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B Meldrum

Publications and source records attributed to B Meldrum.

At least 19 recordsLinked to original sources
PubMed2006

Memory antibody responses of broiler and leghorn chickens as influenced by dietary vitamin E and route of sheep red blood cell administration.

Influences of dietary levels of vitamin E fed to hens and their progeny, and routes of SRBC inoculation on antibody responses of diverse populations of chickens were studied. Populations were a commercial broiler sire line (C), 2 commercial broiler dam lines (A and B), and Leghorn lines selected for high (H) or low (L) antibody response to SRBC. Dams from lines A and B were fed diets supplemented with either 10 or 300 IU/kg of vitamin E, whereas dams from lines H and L received only the diet with 10 IU of vitamin E/kg. Progeny from matings of C males with A and B females as well as H and L females mated to males from their respective lines were hatched on the same day and fed diets supplemented with either 10 or 300 IU/kg of vitamin E. Breeders were the same age and eggs were incubated in the same machine. Chicks were inoculated on d 14 intravenously with 0.1 mL of a 0.5% suspension of SRBC or intramuscularly with 0.1 mL of a 25% suspension of SRBC. Antibody response was measured 6 and 14 d later. Chicks received a booster i.m. inoculation of 0.1 mL of 25% SRBC on d 28. Titers were again measured 6 and 14 d later. Level of vitamin E fed to dams did not affect progeny BW or plasma vitamin E levels. Although titers were higher following i.v. than i.m. inoculation, the degree of difference varied among stocks. Dietary vitamin E level interacted with inoculation route with a greater response to the higher than lower level of vitamin E for i.v., but there was no difference for i.m. There were stock x level of vitamin E and stock x route of inoculation interactions for secondary responses to SRBC inoculation. Stock rankings after the first inoculation were not predictive of the rankings after the second inoculation. The 30-fold increase in dietary level of vitamin E resulted in >12-fold differences in plasma levels of vitamin E. Overall, there was a stock-dependent influence of dietary vitamin E on growth and humoral antibody response.

Animals↗
PubMed2006

Poult performance as influenced by age of dam, genetic line, and dietary vitamin E.

An experiment was conducted to measure the effects of age of dam, genetic line, and dietary levels of vitamin E on growth and immunocompetence of poults. Age of dam was defined as younger (in early egg production) and older (past peak production); line consisted of a commercial sire and dam line; and dietary vitamin E was supplemented into the diet at 10 and 300 IU/kg of feed. Traits measured included body, liver, gizzard, and yolk sac weights at hatch; BW and feed conversion to 9, 28, and 42 d; response to SRBC, Phaseolus vulgaris agglutinin-P, and Escherichia coli administered at 28 d of age; and response to a cold stress on d 5 posthatch. Differences among genetic lines were evident with growth greater for poults from the sire than from the dam line. Performance of poults from older dams was generally superior to that of poults from younger dams. The higher level of vitamin E resulted in a greater than 7-fold increase in blood plasma vitamin E and reduced mortality. There were interactions among the main effects in which the fitness of poults from younger dams was enhanced by the higher level of vitamin E and the effect of breeder age differed among genetic lines.

Age Factors↗
PubMed2003

Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability.

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice.

Animals↗
PubMed2001

Performance of pureline broiler breeders fed two levels of vitamin E.

Reported in this paper is an experiment designed to evaluate responses of two commercial broiler dam purelines (A and B) continuously fed 10 or 300 IU of vitamin E/kg from 168 to 441 d of age. Prior to Day 168, all pullets were fed diets containing 10 IU of vitamin E/kg. During the early laying period, percentage hen-day ovulations and percentage hen-day normal egg production were similar for both lines and diets. During the latter part of the laying cycle, there were differences between lines for these traits (A > B), as well as for BW and egg weight for which line differences were reversed (A < B). Also during this period, percentage hen-day ovulations and percentage hen-day normal egg production differed between diets (300 > 10 IU/kg). These differences between diets were consistent with the greater number of females that entered lay and higher hen-housed egg production of the 300- than 10-IU/kg group. Although during the laying cycle all females received a fixed amount of feed, BW gains were greater for Line B than A and for the 300- than the 10-IU/kg level of vitamin E. Heterophil (H):lymphocyte (L) ratios, percentage livability, and relative asymmetries of shank length and diameter were similar among groups. Pullets from Line B and those fed the higher level of vitamin E exhibited more fear than their counterparts. Head shaking did not differ between vitamin E levels; however, there was a line-by-time of day interaction for this behavior. The 30-fold difference in dietary vitamin E was reflected by a 15-fold difference in plasma vitamin E levels in both lines. For vitamin E level in the yolk, however, there was a line-by-diet interaction. The interaction resulted from no difference between lines at the 10 IU/kg level and differences of 10- and 6+-fold in Lines B and A at the 300 IU/ kg level, respectively. Overall, responses to continuous feeding of vitamin E at these levels were influenced by genetic stock, age, duration of feeding, and measurement criteria.

Age Factors↗
PubMed1997

Anticonvulsant properties of two GABA uptake inhibitors NNC 05-2045 and NNC 05-2090, not acting preferentially on GAT-1.

