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Biomedical subjects

D L Copolov

Publications and source records attributed to D L Copolov.

90 records · Page 5Linked to original sources
PubMed1989

Dopamine uptake by platelets is selective, temperature dependent and not influenced by the dopamine-D1 or dopamine-D2 receptor.

The human platelet, which takes up and releases dopamine, has been proposed as a peripheral model for the study of dopaminergic neurons in the central nervous system (CNS). In addition, the platelet has been shown to possess membrane components with pharmacological properties similar to the dopamine-D1 (DA-D1) and D2 (DA-D2) receptor on dopaminergic neurons. We have therefore studied the specificity of the platelet uptake system for dopamine and, as dopamine uptake comprises both internalised and membrane bound dopamine, the contribution of the DA-D1 and DA-D2 receptor to the uptake of dopamine has been assessed. Significant uptake of 3H-dopamine by platelet rich plasma (PRP) occurred after 10 min incubation at 37 degrees C, uptake being maximal after 90 min. In contrast, at 4 degrees C no uptake of 3H-dopamine occurred up to 60 mins incubation but at 20 degrees C was approximately 8% of the 60 min uptake at 37 degrees C. The neurotransmitters serotonin and dopamine inhibited dopamine uptake by platelets in a dose dependent manner. Uptake of dopamine appeared to be via two systems, one of high affinity with low capacity and the other of lower affinity but high capacity. In contrast, noradrenaline, adrenaline, acetylcholine, gamma-aminobutyric acid and histamine (10 microM) had no effect on dopamine uptake by platelets. The DA-D1 receptor antagonist SCH 23390 (10 microns) and the DA-D2 receptor antagonists (10 microM) spiperone, domperidone and (+)-butaclamol did not significantly affect dopamine uptake by platelets. In addition, ouabain and desipramine (100 microM) inhibited dopamine uptake by 21% and 24% respectively whilst reserpine and imipramine (100 microM) increased uptake by 14% and 15%. We therefore conclude that platelets take up dopamine via a selective, temperature dependent mechanism. Our data also suggest that dopamine uptake by platelets does not involve the DA-D1 or DA-D2 receptor.

Biological Transport↗
PubMed1989

Origins and establishment of the schizophrenia research programme at Royal Park Psychiatric Hospital.

This paper documents the initial phase of a new research direction which began in 1984 at Royal Park Hospital. Attention is focussed on the place of the university and the research institute in the psychiatric hospital and on the perceived need for concerted research on the major psychoses in Australia. The focal point of the Royal Park research programme, the Aubrey Lewis Clinical Research Unit, has been open since October 1984. The development of the unit's research activities during the initial few years of its existence required an awareness of specific scientific, administrative and political issues. These are discussed in detail in order to convey something of the process, as well as the content of such development, and in an attempt to provide some assistance to others undertaking similar developments.

Female↗
PubMed1989

The validity of the assessment of psychopathology in the psychoses.

This paper reviews recent progress in the assessment of the psychopathology of psychosis and focuses upon a number of persistent limitations. In particular the over-emphasis upon reliability at the expense of validity is highlighted and the relationship between reliability and validity is reconsidered. A number of strategies aimed at improving the validity of psychopathological measures are outlined. Proposals to deploy such variables differently in research strategies and analyses are endorsed.

Humans↗
PubMed1988

i.r. Beta-endorphin, corticosterone, cholesterol and triglyceride concentrations in rat plasma after stress, cingulotomy or both.

Plasma i.r. beta-endorphin, corticosterone, cholesterol and triglyceride concentrations were determined in male Sprague-Dawley rats after exposure to running or swimming stressors or after surgical ablation of the cingulum bundle. While cingulotomy alone altered only the plasma triglyceride concentrations, the combination of cingulotomy plus running stress significantly increased plasma i.r. beta-endorphin and triglyceride concentrations above those seen in animals receiving only a running stress. Triglyceride concentrations in cingulotomy plus swimming stress were significantly elevated above those in animals receiving a severe stress only. While the exposure to running and swimming increased plasma beta-endorphin significantly above control levels, plasma corticosterone was not affected by these stressors. Changes in plasma cholesterol and triglycerides were also differentially affected by cingulotomy or stress exposure. These results indicate that various stress hormones are affected differentially by exposure to various experimental procedures which are employed as stressors.

Animals↗
PubMed1988

Cingulotomy in the rat fails to block opiate withdrawal effects but elevates stress-induced plasma beta-endorphin.

