N-acetylcysteine supplementation reduces oxidative stress for cytosine arabinoside in rat model.

Cytosine arabinoside (ARA-C) is a pyrimidine analog that may cause keratoconjunctivitis when used in high doses. The underlying mechanism may be the increased amounts of reactive oxygen radicals that may damage the DNA synthesis of corneal and conjunctival epithelial cells. Topical corticosteroids are one of the prophylactic treatments for keratoconjunctivitis induced by ARA-C. Forty Wistar-type albino rats were included in this study the rats were divided into four groups. The first group (Group 1) received only ARA-C, the second group (Group 2) received ARA-C and N-acetylcysteine (NAC), the third group (Group 3) received only NAC and the fourth group (Group 4) was the control group. The total oxidant status (TOS), the total antioxidant capacity and the oxidative stress index (OSI) measurements of the cornea and the conjunctiva were evaluated in these four groups. The mean TOS and OSI value was the highest in Group 1 and the lowest in Group 3. The differences in TOS and OSI values were statistically significant between Group 1 and Group 2. There are decreases in TOS and OSI values in rats which received ARA-C with NAC administration. NAC may have a protective effect on ARA-C-induced keratoconjunctivitis.

Pentraxin-3 Levels in Beta Thalassemia Major and Minor Patients and Its Relationship With Antioxidant Capacity and Total Oxidant Stress.

Thalassemia major (TM) results in hemolytic anemia, an increase in intestinal iron absorption, and occurrence of iron loading due to erythrocyte transfusion; the disease is characterized by oxidative damage in major organs. Oxidative stress leads to vascular endothelial damage and forms the basis for serious cardiovascular diseases. Pentraxin-3 (PTX-3) is one of the markers of vascular endothelial damage that increases in response to the oxidative stress, which can be used as an early diagnostic marker for inflammation. This study's purpose is to define the relation between PTX-3 and the vascular endothelial damage that increases with oxidative stress in thalassemia patients. Our study included 35 TM patients, 30 ß-thalassemia minor patients, and 30 healthy children. As a result of our study, in TM patients, a positive relation was detected between the PTX-3 levels and the total oxidative stress, triglyceride, and very low-density lipoprotein values, whereas a negative relation was detected with the total antioxidant capacity and high-density lipoprotein values. This result shows that as oxidant stress increases, PTX-3 levels also increase; very low-density lipoprotein and triglyceride contribute to the endothelial damage occurring with oxidative stress. As a result, it was concluded that vascular endothelial damage in thalassemia patients can be evaluated through the serum PTX-3 level.

Evaluation of Reticulocyte Parameters in Iron Deficiency, Vitamin B12 Deficiency and Mixed Anemia.

BACKGROUND: Reticulocytes are the youngest erythrocytes released from the bone marrow into the blood and they circulate for 1-2 days before becoming mature erythrocytes. In literature, there were studies about reticulocyte parameters that could help in differentiation of iron deficiency anemia (IDA) from vitamin B12 deficiency anemia. However, in those studies there were no data about differentiation of mixed anemia (vitamin B12 deficiency and IDA). The purpose of this study is to explore a response to 'could reticulocyte parameters help in differential diagnosis of mixed anemia?' in 6-12 years old children. METHODS: The study enrolled 26 patients with IDA, 22 patients with mixed anemia, 32 patients with vitamin B12 deficiency, and 32 age and gender matched healthy controls. Blood for hematological parameters such as complete blood count, reticulocyte count, CHr, MCVr, CHCMr were collected into standard tubes containing EDTA. RESULTS: There is a statistically significant difference of both MCV (mean corpuscular volume)/MCVr (Reticulocyte mean corpuscular volume) ratio and MCVr between IDA and controls; in controls and vitamin B12 deficiency anemia; in controls and mixed anemia; in IDA and vitamin B12 deficiency anemia; in IDA and mixed anemia. Also in terms of both CHr and CHCMr (Corpuscular mean hemoglobin concentration of reticulocyte), there is a statistically significant difference between controls and IDA; controls and mixed anemia; IDA and mixed anemia; IDA and vitamin B12 deficiency anemia. CONCLUSIONS: In mixed anemia, MCV could be normal or decreased, and in peripheral blood smear erythrocytes cells could be morphologically normal. For this reason diagnosis of mixed anemia is not easy and needs additional laboratory investigations. Our results suggest that in a differential diagnosis of mixed anemia from vitamin B12 deficiency, IDA, and healthy controls, CHr, CHCMr, and MCVr (together with MCV and individually) could be useful. So, with a simple and cheap laboratory parameter, differentiation of mixed anemia could be done.

