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D A Denham

Publications and source records attributed to D A Denham.

At least 91 records · Page 5Linked to original sources

Infections of Brugia pahangi in conventional and nude (athymic) mice.

AKR, BALB/c and CBA/Ca and T.O. mice were completely resistant to infection with third stage infective larvae of Brugia pahangi. Third, fourth and fifth stage worms transplanted from the peritoneal cavity of jirds into the peritoneal cavity of mice continued to develop. BALB/c mice were the most susceptible of the strains tested and adult worms were obtained after each type of transplanted infection. Congenitally athymic nude mice were much less resistant to transplanted worms and infective larvae developed to full maturity in most of them. Ten of 14 athymic mice infected by the intraperitoneal (ip) inoculation of infective larvae had microfilariae in their blood or peritoneal cavities. At autopsy a percentage recovery of adult worms of 0-38% (mean 11.1%) was obtained. Microfilariae were only found in the blood of 2 of 6 athymic mice infected by subcutaneous (sc) infection and at autopsy 0-19.1% (mean 6.1%) recoveries were obtained. The thymic littermates of the nudes were more resistant than those most of the other strains used.

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A comparison of the anthelmintic effects of oxfendazole and oxibendazole on Trichinella spiralis in mice.

Oxfendazole was shown to be a very potent agent in killing Trichinella spiralis. A single dose of 1.6 mg/kg per os killed 99% of preadults. Adults were much more resistant; 25 mg/kg killed 56%, even 3,200 mg/kg only killed 94%. Developing and encysted muscle larvae were also killed; 7 X 50 mg/kg killed 99% and 98%, respectively. Oxibendazole was less effective. 6.25 mg/kg killed 99% of preadults, and 3,200 mg/kg killed only 69% of adults. Although oxibendazole also killed developing and encysted muscle larvae, much higher dosages were required; 7 X 200 mg/kg killed 99% of developing larvae and 82% of encysted larvae.

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Chemoprophylactic activity of flubendazole against adult Brugia pahangi transplanted into the peritoneal cavity of jirds.

Jirds were treated by the subcutaneous injection of 100 mg flubendazole per kilogram. They were infected subsequently by the implantation of adult Brugia pahangi intraperitoneally at different times. No adult worms survived in jirds treated 9 wk before infection. Thereafter, increasing numbers of adult worms survived so tht by 21 wk there were almost as many worms in the treated jirds as in untreated controls.

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Brugia pahangi infections in normal kittens (Felis cattus) and kittens born to Brugia spp. infected mothers.

Kittens mothered by normal cats challenged within 14 days of birth were as susceptible to infection with Brugia pahangi as more mature cats. When kittens mothered by cats which were infected with Brugia spp. were challenged very variable results were observed. Several of the kittens were resistant to infection, but this did not appear to be related to the degree of resistance shown by their mothers.

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The anthelmintic effects of flubendazole on Brugia pahangi.

The anthelmintic effects of flubendazole (methyl [5-(4-fluorobenzoyl)-1-H-benzimidazol-2-yl] carbamate) (Janssen Pharmaceutica) were evaluated in jirds (Meriones unguiculatus) and cats (Felis cattus) infected with Brugia pahangi. Flubendazole was macrofilaricidal at 5 x 2.5 mg/kg and 1 x 25 mg/kg in jirds and 1 x 100 mg/kg in cats when administered by subcutaneous injection. It also killed developing larvae in jirds. It was not microfilaricidal.

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Effects of immune serum and cells on newborn larvae of Trichinella spiralis.

Serum and cells, collected from mice immunized by infection either with newborn larvae (NBL) or per os with infective larvae of Trichinella spiralis, were passively transferred to mice which were challenged with NBL. Serum always gave very strong protection if given before challenge but not if given within 2 h after challenge. Cells from mice immunized with NBL also gave good protection, whereas those from mice immunized per os did not. If NBL were incubated in serum from immunized mice their infectivity was reduced, but if the serum was pre-absorbed with NBL this effect was lost. Such absorbed serum did not confer immunity on recipient mice.

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Successful vaccination of cats against Brugia pahangi with larvae attenuated by irradiation with 10 krad cobalt 60.

Cats were vaccinated by the inoculation on 10 occasions of approximately 300 larvae of Brugia pahangi which had been irradiated with 10 krad cobalt 60. They were challenged on 3 occasions with normal larvae of either B. pahangior B. patei. The vaccinated cats were resistant to challenge as demonstrated by either longer pre-patent periods or failure to become microfilaraemic and by having fewer third, fourth or adult worms than normal controls. Although the vaccination procedure was unpractically heavy these results lend encouragement to the possibility of developing vaccines against filarial infections.

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Studies with Brugia pahangi. 20. An investigation of 23 anthelmintics using different screening techniques.

