Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new experimental model was employed to investigate alterations of cerebral metabolic activity in rats subjected to extensive subarachnoid hemorrhage (SAH). The hemorrhages were produced in anesthetized animals by inserting 0.37 ml fresh autologous arterial blood into the subarachnoid space. Rats that underwent sham operations received subarachnoid injections of mock CSF to study the effects of sudden raised intracranial pressure (ICP). Forty-eight hours after subarachnoid injection, the unanesthetized rats were given intravenous injections of [14C]2-deoxyglucose. Experiments were terminated 45 min later by decapitation, and the brains were removed and frozen. Regional brain metabolic activity was studied employing quantitative autoradiography. In comparison with control animals, cerebral metabolic activity was diffusely decreased following SAH. Statistically significant decreases in metabolic activity of less than 34% were observed in 17 of 30 brain regions studied. The largest percentage reductions were in regions displaying the highest basal metabolic rates. Subarachnoid injections of mock CSF also produced depression of cerebral metabolic activity, but quantitatively these changes were not as pronounced as in the hemorrhage group. These studies demonstrate regional changes in brain function following SAH. The data relate these changes to both the presence of blood in the subarachnoid space and sudden raised ICP.
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PMID:Regional cerebral metabolic activity in the rat following experimental subarachnoid hemorrhage. 310 55

The concentration of thyrotropin-releasing hormone (TRH), a tripeptide (pyroglutamylhistidylprolin-amide), in the CSF of drug-free patients with DSM-III major depression, somatization disorder, and peripheral neurological disorders was measured with a sensitive and specific radioimmunoassay. The depressed patients had markedly higher CSF TRH concentrations than the other patient groups, and this finding could not be attributed to any demographic variables. The elevation of TRH in CSF provides further evidence of hypothalamic-pituitary-thyroid dysfunction in depression.
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PMID:Elevation of immunoreactive CSF TRH in depressed patients. 314 69

The onset of therapeutic effectiveness of carbamazepine is generally very rapid in the treatment of seizure and paroxysmal pain disorders, shows some lag in the treatment of mania, and exhibits the longest lag in depression. These time course variations may indicate that different mechanisms underlie the efficacy of carbamazepine in the differential neuropsychiatric syndromes. Biochemical and pharmacological data suggest that the anticonvulsant effects of carbamazepine are related to "peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems and to its ability to stabilize sodium channels. GABAB (baclofen-like) actions appear to be involved in antinociceptive, but not anticonvulsant, effects. The relatively acute time course of antimanic efficacy may be related to the above-mentioned mechanisms or to other effects related to systems postulated to be altered in the manic syndrome. These effects might include carbamazepine's ability to increase acetylcholine in the striatum, decrease probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decrease CSF norepinephrine in manic patients, inhibit adenylate cyclase activity (in response to norepinephrine, dopamine, adenosine, or ouabain), decrease GABA turnover, or act as a vasopressin agonist. Efficacy in depression may be related to actions in man that take time or chronic drug administration to develop, such as increases in plasma tryptophan, decreases in CSF somatostatin, decreases in thyroid indices, and increases in urinary free cortisol excretion and, in animals, increases in substance P sensitivity and increases in brain adenosine receptors. The ability of carbamazepine to block the development of lidocaine- and cocaine-induced seizures also requires chronic administration, suggesting that these seizure models may provide a unique perspective for understanding mechanisms of time-dependent effects.
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PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60

In order to investigate the role of serotonergic mechanisms in depressive disorders, the fenfluramine challenge test was performed in 31 patients suffering from different types of depression. The strategy was to select a simple method (i.e., easier to perform than CSF studies for instance) to be applied to a wide range of patients, as close as possible to everyday cases in a clinical setting (i.e., not only to such severe or highly selected groups as is normally the case in biological research in psychiatry). The neuroendocrine test (which consisted of the measurement of variations in the secretion of prolactin, growth hormone and Cortisol after the administration of 60 mg dl-fenfluramine p. o.) did not correlate with symptoms of behavior patterns previously identified with a "serotonin deficit" (i. e., suicidal behavior or attempts, lowering of the control of impulses, sleep disturbances) but only with the severity of the diagnosis (in the DSM-III hierarchical scale) or with indexes of endogeneity (Newcastle scale). This fact could be explained by methodological artifacts (i. e., dlfenfluramine is not a clean probe, showing influence in the dopamine and noradrenaline metabolism; the absorption of fenfluramine was not controlled) or by the fact that the involvement of serotonin in affective disorders is not a selective, isolated dysfunction, but is integrated in more complex interrelationships. Nevertheless, our preliminary findings (even without the results of the comparison with a control group and the evaluation of a few more data and cases) do coincide with the absence of predictors or the lack of specific patterns of response of symptoms with new selective re-uptake blockers of serotonin antidepressants.
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PMID:The fenfluramine challenge test in the affective spectrum: a possible marker of endogeneity and severity. 328 85

