The opposing physiological effects of high pressures and inert gases.

The physiological effects on mammals of elevated pressures (approximately 100 atmospheres) must be considered in the context of the inert gases breathed. The most striking effect of pressure per se is a central hyperexcitability manifest at first by trembling of the entremities and finally by convulsions. Paralysis and death occur at higher pressures. The primary effects of the inert gases breathed are inert gas narcosis and general anesthesia. The exciting effects of pressure per se and the depressive effects of the inert gases tend to oppose each other. Thus consciousness may be restored to anesthetized mice by raising the pressure, and conversely the threshold pressure that causes convulsions is elevated in the presence of anesthetics. These mutually antagonistic effects can be rationalized in terms of model which proposes that both anesthetics and pressure non-specifically perturb thelipid bilayer regions of neutral membranes. This model is termed the critical volume hypothesis. Anthesthetics dissolve in and expand these lipid bilayer regions, while pressure causes mechanical compression. Expansion leads to anesthesia and compression to convulsions if a critical degree of change is achieved. At elevated partial pressures of inert gas the gas-induced expansion is opposed by the compression of pressure per se. With very insoluble gases, such as helium, this expansion is so small that net compression results and the effects of helium differ little from those of pressure per se. With more soluble gases, such as nitrogen, net expansion results in inert gas narcosis and anesthesia. The critical volume hypothesis enables "safe" mixtures of "expanding" and "compressing" gases to be defined. These enable higher pressures to be better tolerated by mammals.     

Catecholamines in the rat brain during hypoglycemic convulsions and coma

The purpose of the study was to investigate the relation between the catecholamines: noradrenaline and dopamine in the rat brain on one hand and hypoglycemic convulsions and coma on the other. Concentrations of noradrenaline in the hypothalamus, brain stem and cerebral cortex were decreased during hypoglycemic convulsions and were lower during coma than those during convulsions. Dopamine concentration in the striatum was decreased during convulsions and coma. It was shown that the decrease in concentration of catecholamines was a result of hypoglycemia but not of insulin action itself. Clonidine- alpha 2 agonist accelerated occurrence and prolonged duration of hypoglycemic convulsions. Haloperidol-dopamine receptor blocker had no effect on the time of occurrence or duration of convulsions and coma. The results indicate that noradrenaline may exert an inhibitory influence on hypoglycemic convulsions. No evidence has been provided to support involvement of dopamine in the control of hypoglycemic convulsions and coma.     

A BARBITURATE ANTIDOTE—Use of Methylethylglutarimide in Barbiturate Intoxication and in Terminating Barbiturate Anesthesia

Methylethylglutarimide was administered to 488 patients ranging in age from 7 to 89 years, in a study on sleep-reversal after harbiturate anesthesia. Sodium surital or sodium pentothal were the barbiturates used. The drug was administered intravenously in doses varying from 25 to 200 mg. Dosage below 25 mg. was found to be ineffective. Almost all patients showed signs of awakening as evidenced by the return of corneal and conjunctival reflexes, the opening of the eyes, and stirring or moving about. Many responded to questioning. Almost all showed evidence of greater responsiveness within five minutes. No untoward reactions were noted. No convulsions were produced.Five patients ranging in age from 24 to 70 years were treated for barbiturate poisoning with Mikedimide® given intravenously in doses varying from 550 mg. to 1950 mg. All recovered consciousness within 30 minutes to an hour. No convulsions were produced.While it is not known whether Mikedimide is a direct barbiturate antagonist, or whether it is an analeptic, it appears to be a useful drug in reversing the respiratory depression and the cerebral depression produced by harbiturate intoxication and barbiturate anesthesia.     

Underreporting of AIDS cases in Canada: a record linkage study.

