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)

Preliminary disposition studies of the investigational, long-acting muscle relaxant doxacurium chloride (Nuromax) have demonstrated dual elimination by renal and hepatobiliary pathways, as well as slow hydrolysis by plasma cholinesterase. The present study compares the kinetics and dynamics of doxacurium in eight ASA physical status I or II elderly patients (67-72 yr of age) and eight ASA I or II young patients (22-49 yr of age). After institutionally approved written informed consent, kinetic and dynamic measurements were made after a 25-micrograms/kg bolus injection of doxacurium during 1.25 MAC nitrous oxide/oxygen/isoflurane anesthesia. Maximum twitch depression was similar in older patients (96.4% +/- 1.3%) to that in the young patients (96.6% +/- 1.8%). The time to achieve this level of block was significantly longer in the elderly than in the young (11.2 +/- 1.1 min versus 7.7 +/- 1.0 min, respectively). Recovery times to twitch heights of 5% and 25% of control tended to be prolonged and were more variable in the elderly (82.6 +/- 17.2 and 97.1 +/- 20.1 min, respectively) than in the young (54.8 +/- 9 and 67.5 +/- 8.2 min, respectively). Elimination half-life (96 +/- 20 min) and clearance (2.47 +/- 0.69 mL.kg-1.min-1) in the elderly patients were not statistically different from values found in the younger group. Volume of distribution at steady state in the elderly (220 +/- 80.2 mL/kg) was significantly larger than in the young (150 +/- 40.0 mL/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics and pharmacodynamics of doxacurium in young and elderly patients during isoflurane anesthesia. 214 83

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered by infusion to 10 cats that were anesthetized with isoflurane and oxygen to allow transplantation of a myocutaneous flap. Five of the cats were given cyclosporine (20 mg/kg of body weight, PO q 12 h in divided doses) for 2 days prior to anesthesia, and prednisolone (0.25 mg/kg, PO) on the morning of surgery. The other 5 cats were not given either drug. Neuromuscular blockade was assessed, using the train-of-four stimulation, and throughout surgery, the infusion rate was adjusted to maintain the first-twitch response (T1) at 90 to 95% depression from baseline. At completion of surgery, atracurium was discontinued, and the infusion rate and the time for recovery (the time for the train-of-four ratio to increase from 50 to 75%) were recorded. Once the train-of-four ratio had been stable for 10 minutes, edrophonium (0.5 mg/kg), a cholinesterase inhibitor, was administered IV, and neuromuscular blockade was monitored for another 10 minutes. Mean (+/- SD) duration of the atracurium infusion was 302.1 +/- 70.5 minutes for the control group and was 323.9 +/- 61.7 minutes for the cats given cyclosporine and prednisolone. In the cats of the control group, the infusion rate required to induce 90 to 95% T1 depression from baseline was 3.7 +/- 0.7 micrograms/kg/min. This rate was not significantly different from that of 2.8 +/- 1.2 micrograms/kg/min in cats given cyclosporine and prednisolone. Significant difference in recovery time was not evident between the control group and the treated group (6.4 +/- 4.5 minutes vs 6.2 +/- 2.5 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atracurium administration, as an infusion, to induce neuromuscular blockade in clinically normal and temporarily immune-suppressed cats. 225 41

An illness characterized by weakness, dizziness, and gastrointestinal symtoms was identified among a crew of 30 migrant field-workers employed by a grape grower in Madera County, California, during August 1987. The onset of symptoms occurred between August 24 and August 30 and a median of 9 days from the date of first employment. The first crew member sought medical treatment on August 26, and 10 crew members were admitted to hospital between August 27 and August 30. For most workers, gastrointestinal and constitutional symptoms resolved shortly after admission, but 4 patients had episodes of severe sinus bradycardia persisting for several days. On the day of admission, transient atrioventricular dissociation developed in 2 persons. Interviews with 16 crew members not admitted to the hospital identified only 1 additional worker ill with gastrointestinal symptoms, but all 16 had moderate to severe inhibition of both plasma and red blood cell cholinesterase. Four other workers who were tested but not interviewed also had cholinesterase depression. The crew had had exposure since August 19 to the organophosphate insecticide phosalone, which was last applied to the vineyard on July 21, or 29 days earlier. Although this is the first report unequivocally linking phosalone to field-worker poisoning, the delayed onset and nonspecific nature of the symptoms associated with subacute poisoning may have hindered the recognition of previous similar episodes.
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PMID:Subacute poisoning with phosalone, an organophosphate insecticide. 229 66

