Biomedical subjects

G M Vaughan

Publications and source records attributed to G M Vaughan.

At least 37 records · Page 2Linked to original sources

PubMed1988

Hormonal consequences of subcutaneous 6-methoxy-2-benzoxazolinone pellets or injections in prepubertal male and female rats.

Prepubertal 27-day-old female rats maintained in a 14L:10D cycle (lights on 06:00 h) were injected s.c. at 13:00 h with saline or 2, 20 or 200 micrograms 6-methoxy-2-benzoxazolinone (6-MBOA) and killed 25-27 h later. No significant differences in body, pituitary or ovarian weight were noted. Differences in uterine weight (mg/100 g body weight) and in circulating free thyroxine index fit the pattern of a reduction after the lower doses with reversal of this effect after the highest dose. A dose-related rise in plasma prolactin concentration was accompanied by a significant increase in pituitary prolactin at the lowest (2 micrograms) dose. When 27-day-old prepubertal male and female rats maintained in a 14L:10D cycle were implanted with a beeswax pellet or a wax pellet that contained 100 micrograms or 1 mg 6-MBOA and killed 3 days later between 14:00 and 16:00 h, body and absolute ventral prostate weights (but not weights of other accessory organs, testes or relative ventral prostate weights) in males were lower. Pituitary (but not plasma) prolactin concentrations were higher after the lower dose compared to the controls; pituitary and plasma values of LH and FSH were unchanged. In females, reproductive variables were unchanged except for a reduction of pituitary prolactin after the 1 mg dose. Triiodothyronine and its free index were elevated after the higher dose in males and the lower dose in females. The free thyroxine index appeared raised after the larger dose only in males.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Nyctohemeral rhythms of gonadal, thyroid and pineal function in the hyperprolactinemic male rat.

In young adult male rats bearing a donor anterior pituitary gland grafted for 3 weeks under a kidney capsule, serum prolactin (PRL) concentrations were elevated and exhibited a rhythm with the highest values in the light phase. Serum PRL in control animals did not exhibit a significant rhythm. Eutopic pituitary PRL content, manifesting a biphasic (12-hr) rhythm with crests during the day and night in controls, exhibited a similar pattern in grafted rats though an overall reduction in pituitary PRL content was seen in the grafted animals. Neither the normal biphasic serum testosterone rhythm nor the normal 24-hr rhythm (nocturnal surge) of pineal N-acetyltransferase activity and melatonin content were altered in the hyperprolactinemic rats. Serum thyroxine (T4) and triiodothyronine (T3) and their free indices (FT4I, FT3I) and serum thyrotropin (TSH) were highest during the day in controls and grafted rats and a 12-hr rhythmic component was detected in data for these variables. In the grafted animals, the 12-hr component was reflected in an additional peak at night detectable by testing of means. The overall serum T4, FT4I, and TSH levels were lower in grafted rats though overall T3 and FT3I levels did not differ between grafted and controls. T3 uptake (T3U) values were similar between controls and grafted rats, in both cases exhibiting a fall during the night. Changes in serum thyronines could not be explained by changes in serum binding as assessed by the T3U, and thus may represent changes in thyroidal secretion of T4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Elevated daytime rat pineal and serum melatonin levels induced by isoproterenol are depressed by swimming.

Isoproterenol (1 mg/kg) was subcutaneously injected into adult male rats during the day to stimulate pineal N-acetyltransferase (NAT) activity and pineal and serum melatonin levels. Two hours after isoproterenol administration when levels of each of these variables had increased significantly, the experimental animals swam for 10 min in 22 degrees C water. At 15 min after swimming onset, pineal and serum melatonin levels were highly significantly depressed compared to those in control animals that did not swim. The high NAT level was not influenced by swimming. In a second study, isoproterenol injected rats swam for either 1, 3, 6 or 10 min and were sampled 15 min after the onset of swimming. The reduction in the elevated pineal melatonin in these animals was correlated with the length of the swim, i.e., as the duration of swim increased the percent reduction in pineal melatonin also increased. Neither pineal NAT nor hydroxyindole-O-methyltransferase (HIOMT) activities were influenced by swimming. The results suggest that elevated pineal and serum melatonin induced by isoproterenol can be depressed with no effect on the activity of the enzymes which convert serotonin to melatonin.

Animals↗

PubMed1987

Characterization of type-II thyroxine 5'-deiodinase activity in rat Harderian gland.

