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Biomedical subjects

M A Collins

Publications and source records attributed to M A Collins.

At least 91 records · Page 5Linked to original sources
PubMed1989

Striatal dopaminergic toxicity following intranigral injection in rats of 2-methyl-norharman, a beta-carbolinium analog of N-methyl-4-phenylpyridinium ion (MPP+).

Methylated beta-carboline compounds are mammalian indole metabolites that we have proposed to be endogenous neurotoxins due to their structural similarity to MPP+, the active oxidized product of the dopaminergic toxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Several laboratories have demonstrated that MPP+ administration into the substantia nigra or median forebrain bundle of rats results in extensive depletion of striatal dopamine and its metabolites. We now report that three weeks after intranigral injection of the beta-carboline, 2-methyl-norharman, striatal dopamine, DOPAC, and homovanillic acid (HVA) concentrations ipsilateral to the injection are reduced 41-64% compared to vehicle-injected controls; in individual animals dopamine depletions of 96% were achieved. In addition, at the 2-methyl-norharman injection site in the substantia nigra, large lesions and gliosis were apparent under light microscopic examination. This is the first direct demonstration that a 2-methyl-beta-carbolinium ion is neurotoxic. It lends further validity to the hypothesis that MPP+-like beta-carbolines may be endogenous causative agents in Parkinson's disease.

1-Methyl-4-phenylpyridinium↗
PubMed1989

Circadian specificity in exercise training.

The purpose of this study was to determine whether metabolic and cardiorespiratory adaptations to exercise training are greater at the time of day of training than at another time. Twenty-seven subjects performed cycle ergometer tests in the morning (AM) and in the afternoon (PM) before and after a 6-wk period during which ten subjects trained regularly in the morning, seven subjects trained in the afternoon, and ten did not train. Training caused decreases in HR, VE, and rating of perceived exertion during submaximal exercise; a 7.7% increase (p less than 0.01) in VO2 max; and a 9.1% increase (p less than 0.01) in performance time. Adaptations (training effects) were independent of time of day of training for all variables except VO2 at the ventilatory threshold. Compared with each other, subjects who trained in the morning had relatively higher post-training thresholds in the morning, while subjects who trained in the afternoon had relatively higher values in the afternoon (p less than 0.05). This is evidence of circadian specificity in training and supports the notion of planning physical preparation to coincide with the time of day at which one's critical performance is scheduled.

Adult↗
PubMed1989

Effect of time of day on perceived exertion at work rates above and below the ventilatory threshold.

The effect of time of day on ratings of perceived exertion (RPE) at various intensities of cycling exercise, both below and above the ventilatory threshold, was studied in 32 subjects, 18 to 35 years of age. The ventilatory threshold occurred at the same (p greater than .05) mean (+/- SD) work rate in the morning (110.6 +/- 27.0 watts) and in the afternoon (111.9 +/- 23.9 watts) and was perceived as equally strenuous (p greater than .05) in the morning (RPE = 13.8 +/- 2.4) and in the afternoon (RPE = 13.6 +/- 2.8). At intensities below the ventilatory threshold, RPE was the same (p greater than .05) in the morning and in the afternoon; above the ventilatory threshold, RPE was lower (p less than .05) in the morning. We conclude that, during incremental submaximal cycling exercise above the ventilatory threshold, a particular work rate is perceived as less strenuous in the morning than in the afternoon. About 20% of this difference in RPE is explained by lower ventilatory demands in the morning.

Adolescent↗
PubMed1989

Relation of plasma volume change to intensity of weight lifting.