Rats injected intravenously with monoclonal antibodies reactive with brain acetylcholinesterase (AChE) developed a prolonged depression of plasma AChE without changes in butyrylcholinesterase, lactic acid dehydrogenase, or hematocrit. One antibody, ZR1, accumulated in the brain and spinal cord. Within 3 days of injection, ZR1 bound to most of the AChE in cerebral cortex and certain other regions of the CNS. Examination of the molecular forms of cortical 10S AChE, whereas 4S AChE remained free. In vitro, however, ZR1 bound equally to solubilized 4S and 10S forms. These data provide direct evidence for the compartmentalization of different AChE forms in the CNS, 10S being mainly extracellular and 4S apparently intracellular. Development of a striking and persistent bilateral ptosis within hours of injection suggests that AChE in the autonomic nervous system is also accessible to antibodies and, furthermore, is the site of an immunopathological lesion. This novel model of cholinergic autoimmunity may have relevance for human neurological disorders of unknown etiology.
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PMID:Selective complexing of acetylcholinesterase in brain by intravenously administered monoclonal antibody. 229 14

Brain cholinesterase (ChE) activities of songbirds collected in pecan groves 6 to 7 hr after separate applications of the organophosphorus pesticides, phosalone and disulfoton, were compared to mean ChE activities of controls (normals) as a measure of insecticide exposure. In general, reduction of brain ChE activity greater than or equal to 2 standard deviations below the control mean indicates exposure to an anticholinesterase compound. Phosalone had little effect on brain ChE activity of birds from treated groves; only slight to moderate (21 to 38%) ChE inhibition was detected in blue jays (Cyanocitta cristata) and red-bellied woodpeckers (Melanerpes carolinus). However, 11 of 15 blue jays from disulfoton-treated groves had moderate to severe ChE depression, ranging from 32 to 72%. Inhibition greater than or equal to 50% of normal may be diagnostic for cause of death. Direct mortality was not observed, but studies have shown that bird carcasses disappear rapidly from agricultural areas, many within 24 hr. We recommend additional field studies of the effects of disulfoton to wildlife, since large wheat-growing areas in the western United States are being considered for disulfoton treatment to control the Russian wheat aphid (Diuraphis noxia).
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PMID:Brain cholinesterase inhibition in songbirds from pecan groves sprayed with phosalone and disulfoton. 230 90

A reference range for erythrocyte acetyl cholinesterase (EAChE) in 46 mentally normal subjects aged 65 years or over has been established. Previous reports of a relationship between changes in (EAChE) levels and mental illness (dementia and depression) in the elderly suggested that this determination may be useful in screening elderly subjects for these illnesses or as an aid to diagnostic classification. A study of normal and mentally ill elderly subjects in the community in Liverpool does not confirm a relationship with either senile dementia or depression and many of the changes in EAChE levels noted previously can be accounted for either by variations in the haematocrit or by a hitherto unreported lowering of EAChE levels in normal women over 80 years of age.
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PMID:Erythrocyte acetyl cholinesterase in elderly patients with dementia and depression compared with normal controls. 233 4

Three outbreaks of food poisoning involving watermelons or cucumbers and caused by the carbamate pesticide aldicarb occurred in California between 1985 and 1988. For each outbreak, and for an outbreak of aldicarb poisoning associated with English cucumbers previously reported in the literature, dosages of aldicarb sulfoxide that caused the illnesses were estimated. Estimated dosages ranged between 0.0023 [corrected] and 0.06 mg/kg body weight, and most were well below the 0.025 mg/kg Lowest Observed Effect Level (LOEL) for subclinical blood cholinesterase depression previously reported for humans. These findings are consistent with aldicarb sulfoxide (ASO) illnesses that have occurred in other states. Aldicarb appears to be more toxic than previously suspected. Scientific and regulatory implications are discussed.
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PMID:Aldicarb food poisonings in California, 1985-1988: toxicity estimates for humans. 238 19

