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Biomedical subjects

A Breier

Publications and source records attributed to A Breier.

At least 163 records · Page 9Linked to original sources
PubMed1991

Application of adsorption kinetics for estimation of dissociation constants.

Substances such as drugs, as well as special ligands with expressive biospecific properties, all with different affinities, interact with proteins which can be characterized by dissociation constants. The method for estimation of the dissociation constant on the basis of adsorption kinetics was verified for two typical cases: adsorption of lactate dehydrogenase onto bead cellulose derivatized by reactive dyes C.I.2. or C.I.19, and adsorption of different drugs (neuroleptics and local anesthetics) onto calmodulin immobilized on agarose gel. The real equilibrium values obtained by using the complete time-concentration model of adsorption were fitted according to the respective adsorption isotherms by non-linear regression.

Adsorption↗
PubMed1991

Increased activity of sarcolemmal (Na+K+)-ATPase is involved in the late cardioprotective action of 7-oxo-prostacyclin.

The delayed effects of 7-oxo-prostacyclin, protecting the heart against extrasystoles, ventricular fibrillation, and cardiac arrest induced by high doses of ouabain or in ischemia and postischemic reperfusion, have already been described; but little is known about the molecular mechanisms involved. In this study, 50 micrograms.kg-1 7-oxo-prostacyclin administered intramuscularly significantly stimulated the activity of (Na+K+)-ATPase in rat heart sarcolemma 24 and 48 hours after application (p less than 0.01 and p less than 0.001, respectively). Kinetic analysis revealed a mixed type of stimulation of ATPase activity, with increased Vmax and decreased Km values. Cycloheximide (1 mg.kg-1) applied together with 7-oxo-prostacyclin, significantly antagonized the stimulatory effect of 7-oxo-prostacyclin, and had a modulatory effect on the kinetics of the (Na+K+)-ATPase both 24 and 48 hours after administration. The results show that protein synthesis is involved in the mechanism of the increase in enzyme activity.

Animals↗
PubMed1991

Panic disorder: clinical features, neurobiology, and pharmacotherapy.

Anxiety disorders are common, debilitating illnesses. Panic disorder is an anxiety disorder with a characteristic clinical presentation. A growing body of neuroanatomical and neurochemical data is beginning to elucidate its pathophysiology. There are currently three types of effective pharmacotherapies for panic disorder: tricyclic antidepressants, monoamine oxidase inhibitors, and highpotency benzodiazepines. The choice of a pharmacologic approach may be guided by considerations of potential side effects and other clinical/pharmacologic concerns.

Antidepressive Agents↗
PubMed1990

Cerebrospinal fluid and plasma monoamine metabolites and their relation to psychosis. Implications for regional brain dysfunction in schizophrenia.

The relationship between central (cerebrospinal fluid [CSF]) and peripheral (plasma) monoaminergic metabolites and psychotic symptoms was examined in 22 drug-free schizophrenic inpatients. The CSF homovanillic acid levels did not differ significantly between patients and normal controls (n = 33). The CSF homovanillic acid levels, however, were negatively correlated with ratings of psychosis and positive symptoms, and the CSF homovanillic acid and 5-hydroxyindoleacetic acid levels correlated negatively with individual deficit symptoms. Stepwise and hierarchical multiple-regression analysis revealed that among monoaminergic measures, only the CSF and plasma homovanillic acid levels contributed significantly to the total Brief Psychiatric Rating Scale and positive symptom variance with negative and positive partial correlations, respectively. Levels of CSF 3-methoxy-4-hydroxyphenylglycol, but not of CSF norepinephrine, were significantly elevated in the schizophrenic patients compared with controls, and plasma 3-methoxy-4-hydroxyphenylglycol levels were positively correlated with negative symptoms. We discuss the potential implications of these findings for a model of dopaminergic dysfunction in schizophrenia involving distinct cortical and subcortical contributions.

Adult↗
PubMed1990

Prednisone effects on neurochemistry and behavior. Preliminary findings.

To evaluate the neurochemical, neuroendocrine, and behavioral effects of exogenous corticosteroids in humans, we administered prednisone (80 mg/d orally for 5 days) in a double-blind manner to 12 medically healthy volunteers. Behavioral measures were assessed before, during, and after prednisone administration in all 12 subjects, and cerebrospinal fluid biochemistry was assessed before and during prednisone administration in 9 of the subjects. Prednisone administration was associated with decreases in cerebrospinal fluid levels of corticotropin, norepinephrine, beta-endorphin, beta-lipotropin, and somatostatinlike immunoreactivity. No significant changes were noted in cerebrospinal fluid levels of alpha-melanocyte-stimulating hormone, corticotropin-releasing hormone, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, or 5-hydroxyindoleacetic acid. No consistent or significant group mean changes were observed in structured behavioral ratings, although 9 (75%) of the volunteers studied reported mild behavioral changes while receiving prednisone. Correlations between the neurochemical and behavioral changes are discussed.

Adult↗
PubMed1990

Prednisone effects on blood-brain barrier permeability and CNS IgG synthesis in healthy humans.