Adipocytokine concentrations in children with different types of beta-thalassemia.

BACKGROUND: Beta-thalassemia is an inherited blood disorder. It results from the impaired production of ß-globin chains, leading to a relative excess of alpha-globin chains. Clinical severity separates this disease into three main subtypes: ß- thalassemia major, ß-thalassemia intermedia and ß-thalassemia minor, the former two being clinically more significant. Inflammatory processes may play an important role in some of the complications of thalassemia. Adipose tissue is one of the most important endocrine and secretory organs that release adipocytokines like adiponectin, resistin and visfatin. AIM: The aim of our study was to analyze adipocytokine concentrations (adiponectin, resistin and visfatin) in different types of ß-thalassemia patients and determine any possible correlations with disease severity. METHODS: We recruited 29 patients who were transfusion-dependent ß-thalassemia-major patients, 17 patients with ß-thalassemia intermedia, 30 ß-thalassemia minor patients. The control group consisted of 30 healthy children. Anthropometric measurements, complete blood count, biochemical parameters, serum concentrations of adiponectin, resistin, visfatin were performed for all subjects. RESULTS: Resistin and visfatin concentrations were significantly higher in ß-thalassemia minor patients than in controls. Adiponetin, resistin and visfatin concentrations were significantly higher in both ß-thalassemia intermedia and major patients than in controls. The concentrations of adiponectin, resistin and visfatin were significantly higher in both ß-thalassemia intermedia and major patients than in ß-thalassemia minor patients. There was no significant difference between ß-thalassemia intermedia and ß-thalassemia major patients for adipocytokines concentrations. CONCLUSION: We speculate that these adipocytokines may play a role in the development of complications in ß-thalassaemia.

Serum vitamin B12 and folate concentrations and the effect of the Mediterranean diet on vulnerable populations.

Low vitamin B12 and folate levels in expectant mothers may lead to low stores in babies. The aim of this study was to determine the frequencies of vitamin B12 and folate deficiencies in pregnant women and neonates, and to assess the effect of maternal vitamin status on babies' vitamin levels in the Aegean region of Turkey, where the Mediterranean diet (mainly fresh fruits and vegetables) is adopted. We studied 72 pregnant women and their singleton-term babies. Venous blood samples of expectant mothers were collected 1 h before delivery and cord blood of babies were obtained at birth. The mean vitamin B12 in maternal and cord blood serum was 163.1 ± 72.0 pg/mL and 146.2 ± 102.5 pg/mL, and the mean folate, 9.8 ± 4.8 ng/mL and 15.8 ± 3.8 ng/mL, respectively. There were statistically significant correlation between maternal and cord blood serum vitamin B12 (r = 0.61, P = .04) and folate levels (r = 0.65, P < .001). 70.8% of the mothers and 83.9% of the babies were vitamin B12 deficient (<200 pg/mL). Neither group showed folate deficiency. The mean level of vitamin B12 in mothers significantly varied by the type of diet (241.6 (72.1) pg/mL versus 155.9 (68.2) pg/mL; P = .012). Vitamin B12 deficiency in pregnant women and neonates may be a public health problem in our community. The Mediterranean diet in these vulnerable groups may be an aggravating factor for vitamin B12 deficiency. Prenatal screening of all expectant mothers, prenatal supplementation of vitamin B12, and an increase in animal-source food intake may improve expectant mother's vitamin B12 level.

Cerebral sinovenous thrombosis associated with MTHFR A1298C mutation in the newborn: a case report.

Although cerebral sinovenous thrombosis (CSVT) is a rare condition in the neonatal period, high rates of morbidity and mortality necessitate the establishment of an early diagnosis. Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the folate cycle and mutations of MTHFR are associated with vascular disease. While the C677T common missense mutation is the most well-defined MTHFR polymorphism, another common missense mutation, A1298C also exists. There has been no reported case of CSVT associated with MTHFR A1298C mutation in the neonatal period. Herein, we report a neonate with CSVT who was found to have MTHFR A1298C homozygosity.

