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Biomedical subjects

J D Doherty

Publications and source records attributed to J D Doherty.

At least 19 recordsLinked to original sources
PubMed1994

Age-dependent differences in the susceptibility of rats to deltamethrin.

Separate groups of weanling and adult rats were exposed to both behaviorally active and lethal doses of deltamethrin to examine age-dependent toxicity of a pyrethroid over a wide dose range. The acoustic startle response (ASR) was selected for comparison at low doses since it is a sensitive, quantifiable biological indicator of pyrethroid effects in rats. Acute mortality was included for comparison at the upper limit of the dose-response. Deltamethrin was administered by gavage as a single dose in corn oil for all tests. Effects on the ASR were comparable in 21- and 72-day-old rats, with a 4-mg/kg dose decreasing ASR amplitude by approximately 50% (ED50) at both ages. By comparison LD50 values in 11-, 21- and 72-day old male rats were 5.1, 11, and 81 mg/kg, respectively. Thus, 11- and 21-day-old male rats were 16 and 7 times, respectively, more sensitive than adults to acute lethality. The concentration of deltamethrin was measured in whole-brain tissue from weanling and adult males treated with ED50 and LD50 doses. The brain concentration of deltamethrin at the ED50 dose of 4 mg/kg was higher in weanling rats than adults. This suggests a possible functional difference, with weanling rats being less susceptible than adults to a low dose. By comparison, there was an equivalent concentration of deltamethrin in brain tissue following an LD50 dose of 12 mg/kg in weanling rats and 80 mg/kg in adults. These results support age-related differences in pharmacokinetics as the basis for the markedly greater sensitivity of young rats to a lethal dose of deltamethrin.

Acoustic Stimulation↗
PubMed1990

Electrophysiological changes in animal model of chronic cardiac failure.

STUDY OBJECTIVE: The aim of the study was to examine right ventricular electrophysiological changes in an animal model of chronic cardiac failure. DESIGN: Cardiac failure was induced in rabbits by intravenous doxorubicin 1 mg.kg-1 twice weekly for 8 weeks. Controls were injected with saline. Electrophysiological recordings were made in conscious animals using bipolar pacing electrodes implanted in the right ventricular apex. SUBJECTS: Adult male New Zealand white rabbits, weight 2.5-3.5 kg, were used (n = 27 doxorubicin treated, 20 control). MEASUREMENTS AND MAIN RESULTS: Recordings were made of effective refractory period and of the stimulus-T interval (Stim-T) of the paced evoked response, an index of ventricular repolarisation time. Progressive shortening of Stim-T and effective refractory period occurred in doxorubicin treated animals, with a reduction of 12% in repolarisation and 14% in refractoriness by week 10. No significant changes in Stim-T or effective refractory period occurred in controls. Right ventricular papillary muscles from doxorubicin treated animals in vitro also showed shortening of intracellular action potential duration and effective refractory period compared with controls. Changes in the doxorubicin treated animals were not attributable to a direct acute electrophysiological effect of doxorubicin or to differences in plasma electrolytes, noradrenaline or renin. CONCLUSIONS: Shortening of ventricular repolarisation and refractory period in heart failure may represent an intrinsic mechanism predisposing to arrhythmia and sudden death.

Action Potentials↗
PubMed1988

Pyrethroids and the striatal dopaminergic system in vivo.

1. Type I (permethrin and allethrin) or type II (cypermethrin and fenvalerate) pyrethroids caused 23-37% increases in the striatal content of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC). 2. Toxicity symptoms and increases in DOPAC were associated with higher brain concentrations for type I (2.6-5.8 micrograms/gm) than type II pyrethroids (0.4-0.6 micrograms/gm). 3. No specific difference in the interaction between type I and II pyrethroids and the striatal dopaminergic system were recognized.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Height of women, twinning and breast cancer: epidemiological evidence of a relationship.