When an automated counting instrument using an esterase stain was employed, decreased monocyte counts were observed in a group of process workers exposed to organophosphate esters. Their monocyte counts were not found to be depressed with manual counting or with an automated counter using another staining method. The apparent depression was transient. In these workers and a comparison group, theoretical adverse consequences of decreased monocyte esterase and also possible changes in other esterases were explored. No anergy was seen with mumps or staphylococcal phage lysate hypersensitivity skin tests. Histology of the mumps reaction was similar in both groups. The depressed monocyte counts were significantly associated with a mild reduction in erythrocyte cell acetylcholinesterase, but no reduction was seen in plasma pseudocholinesterase or lymphocyte neurotoxic esterase.
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PMID:Industrial exposure to organophosphorus compounds. Studies of a group of workers with a decrease in esterase-staining monocytes. 241 79

An aerosol preparation containing 2.5% chlorpyrifos was applied to the tail and umbilicus of newborn pigs. Mortality was 7/7 pigs treated 0-3 hr after birth, 3/5 pigs treated at 24-30 hr, and 0/3 pigs treated 30-36 hr after birth. Clinical signs consistent with organophosphate (OP) toxicosis were demonstrated by pigs that subsequently died or were euthanatized in extremis. Blood and brain cholinesterase (ChE) activities were depressed in affected pigs compared to controls. Only 1/3 pigs treated 30-36 hr after birth had a diagnostically significant depression in blood ChE. These results indicate that piglets one day or less of age are susceptible to OP toxicosis by cutaneous absorption of chlorpyrifos.
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PMID:Age related susceptibility of newborn pigs to the cutaneous application of chlorpyrifos. 242 59

1. The amplitudes of end-plate currents (EPCs) evoked by stimulating the nerve with frequencies ranging from 1 to 5 Hz and the amplitudes of miniature end-plate currents (MEPCs) gradually diminish if choline uptake is blocked by hemicholinium-3 (HC-3, 20 microM). This reduction of EPC amplitudes is predominantly of presynaptic origin, although an observed decrease in MEPC amplitudes suggests that some postsynaptic changes [due to direct action of HC-3 on acetylcholine (ACh) receptors or on open ACh channels] also occurs. 2. Shortening of both EPCs and MEPCs is observed during high-frequency stimulation (5 Hz) in the presence of cholinesterase inhibitor after impairment of ACh synthesis. Shortening of MEPCs probably results from a direct blocking action of HC-3 on open ACh channels, as well as from reduction in quantal size. Shortening of EPCs is more pronounced (EPCs eventually have shorter time courses than MEPCs) and usually does not result from a gradual reduction in the spatial overlap of quantal events (because of reduced quantal content) or from a diminished 'lingering ACh' (ACh that remains in the synaptic cleft between nerve impulses), but rather from a much reduced quantal size of nerve-evoked quanta. 3. It therefore appears that the quanta that are released by nerve stimulation are preferentially filled with newly synthesized ACh. In its absence nerve stimulation leads to secretion of only partially filled quanta. This occurs simultaneously with spontaneous secretion of almost normally filled quanta. Hence it seems that the quantal discharge is not strongly dependent, if at all, on its ACh content. Moreover, the correspondence between the quantal sizes of nerve-evoked and spontaneously released quanta does not remain valid during high-frequency prolonged stimulation. 4. Even with the choline uptake system intact, prolonged high-frequency stimulation leads to a gradual shortening of EPCs and, to a small extent, MEPCs. Shortening of EPCs appears to be mainly a result of a reduction of their quantal size. 5. It is estimated from the shortening of EPCs and the known EPC versus MEPC relationship that the reduction of the quantal sizes of nerve-evoked quanta probably contributes very significantly to synaptic depression that occurs during prolonged high-frequency nerve stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Synaptic depression in frog neuromuscular junction. 244 Oct 3


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