Dendritic cells modification during sublingual immunotherapy in children with allergic symptoms to house dust mites.

The importance of dendritic cells (DCs) in the initiation of the Th2-mediated inflammatory response to allergens is well known and more recently it has been proposed that DCs have a pivotal role in maintaining tolerance to allergens. The aim of this study was to investigate whether the success of sublingual immunotherapy (SLIT) in allergic asthma is mediated by the induction of changes of DCs functions. Ten children with allergic asthma sensitive to house dust mite were studied before and after 12 months of SLIT. Immature DCs were derived from peripheral blood monocytes cultured for 6 days in presence of interleukin (IL)-4 and GM-CSF and stimulated with lipopolysaccharide for the last 24 hours to induce maturation. After 12 months of SLIT, mature DCs derived from SLIT-treated patients showed a statistically significant defect of CD86 up-regulation, an increase of IL-10, and a reduction of IL-12 production. SLIT induces changes in DCs functions that might be responsible for an impairment of T cell activation or drive T cells towards a regulatory activity, thus restoring immune tolerance to allergens

Impact of hyperglycemia on neuropathological alterations during critical illness

Context: Although preventing excessive hyperglycemia during critical illness may provide clinical neuroprotection, it remains debated whether normoglycemia is without risk for the brain. Objective: To address this question, we compared the neuropathological alterations in microglia, astrocytes, and neurons, with uncontrolled hyperglycemia, moderately controlled hyperglycemia, and normoglycemia during human critical illness. We further investigated the time course in an animal model. Design and Setting: We analyzed brain specimens from patients who died in the intensive care unit and from critically ill rabbits randomized to hyper- or normoglycemia. Patients/Other Participants: We compared 10 critically ill patients randomized to normoglycemia (104 ±9 mg/dl) or moderate hyperglycemia (173 ±32 mg/dl), and five patients with uncontrolled hyperglycemia (254 ±83 mg/dl) with 16 controls (out of hospital sudden deaths). Critically ill rabbits were randomized to hyperglycemia (315 ±32 mg/dl) or normoglycemia (85 ±13 mg/dl) and studied after 3 and 7 d. Interventions: Insulin was infused to control blood glucose. Main Outcome Measures and Results: Patients with uncontrolled hyperglycemia showed 3.7- 6- fold increased microglial activation, 54-95% reduced number and activation of astrocytes, more than 9-fold increased neuronal and glial apoptosis, and a 1.5-2-fold increase in damaged neurons in hippocampus and frontal cortex (all P≤0.05). Most of these abnormalities were attenuated with moderate hyperglycemia and virtually absent with normoglycemia. Frontal cortex of hyperglycemic rabbits that had been critically ill for 3 d only revealed microglial activation, followed after 7 d by astrocyte and neuronal abnormalities similar to those observed in patients, all prevented by normoglycemia. Conclusions: Preventing hyperg

Congenital solitary kidney size at birth could predict reduced eGFR levels later in life

Objectives: To evaluate the impact of congenital solitary functioning kidney (CSFK) length, measured early in life, on the eGFR levels during the follow-up. Study design: We retrospectively selected 162 CSFK patients undergoing, within 60 days of life, renal length (RL) measurement by ultrasound. We divided the population in:Group 1 = RL ≥ 2 standard deviation score (SDS).Group 2 = RL 2 SDS within 60 days of life was a significant protective factor (hazard ratio = 0.13; 95% C.I. 0.02–0.97) against development of primary outcome. Conclusion: RL ≥ 2 SDS within 60 days of life could identify a population of CSFK with reduced risk of presenting reduced eGFR levels later in life