Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D01453 (caffeine)
 21,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhabdomyolysis without renal failure was noted after suicidal ingestion of 29 tablets of Spalt N containing 7.25 g of acetaminophen, 7.25 g of phenazone and 1.45 g of caffeine by a 29 year-old weighing 73 kg. The maximum serum creatine kinase was 1920 U/L, serum myoglobins were 49 to 167 ng/mL. Acetaminophen, phenazone and caffeine were quantified and identified in serum by gas chromatography and gas chromatography/mass spectrometry. It is suggested that rhabdomyolysis might have been caused by caffeine.
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PMID:Rhabdomyolysis after suicidal ingestion of an overdose of caffeine, acetaminophen and phenazone as a fixed-dose combination (Spalt N). 174 57

We investigated German Landrace pigs from a special breeding program producing animals which were of three genotypes with respect to in vivo halothane inhalation (i.e., exposure to 3% halothane for up to 3 min): (1) Hal NN, i.e. homozygous normal exhibiting no response; (2) Hal Nn, i.e. heterozygous, also responding with a normal reaction; and (3) Hal nn, i.e. homozygous for the 'halothane gene n' which exhibited signs of malignant hyperthemia (MH). Additional characteristics of these three groups of animals were studied using accepted methodology from the fields of animal science, clinical testing, and food science. The following characteristics of group (2) and (3) were different from those of the normal animals: 1) creatine kinase levels; 2) in vitro sensitivities of muscles to caffeine and halothane administration (contracture test) and 3) postmortem muscle properties. In humans, results of the in vitro contracture test are indicative of susceptibility to MH. In humans, MH is considered to be inherited as an autosomal dominant trait. Similarly the results of the in vitro contracture test described here also indicate that MH is inherited as an autosomal dominant trait in German Landrace swine.
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PMID:Characterization of swine susceptible to malignant hyperthermia by in vivo, in vitro and post-mortem techniques. 185 98

This study provides the first comprehensive characterisation of the calcium (Ca) homeostasis defects found in muscle and lymphocytes of a malignant hyperthermia (MH)-susceptible dog. Novel findings regarding this dog are reported, compared to controls. First, a canine stress syndrome occurs, analogous to the porcine stress syndrome; susceptibility can be identified by exercise challenge testing. Secondly, caffeine causes Ca release from muscle sarcoplasmic reticulum in a greater amount and at a greater rate. Thirdly, there is a compensatory increase in Ca sequestration by sarcoplasmic reticulum. Fourthly, lymphocytes have lower cytosolic-free Ca and a greater ability to prevent Ca increase. Halothane increases Ca by a greater amount and rate. Fifthly, muscle is more resistant to the contracture-producing effects of caffeine, as occurs in the non-rigid variant of MH susceptibility in man. This resistance, despite increased caffeine-induced release through the Ca channel, may be attributable to increased Ca sequestration by sarcoplasmic reticulum. Finally, erythrocyte osmotic fragility and creatine kinase tests fail to distinguish between the MH-susceptible dog and controls.
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PMID:Canine stress syndrome/malignant hyperthermia susceptibility: calcium-homeostasis defect in muscle and lymphocytes. 230 Jul 6

Signs of malignant hyperthermia, including progressive increases in PaCO2, skin temperature and heart rate, and elevated serum levels of potassium, inorganic phosphate, and creatine kinase, were identified in a halothane-anesthetized horse. Treatment was discontinuing halothane administration, applying ice and cold fluids, and hyperventilating with 100% oxygen. After an initial recovery, bilateral hindlimb myopathy and pigmenturia developed. The myopathy resolved after treatment with oral dantrolene, IV fluids, and hydrocortisone. Results of caffeine-halothane challenge, using semimembranosus muscle collected 2 weeks after the episode, were considered within normal limits for horses. The intraoperative abnormalities were evidently predictive of postanesthetic myopathy but the cause in this horse remained unclear.
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PMID:Postanesthetic equine myopathy suggestive of malignant hyperthermia. A case report. 260 79

