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Biomedical subjects

P Lomax

Publications and source records attributed to P Lomax.

At least 37 records · Page 2Linked to original sources
PubMed1984

The effect of spontaneous seizures on pentylenetetrazole and maximum electroshock induced seizures in the Mongolian gerbil.

The seizure sensitive Mongolian gerbil, a genetic model of epilepsy, has been used to investigate the effects of prior spontaneous seizures on the threshold for pentylenetetrazole (PTZ) and maximum electroshock (MES) induced convulsions. In animals which had spontaneous epileptic seizures prior to testing the threshold for PTZ induced convulsions was raised compared to non-seized animals. This inhibitory effect of a spontaneous seizure was not observed for MES convulsions. Pretreatment with naltrexone, an opioid antagonist, attenuated the post-ictal inhibitory effect on PTZ induced convulsions. It is concluded that a spontaneous seizure in the epileptic gerbil leads to non-specific post-ictal inhibition of seizure sensitivity. Endogenous opioids may exert a modulatory action in mediating this phenomenon.

Animals↗
PubMed1984

Neuropeptides: a role as endogenous mediators or modulators of epileptic phenomena.

As more small peptidergic components of the central nervous system are isolated, their role in disease states is being investigated. Several of these neuropeptides, especially the opioidlike peptides, adrenocorticotropic hormone, and some hypothalamic releasing factors, have been found to alter neuronal excitability. This finding has led to the proposal that these peptides may play a role in the pathogenesis of the epilepsies. We tested this hypothesis in a genetic model of epilepsy. At nontoxic doses, several exogenously administered peptides had anticonvulsant properties, while others were proconvulsant. The most potent anticonvulsant was the opioidlike peptide beta-endorphin. Its effect was similar to that of the opioid alkaloids. Using the potent antagonist naloxone hydrochloride to block possible endogenous opioid-like peptides, we found no effects on seizures in naive animals. Naloxone did alter postictal events, however, by partially blocking the postictal refractoriness to further seizures. We speculate that one possible role for the endogenous opioid peptides may be to limit the spread of seizures or to modulate postictal susceptibility to further seizures. Naloxone was effective in this model only after stressful situations occurred that modified the seizures and presumably induced a release of endogenous opioidlike peptides. Support for this hypothesis from other epilepsy models is discussed. Other peptidergic systems may also be active in various epileptic models, and the current understanding of their roles is reviewed.

Adrenocorticotropic Hormone↗
PubMed1984

Role of the gamma-aminobutyric acid receptor-ionophore complex in seizure disorders.

The possibility of a role for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in seizure disorders has been strengthened by biochemical studies showing that various nervous system depressant drugs can modulate GABA receptor binding in vitro. In particular, two classes of anticonvulsant agents, the benzodiazepines and the barbiturates, have modulatory receptor sites on the GABA receptor-ionophore protein complex of the postsynaptic membrane. Furthermore, it is well established that direct block of GABA function causes seizures and that augmentation of GABA function can protect against seizure activity. Direct evidence for altered GABA synaptic markers has been obtained in some animal models of epilepsy, as well as in human focal epilepsy. We present preliminary evidence for a deficit in benzodiazepine receptor binding in the midbrain of seizure-susceptible Mongolian gerbils. These data would be consistent with an impairment of GABA-mediated inhibitory synaptic transmission that contributes to susceptibility to the genesis or spread of seizures in some kinds of epilepsy.

Animals↗
PubMed1984

Similar anticonvulsant, but unique, behavioural effects of opioid agonists in the seizure-sensitive Mongolian gerbil.

Opioid agonists were used to investigate the modulation of seizures mediated by mu, kappa and delta opiate receptors in the seizure-sensitive Mongolian gerbil. Morphine (1.0-25 mg/kg, s.c.) were used as prototypic agonists for mu, kappa and delta opiate receptors. Each opioid decreased the incidence and severity of the seizure as compared to control values. The anticonvulsant effects of morphine (10 mg/kg, s.c.) and ketocyclazocine (0.5 mg/kg, s.c.) were reversed by naloxone (1.0 mg/kg, s.c.), while the anticonvulsant effects of N-allylnormetazocine (2 mg/kg, s.c.) were not significantly changed by naloxone. Additionally, abnormal behavior was observed following administration of the opioids. Morphine (10 mg/kg, s.c.) produced excitation and hyperresponsiveness with intermittent cataleptic-like states. Ketocyclazocine (10 mg/kg, s.c.) predominantly produced a stuporous, immobile state, accompanied by some loss of posture. N-allylnormetazocine (10 mg/kg, s.c.) produced ataxia and stereotypic side-to-side head nodding . Naloxone was able to reverse the behavioral effects produced by morphine and ketocyclazocine but not those produced by N-allylnormetazocine. The data presented are consistent with earlier studies which demonstrated the anticonvulsant effects of beta-endorphin in the gerbil. This study further suggests that opioids have a protective role against seizure activity in the gerbil and the opioid anticonvulsant effect is not specific to one type of opioid agonist.

