPCR, respectively. RESULTS: CYP1A1 associated ethoxyresorufin-O-deethylase activity of control and EH-treated animals were found as 6.54 ± 1.21 and 4.48 ± 1.67 nmol/min/mg, respectively. CYP2E1 associated aniline 4-hydroxylase of control and EH group were 0.537 ± 0.011 and 0.109 ± 0.01 nmol/min/mg, respectively. However, EH treatment increased the GPx and NQO1 activities from 0.069 ± 0.015 to 0.107 ± 0.026 nmol/min/mg and from 163.34 ± 92 to 588.3 ± 14 nmol/min/mg, respectively. Furthermore, protein and mRNA expression analysis revealed that CYP1A1 and CYP2E1 levels were decreased while those of NQO1 and GPx increased after EH treatment. DISCUSSION AND CONCLUSION: Our current data suggest that the metabolism of xenobiotics, including drugs, may be altered due to changes in the expression and activity of these proteins by EH.