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Biomedical subjects

M Hay

Publications and source records attributed to M Hay.

At least 19 recordsLinked to original sources
PubMed2000

Assessment of hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity in pregnant sows through the measurement of glucocorticoids and catecholamines in urine.

We validated the use of urine to monitor changes in the activity of both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) in swine. Ten pregnant sows were fitted with venous catheters 3 wk after mating. In the early (wk 6), middle (wk 9), and late (wk 14) stages of gestation, blood and urine were collected over 24 h to monitor diurnal changes in plasma cortisol, urinary cortisol, and urinary catecholamines (norepinephrine [NE] and epinephrine [EPI]). Dexamethasone suppression tests (DST) and ovine corticotropin-releasing hormone (CRH) challenge tests were also performed at each stage of gestation. All plasma and urinary values changed markedly around the clock. Diurnal variations of urinary cortisol were comparable to those in plasma, with a late nocturnal peak and a trough occurring in the evening. During the dark period, urinary catecholamines were lower than during the light period. Norepinephrine increased sharply after lights came on and peaked after meal time. Epinephrine began to rise at the end of the dark period and peaked just before meal time. Average plasma cortisol increased with the stage of gestation, due to higher levels during daylight hours. Dexamethasone at 2000 (20 microg/kg i.v.) decreased plasma cortisol at 0830 and nocturnal cortisol excretion. The magnitude of the decrease in plasma ACTH and urinary cortisol after DST was lower in late than in early and midgestation, indicating increased feedback resistance at that stage. The CRH (1 microg/kg i.v.) increased plasma and urinary cortisol. Peak levels occurred 30 min and 2 to 3 h after the injection, respectively. Catecholamines and cortisol in urine produced during the night (2000 to 0800) and the early morning (0400 to 0800 and 0800 to 0900) were highly correlated with their 24-h excretion rate. These results indicate that it is possible to monitor changes in the HPA axis and SNS activity through urinary measurements in pigs.

Adrenocorticotropic Hormone↗
PubMed1999

Heterogeneity of metabotropic glutamate receptors in autonomic cell groups of the medulla oblongata of the rat.

Metabotropic glutamate receptors (mGluRs) in the medulla oblongata have been suggested to be involved in the regulation of autonomic function. The aim of the present study was to examine the localization and expression of four types of mGluRs: mGluRla, mGluR2/3, mGluR5, and mGluR7 in the dorsal and ventral autonomic nuclei of the medulla of the rat. The four mGluR subtypes studied were differentially distributed in distinct subnuclei in the nucleus of the solitary tract (NTS). mGluRla immunoreactivity was identified in cell bodies, dendrites, and axonal processes in the intermediate, dorsal lateral, and interstitial subnuclei of the NTS. No mGluRla immunoreactivity was observed in the commissural or medial NTS subnuclei. Immunoreactivity for mGluR2/3 and mGluR5 as observed in fibers and putative axonal processes in the interstitial, intermediate, and dorsolateral subnuclei of the NTS. In contrast, mGluR7 was expressed primarily in fibers and terminals in the central and commissural NTS subnuclei. Expression of mGluR2/3 was clearly evident in cell bodies, dendrites, and axonal processes within the area postrema. The vagal outflow nuclei were also studied. The dorsal motor nucleus of the vagus (DMN) contained mGluRla cell bodies, dendrites, and axonal fibers and light mGluR2/3 processes. Throughout the rostral-caudal extent of the compact and semicompact formation nucleus ambiguus, mGluRla was found in cell bodies and fibers. Within the caudal and rostral regions of the ventral lateral medulla, mGluRla was observed in cell bodies and fibers. Cell bodies containing mGluRla were found adjacent to cells staining positive for tyrosine hydroxylase (TH) in these regions but were not colocalized with the TH staining. However, mGluRla-expressing neurons in the ventral lateral medulla did appear to receive innervation from TH-containing fibers. These results suggest that the mGluRla-expressing neurons within the ventral lateral medulla are predominantly not catecholaminergic but may be innervated by catecholamine-containing fibers. These data are the first to provide a mapping of the different mGluR subtypes within the medulla and may facilitate predictions regarding the function of L-glutamate neurotransmission in these regions.