Two novel nipecotic acid derivatives, 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(4-methoxyphenyl)-4-piperidino l (NNC 05-2045) and 1-(3-(9H-Carbazol-9-yl)-l-propyl)-4-(2-methoxyphenyl)-4-piperidino l (NNC 05-2090) have been tested for inhibition of gamma-amino butyric acid (GABA) transporters in synaptosomal preparations of rat cerebral cortex and inferior colliculus and found to differ markedly from gabitril (tiagabine), a selective GAT-1 inhibitor. IC50 values for inhibition of [3H]GABA uptake into synaptosomes from cerebral cortex for NNC 05-2045 and NNC 05-2090 were 12 +/- 2 and 4.4 +/- 0.8 microM, respectively. In synaptosomes from inferior colliculus in the presence of 1 microM 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid (NNC 05-0711), a highly potent and selective GAT-1 inhibitor, IC50 values for inhibition of [3H]GABA uptake were 1.0 +/- 0.1 and 2.5 +/- 0.7 microM, respectively. A receptor profile showed that NNC 05-2045 has binding affinities to sigma-, alpha 1- and D2-receptors of 113, 550 and 122 nM, respectively. NNC 05-2090 displayed alpha 1- and D2-receptor affinity of 266 and 1632 nM, respectively. The anticonvulsant action of both compounds was tested in four rodent models after intra peritoneal (i.p.) injection. Both NNC 05-2090 dose-dependently inhibited sound-induced tonic and clonic convulsions in DBA/2 mice with ED50 values of 6 and 19 mumol/kg, respectively. NNC 05-2045 also antagonized sound-induced seizures in genetic epilepsy prone rats (GEP rats) with ED50 values against wild running, clonic and tonic convulsions of 33, 39 and 39 mumol/kg, respectively (NNC 05-2090 was not tested in GEP rats). Both NNC 05-2045 and NNC 05-2090 dose-dependently antagonized tonic hindlimb extension in the maximal electroshock (MES) test with ED50 values of 29 and 73 mumol/kg, respectively. In amygdala kindled rats NNC 05-2045 and NNC 05-2090 significantly (P < 0.05) reduced generalized seizure severity (seizure grade 3-5) at highest doses (72-242 mumol/kg) and NNC 05-2090 also significantly reduced afterdischarge duration at these doses (P < 0.05). These data show that inhibition of GABA uptake through non-GAT-1 transporters has different anticonvulsant effects than selective GAT-1 inhibitors (e.g. tiagabine) in that enhanced efficacy against MES and reduced efficacy against kindled seizures is observed. Although a contribution of adrenergic agonistic effects cannot be entirely ruled out, it is proposed that inhibition of GAT-3 (mouse GAT4) is primarily responsible for the anticonvulsant action of these two nipecotic acid derivatives in MES, amygdala kindled rats and in sound-induced seizures in GEP-rats and DBA/2 mice.

Animals↗
PubMed1994

Excitatory amino acids, free radicals and the pathogenesis of motor neuron disease.

The cause of motor neuron disease (MND) remains unknown, but the pathogenic involvement of excitatory amino acid (EAA) neurotransmitters and related exogenous compounds has been proposed. We discuss current concepts of the mechanisms of action of EAAs and the evidence for links between these neurotransmitters and free radical hypotheses of neuronal damage. These concepts are especially pertinent following reports of mutations in the gene encoding the free radical scavenging enzyme, copper-zinc superoxide dismutase, in familial MND. New approaches to treatment are suggested by advances in understanding of the disease.

Animals↗
PubMed1992

Effect of NO synthase inhibition on NMDA- and ischaemia-induced hippocampal lesions.

We assessed the effect of NG-Nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, on the hippocampal lesions induced either by the focal injection of N-methyl-D-aspartate (NMDA) or (s)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (s-AMPA) or by 10 min of severe forebrain ischaemia (4-vessel occlusion), in the rat. We find that L-NAME, 20 or 40 mg kg-1, selectively decreases NMDA-induced CA1 lesions while it has no effect on AMPA toxicity. L-NAME, 20 mg kg-1, does not decrease hippocampal damage induced by ischaemia. These results suggest that NO contributes to NMDA toxicity and support data indicating that NMDA receptor antagonists fail to protect against hippocampal CA1 lesions in the 4-vessel occlusion model.

Amino Acid Oxidoreductases↗
PubMed1991

Excitotoxicity and epileptic brain damage.

The two forms of epileptic brain damage, that found in patients with chronic epilepsy (post-mortem or in an anterior temporal lobectomy specimen) and that occurring acutely after status epilepticus, have much in common but are not identical. Hippocampal lesions occurring acutely after status epilepticus show a high degree of selectivity for hilar interneurones, CA1 pyramidal neurones and CA3 pyramidal neurones. Hippocampal lesions in anterior temporal lobectomy specimens tend to involve the subfields less selectively with CA1 being only slightly more severely affected than dentate granule cells, CA3 and CA2 pyramidal neurones. The most severely damaged hippocampi may result from a combination of acute damage early in life (commonly from prolonged febrile convulsions) and cumulative damage associated with seizures. Less severe degrees of damage are probably a consequence of repeated seizures. The abnormal patterns of firing associated with epileptic activity are almost certainly responsible for cell death occurring acutely after status epilepticus; they may contribute to the progressive cell loss occurring in chronic epilepsy.

