Search PubMed⌕ Search

Biomedical subjects

M Rosenthal

Publications and source records attributed to M Rosenthal.

At least 163 records · Page 9Linked to original sources
PubMed1988

MPP+-induced increases in extracellular potassium ion activity in rat striatal slices suggest that consequences of MPP+ neurotoxicity are spread beyond dopaminergic terminals.

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces symptoms similar to idiopathic Parkinson's disease in primates. A metabolite of MPTP, MPP+ (1-methyl-4-phenylpyridinium), is actively accumulated by dopaminergic (DA) terminals and selectively destroys nigrostriatal DA neurons. The mechanism of this effect remains unknown but reports that MPP+ inhibits electron transport in isolated mitochondria and increases oxidation of cytochrome b in striatal slices suggest that depression of ATP production is involved. To relate metabolic effects of MPP+ with tissue electrophysiology, extracellular potassium ion activity [K+]o was measured by microelectrodes simultaneous to optical monitoring of reduction/oxidation (redox) activity of cytochrome b during superfusion of MPP+ onto rat striatal and hippocampal slices. MPP+ increased oxidation of cytochrome b and increased [K+]o in slices of striatum. These increases were greater than expected from a selective effect of MPP+ on DA terminals which likely comprise no more than 3% of the total striatal mass. These effects of MPP+ were slowed by a dopamine uptake inhibitor (mazindol) and did not occur in hippocampal slices. These findings indicate that MPP+ influences ion transport as well as metabolic activity and that these actions require the presence of functioning DA terminals. However, the large amplitudes of the MPP+-induced changes suggest that consequences of MPP+-neurotoxicity are not ultimately confined to DA terminals. Two hypothesis are proposed: that energy failure in DA terminals results in leakage of neurotoxic substances or metabolites altering membrane conductance properties of adjacent cells and thereby placing additional demand upon ion transport pumps and mitochondrial oxidative phosphorylation; or that there is secondary uptake of MPP+ leading to mitochondrial inhibition in cells neighboring DA terminals.

1-Methyl-4-phenylpyridinium↗
PubMed1988

Depth profile of local oxygen tension and blood flow in rat cerebral cortex, white matter and hippocampus.

Microregional oxygenation and blood flow were measured in rat cerebral cortical lamina, subcortical white matter and hippocampus. This was done to examine relationships between oxygenation and blood flow at a local level, to determine effects of craniotomy, and to consider whether flow/oxygenation relationships might be predictive of selective vulnerability known to accompany anoxia or ischemia. Blood flow and oxygen tension were measured with closely apposed polarographic microelectrodes. Oxygen tension was highest in white matter, lower in the region of cortical laminae IV-V and lowest in the hippocampus. Blood flow in the hippocampus was higher than that in white matter or laminae IV-V of cerebral cortex. Ratios of blood flow to oxygenation were similar throughout the cortex, higher in white matter but oxygenation in hippocampus was significantly less than expected from measurement of hippocampal blood flow reflecting increased oxygen consumption or relative hypoxia due to increased diffusion distances for oxygen in hippocampus. Comparison of data from closed vs opened skull animals indicated that diffusion of oxygen and hydrogen influenced data to approximately 1000 micron below the cerebral surface.

Animals↗
PubMed1988

1-Methyl-4-phenylpyridinium (MPP+) increases oxidation of cytochrome-b in rat striatal slices.

Effects of 1-methyl-4-phenylpyridinium, (the active metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), on reduction/oxidation activity of mitochondrial cytochromes were studied in rat striatal slices using scanning spectrophotometry. The objective was to test the hypothesis that the neurotoxin alters electron transport in the mitochondrial respiratory chain. Incubation of rat striatal slices with MPP+ (1 microM) produced a time-dependent oxidation of Cytochrome-b in a manner consistent with the concept of a block in electron transport in the intramitochondrial respiratory chain between nicotinamide adenine dinucleotide (NAD) and Cytochrome-b. This effect of MPP+ was decreased by co-incubation with a potent dopamine uptake inhibitor (mazindol), or when studied in a tissue with low dopaminergic innervation (hippocampus). The amplitude of Cytochrome-b oxidation was greater than that expected from a selective effect of MPP+ on dopaminergic neurons suggesting that neighboring cells are influenced secondary to the MPP+ effect on dopaminergic terminals.

