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Biomedical subjects

D J Morton

Publications and source records attributed to D J Morton.

At least 55 records · Page 3Linked to original sources
PubMed1990

Alteration of plasma cation levels in rats kept in constant light.

A variety of reports indicate that some kind of interaction may exist between the pineal gland and cations. Of particular interest are the reports that indicate comparatively high levels of copper, manganese, and zinc in the pineal gland and that the pineal gland exhibits a circadian rhythm in calcium, magnesium, potassium, and sodium. There are, unfortunately, no reports suggesting a functional role for these findings. This study investigated circadian rhythms in circulating plasma cations in rats under 12/12 h light-dark cycle and in rats whose pineal function had been suppressed by exposure to constant light for 1 and 7 days. Neither of the treatments affected circulating potassium levels but had some significant effects on sodium concentration at a number of time points without affecting the total amount of sodium circulating in a 24 h period. Calcium, magnesium, and zinc plasma concentrations were little affected by 1 day of constant light, while 7 days of constant light caused a dramatic and highly significant increase in the circulating levels of the three cations. The plasma levels of copper, on the other hand, while also being unaffected by 1 day were significantly depressed by 7 days of constant light. It is apparent, therefore, that the pineal gland may be involved in regulation of circulating levels of the cations measured. The functional significance of these observations is not clear at this stage but warrants further investigation.

Animals↗
PubMed1990

Some properties of pineal gland hydroxyindole-O-methyltransferase from black rhinoceros (Diceros bicornis).

Pineal glands were obtained from two young female black rhinoceri that had died as a result of postcapture trauma during a translocation exercise. Hydroxyindole-O-methyltransferase (HIOMT) from these pineal glands showed a peak activity at pH 8.2, although high activity extended over a fairly wide pH range (7.8-8.4). N-acetylserotonin was the best hydroxyindolic substrate for the enzyme, although other hydroxyindoles were methylated, the relative affinities being similar to values previously reported for bovine HIOMT. Kinetic analyses revealed that black rhinoceros HIOMT was subject to substrate inhibition by both substrates at high concentration; this observation is unlikely to have physiological significance. The catalytic mechanism was found to be ordered Bi-Bi, in which S-adenosylmethionine is the obligatory first substrate to bind to the enzyme, such binding allowing for binding of the hydroxyindolic substrate followed by catalysis, products again leaving the catalytic site in a sequential fashion.

Acetylserotonin O-Methyltransferase↗
PubMed1990

Development of an organ culture technique capable of monitoring most pineal gland indole metabolites.

An intact pineal gland organ culture technique was developed which utilised radiolabelled tryptophan as the indolic precursor and two-dimensional thin-layer chromatography to separate the various indole metabolites produced. The method was capable of reproducibly separating and quantitating all tryptophan metabolites except 5-methoxytryptophan which co-chromatographed with tryptophan in all the solvent systems evaluated. Noradrenergic stimulation of cultured pineals led to a predictable increase in N-acetyl-serotonin and melatonin production, suggesting that the method was useful for biochemical and pharmacological studies on the pineal gland. Similarly evaluation of the results revealed that a strong linearity existed between N-acetylserotonin and melatonin production and between actual and theoretical methylation as previously reported, again verifying the usefulness of the method developed.

Acetylserotonin O-Methyltransferase↗
PubMed1990

Epidemiology of head trauma and neurocognitive impairment in a multi-ethnic population.

This study tested two hypotheses. These were: (1) that mild cognitive impairment of the type that may characterize early-onset dementia of the Alzheimer type varies by ethnic group among the noninstitutionalized elderly, and (2) that head trauma is a risk factor associated with the development of this disease. The study sample consisted of a cohort of 2,105 Black, Mexican-American and White subjects aged 45 years and over at baseline in 1985-1987 in San Diego, Calif. Intellectual functioning was measured by Pfeiffer's Short Portable Mental Status Questionnaire. Percent prevalence of test failure after Pfeiffer's adjustment for education and ethnicity was highest for Whites (5.7%, CI = 4.26, 7.57) and lowest for Blacks (1.3%, CI = 0.61, 2.63), with Mexican-Americans intermediate (3.5%, CI = 2.28, 5.29). The difference between Blacks and Whites was statistically significant at the 0.05 level. Females failed more often (4.2%, CI = 3.15, 5.56) than males (3.1%, CI = 2.13, 4.47) across all ethnic groups, but the difference was not statistically significant after Pfeiffer's adjustment for education and ethnicity. Self-reported head traumas and other possible risk factors for dementia of the Alzheimer type were examined by logistic regression in a case-control analysis. A statistically significant association (OR = 8.577, CI = 3.056, 24.064) was noted for those with mild intellectual impairment who reported head traumas in a multivariate environment.