To estimate the rate of underreporting of AIDS (acquired immune deficiency syndrome) to the Federal Centre for AIDS (FCA), in 1988 the initials, date of birth and place of residence of 66 patients with AIDS known to the Toronto Sexual Contact Study (TSCS), 65 patients with AIDS known to the Vancouver Lymphadenopathy-AIDS Study (VLAS) and other participants in both studies who did not have AIDS were sent to the Bureau of Epidemiology and Surveillance, FCA. The FCA conducted a manual record linkage to link these data to the national registry of reported cases. The rate of underreporting was 12% (8/65) for the VLAS and 18% (12/66) for the TSCS. The specific diagnosis was not related to the rate of underreporting. For the TSCS the rate of underreporting had increased from 0% in 1983-84 to 44% in 1987-88 (p = 0.001). Differences in the observed rates of underreporting between the two studies are likely the result of differences in the reporting responsibilities of physicians involved in the studies.     

Two-helper-strain co-culture system: a novel method for enhancement of 2-keto-l-gulonic acid production

A novel two-helper-strain co-culture system (TSCS) was developed to enhance 2-keto-l-gulonic acid (2-KLG) productivity for vitamin C production. Bacillus megaterium and B. cereus (with a seeding culture ratio of 1:3, v/v), used as helper strains, increased the 2-KLG yield using Ketogulonigenium vulgare compared to the conventional one-helper-strain (either B. cereus or B. megaterium) co-culture system (OSCS). After 45 h cultivation, 2-KLG concentration in the TSCS (69 g l^?1) increased by 8.9 and 7 % over that of the OSCS (B. cereus: 63.4 g l^?1; B. megaterium: 64.5 g l^?1). The fermentation period of TSCS was 4 h shorter than that of OSCS (B. cereus). The increased cell numbers of K. vulgare stimulated by the two helper strains possibly explain the enhanced 2-KLG yield. The results imply that TSCS is a viable method for enhancing industrial production of 2-KLG.     

A microwave-hyperthermia model of febrile convulsions

While convulsions associated with fever represent a serious problem in pediatric medicine, conventional animal models of febrile convulsions suffer numerous technical limitations. A microwave-hyperthermia model that eliminates these problems was tested. Microwave energy was used to increase the core temperature of 13- and 17-day-old rats, resulting in convulsions similar to febrile convulsions in human infants. Rats were irradiated for 10 min in circularly polarized waveguides at 918 MHz, CW (average SAR = 9.4 W/kg at 13 days and 18.0 W/kg at 17 days as determined by twin-well calorimetry). Day 17 irradiated rats were less susceptible to convulsions than were day 13 irradiated rats, indicating an age-dependent decline in susceptibility. Contrary to findings of earlier models using infrared or hot-oven heating, convulsions induced with microwave hyperthermia impaired neither brain growth nor subsequent performance during behavioral testing. Simultaneous measurement of brain and rectal temperatures during microwave irradiation revealed differential heating rates that favor thermal homeostasis in brain tissue.     

Spermine and spermidine polyamines in the brain and liver of rats under hyperoxic action

The effect of hyperbaric oxygenation (6 atmospheres) on the content of polyamines spermine and spermidine in the rat brain and liver was studied. A decrease of the spermidine content in the brain and liver during oxygen convulsions and four hours after decompression was revealed. The spermine content in the brain during oxygen convulsions decreased as well, but four hours after decompression it increased significantly not eaching the control level. The spermine content in the liver failed to alter during oxygen convulsions, but the next four hours rose sharply. The role of polyamines in the regulation of protein biosynthetic processes under hyperoxia is discussed.     

Nonthermal electromagnetic fields and estimation of the probable development of the convulsive syndrome

Development of the convulsive syndrome occurs during exposure to electromagnetic fields (EMFs) during physiotherapy and under conditions of professional work. Some researchers believe that EMFs may have medical effects during the treatment of the epilepsy syndrome. Some publications have noted the development of epileptic convulsions in experiments using EMF exposures at various frequencies. Four conditions that may promote the development of convulsions upon EMF exposure are considered.     