Thyroxine 5'-deiodinase activity was studied in male rat Harderian gland homogenates. The reaction rate was proportional to the tissue content in the homogenate and dependent on pH, with an optimum pH of 7.0, and temperature, between 4-37 degrees C. 5'-deiodinase activity was increased by dithiothreitol (DTT) in a dose-dependent manner, and inhibited moderately by propylthiouracil (PTU) and strongly by iopanoic acid (IA). Thyroidectomy enhanced the enzymatic activity (30-fold above the control value) but this increase is totally prevented by the in vivo iopanoic acid treatment. Thyroxine 5'-deiodinase activity was also dependent on T4 concentration (Km = 3.3 nM; Vmax = 10 fmol 125I-released/mg protein/h) and exhibited a nyctohemeral rhythmicity with a maximal activity at 03.00 h (4-fold above basal values) and minimal activity between 12.00-21.00 h.

Animals↗

PubMed1987

Pineal and retinal lysosomal enzyme rhythms.

Pineal glands and the neurosensory portion of the retinae of adult male rats adapted to a 24-h cycle with lights on from 06.00 to 20.00 h were collected at 9 timepoints during the cycle. Significant rhythms in both pineal and retinal hexosaminidase, beta-glucuronidase, acid phosphatase and beta-glucosidase were observed. For each enzyme, pineals had greater overall activity per unit amount of protein than did retinae. All 4 significantly rhythmic pineal enzymes peaked within 30 min of each other (18.30-19.00 h) whereas the retinal enzymes peaked some 6 h earlier, between 11.30 and 13.45 h. To our knowledge, this is the first report demonstrating 24-h rhythms in lysosomal enzymes in the pineal gland and retina. Since the acrophases (peak times) of these enzymes within each tissue are tightly synchronized yet different between tissues, lysosomes may play unique roles in the physiology of different structures in the photoneuroendocrine system with respect to time in the light-dark cycle.

Acid Phosphatase↗

PubMed1987

Splenic hypertrophy and extramedullary hematopoiesis induced in male Syrian hamsters by short photoperiod or melatonin injections and reversed by melatonin pellets or pinealectomy.

Adult male Syrian hamsters either placed in a short photoperiod alone or kept in a long photoperiod and given daily afternoon injections of the pineal indole melatonin (25 micrograms) exhibited splenic hypertrophy and extramedullary hematopoiesis in addition to a marked regression in testicular weight. The testicular regression as well as the changes in spleen weight and histology could be prevented if the animals in short photoperiod were either pinealectomized or implanted subcutaneously with a pellet containing 1 mg melatonin. Female Syrian hamsters given afternoon injections of melatonin for 7 or 12 weeks had ovaries devoid of corpora lutea; additionally, these animals had reduced relative spleen weights compared to the control animals. In conclusion, it is apparent that spleen weight varies with the functional status of the gonads. Splenic hypertrophy accompanied by pineal-induced testicular regression in males may be related to splenic extramedullary hematopoiesis.

Animals↗

PubMed1987

Injections of alpha-melanocyte stimulating hormone affect pineal serotonin, melatonin and N-acetyltransferase activity.

To determine if exogenously administered alpha-melanocyte stimulating hormone (alpha-MSH) affects nighttime pineal N-acetyltransferase activity, pineal levels of 5-hydroxytryptophan, serotonin and melatonin, and plasma prolactin levels, adult male hamsters were injected at 1900 hr (lights out 2000-0600 hr) with two doses of the peptide and killed at 0300 hr. The low dose of alpha-MSH (200 ng) produced a significant fall in pineal serotonin, pineal NAT activity and plasma prolactin values. The high dose of the peptide (20 micrograms) increased circulating prolactin titers and pineal serotonin levels and caused a concomitant decrease in pineal melatonin levels.

5-Hydroxytryptophan↗

PubMed1987

Nyctohemeral rhythm in melatonin response to isoproterenol in vitro: comparison of rats and Syrian hamsters.

The in vitro response of melatonin synthesis was assessed by incubation of individual whole pineal glands for 4 hr without or with different concentrations of isoproterenol in the medium. Pineals were taken either at the end of the 14-hr light phase (day), or at 6 1/2 hr into the 10-hr dark phase (night) after a 30-min exposure of the animals to light just before sacrifice at night. The response was greater in pineals taken at night than in those taken at the end of the light phase in rats, but was absent at the end of the light phase in Syrian hamsters. Hamster pineals taken at night responded, though higher isoproterenol concentrations were required than in the rats. Unresponsiveness of hamster pineals during the day may explain previous failure of isoproterenol administration to stimulate pineal MEL content in this species.