1-Methyl-4-phenylpyridinium↗
PubMed1988

Changes in urinary amino acid fractional excretion in neonates undergoing total parenteral nutrition.

The paper examines the possible reasons why there was a different weight gain pattern in two groups of sick neonates fed two different amino acid solutions during a prospective double-blind trial of otherwise identical total parenteral nutrition. During the 13-month study period, 14 neonates (eight less than 32 weeks gestation) received Vamin as their amino acid source, and 18 (eight less than 32 weeks gestation) received a new amino acid solution, Paedmin. The older group of neonates gained weight far better when fed Vamin (P less than 0.003), neonates of less than 32 weeks gestation gained weight better when fed Paedmin (P less than 0.004). These differences in weight gain were reflected in differences in plasma amino acid concentration in that the levels were lower in the groups gaining weight less well; and in urinary fractional excretion where the groups gaining weight less well had a markedly higher fractional excretion and total urinary loss of amino acids (P less than 0.001). It is suggested that these differences in amino acid handling of two different amino acid solutions may lead to differences in weight gain.

Amino Acids↗
PubMed1988

Inhibition of glycolysis alters potassium ion transport and mitochondrial redox activity in rat brain.

To examine the relationships between brain glycolysis, ion transport, and mitochondrial reduction/oxidation (redox) activity, extracellular potassium ion activity (K+0) and redox shifts of cytochrome oxidase (cytochrome a,a3) were recorded previous to and during superfusion of rat cerebral cortex with the glycolytic inhibitor iodoacetic acid (IAA). IAA produced oxidation of cytochrome a,a3, increased local oxygenation, increased K+0, and, in response to neuronal activation, slowed rates of K+0 reaccumulation. Rates of rereduction of cytochrome a,a3, after the oxidation of this cytochrome by stimulation, were also slowed by IAA. These effects of IAA demonstrate the dependence of K+0 reaccumulation on the integrity of glycolysis, support the concept that active processes are involved in brain ion transport, and suggest a link between ATP supplied by glycolysis and ion transport activity. These data are also compatible with the suggestion that residual dysfunctions after brain ischemia result from derangements in glycolytic functioning rather than from limitations in oxygen availability or oxidative metabolic activity.

Animals↗
PubMed1988

Potassium ion homeostasis and mitochondrial redox activity in brain: relative changes as indicators of hypoxia.

This study was directed at relating ion transport and mitochondrial redox activity during hypoxia, as a step toward definition of brain oxygen sufficiency. To accomplish this, extracellular potassium ion activity (K+o) was recorded by ion-selective microelectrodes while reduction/oxidation (redox) ratios of cytochrome oxidase (cytochrome a,a3) were monitored by reflection spectrophotometry in cerebral cortex of rats anesthetized with pentobarbital. In normoxia, neuronal activation by direct cortical stimulation produced transient oxidation of cytochrome a,a3 and elevation of K+o. Moderate hypoxia (PaO2 above 50 mm Hg) resulted in reduction of cytochrome a,a3 but only slight elevation of K+o. At this level of hypoxia, cytochrome a,a3 continued to respond to neuronal activation with transient shifts toward oxidation and rates of K+o reaccumulation were unchanged from control. When PaO2 was further decreased below a critical threshold, stimulus-provoked oxidative responses of mitochondrial reactants were replaced by shifts toward reduction, but rates of reaccumulation of K+, spilled into the extracellular space by neuronal activation, remained unchanged. Only during severe hypoxia (PaO2 less than 20 mm Hg) was it possible in some animals to record a slowing in the reaccumulation of K+o without provocation of spreading cortical depression. These data indicate that ion transport activity in cerebral cortex is more refractory to hypoxia than is mitochondrial redox functioning. They suggest an in vivo parallel to the "cushioning" effect of mitochondria in vitro, in which oxygen consumption remains constant despite fluctuations in oxygenation and redox ratios, and also that there may be a greater anaerobic capacity to provide energy for ion transport in mammalian brain than has previously been appreciated.

