Biomedical subjects

D L Armstrong

Publications and source records attributed to D L Armstrong.

135 records · Page 8Linked to original sources

PubMedDate not supplied

Effects of trimethyltin on evoked potentials in mouse hippocampal slices.

The effects of trimethyltin (TMT) on responses to orthodromic stimulation in the CA1 pyramidal cell layer and dentate gyrus were investigated in mouse hippocampal slices. In both regions exposure to 10.0 microM TMT produced an 80 to 90% reduction in population spike amplitude. Smaller decreases in spike amplitude occurred after 5 microM TMT and these effects were reversible in the pyramidial cell layer. The latency of 5.0 microM effects was longer in the dentate gyrus and were preceded by a slight (20%) increase in spike amplitude. The smallest dose of TMT tested (1.0 microM) did not change response amplitude, but did increase the occurrence of multiple population spike potentials. When TMT was applied during paired-pulse stimulation of the perforant path the potentiation of the second response was not selectively reduced. The results indicate that orthodromic excitability of both pyramidal and granule cells in the mouse hippocampus is decreased by TMT with small differences occurring in latency and reversibility at certain doses.

Animals↗

PubMedDate not supplied

Air righting: role of the NMDA receptor channel and hippocampal LTP.

Air righting results in an animal turning over when it is dropped from a height in an inverted position. In the rat, air righting is a complex set of movements that depends only on an intact labyrinth and the normal vestibular input. Visual modulation of air righting does not develop until adulthood; and the ability to estimate the time to impact requires bilateral visual cues and indicates that air righting is a complex set of perceptually controlled movements and learning. The general purpose of this study was to determine the role of the NMDA receptor-ion channel on air righting and hippocampal LTP. Specifically: to measure the effects of various doses of CPP, an NMDA receptor antagonist, and MK-801, an ion channel blocker, on (a) air righting and (b) hippocampal LTP induction in medial perforant path-granule cell synapses. The following doses were used: CPP-0, 1, 5, and 10 mg/kg i.p.; MK-801-0. 0, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg i.p. Data were analyzed by appropriate ANOVAs and post hoc tests. Results were significant and demonstrate dose-dependent impairment of air righting and inhibition of LTP for both CPP and MK-801, implicating the role of the NMDA receptor and Na(+)/K(+)/Ca(2)+ channel in these effects. Air righting is a complex behavior and appears to be dependent upon NMDA mediated hippocampal LTP.

Analysis of Variance↗

PubMedDate not supplied

Ethanol affects hypothalamic neurons projecting to the hippocampus and inhibits dentate granule cell LTP.

In previous studies we demonstrated that ethanol inhibition of hippocampal granule cell long-term potentiation (LTP) is mediated by angiotensin II (AII), and the inhibition can be blocked by losartan, a specific AII receptor antagonist. The purpose of the present study was to demonstrate that this low-dose ethanol inhibition of dentate granule cell LTP induction is mediated by lateral hypothalamic (LH) afferents that project to the granule cells. In urethane anesthetized rats, we compared the effects of ethanol infusion, 6.0 microliter/30 min, by means of an open-ended push-pull type cannula, in both the LH and the dentate gyrus, on dentate granule cell LTP. Results demonstrate a dose-dependent inhibition of LTP induction when the LH is perfused that can be blocked by losartan, 10 mg/kg i.p.. Four doses of ethanol were used: 5, 10, 20, and 30 mM. There was no effect when the dentate gyrus was infused with 30 mM ethanol and normal granule cell LTP was observed. Also, these results demonstrate for the first time a low-dose ethanol effect on a physiological function, LTP in a specific neural pathway, directly related to the anterograde amnesia produced by ethanol on short-term memory. Therefore, these data support our hypothesis that ethanol inhibition of LTP induction at the medial perforant path-granule cell synapse can be attributed to a presynaptic release of AII and cannot be explained in terms of a direct postsynaptic effect on the granule cells.

Angiotensin II↗

PubMedDate not supplied

Losartan improves the performance of ethanol-intoxicated rats in an eight-arm radial maze.

