Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data reflecting affect, mood, and personality attributes of 23 normal men were compared after two weeks of placebo administration and two weeks of therapeutic serum lithium levels (mean, 0.91 mEq/liter). The study was a placebo-controlled, split-half crossover, double-blind design. Affect and mood were measured by three self-rating instruments, independent rater observation, and by the subjects' "significant others." Two personality inventories were administered. Substantial affect and mood changes are induced by lithium carbonate. Lethargy, dysphoria, a loss of interest in interacting with others and the environment, and a state of increased mental confusion were reported. No generalized effects were found in the responses to ther personality inventories.
Arch Gen Psychiatry 1977 Mar
PMID:The effect of lithium carbonate on affect, mood, and personality of normal subjects. 32 Sep 56

Experimental transmission of the Stetsonville, Wisconsin, U.S.A. source of transmissible mink encephalopathy (TME) to outbred Syrian golden hamsters resulted in two distinct syndromes, termed hyper (HY) and drowsy (DY), that diverge by the third hamster passage. The syndromes differed with respect to clinical signs, incubation period, brain titre, brain lesion profile and pathogenicity in mink. HY hamster TME had an incubation period of 65 +/- 1 days and was characterized by clinical signs of hyperaesthesia and cerebellar ataxia. Lethargy and the absence of hyperexcitability or cerebellar ataxia were representative of DY hamster TME which had an incubation period of 168 +/- 2 days. At endstage, HY and DY infected animals had brain titres of 10(9.5) LD50/g and 10(7.4) LD50/g of tissue, respectively, indicating that the replication kinetics of these two strains is different. Hamster TME passaged back into mink revealed that only DY retained mink pathogenicity. This suggests that the DY agent is the major mink pathogen in the Stetsonville TME source that is also pathogenic in hamsters after a long incubation period. The HY agent is likely to be a minor component of the original TME mink brain that replicates more rapidly than DY agent in hamsters, but alone is non-pathogenic in mink. The presence of the HY and DY strains of agent that retain their biological characteristics on repeated hamster passage in the Stetsonville TME source requires that the informational molecule encoding these transmissible agents has the capacity to account for this biological diversity.
J Gen Virol 1992 Feb
PMID:Identification of two biologically distinct strains of transmissible mink encephalopathy in hamsters. 153 75

A temperature-sensitive mutant of vesicular stomatitis virus (VSV), tsG31-KS5 VSV, intracerebrally inoculated into BALB/c (+/+) or Swiss outbred mice yielded a clinically asymptomatic persistent infection of the central nervous system (CNS). BALB/c nude (nu/nu) mice infected with tsG31-KS5 VSV, however, all perished within 26 days of infection. All the nude mice were afflicted with a slowly progressing CNS disorder, with symptoms including lethargy, curvature of the spine, hind-limb paralysis and other neurological disorders, before they succumbed to the infection. Wild-type (wt) VSV infection of either normal or nude mice, on the other hand, invoked a rapidly lethal disease with all animals dying within 4 days of infection. When nude mice were reconstituted with 5 x 10(6) syngeneic T lymphocyte-enriched splenocytes, over 70% of them not only survived the tsG31-KS5 VSV infection but appeared to be free of any neurological disorders. Only 20% of these reconstituted mice infected for 20 days with tsG31-KS5 VSV endured a wt VSV challenge. In contrast, BALB/c (+/+) mice infected for 20 days with tsG31-KS5 VSV all survived a wt VSV challenge. Reconstitution of nude mice with 5 x 10(6) T lymphocytes did not elicit a vigorous secondary humoral antibody response against VSV. All the animals reconstituted with 5 x 10(7) T lymphocytes and infected with tsG31-KS5 VSV, however, had both late and early humoral responses that equalled antibody responses of BALB/c (+/+) mice. Reconstitution with either 5 x 10(6) or 5 x 10(7) T lymphocytes afforded the nude mice equivalent protection from the CNS disorder triggered by tsG31-KS5 VSV. Reconstitution with 5 x 10(6) T lymphocytes, therefore, protected nude mice from the neurological disease induced by the persistent virus without eliciting a robust humoral antibody response. Infectious, temperature-sensitive VSV was retrieved from the CNS of the nude mice that had been reconstituted with 5 x 10(6) T lymphocytes and infected for up to 30 days with tsG31-KS5 VSV. The CNS-isolated VSV was less temperature-sensitive than tsG31-KS5 VSV. When the CNS-isolated VSV was intracerebrally inoculated into Swiss outbred mice, an aggressive disease ensued with most of the mice developing a CNS disorder. In comparison, Swiss outbred mice were asymptomatically infected with tsG31-KS5 VSV. The VSV isolated from the CNS was more lethal to the mice than tsG31-KS5 VSV possibly because it was less temperature-sensitive.
J Gen Virol 1988 Aug
PMID:Reconstitution with T lymphocytes protects nude mice from a central nervous system disorder induced by a temperature-sensitive vesicular stomatitis virus. 284 9