Animals↗
PubMed1984

Opiate receptor binding in the brain of the seizure sensitive Mongolian gerbil (Meriones unguiculatus).

Opiate receptor binding was studied in seizure sensitive (SS) and seizure resistant (SR) strains of the Mongolian gerbil. Cryostat sections of the brain were labeled with [3H]-dihydromorphine, subjected to autoradiography and analysed by microdensitometry. SS gerbils, prior to seizure induction, demonstrated overall greater brain opiate binding when compared to SR animals. Immediately following a seizure, binding in the interpeduncular nucleus fell to levels found in SR animals. The increased opiate binding in the SS (pre-seizure) compared to SR gerbils could reflect a deficit of endogenous ligand which could underlie the seizure diathesis in the gerbil.

Animals↗
PubMed1984

Does seizure activity produce Purkinje cell loss?

Eight Wistar rats were exposed to 140 electroconvulsive seizures over 50 days. Ten rats served as controls. The density of Purkinje cells in cerebellum ranged from 15.3 to 18.5/mm in the treated rats and from 15.2 to 19.1/mm in the controls. No Purkinje cell loss was disclosed in the rats subjected to electroconvulsive seizures. Twenty-five Mongolian gerbils of the seizure-susceptible strain were selected according to seizure score with five animals in each group. Five Mongolian gerbils of a seizure-resistant strain served as controls. The density of the Purkinje cells ranged from 21.4 to 29.8/mm in the seizure-susceptible animals and from 27.6 to 31.5/mm in the controls, with a lower density in the gerbils with seizures compared with the controls (p less than 0.05). There was no relation to type or number of seizures. Eight gerbils of the seizure-susceptible strain were included as a supplementary group, to disclose any possible genetic trait as an explanation of the lower Purkinje cell density. The Purkinje cell density in these animals ranged from 24.8 to 30.9/mm and did not differ from the density in the seizure-resistant gerbils. Thus the lower density of Purkinje cells in the seizure-susceptible Mongolian gerbils is a result of seizure activity. The excessive epileptic input with stimulation of the glutamatergic innervation of the Purkinje cells resulting in a persistent elevated gamma-aminobutyric acid (GABA) tone may explain the damage to the Purkinje cells in the gerbils and the loss of Purkinje cells found in patients with severe epilepsy.

Animals↗
PubMed1984

A primate model of human postmenopausal hot flushes.

The hot flush is the only symptom specifically attributable to the menopause. Hot flushes appear to represent an episodic derangement of thermoregulation as a result of estrogen deficiency but the underlying physiological mechanisms are unknown. We have developed an animal model for the study of hot flushes. Two female monkeys (Macaca arctoides) were trained to accept monitoring of scalp cutaneous temperatures. After baseline temperature recordings were obtained both monkeys were ovariectomized. A few days after operation the previously stable scalp temperature changed to an undulating pattern with cycles lasting approximately 40-50 min. Ethinyl estradiol (20 micrograms orally or im) and (7 alpha,17 alpha)-17-hydroxy-7-methyl-19-nor-pregn-5(10)-en-20-yn-3-one (2.5 mg orally), a steroid with weak estrogenic, progestogenic, and androgenic properties, suppressed the characteristic undulating temperature pattern; this returned after withdrawal of replacement therapy. Clonidine (0.15 mg twice a day) suppressed the cyclic changes for 2 to 3 h. Domperidone and naloxone had no significant effect. This animal model may be useful for the investigation of alternative therapy for the management of menopausal flushes.

Anabolic Agents↗
PubMed1983

Opioid peptides and seizures in the spontaneously epileptic Mongolian gerbil.

The naturally epileptic Mongolian gerbil was used to investigate the epileptogenic properties of beta-endorphin, dynorphin, met-enkephalin and morphine. The results indicate that opioid induced "seizures" are different from naturally spontaneous seizures in the gerbil in respect to EEG recording and motor behavior. Evidence for a protective role in preventing seizures is also presented.

Animals↗
PubMed1982

Cold acclimation and resistance to ethanol-induced hypothermia.

The fall in core temperature induced by a fixed dose of ethanol (1 g x kg-1 i.p.) was an exponential function of the ambient temperature over the range 0-18 degrees C. In rats acclimated to 4 degrees C for 7 days the dose response curve relating the fall in body temperature to ethanol was markedly attenuated. The hypothermic effect of ethanol declined exponentially over 20 days of exposure to 4 degrees C and by the 20th day the fall was no greater than in saline injected controls. Blood ethanol concentrations were similar in acclimated and non-acclimated rats indicating that pharmacokinetic factors do not account for the altered responses. Although the time course of the development of resistance to the hypothermic effect of ethanol parallels that of cold acclimation to 4 degrees C, and the development of non-shivering thermogenesis, the attenuated drug effect does not appear to be due to the altered metabolic activity of brown adipose tissue. It is suggested that the modulation of the effect of ethanol in lowering the thermoregulatory set point results from central nervous system adaptation to the environmental thermal stress.