1. Male, albino, Sprague Dawley rats underwent surgical cingulotomy or sham operation and were then implanted with subcutaneous morphine pellets or exposed to forced running. 2. The conditions of cingulotomy or forced running alone did not cause a significant increase in plasma i.r. Beta endorphin concentrations. 3. The combined treatment of cingulotomy plus forced running caused a significant elevation of plasma beta-endorphin concentrations. 4. The cingulum is involved in the elicitation of stress hormone responses in the rat.

Animals↗
PubMed1987

The Zelig phenomenon: a specific form of identity disturbance.

A variety of identity disturbances has been described in psychiatric patients. Although such disturbances possess some common features linked to shared or core psychological structures, qualitative differences that allow them to be distinguished from one another also exist. The cases reported are intended to draw attention to a severe and striking type of identity disturbance observed in psychotic patients, for which we have proposed the eponym, 'the Zelig phenomenon'. The discussion focuses upon the issue of the coexistence in psychopathology of continuity and discontinuity. This apparent paradox can be regarded as an example of parallax, in which two quite different, yet equally valid, perspectives are possible and may be brought alternately into play. It is, however, argued that in the delineation of psychopathological entities it is necessary to adopt the perspective that considers discontinuities and matters of form, even though they may be at times overshadowed by continuities that derive from the alternate perspective.

Adult↗
PubMed1986

Type A, test performance and salivary cortisol.

Forty first year medical students, previously screened for the presence or absence of the Type A behavior pattern, collected saliva samples for four days leading up to the first major examination of their medical school course. It was observed that the day of the examination produced substantially different patterns of salivary cortisol concentrations for Type A and non-A subjects, depending on their level of performance. The Type A subjects who scored above the median on the examination showed higher concentrations of salivary cortisol than Type A subjects who scored below the median. The reverse of this pattern was found for non-A subjects. Visual analog scale ratings of subjective stress showed no behavior pattern effects and a very low correlation with the salivary cortisol concentrations. The results support the view that the occurrence of physiological arousal associated with the Type A behaviour pattern is intermittent and dependent on situational factors such as expectation of success and actual success. This is consistent with conceptualizing the Type A pattern as a strategy for resource allocation which may be elective, rather then the behavioural manifestation of an automatic physical response to stress.

Achievement↗
PubMed1985

The role of endogenous opioid peptides in the effects of constant illumination on reproductive function in the rat.

The present experiments assessed the involvement of endogenous opioids in the inhibition of FSH and LH release, ovulation and continuous sexual receptivity following exposure to constant illumination. In the first experiment, exposure to constant illumination resulted in persistent vaginal oestrus in all rats. The injection of naloxone resulted in marked elevations in serum FSH and LH, induced ovulation and increased the frequency of lordosis behaviour. It was concluded that endogenous opioid(s) participate in these effects. In Experiment 2, levels of beta-endorphin were found to be elevated in anterior pituitary and neurointermediate lobe tissue extracts from rats exposed to constant illumination, compared to levels in pro-oestrus rats. Naloxone injection into those rats exposed to constant illumination significantly increased hypothalamic levels of beta-endorphin compared to saline injected controls. This suggests that the blockade of opiate receptors increases beta-endorphin production, uptake and/or decreases its release from the hypothalamus. These results, and the known inhibitory action of beta-endorphin on LH release suggest that it may be this opioid, perhaps in conjunction with pineal products, which is responsible for the observed anti-reproductive effects of constant illumination.

Animals↗
PubMed1985

Pre- and post-dexamethasone salivary cortisol concentrations in major depression.

Seventy patients fulfilling DSM-III criteria for major depression were given the 1.0 mg overnight dexamethasone suppression test, with salivary cortisol concentrations being measured as the dependent variable. Using both the DSM-III and the Research Diagnostic Criteria, we categorized the patients into four groups based on increasing frequency of endogenous symptomatology. Among these four groups there were no significant differences in salivary cortisol concentrations either before dexamethasone or eight, 16, and 24 h after dexamethasone. Similarly, there were no significant differences among the groups in either the ratios of post- to pre-dexamethasone salivary cortisol or the frequencies of positive tests based on several criterion levels of cortisol for the three post-dexamethasone samples. Multiple regression analyses indicated that the Hamilton depression rating scale item "somatic anxiety" was significantly negatively related to post-dexamethasone cortisol concentrations. We conclude that, for our sample of major depressives, the salivary cortisol dexamethasone suppression test showed no utility as a laboratory correlate of depressive episodes with endogenous features.

Adult↗
PubMed1985

Opioid biology: the next set of questions.