Animals↗

PubMed1987

Influence of psoralen on NAT activity and melatonin levels in rat pineal gland during the daily period of darkness.

A single injection of either 5 or 10 mg/kg 8-methoxypsoralen (8-MOP) was given intraperitoneally to male rats at the end of the 14 h light phase (at 2000 h). Two h later (at 2200 h), when the normal nocturnal surge of N-acetyltransferase (NAT) activity and melatonin content in the pineal gland had begun in vehicle-injected controls, mean pineal NAT after the 10 mg/kg 8-MOP was 1.8-fold higher than that after vehicle, though pineal melatonin content did not differ between vehicle- and drug-injected rats. By 4 h into the dark period (at 2400 h), the NAT activity in both 8-MOP injected groups of rats was greater than that in vehicle treated animals; again, however, 8-MOP treatment did not influence the pineal melatonin content. At 0200 h (6 h into the dark period), the difference between the NAT activity in pineals of rats treated with 5 mg/kg 8-MOP and the vehicle was not statistically significant, but the animals that received 10 mg/kg drug still had statistically elevated levels of the serotonin acetylating enzyme. At 0200 h the pineal melatonin levels were equivalent among the three treatment groups. Rats given 5mg/kg 8-MOP always had NAT values intermediate between those of rats injected with vehicle and those that received 10 mg/kg 8-MOP suggesting that the NAT response to the drug was dose related. These results show that the pineal response to psoralen involves an elevation of NAT activity without a commensurate change in the melatonin content of the gland.

Acetyltransferases↗

PubMed1987

Norepinephrine or isoproterenol stimulation of pineal N-acetyltransferase activity and melatonin content in the Syrian hamster is restricted to the second half of the daily dark phase.

Seven experiments were performed to investigate the sensitivity of the hamster pineal gland to exogenously administered norepinephrine (NE). In these studies NE (1 mg/kg) administration was preceded (10 min earlier) by the injection of the catecholamine uptake inhibitor desmethylimipramine (DMI; 5 mg/kg). When DMI and NE were given at night, the hamsters were exposed to light to depress pineal N-acetyltransferase activity and melatonin values to low levels; the drugs were then given 20 (DMI) and 30 (NE) min later, and the subsequent changes in pineal N-acetyltransferase and melatonin were monitored. The combination of DMI and NE administration anytime during the normal light period or during the first 4 h of the normal dark period failed to stimulate either pineal N-acetyltransferase activity or melatonin levels. Conversely, DMI followed by NE (injected either intraperitoneally or subcutaneously) in the second half of the dark phase typically stimulated pineal melatonin production. Likewise, the NE agonist isoproterenol promoted pineal melatonin production only in the latter half of the dark phase. If hamsters were exposed to continual light at night or if they were superior cervical ganglionectomized, a procedure which sympathetically denervates the pineal gland, the stimulatory effect of NE on melatonin production was significantly suppressed. Thus, the hamster pineal gland is sensitive to NE only during the latter half of the normal dark period and both darkness and an intact sympathetic innervation to the pineal gland are required for the gland to develop maximal sensitivity to the catecholamine. Also, the hamster pineal seems not to exhibit a supersensitivity response to NE following a period of reduced exposure to the catecholamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗

PubMed1987

Central hypogonadism in burned men.

Serum samples were obtained from 30 burned men at different times up to the fourth month after injury. Mean concentrations of estradiol (E2) were elevated above those for healthy control subjects. Mean serum total testosterone (T), sex hormone-binding globulin (SHBG), bioassayable luteinizing hormone (LH), thyroxine (T4), triiodothyronine (T3) and their free indices (FT4I and FT3I) were depressed below those of controls during the first postburn week. Mean values for T and LH were progressively higher in samples taken from later time periods but remained depressed. Mean SHBG and thyroid hormones rose and were not significantly different from control values during later periods of the study. Calculated non-SHBG-bound T (NSBT) was below normal in each time period. The close correlation of SHBG values with those of T3 and FT3I in the patients suggests that SHBG responds to the altered thyroid hormone milieu of burn injury. It is postulated that elevated serum E2 perhaps from adrenal precursors promotes an alteration of hypothalamic function resulting in a markedly reduced secretion of bioactive LH and diminished Leydig cell function.

Adolescent↗

PubMed1987

The Syrian hamster pineal gland responds to isoproterenol in vivo at night.