Animals↗
PubMed1999

AMPA receptor activation of area postrema neurons.

This study reports on the effects of activation of ionotropic glutamate receptors on area postrema neuron cytosolic calcium concentration ([Ca2+]i). In 140 of 242 area postrema neurons isolated from postnatal rats, application of 100 microM L-glutamate (L-Glu) resulted in a significant increase in [Ca2+]i. The remaining neurons were unaffected. The effects of L-Glu on area postrema [Ca2+]i were dose dependent, with a threshold of response near 1.0 microM and maximal response near 100 microM. To determine if the response of L-Glu in area postrema neurons was due to activation of ionotropic glutamate receptors, the effects of the broad-spectrum ionotropic glutamate receptor antagonist kynurinic acid (Kyn) was determined. Application of 1.0 mM Kyn resulted in a 62.6 +/- 4% inhibition of the L-Glu-evoked response. Application of the selective N-methyl-D-aspartic acid (NMDA) antagonist 2-amino-5-phosphonopentanoic acid had no effect on the response of area postrema neurons to 100 microM L-Glu. In contrast, application of the selective DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline (DNQX) effectively blocked the 100 microM L-Glu response. Application of (+/-)-AMPA mimicked the effects observed with L-Glu and was selectively blocked by DNQX. These results suggest that L-Glu activation of area postrema neurons involves activation of AMPA receptors but not NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1999

Cardiovascular response to group I metabotropic glutamate receptor activation in NTS.

Glutamate is the proposed neurotransmitter of baroreceptor afferents at the level of the nucleus tractus solitarius (NTS). Exogenous glutamate in the NTS activates neurons through ionotropic and metabotropic glutamate receptors (mGluRs). This study tested the hypothesis that group I mGluRs in the NTS produce depressor, bradycardic, and sympathoinhibitory responses. In urethan-anesthetized rats, unilateral 30-nl microinjections of the group I-selective mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) into the NTS decreased mean arterial pressure, heart rate, and lumbar sympathetic nerve activity. The dose of drug that produced 50% of the maximal response (ED50) was 50-100 microM. The response to microinjection of equal concentrations of DHPG or the general mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) produced similar cardiovascular effects. The cardiovascular response to injection of DHPG or ACPD was abolished by NTS blockade of mGluRs with alpha-methyl-4-carboxyphenylglycine (MCPG). Blockade of ionotropic glutamate receptors with kynurenic acid did not attenuate the response to DHPG or ACPD injection. These data suggest that DHPG and ACPD activate mGluRs in the NTS and do not require ionotropic glutamate receptors to produce their cardiovascular response. In the NTS the group I mGluRs produce responses that are consistent with excitation of neurons involved in reducing sympathetic outflow, heart rate, and arterial pressure.

Animals↗
PubMed1999

The impact of HIV infection on Mycobacterium kansasii disease in South African gold miners.

The impact of human immunodeficiency virus (HIV) infection on Mycobacterium kansasii disease in miners was investigated with a retrospective study covering a single workforce. M. kansasii, isolated from 43 HIV-positive and 202 HIV-negative miners, was the most common nontuberculous mycobacterial (NTM) species in both HIV groups. CD4 counts were unusually high for M. kansasii disease (mean 490 x 10(6)/L, from 14 HIV-positive men). Treatment outcomes were similar: mortality during treatment was higher in HIV-positive than in HIV-negative men (9% and 2%, respectively), but not significantly so. The majority of a sample of 31 HIV-positive and 92 HIV-negative men had radiological silicosis and/or old tuberculosis scarring prior to M. kansasii disease. A normal premorbid radiograph was more common in HIV-positive men (45% versus 24%; odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.01 to 6.67). New cavitation was less common (55% versus 78%; OR, 0.34; 95% CI, 0.13 to 0.88) and new hilar adenopathy more common (OR, 5.07; 95% CI, 1.24 to 21.9) in HIV-positive than in HIV-negative men. Miners, who have additional NTM risk factors, develop M. kansasii disease that occurs at an earlier stage of HIV infection and more closely resembles disease in HIV-negative men than has been found for HIV-associated M. kansasii disease in other settings.