To determine the relation of plasma volume change to intensity of weight lifting, blood samples were obtained from 15 males [mean (+/- SD) age = 22.3 +/- 3.2 yr; height = 176.3 +/- 6.9 cm; weight = 73.0 +/- 11.7 kg] before and over a 60-min period following weight lifting at four different intensities [40, 50, 60, and 70% of one-repetition maximum (1-RM)]. Weight lifting consisted of completing three circuits of four exercises (bench press, bent-over row, arm curl, and parallel squat), with 10 repetitions of each exercise performed over a 30-s period followed by 30 s of rest. Mean (+/- SE) oxygen uptakes (VO2) during weight lifting at the four intensities were 1.31 +/- 0.04, 1.50 +/- 0.07, 1.72 +/- 0.07, and 1.86 +/- 0.08 1.min-1, or 33-47% of treadmill-determined VO2max, respectively. Mean (+/- SE) blood lactates were 6.5 +/- 0.5, 8.7 +/- 0.5, 9.4 +/- 0.6, and 12.0 +/- 0.6 mmol.1(-1), respectively. Mean (+/- SE) heart rates (HR) were 124 +/- 4, 134 +/- 4, 148 +/- 5, and 161 +/- 4 bpm, or 63-82% of treadmill-determined HRmax, respectively. Plasma volume decreased linearly in relation to intensity of weight lifting with mean responses of -7.7 +/- 0.8, -10.7 +/- 0.8, -12.1 +/- 0.9, and -13.9 +/- 0.8% at 40, 50, 60, and 70% of 1-RM, respectively. It was concluded that plasma volume decreases linearly in relation to intensity (%1-RM) of weight lifting and that the relation is similar to that reported for dynamic, low-resistance exercise such as cycling and running.

Adult↗
PubMed1988

Oxidative decarboxylation of salsolinol-1-carboxylic acid to 1,2-dehydrosalsolinol: evidence for exclusive catalysis by particulate factors in rat kidney.

The decarboxylation of salsolinol-1-carboxylic acid (1-methyl-6,7-dihydroxy-1,2,3,4- tetrahydroisoquinoline-1-carboxylic acid), a novel endogenous catecholic adduct of dopamine and pyruvic acid, was examined in nuclei-free homogenates of rat liver, whole brain, and kidney, as well as in buffer only. Liquid chromatographic analysis of incubations for varying times (30 min to 5 h) showed that the tetrahydroisoquinoline substrate decarboxylated oxidatively, forming one product, 1-methyl-6,7-dihydroxy-3,4-dihydroisoquinolines (1,2-dehydrosalsolinol). No salsolinol was apparent, even with added NADPH. In buffer, decarboxylation occurred by an apparent oxygen radical-mediated process: it was stimulated by cupric ion or elevated pH, and was suppressed by EDTA, superoxide dismutase, metal ion removal with Chelex-100, or low pH (less than 6). In liver or brain, the conversion was qualitatively and quantitatively similar to that in buffer; thus there was no evidence for enzyme involvement. In kidney, however, dehydrosalsolinol formation was significantly greater than that in liver, brain, or buffer, and preboiling reduced it nearly to buffer values. The heat-labile kidney activity, displaying a pH maximum ca. 9, was localized in the particulate fractions. It was blocked completely by N-ethylmaleimide. Added superoxide dismutase was only slightly inhibitory; catalase and dimethyl sulfoxide, a hydroxyl radical trap, were uneffective. Lack of inhibition by indomethacin ruled against peroxidative involvement of kidney prostaglandin synthetase. Physiological amounts of a cofactor for amino acid decarboxylases, pyridoxal-5'-phosphate, also had no effect. The oxidative decarboxylation of 1-carboxylated salsolinol by kidney fractions appears mainly due to a sulfhydryl-containing particulate factor unique to or relatively concentrated in that organ. Its identity, substrate specificity, and possible significance, particularly in alcoholism, where elevated salsolinol-1-carboxylic acid levels have been reported, remain to be ascertained.

Animals↗
PubMed1988

Acetaldehyde and its condensation products as markers in alcoholism.

Several studies show that recently abstaining alcoholics generate higher circulating levels of acetaldehyde than nonalcoholics following ethanol administration. It is conceivable that levels of stable adducts (tetrahydroisoquinolines and tetrahydro-beta-carbolines) derived from acetaldehyde condensations with biogenic amines also might be increased in alcoholics consuming ethanol, thus serving in body fluids as chemical markers that are more persistent than acetaldehyde itself. Limited human and rat studies indicate that urinary excretion of an oxidized tryptamine condensation product (harmane) and of an acetaldehyde/serotonin condensation product is elevated by chronic ethanol. Salsolinol, the derivative of acetaldehyde and dopamine, does not appear to be a meaningful urinary marker, but levels of the related pyruvic acid/dopamine product may be increased by ethanol. Blood assays of condensation products have been limited in number and equivocal. Condensation product measurements are complicated not only by artifacts (formation during analyses), but by other inherent problems. Products of interest often are constituents of diets and alcoholic beverages. For this and perhaps endogenous metabolic reasons, traces of condensation products are normally excreted by nondrinking individuals. Furthermore, the assays require high sensitivity and specificity and are not easily adapted to routine use. Thus, although several condensation products have initial appeal as clinical or pathological indicators in chronic alcoholism, thorough and statistically sound studies are needed before conclusions can be reached concerning any particular biogenic amine-derived product.

