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)

Acute toxicity of cefpirome sulfate (CPR) was examined in 6-week-old mice and rats and immature (5-day-old) rats. The LD50 values of CPR (mg/kg) were as follows: (1) mice: intravenous, 2420 (95% confidence limits, 2122-2758) for males and 2400 (2181-2640) for females; intraperitoneal, 3850 (3407-4351) for males and 4200 (3889-4536) for females; and oral, 16200 (14781-17755) for males and 18500 (17290-19795) for females. (2) 6-week-old rats: intravenous, 1900 (1784-2023) for males and 2080 (1953-2215) for females; intraperitoneal, 6550 (6179-6943) for males and 5800 (5311-6334) for females; subcutaneous, more than 10000 for both sexes; and oral, more than 8000 for both sexes. (3) 5-day-old rats: subcutaneous, between 1750 and 2500 for males and 2080 (1651-2621) for females. Major changes in general health conditions observed in 6-week-old mice and rats were decreased spontaneous activity, lying prone, tremor, respiratory changes (slow or deep respiration, gasping), clonic or clonic-tonic convulsions. In the 6-week-old rats dosed subcutaneously, vocalization, writhing and cutaneous changes at the injection site (dark reddening or blackening, swelling, exfoliation, depilation, induration) were also observed. In the 5-day-old rats dosed subcutaneously, the changes noted were slow respiration, writhing, cyanosis, and dark reddening and swelling of the skin at the injection site. After administration, transient depression of body weight gain or loss of body weight was observed in the mice and rats except the rats dosed orally. These changes disappeared at 7 days after administration at latest, and all surviving animals showed favorable body weight gain thereafter. Necropsies revealed hemorrhage under meninges in the brain in many of the mice and rats which died. Other findings included subcutaneous changes at the injection site in the 6-week-old and 5-day-old rats dosed subcutaneously (dark reddening, retention of dark red fluid, retention of red, white or dark red gelatinous material) and changes in the peritoneal cavity in the 6-week-old rats dosed intraperitoneally (red or dark red spots on the serous membrane, reddening of adipose tissues).
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PMID:[Acute toxicity study of cefpirome sulfate in mice and rats]. 207 98

Part II: The side-effects of Sandimmune that have also been observed clinically include hepatic dysfunction, glucose intolerance, thrombo-embolic complications and nervous system disorders. To determine the cause and significance of such effects, the actions of Sandimmune on the liver, the pancreas, on hematostasis and the nervous system were examined. Comparisons were made between animal and human data obtained in vivo and in vitro, and the clinical setting under which the side-effects occur was analyzed. The actions of Sandimmune on the liver seem to reflect mostly a cholestasis with a small depression in protein synthesis and a mild disturbance in lipid metabolism of uncertain origin. The action of Sandimmune on the pancreas suggests insulin resistance and possibly a secretory disturbance, with no evidence for depressed insulin synthesis, except in animals at high doses. Sandimmune does not seem to promote thromboembolism in man, although fibrinolysis may be depressed and platelet aggregation can be enhanced. The effects of Sandimmune on the nervous system are unclear, for tremor is common but of uncertain origin, whereas seizures and encephalopathy are rare and invariably associated with other risk factors.
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PMID:The pathophysiology of Sandimmune (cyclosporine) in man and animals. 208 72

The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.
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PMID:Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. 221 43

The aim of this study was to determine whether administration of ethanol protects rats against the preconvulsive symptoms of high pressure nervous syndrome (HPNS). Male Sprague-Dawley rats were given either saline or 0.5, 1.5 or 2.5 g/kg ethanol i.p. After injection, the animals were individually exposed to helium-oxygen at 60 atmospheres absolute (atm abs) pressure. The chamber temperature was adjusted to counteract ethanol- and helium-induced hypothermia. Several behavioral parameters were scored continuously during the first 64 min after injection. The time spent in tremor at high pressure was significantly less in the 1.5 and 2.5 g/kg ethanol-treated groups. The number of jerks was significantly lower in the 2.5 g/kg ethanol-treated group. The two highest doses of ethanol induced a characteristic pattern of unsteady locomotion, which was returned to normal in the 1.5 g/kg group at 60 atm abs. Other behavioral effects of ethanol, such as depression of total motor activity, were also reduced. These results indicate that ethanol can significantly ameliorate some of the adverse symptoms of HPNS in freely moving rats.
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PMID:Interaction of ethanol and the high pressure nervous syndrome in rats. 221 48

Patients (n = 150) were randomized to a 6-week, double-blind study to evaluate the relative efficacy and safety of mirtazapine, amitriptyline, and placebo in the treatment of major depressive disorder symptoms. Average daily modal doses were mirtazapine, 18 mg; amitriptyline, 111 mg; and placebo, 4.6 capsules. Mirtazapine- and amitriptyline-treated patients had statistically significantly greater mean Hamilton Rating Scale for Depression (HAM-D) score reductions (weekly visits 1, 2, 4, and endpoint) compared to placebo. These findings were supported by the Montgomery-Asberg Depression Rating Scale (MADRS); the Zung Self-rating Depression Scale (SDS); and the Clinical Global Impressions (CGI) scales. Somnolence and weight gain were the only adverse clinical experiences (ACEs) reported substantially more often by mirtazapine-treated patients than by those in the placebo group. However, more amitriptyline-treated patients reported decreased visual accommodation, dry mouth, dyspepsia, constipation, tachycardia, hypertension, hypotension, discoordination, dizziness, and tremor than mirtazapine- or placebo-treated patients. Results of this study indicate that mirtazapine is more effective than placebo in the treatment of these patients, and superior to amitriptyline in respect to anticholinergic and cardiovascular effects.
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PMID:Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. 223 55