Results of previous research demonstrate that angiotensin II (Ang II) inhibits long-term potentiation (LTP) in medial perforant path-dentate gyrus granule cells and that the inhibition is mediated by the AT1 receptor because it can be blocked by losartan, a specific AT1 receptor antagonist. Ang II impairment of retention and ethanol inhibition of LTP can both be blocked by pretreatment with losartan. Because losartan pretreatment also prevents ethanol intoxication measured in terms of the aerial righting reflex, the purpose of the present study was to assess the effects of 2.0 g/kg ethanol administered by gavage on performance in an eight-arm radial maze, and then to determine the effectiveness of losartan in reducing the impairment of the learning and memory process. Results confirmed the general hypothesis that ethanol-induced cognitive deficits are mediated by Ang II and the AT1 receptor and that the impairment can be reduced by pretreatment with losartan.

Alcoholic Intoxication↗

PubMedDate not supplied

Nicotine blocks ethanol and diazepam impairment of air righting and ethanol impairment of maze performance.

Results of our previous research in rats demonstrate the following: (a) Angiotensin II (Ang II) inhibits long term potentiation (LTP) in dentate granule cell-perforant path synapses and that this inhibition can be blocked by losartan, an Ang II AT1 receptor antagonist; (b) both ethanol and diazepam inhibit LTP induction and this inhibition can be blocked by losartan; (c) impairment of air righting by ethanol and diazepam (DZ) and eight-arm radial maze performance by ethanol can be blocked by pretreatment with losartan: (d) inhibition of dentate granule cell LTP by Ang II can also be prevented by pretreatment with nicotine. Therefore, it seemed reasonable to hypothesize that ethanol and diazepam impairment of air righting and maze performance might also be blocked by pretreatment with nicotine. The purpose of the present study was to determine the effects of nicotine 0.1, 0.2, 0.3, and 0.4 mg/kg subcutaneously (SC) on 2.0 g/kg ethanol per os (PO) and 1.0 and 2.0 mg/kg DZ intraperitoneally (i.p.) induced impairment of air righting; and to determine if the impaired maze performance due to 2.0 g/kg ethanol PO could be prevented by pretreatment with 0.4 mg/kg of nicotine, SC. Results confirm the hypothesis that moderate doses of ethanol, 2.0 g/kg PO, and DZ, 1.0 mg/kg i.p. impair air righting and that the impairment can be prevented by pretreatment with nicotine SC. Nicotine was not effective in blocking the 2.0 mg/kg DZ impairment of air righting. Nicotine, 0.4 mg/kg SC, prevented the impaired maze performance induced by 2.0 g/kg ethanol PO.

Animals↗

PubMedDate not supplied

A randomized trial of two dexamethasone regimens to reduce side-effects in infants treated for chronic lung disease of prematurity.

OBJECTIVE: Dexamethasone has been widely used to reduce the incidence of chronic lung disease in preterm infants. However side-effects are common, and the ideal dose of dexamethasone has not been identified. We aimed to determine whether an individualized course of dexamethasone given to preterm babies at risk of chronic lung disease reduced the total dose of dexamethasone administered and reduced side-effects compared with a standard 42-day course. METHODS: Thirty-three infants in a regional neonatal unit with a birthweight of < or =1250 g who required mechanical ventilation at 7 days of age were randomly assigned to a 42-day course of dexamethasone or an individualized course tailored to their respiratory status. The primary outcome was linear growth at 36 weeks corrected gestational age. RESULTS: Infants in the individualized course received a 40% lower total dose of dexamethasone. However, there was no difference between the two groups in linear growth or in the incidence of any other side-effects of treatment. There was also no difference in respiratory status or neurodevelopmental outcome. CONCLUSION: The individualized course of dexamethasone used in this study reduced the total dose of dexamethasone administered but did not significantly reduce side-effects of treatment or alter outcome in infants at risk of chronic lung disease.

Anti-Inflammatory Agents↗

PubMedDate not supplied

A community diabetes education and gardening project to improve diabetes care in a Northwest American Indian tribe.

PURPOSE: The purpose of this study was to design a culturally appropriate education program for a Northwest American Indian tribe. METHODS: Needs assessment revealed that a community approach rather than clinic-based education would address multiple barriers to diabetes care. Both process and outcome information are described for community and individual level evaluations. RESULTS: This intervention design consisted of community diabetes workshops called "How Healthy Am I?--Treating the Whole Person." The workshops represented a traditional view of health and included 4 specific themes: (1) taking care of the body, with an emphasis on diabetes care and physical activity; (2) mental health needs; (3) foods for healthy living; and (4) spirituality and healing the whole person. Workshops were designed to be social and informational, and involve all community members. A community garden was established to improve access to fresh produce and encourage exercise. CONCLUSIONS: Prior to implementation of the community workshops and evaluations, the tribal government chose to discontinue receiving the federal funding for this project. Elements of a mutually respectful collaboration are outlined and discussed based on the experiences of this project.