Acetaldehyde↗
PubMed1988

Evidence for the conjugal transfer of the broad host range plasmid pIP501 into strains of Lactobacillus helveticus.

The conjugative broad host range plasmid pIP501 was transferred from Streptococcus faecalis to a series of strains of lactic streptococci used commercially as dairy starter cultures. With these transconjugants as donors the plasmid was exconjugated to two strains of Lactobacillus helveticus and a commercially used strain of Strep. thermophilus. There was evidence that the plasmid could transfer between isogenic derivatives of one of the strains of Lact. helveticus. Transfer from Lact. helveticus to Strep. faecalis was also detected but at a low frequency. There was no evidence for the conjugal transfer of plasmid pIP501 into a strain of Lact. bulgaricus by exconjugation from either lactic streptococci or Lactobacillus sp.

Conjugation, Genetic↗
PubMed1988

Muscle hypertrophy in men and women.

It is widely believed that women experience less skeletal muscle hypertrophy consequent to heavy-resistance training than men. The purpose of this study was to test this hypothesis using both traditional indirect indicators as well as a direct measure of muscle size. Seven male experimental (ME), 8 female experimental (FE), and 7 control subjects were studied before and after a 16-wk weight training program, in which ME and FE trained 3 days.wk-1 at 70 to 90% of maximum voluntary contraction using exercise designed to produce hypertrophy of the upper arm and thigh. Strength increased significantly (P less than 0.05) in ME and FE, respectively, on elbow flexion (36.2 and 59.2%), elbow extension (32.6 and 41.7%), knee flexion (12.8 and 24.4%), and knee extension (28.8 and 33.9%) tests. Absolute changes were significantly greater in ME than FE in 2 of the 4 tests, whereas percentage changes were not significantly different. Substantial muscle hypertrophy occurred in the upper arms of both ME and FE as evidenced by significant increases in upper arm circumference (7.9 and 7.9%), bone-plus-muscle (B+M) cross-sectional area (CSA) estimated by anthropometry (17.5 and 20.4%), and muscle CSA determined from computed tomography scanning (15.9 and 22.8%). Changes by ME and FE were not significantly different, except for the absolute increase in estimated B+M CSA, which was significantly greater in ME (11.2 vs 7.4 cm2). No muscle hypertrophy occurred in the thigh of either ME and FE as evidenced by non-significant changes in thigh circumference (1.7 and 2.3%), B+M CSA (4.9 and 6.1%), and muscle CSA (2.9 and 2.9%). Changes by ME and FE in body weight, fat-free weight, and fat weight were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1987

Effect of training on the rating of perceived exertion at the ventilatory threshold.

The purpose of this study was to determine the effect of training on the rating of perceived exertion (RPE) at the ventilatory threshold. College students were assigned to either training (n = 17) or control (n = 10) groups. Trainers completed 18 interval training sessions (five X 5 min cycling at 90-100% VO2max) and 8 continuous training sessions (40 min running or cycling) in 6 weeks. Pre- and post-training, cardiorespiratory, metabolic, and perceptual variables were measured at the ventilatory threshold during graded exercise tests on a cycle ergometer. Ventilatory threshold was that point above which VE X VO2-1 increased abruptly relative to work rate. Post-training means of trained and control subjects were compared using analysis of covariance, with pre-training values as covariates. Following training, the adjusted means for the trained subjects were significantly greater (p less than 0.05) than for controls for VO2max (6%), and for work rate (20%), VO2 (23%), and %VO2max (13%) at the ventilatory threshold. However, adjusted means for RPE at the ventilatory threshold were not significantly different (2%). Both before and after training, exercise at the ventilatory threshold was perceived as 'somewhat hard' to 'hard' (RPE = 13-15) by both groups. The relationship between RPE and %VO2max was altered by training, with trained subjects having a lower RPE at a given %VO2max. It is concluded that RPE at the ventilatory threshold is not affected by training, despite that after training the ventilatory threshold occurs at a higher work rate and is associated with higher absolute and relative metabolic and cardiorespiratory demands.

