Effects of antithrombin III and antivenom on procoagulant activity of Russell's viper venom in a whole blood model.

The procoagulant activities of Russell's viper venom were assessed in an in vitro whole blood model. Sequential samplings showed that the generation of fibrinopeptide A (FPA), a marker of thrombin activity, and platelet factor 4 (PF4), a marker of platelet activity, exhibited bi-phasic kinetics with an initial slow phase followed by a rapid phase of secretion. In the presence of Russell's viper venom, the generation of both FPA and PF4 was accelerated with the bi-phasic kinetics of PF4 being maintained while that of FPA completely disappeared. Administration of either antivenom (1,600 ng) or 10 IU antithrombin III (AT-III) had no antagonistic effect against the venom but combination of both resulted in a significant prolongation of both FPA and PF4 release (p < 0.05). High dose AT-III (20 IU) resulted in normalization of both FPA and PF4 kinetics and serial levels of both parameters were lower than those treated with the combined regimen, although these were not statistically significant. Unlike the untreated venom activated whole blood, there was no clot formation following treatment with either the combined regimen or high dose AT-III. The results of this study suggested that the effect of Russell's viper venom on the clotting cascade is more potent and direct than that on platelet activity. There were complementary effects between antivenom and AT-III is controlling of both FPA and PF4 release induced by the venom. Furthermore, in this in vitro experiment, AT-III alone when administered in a sufficient dose, abolished the procoagulant effects of Russell's viper venom.

Characterization of a monoclonal antibody that neutralizes the hyaluronidase activity of Russell's viper venom.

Three monoclonal antibodies (WPN1, WPN2 and WPN3) raised against a partially purified fraction of Russell's viper venom (RVV) were characterized. All three monoclonal antibodies reacted with crude RVV when tested by ELISA, but only two (WPN1, WPN2) neutralized its hyaluronidase activity. WPN1 was the more potent and was effective at an antigen: antibody ratio of 1:3. Furthermore, WPN1 was shown to recognize only the 14,000 MW component of crude RVV. This has been identified in a previous study to be hyaluronidase. This antibody was also found to recognize some components of Calloselasma rhodostoma venom which also possesses potent hyaluronidase activity. The potential therapeutic role of antibodies that neutralize the hyaluronidase component of snake venoms should be investigated further.

Adherence of human eosinophils to infective filariform larvae of Necator americanus in vitro.

Eosinophilia is common in hookworm infection but the interaction between eosinophils and the larval stage of the parasite is poorly understood. The present study was conducted to test the ability of the eosinophils to adhere to infective filariform larvae of Necator americanus in vitro. Adherence of eosinophils to the larvae was found to be serum dependent. Antibody facilitated eosinophil adherence but this was maximal in the presence of complement. The adherence was greatly diminished by EGTA treated normal human serum (NHS) and was completely abolished when NHS was treated with either EDTA or heat-inactivation, suggesting that the process can be facilitated through complement activation via the alternative pathway. As with other nematodes, the surface of hookworm larvae appeared to be both antigenic and complement-activating. Although it is not known whether eosinophil adherence has any larvicidal effect, the present study demonstrated for the first time a definite interaction between human eosinophils and hookworm filariform larvae.

Hepatitis B problem in Thailand.

HBV infection is hyperendemic in Thailand. Approximately 5 million Thais are chronic HBV carriers. The prevalence of HBV markers in general population varies from 40-60%. Approximately 10-20% of children between the ages 1-5 years have serologic evidence of HBV infection and this prevalence increases with age reaching a plateau of 40-60% by age 20. High risk groups are household contacts of HBsAg carriers and babies born to HBsAg positive mothers. Approximately 75% of the babies born to HBsAg & HBeAg positive mothers become HBsAg positive at 3 months after birth. A few studies showed that the HBV prevalence of hospital personnel and other high risk groups is similar to that of the general population. The prevalence of chronic HBsAg carrier varies from 5-10% and is highest among age groups 10-30 years. Primary hepatocellular carcinoma (PHC) is the first and third most common cancer among Thai males and females, respectively. Approximately 35%-75% of PHC in adults are HBsAg positive. Histological studies showed that 47.3% of cryptogenic cirrhosis, 58%-66% of PHC and 35%-85% of cryptogenic cirrhosis with PHC were HBsAg positive. Studies on Hepatitis B immune globulin and Hepatitis B vaccine revealed a 70% and 56%, respectively, reduction in the HBsAg prevalence of infants born to HBsAg and HBeAg positive mothers. More epidemiologic, clinical and laboratory studies on HBV infection are being carried out by groups of scientists and investigators in the Ministry of Public Health and many medical schools. A national committee has been appointed to plan strategy for controlling HBV.