A consecutive series of 105 outpatients with Parkinson's disease (PD) were examined for the presence of depression. Twenty-one percent met diagnostic criteria for major depression, 20% had minor depression, and the remainder were not depressed. The frequency of depression showed a bimodal distribution over time, with highest frequencies occurring in the early and late stages of the disease. Although other factors such as a positive family history of psychiatric disorders, quality of social functioning, and severity of tremor, rigidity, and akinesia did not show a significant association with depression, depressed patients had significantly higher impairment scores in activities of daily living and cognitive function than nondepressed PD patients. There was also a significant correlation between impairment and depression scores. In addition, among patients with mainly unilateral symptoms, depression was significantly associated with greater left hemisphere involvement. These findings suggest that depression in the early stages of the disease may be related to left hemisphere dysfunction, while later in the disease, depression and impairment in activities of daily living are interrelated. This may indicate more than one etiology of depression or that depression may have an adverse impact on the course of the disease.
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PMID:Depression in Parkinson's disease. 229 85

Eight different synthetic pyrethroids were examined to determine their effects on the excitability of hippocampal granule cells in urethane-anesthetized rats. A paired stimulus approach was used. All eight prolonged the depression of granule cell excitability that follows stimulation of their major synaptic input, the perforant path. The magnitude of this effect depended upon the class to which the pyrethroid belonged. Type I pyrethroids (those primarily producing tremor) prolonged the depression of granule cell excitability for shorter periods than did type II pyrethroids (those primarily producing salivation and choreoathetosis) or pyrethroids producing a mixed type of intoxication. No overlap was found between groups. To determine whether the difference observed between type I and type II pyrethroids was the result of an infelicitous selection of doses, cismethrin (type I) was tested over a dose range of 1.5-24 times the conscious rat iv LD50. Even at the highest dose, the prolongation remained well below that produced by type II pyrethroids. The effect of deltamethrin was shown to be consistent with the production or potentiation of a surmountable inhibitory response. This action of deltamethrin was antagonizable by mephenesin and lidocaine, but not by picrotoxin or halothane. The type of effect, its time course, and the antagonism data suggest that type II pyrethroids enhance inhibition in the dentate gyrus. This action does not appear to be mediated by GABAA receptors.
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PMID:Characteristics of the prolonged inhibition produced by a range of pyrethroids in the rat hippocampus. 233 24

The authors describe two series of patients: 12 treated simultaneously with fluoxetine and a monoamine oxidase inhibitor and 6 patients started on treatment with an MAOI 10 days or more after stopping fluoxetine treatment. All patients had extremely refractory depression and were treated in open fashion before general knowledge was obtained of the side effects that may accompany the fluoxetine-MAOI combination. During the fluoxetine-MAOI trial, most patients continued to receive other psychotropic combinations that had been partially helpful. The use of fluoxetine and an MAOI, either together or in close succession, was accompanied by a very high incidence of adverse effects, especially the "serotonergic syndrome." This syndrome was characterized by mental status changes, such as hypomania and confusion, and physical symptoms, such as myoclonus, hypertension, tremor, and diarrhea. Because of the high incidence of side effects and the lack of definite efficacy, the concurrent use of fluoxetine and MAOIs should generally be avoided. The long half-lives of fluoxetine and norfluoxetine, as well as the prolonged metabolic effects of MAOIs, may also dispose patients to an interaction if one of the drugs is started soon after stopping the other.
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PMID:Adverse consequences of fluoxetine-MAOI combination therapy. 199 42

The presence of depression and cognitive impairments was examined in seventy patients with Parkinson's disease (PD). Forty nine patients of this original cohort were re-examined between three and four years after the first evaluation. While both depressed and non-depressed patients showed a significant decline in cognitive function during the follow up period, intellectual decline was significantly more severe for the depressed group. Depressed patients also showed a faster rate of progression of motor signs (mainly tremor) than the non-depressed group. Patients that died during the follow up period showed significantly more cognitive impairments than patients who were alive at follow up. These findings suggest that either there may be two forms of PD: one with depression and rapid cognitive decline and one without depression and a gradual cognitive decline; or that the mechanisms of cognitive impairment in PD and depression may interact to produce a more rapid evolution in cognitive impairment among PD patients with a previous depression than among patients without a previous depression.
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PMID:Cognitive impairments and depression in Parkinson's disease: a follow up study. 239 25

Several mechanisms have been suggested for the absence of reflex tachycardia in response to the hypotensive effect of the selective alpha 1-adrenoceptor antagonist indoramin, including, in animals, membrane-stabilising activity, prolongation of repolarisation time, and reduction in baroreflex sensitivity. The present study investigated the effect of acute and chronic oral administration of indoramin (50 mg daily for 8 days) on baroreflex sensitivity in six healthy male volunteers. Baroreflex function was measured by determining the relationship between systolic blood pressure (SBP) and R-R interval following intravenous administration of phenylephrine. Indoramin shifted (p less than 0.05) the phenylephrine dose-response curve to the right on days 1 and 8 compared with placebo. Baroreflex sensitivity [R-R (ms)/SBP (mm Hg)] was reduced (p less than 0.05) by indoramin on day 1 compared with placebo (18.3 +/- 1.3 vs. 11.2 +/- 2.2 ms/mm Hg), and on day 8 compared with pretreatment values (18.3 +/- 2.8 vs. 10.8 +/- 1.8 ms/mm Hg). Acute but not chronic administration of indoramin caused (p less than 0.05) sedation; tremor tended to increase with chronic administration. It is suggested that depression of baroreflex sensitivity by indoramin may explain, in part, the lack of reflex tachycardia associated with its antihypertensive effect.
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PMID:Effect of acute and chronic indoramin administration on baroreflex function and tremor in humans. 245 20


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