23 anthelmintics were tested against Brugia pahangi microfilariae and infective larvae in vitro and in Aedes aegypti infected with B. pahagi and jirds (Meriones unguiculatus) infected with a B. pahangi/patei hybrid. There was little correlation between the results obtained in vitro and in infected insects and the results obtained in these tests gave no indication of the activity in jirds. Three of the compounds were macrofilaricidal in jirds and these were tested in cats infected with B. pahangi. One of these--5-benzamido-2(4-thiazolyl)-benzimidazole--was macrofilaricidal in cats and it is suggest that it should be tested in other filarial systems. It is concluded that the insect and in vitro tests are not good primary screens for filaricidal activity.

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Intrauterine development of the microfilariae of Dipetalonema viteae.

The egg shell of Dipetalonema viteae separated from the oolemma and became highly convoluted at an early stage of development. No second oolemma or trilaminate membrane was seen. Channels containing electron dense material (thought to be nutrient material from the uterine wall) were formed between adjacent embryos. Many developing embryos died. Microvilli were formed by the uterine wall and developing embryos were closely apposed to these (again presumably to obtain nutrient). Embryos emerged from the egg in the uterus and were born as unsheathed microfilariae.

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Studies with Brugia pahangi. 15. Cobalt 60 irradiation of the worm.

Infective larvae of Brugia pahangi were irradiated at 10, 25 or 45 krads by means of a Cobalt 60 source. In cats, 10 krads caused the worms to be stunted and sterile but allowed them to become 5th stage, migrate posteriorly into the afferent lymphatic, and produce pathology. 25 krads prevented the worms from developing beyond the early fourth stage and from migrating away from the popliteal lymph node. No gross pathological reacions were evident. 45 krads produced the same effects as 25 krads but the longevity of the worms was much reduced.

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Studies with Brugia pahangi. 16. Precipitation antibody in infected cats detected by counterimmunoelectrophoresis.

In cats infected with normal, or irradiated, infective (L3) larvae of Brugia pahangi counterimmunoelectrophoresis revealed the presence of antibody to soluble antigens derived from microfilariae, adults and infective larvae of the same parasite. Infected cats with a persistently high to moderate microfilaraemia gave positive precipitin reactions to L3, microfilarial and adult worm antigens. Cats which had become amicrofilaraemic had antibody to L3 and microfilarial antigens but not to adult worm antigen. Serum from cats inoculated with irradiated L3 larvae produced a precipitin reaction only to the L3 antigen.

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Studies with Brugia pahangi. 18. Anthelmintic effects of stibocaptate.

Stibocaptate (Asiban, Hoffman--La Roche) killed third stage larvae of Brugia pahangi in vitro at 50 p.p.m. but had no effect on microfilariae at 1 X 10(4) p.p.m No larvae developed in infected mosquitoes fed 1% stibocaptate in 10% sucrose. It was neither micro-nor macrofilaricidal in either jirds or cats but did affect embryogenesis.

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Strongyloides ratti: the effect of betamethasone on the course of infection in rats.

Rats were treated with betamethasone at different stages of infection with Strongyloides ratti. Treatment caused a diminution in the number of adult worms recovered but this residual population was not expelled as were worms from untreated rats. If treatment was started after expulsion had already begun adult worm numbers increased--suggesting that autoinfection occurred. Treatment throughout a primary infection prevented the development of an immune response which expelled, or killed, a challenge infection. Treatment, just before and just after challenge, prevented the expulsion of the challenge infection. Worm expulsion up to day 35 was prevented by treating rats with betamethasone 4, 6, 8 and 10 days after infection.

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Hybridization between Brugia patei, B. pahangi and sub-periodic B. malayi.

Virgin females of Brugia malayi, B. pahangi and B. patei were mated with males of species other than their own to determine whether they would hybridize. Microfilariae were produced in all but one cross (that between B. pahangi males and B. malayi females). Hybrid infective larvae, produced in mosquitoes and inoculated intraperitoneally into jirds, grew to adults but these were unable to produce microfilariae because hybrid males did not produce spermatozoa. Hybrid females were fertile and produced microfilariae when crossed with males of their parental species.

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Studies with Brugia pahangi 17. The anthelmintic effects of diethylcarbamazine.

Diethylcarbamazine (DEC) was active in vitro against infective larvae and microfilariae of Brugia pahangi but only at high concentrations. When fed to mosquitoes which were infected with B. pahangi it had little or no activity. In jirds it was inactive against B. pahangi microfilariae and adults when administered at 300 mg/kg for 5 days either by the intraperitoneal or oral route. In cats given 25 or 50 mg DEC/kg intraperitoneally on 3 or 5 occasions it was not microfilaricidal, but most of the adult worms died within 30 days of the end of treatment. Although most microfilariae disappeared from the blood of cats immediately (i.e., within an hour) after treatment, they reappeared within a few hours in the same numbers. Microfilarial levels were reduced after treatment but there was no precipitate decline as occurs in human B. malayi patients.

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