The role of IL-18 in Th1/Th2 balance in children.

Interleukin (IL)-18 has been identified as a mediator inducing interferon gamma release from type 1 helper (Th1) cells, CD8+ T cells, and natural killer cells, synergizing with IL-12. Several studies report differential roles of IL-18; but little is known about the role of IL-18 in Th1/Th2 balance in children. The aim of this study was to evaluate the role of IL-18 in Th1- and Th2-mediated diseases of children. Serum IL-18 levels were measured in a group of patients with acute asthma exacerbation (n = 24), in a group of patients who had recently been diagnosed as type I insulin-dependent diabetes mellitus (n = 18), and in a group of healthy subjects (n = 20). The groups were compared with respect to IL-18 levels. Significantly lower serum IL-18 levels were found in patients with acute asthma (median, 8.55 pg/mL) and insulin-dependent diabetes mellitus (median, 7.20 pg/mL) than in control subjects (median, 140.10 pg/mL; p < 0.05 and p < 0.001, respectively). We suggest that IL-18 may play an immunoregulatory role in allergic and autoimmune diseases and decreased expression of IL-18 can shift the immune responses to both Th1- and Th2-mediated ways.     

1,25-Dihydroxyvitamin D3 stimulates odontoblastic differentiation of human dental pulp-stem cells in vitro

Background: 1,25-Dihydroxyvitamin D₃ (1,25-OH D₃) plays an important role in mineralized tissue metabolism, including teeth. However, few studies have addressed its role in odontoblastic differentiation of human dental pulp-stem cells (hDPSCs). Aim: This study aimed to understand the influence of various concentrations of 1,25-OH D₃ on the proliferation capacity and early dentinogenesis responses of hDPSCs. Materials and Methods: hDPSCs were obtained from the impacted third molar teeth. Monolayer cultured cells were incubated with a differentiation medium containing different concentrations of 1,25-OH D₃ (0.001, 0.01, and 0.1 µM). All groups were evaluated by S-phase rate [immunohistochemical (IHC) bromodeoxyuridine (BrdU) staining], STRO-1 and dentin sialoprotein (DSP)+ levels (IHC), and alkaline phosphatase (ALP, enzyme-linked immunosorbent assay (ELISA)) levels. Results: The number of cells that entered the S-phase was determined to be the highest and lowest in the control and 0.001 µM 1,25-OH D₃ groups, respectively. The 0.1 µM vitamin D₃ group had the highest increase in DSP+ levels. The highest Stro-1 levels were detected in the control and 0.1 µM 1,25-OH D₃ groups, respectively. The 0.1 µM 1,25-OH D₃ induced a mild increase in ALP activity. Conclusions: This study demonstrated that 1,25-OH D₃ stimulated odontoblastic differentiation of hDPSCs in vitro in a dose-dependent manner. The high DSP + cell number and a mild increase in ALP activity suggest that DPSCs treated with 0.1 μM 1,25-OH D₃ are in the later stage of odontoblastic differentiation. The results confirm that 1,25-OH D₃-added cocktail medium provides a sufficient microenvironment for the odontoblastic differentiation of hDPSCs in vitro.     

Sublingual immunotherapy to house dust mite in pediatric patients with allergic rhinitis and asthma: a retrospective analysis of clinical course over a 3-year follow-up period.

BACKGROUND AND OBJECTIVE: Specific allergen immunotherapy is believed to be the only treatment able to change the natural history of allergic airway diseases. Sublingual immunotherapy (SLIT) is especially preferred because of its easy application and safety. The aim of this study was to describe the effect of SLIT in pediatric patients who have allergic airway disease. METHODS: Children with asthma and rhinitis who were allergic to house dust mite were evaluated. The effect on clinical course of 3 years of SLIT with 50% Dermatophagoides pteronyssinus and 50% Dermatophagoides farinae in a standardized extract was assessed retrospectively. RESULTS: The records of 39 patients (23 boys, 16 girls) were studied. The mean (+/- SD) age for starting SLIT was 8.8 +/- 2.3 years. The mean number of acute asthma attacks at the onset of the disease was 8.18 +/- 3.05. The mean number of attacks after 3 years of SLIT was 0.44 +/- 0.79. There was a statistically significant difference in the number of acute asthma attacks before and after therapy (P < .001). Complete clinical remission of asthma was recorded in 37 (95%) patients. Similarly, complete clinical remission of allergic rhinitis was recorded in 32 (82%) patients. CONCLUSION: This retrospective study shows that SLIT is effective in children who have allergic airway disease which cannot be controlled effectively with allergen avoidance measures only.     

