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)

Detoxification of soman (1,2,2'-trimethylpropyl methylphosphonofluoridate) in the liver was studied in the rat phrenic nerve-diaphragm preparation in situ. Contractions of diaphragm induced by electrical stimulation of the phrenic nerve were continuously recorded. Twitch height depression caused by soman was influenced by the route of application (portal or jugular vein) indicating its rate of detoxification in the liver. Pretreatment with phenobarbital reduced, whereas previous application of tri-O-cresyl phosphate (TOCP) enhanced, effectiveness of soman administered i.p. Possible mechanisms of detoxification and the features of the method are discussed.
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PMID:Phrenic nerve-diaphragm preparation in situ for studying the detoxification of soman in the rat liver. 283 55

The muscle-relaxation reactions of Ca-antagonist (nifedipine) pretreated patients and a control group (5 in each group) were observed after administration of vecuronium bromide using the "priming principle." Twitch depression induced by the "priming dose" of vecuronium bromide (20 micrograms/kg body weight and T4/T1 ratio in the Ca-antagonist-treated patients (35 +/- 13% and 0.42 +/- 0.14%, respectively), was significantly different (P less than 0.01) when compared with the control group (1.2 +/- 2.7% and 0.75 +/- 0.15%). Similarly, the onset time to maximum blockade after the intubating dose of vecuronium bromide (60 micrograms/kg body wt.) was significantly shorter in the nifedipine group (40 +/- 21 s) when compared with the controls (100 +/- 17 s). The duration of the effect observed clinically (until 25% recovery) in the nifedipine group 32.9 +/- 7.3 min versus 25 +/- 8.15 min was enhanced; however, the difference between the treated group and the control group was not significant.
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PMID:[Nifedipine and vecuronium bromide. How does a patient treated with calcium antagonists react to nondepolarizing muscle relaxants? Brief scientific communication]. 286 76

The short elimination half-life of vecuronium suggests it may be delivered more efficiently by continuous infusion than by traditional bolus injections. The objective of this study was to compare manual administration with computer-controlled administration. Anesthesia was induced in 22 patients (American Society of Anesthesiologists [ASA] physical status I and II) with fentanyl and sodium thiopental and maintained with halothane and nitrous oxide in oxygen. Neuromuscular function was assessed at the hypothenar eminence and the adductor pollicis (train-of-four stimulation). A bolus of 0.1 mg/kg of vecuronium was given to obtain 100% twitch depression for tracheal intubation. After twitch height returned to 25% of control, relaxation was maintained by traditional bolus injections (group 1, n = 7), manually controlled continuous infusion (group 2, n = 7), or computer-controlled continuous infusion (group 3, n = 8). In all three groups the desired level of relaxation was 90% twitch depression. Variability of relaxation differed significantly among the three groups (group 1: 10.5%, group 2: 12.4%, group 3: 7.1%). Twitch height was more constant with computer control than with either bolus injections or manual infusion (P less than 0.05). There was no statistically significant difference in the drug requirement (group 1: 1.60 microgram/kg/min, group 2: 1.51 microgram/kg/min, group 3: 1.45 microgram/kg/min). Variability in the mechanomyogram (n = 12) was much higher than in the electromyogram (n = 10). Computer-controlled infusion may be a useful adjunct for the anesthesiologist who desires a stable level of patient relaxation when using short-acting, non-depolarizing relaxants.
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PMID:A comparison of computer-controlled versus manual administration of vecuronium in humans. 289 Jul 19

Interactions between calcium antagonists (CA) and muscle relaxants have been reported however due to the extremely high dosages of CA used in these studies, the clinical relevance of the observed interactions has been questioned. In order to simulate clinical practice--which entails long-term oral treatment and significant reductions in systolic blood pressure--CA were administered to rats orally (by gavage) for 8 days at a dosage that induced a systolic blood pressure decrease of not more than 25 +/- 5 mmHg. Ten groups of six male Sprague-Dawley rats each, body weight (BW) 313 +/- 23 g, were subjected to oral administration of three different CA: nitrendipine (1 mg/kg BW), nisoldipine (1 mg/kg BW), and diltiazem (100 mg/kg BW) or their solvents (control) three times daily by gavage for a period of 8 days. One hour after the last dose of drug or solvent, the rats were anesthetized (pentobarbital 60 mg/kg BW) and mechanically ventilated via tracheostomy. Monitoring included rectal temperature, carotid artery pressure, central venous pressure, heart rate, blood gases, and end-tidal CO2. Evoked train-of-four (T4) twitch tension of the right tibialis anterior muscle was recorded continuously. After equilibration of vital signs and muscle twitch tension, vecuronium (150 micrograms/kg BW) or atracurium (500 micrograms/kg BW) was injected into the internal jugular vein four times at 5-min intervals after twitch tension had totally recovered and T4 fade had disappeared. Twitch depression, duration 90, and onset time of neuromuscular block in CA-pretreated animals were compared to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Atracurium and vecuronium: interaction with three orally administered calcium antagonists in animal experiments]. 289 18

