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)

Potassium picloram was administered either by gavage (acute studies) or in drinking water to male and female Sprague-Dawley-derived rats (14-day and 90-day studies). The acute oral LD50 was 950 mg/kg (812-1120) for males and 686 mg/kg (599-786) for females. Depression, prostration, ataxia, tremors, and convulsions preceded death. There were no consistent biologically significant compound-related effects in rats that received 60, 190, 600 mg potassium picloram/kg/day for 14 days. In the subchronic study, rats received 60, 190, 600, or 1070 mg potassium picloram/kg/day in drinking water for 90 consecutive days. There were only 4 male and 2 female survivors out of 20 rats of each sex at the 1070 mg/kg dose and 16 male and 18 female survivors at the 600 mg/kg dose. Mortality was dose dependent. Administration of picloram appeared to exacerbate renal and hepatic lesions commonly noted in rats of this age. For example, at levels up to 1070 mg/kg mild lesions in the kidney of treated rats, especially in males at 600 mg/kg, were noted. Also noted were an increased incidence of mononuclear liver foci in male rats that received 190 and 600 mg/kg and an increased severity of mononuclear liver foci in females that received 600 mg/kg. There were no other consistent biologically significant compound-related effects. No specific organ site toxicity could be identified in these studies. Toxicity from exposure to picloram in drinking water is apparently low.
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PMID:Acute, 14-day repeated dosing, and 90-day subchronic toxicity studies of potassium picloram. 378 Nov 36

New glutarimide compounds were synthesized by incorporating piperidine (compounds 1 to 7), diethylamine (8 and 9), morpholine moities (10 to 13), and alkyl derivatives of 3,5 dicyanoglutarimide (14 to 20) at position -1 of the nitrogen atom. Only compounds 1 to 7 at a dose of 8 mg/kg i.p. caused hypermotility, ataxia, tachypnoea and mild tremors in mice. At higher doses (32 mg/kg i.p.), all compounds induced tonic and clonic convulsions, respiratory paralysis and death. The LD50 values of compounds 1 to 20 in mice range from 152 to 488 mg/kg i.p. and for compounds 21 to 23, the p.o. values are 484, 500 and 525 mg/kg. The relative toxicity of compounds 1 to 7 and 14 to 20 showed inverse ratio in their numbers. Basic compounds 21 to 23 at high dose levels (64 mg/kg i.p.) induced only hypnotic depression. No change was observed in organ-wise histopathological study except patchy necrosis at the site of injection of basic compounds. The CNS pharmacological studies were negative with reference to anti-convulsion, analgesic, antipyretic tests by conventional methods except at higher doses (32 or 64 mg/kg i.p.), which exhibited synergistic effects in mice and rats.
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PMID:Pharmacology of new glutarimide compounds. 387 5

The changes in brain acetylcholinesterase (AChE), acid phosphatase (APase), and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNP), and plasma butyrylcholinesterase (BuChE) activities were investigated in hens treated with a single, dermal dose (100-1000 mg/kg) of S,S,S-tri-n-butyl phosphorotrithioate (DEF). Three control groups consisted of hens left untreated, given a single, dermal dose of 500 mg/kg tri-o-cresyl phosphate (TOCP, positive control for organophophorous compound-induced delayed neurotoxicity), or 10 mg/kg O,O-diethyl O-4-nitrophenyl phosphorothioate (parathion, negative control). Brain AChE activity, determined 28 days after application, was significantly inhibited in hens given 500-1,000 mg/kg DEF and in TOCP- and parathion-treated hens. In contrast, brain APase and CNP activities were significantly higher in all treatments as compared with those of the untreated hens. Parathion, however, caused the least increase in these enzymatic activities as compared to DEF or TOCP. A single, dermal dose of DEF or TOCP also caused an initial decrease in plasma BuChE activity with maximum depression of enzymatic activity observed 1 to 7 days after administration. This decrease was dose dependent and the enzymatic activity showed partial recovery with time. Hens treated with single, dermal doses of DEF, ranging from 250 to 1000 mg/kg, developed ataxia which progressed to paralysis in some hens. Histopathologic examination revealed axon and myelin degeneration of the spinal cord and peripheral nerves of some hens. The severity and frequency of the neuropathologic lesions were dose dependent. Neurologic dysfunctions and neuropathologic lesions seen in DEF-treated hens were similar to those exhibited in TOCP-treated hens. While parathion produced acute cholinergic effects, it did not cause delayed neurotoxicity. The changes in brain and plasma enzymes are discussed in relation to their role in the pathogenesis of DEF-induced delayed neurotoxicity.
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PMID:Brain acetylcholinesterase, acid phosphatase, and 2',3'-cyclic nucleotide-3'-phosphohydrolase and plasma butyrylcholinesterase activities in hens treated with a single dermal neurotoxic dose of S,S,S-tri-n-butyl phosphorotrithioate. 395 29