Failure of isoproterenol (ISO) injections to raise pineal melatonin content has generated doubt about beta-adrenergic control of the melatonin rhythm in Syrian hamsters. However, the effect of ISO injected at night after light-induced reduction of pineal melatonin has not been reported. In this study, light exposure began at 6 1/4 h into one (normally 10-h) dark phase. The hamsters were injected with either ISO (1 mg/kg) or vehicle 15 min later when pineal melatonin content was low. Light exposure continued. Two h after ISO but not vehicle injection, pineal melatonin content rose more than six-fold. In other animals injected at the end of the usual light phase then kept in light for 2 h, pineal melatonin was equally low after ISO or vehicle injection. The Syrian hamster pineal gland can respond in vivo to a beta-adrenergic agonist injected at the physiologically relevant time of the normal nocturnal melatonin surge. This finding, taken together with the previously reported inhibition of the endogenous nocturnal melatonin surge with a beta-blocking drug, suggests that a beta-adrenergic mechanism controls the hamster pineal melatonin rhythm.

Animals↗

PubMed1986

Effects of environment on infection in burn patients.

Burn patients in an early cohort (n = 173) treated in an intensive care ward without separate enclosures were compared with a later cohort (n = 213) treated in a renovated unit with separate bed enclosures. The number of patients developing infection was significantly reduced in the late group. Observed mortality was compared with mortality predicted on the basis of burn size and age alone. Reduction in observed compared with predicted mortality, inapparent in the early group, was seen in the late group and was restricted to the subgroup of patients with predicted mortality of 25% to 75%, in which the observed mortality of 28.3% was less than the predicted mortality of 48.7%. The incidence of infected patients was reduced from 58.1% in the early cohort to 30.4% in the late cohort. In comparison of the early cohort with the late cohort, the overall proportion of patients with bacteremia was reduced from 20.1% to 9.4%, while the incidences of both pneumonia and burn wound invasion remained unchanged. Providencia and Pseudomonas species, endemic in the early cohort, were eliminated in the late cohort. Reduction of infection by environmental manipulation in burn patients was possible and was associated with improved survival.

Adult↗

PubMed1986

Hypothalamic neuroendocrine correlates of cutaneous burn injury in the rat: I. Scanning electron microscopy.

Rats were given a standard scald burn on 60% of the body surface or only a sham burn and were sacrificed at intervals from 6 hr to 14 days later. Serum thyroxine (T4), free thyroxine index (FT4I) and triiodothyronine (T3) were depressed compared to values in respective shams as early as 6 hr post-burn. T4 and FT4I were less depressed on post-burn days (PBD) 2-3 than on PBD 1 and then exhibited a further fall. T3 remained depressed through PBD 14. Pineal melatonin content was elevated at 6 hr and fell to the normal daytime range in subsequent samples. The ventral portion of the diencephalon was prepared for scanning electron microscopy. Only in the burned rats and beginning on PBD 2, large numbers of supraependymal neurons (SEN) appeared in the ventricular space attached to the inferior walls and floor of the third cerebral ventricle. Transmission electron microscopy was used to confirm the neuronal nature of the SEN. Viewed by scanning electron microscopy, these persisted through PBD 14. SEN were interconnected by cables of their neurites exhibiting varicosities on individual neurites as they passed over perikarya of other SEN. Some SEN were seen to be only partially emerged from the underlying tissue and others were seen to send a thick process into the hypothalamic tissue. These observations indicate that after peripheral injury there is marked plasticity of the brain in an area thought to control the endocrine systems that show abnormalities after such a peripheral injury. The timing, location and nature of these anatomic changes indicate the possibility that at least some aspects of central nervous orchestration of the endocrine metabolic response to injury may be related to the emergence of a neuronal system receiving or sending messages through the cerebrospinal fluid and/or through new neurite circuits along the surface of the third ventricular wall. These structures may appear in response to initial primary hormonal changes and/or may play a role in maintaining the post-injury hormonal milieu manifested in part by a subsequent second fall in serum T4.

Animals↗

PubMed1986

Pineal dependence of the Syrian hamster's nocturnal serum melatonin surge.

The usual nocturnal surge of pineal melatonin content was blocked by bilateral superior cervical ganglionectomy in male Syrian hamsters. Ganglionectomy and pinealectomy each prevented the nocturnal rise of serum melatonin concentration seen in control animals. The normal nocturnal surge of circulating melatonin in this species appears to depend on the pineal gland and its sympathetic innervation.

