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Biomedical subjects

M Rosenthal

Publications and source records attributed to M Rosenthal.

At least 145 records · Page 8Linked to original sources

Age-related modifications of potassium homeostasis and synaptic transmission during and after anoxia in rat hippocampal slices.

Age-related changes in the capacity of the brain to survive short anoxic episodes were studied in stratum pyramidale (region CA1) of hippocampal slices from control (6-7 months) and aged (26-27 months) rats. Our primary interest was in how aging affected the ability of slices to maintain or to recover extracellular potassium ion (K+o) homeostasis and orthodromically-stimulated field potentials during and after anoxia. During anoxia, K+o homeostasis was lost faster in slices from aged rats. Following anoxia, K+o homeostasis recovered more slowly, and synaptic transmission recovered less completely, in aged slices. These studies provide what is believed to be the first demonstration that aging diminishes the capacity of brain tissue to maintain K+o during anoxia and to recover K+o homeostasis and synaptic transmission following anoxia, and support suggestions that the aged brain is more vulnerable to anoxia.

Action Potentials↗

Extracellular pH and suppression of electrical activity during anoxia in turtle and rat brain.

To evaluate the contribution of extracellular H+ activity toward depression of brain electrical activity during anoxia, extracellular pH (pHe) and field potentials were measured in turtle and rat olfactory bulbs with ion-selective microelectrodes. This study tests the hypothesis that unique regulation of pHe contributes to the remarkable tolerance of turtle brain to prolonged anoxia. Hypercapnea (20% CO2 ventilation) depressed olfactory bulb evoked potentials 25-30% in both rat and turtle. During anoxia, evoked potentials were completely abolished within 1 min in rat olfactory bulb but decreased to only 40% of control after 4 h in the turtle despite similar changes in brain pHe. Anoxia-induced acidification of turtle brain was exacerbated by hypercapnea and was attenuated by hypocapnea or by hypocapnea plus intravenous infusion of sodium bicarbonate. However, these manipulations of pHe during anoxia in turtle brain had little effect on depression of evoked potentials. We conclude that energy failure, rather than extracellular acidification, is the major contributor toward suppression of electrical activity in mammalian brain and that preservation of energy balance, rather than unique pH regulation, is responsible for protection of turtle brain during anoxia.

Action Potentials↗

Potassium-induced increases in oxygen consumption are diminished by age in rat hippocampal slices.

Previous reports showed that cytochrome alpha,alpha 3 responded to heightened brain activity with shifts toward oxidation in adult rats but toward reduction in aged animals. To determine whether this change indicates an age-associated limitation in mitochondrial respiratory capacity, the present study compared oxygen consumption in hippocampal slices of young adult (6 month, control) and aged (26 month) rats. Slices were used to insure that results were independent of cerebrovascular factors. Age was without effect on oxygen consumption under 'resting' conditions (i.e. with slices bathed at 3.5 mM K+), but oxygen consumption was not increased as much in hippocampal slices from aged rats under heightened energy demands (produced by raising the extracellular potassium ion activity [( K+]o to 50 mM). This lesser oxygen consumption response to enhanced metabolic demand suggests that there are age-associated limits to the brain's ability to increase its metabolic rate.

Aging↗

Acceptability of an experimental intracervical device: results of a study controlling for selection bias.

We analyzed baseline and 12-month follow-up interview data from 98 women who had volunteered to use an experimental intracervical device (ICD) and from 155 women who had been randomly assigned to two control groups, the levonorgestrel-releasing intrauterine device (LNG-IUD; N = 86) and the copper Nova-T IUD (N = 69). All participants were clinic patients in Helsinki, Finland. Initial analysis of 12-month discontinuation data indicated that a significantly higher percent of ICD users (22.4) discontinued their device than did either LNG-IUD (7.0) or Nova-T (8.7) users. However, we were no longer able to detect significant differences in discontinuation after controlling for baseline variables that assessed predisposition to be dissatisfied with contraception in general. Adjusted probabilities of discontinuing the ICD, LNG-IUD, and Nova-T were 11.8%, 6.2% and 7.9%, respectively. These data indicate that the ICD is likely to be acceptable to Helsinki clinic patients; moreover, they suggest a definite place for hormonal intrauterine devices in the contraceptive armamentarium. Most importantly, the methodology used here can be generalized to acceptability studies of other contraceptive devices and drugs undergoing Phase I and early Phase II clinical trials (in situations where randomization may not be feasible) in order to identify and control for the bias introduced by nonrandom assignment procedures.

