PubMed Health⌕ Search

Biomedical subjects

B A Brooks

Publications and source records attributed to B A Brooks.

At least 37 records · Page 2Linked to original sources
PubMed1987

Behavioral and biochemical studies in monkeys made hemiparkinsonian by MPTP.

Monkeys were required to press a lever rapidly for food, using either the right or the left hand. After stable baseline performance was established, MPTP (N-methyl-4-phenyl-2,3,5,6-tetrahydropyridine) was injected into the internal carotid of one side via a transfemoral catheter. The onset and time course of clinically severe, Parkinson-like symptoms were paralleled by a significant decrease of bar-pressing activity in the side contralateral to injection, while the forelimb in the unaffected side continued normal pressing. The unilaterality of effects was confirmed biochemically after sacrifice by a 95% drop in striatal dopamine (DA) levels of the injected compared to the uninjected hemisphere. The results show that hemiparkinsonism achieved by carotid injection is very stable; that normal motor behavior is maintained on the unaffected side and that goal-achieving strategies remain active, but that the affected side is unable to execute the task unless extrinsic levodopa is provided.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Saccadic eye movement deficits in the MPTP monkey model of Parkinson's disease.

Saccadic eye tracking was studied in a monkey given i.v. injections of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The Parkinson-like symptoms which appeared in the animal's general motor behavior (akinesia, bradykinesia, hypokinesia) were also observed in its eye tracking. Similar oculomotor deficits are seen in patients with idiopathic Parkinsonism. The MPTP model offers excellent possibilities for studying the mechanisms underlying the motor disabilities of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

H-2 modulation of aryl hydrocarbon hydroxylase induction and the mutagenicity of benzo(a)pyrene after 3-methylcholanthrene treatment.

All strains except the DBA/2J, B10.S and B10.RIII exhibited an increase in hepatic cytochrome P-450 levels following MC treatment; furthermore, the P-450 response of the B10.D2 strains was greater than that seen in the B10 and B6 strains. MC treatment increased BP metabolism in all congenic strains relative to their corn oil controls. Both relative and absolute changes in AHH activity were higher in the B10.D2 than the B6 or B10 reference strains. All congenic strains exhibited an enhanced capacity to produce mutagenic metabolites of BP following treatment with MC; the B10.M, B10.WB and B10.D2 segregated with the B6 and B10 in this regard, while the B10.S and B10.RIII changed least following MC administration.

Animals↗
PubMed1986

Variability and functional recovery in the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of parkinsonism in monkeys.

Fourteen macaque monkeys were injected intravenously with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. All developed the cardinal signs of parkinsonism (akinesia, rigidity, etc.) in varying degrees; some required repeated series of injections of the drug, while others developed the syndrome readily after the first series. Most of the subjects that were kept for longer than 4 weeks after the first dose of the drug showed complete or partial recovery after that time. Measurement, in some of the subjects, of the neostriatal levels of dopamine and dihydroxyphenylacetic acid showed the expected depletion of these substances at the peak of the behavioral action of the drug, but no recovery when the animals had returned to, or near, pre-drug behavioral status. No firm conclusion can be reached at this time as to the reasons for the behavioral recovery or the variability of the effects of the drug across subjects.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

Acceptance of physical therapist assistant course work by programs preparing physical therapists.

I developed and sent a questionnaire to the directors of entry-level physical therapy programs to determine if course work taken in an associate degree program could be credited toward requirements leading to a higher degree or certificate in physical therapy. I sent 86 questionnaires; 45 were returned. Results of the survey revealed that basic science courses taken by the physical therapist assistant (PTA) students are more likely to be credited (up to half of the respondents replied positively) toward a higher degree or certificate than are technical courses like therapeutic exercise, fundamentals of physical therapy, or physical modalities. Moreover, as many as 79 percent of the respondents reported that PTAs would not be granted transfer credit for their technical courses. Of those respondents whose programs do give credit for the technical courses, the courses are usually considered as elective hours. Although the concept of upward mobility appears to remain viable in the educational philosophy of the American Physical Therapy Association, students who view the associate degree program as an entry point into a physical therapy program must be aware of the problems of acceptance of PTA credits in an entry-level physical therapy program.

Allied Health Personnel↗
PubMed1985

Effects of repeated doses of enalapril on renal function in man.

