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)

To determine the organ distribution of production of the three endothelin (ET) isopeptides, we have developed three ribonuclease protection assays specific for the messenger RNAs (mRNAs) of rat ETs 1, 2, and 3.12 organs from adult Sprague-Dawley rats were examined: heart, lung, liver, spleen, kidney, stomach, small intestine, large intestine, testis, muscle, salivary gland, and brain. The mRNA for ET1 was five times more abundant in the lung than in any other organ studied, moderate expression was seen in the large intestine, and lower levels of mRNA were detected in each of the other organs examined. ET2 was expressed at high level in both large and small intestine and at low level in stomach, muscle, and heart, but ET2 mRNA could not be detected elsewhere. ET3 mRNA was found in all organs, particularly in small intestine, lung, kidney, and large intestine. Because of reports suggesting that ETs might be involved in the hypoperfusion and hypofiltration observed in postischemic kidneys, we have also studied levels of mRNA in kidneys that had previously been subjected to 25 or 45 min of clamping of the renal pedicle. At 6 h after 45 min of ischemia, ET1 mRNA increased to a peak of 421 +/- 69% (mean +/- SEM, n = 3) of that in a standard renal RNA preparation. By contrast, ET3 mRNA decreased in the postischemic organ, falling to a value of 19 +/- 2% of standard at the same time point. The effects of ischemia on ET1 and ET3 mRNAs were long-lasting, with elevation of ET1 and depression of ET3 persisting for days. ET2 mRNA remained undetectable throughout. These findings (a) support a role for ET1 in postischemic renal vascular phenomena and (b) demonstrate a situation in which the expression of ET isoforms is clearly subject to differential regulation.
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PMID:Organ distribution of the three rat endothelin messenger RNAs and the effects of ischemia on renal gene expression. 152 10

We examined the effect of a dynamic, hypoxic stimulus upon the reflex respiratory responses of 15, conscious rat pups on post-natal days 5-7 in order to ascertain the influence of a non-adapting peripheral chemoreceptor discharge upon respiratory control during hypoxia in the newborn. Respiration was measured as integrated airflow into and out of a body plethysmograph. The respiratory response to 6 minutes of a 16-breath cycle (approximately 5 s) in FiO2 between 0.21 and 0.10 (alternating hypoxia) was compared with the response to 6 min of a constant FiO2 of 0.12 (non-alternating hypoxia). Ventilation increased significantly from a control level of 0.12 +/- 0.02 ml/s (mean +/- SEM) to 0.18 +/- 0.02 and 0.17 +/- 0.02 ml/s in non-alternating and alternating hypoxia runs respectively during the first minute (phase 1) of each run, after which ventilation in both run types fell progressively and significantly back towards control levels to reach, by the sixth minute (phase 2), 0.13 +/- 0.01 and 0.12 +/- 0.02 ml/s respectively. No significant difference was found between the levels of ventilation in non-alternating hypoxia and alternating hypoxia during either phase 1 (P greater than 0.10) or phase 2 (P greater than 0.60). No significant alternation was found in any respiratory variable at the frequency of the 16-breath hypoxic cycle during either phase 1 or phase 2 of non-alternating hypoxia. However, a significant alternation, at this frequency, of 37 +/- 6% (P less than 0.05 compared to control) was found in ventilation during phase 1 of alternating hypoxia which was further increased to 62 +/- 8% (P less than 0.05 compared to phase 1) during phase 2. In phase 1 the alternation was due primarily to significant alternation in inspiratory time whilst in phase 2 significant alternation also occurred in tidal volume, expiratory time and mean inspiratory flow. Our results show that the magnitude of hypoxic ventilatory depression (HVD) in the newborn is not affected by an alternating hypoxic stimulus and that, during phase 2, ventilation can still be stimulated by peripheral chemoreceptors. We suggest that peripheral chemoreceptor adaptation is unlikely to be a major cause of HVD in the newborn rat and that the magnitude of HVD is, in part, the result of a competitive interaction between peripheral chemoreceptor stimulation and a centrally-mediated inhibitory action of hypoxia.
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PMID:The reflex ventilatory responses of conscious, newborn rats to alternations of inspiratory oxygen concentration. 152 66