AIDS-Related Opportunistic Infections↗
PubMed1999

Mycobacterium kansasii and M. scrofulaceum isolates from HIV-negative South African gold miners: incidence, clinical significance and radiology.

SETTING: A South African gold mining hospital. OBJECTIVE: To investigate the clinical significance of non-tuberculous mycobacteria (NTM) isolates, and estimate NTM disease incidence in human immunodeficiency virus (HIV) negative miners. DESIGN: Retrospective case series describing clinical and radiological features associated with NTM sputum isolates from HIV-negative miners between January 1993 and July 1996, and a comparison group with Mycobacterium tuberculosis infection. RESULTS: Of miners with NTM isolates, 90% had been HIV-tested and 81% were HIV-negative. M. kansasii and M. scrofulaceum accounted for 202 (68%) and 41 (14%) isolates respectively. More than 80% of miners with M. kansasii or M. scrofulaceum were smear positive, and new cavitation was present in 78% and 74% respectively. Treatment failure occurred in 3% of M. kansasii and 12% of M. scrofulaceum patients. A normal pre-morbid radiograph was significantly less common in NTM than M. tuberculosis patients (odds ratio 0.26 and 0.10 for M. kansasii and M. scrofulaceum, respectively). NTM disease incidence, defined as NTM isolate plus new cavitation, was estimated at 66 and 12 per 100000 person-years for M. kansasii and M. scrofulaceum, respectively. CONCLUSIONS: M. kansasii and M. scrofulaceum disease are common in HIV-negative South African gold miners. Most isolates are associated with new cavitation against a background of silicosis or old TB scarring.

Adult↗
PubMed1998

Cyclosporine A modulation of Ca++ activated K+ channels in cardiac sensory afferent neurons.

Whole-cell and single channel recordings were used to characterize the effects of the immunosuppressant cyclosporine A (CsA) on cardiac sensory neurons (CSN) of the nodose ganglia. Application of 10 nM CsA resulted in a 29.1% decrease in CSN input resistance and an average -8+/-3 mV hyperpolarization of membrane potential. Application of 10 nM CsA had no effect on evoked Ca++ currents but increased evoked K+ currents by 158.9+/-24%. Application of 10 nM CsA significantly increased the open probability of KCa channels by 183+/-9%. These results suggest that application of CsA results in the activation of KCa channels in cardiac sensory neurons and this effect may contribute to the cellular mechanisms underlying CsA modulation of vagal afferent neurons.

Animals↗
PubMed1998

The effects of social support and education on health care costs after three years.

OBJECTIVE: To determine whether experimentally developed social support, education about appropriate use of the health care system, and their combination are effective in reducing health care costs for people with osteoarthritis at a 3-year followup assessment. METHOD: Three hundred sixty-three health maintenance organization members with osteoarthritis were randomly assigned to 1 of 3 intervention groups or to a control group. Two hundred fifty-six participants completed the 3-year assessment. Health status and health care use were assessed upon entering the study, and after 1, 2, and 3 years. RESULTS: Health care costs in the combined experimental groups were lower than those in the control group by $1,279/participant/year in year 3. There were no significant changes in health status between participants' entry into the study and the year 3 assessment. The 3 interventions had nearly equal effects on health status and health care costs. Implementation costs were least for the social support intervention, but the group that combined education and social support had less attrition and greater persistence. CONCLUSION: Interventions that target appropriate use of the health care system can be highly cost-effective without adversely affecting health status.

Aged↗
PubMed1998

Measurement of synaptic vesicle exocytosis in aortic baroreceptor neurons.