Adolescent↗

Effects of 50-hertz electromagnetic fields on proliferation and on chromosomal alterations in human peripheral lymphocytes untreated or pretreated with chemical mutagens.

Cultivation of human peripheral lymphocytes (HPL) in the presence of 50-Hz electromagnetic fields (EMFs) does not alter the spontaneous frequencies of sister-chromatid exchanges (SCE) and of chromosomal aberrations (CA), but leads to an enhancement of the cell cycle progression of HPLs in vitro. Pretreatment of HPLs with trenimon (TRN), diepoxybutane (DEB), or methylnitrosourea (MNU) in the G0 phase of the cell cycle results in dose-dependent elevations of the SCE frequencies. In some cases culturing of HPLs pretreated with MNU or TRN in the presence of EMFs led to significantly higher frequencies of SCEs when compared to cells cultivated in the absence of EMFs. Since we did not use multiple fixation times these data may rather result from differential influences on HPL subsets than from EMF exposure.

Alkylating Agents↗

MPP+-induced pathophysiology demonstrates advantages of neurotoxicology studies in brain slices.

Since MPTP and its metabolite MPP+ produce nigrostriatal lesions and symptoms similar to Parkinson's disease, recent studies have aimed toward defining their selectivity and neurotoxic mechanisms. In mitochondria in vitro, MPP+ blocked electron transport and decreased oxygen consumption. However, these effects were not selective to striatal mitochondria or even to mitochondria from brain, they required concentrations of MPP+ much greater than those found in vivo, and physiological actions could not be related to intramitochondrial changes. Lower doses of MPP+ did produce highly selective degeneration of dopaminergic (DA) neurons in cell cultures. We report here that MPP+ provoked large (80%) oxidations of cytochrome b and large K+o increments (approximately 30 mM) in rat striatal slices. These effects were slowed by mazindol, which inhibits DA uptake, and were markedly attenuated in rat hippocampal slices which have little DA input. Since DA terminals comprise only 2-4% of the striatal mass, the large MPP+-induced changes suggest that while MPP+ neurotoxicity in brain requires the presence of functioning DA terminals, effects are not confined to these terminals. Such studies illustrate the complexity of MPP+ neurotoxicity and demonstrate the importance of investigations in models such as brain slices with an extracellular space and intracellular relationships as in intact brain.

1-Methyl-4-phenylpyridinium↗

Indo-1 measurements of intracellular free calcium in the hippocampal slice: complications of labile NADH fluorescence.

The use of fluorescent calcium indicator, Indo-1, was evaluated for measuring changes in intracellular free calcium during electrical stimulation and anoxia in hippocampal slices. Fluorescence was measured from slices illuminated with brief (3 ns) light pulses (337 nm wavelength) from a nitrogen laser. This method of illumination produced more intense fluorescence than illumination with light from filtered xenon or mercury arc lamps, and prevented loss of electrical excitability encountered following continuous UV illumination. Background fluorescence in control slices (without Indo-1) was considerable, often approaching 50% of that obtainable after dye loading. A more serious concern, however, was that a large fraction (approximately 10%) of the background fluorescence was labile to both electrical stimulation and anoxia. This fluorescence results from changes in the reduction/oxidation (redox) state of nicotinamide adenine dinucleotide (NAD), which fluoresces in its reduced (NADH) but not oxidized (NAD+) form. Qualitative changes in free calcium could be measured by first determining the ratio of change in NADH fluorescence at 405 and 485 nm (the wavelengths of light used to measure calcium with Indo-1) prior to dye loading. Any arbitrary baseline could be selected as long as the ratio for the baseline at 405 and 485 nm was identical to that determined for labile NADH. By application of this compensation procedure, it was determined that intracellular calcium rose abruptly during the onset of anoxia and again during the spreading depression-like loss of ion homeostasis which inevitably occurred during anoxia in these slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prolactin and corticosterone response to repeated footshock stress in male rats.