In anesthetized spinal cats, perfusion of lumbosacral spinal cord with artificial CSF containing manganese (1.5-3.0 Mm/l) or cobalt (6.0 mM/l) ions, led to reversible suppression of negative dorsal root potentials (DRP), induced by stimulation of ipsilateral hindlimbs' afferent nerves. The depression of the DRP proceeded in connection with the depression of presynaptic inhibition of extensor monosynaptic reflexes induced with impulse volleys in the group I flexor muscle afferents. The depression of inhibition was not associated with changes in amplitudes of testing monosynaptic reflexes. The DRP is concluded to have a synaptic origin.
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PMID:[Suppression of the dorsal root potentials of the cat spinal cord by manganese and cobalt ions]. 341 29

Eleven baboons, anaesthetised with ketamine, had catheters introduced into the cisterna magna. Morphine was injected at lumbar level intrathecally in six and epidurally in five. Cisternal CSF was sampled hourly and the morphine concentration measured using a high pressure liquid chromatograph. In two cases following intrathecal injection peaks of 180 ng/ml at 4 hours, and 2,200 ng/ml at 3 hours were detected. In the latter case there was associated error in sampling therefore this baboon had a repeat injection four weeks later. The maximum level of morphine obtained then was 139 ng/ml at 4 hours. In the epidural group peaks of 113 ng/ml and 53 ng/ml at 1 hour were measured in 2 baboons and 27 ng/ml at 6 hours in a third. In all six other baboons following either procedure no morphine was detected in the cisterna. We conclude that morphine injected either intrathecally or epidurally in primates does migrate centrally in varying quantities. This finding would seem to have some bearing on the unpredictability of reported episodes of respiratory depression following intraspinal morphine.
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PMID:Cisternal cerebrospinal fluid concentrations of morphine following intrathecal and epidural administration in the baboon. 342 84

Pharmacokinetic studies of five biological response modifiers (BRMs) show diverse regulator functions on effector cell responses and a capacity to cause the secretion of specific soluble factors. Of the five BRMs tested, MVE-2, Poly ICLC, OK-432, and alpha beta IFN were capable of stimulating both natural killer (NK) cell and macrophage (M phi) tumoricidal activity, whereas BM 41-332 augmented only NK cells. Following one treatment with the aforementioned BRMs, M phi activity remained elevated for a longer period (10-14 days) than did NK cell activity (6-9 days). Of particular interest, multiple treatment with BRMs led to a downregulation of NK cell activity (hyporesponsiveness). Three soluble secretory products were induced by these BRMs (colony stimulating factor, CSF; prostaglandin E, PGE; and interferon, IFN). Treatment with MVE-2 and Poly ICLC led to a significant increase in bone marrow cellularity and GM-CFV-C. Results of studies with the cyclo-oxygense-inhibited indomethacin indicate that CSF and PGE are produced and/or secreted by different cellular mechanisms. The depression of effector cells (NK, bone marrow, and GM-CFU-C), as the result of cyto-reductive treatment with cyclophosphamide, could be reversed by treatment with MVE-2. A significantly earlier time to recovery of these effector cells was achieved following MVE-treatment. When MVE-2 was used as an adjuvant to initial tumor cyto-reductive chemotherapy, more successful antitumor response was achieved, indicating that MVE-2 functioned to elevate a substantial effector cell response as well as reconstituting bone marrow cellularity.
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PMID:Biological response modifiers: regulators of the cellular immune system and adjuvants in antitumor therapy. 348 34