A comparison was made of the stature of women, twinning rates, and breast cancer mortality for 32 countries. As height increased, so did twinning and breast cancer mortality (P less than 0.005). Dizygotic twinning and breast cancer increased sharply with the mean height of the female population. With due caution in drawing causal inferences when uncontrolled confounding variables are present, it is suggested that these findings are an evolutionary consequence of the high mortality found in twin pregnancy.

Body Height↗
PubMed1988

Perinatal mortality in twins, Australia, 1973-1980: I.

The perinatal outcome of twin births in Australia is described from 1973 to 1980. Over that period, the perinatal mortality rate declined more slowly in twins than singletons. The stillbirth rate actually increased in twins due to a rise in antepartum deaths. An increasing proportion of monozygotic twins may have contributed to this trend. The overall perinatal mortality rate was 82.85/1,000 for twins and 16.49/1,000 for singletons, giving a relative risk of 5.0.

Australia↗
PubMed1988

Perinatal mortality in twins, Australia, 1973-1980: II. Maternal age, lethal congenital malformations and sex.

The influence of maternal age and congenital malformations on perinatal mortality in twins in Australia from 1973 to 1980, is described. Stillbirths and neonatal deaths in twins fell with advancing maternal age. For teenage mothers, the twin perinatal mortality rate was 127.15/1,000. The sex ratio in twins is closer to unity than in singletons. Perinatal mortality due to malformation fell as maternal age increased up to 35 years. The role of zygosity and the distribution of birth weight with maternal age are discussed.

Australia↗
PubMed1988

Fertility, fecundity and twinning: a comparison of the trends in births and twinning in Australia from 1854 to 1982.

The trends in births and in twinning in Australia are compared from 1854 to 1982. Until about 1930 the twinning rate increased as births fell. The two rates then became concordant. The relationship of fecundity to twinning is discussed. Comparison with other countries is made. The period embraces the demographic transition when changing contraceptive practices would have had a variable effect on twinning.

Australia↗
PubMed1986

Synaptic effects of the synthetic pyrethroid resmethrin in rat brain in vitro.

Resmethrin (30 microM) induced release of transmitters was not affected by manipulation of the Na+ current with either choline or tetrodotoxin agents which readily reversed the effects of veratridine, deltamethrin and cypermethrin. Resmethrin (I50: 2.2 microM) inhibited the ATP dependent uptake of Ca2+ but deltamethrin and cypermethrin were much less effective. Resmethrin also displaced Ca2+ from crude synaptosomal membranes. The release promoting effects of resmethrin in rat brain in vitro are better explained by its effects on Ca2+ rather than through a specific effect on the Na+ channel. In contrast, the effects of deltamethrin and cypermethrin promote transmitter release by a Na+ dependent process.

Animals↗
PubMed1986

The secular trend of twinning in Australia, 1853-1982.

The incidence of twinning in Australia from 1853 to 1982 is described. The overall trend was determined by changes in the dizygotic rate and, for more than a century, it has been similar to that found in Finland and the South of Italy. It is not explained by demographic changes and there is no clear relationship with industrialisation or psychosocial factors. Monozygotic twinning has increased, most markedly in the 1970s. No adequate explanation has been given for this increase, so continuing surveillance in many different populations is necessary.

Age Factors↗
PubMed1983

Mn2+-stimulated ATPase in rat brain.

Divalent cation ATPases were prepared from rat brain synaptic vesicles, synaptosomal plasma membranes, and plasma membranes from the brain stem and sciatic nerve and tested for optimal stimulation by Mn2+, Mg2+, or Ca2+. ATPase in the synaptic vesicle subfraction was optimally stimulated by Mn2+. All plasma membrane preparations were optimally stimulated by Mg2+. Separate Mn2+ and Mg2+ ATPases could not be distinguished by either chemical inactivation or substrate preference criteria. Mn2+ stimulated ATPase in the micromolar range and it is suggested that Mn2+ interaction with ATPase may be of physiological and/or toxicological importance by being related to the cellular metabolism of this element.