The present study was designed to evaluate the influence of acrylamide (ACR) on male and female reproductive function. Male rats received ACR in drinking water (50, 100, or 200 ppm) for up to 10 wk. Copulatory behavior, semen, and (for controls and 100 ppm only) fertility and fetal outcomes were evaluated. Females received ACR (25, 50, 100 ppm) for 2 wk prior to initiation of breeding and then throughout gestation and lactation. Hindlimb splaying was apparent in the 200-ppm males by wk 4; less severe splaying appeared in the 100-ppm group at wk 8. Disruptions in copulatory behavior preceded the appearance of this ataxia. These disruptions in mating performance interfered with ejaculatory processes and subsequent transport of sperm, since semen was found in the uterus of only 1 of the 15 females mated with the 100-ppm males at wk 9. Moreover, only 33% of the females mated (wk 10) to the 100-ppm males were pregnant. Postimplantation loss was also significantly increased in this group. Hindlimb splaying appeared in the females receiving 100 ppm ACR during wk 1-2 of pregnancy. Body weight and fluid intake were also depressed. Dams in the 50-ppm group showed depression in these parameters during the last 2 wk of lactation. ACR did not significantly affect mating performance of the females, pregnancy rates, litter size, or survival. However, ACR did significantly depress pup body weight at birth (100-ppm group) and weight gain during lactation through post-weaning, d 42 (50- and 100-ppm groups). Vaginal patency was delayed in the 100-ppm group only.
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PMID:Reproductive toxicity associated with acrylamide treatment in male and female rats. 395 25

A 1:1 mixture of tiletamine hydrochloride and zolazepam hydrochloride was tested on 39 polar bears in and near Churchill, Manitoba, Canada during October 1983. The mean dose for satisfactory immobilization with a single injection was 5.1 mg/kg. Bears showed signs of ataxia from 1-3 min following injection and were usually sitting within 4 min. The mean induction time, taken as the adoption of sternal recumbency, was 5.1 min. Maximum relaxation was usually seen by about 20 min post-injection. The duration of immobilization appeared to be related to the dose of drug received. In bears that received a dose near the mean, recumbency lasted about 2 hr. Cubs of the year recovered more quickly than adults. Preliminary results indicated that the bears did not suffer respiratory depression and were able to thermoregulate while immobilized. Bears could be handled safely while under the effects of the drug and workers could readily evaluate the state of their sedation by their reactions. The drug did not appear to provide good analgesia at the doses tested.
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PMID:Immobilization of polar bears (Ursus maritimus Phipps) with a mixture of tiletamine hydrochloride and zolazepam hydrochloride. 398 43

Ten clinically healthy cats were allotted into 2 groups. Group A was given the low (60 ml), and group B was given the high (120 ml) recommended dose of a commercial hypertonic sodium phosphate enema. Enema retention was enforced. All cats developed clinical and/or laboratory abnormalities, with group B cats being more severely affected. Clinical signs that occurred rapidly included depression, ataxia, vomition, bloody diarrhea, mucous membrane pallor, and stupor; tetany was not seen. One cat in group B died. Laboratory abnormalities included hypernatremia, hyperphosphatemia, hypocalcemia, hyperglycemia, calculated hyperosmolality, and metabolic acidosis with high anion gap probably due to hyperlacticacidemia. There were no significant gross or microscopic lesions associated with enema administration. Therefore, the use of hypertonic sodium phosphate enema at recommended doses is potentially dangerous to cats.
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PMID:Clinical, biochemical, acid-base, and electrolyte abnormalities in cats after hypertonic sodium phosphate enema administration. 401 52

