Shirley X.L. Liu

Novel non-arachidonate-mediated, non-steroidal anti-inflammatory agents

Although corticosteroids are potent anti-inflammatory agents, they produce numerous serious side effects which prevent them from being widely used in the clinics. The classic non-steroidal anti-inflammatory agents (NSAIA) are arachidonate-mediated compounds which are less potent than steroids but which have similar side effects. Therefore, major efforts have been made to search for a novel class of NSAIA. Recent advancement in cytokine research reveals that tumour necrosis factor (TNF), interleukin-6 (IL-6) and particularly interleukin-1 (IL-1), are responsible for most inflammation symptoms. Further, various inflammatory diseases can be treated by the administration of IL-1 receptor antagonists (IL-1ra). Unfortunately, IL-1ra is a polypeptide which is very unstable in the body and requires continuous infusion for hours to be effective as an anti-inflammatory drug. Obviously, a stable, long-acting IL-1 blocker which can be administered orally would be the ideal one to be used in the clinics. Active resear...

Overview Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: Novel, non-traditional, non-steroidal, anti-inflammatory agents

Traditional, non-steroidal anti-inflammatory agents (NSAIAs) are arachidonate metabolite related. Since arachidonate metabolites do not induce the whole range of inflammatory responses, their blockade does not produce anti-inflammatory actions as potent as those of the corticosteroids. The recent development of cytokine research reveals the wide range involvement of IL-1, IL-6 and tumour necrosis factor (TNF) in the inflammatory process. Therefore, cytokine antagonists produce the most effective means of treatment for inflammatory disorders and are as effective, or even more potent, than corticosteroids, without producing the side effects common to such compounds. The only IL-1 blocker available today is the natural IL-1 receptor antagonist (IL-1 RA), a polypeptide which is easily metabolised in the bloodstream with a very short half-life (21 minutes). Thus, active research has been carried out to develop stable, long-acting agents which can be taken by oral administration or by parenteral injections rath...

Prevention of Lens Protein–, Endotoxin– , and Interleukin– 1– induced uveitis with chalcone derivatives

Yao Q-S, Varma RS, Liu SXL, Chiou GCY. Prevention of lens protein-, endotoxin-, and interleukin-1-induced uveitis with chalcone derivatives. Inflammopharmacology. 1994;2:401-409.In order to develop potent non-steroidal anti-inflammatory agents, a new class of agents unrelated to those known to inhibit the arachidonate cascade were investigated. Most of the chalcone derivatives studied, including flavanone hydrazone (RCV/FLV 574), 2’-(o-hydroxyphenol)-5-phenylpyrazoline (RCV-556Pz), 2’-acetoxychalcone-iV-monoacetylhydrazone (RVC-576) and 7V-(o-hydroxybenzoyl) morpholine (RVC-570), inhibited lens protein-induced ocular inflammation effectively at a dose level of 1% (50 μ1 as did prednisolone. Flavanone hydrazone (RCV/FLV 574) was the only compound among all these derivatives which inhibited endotoxin- and interleukin-1 (IL-1)-induced uveitis at 3 mg/kg ip tid this being approximately 7-fold more potent than prednisolone at 20 mg/kg ip tid. It is concluded that a non-steroidal non-arachidonate-mediated potent anti-inflammatory agent based on this compound could be developed with IL-1 blocking activity. However, flavanone hydrazone was rather toxic at effective doses tested. Modification of the chemical structure to reduce its side-effects would, therefore seem essential.

Comparison of Systemic Absorption of Insulin via Conjunctiva with Punctum Sealed and via Normal Eye with Punctum Opened

AbstractIt has been reported that insulin eyedrops are useful preparations for delivering insulin systemically. In order to determine the individual contribution of insulin absorption through the conjunctiva and nasal mucosa, experiments were carried out with and without the puncta occluded, while insulin plus absorption enhancer was instilled into the eye. Blood samples were collected at various time points for blood glucose and plasma insulin determinations. It was found that approximately 28–34% of insulin was absorbed via the conjunctiva and 66–72% through nasal mucosa. The blood glucose was lowered significantly more in rabbits with the puncta opened than in those with the puncta occluded.