The cardiovascular and respiratory effects of the new inhalational anaesthetic agent isoflurane were investigated in dogs. Anaesthesia was induced with thiopentone after premedication with acepromazine. Isoflurane was administered with nitrous oxide and oxygen by spontaneous ventilation after base line values had been determined. Arterial blood pressure decreased as the concentration of administered isoflurane increased. Isoflurane produced a profound and dose related respiratory depression as measured by the increase in end tidal carbon dioxide levels. Isoflurane administration did not produce any visible muscle twitching.
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PMID:Experimental investigation of the cardiovascular and respiratory effects of increasing concentrations of isoflurane in the dog. 308 81

1. The effects of 2,3-butanedione monoxime (BDM, 0.2-10 mmol/l) have been examined at different temperatures on calcium transients (measured with aequorin) and isometric force in intact bundles of fibres from soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles of the rat and on Ca2+-activated isometric force of mechanically skinned soleus and EDL fibres. Ca2+ release and uptake by the sarcoplasmic reticulum has also been investigated directly on skinned EDL fibres at 1 mmol/l BDM at 23 degrees C. 2. BDM bound calcium with low affinity (KCaBDMapp = 55.9 +/- 4.3 M-1 at 22 degrees C, pH 7.10, ionic strength approximately 155 mmol/l) and did not affect the kinetics and quantum yield of the Ca2+-induced aequorin luminescence. 3. BDM reversibly reduced both force- and Ca2+-dependent aequorin light during the twitch and tetanus of all intact-muscle preparations in a dose-related manner. Twitch responses of soleus fibres were more sensitive to BDM than were EDL fibres. Higher concentrations of BDM were needed to abolish the tetanic force response than the twitch response in both muscle types. 4. The initial rate of rise and the decay rate constants of twitches in both soleus and EDL muscles were increased in the presence of BDM. Accordingly, a higher frequency of stimulation was required to produce fusion of the tetanus. This phenomenon could be explained by the reduced magnitude of the Ca2+ transient. 5. BDM reduced maximal Ca2+-activated force development in mechanically skinned soleus and EDL muscle fibres in a dose-dependent fashion. This depression of force was less sensitive to BDM than were the light transients in intact fibres. Furthermore, BDM affected EDL skinned fibres to a greater extent than soleus skinned fibres, in contrast with its effects on intact fibres. 6. At concentrations of BDM greater than 2.5 mmol/l, BDM significantly decreased the sensitivity of the contractile apparatus to calcium. The relative force-pCa (= -log [Ca2+]) curves for both soleus and EDL skinned fibres were shifted to the right (i.e. to higher calcium concentrations) in a dose-related manner. 7. BDM (10 mmol/l) slowed maximal Ca2+-activated force development of skinned preparations of both fibre types at all temperatures investigated (4-24 degrees C). 8. BDM reduced stiffness in skinned preparations maximally activated by calcium in proportion to the reduction in the isometric force response. BDM also inhibited rigor force of all fibres but only if it was present before the onset of rigor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of 2,3-butanedione monoxime on the contractile activation properties of fast- and slow-twitch rat muscle fibres. 325 25

Despite the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs), the current number of reported cases of poisoning is small. However, with the introduction of 'over-the-counter' preparations of NSAIDs in some countries (e.g. ibuprofen in the UK and USA) an increased incidence of acute poisoning from this group of drugs can be expected. Conventionally, NSAIDs are divided into the following groups based on their chemical structure: arylpropionic acids, indole and indene acetic acids, heteroarylacetic acids, fenamates, phenylacetic acids, pyrazolones and oxicams. Unless NSAIDs are ingested in substantial overdose, acute poisoning with these agents does not usually result in significant morbidity or mortality. In most cases the clinical features are mild and confined to the gastrointestinal and central nervous systems, though acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse and cardiac arrest may complicate severe poisoning. Arylpropionic acid derivatives were thought initially to have a low order of toxicity in overdose but, in addition to anticipated gastrointestinal symptoms, headache, tinnitus, hyperventilation, sinus tachycardia, hypoprothrombinaemia, haematuria, proteinuria and acute renal failure have been described. In addition, drowsiness, coma, nystagmus, diplopia, hypothermia, hypotension, respiratory depression and cardiac arrest have been reported in severe cases of poisoning. Oxyphenbutazone and phenylbutazone are considerably more toxic in overdose. Complications of severe poisoning include coma, convulsions, hepatic dysfunction, acute renal failure, sodium and water retention, haematuria, cardiovascular collapse, respiratory alkalosis, metabolic acidosis, hypoprothrombinaemia and thrombocytopenia. In contrast, indomethacin appears to be much less toxic. In addition to gastrointestinal symptoms, indomethacin taken in overdose induces headache, tinnitus, dizziness, lethargy, drowsiness, confusion, disorientation and restlessness. Only 1 case of acute sulindac poisoning has been reported in the literature. A 16-year-old boy was admitted with hypokalaemia (2.2 mmol/L), transient granulocytosis and 'scanty' haematemesis after ingesting 12 g sulindac. No case of acute tolmetin poisoning have been reported. The fenamates (flufenamic acid, meclofenamic acid, mefenamic acid, tolfenamic acid) are, with the exception of mefenamic acid, not as widely prescribed as other groups of NSAIDs. In overdose, mefenamic acid may result in nausea, vomiting, diarrhoea, muscle twitching, convulsions and coma.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management. 353 13