Determination of total oxidative stress and total antioxidant capacity before and after the treatment of iron-deficiency anemia.

BACKGROUND: Oxidative stress is an imbalance between the reactive oxygen species and antioxidant system. In this study, total oxidative stress (TOS) and total antioxidant capacity (TAC) were investigated with a new and practical method in childhood iron-deficiency anemia. METHOD: During the study period 80 children between 6 and 60 months were enrolled; 40 children (study group) had iron-deficiency anemia, and 40 children (control group) were healthy. Complete blood count, serum iron, iron-binding capacity, ferritin levels, TOS, and TAC were evaluated. Children diagnosed iron-deficiency anemia were treated with oral ferric iron. After 2 months of the treatment, blood tests of the study groups were repeated to check the challenge. RESULTS: TAC was similar between both groups (1.55 ± 0.26 in control group 1.53 ± 0.19 mmol Trolox Eq./l). Additionally, TOS was significantly higher in iron-deficiency anemia group before treatment with iron (24.3 ± 18.5, in controls groups 14.4 ± 7.1 mmol Trolox Eq./l). We have shown that TAC did not change (before treatment 1.55 ± 0.26, after treatment 1.54 ± 0.26 mmol Trolox Eq./l) although TOS decreased significantly after the treatment of iron-deficiency anemia (before treatment 24.3 ± 18.5, after treatment 12.4 ± 6.9 mmol Trolox Eq./l). We did not find any correlation between hemoglobin, serum iron, iron-binding capacity, ferritin levels, and TOS or TAC among iron-deficiency anemia patients. CONCLUSION: As a result of this study, oxidative stress increases in children with iron-deficiency anemia and this increase can be returned to normal levels by treatment.

Thrombocytosis associated with enoxaparin: A very rare cause in newborns.

Newborn infants are most vulnerable to the development of thrombosis because of the developing neonatal hemostatic system, perinatal risk factors and different types of medical conditions. Enoxaparin is the current anticoagulant of choice with advantages for the treatment of neonatal thrombosis. Thrombocytosis induced by enoxaparin has been reported as a rare adverse effect of this medication in adults. However, to our knowledge, in newborns there have been no reported cases to date of thrombocytosis induced by enoxaparin.

Psychopathology in thalassemia major.

BACKGROUND: Thalassemia major (TM) is a chronic disease with adverse emotional effects on both the child and the family. The aim of this study was to investigate the psychiatric state and behavioral problems of children with TM. METHODS: Twenty children diagnosed with TM and 34 healthy children were enrolled in this study carried out by the Pamukkale University Faculty of Medicine, Department of Pediatrics. Mothers of the children of both the groups were handed a child behavior check-list for 4-18-year-old children and adolescents as well as a short questionnaire requesting demographic information. RESULTS: The psychiatric diagnosis was significantly higher in the children with TM (55.0%) as compared to the control group (14.7%). The thalassemic children showed an anxiety disorder frequency of 30.0% and a depressive disorder frequency of 15.0%. T scores of the indicators of internalizing problems, externalizing problems, attention problems and social problems contained in the child behavior check-list were shown to be higher in children with TM than in the control group. The TM group demonstrated significantly higher problems in peer relationships and educational success in comparison with the controls. CONCLUSION: Children with TM are posed with an increased risk of psychopathology.

Hemorheological parameters in children with iron-deficiency anemia and the alterations in these parameters in response to iron replacement.

AIM: Iron-deficiency anemia (IDA) is a common disorder in pediatric patients. There are a limited number of studies having controversial results in investigating red blood cell (RBC) deformability and aggregation in adult IDA patients. The aim of this study is to determine the change of hemorheological parameters, including RBC deformability, aggregation, and plasma and whole blood viscosity, in children with IDA following iron supplementation therapy. MATERIALS AND METHODS: The study was performed on 20 children with IDA (average age 35.5 +/- 6.5 months) and 20 age-matched healthy children. The anemia group was treated with 5 mg/kg/day peroral iron for 2 months. Hematological and hemorheological parameters were determined before and after treatment. An ectacytometer was used for the assessment of RBC deformability and aggregation and a cone-plate rotational viscometer for plasma and whole blood viscosities. Hematological parameters were determined using an electronic hematology analyzer. RESULTS: Although IDA resulted in a decrement in RBC deformability, aggregation, plasma, and whole blood viscosities, these parameters returned to control values after iron supplementation therapy. Serum ferritin levels and hematological parameters (Hb, MCV, MCH, MCHC) that were lower in IDA patients were also found to be increased after treatment. CONCLUSION: Iron treatment not only reverses the symptoms of anemia but also may contribute to blood flow regulation by causing increments in the alterations observed in hemorheological parameters during anemia.

