Immunofluorescence study of skin rash in patients with dengue hemorrhagic fever.

Fifty-three skin biopsy specimens obtained from the cutaneous rashes of patients who had dengue hemorrhagic fever (DHF) were studied by immunofluorescence technique. Six specimens showed deposits of IgM, beta 1 C-globulin, dengue antigen, and fibrinogen during the first week of fever. Some but not all of these components (IgM, beta 1 C, dengue antigen) were demonstrated in 29 specimens. Twenty-three of them yielded negative results. Granular deposits of IgM and beta 1 C appeared in the blood vessel walls of dermal papillae. Dengue antigen was seen in mononuclear cells that were closely infiltrated around the blood vessel wall in dermal papillae. Fibrinogen was located within or about the blood vessels. The findings suggest that the cutaneous rashes occurring in DHF are caused by an immunopathologic process.     

Live attenuated tetravalent dengue vaccine

The development of a live attenuated tetravalent dengue vaccine is currently the best strategy to obtain a vaccine against dengue viruses. The Mahidol University group developed candidate live attenuated vaccines by attenuation through serial passages in certified primary cell cultures. Dengue serotype 1, 2 and 4 viruses were developed in primary dog kidney cells, whereas dengue serotype 3 was serially passaged in primary African green monkey kidney cells. Tissue culture passaged strain viruses were subjected to biological marker studies. Candidate vaccines have been tested as monovalent (single virus), bivalent (two viruses), trivalent (three viruses) and tetravalent (all four serotype viruses) vaccines in Thai volunteers. They were found to be safe and immunogenic in both adults and children. The Mahidol live attenuated dengue 2 virus was also tested in American volunteers and resulted in good immune response indistinguishable from those induced in Thai volunteers. The master seeds from the four live attenuated virus strains developed were provided to Pasteur Merieux Connaught of France for production on an industrial scale following good manufacturing practice guidelines.     

Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children

OBJECTIVE: The safety and immunogenicity of tetravalent live-attenuated dengue vaccines after a three dose vaccination series were evaluated in Thai children. METHOD: One hundred three healthy flavivirus-seronegative schoolchildren ages 5 to 12 years were randomized to receive either dengue vaccine containing 3, 2, 1 and 2 log10 of the 50% cell culture infective dose, respectively, of the live-attenuated dengue vaccine serotypes 1, 2, 3 and 4 per dose (F3212; n = 40) or 3, 3, 1 and 3 log10 of the 50% cell culture infective dose (F3313; n = 42) or purified Vero cell rabies vaccine (control group; n = 21) given in a two dose schedule (3 to 5 months apart). A third dose was administered 8 to 12 months after the second dose to 90 subjects. Safety and immunogenicity were evaluated within 28 days after each injection. RESULTS: No serious adverse event related to the vaccines occurred. Most children experienced mild to moderate fever, rash, headache and myalgia occurring within 12 days after Dose 1 and generally lasting 3 days or less. One subject in Group F3212 had a 1-week dengue-like fever. Reactogenicity was minimal after Doses 2 and 3. Transient mild variations in liver enzymes and hematologic indices were noted mainly after Dose 1. After the third dose 89% of the subjects in Group F3212 seroconverted (neutralizing antibody response, > or =10) to all four serotypes, and all children in Group F3313 seroconverted. CONCLUSION: This study demonstrates a moderate although improvable reactogenicity and high seroconversion rates against the four serotypes of dengue after a three dose schedule of tetravalent live-attenuated dengue vaccine in children.     

