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Biomedical subjects

H J Lynch

Publications and source records attributed to H J Lynch.

At least 37 records · Page 2Linked to original sources
PubMed1984

Effects of melatonin on human mood and performance.

The function of melatonin, a hormone secreted by the pineal gland primarily at night, has not been definitively established in humans. To determine if pharmacologic doses of melatonin had any behavioral effects it was administered acutely to 14 healthy men. Their mood, performance, memory and visual sensitivity were assessed. Plasma melatonin concentration was assayed as well. Melatonin significantly decreased self-reported alertness and increased sleepiness as measured by the Profile of Mood States and the Stanford Sleepiness Scale self-report mood questionnaires. The effects were brief. Melatonin also affected performance, slowing choice-reaction time but concurrently decreasing errors of commission. Sustained fine motor performance was not impaired after melatonin administration nor were the tests of memory and visual sensitivity that were administered. It is concluded that melatonin, administered orally in pharmacological quantities, has significant but short acting sedative-like properties.

Adolescent↗
PubMed1984

Light intensities required to suppress nocturnal melatonin secretion in albino and pigmented rats.

Sprague-Dawley albino rats or Long-Evans pigmented rats were exposed during the dark phase of the daily light:dark cycle to various intensities of a sunlight-stimulating white fluorescent light (0.022, 0.044, 0.110, 0.220, 0.440 or 2.200 microW/cm2) for 30 min; pineal glands and trunk blood samples were then collected and assayed for melatonin by radioimmunoassay. Albino rats exposed to irradiances of 0.110 microW/cm2 or less had pineal melatonin levels that were not significantly different from those of unexposed animals; higher irradiances significantly (P less than 0.001) reduced melatonin levels. In contrast, as little as 0.022 microW/cm2 significantly (P less than 0.02) reduced pineal and serum melatonin levels in the pigmented rats. These results suggest that something other than the simple presence or absence of eye pigmentation is the critical factor in determining the sensitivity of the rat's pineal to retinal-mediated photic suppression of melatonin synthesis.

Albinism↗
PubMed1984

Bioavailability of oral melatonin in humans.

We administered crystalline melatonin (80 mg) in gelatin capsules to 5 young male volunteers and measured serum and urinary melatonin levels at intervals. Changes in serum melatonin levels were best described by a biexponential equation with an absorption constant (ka) of 1.72 h-1 (half-life = 0.40 h) and an elimination constant (ke1) of 0.87 h-1 (half-life = 0.80 h). Peak serum melatonin levels, ranging from 350 to 10,000 times those occurring physiologically at nighttime, were observed 60-150 min after its administration, remaining stable for approximately 1.5 h. The fraction of ingested melatonin that was absorbed, estimated from the area under the curve describing serum melatonin concentrations as a function of time after melatonin administration (the concentration-time curve), varied by 25-fold among subjects. 3 additional volunteers received three melatonin-containing capsules (80 mg each) at 60-min intervals. This regimen extended the duration of elevated serum melatonin levels to 4-6 h. Melatonin excretion closely paralleled serum melatonin levels until 9 h after the hormone's administration, after which urinary levels tended to be higher than those predicted from serum levels. However, the area under the concentration-time curve for serum melatonin correlated well (r = 0.96) with the cumulative melatonin excretion during the initial 15 h after melatonin's administration, indicating that either approach can be used to estimate the absorption of orally administered melatonin.

Administration, Oral↗
PubMed1981

Light intensity and the control of melatonin secretion in rats.