A range of biologically different opioid peptides are synthesised as components of three distinct precursors, pro-opiomelanocortin, proenkephalin, and prodynorphin. They interact with a number of receptors which have so far been characterised as mu, delta, kappa, sigma, and epsilon. It is unclear which ligands bind to which receptors under physiological circumstances, but preferential in vitro interactions include enkephalins with delta receptors, dynorphin with kappa receptors, and beta-endorphin with epsilon receptors. Post-translational processing determines which of several opioid products are produced from each precursor, but the identity of the enzymes involved and regulation of processing is unknown. Opioid involvement in the neuroendocrine and cardiovascular systems is reviewed. Naloxone-sensitive opioid mechanisms are implicated in the control of gonadotrophin and adrenocorticotropic hormone secretion and in the hypotension of various types of shock. The investigation of possible dynorphin involvement in neurohypophysial function is taking place because vasopressin and dynorphin A (1-8) have been shown to coexist in the neurosecretory vesicles of magnocellular neurons.

Cardiovascular Diseases↗
PubMed1984

A pituitary tumor producing high molecular weight adrenocorticotropin-related peptides: clinical and cell culture studies.

The tissue-specific processing of proopiomelanocortin (POMC), the precursor of ACTH, beta-endorphin, and their related peptides, is currently of considerable interest. We report a patient with a large aggressive pituitary tumor, Cushing's syndrome, and hyperpigmentation managed by transsphenoidal hypophysectomy, bilateral adrenalectomy, and sellar irradiation. Preoperatively, plasma levels of immunoreactive ACTH (ir-ACTH; 280 ng/liter) and beta-endorphin (ir-beta EP; 520 ng/liter) were moderately elevated. Chromatography of the plasma showed two peaks of ACTH immunoreactivity, with the major peak eluting in the void volume, and two major peaks of ir-beta EP, corresponding to the elution positions of beta-lipotropin and beta-endorphin standards. Plasma ir-ACTH and ir-beta EP were not suppressed by high doses of glucocorticoid or bromocriptine, a degree of autonomy more commonly found with POMC production from ectopic sources than that from pituitary tumors. Tissue removed at operation was enzymatically dispersed, and the cells were cultured in suspension, propagated, and passaged sequentially for over 20 passages. Using this cell line, we demonstrated that the biosynthesis of POMC, its pattern of processing, and the release of POMC/ir-beta EP/ir-ACTH in vitro were consistent with the in vivo evidence of autonomous secretion and abnormal processing of POMC by this pituitary tumor.

Adenoma↗
PubMed1984

Relationship between endogenous opioids and the oestrous cycle in the rat.

The aim of this study was twofold: (1) to document changes in levels of immunoreactive beta-endorphin (Ir-beta-EP) in the hypothalamus, anterior pituitary gland, neurointermediate lobe and plasma during the oestrous cycle of the rat and (2) to investigate stress-induced changes in plasma Ir-beta-EP at different stages of the oestrous cycle. Evidence was found that Ir-beta-EP levels in the hypothalamus, anterior pituitary gland and plasma are not constant during the oestrous cycle and that the Ir-beta-EP response to stress is a function of the phase of the oestrous cycle at which stress is applied. It is suggested that fluctuations in ovarian hormones may influence oestrous Ir-beta-EP levels both under normal conditions and after exposure to stress.

Animals↗
PubMed1983

Enkephalins and Endorphins. Clinical, pharmacological and therapeutic implications.

During the past 8 years there has been substantial progress in our understanding of the structure, distribution and action of endogenous opioid peptides. Currently, there appear to be 2 groups of peptides; those derived from beta-lipotropin and an enkephalin-related group. Some of these peptides have been shown to be distributed widely in the central nervous system and in endocrine tissues. The activity of the peptides probably occurs at several receptors but only 1 relatively specific (mu-receptor) antagonist, naloxone, is well studies. Although there have been many clinical studies of the action of opioids in man, no novel therapeutic applications have yet been established in clinical practice. Of the many areas of involvement attributed to opioids, those of analgesia, reproductive endocrinology, opiate dependence, and certain as yet undefined subtypes of major psychoses seem reasonably promising. Speculation surround opioid involvement in other disorders such as spinal trauma, septic shock, alcohol dependence, "functional' gastrointestinal disease, diabetes and asthma is of considerable interest but is supported by less clinical evidence. It seems that as research in opioids advances, the putative physiological opioid "spheres of influence' widen. At the same time, opioid mechanisms of action are being revealed to be more subtle and complex than previously thought. As a consequence, the expectations of rapid therapeutic application of opioid peptides and their antagonists are being modified and refined and realistic research strategies applied. In view of the work reviewed in this paper it seems reasonable to expect that such work will pay dividends in the not too distant future.