To further investigate the hypothesis that hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with depression may be mediated by hypersecretion of corticotropin-releasing factor (CRF), the authors measured CRF-like immunoreactivity in CSF samples from 138 neurological control, 54 depressed, and 27 nondepressed (23 schizophrenic and four manic) subjects. The CSF CRF concentration was markedly higher (almost twofold) in depressed patients than in control subjects and nondepressed psychiatric patients. The concentration of CSF CRF was slightly but significantly higher in schizophrenic patients than in control subjects. These findings provide further support for the hypothesis that CRF hypersecretion occurs in major depression.
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PMID:CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. 349 2

Since its introduction to North America in 1942, the use of epidural catheter analgesia has increased dramatically. Improved equipment, methods and medications have broadened its application to include among others, surgical anesthesia, chronic pain relief and the management of postoperative pain. Numerous techniques for epidural puncture and insertion of the catheter have been described. Although complications have been associated with placement of an epidural catheter, these are rare when performed by an experienced anesthesiologist. Epidural analgesia was first accomplished by blockade with local anesthetics. Bupivacaine has been called the local anesthetic of choice for epidural infusion. Bolus administration of epidural local anesthetics gives effective analgesia; however, its use is limited by brief duration and occasionally severe hypotension. Epidural local anesthetics have been administered by continuous infusion in an attempt to minimize side effects. Nevertheless, hypotension, as well as motor block, numbness, nausea and urinary retention have occurred. Epidural analgesia with local anesthetics is effective in relieving postoperative pain, but its safety and feasibility have been questioned because of the frequent, potentially serious side effects. These problems led to trials of epidural narcotics for postoperative pain management. The exact site of action of epidural narcotic analgesics is debatable; however, the bulk of evidence supports a direct spinal action. Epidural narcotics appear to specifically inhibit nociceptive stimuli. The prolonged and profound analgesia that occurs with epidural narcotics relative to parenteral administration is due to a higher concentration of drug reaching the CSF through the epidural route. Since nervous transmission is not completely blocked this technique cannot provide anesthesia during operation. Morphine has been the most frequently used narcotic for epidural analgesia. Results of several recent, randomized double-blind studies have shown that epidural narcotics give adequate analgesia comparable with that observed with epidural bupivacaine. Epidural morphine provides a greater duration of analgesia and may cause fewer side effects. Improved analgesia has been reported when epidural narcotics are used in combination with local anesthetics. Continuous administration of low dosage epidural narcotics has been shown to have less frequent side effects than bolus administration. Nevertheless, pruritus, urinary retention, hypotension and severe respiratory depression have been reported with both methods.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epidural catheter analgesia for the management of postoperative pain. 351 98

We used naloxone to investigate the role of central nervous system opiate receptors in the cardiovascular depression of canine hemorrhagic and endotoxic shock. Shock was induced by bleeding dogs into a reservoir to achieve and maintain a mean arterial pressure (MAP) of 45 mmHg for 30 min; at 30 min the reservoir was clamped and the animals were treated with intracerebroventricular (ICV) perfusion of naloxone 0.1 mg/kg (n = 5) or artificial CSF (n = 5) for 30 min. Endotoxemic shock was induced by the iv injection of E. coli endotoxin 1 mg/kg; 15 min later the animals were given naloxone 0.1 mg/kg (n = 5) or artificial CSF (n = 5) ICV for 30 min. ICV naloxone significantly increased MAP, cardiac output (CO), and left ventricular performance (LV dP/dt max) compared to artificial CSF in canine endotoxic shock but not hemorrhagic shock. Naloxone 0.1 mg/kg (n = 5) given into the cisterna magna failed to significantly improve MAP, CO, or LV dP/dt max in dogs subjected to reservoir hemorrhagic shock for 60 min compared to artificial CSF (n = 5). These results are compatible with opiate-receptor-mediated central cardiovascular depression in endotoxic shock and peripheral cardiovascular depression in hemorrhagic shock. Accordingly, the sites of action of naloxone are mainly central in endotoxic shock and peripheral in hemorrhagic shock.
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PMID:Central nervous system is involved in the cardiovascular responses to naloxone in canine endotoxic but not hemorrhagic shock. 359 33


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