Black or African American↗
PubMed1990

A discriminant analysis of severe alcohol consumption among older persons.

A cross-sectional study among older persons (N = 1034) utilized multivariate stepwise discriminate analysis to determine the predictive value of variables affecting alcohol intake. Fifteen per cent of our study sample was classified as severe drinkers. Alcohol consumption before age 40, smoking, male gender and marital status were predictors of severe drinking. In addition, the unimpaired Older Americans Resource and Services (OARS) objective summary ratings for physical status and activities of daily living (ADL) were associated with severe drinking. Assessing the factors that predict alcohol consumption may help to identify initially those persons at possible risk, lending to heuristic and theoretical alcohol prevention policies among the aged.

Activities of Daily Living↗
PubMed1989

Possible mechanisms of inhibition and activation of rat N-acetyltransferase (EC 2.3.1.5.) by cations.

The possible mechanisms of inhibition and activation of various cations on rat pineal N-acetyltransferase (NAT) were elucidated. Copper was found to be a partial mixed noncompetitive inhibitor of NAT with respect to both substrates and this inhibition can be considered to result primarily from impairment of tryptamine (serotonin) binding to the enzyme. Both calcium and magnesium were found to activate NAT by a similar mechanism, with calcium being more effective than magnesium. It appears that the activation results from cation binding to the enzyme causing an increased affinity of tryptamine (serotonin) for binding to NAT and therefore enhancing catalytic activity. The monovalent cations, potassium and sodium, activated NAT by a similar mechanism which differed from the caused by the divalent cations. It can be suggested that tryptamine (serotonin) binds to the enzyme followed by the monovalent cation which enhances binding of the acetyl donor and thereby promotes catalysis. At high potassium or sodium concentration the affinity of acetyl coenzyme A for NAT begins to decrease suggesting that excess monovalent cations can be inhibitory and may represent an endogenous regulatory mechanism controlling in vivo NAT activity. It is possible that certain cations may be involved in regulation of melatonin synthesis although the physiological significance of such modulation remains unknown.

Acetyl Coenzyme A↗
PubMed1989

Probable mechanism of catalysis of pineal gland hydroxyindole-O-methyltransferase (HIOMT) from rainbow trout (Salmo gairdneri).

Activity of trout pineal HIOMT was found to increase with increase in incubation temperature from 5 to 40 degrees C although the activation energy remained constant over this range. From examination of the effects of the products of HIOMT catalysis on the enzyme it was apparent that the catalytic mechanism was ordered Bi-Bi with S-adenosylmethionine as the obligatory first substrate. Trout HIOMT was found to methylate all the common pineal hydroxyindoles with hydroxytryptophol having the greatest affinity for the enzyme. The pH optimum for trout HIOMT was found to be about pH 9.0 although routine use of a pH of 7.9 is recommended to limit potentially deliterious effects caused by degradation of S-adenosylmethionine at elevated pHs.

Acetylserotonin O-Methyltransferase↗
PubMed1989

Utilization of transferrin-bound iron by Haemophilus species of human and porcine origins.

Haemophilus influenzae and H. haemolyticus acquired iron bound to human transferrin but not to human lactoferrin, ovo- or porcine transferrins. Conversely the swine pathogens H. pleuropneumoniae and H. parasuis used iron bound only to porcine transferrin. Growth under conditions of iron deprivation induced the production of siderophores and iron-repressible outer membrane proteins in H. parainfluenzae, H. paraphrophilus and H. parasuis but not in H. influenzae, H. haemolyticus or H. pleuropneumoniae. The latter 3 Haemophilus species appear to sequester transferrin bound iron via a siderophore-independent mechanism. However, the ability to produce iron chelating compounds did not enable H. parainfluenzae or H. paraphrophilus to utilize transferrin bound iron.