The ventilatory response to CO2 was measured to evaluate the degree of respiratory depression after epidural sufentanil. After cesarean section performed with bupivacaine epidural anesthesia, 14 patients received either 30 micrograms (n = 7) or 50 micrograms (n = 7) of epidural sufentanil. Respiratory measurements were made before and 15, 45, and 120 min after sufentanil injection. The presence and severity of sedation and other nonrespiratory side effects were evaluated throughout the study. Plasma sufentanil assays were performed on blood samples obtained at frequent intervals during the first 2 h. Although changes in resting ventilation did not occur, both sufentanil doses depressed the ventilatory response to CO2. After sufentanil 30 micrograms, the slope of the CO2 response curve decreased significantly at 45 and 120 min (control value, 2.33 +/- 0.3 L.min-1.mm Hg-1 [mean +/- SEM] vs 1.61 +/- 0.24 and 1.72 +/- 0.15, respectively, P less than 0.05). After sufentanil 50 micrograms, significant decreases occurred at 15 and 45 min (control value, 2.84 +/- 0.71 vs 1.81 +/- 0.48 and 1.48 +/- 0.31 L.min-1.mm Hg-1, respectively). The mean maximal decrease in the slope occurred at 45 min and was more pronounced after 50 micrograms (-42.3% +/- 7.4%) than after 30 micrograms (-27.4% +/- 9.9%). Analgesia was similar in both groups. Side effects, particularly sedation, were more severe with the 50-micrograms dose. We conclude that 30 micrograms of epidural sufentanil is preferable to the higher dose with regard to both respiratory and nonrespiratory side effects. Even with the lower dose, monitoring of ventilation is advisable for a minimum of 2 h.
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PMID:Respiratory effects of epidural sufentanil after cesarean section. 153 6

Dose-response relationships for doxacurium and neostigmine were established in 24 young (18-40 yr) and 24 elderly (70-85 yr) patients, ASA physical status I or II, anesthetized with thiopental, fentanyl, nitrous oxide, and isoflurane. Mechanomyographic response of the adductor pollicis muscle to the train-of-four stimulation of the ulnar nerve was recorded. Doxacurium (5, 10, 15, or 20 micrograms/kg IV) was administered by random allocation. After maximal blockade, and additional dose, for a total of 30 micrograms/kg, was administered. When first twitch height recovered to 25%, incremental doses of 5 micrograms/kg were administered for maintenance of relaxation. Neostigmine (5, 10, 20, or 40 micrograms/kg) was injected at 25% first twitch recovery, and neuromuscular monitoring was continued for 10 min. The doses of doxacurium (+/- SEM) required to produce a 50%, 90%, and 95% depression of twitch tension in the young patients were, respectively, 13.3 +/- 1.6, 23.6 +/- 2.8, and 28.6 +/- 3.4 micrograms/kg, not statistically different from corresponding values in the elderly, 11.8 +/- 1.3, 21.2 +/- 2.3, and 25.9 +/- 2.9 micrograms/kg, respectively. Time to 25% recovery after 30 micrograms/kg was 80.2 +/- 12.2 min in the young versus 133.0 +/- 17.1 min in the elderly (P less than 0.05). Neostigmine-assisted recovery was not significantly different in both groups. The estimated doses of neostigmine to obtain 70% train-of-four recovery after 10 min were 53.6 +/- 7.5 micrograms/kg in the young and 41.6 +/- 5.8 micrograms/kg in the elderly (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-response relations of doxacurium and its reversal with neostigmine in young adults and healthy elderly patients. 153 72

In previous studies serotonin uptake inhibitors such as citalopram decreased alcohol consumption in alcoholics. The mechanism of the effect is not fully understood. This study tested the hypothesis that it is mediated by changes in desire to drink and alcohol effects. After a 1-week baseline period, subjects (13 men and three women; aged 26 to 69 years; healthy, nondepressed, alcohol-dependent drinkers [mean, 6.6 drinks per day]) were randomized in a double-blind fashion to receive 40 mg/day citalopram and placebo for 1 week each, separated by a 1-week washout period. Daily standard alcoholic drinks (13.6 gm ethanol), nonalcoholic drinks, and tobacco use were recorded; evening urine samples were taken; and interest, desire, craving, and liking for alcohol were rated. Medical status, depression, and anxiety were assessed weekly, but no other treatment or advice was given. Daily alcoholic drinks significantly decreased during citalopram treatment (mean +/- SEM = 4.6 +/- 0.6) compared with placebo (5.7 +/- 0.8; p = 0.01), and the average decrease was 17.5%. Percentage of days abstinent increased during citalopram administration (27.7% +/- 5.7%) compared with placebo (15.5% +/- 3.7%; p less than 0.01). Citalopram decreased interest, desire, craving, and liking for alcohol (all p less than 0.05). There was clear internal validation of these measures in that variations in each correlated with alcohol consumption (all r greater than 0.5, p less than 0.05). Nonalcoholic drinks, self-reports of cigarettes smoked (daily smokers), and body weight did not change significantly. In experimental bar sessions, after the citalopram and placebo periods, subjects were required to consume as many of 18 minidrinks as possible (equivalent to six standard drinks) at 5-minute intervals. Subjects rated their desire for alcohol, intoxication, and mood. Citalopram had no significant effects on the desirability of alcohol or subjective feelings of intoxication. The findings indicate that serotonin uptake inhibitors may act by decreasing the urge to drink and the reinforcing effects of alcohol. Also, a naturalistic outpatient trial is a sensitive, simple, and economic procedure for detecting these drug effects.
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PMID:Citalopram decreases desirability, liking, and consumption of alcohol in alcohol-dependent drinkers. 153 2

The effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial stimulation (tc-MERs) were studied in five healthy human volunteers. Each subject, in four separate sessions, received intravenous bolus doses of propofol 2 mg.kg-1, etomidate 0.3 mg.kg-1, midazolam 0.05 mg.kg-1, and fentanyl 3 micrograms.kg-1. Electrical tc-MERs (tce-MERs) were elicited with anodal stimuli of 500-700 V. Magnetic tc-MERs (tcmag-MERs) were elicited using a Cadwell MES-10 magnetic stimulator at maximum output. Compound muscle action potentials were recorded from the tibialis anterior muscle. Duplicate tce-MERs and tcmag-MERs were recorded before and up to 30 min after drug injection. Reproducible baseline tce-MERs (amplitude 4.7 +/- 0.43 (SEM) mV, latency 29.4 +/- 0.35 ms) and tcmag-MERs (amplitude 3.7 +/- 0.43 mV, latency 31.1 +/- 0.39 ms) were obtained in all subjects. Pronounced depression of tce-MER amplitude to 2% of baseline values (P less than 0.01) was observed 2 min after injection of propofol. Thirty minutes after injection of propofol, amplitude depression to 44% of baseline (P less than 0.05) was still present, despite an apparent lack of sedation. Midazolam caused significant (P less than 0.01) amplitude depression, e.g., tcmag-MER to 16% of baseline values 5 min after injection. Significant depression persisted throughout the 30-min study period. Fentanyl did not cause any statistically significant amplitude changes in this small population. Etomidate caused significant but transient depression of tc-MER amplitude. However, there was considerable intersubject variability. Latency did not change significantly after any drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial electrical or magnetic stimulation in humans. 155 Feb 74

The recently developed ELISA for the thrombin-antithrombin III complex (TAT) is a sensitive, specific, and simplified means of detecting intravascular coagulation. For further evaluation of the thrombogenicity of a polyamide (P) and a Hemophan (H) hollow-fibre dialyzer a cross-over study was done in ten stable patients on maintenance hemodialysis. At the same doses of heparin (mean bolus of 30 U/kg bw and maintenance doses of 86 U/kg bw), thrombin time and partial thromboplastin time were significantly lower using H. At the end of dialysis TAT was significantly higher in H (mean +/- SEM before HD 3.57 +/- .56, at 240 min 14.9 +/- 6.5 ng/ml, p less than 0.05, Wilcoxon-test) than in P (before HD 4.36 +/- .98, at 240 min 8.95 +/- 3.0 ng/ml, p less than 0.05 H 240 vs. P 240, Wilcoxon-test). Visible clotting was more pronounced in the H filter. Among other favourable features of blood compatibility the polyamide/polyvinylpyrrolidone copolymer with a hydrophilic/hydrophobic microdomain structure has less thrombogenicity. The modified cellulosic membrane H has advantages in complement activation and leukocyte depression, but thrombogenicity seems less favourable since the incorporated diethyl-amino-ethyl groups with their positive charge bind and inactivate negatively charged heparin.
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PMID:Formation of thrombin-antithrombin III complex using polyamide and hemophan dialyzers. 163 30