The effect of varying ambient light intensity on the phase and amplitude of urinary melatonin rhythms was studied in rats housed individually in metabolism cages. For 17 days one group (D) was exposed to alternating 12-hour periods of dim light (0.1-0.3 micro/cm2) and total darkness; a second group (L) was exposed alternately to dim light and bright ligh (45-110 micro/cm2). All animals were then exposed to constant dim light for 15 days, after which they were returned to their original lighting regimens (D or L). 18 days later, half of each group was killed at the midpoint of the dim light phase, and the other half 12 h later. Both groups excreted melatonin rhythmically when exposed to daily cycles in light intensity; the L animals excreted 69% of the total daily melatonin output during the dim light phase and the D group of rats excreted 70% during the dark phase. When placed under continuous dim light, L animals continued to excrete melatonin as before, but D rats excreted significantly less, and the melatonin rhythm was dampened. When returned to a diurnal light cycle, both groups again exhibited rhythms in melatonin excretion that were entrained to the light cycle. Animals killed at the time of day coinciding with diminished melatonin excretion had lower pineal and serum melatonin levels (0.2 +/- 0.1 ng/pineal; 30 +/- 8 pg/ml serum) than those killed 12 h later (2.0 +/- 0.4 ng/pineal; 57 +/- 20 pg/ml serum). These observations provide additional evidence that measurement of urinary melatonin levels gives an accurate index of melatonin secretion from the rat pineal. They also show that a given light intensity presented for a part of the 24-hour day (e.g., dim light; 0.1-0.3 micro/cm2) can be interpreted by the mammalian pineal as light or dark, depending on the light intensity available during the rest of the day.

Animals↗
PubMed1980

Artificial induction of melatonin rhythms by programmed microinfusion.

Melatonin was slowly and intermittently infused into rats via an apparatus that allowed it to be discharged from a subcutaneous implant according to a predetermined temporal program. We found that infusion of an aqueous solution of melatonin, mixed with a dye, or of an immiscible fluid lacking melatonin or dye, could be monitored by measuring levels of melatonin or of dye in the rats' urine. We observed a 24-hour rhythm in melatonin excretion which corresponded to the times of its infusion by the apparatus. Approximately 0.1% of infused melatonin was recovered unchanged in the urine. This method of administering exogenous melatonin may facilitate explaining the physiological significance of rhythms in its secretion and rhythms in plasma levels of other hormones.

Animals↗
PubMed1979

Effect of cyclic changes in environmental lighting and ambient temperature on the daily rhythm in melatonin excretion by rats.

Melatonin excretion was measured by radioimmunoassay in 6 h or 12 h urine specimens from individual control rats and from animals previously blinded by bilateral orbital enucleation. Among sighted rats, the rate of melatonin excretion was greatest during the daily 12 h of darkness (1.44 +/- 0.06 ng/12 h dark period vs. 0.53 +/- 0.07 ng/12 h light period; P less than 0.001). Moreover, greater quantities of melatonin were excreted in the latter half of the dark period than in the first half (e.g. 0.55 +/- 0.08 ng/first 6 h vs 0.97 +/- 0.05 ng/second 6 h; P less than 0.001). When the onset of the daily light period was shifted forward by 12 h, 5--7 days were needed for the daily rhythm in melatonin excretion to become re-entrained to the new light--dark cycle. Among blinded rats, the rate of melatonin excretion also varied rhythmically; however, the rhythm was neither synchronized with the light-dark cycle nor influenced by alterations in the lighting schedule. Similarly, artificial cycles in environmental temperature were not effective in entraining the daily rhythm in melatonin excretion among blinded rats.

Animals↗
PubMed1978

Melatonin secretion decreases during the proestrous stage of the rat estrous cycle.

Urine was collected from rats during 12 consecutive daily dark periods and assayed for melatonin and norepinephrine; the phase of the vaginal estrous cycle associated with each urine sample was determined from daily vaginal smears. The proestrous phase of the estrous cycle was consistently associated with significant reductions in the excretions of both compounds. The level of melatonin in any urine sample tended to vary as a function of its norepinephrine content; however, the slope of the curve relating these two compounds in metestrous-diestrous samples differed from that for proestrous-estrous specimens. This difference suggests that factors other than the catecholamine (e.g., gonadal hormones) also affect melatonin secretion. Oophorectomy elevated the melatonin concentration of serum but not that of the pineal; this rise was suppressed by the administration of estrogen plus progesterone. The fate of circulating melatonin (as indicated by the proportion of an exogenous dose excreted into the urine) was not affected by the state of the estrous cycle.

Animals↗
PubMed1978

The measurement of melatonin in mammalian tissues and body fluids.

