Junaidi Khotib

NEUROGENIC MODULATION BY NEUROKININ-1 RECEPTOR ANTAGONIST, CP-96,345 TO INHIBIT RHEUMATOID ARTHRITIS DEVELOPMENT IN ADJUVANT INDUCED ARTHRITIS RAT MODEL

Rheumatoid arthritis (RA) is a chronic form of persistent inflammation. Meanwhile, Substance P is the most associated neuropeptide in neurogenic inflammation and hyperalgesia commonly found in chronic pain. Substance P act by binding to neurokinin-1 receptor. The present study was conducted to evaluate the effect of neurokinin-1 receptor antagonist (CP-96,345) on Adjuvant Induced Arthritis rat model, induced by Complete Freund’s Adjuvant (CFA). The objective is to attenuate neurogenic inflammation which in turn will increase the latency time of hyperalgesia response, decreases neurokinin-1 receptor expression, and inhibits the development of RA in AIA rat model. Rats were intra-articularly injected with CFA 1 hour after the administration of CP-96,345 either by 0.63 µg/gr; 1.25 µg/gr; or 2.5 µg/gr also intra-articularly. Caliper measurements and hot-plate test were performed on day 0, 3, 5, 7, 9, 11, and day 13. Expression of neurokinin-1 receptor in joint tissue were evaluated by immunohistochemistry, and RA progress in joint tissue were observed hystopathologically. CP-96,345 at 2.5 µg/gr significantly increases the latency of hyperalgesia response time on CFA induced rats (p=0.044) and decreased the neurokinin-1 receptor expression in joint tissue (p=0.029) compared to CFA induced rats. There was no significant difference for caliper measurements and RA progress between CFA incduced rats and treated group. Conclusively, CP-96,345 increases the latency of hyperalgesia response time and decreases the NK-1 receptor expression in rat joint but could not inhibit RA progression.

EFFECT OF HYDROXYETHYL STARCH 200/0.5 ON VON WILLEBRAND FACTOR SERUM LEVEL AND ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT)

Hydroxyethyl starch (HES) is a colloid administered frequently for intravascular volume expansion during perioperative period. Impairment of haemostasis have been reported during HES administration, but the volume of solution administered was usually higher than 20 ml.kg-1. The objective of this study was to evaluate the effect of Hydroxyethyl starch 200/0.5 dose less than 20 ml.kg-1 on von Willebrand factor serum level and activated partial thromboplastin time. A prospective, observational study was conducted to evaluate von Willebrand factor and activated partial thromboplastin time of patients receiving Hydroxyethyl starch 200/0.5. Inclusion criteria were patients undergoing elective surgery who were going to receive Hydroxyethyl starch 200/0.5 intraoperatively. Fourty six patients were divided into patients receiving crystalloid only group (n=23 patients) and hydroxyethyl starch (n=23 patients). Coagulation variables were assesed 30 minute after insicion and 60 minute after infusion of crystalloid or colloid. Measurement of von Willebrand within each group after crystalloid or HES 200 infusion showed significant decrease, from (mean±SE) 97.688±15.219 ng/ml to 31.611±10.058 ng/ml (p< 0.001) in crystalloid group and 92.884±15.208 ng/ml to 27.378±6.399 ng/ml (p<0.001) in HES 200 group. Activated partial thromboplastin time change was statistically significant (mean±SE) 31.27±1.39 to 35.61±1.62 in HES group only (p=0.007), but this change was not clinically significant. In conclusion, there was neither significant difference in von Willebrand serum level nor in activated partial thromboplastin time between the two groups. There was no coagulation influence with clinically significant effect in the use of HES 20 ml/kg BW in patients undergoing elective surgery.