Systemic administration of yohimbine augments sympathetic outflow and blocks presynaptic alpha 2-adrenergic receptors, releasing the sympathetic neurotransmitter norepinephrine (NE) into the bloodstream. The present study examined sympathoadrenal and hemodynamic responses to yohimbine in 19 patients with essential hypertension and 19 normotensive control subjects. Baseline mean values for arterial NE, epinephrine, dihydroxyphenylglycol (the main intraneuronal metabolite of NE), spillover of NE into arterial plasma, and corticotropin did not differ between the hypertensive and normotensive groups. Yohimbine (0.125 mg/kg i.v. bolus followed by 0.001 mg/kg/min infusion for a total of 15 minutes) increased mean arterial pressure in all but one subject (by 13 +/- 2% [SEM] in the normotensive and 17 +/- 2% in the hypertensive group) and increased arterial NE levels in all subjects (by 253 +/- 50 pg/ml in the normotensive and 312 +/- 51 pg/ml in the hypertensive group). Among hypertensive patients, pressor, cardiac, output, and arterial NE responses were distributed bimodally. Patients with large hemodynamic and NE responses to yohimbine typically reported a history of anxiety, depression, or other psychopathology and of marked pressor or tachycardic episodes during emotional stress. In the hypertensive and normotensive groups, baseline arterial NE concentrations predicted the magnitude of pressor responses to yohimbine (r = 0.59, r = 0.54,p less than 0.01), whereas baseline mean arterial pressure was unrelated to the pressor response. A yohimbine challenge test can identify patients with pressor hyperresponsiveness and can distinguish patients with pressor hyperresponsiveness due to excessive sympathoadrenal reactivity from patients with enhanced postsynaptic responsiveness to endogenous NE.
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PMID:Sympathetic reactivity during a yohimbine challenge test in essential hypertension. 165 75

Despite its widespread clinical use, the precise mechanism of action of amiodarone (AMI) has not been completely defined. We examined the effects of AMI (20 micrograms/ml) on Vmax and on conduction velocity (theta) during longitudinal (LP) and transverse (TP) propagation with respect to fiber orientation, in 10 strips of uniform anisotropic epicardial muscle obtained from the left ventricle of adult canine hearts. Mean values +/- SEM (standard error of the mean) were calculated as normalized values (beat 50/beat 1) after 4 h of AMI superfusion at five different basic cycle lengths (BCL). Vmax decreased from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.43 +/- 0.03 at a BCL of 300 ms during LP. During TP, Vmax decreased from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.54 +/- 0.05 at a BCL of 300 ms. The differences in the relative changes between both directions at a BCL of 300 ms, as well as at intermediate values of 1,000, 500, and 400, were significant (p less than 0.01). theta during LP (theta L) was depressed from 0.99 +/- 0.01 at a BCL of 5,000 ms to 0.80 +/- 0.04 at a BCL of 300 ms. In contrast, theta during TP (theta T) did not change as the BCL was decreased. In consequence, theta L was significantly more depressed than theta T at BCLs shorter than 1,000 ms (p less than 0.05). Moreover, theta T after AMI was not statistically different from control at any BCL studied. The lack of depression of theta T associated with a marked depression of Vmax during either LP or TP suggests that in addition to its sodium channel blocking properties, AMI could produce a decrease in the effective axial resistivity.
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PMID:Differential effects of amiodarone on Vmax and conduction velocity in anisotropic myocardium. 169 14

In a double-blind cross-over study, 10 patients with stable angina pectoris owing to coronary heart disease were investigated in supine position during rest and bicycle exercise for the effect of 0.4 mg of intravenous (i.v.) isradipine in comparison to 2 mg i.v. nifedipine on cardiac hemodynamics and myocardial ischemia. At rest, both drugs significantly decreased total peripheral resistance (TPR) and mean arterial blood pressure (MAP), whereas heart rate (HR) increased. The pressures and resistance of the pulmonary circulation remained uninfluenced at rest. During symptom limited-exercise, both medications reduced TPR despite an unchanged MAP. Mean pulmonary artery pressure decreased significantly after both medications, whereas right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR) decreased significantly only after nifedipine. The improvement of mean ischemic ST-segment depression averaged 44 +/- 6% (mean +/- SEM, p less than or equal to 0.01) after nifedipine and 45 +/- 7% (p less than or equal to 0.01) after isradipine. The time until angina appeared increased after isradipine by 89 +/- 28% (p less than or equal to 0.05) and after nifedipine by 105 +/- 42% (p less than or equal to 0.01). Significant differences between the two medications appeared only for cardiac output (CO) at rest (p less than or equal to 0.05), during which state the increase after isradipine was higher than after nifedipine, and for exercise HR (p less than or equal to 0.01), during which state only nifedipine induced a significant increase in frequency. We conclude that at the chosen dosages the hemodynamic and antiischemic effects of isradipine are similar to the effects that occur after nifedipine.
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PMID:Antiischemic and hemodynamic effects of intravenous isradipine, a new calcium antagonist, in coronary heart disease: a comparative double-blind cross-over study with nifedipine. 170 98


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