Extracts of spice and food plants from Thai traditional medicine inhibit the growth of the human carcinogen Helicobacter pylori

BACKGROUND: Helicobacter pylori (HP) is a gramnegative bacterium and well recognized as being the primary etiological agent responsible for the development of gastritis, dyspepsia, peptic ulcer disease and gastric cancer. In developing countries, a high prevalence of HP infection is associated with an increased incidence of gastric cancer. Thailand, however, while having a high prevalence of HP infections, has a lower than expected gastric cancer rate than other developing countries. It has been suggested that the diet and life style in Thailand may explain this discrepancy. MATERIALS AND METHODS: The in vitro susceptibility of 18 strains of HP to 20 extracts of spice and food plants used in Thai traditional medicine for the treatment of GI disorders was assessed. RESULTS: Methanol extracts of Myristica fragrans (aril) inhibited the growth of all HP strains with minimum inhibitory concentration (MIC) of 12.5 micrograms/ml; extracts from Barringtonia acutangula (leaf) and Kaempferia galanga (rhizome) had an MIC of 25.0 micrograms/ml; Cassia grandis (leaf), Cleome viscosa (leaf), Myristica fragrans (leaf) and Syzygium aromaticum (leaf) had MICs of 50.0 micrograms/ml. Extracts with an MIC of 100.0 micrograms/ml included Pouzolzia pentandra (leaf), Cycas siamensis (leaf), Litsea elliptica (leaf) and Melaleuca quinquenervia (leaf). CONCLUSION: Plants used in Thai traditional medicine to treat gastrointestinal ailments inhibit the growth of HP. These data indicate that these plants may have chemopreventative activities and thus may partly explain the reduced incidence of gastric cancer in Thailand.     

Interleukin-17 Increased Progesterone Secretion by JEG-3 Human Choriocarcinoma Cells

Problem  JEG-3 choriocarcinoma cell line has previously been reported to express a receptor for interleukin (IL)-17. The involvement of IL-17 in the production of progesterone and human chorionic gonadotropin by placental trophoblast has not been investigated.
Method of study  The present study investigated the in vitro effect of IL-17 on progesterone and human chorionic gonadotropin (hCG) secretion by JEG-3 cells. Both hormones were quantified using enzyme-linked immunosorbent assays.
Results  The results showed that IL-17 significantly increased progesterone secretion at 6 ( P  < 0.001) and 24 ( P  < 0.01) hr, while this cytokine had no effect on hCG secretion.
Conclusion  Interleukin-17 may regulate the function of JEG-3 cells through increased progesterone secretion.     

A single dose-response effect of aflatoxin B1 on rapid liver cancer induction in two strains of rats

To investigate rapid liver cancer induction in rats by aflatoxin B1 (AFB1), different single oral doses of AFB1 were given to 3 groups of 1-year-old Buffalo and Wistar rats. The animals were treated once and all survivors were killed 6 weeks later. Control animals received an equal volume of solvent (DMSO), and both groups of animals were maintained under identical conditions throughout the period of experiment. The survival rates were 40% with low and medium doses in AFB1-treated Buffalo and Wistar rats, and 0% in the high-dose Buffalo rats. Slight ante-mortem elevations in serum concentrations of glutamic pyruvic transaminase (SGOT) and glutamic oxaloacetic transaminase (SGPT) were indicative of the persistent damage effect of AFB1 at week 6. Total protein and albumin concentrations were not altered. The percent incidence of altered cell foci (areas) and neoplastic nodules was higher in Wistar than in Buffalo rats given a similar low dose. Various stages of well differentiated hepatocellular carcinomas (0.1-0.2 cm in diameter) developed in 3 of 8 Wistar rats. It thus appears that Wistar rats are more susceptible to hepatocarcinogenesis following a single oral dose of AFB1 than Buffalo rats.     

Neurovirulence effects of dengue-2 viruses on the rhesus (Macaca mulatta) brain and spinal cord

Vaccines prepared from attenuated virus can cause symptomatic viral infection of the central nervous system. In the present study, dengue-2 parental and its live attenuated viruses were tested by intrathalamic and intraspinal injections in rhesus monkeys. The dengue-2 viruses were found to be only very weakly neurovirulent when injected directly into the brain or spinal cord of rhesus monkeys.