Saadet Akarsu

Serum IL-1β, IL-2, and IL-6 in insulin-dependent diabetic children

Insulin-dependent diabetes mellitus (IDDM) is a chronic disease characterized by T-cell-dependent autoimmune destruction of the insulin-producing β cells in the pancreatic islets of Langerhans, resulting in an absolute lack of insulin. T cells are activated in response to islet-dominant autoantigens, the result being the development of IDDM. Insulin is one of the islet autoantigens responsible for the activation of T-lymphocyte functions, inflammatory cytokine production, and development of IDDM. The aim of this study was to investigate serum concentrations of interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α in children IDDM. The study population consisted of 27 children with IDDM and 25 healthy controls. Children with IDDM were divided into three subgroups: (1) previously diagnosed patients (long standing IDDM) (n : 15), (2) newly diagnosed patients with diabetic ketoacidosis (before treatment) (n : 12), and (3) newly diagnosed patients with diabetic ketoacidosis (after treatment for two weeks) (n : 12). In all stages of diabetes higher levels of IL-1β and TNF- α and lower levels of IL-2 and IL-6 were detected. Our data about elevated serum IL-1β, TNF- α and decreased IL-2, IL-6 levels in newly diagnosed IDDM patients in comparison with longer standing cases supports an activation of systemic inflammatory process during early phases of IDDM which may be indicative of an ongoing β-cell destruction. Persistence of significant difference between the cases with IDDM monitored for a long time and controls in terms of IL-1β, IL-2, IL-6, and TNF-α supports continuous activation during the late stages of diabetes.

Levels of cytokines (IL-1beta, IL-2, IL-6, IL-8, TNF-alpha) and trace elements (Zn, Cu) in breast milk from mothers of preterm and term infants.

It has been well documented that human milk contains several immunomodulator components which are important during infant period when the newborns immune system is still under development. In this study, we aim at examining levels of cytokines, zinc (Zn), and copper (Cu) in milk from mothers of premature and mature infants, and comparing changes during lactation periods consequently. Milk was collected from total of 40 mothers (group M: mothers of mature infants, n = 20; group PM: mothers of premature infants, n = 20) from four lactation stages: colostrum (0–7 days), transitional (7–14 days), mature milk (21 days), and mature milk (2nd month). Levels of cytokines (interleukin [IL]-lβ, IL-2, IL-6, IL-8, tumor necrosis factor-alpha [TNF-α]) were determined by chemiluminesence method, whereas atomic absorption spectrophotometer was used for the determination of Zn and Cu levels. Cytokine levels were determined to be high in colostrum and transient milk from mothers of full-term infants, whereas their levels were reduced drastically in the 21st day and the 2nd month milk (P < .01 , P < .001). Similar trends were observed in milk from mothers of premature infants, but cytokine levels were significantly lower in colostrum compared to colostrum from mothers of mature infants (P < .01). The differences in cytokine levels were continuous in transient milk (P < .05) and mature milk (21 days) (P < .05), whereas there was no statistically significant differences between milk from both groups of mothers in the 2nd month (P > .05). Zn levels in milk from mothers of premature infants were significantly lower compared to the ones from mothers of mature infants (P < .01) and these differences continued through the 2nd month. Although Cu levels were lower in milk from mothers of premature infants, there was no statistically significant difference except colostrum (P > .05). Our results clearly demonstrate that the level of immunomodulating agents such as cytokines and trace elements in milk from mothers of premature infants is less than the level of the same agents in milk from mothers of full-term infants. Although there are commercially available products for infant feeding, human milk is still the best natural nutrient for newborns. Therefore, when premature infants are breastfed, necessary precautions such as supplemantary diets must be considered for possible infections and risks related with immune system deficiency.