Animals↗
PubMed1988

Effects of physical exercise for elderly patients with physical impairments.

Exercise is known to preserve many physiological responses in the healthy elderly, yet those with physical impairments are often discouraged from exercising. The authors studied the effects of a closely supervised exercise program designed specifically for elders with health problems and functional limitations. Tests, selected for their relevance to clinical patient management, included the Self Evaluation of Life Function questionnaire, treadmill performance, and tests of autonomic nervous system and neuromotor functions. Ambulatory volunteers, aged 64 to 83 years, with noncardiac health problems, were randomly assigned to a control group (CG; n = 17) or a 16-week exercise group (EG; 3 hr/wk, n = 18). Nine of the control and 13 of the exercise subjects completed the study. All EG dropouts were due to illness. EG attendance averaged 87%, and subjects trained at a heart rate (HR) of 103 +/- 5 beats/min (SD) (98% of prescription HR). Though EG test responses showed a tendency to improve, none reached statistical significance. This result was affected by the small number completing the study and the variability inherent in such a sample. Though these impaired elderly subjects enthusiastically and safely participated with high attendance and at an exercise intensity adequate to expect benefit, measurable training effects were not demonstrated.

Aged↗
PubMed1988

Ranitidine in the newborn.

An infusion of ranitidine 0.2 mg/kg/hour abruptly halted a life threatening gastrointestinal haemorrhage in an anuric infant of 30 weeks' gestation.

Gastrointestinal Hemorrhage↗
PubMed1988

Congenital hypothyroidism: increased incidence in Asian families.

Screening in the North West health region of England showed a significantly higher incidence of congenital hypothyroidism in Asian families--1/918 compared with 1/3391 in non-Asians. This could only in part be explained by consanguinity. No differences were found in birth order, season of birth, gestational age, or birth weight between normal infants and those with congenital hypothyroidism. There was a significantly higher incidence of additional congenital abnormalities (9%) and a significantly increased mortality (5%) in infants with congenital hypothyroidism compared with unaffected infants.

Asia↗
PubMed1988

Suppression of evoked potentials with continued ion transport during anoxia in turtle brain.

A key to turtle brain survival during anoxia is continued ion transport and avoidance of anoxic depolarization. Previous findings that ATP concentration remained constant during prolonged anoxia and calculations that ATP production decreased indicate that compensatory processes, other than consumption of energy stores or increased anaerobic glycolysis, must also contribute to ion homeostasis and brain survival. To determine whether preservation of ion transport is associated with changes in electrophysiology during loss of oxidative metabolism, the brains of pentobarbital sodium-anesthetized turtles were electrically stimulated 1) to provoke measurable increments in extracellular K+ activity (a degrees k) for determination of rates of K+ reaccumulation at the stimulus site and 2) to elicit polysynaptic extracellular field potentials (evoked potentials) recordable in the olfactory bulb. During anoxia, base-line a degrees k rose only a few millimolar, and rates of reaccumulation of K+, incremented by stimulation were slightly but not significantly slowed. In contrast, postsynaptic orthodromic responses of olfactory bulb granule cells were markedly depressed by anoxia. Monosynaptic responses of granule cells to antidromic stimulation of the lateral olfactory tract were less affected, and compound action potentials in the olfactory nerve were unchanged by anoxia. These data suggest that synaptic transmission in turtle brain, as in that of mammal, is highly dependent on oxidative metabolism and that the turtle brain may effectively conserve energy for ion transport during anoxia by depression of electrical activity.

Animals↗
PubMed1988

Orthodromic field potentials and recurrent inhibition during anoxia in turtle brain.