Ten healthy subjects received 10 mg oral enalapril (MK 421) daily for a period of 8 days. Renal clearances of electrolytes, urate and phosphate were monitored and factored for glomerular filtration rate, as measured by creatinine clearance, with particular emphasis on the first and eighth day of treatment. Apart from a fall of around 10% in creatinine clearance between 1-2 h on both days 1 and 8, GFR remained unchanged throughout the study. Fractional sodium excretion increased in a biphasic manner by approximately 50% over control between 1-2 h and 4-8 h on day 1. Significant chloruresis (+39.0 +/- 12.9%) and kaluresis (+26.5 +/- 10.3%) occurred between 4-8 h. Urinary pH increased between 0-1 h (+0.29 +/- 0.12; P less than 0.05), and between 4-8 h (+0.50 +/- 0.08; P less than 0.01). The biphasic saluretic effect was also seen between 1-2 h and 4-8 h on day 8. Enalapril caused significant increases in urate and phosphate excretion on day 8 of therapy. There was a biphasic increase in fractional urate excretion at 1-2 h (+28.1 +/- 6.9%; P less than 0.05) and at 4-8 h (+21.0 +/- 6.0% P less than 0.01). Significant phosphaturia (+36.8 +/- 5.2%; P less than 0.05) was also observed at 4-8 h on day 8. Urinary drug excretion was also biphasic; over the first 2 h the predominant drug form was unchanged enalapril, whilst the peak excretion of the diacid metabolite, enalaprilat, occurred at 4-8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Renal actions of piretanide and three other "loop" diuretics.

Thirty-nine clearance studies were performed in 17 healthy subjects under conditions of maximal hydration or hydropenia to compare the effects on renal solute and water handling of three sulfamoylbenzoic acid derivatives-piretanide, bumetanide, and furosemide-and the phenoxyacetic acid diuretic ethacrynic acid. Except for furosemide, which caused a 7% fall in effective renal plasma flow (ERPF), and ethacrynic acid, which reduced both the glomerular filtration rate (16%) and ERPF (23%) during maximal hydration, changes in hemodynamics were insignificant. At peak saluresis piretanide induced a mean reduction of -18.3% +/- 4.9% in fractional free-water clearance during hydration and -73.2% +/- 5.9% in fractional free-water reabsorption during hydropenia. The other sulfamoylbenzoates lowered fractional clearance and reabsorption of free water to similar extents, implying a major site of action within the medullary portion of the ascending limb. Ethacrynic acid reduced fractional free-water clearance to a greater degree than did the sulfamoylbenzoates. The mean reduction in fractional free-water reabsorption after ethacrynic acid (71.4% +/- 8.2%) was of the same order as that caused by the sulfamoylbenzoates. Similar excretory maxima for sodium, chloride, potassium, calcium, and magnesium were achieved for all four diuretics. Except for piretanide under hydropenia, sulfamoylbenzoate action did not change urinary pH. Ethacrynic acid consistently lowered urinary pH. During hydration piretanide induced phosphaturia (35.3% +/- 8.8%) and uricosuria (40.9% +/- 9.1%). Both bumetanide and piretanide increased fractional urate clearance during hydropenia (16.7% +/- 5.6% and 34.2% +/- 10.5%). There were no changes in phosphate or urate excretion after ethacrynic acid. Our data support the view that sulfamoylbenzoate diuretics exert additional effects on proximal tubular segments that are not shared by ethacrynic acid. Renal responses to piretanide most closely resemble those to bumetanide.

Absorption↗
PubMed1984

Renal actions of a uricosuric diuretic, racemic indacrinone, in man: comparison with ethacrynic acid and hydrochlorothiazide.

The effects of indacrinone (IND) have been investigated in a two part study. First, a total of 36 clearance studies have been performed in 14 healthy volunteers, under conditions of either maximal hydration or hydropenia, to compare the renal sites of action of single oral doses of IND, 20 mg, ethacrynic acid (EA), 100 mg, and hydrochorothiazide (HCTZ), 100 mg. Under conditions of maximal water hydration, IND increased fractional Na+ excretion from a mean of 1.19 +/- 0.05 to 4.93 +/- 0.67% of GFR. This was similar to the response seen with HCTZ, which increased fractional Na+ clearance up to 3.16 +/- 0.17% of GFR; EA increased fractional Na+ excretion up to 14.5 +/- 2.5% of GFR. The mean reduction in fractional free-water clearance (CH2O/GFR X 100%) invoked by IND, (delta = -34.8% of control) was similar to that produced by EA, (delta = -27.2% of control), and by HCTZ, (delta = -26.6% of control). During hydropenia with superimposed mannitol diuresis, both IND and EA caused a fall in fractional free-water reabsorption (TcH2O/GFR X 100%), delta IND = -20.3% of control, delta EA = -70.1% of control. HCTZ produced a significant increase in fractional free-water reabsorption, delta HCTZ = -20.7% of control. In all studies, single doses of IND were both uricosuric and hypouricaemic. Fractional urate excretion increased from a mean 6.7 +/- 0.1 to 15.2 +/- 2.1% of GFR whilst plasma urate concentration fell from a mean of 0.36 +/- 0.03 to 0.34 +/- 0.03 mM (P less than 0.05) within 2-3 h post drug. HCTZ and EA, in single doses, had little effect on urate excretion. In the second part of the study, a total of 16 healthy volunteers received either IND, 10 mg, or HCTZ 50 mg, orally for 8 days, whilst on a diet of controlled electrolyte content. Both drugs were well tolerated by both sets of subjects with no adverse clinical or pathological findings. Both IND and HCTZ caused a significant reduction in weight and standing systolic blood-pressure during the first 48 h of therapy. At the doses administered, IND and HCTZ displayed similar diuretic responses with respect to water, Na+, Cl-, Ca2+ and PO4(3-) excretion. IND produced less kaliuresis than HCTZ during the first treatment day but cumulative K+ loss was similar for both drugs over the eight days of therapy. Fractional urate excretion after IND remained elevated throughout the 8 days of therapy and the subjects remained isouricaemic for 7 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Body Weight↗
PubMed1984

