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A Farrell

Publications and source records attributed to A Farrell.

47 records · Page 3Linked to original sources

Oxidative damage to hyaluronate and glucose in synovial fluid during exercise of the inflamed rheumatoid joint. Detection of abnormal low-molecular-mass metabolites by proton-n.m.r. spectroscopy.

Proton Hahn spin-echo n.m.r. spectroscopy was employed to detect abnormal metabolites present in rheumatoid synovial fluid that are derived from the deleterious generation of reactive oxygen radical species during exercise of the inflamed rheumatoid joint. A resonance attributable to a low-molecular-mass N-acetylglucosamine-containing oligosaccharide formed by the oxygen-radical-mediated depolymerization of synovial-fluid hyaluronate was clearly demonstrable when subjects with inflammatory joint disease were exercised. Moreover, formate, which may be derived from the attack of OH.radical on synovial-fluid carbohydrates, was also readily detectable in these samples. gamma-Radiolysis of rheumatoid synovial fluid samples and aqueous solutions of hyaluronate also gave rise to the production of the low-molecular-mass hyaluronate-derived oligosaccharide species and markedly elevated concentrations of (non-protein-bound) formate in the biological fluids. As expected, corresponding spectra of gamma-irradiated blood serum samples obtained from normal volunteers did not contain the signal attributable to the low-molecular-mass oligosaccharide species, but the formate resonance (barely detectable in non-irradiated normal serum samples) became clearly visible. Additionally, a curious increase in the effective concentration of non-protein-bound low-molecular-mass metabolites such as acetate, citrate, lactate and glutamine was observed after gamma-radiolysis of all biological fluids studied. The hyaluronate-derived low-molecular-mass oligosaccharide species and formate are suggested as novel markers of reactive oxygen radical activity in the inflamed rheumatoid joint during exercise-induced hypoxic/reperfusion injury.

Adult↗

Behavioral and pharmacological specificity of the feeding elicited by cholinergic stimulation of the substantia nigra in the rat.

Microinjections of the cholinergic agonist carbachol into anterior substantia nigra dose dependently increased food intake in satiated rats. This resulted from a prolongation of the duration of eating. In the absence of food, those doses of carbachol that stimulated food intake (.1 and .5 microgram) had no effect on any other response examined, including gnawing, drinking, locomotion, grooming, sniffing, and rearing. The effect of carbachol depended on the degree of prior food deprivation, but supra-additive effects of carbachol and deprivation were not observed. These results are contrasted with those of previous studies demonstrating the nonspecific behavioral effects of electrical stimulation of the brain and of studies showing that carbachol has radically different behavioral effects at other central nervous system sites. Microinjection of an acetylcholine/eserine sulfate mixture also significantly increased food intake. This response was abolished by prior microinjection of the muscarinic receptor antagonist atropine into the substantia nigra, a result that provides evidence for pharmacological specificity of the behavioral effects. These data provide further evidence for the hypothesis that a functional cholinergic system is present within substantia nigra.

Acetylcholine↗

Age-related decline in receptivity in normal, neonatally androgenized female and male hamsters.

The pattern of female sexual behavior shown by aging male and female hamsters was related to exposure to perinatal androgen. Twenty-five female and 37 male hamsters in Experiment 1 was gonadectomized on the day of birth or at 43 days of age. The received 11 tests for receptivity between the ages of 28 and 66 wk. In Experiment 2, 83 females were implanted with a Silastic pellet containing 3, 1, 3 or 9% testosterone (T) or testosterone propionate (TP) by weight from the second to the tenth day of life, and tested approximately every 2 wk from 22 to 58 wk of age. Receptivity was induced by estradiol benzoate and progesterone injected before each 600 sec mating test. Normal females exhibited the highest lordosis scores, followed by minimally androgenized females and males castrated at birth. High doses of exogenous or endogenous perinatal T suppressed receptivity throughout the animal's lifespan, but did not accelerate the rate of decline in female behavior over time. Non-androgenized animals showed the greatest decrease in receptivity with advanced age.

Aging↗

Suppression of the development of female hamster behaviour by implants of testosterone and non-aromatizable androgens administered neonatally.

Testosterone in its free form, and dihydrotestosterone (DHT) and androsterone, both androgens which are not aromatizable to oestrogen, injected in oil during the neonatal period have been reported not to modify the development of female sexual behaviour. This failure might be due to the short period of activity of these substances when injected in liquid vehicles. In the current study, a Silastic pellet containing 9% of its weight of testosterone, androsterone, or DHT was implanted subcutaneously in 42 female and 38 neonatally castrated male hamsters on day 2 of life and removed on day 10. Pellets of pure Silastic were implanted in 36 control animals. Males were gonadectomized on day 5 and females on day 45. Female sexual behaviour induced by oestradiol benzoate and progesterone was measured in a series of 10-min mating tests with vigorous males, starting at 55 days of age. The duration of lordosis was consistently reduced below control levels in females implanted with testosterone, DHT, and androsterone, and in males, with testosterone and DHT. Thus the free form of testosterone, and some non-aromatizable androgens, when present for a sufficiently long period after birth, can permanently suppress development of female reproductive behaviour.

Androsterone↗

Estrogen receptor (alpha and beta) expression in the excurrent ducts of the adult male rat reproductive tract.

The understanding of estrogen's function in the male reproductive tract is limited, and estrogen receptor (ER) localization in the reproductive tract of the adult male rat has not been described. In the present study, ERalpha was localized by immunohistochemistry using ER21 antibody, which recognizes only ERalpha. Strongest immunoreactivity was seen in epithelia of ductuli efferentes and the initial segment of the epididymis. Nuclei of both ciliated and nonciliated cells were positive. The epithelium of the rete testis, and caput, corpus, and cauda epididymides stained less intensely for ERalpha. The vas deferens epithelium was ERalpha-negative. Stromal tissue in the excurrent ducts was also ERalpha-positive. Using 3H-estradiol autoradiography, specific binding of estradiol was seen in nuclei of ductuli efferentes. Estrogen receptor alpha mRNA expression was greatly enhanced in ductuli efferentes compared to other regions of the male tract and was 3.5x greater than in the uterus. For comparison, the presence of ERalpha was determined using reverse transcription-polymerase chain reaction (RT-PCR) amplification. Estrogen receptor beta mRNA was expressed throughout the male tract and in the prostate. These results indicate that all organs in the male excurrent ductal system of the rat express ERalpha and are potential targets of estrogen. However, the ductuli efferentes are the site of the most intense ERalpha expression. The role of ERbeta remains to be determined, but its expression appears ubiguitous in the male tract.

Animals↗