Animals↗
PubMed1989

Characterization of the outer-membrane proteins of Haemophilus parainfluenzae expressed under iron-sufficient and iron-restricted conditions.

SDS-PAGE of the outer-membrane (OM) proteins of Haemophilus parainfluenzae P205 grown under iron-sufficient conditions revealed three major proteins of 40, 37 and 13 kDa. In addition, growth under conditions of iron-restriction resulted in the expression of at least four iron-repressible OM proteins (IROMPs) of 72, 81, 88 and 90 kDa. OM proteins of 40 and 13 kDa were non-covalently associated with peptidoglycan and were resistant to digestion with trypsin. A 38 kDa peptidoglycan-associated protein, which was masked by the abundant 37 kDa protein, was also observed following tryptic digestion of whole cells or OMs. Neither the 37 kDa protein (which was heat-modifiable) nor the IROMPs were peptidoglycan-associated, and both were cleaved following treatment of whole cells with trypsin, indicating that they are exposed at the cell surface. A variety of IROMPs from five other H. parainfluenzae strains was also observed. In each strain, both the IROMPs and a major protein of 37 kDa were exposed at the cell surface.

Bacterial Outer Membrane Proteins↗
PubMed1989

Effect of methoxyindole administration on plasma cation levels in the rat.

Administration of methoxyindoles to rats in both the morning and the afternoon caused significant changes in circulating plasma cation levels. All the methoxyindoles except melatonin were without effect at doses below 100 micrograms/kg; the observed changes caused by doses of 100 micrograms/kg can, therefore, probably be best described as pharmacological rather than having physiological significance. Melatonin at all doses tested (25, 50, and 100 micrograms/kg) led to a decrease in plasma magnesium levels 3 h after administration in the morning, and this finding is discussed in the light of a possible feedback mechanism between melatonin and circulating magnesium. Melatonin administration in the afternoon was without effect on magnesium levels. Zinc levels were also decreased significantly 3 h after a morning dose of melatonin (50 and 100 micrograms/kg), and the possible functional significance of this observation is discussed. Most of the observed effects can be considered nonspecific and pharmacological, and further work is needed to fully elucidate the involvement, if any, of the pineal gland in regulation of cations.

5-Methoxytryptamine↗
PubMed1989

Inhibition of the catalytic activity of bovine pineal gland hydroxyindole-O-methyltransferase (EC 2.1.1.4) by estrone, estradiol, progesterone, and testosterone but not pteridines.

The effect of pteridines and sex hormones on hydroxyindole-O-methyltransferase (HIOMT) catalysis was examined. Equivalent quantities of partially purified bovine HIOMT was incubated in the presence and absence of the various test substances and the results fitted to the Michaelis-Menten equation. The pteridines (triampterene and xanthopterin) had no noticeable effect on HIOMT catalysis, while all the sex hormones examined were found to be competitive inhibitors of the enzyme with respect to the hydroxy-substrate. Testosterone concentrations causing noticeable inhibition were above physiological while estrone, estradiol, and progesterone all caused inhibition within the physiological range; estrone was the most potent and progesterone the least potent inhibitor. The possible significance of these findings are discussed.

Acetylserotonin O-Methyltransferase↗
PubMed1989

Pineal gland hydroxyindole-O-methyl transferase (HIOMT) from rainbow trout (Salmo gairdneri) subject to temperature-dependent substrate inhibition by N-acetylserotonin.

The effect of different incubation temperatures on the activity of trout hydroxyindole-O-methyltransferase (HIOMT) was determined in order to study the potential effects of changes in environmental temperature on production of melatonin. In the study, N-acetylserotonin (NAS) was found to inhibit trout pineal HIOMT, inhibitory concentration decreasing with a decrease in incubation temperature. An increase in incubation temperature was accompanied by an increase in maximal velocity (Vm) and a decrease in affinity of the substrate NAS for the enzyme, while the affinity of the inhibitor NAS remained more or less constant with increase in temperature up to 30 degrees C. It was interesting to note that at subinhibitory concentrations of NAS, possibly concentrations within the normal physiological range, there was a balance between increased velocity and decreased affinity for substrate, with increase in temperature resulting in a constant rate of melatonin production. On the basis of these results it is suggested that substrate inhibition might be involved in modulation of melatonin production and that trout pineal HIOMT can maintain a constant rate of melatonin production over a wide range of temperatures by a combination of compensatory changes in enzyme kinetic parameters.