Conjunctival melanoma in a six-year-old female.

Conjunctival melanoma (CM) is a highly malignant tumor that derives from melanocytes and is rarely seen in children. This report describes a 6-year-old female diagnosed with CM.

Two cases of Cushing's syndrome due to overuse of topical steroid in the diaper area.

Topical use of corticosteroids may cause immunosuppression and iatrogenic Cushing's syndrome via hypothalamic-pituitary-adrenal axis. We report two cases with iatrogenic Cushing's syndrome with different clinical outcomes due to abuse of same potent topical steroid clobetasol propionate. One of them died because of fatal disseminated cytomegalovirus infection. The other patient recovered completely. Physicians and parents should be informed about the adverse effects of such potent topical corticosteroids and physicians should prescribe less potent agents, especially during infancy.

Pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis: Case report.

Adenovirus is an infectious viral agent that causes variety of clinical presentations such as respiratory disease, conjunctivitis, and gastroenteritis. Hepatitis, pancreatitis, myocarditis, encephalitis, and disseminated infection are primarily seen in immunocompromised patients. Rarely, adenovirus infection can present with pertussis-like syndrome. Described here is case of pertussis-like syndrome associated with adenovirus presenting with hyperleukocytosis.

Familial mutation in Caffey disease with reduced penetrance: A case report.

Caffey disease is a rare condition of early infancy, characterized by soft tissue swelling, bone lesions, and hyperirritability. Its typical radiological finding is periosteal new bone formation. It can be sporadic or inherited in an autosomal dominant manner. There is no specific treatment. In symptomatic cases, non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, or naproxen can be used. This is a report of an infant who presented with restlessness, irritability, and swelling over his shins, diagnosed as Caffey disease. Although there was no family history, the genetic analysis revealed heterozygous missense mutation (c.3040C > T) in type-I-collagen-alpha-1-chain gene in the patient in addition to his mother, grandmother, aunt, and cousin. After indomethacin therapy, the complaints of the patient were completely resolved and his bone lesions were significantly improved. This case report is a familial form of Caffey disease from Turkey, with proven heterozygous mutation in the patient and the family members.

Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor.

OBJECTIVES: Evaluation of the peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements in children with thalassemia minor. METHODS: In this cross-sectional and comparative study, 30 thalassemia minor patients and 36 controls were included. Heidelberg spectral domain optical coherence tomography was used for peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements. RESULTS: There was no statistically significant difference in retinal nerve fiber layer thickness and subfoveal choroidal thickness between the two groups (p > 0.05). There was no correlation between retinal nerve fiber layer thickness and hemoglobin values. Both the arterioral and venular calibers were higher in thalassemia minor group (p < 0.05). CONCLUSION: There is increased retinal arterioral and venular calibers in children with thalassemia minor compared with controls.

Hemophagocytic Syndrome due to Leishmania Infection Diagnosed with Immunofluorescence Antibody Test.

Leishmaniasis is a reticuloendothelial system disease that mostly observed before the age of 5. Visceral infection causes long-standing fever, weight loss, weakness, pancytopenia, and hepatosplenomegaly. Leishmania infantum is responsible for visceral leishmaniasis (VL) in Turkey. We present a case of hemophagocytic syndrome due to Leishmania infection diagnosed with an immunofluorescence antibody test (IFAT). Leishmania amastigotes were not observed on bone marrow aspiration. We consider that IFAT is very important for parasite detection in the diagnosis of VL in children, particularly when amastigotes are not obtained on bone marrow aspiration.

Impaired Hemorheological Parameters and Increased Carotid Intima-Media Thickness in Children with Subclinical Hypothyroidism.