Antineutrophil Cytoplasmic Antibodies in Juvenile Chronic Arthritis

We present the results of antineutrophil cytoplasmic antibody (ANCA) staining in patients with juvenile chronic arthritis (JCA). Thirty-one patients with an age range of 1-16 years were included in the study: 13, 15 and three patients, respectively, were classified having oligoarticular, polyarticular and systemic-onset disease. Indirect immunofluorescence analysis revealed ANCA staining in 45% of the patients. All, except one, revealed atypical pANCA staining. ELISA studies for anti-myeloperoxidase were positive in only one patient with typical pANCA staining. PR-3 ANCA tested negative in all patients. There were no significant correlations between ANCA staining and the clinical parameters of the patients. We conclude that, although the specificity of ANCA in JCA remains to be elucidated, it may be effective in the pathogenesis of the disease.     

Growth and bone mineralization in patients with juvenile idiopathic arthritis

Objective  To investigate growth, development and bone mineralization of children with juvenile idiopathic arthritis (JIA). Methods  Thirty patients between 4–17 years of age (mean 11.34 ± 3.88) resistant to therapy were studied. Enrollment began in November 1999 and continued through November 2004 and children with chronic disease were excluded. Data like height, weight, medications and acute phase reactants were obtained from medical records. On study-visit, puberty was assessed by physical examination and bone mineral density (BMD) was measured. Serum Ca, P, ALP, insulin-like growth factor-1 (IGF-1) and urinary Ca/Cr and hydroxyproline /Cr levels were measured. Results were compared with the control group that consisted of 30 cases of similar age and gender. Results  Patients with JIA had decreased height standard deviation score (SDS) and growth retardation. BMD of the cases in the study group was lower than the control group (p<0.05). Patients who were at younger age at the onset of the disease had lower BMD. Among the drugs, only steroids had a negative effect on growth. Serum IGF-1 levels of the study group were significantly lower than the control group (p<0.0001). Conclusion  Early diagnosis and suppression of disease activity is important in prevention of osteoporosis and growth retardation in children with JIA. BMD has to be measured yearly in patients for accurate diagnosis of osteoporosis. Vitamin D and Ca-rich nutrition with promotion of physical activity and controlled use of steroids may protect the children against bone loss.     

Potentiation of cytotoxicity by combination of imatinib and chlorimipramine in glioma

Rat C6 glioma is a chemo-resistant experimental brain tumor that is difficult to treat with various drug combinations. Previous studies suggested that imatinib mesylate (Gleevec) is effective in pre-clinical trials for glioblastoma. Also, chlorimipramine (Anafranil) is an anti-depressant drug in use in the clinic and shown to have anti-neoplastic activity. We hypothesized that treatment of resistant C6 glioma with combination of imatinib and chlorimipramine may potentiate cytotoxicity and reverse resistance. C6 glioma was examined both as monolayer and as spheroid cultures. Several experimental designs were examined all of which showed synergistic activity albeit at different time kinetics. Combination treatment resulted in inhibition of cell growth and enhanced cell death as determined by dye exclusion. Further, the combination treatment resulted in significant induction of apoptosis as determined by Annexin V-FITC and PI. Also, there was inhibition of DNA synthesis and cAMP. Altogether, these findings supported the anti-proliferative and cytotoxic effects of the combination treatment. Morphological studies were also performed using transmission and scanning electron microscopy. Significant synergistic apoptosis was detected by the combination treatment in both the monolayers and spheroid cultures. There was also a synergistic effect in autophagy by the combination. Several altered morphological features were noted by both the individual compound and enhanced by the combination treatment. The present findings support our hypothesis and demonstrate the potentiation of cytotoxicity by the combination of imatinib and chlorimipramine in C6 glioma. Further, the findings suggest the potential clinical application of the combination in the treatment of drug-resistant glioma.     

The epidemiology and economic impact of varicella-related hospitalizations in Turkey from 2008 to 2010: a nationwide survey during the pre-vaccine era (VARICOMP study)

Varicella can cause complications that are potentially serious and require hospitalization. Our current understanding of the causes and incidence of varicella-related hospitalization in Turkey is limited and sufficiently accurate epidemiological and economical information is lacking. The aim of this study was to estimate the annual incidence of varicella-related hospitalizations, describe the complications, and estimate the annual mortality and cost of varicella in children. VARICOMP is a multi-center study that was performed to provide epidemiological and economic data on hospitalization for varicella in children between 0 and 15?years of age from October 2008 to September 2010 in Turkey. According to medical records from 27 health care centers in 14 cities (representing 49.3% of the childhood population in Turkey), 824 children (73% previously healthy) were hospitalized for varicella over the 2-year period. Most cases occurred in the spring and early summer months. Most cases were in children under 5?years of age, and 29.5% were in children under 1?year of age. The estimated incidence of varicella-related hospitalization was 5.29-6.89 per 100,000 in all children between 0-15?years of age in Turkey, 21.7 to 28 per 100,000 children under 1?year of age, 9.8-13.8 per 100,000 children under 5?years of age, 3.96-6.52 per 100,000 children between 5 and 10?years of age and 0.42 to 0.71 per 100,000 children between 10 and 15?years of age. Among the 824 children, 212 (25.7%) were hospitalized because of primary varicella infection. The most common complications in children were secondary bacterial infection (23%), neurological (19.1%), and respiratory (17.5%) complications. Secondary bacterial infections (p?相似文献   