Use of Phototherapy for Neonatal Hyperbilirubinemia Affects Cytokine Production and Lymphocyte Subsets

Background: Most studies regarding the influence of ultraviolet radiation on levels of inflammatory cytokines were conducted mainly in cultures of human keratinocytes or in laboratory animals. Few studies were also performed in human subjects. Objectives: To investigate the influence of the use of phototherapy on the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 such as cytokines expressed from keratinocytes and on the expression of some lymphocyte subsets in the prevention or treatment of neonatal hyperbilirubinemia. Methods: The study group included 21 term newborns with hyperbilirubinemia and the control group included 16 healthy term newborns. Blood samples were obtained from hyperbilirubinemic newborns before and at 72 h of exposure to phototherapy and from controls at the examination time. The levels of TNF-α, IL-1β, IL-6, IL-8 and lymphocyte subsets were measured in the samples using appropriate methods. Results: Serum TNF-α, IL-1β, IL-6, and IL-8 levels are similar in study and control groups. At 72 h of exposure to phototherapy serum TNF-α, IL-1β and IL-8 levels are significantly increased, while the serum IL-6 level at the same time is not significantly changed. Lymphocytes, lymphocyte subsets and white blood cell levels are similar in the study and control groups. Only, the percentage of CD3+ lymphocyte subset is significantly lower in newborns at 72 h of exposure to phototherapy. All other lymphocyte subsets are decreased by the exposure to phototherapy, and this change was not statistically significant. Conclusions: The results demonstrate that in addition to the well-known positive effect of phototherapy on the neonatal serum bilirubin level, this treatment can affect the function of the immune system in newborns via alterations in cytokine production.

The differential diagnostic values of cytokine levels in pleural effusions.

The aim is to examine whether the changes in pleural fluid interleukin (IL)-1β, IL-2, IL-6, and IL-8 levels were significant in differential diagnosis of childhood pleural effusions. IL-1β, IL-2, IL-6, and IL-8 levels in pleural fluids of all 36 patients were measured. The levels of IL-1β, IL-2, IL-6, and IL-8 in pleural fluids were statistically significantly higher in the transudate group compared with those of the exudate group. The levels of IL-1β, IL-6, and IL-8 were also found to be statistically significantly higher in the empyema group compared with both the parapneumonic and the tuberculous pleural effusion groups. The levels of IL-2 and IL-6 were detected to be statistically significantly higher in the tuberculous pleural effusion group in comparison with those of the parapneumonic effusion group. The results showed that pleural fluids IL-1β, IL-2, IL-6, and IL-8 could be used in pleural fluids exudate and transudate distinction.

Treatment of Iron Deficiency Anemia with Intravenous Iron Preparations

Objective: We aimed to determine the effects of intravenous iron therapy on blood parameters in pediatric patients who do not tolerate oral iron therapy for any reason. Patients and Methods: The patient group consisted of candidates for elective operations requiring blood transfusions in order to raise hemoglobin (Hb) concentrations rapidly and for whom oral iron administration is useless and compliance with long-term treatment is definitely impossible due to sociocultural factors. Sixty-two children were included in the study. Venous blood samples were taken at diagnosis, and after 1 week and 1, 2 and 3 months. Hb, hematocrit, erythrocyte indices (mean erythrocyte volume, mean erythrocyte Hb and mean erythrocyte Hb concentration), serum iron (SI) levels, iron binding capacity, transferrin receptor (CD71) and serum ferritin levels were measured. Iron sucrose was used as an intravenous iron preparation. Results: All children showed improvements in iron deficiency anemia. A statistically significant elevation occurred between the time of diagnosis and week 1 (p<0.05) in nearly all parameters. SI was raised until at least 1 month of therapy. There was no significant difference between transferrin receptors measured before and after the intravenous iron therapy. Ferritin did not exceed the values achieved in the 1st month. Mild side effects were encountered in only 8 (12.9%) patients. Treatment was not discontinued because of side effects in any case. The patients in the control group were given an oral form containing ferroglycine sulfate. Conclusion: Intravenous iron therapy can replace oral therapy in patients whose blood parameters must be raised rapidly and in situations where oral iron administration would not be appropriate for any reason. However, reinforcement with oral iron therapy or additional intravenous doses would be appropriate.