Acupuncture Therapy↗
PubMedDate not supplied

Positive and negative symptoms in the psychoses: principal components analysis of items from the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms.

The present study investigated the factor structure of the items contained in Andreasen's scales for the assessment of positive and negative symptoms (SAPS and SANS) by use of a series of principal components analyses (PCAs) with oblique rotations of the axes. It was found that the structure could be summarized by three major components labeled negative symptoms, thought disorder, and delusions/hallucinations. Dimensionality could meaningfully be increased to five components. Negative symptoms was found to separate into two components that we labeled negative signs and social dysfunctions. The delusions/hallucinations factor could be separated into two components, delusions and hallucinations, with "loss of boundary" delusions being related to both factors. Delusions of persecution were independent of other symptoms. The thought disorder factor did not decompose meaningfully within the investigated dimensionality. A two-factor solution did not explain the correlation between symptoms adequately. The results do not support the simple dichotomy between positive and negative symptoms in psychosis, but suggest that a wider dimensional concept may be more useful in future studies.

Delusions↗
PubMedDate not supplied

DSM-III melancholia: do the criteria accurately and reliably distinguish endogenous pattern depression?

The Structured Clinical Interview for DSM-III (SCID), Newcastle Endogenous/Reactive Index, Feinberg-Carroll Discriminant Index, and Hamilton Depression Scale were used to assess 70 depressed patients in order to determine similarities and differences in symptom structure and severity in those patients with and without endogenous/melancholic depression. All patients with melancholia according to DSM-III had definite endogenous major depression by the Research Diagnostic Criteria (RDC), but only 20 out of 35 patients with RDC definite endogenous depression were DSM-III melancholic. There was a greater difference in symptom pattern between those patients with definite endogenous depression and those with probable or non-endogenous depression than there was between the melancholic and non-melancholic definite endogenous depressives. A prerequisite for the valid delineation of a nosological category is the establishment of good reliability for diagnostic criteria. Using SCID ratings of audiotaped interviews of 9 patients (5 with major depression), the 8 raters in this study achieved a kappa coefficient of 0.79, suggesting that the use of a structured interview can improve the reliability of DSM-III diagnoses. Interrater reliabilities for most of the individual DSM-III major depressive episode and melancholia items were reasonable, but some were low. The low reliabilities could be improved by redefinition of the items to reduce ambiguity and by development of a SCID glossary.

Adult↗
PubMedDate not supplied

Current concepts in functional psychosis. The case for a loosening of associations.

The recent explosion in knowledge in the neurosciences has heightened both the expectation of significant progress in understanding the underlying mechanisms involved in the psychoses as well as frustration over the failure of such progress to occur. As biological sophistication increases, it contrasts with the obsolescence of our nosological tools, which, through their influence upon research strategy, constitute a potential obstacle to progress. Currently dominant nosological paradigms are heavily based upon assumptions concerning the links between pathophysiology and symptoms, and between symptoms and the more distal consequences of disease. This review seeks to illustrate that the linkages between disease and its consequences are in fact much looser and more plastic than acknowledged by existing paradigms, which are constrained by tradition. Since faulty assumptions concerning these linkages are so fundamental to the current nosology, it is argued that major reform is necessary. While this can be justified on research grounds alone, there are also compelling clinical reasons why reform of this kind is important and overdue.

Disability Evaluation↗
PubMedDate not supplied

A proposed pathological model in the hippocampus of subjects with schizophrenia.

1. The hippocampal formation plays an important role in the normal functioning of the brain, being implicated in cognition and sensory gating, both of which are affected in schizophrenia. The hippocampal formation receives information from the association cortices, which is processed by glutamatergic transmission within the hippocampus. Dopamine, noradrenaline, 5-hydroxytryptamine (5-HT), acetylcholine and GABA, all of which have been proposed to play a role in the neurobiology of schizophrenia, can affect this transmission. 2. The advent of the 'atypical' antipsychotics, with their broad pharmacological spectra and improved therapeutic outcome, has revitalized research into neurotransmitter dysfunction other than that of dopamine. In particular, there has been interest in the serotonergic and cholinergic systems within the hippocampal formation because these are two of the transmitter systems targeted by clozapine and olanzapine. 3. From the study of these systems, using tissue obtained postmortem from subjects with schizophrenia, we propose that there is a hyperserotonergic state in the hippocampal formation of some subjects with schizophrenia caused by a conformational change in the 5-HT transporter. The model we propose allows us to construct further studies that will test the consequences of such a hyperserotonergic state in the hippocampal formation. This model has the potential to open new avenues in schizophrenia research.

Carrier Proteins↗