Status epilepticus in children: Causes,clinical features and short‐term outcome

Background: We aimed to evaluate the cause, clinical profile, and short‐term outcome of status epilepticus cases that were admitted to our pediatric emergency unit between 1 January and 31 December 2008. Methods: We studied the clinical features of 59 seizures that occurred in 56 patients aged between 3 months and 15 years with the diagnosis of status epilepticus. We observed the clinical course and outcome of 53 cases for 6 to 18 months. The correlation between the cause of the seizure and the patient's age at the time of status epilepticus was evaluated as well as the correlation between the risk of seizure recurrence and family history of seizure, the neurological status of the patient prior to seizure and the presence of epilepsy. Results: The most common cause of status epilepticus is febrile illness in children younger than 2 years and idiopathic/cryptogenic and remote symptomatic causes in children older than 2 years. The rate of recurrence of seizure was significantly higher in cases with existing neurological abnormalities, prior epilepsy and seizures with remote symptomatic causes. The most common triggering factors of status epilepticus development in cases with epilepsy were noncompliance for anti‐epileptic drugs and infectious fever. Conclusions: In our study, the risk factors for seizure recurrence were the presence of prior epilepsy, existence of neurological abnormalities and remote symptomatic causes. We argue that improving the compliance of patients and their families to take medicine appropriately and training them in how to cope with febrile illnesses may decrease the recurrence of seizures.     

Does hypereosinophilic syndrome precede common B acute lymphoblastic leukaemia in childhood? A case report

Hypereosinophilic syndrome (HES) and the association of hypereosinophilia with acute lymphoblastic leukaemia (ALL) are both rare in children. Some acute myelogenous leukaemias can present with eosinophilia, but the relationship between HES and ALL is not well known and is rarer than the relationship between HES and acute myelogenous leukaemia. Patients are diagnosed with HES when no cause is found to explain the eosinophilia leading to end organ damage. For this reason, it is recommended that patients presenting with hypereosinophilia be carefully assessed to exclude any malignant clonal proliferation. HES may present with severe clinical manifestations such as high leucocyte count, anaemia, thrombocytopaenia, hepatosplenomegaly or cardiac and neurological involvement, all of which are primarily features of myeloproliferative disorders. Some patients with HES can develop chronic eosinophilic leukaemia. Successful treatment of HES with agents used in chronic myeloid leukaemia supports the idea that HES can be a chronic myeloid disorder. There are few cases reporting an association between ALL and hypereosinophilia that precedes or is concomitant with ALL. Here we report the case of a 14-year-old girl who developed common B ALL 7 months after diagnosis and treatment of HES. Interestingly, eosinophilia was not concomitant with the diagnosis of ALL.     

Nitric oxide directly inhibits ghrelin-activated neurons of the arcuate nucleus

The hypothalamic arcuate nucleus (Arc) is a target site for signals regulating energy homeostasis. The orexigenic hormone ghrelin directly activates neurons of the medial arcuate nucleus (ArcM) in rats. Nitric oxide (NO) is a neuromodulator implicated in the control of food intake and body weight. NO is produced by nitric oxide synthase (NOS) and induces the formation of cyclic guanosine monophosphate (cGMP) via a stimulation of soluble guanylate cyclase (sGC). Both enzymes NOS and sGC have been identified in the Arc. Using extracellular recordings we characterized the effects of NO signaling on ArcM neurons and their co-sensitivity to ghrelin. The artificial NO donor sodium nitroprusside (10(-4) M) reversibly inhibited 91% of all ArcM neurons by a direct postsynaptic mechanism. 52% of ArcM neurons were excited by ghrelin. In all but one of these neurons SNP caused inhibitory responses. The SNP-induced inhibitions were mediated by cGMP since they were blocked by the specific sGC inhibitor ODQ (1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one, 10(-4) M). Furthermore, the membrane permeating cGMP analogue 8-Br-cGMP (10(-4) M) mimicked the inhibitory responses of SNP. In immunohistological in vitro studies SNP induced a cGMP formation, which could also be blocked by ODQ. The current studies demonstrate that NO/cGMP signaling inhibits a large population of ArcM neurons including ghrelin-excited cells. Since an activation of the latter neurons is regarded as a correlate of negative energy balance, NO may represent an anorectic neuromodulator in the Arc and/or restrain the action of signals promoting energy intake. NO signaling in the Arc is also induced following inflammation suggesting a possible role of Arc-intrinsic NO in disease-related anorexia.