Pancreatic A cell response to arginine was measured in hedgehogs during the periods of lethargy and arousal and then during activity. Spontaneous plasma glucagon concentrations were lower during lethargy than during activity, and they increased during arousal. Arginine administration induced a slight, but significant delayed increase in plasma glucagon concentration in the lethargic hedgehog (body temperature: 6 degrees). During arousal, in vitro glucagon secretion was temperature dependent suggesting that body rewarming might, in itself, be an important stimulating factor of the A cells. In the presence of arginine, the glucagon output of the pancreas of lethargic hedgehogs was high at low temperatures. It decreased to a nadir at 19 degrees and increased up to 37 degrees. However, the basal or arginine-stimulated glucagon secretion of animals in lethargy was higher than that of animals in activity. These characteristics suggested the presence of a particular pool of cold-adapted enzymes in the A cells of lethargic hedgehogs.
Gen Comp Endocrinol 1983 Oct
PMID:Pancreatic A cell response to arginine in the hibernating hedgehog (Erinaceus europaeus). 635 39

In order to determine the influence of hibernation depth upon the secretion and the effect of insulin, two groups of edible dormice were maintained in winter under different climatic and nutritional conditions, and their pancreatic B-cell function was tested during the spring arousal. The first group of animals was exposed to a moderate temperature and fed ad libitum. Their periods of hypothermia were short and irregular and the active periods sometimes lasted several days; their body weight increased during the winter months; in spring, the sensitivity of B cells to glucose was low, decreasing insulin secretion in vivo and in vitro, and the adipocytes were insulin resistant. The second group of fasting animals was exposed to a low and constant temperature (5 degrees). Their phases of lethargy were long and regular (about 15 days), separated by active periods (6-8 hr); their body weight decreased during the winter months; in spring the B-cell secretion was increased and the sensitivity of the tissues to insulin ensured a high peripheral glucose utilization. These data show that the winter climatic and nutritional conditions which influence the depth of hibernation modify the edible dormouse B-cell activity during the spring arousal.
Gen Comp Endocrinol 1984 Apr
PMID:Hibernation depth influences the edible dormouse pancreatic B cell during the spring arousal. 637 92

Single and repetitive tryptophan loads were consumed by normal, adult male volunteers, and blood concentrations of tryptophan, serotonin, and kynurenine, their time courses, and their distributions within blood were measured. Repeated measures of basal and tryptophan-induced changes in tryptophan and serotonin blood concentrations were characteristic for individual subjects. Tryptophan dose-responsive increases in measured substances returned to basal levels within 24 hours after single tryptophan loads. However, cumulative increases in serotonin concentration in early-morning, predose blood samples were seen following repetitive daily tryptophan administration. Extra-platelet serotonin could be detected in blood samples taken after tryptophan loading and after repetitive daily tryptophan consumption but not in baseline samples taken before short-term loading. Neither platelet number nor size was altered by the loading procedures. Tryptophan loading produced lethargy and drowsiness within 30 minutes of ingestion under all loading conditions. Subjects with the slowest kynurenine response to tryptophan were most behaviorally affected.
Arch Gen Psychiatry 1981 Jun
PMID:Short-term and repetitive administration of oral tryptophan in normal men. Effects on blood tryptophan, serotonin, and kynurenine concentrations. 724 25

Intravenous naloxone hydrochloride (20 mg) was administered to eight normal control subjects and 12 affective disorder patients manifesting manic or hypomanic symptoms. On two consecutive days, in a counterbalanced order, naloxone and placebo were given in a double-blind crossover design. The overall effect of naloxone was to decrease pulse rate and to promote lethargy and inactivation. The normal controls manifested reduced feelings of well-being, and the manic patients noted a subjective sense of slowing. There was a variable response pattern to naloxone in the manic patients in which four of the 12 patients manifested an observable reduction in their manic symptoms and behavior after the naloxone administration. Naloxone seems to have had a nonspecific subduing effect in both normal subjects and patients and may also have had a selectively greater effect in a small subsample of the manics.
Arch Gen Psychiatry 1980 May
PMID:Naloxone-induced behavioral and physiological effects in normal and manic subjects. 737 16