The Levels of Ghrelin, TNF-α, and IL-6 in Children with Cyanotic and Acyanotic Congenital Heart Disease

Background/Aim. Ghrelin has effects on nutrient intake and growth. The cause of growth retardation in congenital heart disease is multifactorial. The aim of the present study is to investigate the ghrelin in congenital heart disease and the association of ghrelin with TNF-α and IL-6. Materials and methods. We measured serum ghrelin, TNF-α, and IL-6 levels using spesific immunoassay in 68 patients (47 acyanotic, 21 cyanotic with congenital heart disease) and in 25 control subjects. Results. In comparison to controls, serum ghrelin, TNF-α levels were significantly higher in acyanotic patients and cyanotic patients with congenital heart disease (P<.0001). In acyanotic and cyanotic patients with congenital heart disease, there was a positive correlation between ghrelin and TNF-α (r=.485, P<.05 and r=.573, P<.01, resp.). Conclusion. Serum ghrelin levels is elevated in acyanotic and cyanotic patients with congenital heart disease. Increased ghrelin levels represents malnutrition and growth retardation in these patients. The relation of ghrelin with cytokines may be explained by the possible effect of chronic congestive heart failure and chronic shunt hypoxemia.

Plasma ghrelin levels in various stages of development of iron deficiency anemia.

Objectives Ghrelin stimulates food intake and induces metabolic changes leading to an increase in body weight and body fat mass. Iron-deficiency anemia (IDA) is the most frequently seen cause of nutritional anemia, that is a type of starvation. There is no available study related to levels of ghrelin in IDA. The aim of this study is to show an association with ghrelin levels and iron deficiency and to demonstrate whether changes seen in iron deficiency (ID) are explained by ghrelin, as opposed to whether ghrelin levels correlate with ID. Materials and Methods The study group was consisted of children who were admitted in the outpatient clinic of pediatrics. Control group (C) was defined as cases with normal hemoglobin (Hb), serum iron (SI), transferrin saturation (TS), and ferritin (F) (>12 ng/mL) values; group hypoferritinemia (IDec) Hb: N, SI: N, TS: N, F<12 ng/mL; group iron deficiency (IDef), Hb: N, SI: decreased, TS ≤16%, F<12 ng/mL, and group IDA, Hb and SI decreased, TS ≤16%, F<12 ng/mL. The patients were categorized into 4 groups [group 1 (C), n=25, age=82.4±16.56 mo, F=40.87±6.17 ng/mL; group 2 (IDec), n=30, age=57.5±20.71 mo, F=29.95±3.77 ng/mL; group 3 (IDef), n=28, age=50.21±19.87 mo, F=14.82±3.41 ng/mL; group 4 (IDA), n=25, age=31.55±13.21 mo, F=11.75±4.01 ng/mL]. Results Mean value of ghrelin was detected to be 396.53±85.56 pg/mL, 332.26±74.35 pg/mL, 309.66±68.62 pg/mL, and 177.66±27.81 pg/mL in control, groups IDec, IDef, and IDA, respectively. A statistically significant difference was detected between groups control and IDef (P<0.01), control and IDA, IDec and IDA, IDef and IDA (P<0.001). Conclusions A significant positive correlation was demonstrated between iron status of the body and levels of ghrelin. Decrease in ghrelin levels in IDA can lead to loss of appetite, desire to eat diverse foods with resultant delay in growth and development.

Frequency of hypoferritinemia, iron deficiency and iron deficiency anemia in outpatients.