Adult↗

PubMedDate not supplied

Effects of iontophoretic application of trimethyltin on spontaneous neuronal activity in mouse hippocampal slices.

Changes in spontaneous activity in various regions of mouse hippocampal slices were observed following iontophoretic application of trimethyltin (TMT). TMT (0.5 mM) dissolved in 0.15 M NaCl and ejected in 30 sec periods from four barrel micropipettes using anodal ejection currents (3-28 nA) produced dose dependent increases in the spontaneous activity of 67.6% of the 34 dentate gyrus cells tested. Seventy percent of the 25 CA3 cells tested displayed prolonged (30-200 sec) decreases in activity. The majority of CA1 and CA2 cells examined also displayed a decrease in firing rate. Repeated applications of TMT produced increased variability in spontaneous firing rates in all regions tested. When slices were maintained in a low Ca++, high Co++ perfusion fluid to inhibit synaptic activity, the TMT induced increase of dentate gyrus cell firing rate was not observed. The results demonstrate that direct application of TMT produces immediate changes in hippocampal cell activity that is specific for certain regions. Significant increases in firing rate were only observed in the dentate gyrus and these effects were calcium dependent.

Action Potentials↗

PubMedDate not supplied

Regulation of sperm function by protein tyrosine phosphorylation in diverse wild felid species.

Protein tyrosine phosphorylation is associated with sperm capacitation and the acrosome reaction in several mammalian species. Changes in phosphorylation of a 95-kDa protein in human, mouse, and domestic cat spermatozoa are known to be influenced by capacitation and exposure to zona pellucida (ZP) proteins. We previously reported diminished phosphorylation of 95- and 160-kDa proteins in spermatozoa from teratospermic cats, compared with normospermic domestic cats. To determine if these proteins and mechanisms are present in other species in the phenotypically diverse Felidae family, we examined the relationship between tyrosine-phosphorylated sperm proteins and sperm morphology in the leopard cat (approximately 65% normal sperm/ejaculate), tiger (approximately 65%), clouded leopard (approximately 15%), and cheetah (approximately 30%). Furthermore, we investigated the involvement of cyclic adenosine monophosphate (cAMP) in the regulation of sperm protein tyrosine phosphorylation. Specifically, we assessed the following: 1) presence of tyrosine-phosphorylated proteins in sperm extracts; 2) changes in protein tyrosine phosphorylation after sperm capacitation and swim-up separation; 3) impact of tyrosine kinase inhibition on leopard cat sperm protein phosphorylation and ZP penetration; and 4) involvement of a cAMP-dependent pathway in the regulation of protein tyrosine phosphorylation. Immunoblotting analysis with anti-phosphotyrosine antibody (PY20) indicated that a 95-kDa protein was present in all four species. Additional phosphorylated proteins were detected in the leopard cat (145- and 175-kDa proteins), tiger (185-kDa protein), clouded leopard (160- and 190-kDa proteins), and cheetah (115- and 155-kDa proteins). Sperm capacitation in vitro increased phosphorylation of one or more proteins in the leopard cat, tiger and clouded leopard, but not in the cheetah. Although swim-up separation increased the proportion of morphologically normal spermatozoa in the clouded leopard and cheetah, no changes were observed in phosphorylation of the 95-kDa sperm protein. Thus, phosphorylation of the 95-kDa protein appeared to be related to the condition of teratospermia. Exposing leopard cat spermatozoa to the tyrosine kinase inhibitor, tyrphostin, reduced (P < 0.05) phosphorylation of the 95- and 145-kDa proteins, as well as ZP penetration, without affecting sperm motility. Similarly, when spermatozoa were incubated in the presence of cAMP analogs or active and inactive stereoisomers of cAMP, phosphorylation of sperm proteins was either stimulated or inhibited. Together, these data suggest that protein tyrosine kinase mechanisms appear conserved within the family Felidae and are regulated by a cAMP/protein kinase A pathway.

Animals↗