Amino Acids↗
PubMed1990

Excitatory amino acid neurotoxicity and neurodegenerative disease.

The progress over the last 30 years in defining the role of excitatory amino acids in normal physiological function and in the abnormal neuronal activity of epilepsy has been reviewed in earlier articles in this series. In the last five years it has become clear that excitatory amino acids also play a role in a wide range of neurodegenerative processes. The evidence is clearest where the degenerative process is acute, but is more controversial for slow degenerative processes. In this article Brian Meldrum and John Garthwaite review in vivo and in vitro studies of the cytotoxicity of amino acids and summarize the contribution of such toxicity to acute and chronic neurodegenerative disorders.

Amino Acids↗
PubMed1990

Quantitative autoradiographic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem.

Using quantitative autoradiography, the anatomical distribution of the binding sites (kainate, N-methyl-D-aspartate and quisqualate) for the excitatory neurotransmitter glutamate has been established in the hippocampal formation from control and schizophrenic brains, post mortem. There is a loss of the kainate subtype particularly in schizophrenic hippocampi mainly from the CA4/CA3 mossy fibre termination zone of the cornu ammonis (CA4 and CA3; control and schizophrenic left hippocampus, respectively, 54.2 and 66.6 pmol/g; 18.3 and 17.9 pmol/g), as well as bilateral losses in the dentate gyrus (left 14.2 pmol/g and right 28.0 pmol/g; left 9.5 pmol/g and right 7.9 pmol/g, control and schizophrenic, respectively) and parahippocampal gyrus (left 50.8 pmol/g and right 41.7 pmol/g, left 27.7 pmol/g and right 25.3 pmol/g, control and schizophrenic, respectively). There is complete preservation of N-methy-D-aspartate sites in schizophrenic hippocampi, and a marginally significant loss of the quisqualate binding site in CA4/CA3 regions (left 249 fmol/g and right 306 fmol/g, left 157 fmol/g and right 148 fmol/g, control and schizophrenic, respectively). These findings reflect the possible importance of glutamate in the pathophysiology of schizophrenia and represent novel targets for therapeutic manipulation in schizophrenia.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission.

An excitotoxic action of glutamate and aspartate contributes to the pathological outcome after transient global cerebral ischaemia, focal ischaemia, neonatal hypoxia/ischaemia, and secondary ischaemia following brain trauma. This provides a therapeutic approach utilising drugs acting on (i) glutamate release, (ii) postsynaptic glutamate receptors, and (iii) the secondary events following receptor activation (including the arachidonic acid cascade). Both NMDA and non-NMDA receptors are involved in the excitotoxic effects of glutamate and aspartate. The availability of competitive and noncompetitive antagonists acting at the NMDA receptor has permitted the demonstration of cerebroprotective effects of these compounds in animal models of global, focal, neonatal, and secondary cerebral ischaemia. Protection is seen with antagonist administration prior to and after the onset of ischaemia. The postischaemic therapeutic time window is not fully defined for the different models but is in the range of 0-20 min for incomplete global ischaemia and 1-3 h for focal ischaemia. The clinical usefulness of this approach remains to be established.

Animals↗
PubMed1988

Anti-epileptic effects of focal micro-injection of excitatory amino acid antagonists.

The role of excitatory synaptic activity at various brain regions in the development and spread of seizure activity has been investigated by the focal microinjection of 2-amino-7-phosphono-heptanoate (2-APH), a selective antagonist at the N-methyl-D-aspartate preferring receptor, or gamma-D-glutamyl-aminomethyl sulphonate (GAMS), a partially selective antagonist at the kainate receptor. In genetically epilepsy prone rats the seizure response to a loud sound in most effectively suppressed by focal injections of 2-APH, 0.1-1.0 nmol, in the inferior colliculus. Protection is also seen after injections of 2-APH, 25 nmoles, in the substantia nigra (pars reticulata) or the midbrain reticular formation. Motor limbic seizures induced by pilocarpine, 380 mg/kg intraperitoneally, are prevented by prior injection into the substantia nigra, pars reticulata, or the entopeduncular nucleus, of 2-APH, 10 nmol or 10 pmol, respectively. Similar protection follows the injection of 2-APH, 1-5 pmol in the piriform cortex. The convulsant effects of pilocarpine are also blocked by the focal injection of GAMS, 10 nmol in the entopeduncular nucleus. This experimental approach can indicate critical sites at which seizure activity is initiated in particular models (e.g., inferior colliculus in sound-induced seizures, and piriform cortex in limbic seizures) and the pathways controlling seizure expression, such as the basal ganglia outputs. It also identifies specific receptors at which anticonvulsant drugs may operate.

2-Amino-5-phosphonovalerate↗