Corticosteroids reportedly decrease blood-brain barrier (BBB) permeability and/or IgG synthesis in patients with multiple sclerosis or brain tumors. However, these effects have not been studied in healthy humans. We investigated the effects of prednisone, 80 mg/day for five days, on the ratio of cerebrospinal fluid (CSF) albumin/serum albumin, a measure of blood-brain barrier (BBB) permeability, and on CSF and serum IgG levels in six healthy, normal volunteers. We found significant steroid-induced decreases in serum and CSF albumin levels and in serum IgG levels. However, we found only a nonsignificant decrease in BBB permeability and no significant change in CNS IgG synthesis. These findings, based on a small number of volunteers, suggest that it may be difficult to further decrease BBB permeability and CNS IgG synthesis in medically healthy subjects.

Adult↗
PubMed1990

Differential effects of controllable and uncontrollable acute stress on lymphocyte proliferation and leukocyte percentages in humans.

This study examined the effects of a 30-min laboratory stressor on aspects of immune function in 24 men and whether behavioral control over the stressor moderates stress effects. The stressor consisted of mild (2.5 mA) electric shock and loud (100 dB) white noise administered in an unpredictable, intermittent fashion. During stress sessions, only half of the subjects were able to control the stressor. Subjects with control were yoked to subjects who could not control the stressor so that both groups were exposed to identical intensity and duration of noise and shock. Immunologic function was assessed across stress and nonstress conditions by measuring changes in lymphocyte proliferation to concanavalin A (Con A) and phytohemagglutinin (PHA) and by measuring changes in percentages of lymphocytes and their subpopulations, granulocytes, and monocytes. Results revealed that exposure to the uncontrollable stressor altered mood but did not affect immune function. In contrast, exposure to controllable stress did not alter mood but did result in lowered lymphocyte proliferation to Con A. Poststress percentages of monocytes were also lower in subjects exposed to the controllable stressor. Results suggest that acute stress can alter aspects of immune function in humans and underscore the importance of stressor controllability in moderating stress effects on human immunity.

Affect↗
PubMed1990

Neurochemical and neural mechanisms of positive and negative symptoms in schizophrenia.

It is difficult to come away from review of pharmacologic and metabolite studies without concluding that dopaminergic mechanisms play a significant role in mediating both negative and positive symptoms. Nevertheless, the characteristics of dopaminergic involvement are unclear. Whereas compelling evidence continues to link the mechanism of action of neuroleptic drugs, including therapeutic effects on negative and positive symptoms, to blockade of D2 receptors, neuroleptic-induced alterations in dopaminergic function are time-dependent and may include reductions in variability as well as in net dopamine activity. Moreover, pharmacologic enhancement of dopaminergic function may at least transiently improve symptomatology (negative greater than positive) and levels of CSF HVA appear to be reduced or are negatively correlated with symptoms in some schizophrenic patients. Thus, there is support for both increased and decreased dopamine function in schizophrenia. Functional brain imaging has, after only a few years of application, made significant contributions to our understanding of the pathophysiology of schizophrenia. Studies of cerebral metabolism and regional CBF have shown remarkable consistency in their identification of abnormal function of the frontal cortex in schizophrenia. It should be pointed out, however, that agreement across studies remains largely conceptual with significant discrepancies still existing with regard to the precise localization of dysfunction and its relationship to cognitive activation. Although less well documented than 'hypofrontality' itself, negative symptomatology appears to bear some relationship to this defect. The idea that positive symptoms might be associated with increased subcortical and/or metabolism is less well supported. The recent advances in our understanding of structure and function of CNS dopaminergic systems may help to integrate these two bodies of data into more dynamic models of dopaminergic defects in schizophrenia. For example, the concept that diminished mesocortical coupled with increased subcortical dopaminergic activity might be a 'substrate' for psychosis is compatible with neurochemical evidence suggesting both diminished and enhanced dopaminergic processes as well as with metabolic hypofrontality. Better understanding of the regulatory mechanisms involved in establishing functional balance between cortical and subcortical systems might, therefore, identify new possibilities for biological dysfunction in schizophrenia. The recent study by Weinberger et al. which correlates CSF HVA levels with neuropsychologically induced frontal CBF is an example of how neurochemistry can enhance brain imaging data.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗
PubMed1990

Cognitive effects of corticosteroids.

In three independent studies with different designs and groups of subjects, the authors found that 1) depressed patients who did not suppress cortisol when given dexamethasone (compared to suppressors and normal control subjects), 2) healthy volunteers given a single 1-mg dose of dexamethasone (compared to those given placebo), and 3) healthy volunteers given 80 mg/day of prednisone for 5 days (compared to those given placebo) all made significantly more errors of commission in verbal memory tasks, with no significant change in their rates of errors of omission. These findings raise the possibility of specific corticosteroid-related cognitive impairments.

Adrenal Cortex Hormones↗
PubMed1990

Plasma norepinephrine in chronic schizophrenia.