The prolactin (PRL) and corticosterone (CORT) responses to footshock stress were measured in rats after the first, fifth, and 57th exposure to the stress procedure. No reduction in the PRL or CORT responses was seen after repeated application of the footshock stress and the animals showed similar behavioral responses throughout. These results indicate that the hormonal and behavioral responses to footshock stress are not attenuated after an animal has been repeatedly exposed to the stress.

Animals↗

[Computed tomography and magnetic resonance tomography of the lower leg in chronic venous insufficiency].

Sixty-two lower limbs in 29 women and six men with chronic venous insufficiency (CVI) of grade II and III were examined by CT and eight of these additionally with MRI. The changes were compared with the findings in 21 patients of similar age, but without venous abnormalities. The most important findings were subcutaneous fibrosis with or without calcification, nonspecific infiltration of the extrafascial spaces and degeneration of the Achilles' tendon. The simultaneous occurrence of these changes can be regarded as typical of advanced CVI. CT was somewhat superior to MRI; its use can be justified as part of posttherapeutic follow-up and for special problems.

Adult↗

Lithium carbonate for aggressive behavior or affective instability in ten brain-injured patients.

Lithium carbonate (LiCO3) was used to treat 10 brain-injured patients with severe, unremitting, aggressive, combative, or self destructive behavior or severe affective instability. Five patients had a dramatic response that resulted in significant improvement in their participation in a rehabilitative program. One other patient had a moderate response. A seventh patient improved dramatically, but regressed after 7 wk. Three other patients had neurotoxic side effects that precluded continued use of the medication. Two of them were simultaneously taking neuroleptic agents. These case reports provide further evidence that LiCO3 can be a useful medication in the treatment of aggressive behavior and affective instability after brain injury, but that it has significant potential for neurotoxicity in this population, particularly when used in conjunction with neuroleptic agents.

Adult↗

Effects of age on complications in adult onset diabetes.

The prevalence of diabetes is greatest among older persons, yet few studies have specifically addressed the impact of age on diabetic complications. The present study examines the prevalence of four diabetic complications: retinopathy, peripheral neuropathy, autonomic neuropathy, and hypertension, as well as depression, in older male patients with noninsulin-dependent diabetes. Participants ranged in age from 53 to 80 years. Multiple risk factors, including age, duration of illness, type of treatment, metabolic control, and obesity were evaluated as predictors of these complications using logistic regression. Results suggest a significant increase in the prevalence of retinopathy with aging, independent of the effects of metabolic control, duration of illness, and other risk variables. Age was also related to prevalence of peripheral neuropathy symptoms, hypertension, and impotence. Current metabolic control was significantly associated with retinopathy, peripheral neuropathy, and hypertension prevalence. Time since diagnosis was only independently related to impotence and hypertension. These findings suggest that the increase in many diabetic complications in older persons cannot be wholly accounted for by simple disease status variables, and may result from an interaction of diabetes variables and general age-related changes.

Age Factors↗

Energy metabolism, ion homeostasis, and evoked potentials in anoxic turtle brain.

