Interleukin-33 (IL-33) is a well-recognized immunomodulatory cytokine which plays critical roles in tissue function and immune-mediated diseases. The abundant expression of IL-33 in brain and spinal cord prompted many scientists to explore its unique role in the central nervous system (CNS) under physiological and pathological conditions. Indeed emerging evidence from over a decade's research suggests that IL-33 acts as one of the key molecular signaling cues coordinating the network between the immune and CNS systems, particularly during the development of neurological diseases. Here, we highlight the recent advances in our knowledge regarding the distribution and cellular localization of IL-33 and its receptor ST2 in specific CNS regions, and more importantly the key roles IL-33/ST2 signaling pathway play in CNS function under normal and diseased conditions.
SummarySodium hyaluronate solutions have been advocated in the management of a variety of dry-eye states. By virtue of their non-Newtonian rheological properties, for mulations exhibiting high zero-shear viscosities may be used as an artificial tear with the expectation of prolonged precorneal residence times and improved tolerance.Quantitative gamma scintigraphy was used to evaluate the residence times of 0.2% and 0.3% sodium hyaluronate solutions and a polymer-free solution of buffered saline in 12 patients with keratoconjunctivitis sicca and a group of six normal volun teers. Using several indices of residence time, mean values for the sodium hyalur. onate solutions were significantly longer than those for buffered saline. Parallel changes in tear film thickness were also demonstrated using a technique based on laser interferometry.Although a variety of therapeutic strategies can be utilised in the management of dry-eye disorders,1.2 the basis of therapy remains the artificial tear. The principal limitation of currently available tear substitutes is the short duration of symptom control experienced by some patients. A number of approaches have, therefore, been adopted to prolong the time they remain in contact with the ocular surface including the use of high viscosity formula tions,"· slow-release artificial tears' and occlusion of the lacrimal puncta.1> However, none of these methods have met with uniform success.Polymer solutions formulated at high vis cosity have longer residence times, 7 .H but are poorly tolerated because of transmitted 'University of Oxford, Department of Ophthalmology.shearing forces associated with blinking and rapid eye movements. It is in this respect that formulations of polymers that display non Newtonian or pseudoplastic properties offer a potential therapeutic advantage over conven tional artificial tears. At concentrations of 0. 2% and 0.3% , sodium hyaluronate solu tions exhibit high static. or zero-shear, vis cosities but undergo dramatic reduction in viscosity with increasing shear rate� (Fig. 1), thereby offering significantly less resistance to the movement of the lid over the globe than viscous Newtonian formulations. It is the expectation of prolonged residence time asso ciated with high zero-shear viscosities, and of patient acceptance owing to its shear-thinning behaviour, that has lead to the investigation of
The International Association for the Study of Pain, has defined pain as "an unpleasant sensory and emotional experience connected with actual or potential tissue damage or described in terms of such damage". It was thought that the newborn baby does not experience pain because of incompletely developed nervous system. However, it has been shown that neurological system known to be associated with pain transmission and modulation, is intact and functional. A study was conducted in our center to study the analgesic effect of administration of oral glucose in various concentrations, in neonates undergoing heel punctures, for collection of blood for investigations. This was compared with the analgesic effects of breast milk (which contains lactose). 125 full term normal neonates with no history of birth asphyxia or underlying neurological abnormality, requiring heel punctures for collection of blood for various investigations were selected for the study. They were matched for gestational age, birth weight and sex distribution and divided into 5 groups of 25 each. One group comprised control subjects and was administered sterile water. 3 groups were administered 1 ml of varying strengths of glucose solutions i.e. 10%, 25% and 50% respectively. The last group was given 1 ml of expressed breast milk (EBM). Prior to heel pricks, state of arousal, baseline heart rate (HR) and transcutaneous oxygen saturation (SpO 2 ) were recorded by pulse oximeter in each neonate. Autolet, a mechanical device for capillary sampling, was used for heel pricks to give equal strength of painful stimulus in each procedure. Audio tape recorder was used to record the cry. The oral solution was administered slowly over 30 seconds by means of a syringe placed in the mouth. Heel puncture was done after 2 minutes, taking all aseptic precautions. HR and SpO 2 were monitored using pulse oximeter. Pain response was assessed, by recording duration of crying, change in HR, change in SpO 2 and facial action score after the procedure. Mean duration of cry and total cry over 5 minutes was significantly less in groups given 25% and 50% glucose solutions as compared to the control group and babies given EBM. Difference in mean increase in HR, fall in SpO 2 were statistically significant between control group, EBM group and neonates given 25% and 50% glucose solutions respectively. Compared to control group, all other administered solutions (10%, 25%, 50% glucose and EBM) were found to reduce physiological and behavioral responses in neonates undergoing heel punctures. 25% and 50% glucose solutions were found to have maximal analgesic effect and both were found to be equally effective. EBM and 10% glucose solution have an equal analgesic effect but less than 25% or 50% glucose. This simple, cheap and safe method of oral analgesia can be easily used in neonates undergoing heel prick procedures during routine neonatal care. MJAFI 2003; 59 : 100-104
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