Abnormal motor activity during anaesthesia in a dog: a case report

Seizures or convulsions that occur during anaesthesia in veterinary patients are infrequently reported in the literature. Consequently, the incidence of such events is unknown. Several drugs commonly used in clinical veterinary anaesthesia have been shown to induce epileptiform activity in both human clinical patients and experimental candidates. The present case report describes convulsions in a four-year old male Bernese mountain dog during maintenance of anaesthesia with isoflurane after premedication with acepromazine and methadone followed by co-induction with propofol and ketamine. The dog had no history of previous convulsions. The use of several sedative and anaesthetic drugs makes it difficult to find one single causative pharmaceutical.     

Na, K-ATP-ase and acetylcholinesterase activity of the membrane structures of the rat brain and spinal cord during the seizure process]

The activity of ATP-ase and acetylcholinesterase (AChE) in crude mitochondrial fraction (CMF) and microsomal fraction of rat brain cortex and the spinal cord was studied in clonic seizures evoked by electroshock and 5 min after them. Inhibition of the Na, K-ATP-ase activity of the CMF of the brain at the clonic phase of convulsions and an increase in the activity of this enzyme in all the fractions of the tissues under study at the postconvulsive period were revealed. The activity of Ca-ATP-ase in the CMF of the brain increased during the convulsions and decreased at the postconfulsive period. The activity of Mg-ATP-ase remained unchanged. The AChE activity, as a rule increased during the convulsions, and grew even more during the postconvulsive period; the spinal cord tissue displayed a reduction of the activation effect. A possibility of structural reconstructions in the excitable neuron membranes during the convulsive activity is discussed.     

The effect of multiple audiogenic seizures upon the sleep organization in rats

The organization of sleep during and after frequentative convulsions, consisting of 2, 3, or 5 comparatively rare seizures (following one another with a 90-minute interval) or of 3, 5 or 9 comparatively frequent seizures (following one another with a 45-minute interval) of generalized tonic-clonic character in Krushinskii-Molodkina strain rats with inherited predisposition to audiogenic convulsions, was studied. In frequentative convulsions with rare seizures, between separate seizures, passive wakefulness (75.2 +/- 4.6% time) prevailed under low (24.8 +/- 4.3%) slow-wave sleep and full absence of fast-wave sleep. In rats under frequentative convulsions with frequent seizures, in interictal period, only passive wakefulness was observed under reduction of slow-wave sleep and fast-wave sleep, i.e. total sleep deprivation. Minimal latensy of first episodes of the slow-wave sleep after frequentative convulsions was 59.9 +/- 10.8, and of fast-wave sleep: 158.2 +/- 13.4 min. First episodes of slow-wave sleep and fast-wave sleep had normal structure, though they were lesser and shorter than in control experiments. In spite of long-lasting (up to 7 hrs) absence of slow-wave sleep during seizure and prolonged (8.5 hrs) reduction of fast-wave sleep with no subsequent compensatory increase, these conditions occurred in the wakefulness-sleep cycle during 12-hour reconstruction after convulsions. The reconstruction period after frequentative convulsions was characterized by increase in general share of wakefulness and reduction of total slow-wave and fast-wave sleep as compared with control data. Paroxysmal status seems to disorganize work of the brain somnogenic structures. The function of systems responsible for slow-wave sleep are affected to a lesser extent, but disorganization of the system responsible for fast-wave sleep is more significant and associated with mechanisms of starting the phase of sleep in the first place.     

Systemic and regional hemodynamics during audiogenic convulsions in rats genetically epilepsy-prone]

Changes in systemic and regional hemodynamic during sound-induced convulsions were measured with microsphere technique in genetically epilepsy-prone rats of Krushinsky-Molodkina (KM-rats) strain. Blood pressure increased from 103 till 178 mm Hg and cardiac index rose from 27.3 till 49.3 ml/min/100 g b. w. during convulsions. Blood flow was increased in the brain and in the heart by 140-700%, whereas in most of internal organs it was decreased by 40-94%.     