Comparative studies were pursued to investigate the locomotor activity induced by phencyclidine hydrochloride in CD-1 male mice. Horizontal, vertical, and rotational activity counts were quantitated using an infrared beam animal activity monitor. Five doses (1.5, 2.5, 3.5, 5.0, and 10.0 mg/kg, i.p.) of phencyclidine were compared. At the 1.5 mg/kg dose, no locomotor activity changes were observed when compared to a saline control group. Increased activity was observed at the 2.5, 3.5, and 5.0 mg/kg doses. Decreased activity was observed at the 10.0 mg/kg dose when compared to the 5.0 mg/kg dose possibly due to ataxia. In addition, the locomotor activity produced by acute d-amphetamine and acute phencyclidine was compared at doses of 2.5 mg/kg and 5.0 mg/kg respectively. The overall locomotor activity levels produced by acute d-amphetamine and phencyclidine were not significantly different at p less than 0.05. The time to peak activities and peak level activities were also similar and occurred at 20-25 minutes and 1100-1300 inches respectively after i.p. administration. Administration of apomorphine after phencyclidine did not change overall locomotor activity. The data implies that phencyclidine may act primarily as a dopamine reuptake inhibitor rather than a dopamine release stimulator. Phencyclidine also affects other activity (unlike amphetamine) as seen by the severe depression of vertical activity.
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PMID:Comparison between locomotor activity changes produced by phencyclidine and D-amphetamine in CD-1 male mice. 402 8

Polyoxyethylene (20) sorbitan monooleate (polysorbate 80, Tween 80), a surfactant, has been widely used as a solvent for pharmacological experiments. In the present study, polysorbate 80 was found to have toxicity of a low order in both the mice and rats when given by i.p. and p.o. routes. It produced mild to moderate depression of the central nervous system with a marked reduction in locomotor activity and rectal temperature, exhibited ataxia and paralytic activity and potentiated the pentobarbital sleeping time. On intravenous administration in dogs, it had a dose-dependent hypotensive effect. Polysorbate 80 did not have a direct stimulant or relaxant effect on either guinea pig ileum or rat uterus, however, it antagonised the contractions induced by acetylcholine, histamine, barium, 5-hydroxytryptamine and carbachol in a dose-dependent manner. A direct relaxant effect was observed on rabbit jejunum. A dose-dependent myocardial depressant effect was observed on guinea pig and rabbit paired atrial preparations. On the electrically-driven guinea pig left atrial preparation, polysorbate 80 exhibited a dose-dependent negative inotropic action. Polysorbate 80 did not induce diuresis in rats upto a dose of 2.5 ml/kg. The results of the present study indicate that polysorbate 80 can neither be used as a solvent for isolated tissue experiments nor when considered for intravenous administration. However, polysorbate 80 can be employed safely as a vehicle for neuropsychopharmacological experiments in doses not exceeding 1 ml/kg.
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PMID:Polysorbate 80: a pharmacological study. 402 3

Arsenic toxicosis and suspected chromium toxicosis were diagnosed in a herd of cattle that ingested ashes from lumber treated with copper, chromium, and arsenic. Findings included peracute death, depression, ataxia, weakness, recumbency, and watery diarrhea. Chemical analyses of liver, kidney, abomasal contents, rumen contents, and ashes revealed high concentrations of arsenic and chromium. Histologically, specimens of abomasum and duodenum had diffuse mucosal degeneration and engorged capillaries. Epithelial cells of the proximal convoluted tubules and distal collecting tubules of the kidney were swollen and had mild granular cytoplasmic degeneration. Burning lumber treated with copper, chromium, and arsenic does not remove the heavy metals from them, and ingestion of the ashes from the wood constitutes a hazard to livestock health.
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PMID:Arsenic toxicosis and suspected chromium toxicosis in a herd of cattle. 403 Apr 55

Biochemical parameters in 20 sheep were investigated following administration of quinuronium sulfate or diminazene diaceturate. The usual signs of salivation, micturition, anorexia, depression, muscular tremors and ataxia were observed within 20 min in sheep receiving therapeutic and double doses of quinuronium sulfate. There was an increased dose dependent plasma LDH activity above baseline values following administration of quinuronium sulfate and a non-dose dependent increased trend in diminazene diaceturate treatment. Plasma CK activity had an increased trend (p less than 0.05) above baseline values following administration of the two babesicides. Plasma BUN levels increased significantly (p less than 0.05) following administration of the two drugs. This study indicated that quinuronium sulfate is more organotoxic and hypotensive than diminazene diaceturate at therapeutic and/or above therapeutic dosages.
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PMID:Comparative studies of the effects of quinuronium sulfate and diminazene diaceturate in sheep. 408 73


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