Stereo-specificity of diuretic receptors in the nephron: a study of the enantiomers of indacrinone (MK-196) in man.

Urinary clearance techniques have been employed to compare the renal sites of action of three phenoxyacetic acid diuretics in man: ethacrynic (etacrynic) acid and the two enantiomers of indacrinone (MK-196). The effects of these compounds on fractional free-water clearance and reabsorption during maximal hydration and hydropenia, respectively, indicate that whilst ethacrynic acid and (-)-indacrinone have their natriuretic site of action in the medullary portion of the thick ascending limb of Henle's Loop, the (+)-enantiomer of indacrinone acts in the 'cortical diluting segment' or early distal tubule. The natriuretic potencies of all three agents are different as is their effect on the renal handling of uric acid. Ethacrynic acid produces minor urate retention whilst both enantiomers of indacrinone produce uricosuria and hypouricaemia. The apparent difference in the renal sites of action of the enantiomers of indacrinone is discussed in relation to our current knowledge of stereo-selectivity in other pharmacological systems.

Absorption↗
PubMed1983

Effect of starvation and refeeding on activity of a Ca2+-dependent protease in rat skeletal muscle.

The effects of starving, refeeding, and restarving rats for different periods on content of sarcoplasmic and contractile proteins and on activity of the Ca2+-dependent proteinase (CAF) in skeletal muscle was determined. Groups of five to six male rats, 8 to 11 weeks old, were starved up to 8 days, refed up to 6 days, and in two experiments, restarved up to 10 days. CAF activity was assayed in P 0-45 crude CAF fractions prepared so as to remove a protein inhibitor of CAF; the assays were demonstrated to be specific for CAF. Sarcoplasmic protein content of rat skeletal muscle changed little until after 6 days of restarvation when it decreased to 68-89% of control level (P less than 0.05). Contractile protein content decreased to 65% of control level (P less than 0.01) after 8 days of starvation, remained at this level for 4 days of refeeding, then increased to approximately 80% of control level after 6 days of refeeding, remained at this level for 2 days of restarvation, and then decreased to approximately 65% of control level (P less than 0.01) after 6 and 8 days of restarvation. Muscle CAF activity did not change during the first 8 days of starvation but increased to 113% above control level (P less than 0.01) after 6 days refeeding and then decreased to only 29% of control level (P less than 0.01) after 8 days of restarvation. These changes in muscle CAF activity are consistent with the proposed role for CAF in initiating metabolic turnover of contractile proteins, but because actual measurements of myofibrillar protein were not made and because in vivo CAF activity is difficult to assess, they do not prove this role for CAF nor do they exclude participation of other proteinases.

Animals↗
PubMed1983

The effect of enalapril on serum prolactin.

Twelve healthy male volunteers received single daily oral doses of enalapril (EN) 10 mg for 8 consecutive days. Serum samples for prolactin (PRL) assay were taken on day 0 (baseline) at 12.00 h and 16.00 h, and on days 1 and 8 at 08.00 h (pre-drug), 12.00 h and 16.00 h. The 08.00 h values on day 1 served as the pre-drug baseline. There were no significant changes from baseline in serum PRL levels on days 1 and 8. All mean serum PRL levels on day 8 were significantly (P less than 0.01) lower than the upper limit of the normal range (2-15 ng/ml) found for healthy males in this laboratory. It is concluded that therapeutic doses of EN (10 mg/day, p.o.) for 8 consecutive days do not raise mean serum PRL levels above the normal range in healthy male volunteers.

Adult↗
PubMed1983

Effect of alloxan diabetes on a Ca2+-activated proteinase in rat skeletal muscle.