Failure of phenobarbitone to prevent febrile convulsions.

One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage.     

Effects of repeated injection of cyclosporin A on pentylenetetrazol-induced convulsion and cyclophilin mRNA levels in rat brain

To investigate the relationship between the immune system and convulsions in an animal model, we examined the effects of repeated administration with the immunosuppressant cyclosporin A on pentylenetetrazol (PTZ)-induced convulsions and the changes in the mRNA expression of its binding protein cyclophilin in the rat brain. The consecutive administration of cyclosporin A (5 mg/kg s.c., 14 days) significantly aggravated the severity of convulsions induced with PTZ 75 mg/kg i.p. Furthermore, it down-regulated the levels of cyclophilin mRNA in several brain regions and inhibited the PTZ-induced increase of hippocampal cyclophilin mRNA. Compared with the group without PTZ pretreatment or the group treated with chronic vehicle administration after the PTZ-preinjection, chronic cyclosporin A administration after the initial injection of PTZ apparently aggravated convulsions after the second PTZ injection. Interestingly, the increase in hippocampal cyclophilin mRNA observed after a single PTZ injection was not found after the second PTZ injection in the group with PTZ pretreatment. Therefore, these findings suggest that cyclosporin A administered peripherally can affect the central nervous system, and that an immune response associated with the first convulsive episode plays a key role in severity during subsequent attacks.     

Altered response to GABAergic agents following electro and chemo convulsions in mice.

Effects of GABAergic agents and that of electroconvulsive shock (ECS) treatment were studied on bicuculline and picrotoxin (PTX)-induced convulsions in mice. Neither acute nor chronic ECS had any significant effect on bicuculline-induced convulsions, whereas the latency for PTX-induced convulsions was delayed by both acute and chronic ECS. Baclofen treatment delayed significantly the latency for PTX-induced convulsions in animals which were subjected to both acute and chronic ECS, whereas in bicuculline-induced convulsions, it shortened the latency of convulsions 24 hr after acute ECS. Progabide delayed the bicuculline-induced convulsions except in the case of 24 hr after acute ECS and PTX-induced convulsions except in the case of animals treated chronically with ECS. Fengabine showed no significant effect on bicuculline-induced convulsions. However, on PTX-induced convulsions, the latency was delayed in animals not subjected to ECS and in those subjected to chronic ECS. The possible explanations for the alterations in the effect of GABAergic agents following electro and chemo convulsions are (i) differences in the nature of antagonism by bicuculline and PTX, (ii) alterations in receptor sensitivity or number, and (iii) alterations in the levels of endogenous neurotransmitters, the latter two resulting as a result of acute or chronic ECS.     

Effects of dieldrin, picrotoxin and Telodrin on the metabolism of ammonia in brain

1. Increases in the concentrations of lactic acid and pyruvic acid in rat brain during acute dieldrin poisoning are associated with hyperactivity of the brain, whereas an increase in the cerebral alanine concentration occurs before the convulsions. Throughout the dieldrin-induced seizure pattern, fluctuations in the concentration of brain ammonia are out of phase with the actual convulsions. 2. Increases in the concentrations of alanine, ammonia and lactic acid in rat brain accompany picrotoxin-induced seizures; there is no increase in the concentration of glutamine. These changes are consistent with the inhibition of glutamine synthesis. 3. In addition to previously reported changes in the concentrations of intermediary metabolites of the brain after the administration of Telodrin (Hathway & Mallinson, 1964), increases have now been found in the alanine and lactic acid concentrations. Since increases in the alanine and glutamine concentrations occur before the convulsions, liberation of ammonia also occurs before the onset of convulsions and throughout their course. Ammonia-binding mechanisms later become inadequate and free ammonia accumulates in cerebral tissues. 4. An increase in the pyruvic acid concentration of the brain after the intraperitoneal injection of either dieldrin or Telodrin is endogenous in origin. 5. The parenteral administration of a small dose of glutamine increases the cerebral concentrations of alanine and glutamic acid. Some animals previously treated with glutamine resisted Telodrin convulsions. 6. Mechanisms for the disposal of ammonia liberated in brain are discussed.     