Recent evidence suggests that suppression of electrical activity, with the likely reduction of energy use, provides a necessary strategy for prolonged anoxic tolerance of turtle brain. The present study was aimed toward defining mechanisms underlying anoxia-induced suppression of electrical activity in turtle brain. Goals were to determine whether effects of anoxia were selective to excitatory or inhibitory processes and to test the hypothesis that enhanced inhibition underlies suppression of orthodromic field potentials in olfactory bulb. Amplitudes of "conditioning" and "test" responses, provoked by pairs of stimulus pulses to the olfactory nerve, were evaluated before, during, and after anoxic insults in the brains of turtles anesthetized with pentobarbital sodium. Suppression of conditioning responses was proportionally greater than that of test responses, indicating that inhibition was decreased and that enhanced inhibitory activity is not responsible for suppression of field potentials in turtle olfactory bulb during anoxia. When normoxia was restored, conditioning responses recovered but test responses remained suppressed. These data confirm that the inhibitory effect of a conditioning pulse on responses to a second pulse of stimulation results from a recurrent circuit and suggest that anoxia-induced changes in field potentials are independent of this recurrent circuit. Enhanced inhibition during the early period of recovery after anoxic insults may provide advantages for restoring energy status and cell physiology by suppressing electrical activity and energy use.

Animals↗
PubMed1987

Role of pulmonary edema in phasic changes of cerebral oxygenation during serial seizures.

To examine whether pulmonary dysfunction leads to episodes of cerebral hypoxia during recurrent seizures, measurements were made of arterial blood pressure, blood-gases, cerebral pO2, and relative changes in cytochrome a,a3 redox levels in anesthetized, paralyzed rats. Seizures were induced serially with bicuculline (BIC) or pentylenetetrazol (PTZ). During early seizures, cerebral oxygenation increased phasically. As seizures continued, a transition often occurred following which seizures were accompanied by phasic decreases in cerebral oxygenation. In addition, pulmonary edema often occurred at an unpredictable point during a series of seizures. Seizure-associated pulmonary edema was less likely to occur with pentobarbital anesthesia and PTZ seizures, than with nitrous oxide anesthesia and BIC seizures. Pulmonary edema was always accompanied by prolonged increases in blood pressure and paroxysmal electrocortical activity, and by hypoxemia, acidemia, and decreased cerebral oxygen supply. Despite the severity of these physiological changes, the transition from phasic increases to decreases in cerebral oxygenation during serial seizures occurred with virtually the same frequency in rats with and without pulmonary edema. This indicates that this transition is independent of pulmonary edema.

Animals↗
PubMed1987

Reducing roentgenography use. Can patient expectations be altered?

Many roentgenographic tests, including lumbar spine roentgenograms, may be overutilized. We examined the psychological, functional, and financial consequences of omitting spine films for patients with back pain with little risk of underlying systemic illness. Patients were randomized to receive immediate roentgenograms (n = 49) or a brief educational intervention, with roentgenography only for failure to improve (n = 52). After three weeks, 73% of the roentgenography group believed "everyone with back pain should have an x-ray," vs 44% of the education group. After three months, although 31% in the education group had received roentgenograms, overall radiology charges were still far less than those of the roentgenography group. No serious diagnoses were missed, and symptom resolution, functional improvement, and satisfaction were similar for the two groups. Thus, eliminating or delaying spine films need not cause anxiety, dissatisfaction, or dysfunction. This strategy may modify future expectations of roentgenography use and reduce health care costs.

Adult↗
PubMed1987

A double blind comparison of a new paediatric amino acid solution in neonatal total parenteral nutrition.