BACKGROUND: Subclinical hypothyroidism (SH) is defined as elevated serum thyroid-stimulating hormone (TSH) concentration associated with normal serum-free thyroxine levels. Effects of hypothyroidism on hemorheology had widely attracted the attention of researchers during the last decade. OBJECTIVE: The purpose of this study is to determine alterations in hemorheological parameters and carotid intima-media thickness (CIMT) in children with SH. METHODS: Fifty-three SH children and 31 healthy controls were enrolled. Erythrocyte deformability and aggregation were determined by an ektacytometer and plasma viscosity (PV) by a cone-plate rotational viscometer. CIMT was evaluated sonographically. RESULTS: Erythrocyte deformability of the SH group measured at 0.53 and 1.69-30 Pa was lower than that of the control group. The erythrocyte aggregation index, aggregation half time and PV were not different between the groups. However, the aggregation amplitude and mean corpuscular hemoglobin concentration were significantly higher in SH compared to the control group. There was a negative correlation between TSH and deformability values measured at 5.33-30.0 Pa. CIMT in patients with SH was significantly higher than in the control group (p = 0.001; SH = 0.48 ± 0.04 mm, control group = 0.43 ± 0.03 mm). CONCLUSION: Impaired hemorheology and increased CIMT are well-known risk factors for developing cardiovascular pathologies. The results of the current study suggest the treatment of children with SH in order to avoid early circulatory problems.

A Hemophagocytic Lymphohistiocytosis Case with Newly Defined UNC13D (c.175G>C; p.Ala59Pro) Mutation and a Rare Complication.

Hemophagocytic lymphohistiocytosis (HLH) represents a severe hyperinflammatory condition with cardinal symptoms of prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages with impaired function of natural killer cells and cytotoxic T lymphocytes. A 2-month-old girl, who was admitted with fever, was diagnosed with HLH and her genetic examination revealed a newly defined mutation in the UNC13D (c.175G>C; p.Ala59Pro) gene. She was treated with dexamethasone, etoposide, and intrathecal methotrexate. During the second week of treatment, after three doses of etoposide, it was noticed that there was a necrotic plaque lesion on the soft palate. Pathologic examination of debrided material in PAS and Grocott staining revealed lots of septated hyphae, which was consistent with aspergillosis infection. Etoposide was stopped and amphotericin B treatment was given for six weeks. HLH 2004 protocol was completed to eight weeks with cyclosporine A orally. There was no patient with invasive aspergillosis infection as severe as causing palate and nasal septum perforation during HLH therapy. In immunocompromised patients, fungal infections may cause nasal septum perforation and treatment could be achieved by antifungal therapy and debridement of necrotic tissue.

Evaluation of soluble transferring receptor levels in children with iron deficiency and beta thalassemia trait, and in newborns and their mothers.

In this study we first aimed to investigate the value of soluble transferrin receptor levels (sTfR) in healthy, iron deficient and beta thalassemia trait children and to determine whether sTfR is a useful indicator of iron deficiency. Secondly, we investigated the effects of iron supplementation of sTfR levels in a group of iron deficient children. Third was to describe sTfR in newborn infants and determine whether or not maternal iron deficiency is an important predictor of infant sTfR. Six groups were formed: Children with iron deficiency (n=22), post-iron therapy (n=16), beta thalassemia traits (n=19), healthy children (n=19), full-term newborns (n=20), and their mothers (n=19), Complete blood count (CBC), serum iron, iron-binding capacity, ferritin and sTfR levels were measured. sTfR/log ferritin indexes were calculated. sTfR levels of children with iron deficiency and with beta thalassemia trait were found to be significantly higher than those of healthy children (p<0.0001 and p<0.001). Children with iron deficiency showed a greater increase in the levels of sTfR than those with beta thalassemia traits (p=0.008). Although sTfR levels of subjects having iron therapy decreased, the levels still remained high compared to controls (p=0.002). Newborns had significantly higher levels of sTfR than controls (p<0.0001). Although sTfR levels of mothers with iron deficiency were higher than those of mothers having no iron deficiency (p=0.009), there was no difference in the levels of sTfR between newborns of both groups of mothers (p=0.790). sTfR is a useful parameter which shows body iron status as well as erythropoietic activity in children. It is independent of mother's iron status, and is due to erythropoietic activity in newborns.