Acetylserotonin O-Methyltransferase↗
PubMed1989

Swimming-induced suppression of rat pineal melatonin is prevented by pretreatment with calcium channel blockers.

Young adult male rats were treated with isoproterenol during the day to induce high levels of pineal N-acetyltransferase (NAT) activity and melatonin. Roughly 2 hr later when pineal NAT activity and melatonin levels were elevated, animals were given either an injection of a calcium channel blocker, i.e., either nifedipine or verapamil, or diluent. The rats were then forced to swim for 10 min in room temperature (22 degrees C) water. Fifteen minutes after swimming onset, pineal glands were collected for measurement of NAT activity and melatonin. Swimming caused a dramatic reduction in pineal melatonin content without influencing NAT activity. Nifedipine substantially and verapamil completely blocked the drop in pineal melatonin levels due to swimming without influencing NAT activity. The results suggest that calcium may be somehow directly or indirectly involved in melatonin release from the rat pineal gland.

Acetyltransferases↗
PubMed1989

Pharmacokinetics of aspirin and its application in canine veterinary medicine.

In preliminary investigation of the pharmacokinetics of aspirin in dogs it became apparent that the drug was well absorbed following oral ingestion with food. Multiple dosing appeared to lead to a substantial increase in half-life; a twice daily dosage regimen would, therefore, be adequate for maintenance of therapeutic levels in dogs. The marked variation in pharmacokinetic parameters observed suggested that therapeutic drug monitoring would be benefit in the control of canine inflammatory conditions using aspirin. Therapeutic monitoring of dogs (n = 20) showed that clinical improvement paralleled plasma salicylate concentrations and the therapeutic concentrations so determined were within the range considered therapeutic in humans. No overt gastric irritation was noted in this study over a period of a year which suggests that aspirin can be successfully used to treat canine inflammatory disorders, routine monitoring of plasma salicylate being recommended to ensure therapeutic success.

Animals↗
PubMed1989

A comparative bioavailability of 2 oral solid phenytoin dosage forms.

The comparative bioavailability of two phenytoin products, Phenytoin Sodium (CAPS (Pvt) Ltd) and Epanutin (Parke-Davis (Pty) Ltd) was studied. Single dose studies carried out in eight healthy volunteers showed that CAPS Phenytoin exhibited a small but significantly higher bioavailability (P less than 0.05). The AUC (0-72 hr) for CAPS Phenytoin was 50.61 microgram/ml/hr compared to 45.09 au/ml/hr for Epanutin. The time to peak concentrations, Tmax, was significantly longer in CAPS Phenytoin when compared to Epanutin being 3.75 hr and 3.25 hr respectively (P less than 0.05) and the peak concentrations Cmax, achieved after single dose administration showed that CAPS Phenytoin exhibited higher levels than Spanutin (1.76 au/ml and 1.58 au/ml respectively) although these differences were not statistically significant. Multiple dose studies carried out in four healthy volunteers and two epileptic patients showed that changes from one product to the other did not produce any significant differences in the steady state phenytoin levels.

Administration, Oral↗
PubMed1988

Pineal gland N-acetyltransferase and hydroxyindole-O-methyltransferase activity in the rainbow trout (Salmo gairdneri): seasonal variation linked to photoperiod.

The activities of rainbow trout pineal gland N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were determined at various times during a 24 h period in mid-winter and mid-summer. The results indicate a small diurnal fluctuation in HIOMT and a marked diurnal fluctuation in NAT activity with peak enzyme activities occurring during the dark phase. NAT can be assumed to be the rate limiting enzyme for the production of melatonin and, as NAT activity increases were associated with the dark phase, it can also be assumed that melatonin production would be greater in winter than in summer.

Acetylserotonin O-Methyltransferase↗