The time course of brain and blood catecholamines, catechol O-methyltransferase, and amino acids in rats convulsed by oxygen at high pressure.

The time course of changes in blood and brain catecholamines, catechol O-methyltransferase (COMT), ammonia, and amino acids leading to convulsion by high pressure oxygen breathing (OHP) in rats has been investigated. Brain catecholamines were suppressed by OHP. They changed in phase with brain COMT concentration and consequently were not due to the action of this degrading enzyme. Convulsive actions seem not to be influenced by brain catecholamine concentration. Blood adrenaline concentrations are, however, significantly elevated both prior to and during convulsions. In both brain and blood, ammonia concentration increases, glutamate decreases, and glutamine-aspargine increases. It is proposed that the efficacy of the glutamate-glutamine ammonia buffering system in blood and brain is important in the prevention of the onset of convulsions but that when brain gamma-aminobutyric acid is depressed to critical levels, convulsions result.     

Renal functions following hyperbaric oxygen toxicity in conscious rats

The after-effects of renal function were studied in rats exposed to hyperbaric oxygen (HBO) at either 4.8 ATA for 60 min or 6.8 ATA until the onset of convulsions. Only the rats which suffered from HBO convulsions were found to have alterations in renal function. It was observed that 4 hr after convulsions, there was a decrease in urinary excretion of urea and creatinine, which resulted in an elevation of blood urea nitrogen (BUN) and creatinine. Clearances of inulin and p-aminohippuric acid showed a decrease in the glomerular filtration rate and effective renal blood flow 4 hr after HBO convulsions. These parameters nearly returned to normal in 24 hr after convulsions. The renal handling of a large volume of infused saline was also retarded 4 hr after HBO convulsions, but by the end of 24 hr after HBO convulsions, it was much improved. Therefore, it was concluded that the renal function was altered after HBO convulsions, but nearly recovered in 24 hr.     

The Wakayama epileptic rat (WER), a new mutant exhibiting tonic-clonic seizures and absence-like seizures.

A new mutant, the Wakayama epileptic rat (WER), exhibiting both spontaneous absence-like behavior and tonic-clonic convulsions, was identified in a colony of Wistar rats. To determine clear seizure characteristics of this mutant strain, we analyzed the mode of inheritance of the convulsion and observed patterns of electroencephalogram (EEG) during the seizures. F1 progeny were produced between the founder male and normal females of the same colony. Animals were monitored through the inbreeding course to analyze genetic control of epileptic behavior. EEGs were recorded using affected animals in the F3-4 and post F13 generations. After the F2 generation, affected rats spontaneously exhibited both absence-like immobile behavior and tonic-clonic convulsions. The absence-like seizures were characterized by motor arrest and head droop. The tonic-clonic convulsions began with neck and forelimb clonus, wild jumping/running, and opisthotonic posturing, and evolved to tonic, then clonic convulsions. Most convulsion onsets occurred between 25-70 days of age. Mating experiments revealed that 0%(0/18) of the animals in F1, 10%(3/26) in F2, 17%(1/6) in backcross progeny and 86% (100/116) in progeny of crosses between epileptic rats showed tonic-clonic convulsions. Ictal cortical EEGs were characterized by 4-6 (5.1 +/- 0.4, mean +/- SD) Hz spike-and-wave complexes in the absence-like seizures and by low-voltage fast waves in the tonic-clonic convulsions. This new mutant rat spontaneously exhibited both absence-like and tonic-clonic seizures. The tonic-clonic seizure was inherited as an autosomal recessive trait with 86% incidence. Thus, the new mutant rat may become a useful model for studying human inherited epilepsies.