A quantitative bioassay for melatonin and a radioimmunoassay for melatonin are described and evaluated in terms of their specificity, sensitivity, and practicability. A thin-layer chromatographic method is presented whereby the specificity of the radioimmunoassay for melatonin in blood and tissue extract is affirmed and its specificity in the assay of urinary melatonin is described. Preliminary observations on the relationship between the rate of melatonin excretion and blood levels of melatonin are also reported.

Animals↗
PubMed1977

The adrenal medulla may mediate the increase in pineal melatonin synthesis induced by stress, but not that caused by exposure to darkness.

As previously shown (Lynch et al.: Proc. Nat. Acad. Sci. [U.S.A.] 70, 1704-1707 [1973]), the activity of the enzyme serotonin-N-acetyltransferase (NAT) in the rat pineal increases when the animal is placed in darkness or is subjected to the stress of physical immobilization; partial sympathetic denervation (i.e., pretreatment of the animal with intravenous 6-hydroxydopamine [6-OHDA]) does not block either response. The present studies explored the roles of the pineal sympathetic nerves and the adrenal medullas in mediating these responses. The stress-induced increase in pineal NAT activity was blocked by bilateral adrenalectomy, but not by bilateral superior cervical ganglionectomy or by treatment with 6-OHDA (both of which potentiate the NAT response in normal rats and restore it in adrenalectomized ones). The increase in pineal melatonin content caused by immobilization was also blocked by adrenalectomy, but potentiated by pineal sympathetic denervation. In contrast, bilateral adrenalectomy did not affect the darkness-induced rise in pineal NAT activity, although pineal sympathetic denervation (by bilateral superior cervical ganglionectomy) did block this response. 6-OHDA pretreatment neither blocked the response to darkness nor restored it in ganglionectomized animals; thus, this treatment apparently fails to produce a complete pineal denervation. The pineal response to stress has previously been shown to be blocked by beta-adrenergic blocking agents. The present studies demonstrate that alpha-adrenergic blockade (with phenoxybenzamine) potentiates this response in intact animals and restores it in adrenalectomized rats (possibly by acting presynaptically on receptors on pineal sympathetic terminals and thereby augmenting norepinephrine release). These observations show that the rat pineal organ normally receives information from two "channels", i.e., trans-synaptically (from pineal sympathetic nerves) and via the circulation (from the adrenal medullas and, perhaps, from distant sympathetic nerves).

Acetyltransferases↗
PubMed1976

Melatonin in rat pineal, plasma, and urine: 24-hour rhythmicity and effect of chlorpromazine.

The concentrations of melatonin in rat pineals and in samples of rat plasma and urine were measured by bioassay or radioimmunoassay. Melatonin excretion during the daily dark period (0.98 +/- 0.07 ng/12 h, by bioassay; 1.40 +/- 0.08 ng/12 h, by radioimmunoassay) was much greater than during the light period (0.18 +/- 0.04 ng/12 h, by bioassay; 0.40 +/- 0.04 ng/12 h by radioimmunoassay). (The radioimmunoassay is not completely specific when applied to materials extracted from utine.) Pineal glands and plasmas obtained from animals killed during the daily dark period also contained much more melatonin than samples from animals killed during the light period. Pretreatment with chlorpromazine slowed the disappearance of exogenous melatonin from rat plasma and markedly raised the concentrations of endogenous melatonin in both the pineal gland and the plasma.

Animals↗
PubMed1976

Presence of melatonin in plasma and urine or pinealectomized rats.

Melatonin was shown to occur in rat plasma and urine after pinealectomy by bioassay, radioimmunoassay, and thin-layer chromatography. Total daily excretion of melatonin in pinealectomized rats was about 20% of control. Light-dark rhythms of plasma melatonin levels and urinary excretion rates disappeared after pinealectomy.

Animals↗
PubMed1975

Daily rhythm in human urinary melatonin.

The melatonin in urine samples from six healthy adult volunteers was concentrated on Amberlite XAD-2 resin, eluted with organic solvents, and quantitated by use of a bioassay technique (the dermal melanaphore response of larval anurans to melatonin in their bathing medium). The melatonin content of samples collected between 11 p.m. and 7 a.m. was, in each case, several times higher than that of samples collected between 7 a.m. and 3 p.m. or between 3 p.m. and 11 p.m.

Adult↗