During the last 4 years different diagnostic procedures for the detection of malignant hyperthermia (MH) susceptibility have been used at the authors' clinical unit; this study was designed to compare the results of these tests. PATIENTS AND METHODS. Since March 1983, 158 patients have been referred for the following reasons: group A: probands (n = 17) who had had symptoms of MH during anesthesia; group B: patients of probands (n = 48) if the latter were not tested because of age (n = 24) or death (n = 2); group C: relatives from MH families (n = 86); group D: patients (n = 5) who developed fever during stress and/or physical activity (n = 3), had myotonia (n = 1), or developed rhabdomyolysis during intensive care (n = 1); group E: controls (n = 2). Two static halothane and two static caffeine tests according to the European protocol were performed in all patients (n = 158). Histological examinations of skeletal muscle (fixed in glutaraldehyde, stained with hematoxylin-eosin, Gieson, and toluidine blue) were done in the first 100 patients; all specimens were scored by the same investigator (E.S.). Score 0: normal; 1: increased number of sarcolemma cores; 2: 1+cores forming groups; 3: 1+2+fiber degeneration; 4: specific changes-myopathies. Plasma levels of creatine kinase (CK) were determined in the first 50 patients. Complete neurological examinations, including electromyography (EMG), were done in ten patients who had increased CK levels as well as histological scores of 3 or 4 (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Malignant hyperthermia in Austria. II. A comparison of the results of diagnostic test procedures]. 341 55

A 23-year-old man with "myopathy with tubular aggregates" had suffered from exercise-induced muscle cramps for 1 year. His general and neurological findings were normal. Laboratory investigations were within normal limits except for a slightly elevated serum creatine kinase level. Muscle biopsy showed some small angular fibres and scattered type 2B fibres with prominent tubular aggregates originating from the sarcoplasmic reticulum. Since the muscle fibres contracted at a lower concentration of caffeine, increased muscle fibre sensitivity to caffeine is probably related to muscle cramps in this disorder. Tubular aggregates are then secondarily formed in the muscle fibres.
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PMID:A case of "myopathy with tubular aggregates" with increased muscle fibre sensitivity to caffeine. 365 46

The pathogenesis of the calcium paradox has not been established. In calcium-free perfused hearts, caffeine, which releases calcium from the sarcoplasmic reticulum, causes severe myocardial injury, with creatine kinase (CK) release and contraction band necrosis similar in many respects to the calcium paradox. It has been postulated that contracture, initiated by a small rise in intracellular calcium, may cause sarcolemmal injury in both the calcium paradox and caffeine-induced myocardial injury. The present study was initiated to determine whether interventions which modulate caffeine-induced contracture will also correspondingly alter cellular injury. The effects of caffeine dose, procaine, extended calcium-free perfusion, elevated potassium, temperature, and increasing intracellular sodium on caffeine-induced contracture were examined in Langendorff-perfused adult rat hearts. Caffeine-induced contracture at 22 C increased over a dose range of 5-40 mM caffeine. Procaine, which inhibits caffeine-induced calcium release at doses between 5 and 20 mM, progressively reduced contracture caused by addition of 20 mM caffeine at 22 C. Hearts perfused with calcium-free solution containing 16 mM K+ showed a reduction in caffeine-induced contracture. Extended calcium-free perfusion (20 minutes) at temperatures from 18 to 37 C resulted in a progressive reduction of caffeine-induced contracture. Each of these interventions was also found to inhibit caffeine-induced injury at 37 C. Low temperature was found to have complex effects. Hypothermia enhanced caffeine contractures but also protected hearts from cell separations and CK release. Increasing intracellular sodium was found to enhance caffeine-induced contracture at 37 C. There was a direct correlation between measured intracellular sodium levels and the magnitude and duration of caffeine-induced contracture. These results demonstrate a direct correlation between the magnitude of contracture and myocardial injury in calcium-free hearts. It is proposed that contracture is the primary mediator of sarcolemmal membrane injury in hearts with intercalated disks weakened by prior calcium-free perfusion.
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PMID:Modification of caffeine-induced injury in Ca2+-free perfused rat hearts. Relationship to the calcium paradox. 370 96