Naked mole-rats have no access to obvious sources of vitamin D and therefore have an impoverished vitamin D status. In an investigation into the effects of vitamin D supplementation, inadvertently supraphysiological doses of 130,000 times the normal dose of vitamin D were administered. Within 5 days animals appeared lethargic, with reduced food intake. All but one of the seven animals were killed and blood was collected. Plasma vitamin D metabolites 25(OH)D and 1,25(OH)2D and calcium were determined. Both vitamin D metabolite concentrations exceeded the upper limits of sensitivity of the assays (> 100 ng/ml 25(OH)D and > 210 pg/ml 1,25(OH)2D). Active calcium uptake in the intestine was evident along with concomitant increases in calcium concentration in plasma, bone, and teeth. The remaining animal survived, but showed scab-like formations in the skin around the lower jaw and along the nipple line. X-ray analyses revealed calcium deposition in these cornified regions, although there was no evidence of metastatic calcification in other tissues. Deposition of excess calcium in skin that is regularly sloughed off and in teeth that are continuously worn down and replaced may reduce the vitamin D-induced hypercalcaemia and thus alleviate the effects of vitamin D intoxication.
Gen Comp Endocrinol 1995 Jul
PMID:Vitamin D3 intoxication in naked mole-rats (Heterocephalus glaber) leads to hypercalcaemia and increased calcium deposition in teeth with evidence of abnormal skin calcification. 765 55

To determine whether the aetiological agent of bovine spongiform encephalopathy (BSE) is pathogenic for mink, standard dark mink were inoculated with coded homogenates of bovine brain from the U.K. Two homogenates were from cows affected with BSE. The third was from a cow that came from a farm with no history of having had BSE or having been fed ruminant-derived, rendered by-products, the proposed vehicle for introduction of the BSE agent. Each homogenate was inoculated intracerebrally into separate groups of mink and a pool of the three was fed to a fourth group. Signs of neurological disease appeared in mink an average of 12 months after intracerebral inoculation and 15 months after feeding. Decreased appetite, lethargy and mild to moderate pelvic limb ataxia were the predominant clinical signs, quite unlike the classic clinical picture of transmissible mink encephalopathy (TME). Microscopic changes in brain sections of most affected mink were those of a scrapie-like spongiform encephalopathy. Vacuolar change in grey matter neuropil was accompanied by prominent astrocytosis. Varying greatly in severity from one mink to another, the degenerative changes occurred in the cerebral cortex, dorsolateral gyri of the frontal lobe, corpus striatum, diencephalon and brainstem. Although resembling TME, the encephalopathy was distinguishable from it by less extensive changes in the cerebral cortex, by more severe changes in the caudal brainstem and by sparing of the hippocampus. The results of this study extend the experimental host range of the BSE agent and demonstrate for the first time the experimental oral infection of mink with a transmissible spongiform encephalopathy agent from a naturally infected ruminant species.
J Gen Virol 1994 Sep
PMID:Experimental infection of mink with bovine spongiform encephalopathy. 807 14

1. Dapsone is a potent anti-inflammatory and anti-parasitic compound, which is metabolised by cytochrome P-450 to hydroxylamines, which in turn cause methaemoglobinaemia and haemolysis. However, during the process of methaemoglobin formation, erythrocytes are capable of detoxifying the hydroxylamine to the parent drug, which may either reach the tissues to exert a therapeutic effect or return to the liver and be re-oxidised in a form of systemic cycling. This glutathione-dependent effect, combined with the un-ionised state of the drug at physiological pH, may contribute to its efficacy. 2. Paradoxically, other aspects of the glutathione-dependent cycling of the hydroxylamine metabolite may contribute to the major adverse reaction of the drug, agranulocytosis. Erythrocytes exposed to the metabolite and repeatedly washed may still release the hydroxylamine in sufficient concentration to kill mononuclear leucocytes in vitro. Thus, erythrocytes may be a conduit for the hydroxylamine to reach the bone marrow to covalently bind to granulocyte precursors, which may trigger an immune response in certain individuals and may lead to the potentially fatal eradication of granulocytes from the circulation. 3. Attempts to increase patient tolerance to dapsone have been most successful using a metabolic inhibitor to reduce hepatic oxidation of the drug to the hydroxylamine. Methaemoglobin formation in the presence of cimetidine was maintained at 30% below control levels for almost 3 mo, and patients' reported side effects such as headache and lethargy were significantly reduced. 4. As clinical application of new and safer dapsone analogues is years away, the use of cimetidine provides an immediate route to increasing patient compliance during dapsone therapy, especially in those maintained on dapsone dosages in excess of 200 mg/day.
Gen Pharmacol 1995 Nov
PMID:Dapsone toxicity: some current perspectives. 869 Feb 32


1 2 Next >>