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Biomedical subjects

S M Reppert

Publications and source records attributed to S M Reppert.

136 records · Page 8Linked to original sources

Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey.

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

Amino Acids↗

Ontogeny of the pineal melatonin rhythm in the Syrian (Mesocricetus auratus) and Siberian (Phodopus sungorus) hamsters and in the rat.

The ontogeny of the pineal melatonin rhythm was determined in three rodent species. Pineal glands were obtained either during the day or during the expected peak in melatonin at night. In all species the rhythm was first detected during the second week of life. Investigations of the photic regulation of pineal melatonin revealed that light could inhibit the nocturnal increase in melatonin in all species by the end of the second week of life. These studies indicate that for these species the development of the rhythm in pineal melatonin and the development of the mechanism involved in the photic suppression of the nocturnal increase in melatonin are independent of the role the pineal gland plays in regulating reproductive function in response to changes in environmental lighting.

Aging↗

Studies on the daily pattern of pineal melatonin in the Syrian hamster.

In the Syrian hamster, a sharp peak in pineal melatonin occurs toward the end of the dark period. In the present communication, we describe characteristics of this rhythm. First, the time of the initial increase in pineal melatonin is not altered by daily melatonin injections that induce gonadal regression. Second, the rapid decrease of pineal melatonin in the morning is not prevented by acutely extending the dark period. Third, a consistent nocturnal increase in pineal melatonin is not observed in a 20-h light, 4-h darkness lighting schedule. However, acute exposure to a longer dark period, at the appropriate time of day, allows expression of the pineal melatonin rhythm in these animals. Finally, the rhythm in pineal melatonin appears to be truly circadian and is tightly coupled to the circadian rhythm in running activity.

Animals↗

Maternal-fetal transfer of melatonin in the non-human primate.

Melatonin was detected in the circulation of the near-term rhesus monkey (Macaca mulatta) and baboon (Papio papio) fetus. We determined whether the source could be the mother by studying placental transfer of melatonin in the rhesus monkey. When [3H]melatonin was administered i.v. to the mother it promptly appeared in the fetal circulation; the rates of disappearance of [3H]melatonin in the maternal and fetal circulations were parallel. The rapid decrease in circulating [3H]melatonin was associated with a rapid accumulation of [3H]melatonin-metabolites in the maternal and fetal circulations. Although the pattern of appearance of metabolites was similar in both circulations, relatively less [3H]melatonin-metabolites appeared in the fetal circulation. Acute changes in total maternal plasma melatonin, experimentally produced by giving a 20 min infusion of melatonin, were rapidly reflected in the fetus. This suggests that a daily rhythm in maternal melatonin would generate a similar rhythm in the fetus. The fetal monkey pineal was found to have the two enzymes necessary for the conversion of serotonin to melatonin. It is, however, not known whether fetal melatonin synthesis is rhythmic or the extent to which it could contribute to circulating melatonin levels at this or earlier stages of gestation.

Acetylserotonin O-Methyltransferase↗

A diurnal melatonin rhythm in primate cerebrospinal fluid.

Melatonin was measured in cerebrospinal fluid (CSF) withdrawn continuously from partially restrained rhesys monkeys. There was a daily rhythm in CSF melatonin with peak night values 2- to greater than 15-fold higher than day values. The increase occurred shortly after lights were turned off, and the decrease occurred soon after lights were turned on. There was substantial variation in the magnitude of the rhythm among animals. However, there was little day to day variation in the rhythm of individual animals studied for 3 or 6 consecutive days. Although the concentration of melatonin in CSF was lower than that in plasma, the changes in CSF melatonin concentrations seemed to reflect large daily changes in plasma melatonin concentrations.

Animals↗

Transport of maternal[3H]melatonin to suckling rats and the fate of [3H]melatonin in the neonatal rat.

The question of whether maternal melatonin could be transported in milk to suckling rats was investigated because melatonin is probably not produced in these animals during the first 10 days of life. [3H]Melatonin was found to be rapidly transferred from the maternal circulation into lactating mammary tissue, and the stomach of each suckling rat was found to contain [3H]melatonin. To study the fate and tissue distribution of [3H]melatonin originating in the neonatal stomach, suckling rats were given [3H]melatonin by stomach tube; [3H]melatonin was recovered from plasma and seven tissues, including brain, 15 and 60 min later. The general tissue distribution of [3H]melatonin was similar to that found in adult rats. The major [3H]melatonin metabolites in the urine of suckling rats, as the adult rats, were the conjugates of 6-hydroxy-melatonin.

Animal Population Groups↗

The treatment of pneumopericardium in the newborn infant.

Pneumopericardium with cardiac tamponade is a life-threatening emergency in the newborn infant. The case fatality rate is high (75% in 41 documented cases in the English literature), and diagnosis often delayed (in 13 of 29 deaths the pneumopericardium was diagnosed postmortem). Treatment is frequently unsatisfactory, and recurrence of the pneumopericardium with tamponade is likely after initial pericardial needle aspiration--an incidence of 53%. A case of pneumopericardium in a critically ill newborn is reported; the details of successful management, using a large bore intrapericardial catheter with continuous drainage, are discussed.

Cardiac Catheterization↗