Contractions of rat extensor digitorum longus (EDL, a fast muscle) and soleus (SOL, a slow muscle) muscles of different ages (1-4 weeks) were recorded in vitro with direct stimulation and at different temperatures (range 35-10 degrees C). Twitch tension in 4-week-old EDL muscle increased in cooling from 35 to 20 degrees C (cooling potentiation); the tension decreased in further cooling below 20 degrees C. This pattern of temperature dependence of twitch tension was seen in fast muscles of all ages (1-4 weeks). Twitch tension in 4-week-old SOL muscle decreased monotonically in cooling from 35 to 10 degrees C (cooling depression). This pattern of cooling depression was not clearly evident in younger SOL muscles. There was a marked hysteresis in the temperature dependence of twitch tension in the 1-week-old SOL muscles. Tetanic tension was depressed by low temperature in both EDL and SOL muscles at 1 week and at 4 weeks of age. Results show that the processes concerned with contractile activation are nearly fully developed in the fast muscle fibers at an early age (1 week), whereas they develop later in the slow muscle fibers.
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PMID:Temperature dependence of contraction characteristics in developing rat muscles. 368 50

1. Physiological properties of motor units in the soleus muscle were studied in anaesthetized cats using intracellular stimulation of motoneurones to ensure functional isolation of single units. The muscle fibres belonging to 6 units were identified by glycogen depletion following prolonged stimulation, permitting analysis of their histochemical profiles and anatomical organization.2. The studied units in soleus were all classed as type S and were extremely resistant to fatigue during prolonged stimulation. Twitch contraction times ranged from 64 to 131 msec (mean 97.1 msec) and tetanic tensions ranged from 3.5 to 36 g (mean 10.5 g). Most units exhibited depression of twitch tension in the wake of a short high-frequency tetanus and few of the units showed any significant degree of post-tetanic twitch potentiation.3. Muscle fibres belonging to single soleus motor units were found to be scattered through territorial volumes occupying a large fraction of the total muscle volume. The available data suggest that different soleus motoneurones may innervate from less than 50 to more than 400 muscle fibres, with an average innervation ratio between 140 and 190 muscle fibres per unit.4. The results were compared with observations on type S motor units in the synergist gastrocnemius, obtained under similar conditions. The evidence suggests that soleus units are not equivalent to the type S units of the mixed gastrocnemius but rather constitute a unique population.
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PMID:Motor units in cat soleus muscle: physiological, histochemical and morphological characteristics. 427 82

The actions of pyridostigmine (Pyr), an anticholinesterase agent, were studied on the acetylcholine (ACh) receptor-ion channel complex and on the electrically excitable membrane of the frog cutaneous pectoris and sartorius muscles and the chronically denervated soleus muscle of the rat. Pyr at concentrations of 0.2-0.4 mM potentiated the indirect evoked muscle twitch and at concentrations greater than or equal to 0.8 mM depressed the indirect twitch with an IC50 of about 2 mM. Twitch depression produced by Pyr was reversed slowly, and after a 60-min wash only 59% of the control muscle twitch had returned. Pyr did not affect either the membrane potential or the muscle action potential. Pyr had several effects at the neuromuscular junction of the frog and rat. It decreased the peak amplitude of the end-plate current (EPC) in a voltage- and concentration-dependent manner. In contrast to diisopropylfluorophosphate, which depresses the EPC amplitude and induces a double exponential decay of the EPC and miniature end-plate current (MEPC), Pyr produced a marked prolongation of the time constants of EPC and MEPC decay while maintaining a single exponential decay. The decrease caused by Pyr of indirect twitch tension, EPC amplitude, and ACh sensitivity indicates mechanisms which limit the number and/or properties of conducting channels. The drug decreased channel conductance and prolonged channel lifetime as revealed by Fourier analysis of ACh-induced end-plate current fluctuations. An altered form of the conducting species induced by Pyr appears to be responsible for either the apparent agonist-induced depolarization or its ability to increase the affinity of ACh for its recognition site. Pyr was also found to inhibit the binding of ACh and alpha-bungarotoxin to receptor-rich membrane from the electric organ of Torpedo nobiliana, and to have a higher affinity for the receptor than for the ion channel binding sites. These actions are distinct from acetylcholinesterase inhibition caused by the agent. Strong evidence suggests that the direct influences of the agent on neuromuscular transmission involve at least three distinct, although possibly interacting, mechanisms: (a) a weak agonist action, (b) the formation of desensitized receptor-complex intermediates, and (c) the alteration of the conductance properties of active channels.
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PMID:The nature of the interactions of pyridostigmine with the nicotinic acetylcholine receptor-ionic channel complex. I. Agonist, desensitizing, and binding properties. 632 55


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