All infants requiring parenteral nutrition over a continuous 13-month period were allocated to receive either Vamin or a new paediatric amino acid solution, Paedmin, as their protein source in a double blind prospective study. Those of 32 weeks gestation and less gained weight more rapidly when fed Paedmin than Vamin (P less than 0.004), but there were significant changes in liver function after 14 days nutrition. Babies of 33 weeks gestation and greater gained weight more rapidly when fed Vamin than Paedmin (P less than 0.003) but without liver function changes. There were no differences in the rate of head growth. Amino acid analysis of serum and urine showed a greater urinary loss of amino acids for a given serum concentration in babies of 32 weeks and less for both nutrition groups. The apparent benefit of Paedmin in the immature group of infants must be further evaluated and weighed against changes in liver function.

Amino Acids↗
PubMed1987

Detection of an oxidizable fraction of cytochrome oxidase in intact rat brain.

Rapid-scanning reflectance spectrophotometry was used to evaluate the reduction-oxidation state of cytochrome oxidase in normoxic rat brain. Reflectance spectra were recorded from intact blood-perfused cerebral cortices after increased oxidative metabolic activity induced by direct cortical stimulation. Reflectance spectra taken from blood-free rat brain and from the rat ear vascular bed were used to identify cytochrome and hemoglobin components of spectra taken from intact brain. Cortical stimulation provoked shifts toward increased oxidation of cytochrome oxidase that were detectable in reflectance spectra. Observations of an oxidizable fraction of cytochrome oxidase demonstrate that a fraction of the cytochrome oxidase pool exists in a reduced state in normoxic brain. The presence of reduced cytochrome oxidase suggests that oxygen delivery to the brain is restricted by microvascular control mechanisms either as a function of brain metabolic physiology or as protection against oxygen toxicity.

Absorption↗
PubMed1987

Seizure-associated pulmonary edema and cerebral oxygenation in the rat.

Cerebral partial pressure of O2 (PO2), relative changes in the ratio of reduced/oxidized cytochrome aa3, blood flow, and the arteriovenous difference in O2 content were measured during seizures with and without pulmonary edema. Seizures were induced with bicuculline (0.2-1.2 mg/kg iv) in rats anesthetized with 70% N2O and paralyzed with curare. Briefer seizures were accompanied by increased cerebral PO2 and increased oxidation of cytochrome aa3. Lung water content and arterial O2 partial pressure (PaO2) remained normal. Longer duration seizures were also accompanied initially by increases in cerebral oxygenation. Within minutes, however, PaO2 fell from a mean of 118 to 51 mmHg, and lung water content increased from 76.2 to 83.6%. Cerebral PO2 fell but most often rose back to or above control levels, while cytochrome aa3 became markedly reduced. Simultaneously, cerebral blood flow increased more than 300% above preseizure values and O2 delivery increased more than O2 consumption. The reductive shift of cytochrome aa3 was greater than that produced by lowering PaO2 to equivalent values in seizure-free rats. The reductive shift of cytochrome aa3, despite increased O2 delivery, may be indicative of derangements in cerebral O2 diffusion or energy metabolism.

Animals↗
PubMed1987

Secular decline in death rates due to ischemic heart disease in Mexican Americans and non-Hispanic whites in Texas, 1970-1980.

Although the decline in ischemic heart disease mortality is now entering its third decade, there has been no definitive information on the experience of Mexican Americans, the nation's second largest minority group. Earlier studies carried out in the 1970s were hampered by the unavailability of satisfactory population data beyond 1970. In the present study we have used 1970 and 1980 census data to compute death rates in Mexican Americans and non-Hispanic whites from Texas for the periods 1969-1971 and 1979-1981. All four sex-ethnic groups showed statistically significant declines in death rates due to all causes, due to total ischemic heart disease, and due to acute myocardial infarction between 1969-1971 and 1979-1981. Declines in the latter two causes of death were least marked in Mexican American men. This sex-ethnic group was also the only one that failed to show a decline in death rates due to chronic ischemic heart diseases. The fact that Mexican Americans have been shown to be less well informed about and less likely to adopt lifestyle changes aimed at reducing heart disease risk than non-Hispanic whites may account for the less striking mortality decline observed in Mexican American men, but is harder to reconcile with the apparent equal decline in Mexican American women compared with non-Hispanic whites.

Adult↗