Animals↗

PubMed1986

Rhythmic melatonin response of the Syrian hamster pineal gland to norepinephrine in vitro and in vivo.

Norepinephrine (NE, 10(-6) M) stimulated melatonin accumulation in the incubation medium of rat (but not Syrian hamster) pineals taken at the end of the light phase. However, NE elevated melatonin accumulation in the medium of pineals taken after 20 min of light exposure of animals of either species at 6 h into the 10-h dark phase. A dose response to 10(-7)-10(-5) M NE was observed in both the medium and pineals upon incubation of pineals taken from rats at 4 h into the light phase and from hamsters after 20 min light exposure at 6 h into the dark phase. Approximately 95% of the melatonin present was in the medium. The incubation time was 4 h in all cases. Subcutaneous injection of 1 microgram/g NE (either at the end of the light phase or after 30 min of light at 6 h into the dark phase) did not stimulate in vivo Syrian hamster pineal melatonin content determined 1 or 2 h after injection, whether the hamsters were placed in light or darkness after the injection. However, after 30 min of light beginning at 6 h into dark, injection of 5 micrograms/g desipramine (DMI, a blocker of catecholamine uptake into nerve endings) allowed a dramatic hamster pineal melatonin response to additional injection of 1 microgram/g NE, observed at 1 and 2 h in light after injection. A small effect of DMI alone was seen. DMI also potentiated the effect of NE (each 10(-6) M) on melatonin accumulation in the medium of incubated hamster pineals taken after a short light exposure at night. No significant stimulatory effect of NE and/or DMI was seen in vivo or in vitro near the middle of the light phase. Measurement of melatonin in the incubation medium is a useful method for studying pineal function. The Syrian hamster pineal has rhythm of sensitivity to NE (sensitivity evident at night) and even at night is protected by neuronal uptake from circulating NE-induced stimulation of melatonin production. NE appears to be the neurotransmitter for stimulation of pineal melatonin production in the Syrian hamster. The sensitivity rhythm and uptake protection might provide specificity of control of the nightly melatonin signal by reducing the chance of a melatonin response during the day or a response to circulating catecholamines from general sympathetic stimuli.

Animals↗

PubMed1986

Serum melatonin after a single aqueous subcutaneous injection in Syrian hamsters.

A single injection of 25 micrograms melatonin was given subcutaneously in 0.1 ml saline either at 3 h into the light phase (morning) in female Syrian hamsters or at 1 h before the beginning of the dark phase (evening) in males (L/D 14/10 h). In both cases, the maximal mean serum values seen at 20 min after injection (50 ng/ml) were more than 1,000 times the normal nocturnal melatonin concentration. By 1 h after injection, serum melatonin had fallen to 10% (morning) or 4% (evening) of the respective 20-min value. The average half-times for plasma concentration during the second hour after injection were 14 min in the morning and 13 min in the evening. After either morning or evening injection, serum melatonin reached normal daytime concentration between 2 and 4 h after injection.

Animals↗

PubMed1986

Reproductive effects of 6-chloromelatonin implants and/or injections in male and female Syrian hamsters (Mesocricetus auratus).

Adult female hamsters were injected each afternoon for 9 weeks with 2.5, 15 or 25 micrograms of melatonin or 6-chloromelatonin (CM). Each drug resulted in a significant dose-related depression in uterine, ovarian and anterior pituitary gland weights. Additionally, plasma and pituitary concentrations of prolactin fell with increasing dose of either indole whereas pituitary levels of LH and FSH were positively correlated with dose. There was no difference in effectiveness between the two drugs. Adult male hamsters treated for 10 weeks with daily afternoon injections of melatonin and a blank beeswax pellet had depressed testicular and accessory organ weights and plasma and pituitary concentrations of prolactin. Implantation of a 1 mg melatonin or CM beeswax pellet in hamsters concurrently receiving daily afternoon injections of melatonin prevented the organ weight and hormonal changes, except for plasma prolactin. Adult male hamsters treated for 10 weeks with daily afternoon injections of CM and a blank beeswax pellet had depressed reproductive organ weights and pituitary and plasma concentrations of prolactin; this depression in hormonal values and organ weights was totally prevented if the CM-injected hamsters were also bearing a beeswax-melatonin pellet. In conclusion, 6-chloromelatonin is as effective as melatonin with regards to antigonadotrophic and counter-antigonadotrophic effects in male and female Syrian hamsters.

Animals↗