Several lines of evidence indicate altered noradrenergic function in schizophrenia. The authors examined resting, standing, and change (standing minus resting) in plasma norepinephrine levels in 14 drug-free patients with chronic schizophrenia or schizoaffective disorder and in 33 age- and sex-matched healthy volunteers. Schizophrenic patients had significantly higher resting and standing plasma norepinephrine levels and significantly greater change. Resting and standing levels were significantly related to positive and negative symptoms. There was a significant positive correlation between resting plasma and CSF norepinephrine levels and a significant negative correlation between CSF homovanillic acid and resting, standing, and change in plasma norepinephrine levels.

Adult↗
PubMed1990

[The role of Na(+) pump inhibition induced by Ca2(+) ions in the development of pathologic changes during calcium overload in myocardial cells].

Ca2+ ions cause marked inhibition of (Na+ + K+)-ATPase. Strontium and barium ions exert a less pronounced inhibition of (Na+ + K+)-ATPase activity. These findings suggest the existence of a regulatory binding site for calcium ions on the (Na+ + K+)-ATPase molecule. Under physiological conditions, this binding site is presumably involved in stopping the activity of (Na+ + K+)-ATPase during depolarization of the sarcolemma. In pathological conditions which are characterized by calcium overload of cardiomyocytes inhibition of (Na+ + K+)-ATPase by calcium ions can significantly contribute to massive damage of myocardial cells. (Fig. 3, Ref. 26.).

Animals↗
PubMed1990

Interaction of Cibacron Blue 3GA and Remazol Brilliant Blue R with the nucleotide binding site of lactate dehydrogenase and (Na+ + K+)-ATPase.

The interaction of Cibacron Blue 3GA (C.I.2) and Remazol Brillant Blue R (C.I.19) with purified preparations of Lactate dehydrogenase (LDH) and (Na+ + K+)-ATPase was studied by means of the enzyme kinetics method. LDH was found to be inhibited by both C.I.2 and C.I.19, with the former being a stronger inhibitor. This may be explained by the fact that in contrast to C.I.19, C.I.2 resembles the whole molecule of the specific cofactor. (Na+ + K+)-ATPase activity was inhibited by both dyes to approximately similar degree. C.I.2 and C.I.19 resemble the ATP molecule to approximately similar extent, particularly as concerns the molecule shape and size. The results obtained confirmed the applicability of C.I.2 and C.I.19 as nucleotide-specific ligands.

Anthraquinones↗
PubMed1989

Fluphenazine treatment reduces CSF somatostatin in patients with schizophrenia: correlations with CSF HVA.

CSF somatostatin and homovanillic acid (HVA) were measured in 14 schizophrenic patients while they were drug-free and during chronic fluphenazine treatment. CSF somatostatin was significantly reduced and CSF HVA was significantly elevated (p less than 0.002) during fluphenazine treatment. There was a trend toward correlation between CSF somatostatin and CSF HVA in the 14 schizophrenic patients when drug-free (r = 0.49, p less than 0.07) and fluphenazine-treated (r = 0.47, p less than 0.08). When examined in a larger group (n = 46) of drug-free schizophrenics, this relationship was highly significant (r = 0.59, p less than 0.001). These clinical data are consistent with preclinical evidence indicating a functional interaction between CNS somatostatin and dopamine systems.

Adult↗
PubMed1989

A.E. Bennett award paper. Experimental approaches to human stress research: assessment of neurobiological mechanisms of stress in volunteers and psychiatric patients.

This article presents a series of experiments that involves the development of three novel strategies for human stress research and the utilization of these strategies to examine neurobehavioral processes of stress in healthy volunteers, schizophrenia, and affective illness. The first strategy involved intravenous 2-deoxy-D-glucose (2DG) administration, a glucoprivic stressor. We found that glucoprivic stress results in dissociation of hypothalamus-pituitary-adrenal (HPA), adrenomedullary, and sympathoneural activity. In addition, glucoprivic stress in neuroleptic-treated schizophrenic patients caused heightened dopamine activity, as reflected by increased plasma homovanillic acid (HVA) levels and decreased adaptive responses as assessed by decreased food consumption following 2DG administration. These data suggest that neuroleptics do not prevent stress-related increases in dopamine activity and that schizophrenia may be associated with abnormalities in the stress response. The second strategy assessed effects of uncontrollable and identical amounts of controllable stress in volunteers and depressed patients. In volunteers, it was found that uncontrollable in comparison to controllable stress results in specific behavioral and neuroendocrine alterations. Moreover, uncontrollable stress exposure in depressed patients in comparison to volunteers produced greater alterations in behavioral ratings and plasma cortisol levels and that the uncontrollable stress related increases in helplessness ratings and cortisol levels were significantly correlated. These data suggest that depressed patients may have increased sensitivity to uncontrollable stress and that there may be an important interrelationship between the cognitive deficits of depression and the heightened HPA axis activity observed in these patients. Lastly, we used a naturalistic strategy to examine mechanisms relating childhood parental loss and the development of adult affective illness and found that among subjects with early parental loss histories, those who developed adult psychiatric illness had increased resting plasma levels of cortisol and beta-endorphin (ir) as compared with subjects with early loss and no adult history of psychiatric illness. Moreover, increased HPA activity in adulthood was significantly related to poor childhood adjustment to parental loss. The implications of the results of these studies are discussed.

Adrenocorticotropic Hormone↗