The effect of making rats diabetic by alloxan injection on activity of the muscle Ca2+-activated proteinase (CAF) was investigated. Groups of four to seven control or alloxan-injected rats were killed 10 min (0 day) and 10, 17, and 24 days after a second alloxan injection. The second alloxan injection was given 3 days after the first. CAF activity was assayed in fractions precipitated between 0 and 45% ammonium sulfate saturation (P0-45 crude CAF fractions) that had been prepared so as to remove the protein inhibitor of CAF. Gel permeation, followed by DEAE-cellulose chromatography of pooled P0-45 crude CAF fractions from each time-treatment group, demonstrated that the assays used in this study were specific for CAF activity. Muscle CAF activity was up to 50% higher in alloxan-injected rats than in control rats, regardless of whether activity was expressed per gram sarcoplasmic protein, per gram contractile protein, or per gram skeletal muscle fresh weight. Alloxan injection diminished rate of muscle mass accumulation but did not change the proportion of sarcoplasmic or contractile protein in skeletal muscle. Hence, alloxan injection decreased the rate of contractile protein deposition. The elevation of muscle CAF activity in alloxan-injected rats is consistent with the proposed role of CAF in initiating metabolic turnover of myofibrillar proteins but does not prove this role nor exclude participation of other proteinases.

Alloxan↗
PubMed1981

Suppressive effects of a peripheral grating displacement during saccadic eye movement and during fixation.

Rapid displacement of a peripheral grating reduced sensitivity to test flashes presented at the center of gaze equally well, whether the displacement was produced by mirror movement during fixation or by saccadic eye movement with the grating stationary. Small 0.5 degree flashes in the retinal periphery were not affected by distant grating displacements, but large (5.0 degree) flashes were suppressed. Thus there is a size-selective suppressive mechanism which does not affect small stimuli except at the fovea.

Animals↗
PubMed1980

Perception of images moving at saccadic velocities during saccades and during fixation.

During saccadic eye movements, images of external objects move rapidly across the retina. Small, unpredictable displacements imposed upon a target moving at saccadic velocity were detected with equal accuracy when (1) the retinal image velocity was caused by an eye movement, or (2) when the same velocity was produced during fixation (simulated saccadic conditions). The results provide no evidence of a specific non-visual suppression of vision during saccades, nor of any other compensatory modification of afferent visual inflow which might contribute to our sense of directional stability during saccades.

Eye Movements↗
PubMed1980

Influence of background luminance on visual sensitivity during saccadic eye movements.

Detection thresholds were measured for a brief test flash projected on a uniform background before, during, and after saccadic eye movement. The amount and duration of threshold elevation during saccades was directly dependent on back-ground illumination; no significant elevations occurred at backgrounds of 2.0 log fl or less. Similar results were obtained during fixation when the backgrounds were "saccadically" displaced. An occipital evoked potential was recorded in association with both eye movements and background displacements at higher background luminances (no test flash). These results may indicate an activation of a selected population of neural elements - probably the "Y" channels - which occurs during saccades in illuminated environments and which renders the channels less responsive to additional, simultaneous, and appropriately structured stimuli.

Adult↗
PubMed1980

Studies on the mechanism and characteristics of action of a uricosuric diuretic, indacrinone (MK-196).

1 The renal action of indacrinone (MK-196), a phenoxyacetic acid derivative with diuretic and uricosuric properties, has been studied in fifteen male subjects. 2 Increasing single doses of up to 60 mg of oral indacrinone produced a linear increase in urinary volume and excretion of Na+ and Cl-, whilst the responses of urinary K+, Ca2+, Mg2+ and uric acid excretion, rose to a plateau at the 40 mg dose. 3 Indacrinone evoked a rapid diuretic response which reached a maximum of 2-4 h and was largely complete at 8-12 h after administration. 4 During maximal hydration, indacrinone produced a substantial fall in fractional free water clearance (CH2O), from 8.89% to 5.83% of the filtered load of water, associated with an increase in osmolal clearance, from 1.38% to 5.78% of the filtered load of solute. The reduction in CH2O was of the same order as that produced by a dose of ethacrynic acid with comparable saluretic activity and significantly greater than that produced by an equi-saluretic dose of hydrochlorothiazide. These findings imply an action of indacrinone upon solute transport in the diluting segments of the distal tubule. 5 At the time of maximal indacrinone-induced saluresis, which amounted to an increase from 0.48% to 4.61% of the filtered load of NaCl, fractional urate clearance increased from 5.16% to 12.24% of the filtered load of uric acid. 6 Indacrinone is a long acting diuretic, sharing some properties in common with both loop diuretics and benzothiadiazines. The results are discussed in relation to structure-activity amongst derivatives of phenoxyacetic acid.

Diuresis↗