Search PubMed⌕ Search

Biomedical subjects

G D Gray

Publications and source records attributed to G D Gray.

At least 55 records · Page 3Linked to original sources

Relapse of monomorphic and pleomorphic Trypanosoma brucei infections in the mouse after chemotherapy.

Infections in mice were initiated with trypomastigotes from two lines of Trypanosoma brucei derived from the same primary isolated. Infections with one line were initiated by inoculation of metacyclic trypomastigotes from infected tsetse flies and the resulting infections were pleomorphic. The other line had been passaged 32 times in rodents and inoculation of bloodstream trypomastigotes gave rise to monomorphic infections. In both infections there were high levels of parasitaemia until death up to 4 weeks later if the infection was untreated. It was shown that after chemotherapy with 40 mg/kg diminazene aceturate (Berenil) relapses occurred in both types of infection after an aparasitaemic period of 2--3 weeks. Further, it was shown that 3 days after chemotherapy, brain tissue but neither spleen, liver nor blood was capable of transferring infection to normal recipient mice. There were two major differences in the response of the two infections to chemotherapy. First, treatment of the pleomorphic infection as soon as day 6 after infection resulted in a subsequent relapse while the monomorphic infection had to be at least 12 days old at the time of treatment before occurred. Second, following treatment of the pleomorphic, but not of the monomorphic infection there was an early transient recrudescence of low numbers of trypanosomes which were found to be non-infective to recipient mice. The early transient relapse was followed by a further aparasitaemic period and then the late continuous relapse characterised by large numbers of infective trypanosomes.

Amidines↗

The use of Erlangen diamidine 98/202 in relapsing Trypanosoma brucei infections in mice.

Mice infected with T. brucei GVR 23/1 or T. brucei GVR 35/1 for 21 days were treated with the Erlangen diamidine 98/202 (6-amidino-2-[4' amidino-phenyl] thionaphthene-dilacate) at either 5 mg/kg or 35 mg/kg. At both these dose levels the parasites were initially cleared from the circulation although the infections eventually relapsed due to reinvasion from the central nervous system. If the 98/202 therapy is followed by treatment with 5-nitroimidazole only a small number of mice are permanently cured. Adverse reactions, especially at the 35 mg/kg dose level, were noted in one experiment. The Erlangen diamidine given to infected mice three days after infection was able to permanently cure both Trypanosoma brucei stabilates.

Amidines↗

Chemotactic requirements of bovine leukocytes.

A system was described for studying bovine leukotaxis. Chemotaxis was readily observed toward bovine serum activated by zymosan of agarose. However, bacterial culture filtrates and peptides, which were potent chemotaxins for leukocytes from other species, failed to affect bovine leukotaxis. Using conditions suitable for studying binding to leukocytes from other species, specific binding of a radiolabeled chemotactic peptide to bovine leukocytes was not apparent. These data indicate that bovine leukocytes have chemotactic requirements distinct from those of other species.

Animals↗

Dissociation of adrenal corticosteroid production from ACTH in water-restricted female rats.

These experiments were undertaken to investigate the mechanism whereby a precipitous drop in plasma corticosterone concentration is brought about following drinking in rats on a restricted water schedule. No alteration in adrenocorticotrophic hormone (ACTH) output was found, nor was catabolism of corticosterone sufficient to account for the drop. It is concluded that corticosterone level is controlled under these conditions by a mechanism independent of ACTH concentration.

Adrenal Glands↗

Use of sorbitol in the cryopreservation of babesia.

Blood collected from mice infected with Babesia microti was frozen at two different rates to -196 degrees C using 19 per cent (w/v) glycerol as cryoprotectant. Survival of the parasites was measured by recording the parasitaemias of mice inoculated with thawed blood. Parasite survival was increased by using a solution of sorbitol in saline rather than Hanks' balanced salt solution as the diluent for the glycerol and for washing the recovered blood.

Animals↗

Effects of centrifugation stress on pituitary-gonadal function in male rats.

The effects of centrifugation for various lengths of time were investigated on circulating levels of luteinizing hormone (LH) and testosterone in male rats. In a chronic 52-day experiment, centrifugation at 4.1 G significantly reduced LH and testosterone levels for the entire period. Centrifugation at 2.3 G had less effect inasmuch as LH levels were not significantly decreased and testosterone levels were significantly reduced only during the first few days of centrifugation. In more acute experiments, centrifugation at 4.1 G for 4 h resulted in reduced testosterone levels, whereas centrifugation for 15 min did not significantly alter the hormone levels. These results indicate that centrifugation can decrease circulating LH and testosterone levels if the gravitational force is of sufficient magnitude and is maintained for a period of hours. Chronic centrifugation may also inhibit the acute excitatory response of LH to handling and ether stress.

Animals↗

Gonadotropin regulation in middle-aged male rats.