Canatoxin is a toxic protein isolated from Canavalia ensiformis seeds. It induces death preceded by convulsions of spinal cord origin and also produces in vitro aggregation of platelets in rabbit, human and guinea-pig plasma. The aggregating effect is dose-dependent at nanomolar concentrations. Rabbit platelets pretreated with canatoxin became refractory to a second exposure to this protein or to collagen, but were still responsive to ADP, Paf-acether or arachidonic acid. [14C]-5-hydroxytryptamine was released from pre-labelled platelets on stimulation with canatoxin. Washed rabbit platelets, but not thrombin-degranulated ones, aggregated on stimulation with canatoxin provided that fibrinogen was added before the toxin. Canatoxin's pro-aggregating activity was inhibited by mepacrine, EDTA, caffeine, prostacyclin, adenosine monophosphate and also by the ADP scavenger system, creatine phosphokinase/creatine phosphate. Furthermore, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW 755C), eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) were potent inhibitors of canatoxin-induced aggregation. In contrast, no inhibition was seen with indomethacin. The data indicate that canatoxin is mainly a release-reaction-promoting agent, being devoid of any direct aggregating activity. Thus the aggregation is totally dependent on the release of ADP. Furthermore, canatoxin-induced platelet activation is probably dependent on platelet phospholipase A2 and lipoxygenase activity but is not dependent on cyclo-oxygenase products or the release of Paf-acether.
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PMID:Platelet release reaction and aggregation induced by canatoxin, a convulsant protein: evidence for the involvement of the platelet lipoxygenase pathway. 391 94

Seventy-seven patients who developed masseter muscle rigidity (MMR) after receiving succinylcholine to facilitate tracheal intubation were evaluated for malignant hyperthermia (MH) susceptibility by in vitro halothane and caffeine contracture tests. Thirty-nine patients were diagnosed as MH-susceptible. Neither age, sex, nor type of surgery or anesthesia distinguished MH-susceptible from nonsusceptible patients. Two susceptible and two nonsusceptible patients had evidence of a myopathy. Fifty-two patients had serum creatine phosphokinase (CPK) levels measured in the perioperative period. Although all values were above normal, CPK values equal to or greater than 20,000 IU within 24 hr of trismus (in the absence of myopathy) were observed in six of 30 patients diagnosed as MH-susceptible, but were found in none of the nonsusceptible patients. Considering the high percentage of patients exhibiting MMR that are indeed susceptible to MH (approximately 50%) compared to estimates of MH in the population as a whole (approximately 0.005%), MMR should be considered a presumptive sign of MH. Perioperative CPK values greater than 20,000 IU are highly suggestive of MH susceptibility. Patients exhibiting MMR should be evaluated for MH susceptibility and myopathies. Succinylcholine should be avoided for subsequent anesthetics in patients with a history of MMR.
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PMID:Masseter muscle rigidity and malignant hyperthermia susceptibility. 394 3

Hearts depleted of extracellular calcium become susceptible to injury caused by repletion of extracellular calcium (calcium paradox). It has been suggested that calcium-free perfusion causes weakening of intercalated disks and that the physical stress of contracture may cause sarcolemmal membrane rupture and creatine kinase (CK) release. To further investigate this hypothesis, the effects of caffeine on contracture, cellular morphology, and CK release were studied in control and calcium-free perfused isolated rat hearts. Control hearts perfused with 2.5 mM calcium retained normal ultrastructure for long periods of perfusion. Calcium-free hearts perfused for 12 minutes developed separations of fascia adherens portions of intercalated disks but retained intact nexus junctions. Hearts subjected to 5-minute calcium-free perfusion, followed by calcium repletion, developed a massive CK release and extensive contraction band necrosis (calcium paradox). Ten millimolar caffeine, which causes rapid calcium release from sarcoplasmic reticulum (SR), produced contracture, but not CK release, from control hearts perfused with medium containing 2.5 mM calcium. In calcium-free perfused hearts, caffeine caused sudden CK release accompanied by contracture, development of contraction bands, wide separations of cells at intercalated disks, and sarcolemmal membrane injury. Caffeine-induced injury occurred despite 3 mM amobarbital inhibition of mitochondrial respiration. Hearts perfused with caffeine in the presence of calcium relaxed when made calcium-free and did not release CK. Addition of caffeine following calcium-free perfusion at 22 C, which protects the heart from the calcium paradox, produced a rapid, transient contracture. These results are compatible with the hypothesis that myocardial cell injury in calcium-free hearts is not dependent on repletion of extracellular calcium or mitochondrial function, but can result from contracture following caffeine-induced release of intracellular calcium from the SR.
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PMID:Caffeine-induced myocardial injury in calcium-free perfused rat hearts. 396 37


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