Adenosine Triphosphatases↗
PubMed1982

Role of phospholipids in the inhibitory action of DDT and permethrin on the nerve ATPase of lobster, Homarus americanus.

Efforts were made to understand the nature of the site of 1,1-bis-(p-chlorophenyl)-2,2,2-trichloroethane (DDT) inhibition of nerve ATPase. THe phospholipid content of nerve preparations from the walking leg of the lobster was reduced by treating them with phospholipase A, or with a chloroform-methanol mixture at -75 degrees. By these treatments the enzymes lost approximately 70 or 95% of their phospholipids and 50-80% of their Na,K- and Ca-ATPase activities. The lost ATPase activities could be partially restored by the addition of phospholipids, either the ones extracted from the lobster nerves or those from commercial sources. ATPase inhibition by DDT and permethrin was found to be highest in preparations where the phospholipids were removed by the above treatments, next highest with the untreated original enzyme, and least with the reconstituted ATPase regardless of the source of phospholipids used for reconstitution. This tendency was more pronounced in the case of Ca-ATPase. The effects of DDT and permethrin on inhibition of reconstituted Ca-ATPase were higher when the insecticide was first added to the protein portion and the enzyme was then reconstituted with the phospholipids, than when the same amount of insecticide was first added to the phospholipids which were then used for reconstitution.

Adenosine Triphosphatases↗
PubMed1980

The effect of phencyclidine on dopamine synthesis and metabolic in rat striatum.

Previous behavioral and neurochemical studies indicate that phencyclidine (PCP), a potent psychotomimetic agent, interacts with central dopaminergic systems. We have examined the effects of PCP on the rate of accumulation of 3,4-dihydroxyphenylalanine (DOPA) after the inhibition of L-aromatic amino acid decarboxylase and on the levels of dopamine (DA) metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum. PCP, in doses from 2.5 to 50 mg/kg, decreased the rate of striatal DOPA accumulation. PCP did not antagonized the increase in the rate of striatal DOPA formation caused by haloperidol, reserpine or gamma-butyrolactone (GBL). When given alone, PCP decreased striatal levels of DOPAC and HVA, while it greatly potentiated the haloperidol-induced rise in striatal levels of these two metabolites. PCP is considerably less effective than d-amphetamine in promoting the release of 3H-DA from preloaded striatal slices in vitro. Our results are consistent with the interpretation that PCP potentiates the synaptic effects of endogenous DA. Its mechanism of action appears to be closely related to that of a category of drugs known as non-amphetamine stimulants, which, among others, includes methylphenidate, amfonelic acid and cocaine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1978

Identification of endogenous gamma-hydroxybutyrate in human and bovine brain and its regional distribution in human, guinea pig and rhesus monkey brain.

Gamma-Hydroxybutyric acid (GHB), a compound that has interesting neuropharmacological actions when administered systemically, was shown by means of gas chromatography-mass spectrometry to be present in postmortem samples of human brain in concentrations ranging from 2 to 20 nmol/g. Tissue samples from the basal ganglia contained 2 to 3 times as much GHB as tissue samples from cortical regions. The regional brain distribution of GHB was examined in the guinea pig and rhesus monkey and found to parallel the distribution observed in human brain. The levels of GHB found in the regional areas of human and monkey brain investigated were higher than the levels found in similar regions of guinea-pig brain. Additional studies demonstrated that there is a slow postmortem increase (about 2-fold) in the endogenous levels of GHB in bovine caudate and guinea-pig brain which is maximal about 6 hr postmortem. This postmortem increase could in part explain the higher levels of GHB found in human brain. However, postmortem changes could not account for the large differences observed in the levels of GHB found in bovine caudate and those found in guinea-pig, monkey and human caudate. Only traces of GHB could be detected in human blood and cerebrospinal fluid.

Animals↗