Gonadotropin regulation was compared in middle-aged (13 months old) and young adult (3 months old) male rats. Two experiments were conducted on castrated animals given testosterone in Silastic capsules; the dimensions were adjusted to insure equivalent circulating testosterone levels in the two age groups, as validated by RIA. Plasma LH and FSH were also measured by RIA. In Exp 1, each animal was implanted immediately after castration with multiple capsules sufficient to maintain tonic suppression of LH. One capsule was removed each week, thereby reducing testosterone levels in 0.4 ng/ml steps, in order to determine the testosterone level (threshold) at which LH is released from tonic suppression. Middle-aged animals had a threshold 50% lower than young animals, requiring much less testosterone to maintain tonic LH levels. They also showed an attenuated rise in LH and FSH after release from tonic suppression. In Exp 2, long term castrates were given capsules which produced plasma testosterone levels of approximately 1.5 ng/ml in order to evaluate the negative feedback effects of testosterone on elevated LH levels. The testosterone was more effective in suppressing LH in middle-aged rats than in young animals. These results indicate that: 1) middle-aged male rats develop an increased sensitivity to the feedback effects of testosterone, and this increased sensitivity is operative within the normal physiological range of LH and testosterone; and 2) middle-aged animals have a reduced capacity to increase LH and FSH levels after release from tonic suppression. These changes in gonadotropin regulation can account, to a large extent, for the pituitary-testicular decline which develops during middle age in male rats.

Aging↗

Age-related changes in penile erections and circulating testosterone in middle-aged male rats.

The relationship between aging changes in pituitary-testicular function and the penile erection reflex was examined in middle-aged male rats. Significant decline in circulating LH and testosterone is first apparent in male rats during middle-age (13-15 mos). In Experiment 1, middle-aged (13-15 mos) and young (3-4 mos) rats were tested for erections responses. The erections were measured in animals held supine and mechanically stimulated by retraction of the penile shealth. Middle-aged rats had substantially fewer erections than young animals. In Experiment 2, groups of middle-aged and young animals were castrated and provided equivalent levels of circulating testosterone (T) through the use of Silastic capsules. The levels were measured directly by radioimmunoassay of plasma T. In animals with supraphysiological T levels, erection frequency was low, but there was no significant difference between middle-aged and young animals. The results suggest that middle-aged rats do not have irreversible deficiencies in the somatic and neural mechanisms regulating erection nor are they significantly less responsive to androgen stimulation. The decline in circulating testosterone with age may therefore be a primary factor in the reduction of penile erections in middle-aged rats.

Aging↗

Effects of lesions in various structures of the suprachiasmatic-preoptic region on LH regulation and sexual behavior in female rats.

Lesions of the suprachiasmatic nuclei (SCN) completely eliminated phasic LH release in ovariectomized rats as measured by the positive feedback response to estradiol benzoate (EB)/progesterone or the response to mating. Basal LH levels and the negative feedback response to EB were not affected. Lesions of the medial preoptic area (MPOA) or bed nucleus-dorsal MPOA also inhibited phasic LH release in ovariectomized rats as measured by positive feedback. However, the inhibition was not complete if there was no damage to the SCN, and the degree of inhibition was correlated with the size ofthe lesion. Basal LH levels and negative feedback were not significant affected. It is suggested that both the SCN and MPOA are involved in phasic LH release, the former in its role as a neural regulator of circadian rhythms and the latter as part of a diffuse system possibly including estrogen-sensitive and/or LH-RH neurons. Sexual behavior (lordosis) in hormone-primed, ovariectomized rats was not significantly affected by lesions of any structure in the suprachiasmatic-preoptic region.

Animals↗

Comparison of the effects of restricted morning or evening water intake on adrenocortical activity in female rats.

The effects of restricting daily water intake to either a 30-min morning or evening period were investigated on: (1) the overall circadian pattern of adrenocortical activity, and (2) adrenocortical activity during the 20-min period immediately after water presentation. Morning water restriction produced a substantial increase in pre-water levels of circulating corticosterone without affecting evening levels, thereby changing the form of the circadian pattern. In contrast, evening water restriction did not elicit any pre-water increase in corticosterone levels, and there was no change in the circadian pattern. Both morning and evening water restricted animals showed a pronounced and rapid decline in corticosterone levels during the 20-min post-water period, with levels dropping by more than 50% within 10 min of water presentation. The dissociation of the pre-water elevation and post-water decline in corticosterone evident in evening water animals indicates that these 2 processes may be governed by different factors. It is suggested that the pre-water effect involves circadian regulatory mechanisms whereas the post-water effect is associated with the process of reinforcement.

Adrenal Cortex↗

Neuroendocrine mechanisms mediating the suppression of circulating testosterone levels associated with chronic stress in male rats.

Neuroendocrine mechanisms involved in the reduction of testosterone (T) levels induced by the chronic surgical stress of s.c. gauze implantation were investigated in male rats. The reduction resulted from a decline in T secretion and not an increase in clearance of the hormone from the circulation. In most cases, the decrement was accompanied by a reduction in LH levels, indicating that decreased LH stimulation is the primary factor mediating the drop in T levels. The suppressive effect of surgical stress on LH and T levels was apparently not mediated by the pituitary-adrenal system.

Adrenal Glands↗