Adult↗
PubMed1987

Inhibition of catechol-O-methyltransferase by 6,7-dihydroxy-3,4-dihydroisoquinolines related to dopamine: demonstration using liquid chromatography and a novel substrate for O-methylation.

We report that 6,7-dihydroxy-3,4-dihydroisoquinolines related to dopamine are potent inhibitors of catechol-O-methyltransferase (COMT), but are not apparent substrates for the enzyme in vitro or in vivo. Three dihydroxy (catecholic) dihydroisoquinolines, including the 1-benzyl (DesDHP) and the 1-methyl (DSAL) analogs, were found to inhibit COMT activity in rat liver supernatant more effectively than the well-known inhibitor, tropolone. Inhibition of O-methylation was uncompetitive with substrate, and O-methylated products of the catecholic dihydroisoquinolines were undetectable. For these in vitro studies, a facile liquid chromatographic assay was developed utilizing as a site-specific substrate, 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline-1-carboxylate (salsolinol-1-carboxylate). This catechol produces only one phenolic product isomer when incubated with liver supernatant and S-adenosylmethionine. Following central injection of DSAL in rats, inhibition of brain COMT in vivo was indicated by the reduced brain levels of homovanillic acid, but not of 3,4-dihydroxyphenylacetic acid. Furthermore, O-methylated DSAL metabolites could not be detected in brain by liquid or gas chromatography. We suggest that 6,7-dihydroxy-dihydroisoquinolines are "nonmethylatable" COMT inhibitors because they exist as quinoidal tautomers resembling pyridones or tropolones rather than as catechols. Quinoid formation is supported by the fluorescence and ultraviolet spectra for DSAL and its O-methyl derivatives. The experiments reveal a new class of COMT inhibitors that may be of pharmacological and mechanistic value. Additionally, 3,4-dihydroisoquinolines could arise endogenously via oxidation of the 1,2,3,4-tetrahydroisoquinolines which are ingested or produced from cellular catecholamine condensations. However, it is unlikely that dihydroisoquinoline (e.g., DSAL) concentrations necessary to inhibit COMT significantly would be attained via endogenous pathways.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Plasma volume change during heavy-resistance weight lifting.

Blood samples were obtained from six young men before, and over a 60-min period following a bout of heavy-resistance weight lifting to determine changes in plasma volume. Weight lifting consisted of three sets of four exercises (arm curl, bench press, bent-arm row, and squat) performed using 70% of one-repetition maximum for as many repetitions as possible. Plasma volume change was determined from haematocrit and haemoglobin concentration. During weight lifting, mean oxygen uptake and heart rate were 1.96 L X min-1 and 158 bt X min-1, respectively. Plasma volume was decreased -14.3% (p less than 0.05) immediately following exercise and -7.0% (p less than 0.05) at 15 min into recovery, but had returned to the resting level within 30 min. It was concluded that heavy-resistance weight lifting elicits a significant decrease in plasma volume, which is similar in magnitude to that observed during running and cycling at 80-95% of maximal oxygen uptake.

Adult↗
PubMed1986

The histology and development of hepatic nodules in C3H/He mice following chronic administration of phenobarbitone.

Male C3H/He mice were given 0 (control) or 85 mg/kg/day phenobarbitone (PB). Groups of five control and five treated animals were killed at 5, 10, 25, 40 and 55 weeks; additional animals were allowed to live out their natural life span or killed at the termination of the experiment at 100 weeks. Small nodules of basophilic cells were seen in control animals at 55 weeks. These increased both in size and number so that at term nodules were found in 17/35 animals examined. Animals given PB showed typical centrilobular hypertrophy. Basophilic nodules were also seen in the treated animals and these were similar in form and in number to those seen in control animals. The total number of liver nodules seen in animals given PB was, however, greater than the number seen in control animals. The increased nodule burden was a result of the development of a second nodule type that was first seen in animals killed at 40 weeks. These nodules were formed of large eosinophilic cells that had a similar appearance to the hypertrophied cells of the centrilobular region. In contrast the incidence of carcinoma in PB-treated animals was not increased over that of the control group.

Animals↗