Unlike the mammalian brain, the turtle brain maintains ion homeostasis and avoids anoxic depolarization during prolonged anoxia. The mechanisms by which turtle brains avoid and recover from anoxic depolarization were investigated by relating changes in cellular ATP levels to extracellular K+ (K+o) and evoked potential activities after 6 h of anoxia and during anoxic depolarization induced by superfusion of the brain surface with iodoacetate during anoxia. ATP levels were maintained during 6 h of anoxia despite marked decreases in energy production, but ATP was lowered during inhibition of both oxidative phosphorylation and glycolysis. K+o activity was unchanged during 6 h of anoxia but increased when ATP levels decreased. Ion homeostasis in the turtle brain appears to be linked to ATP levels but is unaffected by rate of energy production. In contrast, amplitudes of evoked potentials decreased when ATP levels were maintained, but rate of energy production declined. ATP and K+o levels recovered after anoxic depolarization, but evoked potential activity was not restored. These data suggest that the basic strategy for turtle brain to survive anoxia is to avoid anoxic depolarization by maintaining ATP levels.

Animals↗

Ion leakage is reduced during anoxia in turtle brain: a potential survival strategy.

The turtle brain maintains ATP levels, ion homeostasis, and some neural function during prolonged anoxia despite significant decreases in the rate of ATP production. To test the hypothesis that reduced ATP production during anoxia was compensated partly by conserving energy through reduced ion leakage, the rate of K+ leakage was measured in normoxic and anoxic turtle brains in which Na(+)-K(+)-adenosinetriphosphatase was inhibited with ouabain. Rates of K+ leakage were significantly lower in brains subjected to 2 h of anoxia than in normoxic brains. These data support the suggestion that reduced ion leakage is an important mechanism for energy conservation during anoxia.

Acclimatization↗

Regulation of tyrosine hydroxylase mRNA in catecholaminergic cells of embryonic rat: analysis by in situ hybridization.

In situ hybridization was used to examine the appearance of mRNA specific for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine (CA) biosynthesis, in neural crest derivatives of the rat embryo. These derivatives include sympathetic ganglia and transient catecholaminergic cells of embryonic intestine. Messenger RNA is first detected in sympathetic ganglia at E11.5, the age corresponding to the initial immunocytochemical expression of TH protein. In older embryos increased accumulation of TH-specific mRNA in sympathetic ganglia parallels the increase in TH immunoreactivity. By contrast, mRNA for TH is difficult to detect in embryonic intestines at E11.5 but is found instead in cells clustered at the dorsal boundaries of the pharynx and foregut. Cells expressing TH mRNA are infrequently found in embryonic intestines at any age, even though TH protein is immunohistochemically apparent. Treatment of pregnant rats with doses of reserpine, known to increase circulating levels of glucocorticoid hormones and prolong the expression of TH protein in embryonic gut cells, dramatically but transiently increases the number of gut cells at E12.5 with detectable TH mRNA. After E13.5 TH mRNA is undetectable even in reserpine-treated guts. Reserpine treatment also increases the labeling density in sympathetic ganglia. Taken together, these data are consistent with the hypothesis that the microenvironment of the embryonic intestine affects gene expression directly to alter phenotype. Moreover, although reserpine administration briefly increases TH mRNA levels, the effect is short-lived and does not alter neurotransmitter phenotypic conversion.

Animals↗

Menstrual pattern change 1 year after sterilization: results of a controlled, prospective study.

To determine if female sterilization is associated with adverse menstrual change, we compared prospectively collected menstrual data from women who underwent sterilization via bipolar cauterization, banding, and Pomeroy ligation with data from women whose husbands obtained a vasectomy and from women who were not planning sterilization. At first-year follow-up, sterilization via banding with Falope rings was not associated with adverse change. After excluding initially abnormal cases: (1) cauterization women were bleeding more heavily than all other groups excepting Pomeroy; (2) cauterization and Pomeroy women experienced more dysmenorrhea than women not planning sterilization; and (3) more cauterization and Pomeroy women (collapsed samples) developed abnormal length cycles than did the two control groups. There were no group differences regarding development of beneficial/neutral change (e.g., decreased dysmenorrhea). However, cauterization and Pomeroy groups experienced a significantly higher average number of adverse changes than did the other groups and were at significantly greater risk of developing one or more adverse changes than were women not planning sterilization. The only pattern of association among adverse menstrual changes occurred significantly more often in the cauterization and next in the Pomeroy groups.

Adult↗