Acclimatization↗
PubMed1981

Thermoregulatory mechanisms and ethanol hypothermia.

The mechanisms underlying the hypothermic effect of ethanol have been investigated in rats. At an ambient temperature of 26 degrees C, at which tail skin blood flow will normally be expected to play a role in regulating core temperature, no change in tail cutaneous temperature occurred during the period in which the core temperature was falling after administration of ethanol. As the drug effect waned tail skin temperature fell below the initial temperature as the hypothermia was corrected. This last observation confirms earlier results indicating a shift in the thermoregulatory set point after administration of ethanol. There was no significant change in oxygen consumption related to the ethanol induced fall in core temperature so decreased heat production would not appear to be a factor in the thermal imbalance. Neither was there any change in respiratory rate or minute volume to account for an increase in convective or evaporative heat loss via the lungs. From these results it is not clear by what mechanism the ethanol induced lowering of the set point leads to a fall in core temperature. Other avenues of heat loss, for example from other cutaneous surfaces, and further detailed thermal balance studies will be needed to resolve this problem.

Animals↗
PubMed1981

Association of waking episodes with menopausal hot flushes.

To examine the possible relationship between the occurrence of menopausal hot flushes and waking episodes, a study was conducted of nine postmenopausal women with severe hot flushes and five asymptomatic premenopausal women. Measurement of simultaneous changes of finger temperature and skin resistance over the sternum was used as an objective marker of hot flushes. During cumulative sleep 47 objectively measured hot flushes occurred, and 45 were associated with a waking episode measured by polygraphic techniques. In eight of nine subjects, a significant correlation was observed between the occurrence of hot flushes and waking episodes. A similar association was not observed in premenopausal subjects. Estrogen administered to symptomatic patients resulted in significant reductions of both hot flushes and waking episodes. These data suggest the menopausal flushes are associated with a chronic sleep disturbance, and both can be improved by estrogen therapy.

Age Factors↗
PubMed1981

Monitoring the pathophysiological correlates of post-menopausal hot flushes.

Clinical assessment of the severity and frequency of post-menopausal hot flushes can be made objectively by measuring the associated changes in skin conductance and skin and core temperature. Such measurements provide a more reliable index of the response to therapy than does subjective reporting which has been employed in the past. The design and use of a working analyzer is presented that is sufficiently simple, rugged, safe and portable to be used under normal clinical conditions to provide a permanent record of the attacks.

Body Temperature↗
PubMed1981

Hippocampal neuron density and seizures in the Mongolian gerbil.

Mongolian gerbils of the seizure-sensitive strain exhibit epileptic seizures in relation to changes in the environment, a characteristic which has been increased to about 100% by inbreeding. The seizures vary from animal to animal but are rather stable in the individual animal, which makes it possible to study the neuron densities in the hippocampus of the gerbil in relation to seizure type and seizure intensity. Five groups of gerbils with seizures ranging from minor movements and motor arrest to intense generalized convulsions were investigated with a quantitative method including cell counting by light microscope and estimation of possible brain shrinkage, as well as determination of nucleoli and nuclei diameters. The cell densities were determined in different areas of the pyramidal cells of the hippocampus (H-fields). The study discloses a reduction of cell densities in fields H2 and H3 in relation to intense generalized convulsions. It is suggested that the reduction in cell density in field H2 is a result of seizure activity, whereas the field H3 cell loss can be the result of both the hypoxia and the seizure activity.

Animals↗
PubMed1981

Histaminergic neurons in the hypothalamic thermoregulatory pathways.

Based on neurochemical and neurophysiological research, especially over the past decade, considerable evidence exists for accepting histamine as a central neurotransmitter along-side the other neuroamines. The data supporting a functional role are not complete, but they do exhibit a consistent pattern in the case of the central thermoregulatory pathways. Thus, the region of the thermoregulatory centers in the rostral hypothalamus contains relatively high concentrations of histamine and the enzyme systems for its synthesis and degradation; degeneration studies indicate histaminergic pathways in the hypothalamus; thermoregulatory changes can be induced by activation of either H1 or H2 receptors; behavioral studies reveal different functional roles for H1 and H2 receptors; and the thermoregulatory responses to histamine are detectable across different species, even in nonhomeothermic animals. This evidence supports assigning a transmitter function to histamine in the central thermoregulatory pathways that would appear to be as well-founded as the comparable data amassed for other neuroamines.

Animals↗