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Biomedical subjects

J Doull

Publications and source records attributed to J Doull.

64 records · Page 4Linked to original sources
PubMedDate not supplied

Hemoperfusion and pharmacokinetic studies with methamidophos in the rat.

A gas chromatographic method for quantifying methamidophos in plasma was developed and used to study the kinetics of methamidophos in the rat and to evaluate the efficacy of hemoperfusion therapy for treating organophosphate insecticide poisoned individuals. Intravenous administration of methamidophos resulted in a plasma decay curve which corresponded to a one compartment pharmacokinetic model with the following pharmacokinetic parameters: t1/2 = 1.5 hr; Vd = 0.81 L/kg; C1 = 5.8 mL/min/kg; kel = 0.45 hr-1. Hemoperfusion with activated charcoal effectively removed methamidophos from the blood of intoxicated rats, and significantly decreased the body burden of methamidophos; 27% of the administered dose of methamidophos was removed during five hours of perfusion. Despite a rapid reduction in the body burden of the insecticide, rats were not protected against a lethal dose of the insecticide. Because of the rapid and slowly reversible inhibition of acetylcholinesterase by organophosphate insecticides, hemoperfusion alone will not improve the clinical status of organophosphate insecticide poisoned patients.

Animals↗
PubMedDate not supplied

Teratogenic and antiteratogenic effects of nicotinamide derivatives in chick embryos.

Teratogenic and antiteratogenic effects of nine nicotinamide analogs in chick embryos were investigated. Further, the teratisms of 6-aminonicotinamide (6-AN), nicotinamide analogs, and an organophosphate (diazinon) were compared. White leghorn chick embryos were used. Agents were injected into the yolk of eggs on d 3 of incubation. Morphological observations were made on d 17 of incubation. Chemical names for compounds I to IX are: I, 6-dimethylaminonicotinamide; II, 6-diethylaminonicotinamide; III, 6-methylamino-3-(N-methyl)-nicotinamide; IV, 6-dimethylamino-3-pyrimidine carboximide; V, 6-(dimethylamino)-nicotinic acid; VI, 6-chloro-3-[N-(5-diethylamino)-2-pentyl]-nicotinamide; VII, 6-mercaptonicotinamide; VIII, [N-acetyl-N'-(3-pyridyl)-carbonyl]-hydrazine; IX, nicotinamide 1-N-oxide. The LD50 values in mumol per egg were as follows: 6-AN, 0.073; compound II, 0.23; compound III, 1.11; compound I, 1.32; compound VI, about 3. Compounds IV, V, VII, VIII, and IX showed no toxicity or lethality at the highest doses tested (10 mumol/egg). Among the nine nicotinamide analogs, compounds I, II, and III, which have an amino group at the 6-position of the pyridine ring, were teratogenic. Their teratogenic signs were similar to those caused by 6-AN: they showed growth retardation, anteriorly directed short legs, and coarse, dense feathering. The teratogenic effects of compounds I, II, and III were prevented by pretreatment with nicotinamide, as were the effects of 6-AN and diazinon. Among the nine analogs, only compound VIII had an antiteratogenic effect against the diazinon-induced micromelia (in which the cardinal signs were tibiotarsal angulations and poor feathering). For teratisms produced by 6-aminonicotinamide analogs and organophosphates, nicotinamide was an effective antiteratogenic agent. However, some differences in the malformations induced by both types of agents were found. We suggest that the addition of a 3-acetylpyridine type to the nicotinamide-related teratisms (6-AN type, 3-acetylpyridine type, and organophosphate type) will provide a clearer distinction among the types.

Animals↗
PubMedDate not supplied

Teratogenic effects of cholinergic insecticides in chick embryos. III. Development of cartilage and bone.

Teratogenic effects of two organophosphate insecticides, diazinon and dicrotophos, were investigated in regard to skeletal development, particularly of the extremities and vertebrae. Cartilage and calcified bone were examined with alcian blue and alizarin red S staining techniques, respectively, in chick embryos of d 5 to 17 of incubation. The age-related development of both cartilaginous and ossified portions of the hind leg was measured in control and insecticide-treated groups. Diazinon and dicrotophos (200 micrograms/egg), injected on d 3, inhibited growth of the following skeletal elements: femur, tibia, metatarsi and digits of the leg. The inhibition was noticeable from the 9th d of incubation. The greatest reduction of the skeletal length was observed in tibia and metatarsi, and was characterized by angulations toward the dorsal side. Percent of growth inhibition of the calcified region in the legs was similar to that of the entire length of each skeletal element, but there was no difference between control and insecticide-treated groups on the time-related appearance of cartilaginous or calcified long bones, digits, and phalanges of legs. In the cervical region of embryos treated with the insecticides, unique deformities such as an "undulating" notochord and fused cervical rings were seen at an early stage (d 6). We suggest that the organophosphate-induced malformations in legs are mainly due to growth retardation of later stages of development of each skeletal element. On the other hand, the neck deformities result from a profound alteration of differentiation at early stages of development.

Abnormalities, Drug-Induced↗