The prevalence rates of hypoferritinemia (IDec/one abnormal indicator), iron deficiency (IDef/two abnormal indicators) and iron deficiency anemia (IDA) in children who were referred to the outpatient clinics of the Department of Pediatrics for the first time within 1 month were investigated. Exclusion criteria were iron therapy before and during the study period and a history of chronic illness. Acute-phase reactants, such as erythrocyte sedimentation rate and C-reactive protein levels, were measured in all cases indicative of infectious diseases. Blood samples were obtained from each study patient admitted to the outpatient clinics during the study period. The hospital charts were later further evaluated, and samples of patients with any current illness known to interact with the iron status of the patient were discarded, and patients were contacted to supply new samples about 1 month after treatment of the infection. Thus, in patients with indications of an infection, samples obtained 1 month after treatment were assessed.The children (n = 557) were divided into four age groups: those aged 4 months to 2 years (group I), 2–6 years (group II), 7–12 years (group III) and 12–18 years (group IV). Children with a decrease in serum ferritin levels without anemia (IDec), and those with lower ferritin, transferrin saturation (TS) and serum iron (SI) concentration (IDef) were evaluated. IDA was diagnosed if hemoglobin (Hb) concentrations were lower than those adjusted for age, ferritin <12 ng/ml and TS ≤16% and if SI was decreased. IDec, IDef and IDA were detected in 26, 11.1 and 12.7% of the patients, respectively. Only 50.1% of the patients visiting the outpatient clinics were found to be normal. The rates of IDec (28.9%), IDef (21.9%) and IDA (26.2%) were highest in group I. IDec had the highest percentages in all groups. In group I, the rates of IDec, IDef, and IDA were 37.2, 66.1 and 69%, respectively. SI concentration was abnormal in 77.1% of the cases in group I (4 months to 2 years of age). Half of the patients referred to the outpatient clinics were suffering from abnormalities related to lower SI concentrations. Close monitoring and treatment of iron deficiency is advised especially in early childhood.

Nipple and areola diameter in Turkish pubertal girls

The nipple and areola diameter of 498 girls aged 8-17 years were studied with the aim of finding measurable criteria for sexual maturation, including breast and pubic hair development during female puberty. All measurements were made holding a transparent ruler on both sides by the same observer. The smaller of the two measurements was used in the analysis. Significantly nipple and areola development occurred between breast stages B1 (2.56 and 14.35 mm), B2 (3.32 and 20.26 mm), B3 (5.21 and 28.84 mm), and B4 (6.28 and 32.03 mm). The nipple and areola diameter were also significantly greater in pubic hair stage (PH)3 (5.05 and 25.24 mm) with respect to PH2 and PH1 (3.46, 2.62 mm and 19.32, 15.37 mm, respectively), in PH5 (6.79 and 35.62 mm) with respect to PH4 (6.55 and 32.56 mm). A significant increase in nipple and areola diameter occurs between premenarchal girls and girls older than 0-2 years postmenarche. Sexual maturation staging by nipple size and by areola size appears to be feasible for female adolescent. However, staging by nipple size does not appear to be feasible for B4 and B5 stage, because the incremental gradations are small.

Neonates with Culture Proven Sepsis Have Lower Amounts and Percentage of CD45RA+ T Cells

To evaluate the expression of lymphocyte subsets in newborns diagnosed as culture proven or culture negative sepsis and to investigate the differentiation. The aim of this study is to explore neonatal immunology in newborns diagnosed as culture proven or culture negative neonatal sepsis and to identify their place in the diagnosis. This prospective study was performed in newborns who were diagnosed as neonatal sepsis and hospitalized in a tertiary care hospital and who were classified as culture proven sepsis (n = 12), as culture negative sepsis (n = 21) and healthy (n = 17). Lymphocyte subsets were obtained at time of diagnosis. Culture proven sepsis had statistically significant increase of WBC compared to culture negative sepsis and control groups (p < 0.05). Significant decreases were observed of percentage of lymphocyte, when compared to culture negative sepsis and control group (p < 0.05). Percentage of CD4+ was lower in culture proven sepsis and absolute count of CD4+ was lower in culture negative sepsis (p < 0.05). Percentage and absolute count of CD45RA+ were lower in culture negative sepsis than control and percentage of CD45RA+ was lower in culture proven sepsis than control (p < 0.05). Percentage of CD45RO+ was higher in culture proven sepsis than control group (p < 0.05). It is clear that during neonatal sepsis lymphocyte subsets are different from healthy controls. Whether the described abnormalities represent the absence of a normal maturation process, rather, pathological events is still not clear.