The purpose of this study was to evaluate the use of the fluorescent membrane label FM1-43 as a measure of synaptic terminal exocytosis during stimulation of labeled aortic baroreceptor and unlabeled nodose ganglia neurons. Activation of the nerve terminals with electrical stimulation or depolarization with 90 mM KCl in the presence of 2.0 microM FM1-43 resulted in bright, punctate staining of synaptic boutons. Additional depolarization in the absence of dye resulted in destaining with a time course that was consistent and repeatable in multiple boutons within a given terminal. Destaining was dependent on calcium influx and was blocked by bath application of 100 microM CdCl2. Whole cell patch-clamp studies have reported that depolarization-induced calcium influx in aortic baroreceptor cell bodies is predominantly caused by the activation of omega-conotoxin GVIA (omega-CgTx)-sensitive N-type calcium channels. In addition, these N-type channels have been shown to be inhibited by activation of metabotropic glutamate receptors. In the present study, exocytosis in aortic baroreceptor terminals was not affected by bath application of 5 microM nifedipine and only partially inhibited by bath application of 2.0 microM omega-CgTx. However, depolarization-induced exocytosis was significantly inhibited by bath application of 200 microM L-AP4, a type III metabotropic glutamate receptor agonist. Results from this study suggest that 1) FM1-43 can be used to measure synaptic vesicle exocytosis in baroreceptor neurons; 2) the N-type calcium channel may not be involved in the initial phase of vesicle exocytosis; and 3) activation of L-AP4-sensitive metabotropic glutamate receptors inhibits 90 mM KCl-induced vesicle release.

Animals↗
PubMed1998

Glutamate in the nucleus of the solitary tract activates both ionotropic and metabotropic glutamate receptors.

Glutamate is the proposed neurotransmitter of baroreceptor afferents at the level of the nucleus of the solitary tract (NTS). Blockade of ionotropic glutamate receptors with kynurenic acid blocks the arterial baroreflex but, paradoxically, does not abolish the response to exogenous glutamate. This study tested the hypothesis that exogenous glutamate in the NTS activates both ionotropic and metabotropic glutamate receptors (mGluRs). In urethan-anesthetized rats, unilateral microinjections of glutamate into the NTS decreased mean arterial pressure, heart rate, and lumbar sympathetic nerve activity. The cardiovascular response to injection of glutamate was not altered by NTS blockade of mGluRs with alpha-methyl-4-carboxyphenylglycine (MCPG). Blockade of ionotropic glutamate receptors with kynurenic acid attenuated the response to glutamate injection. After combined NTS injection of MCPG and kynurenic acid, the response to glutamate was blocked. These data suggest that exogenous glutamate microinjected into the NTS acts at both ionotropic glutamate receptors and mGluRs. In addition, blockade of both classes of glutamate receptors is required to block the cardiovascular response to microinjection of glutamate in the NTS.

Animals↗
PubMed1997

Determination of catecholamines and methoxycatecholamines excretion patterns in pig and rat urine by ion-exchange liquid chromatography with electrochemical detection.

A simplified liquid chromatographic method for the simultaneous determination of free or total catecholamines and methoxycatecholamines in rat and pig urine is presented. The extraction procedure involves a two-stage batch extraction, with successive adsorption on cation- (catecholamine elution) and anion-exchange columns (methoxycatecholamine elution). The column eluates are successively monitored by reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection. The proportion of conjugates for each compound was assessed in both species, through the comparison of concentrations with or without hydrolysis pretreatment. Conjugates were found to account for a small fraction of total catecholamines and methoxycatecholamines excretion (0 to 35%). The free fraction of each compound was highly correlated with the total amount. Furthermore, the hydrolysis procedure leads to partial degradation of metanephrine (25%) and to the production of compounds giving artefactual peaks. Thus, we do not recommend hydrolysis of rat and pig urines for catecholamine and methoxycatecholamine determination.

Animals↗
PubMed1997

Improved determination of urinary cortisol and cortisone, or corticosterone and 11-dehydrocorticosterone by high-performance liquid chromatography with ultraviolet absorbance detection.

A sensitive assay was developed for the determination of low levels of free (unconjugated) glucocorticoids in human, swine (cortisol and cortisone) and rat urine (corticosterone and 11-dehydrocorticosterone), using solid-phase extraction and HPLC with UV absorbance detection (254 nm). Precise quantitation is allowed by the use of internal standards (dexamethasone for swine urine and Reichstein's substance S for rat urine). This simple method allows the use of small urine samples (less than 2 ml), and is suitable for a wide range of applications in human and animal clinical and physiological studies.

Animals↗
PubMed1997

Interactions between vasopressin and baroreflex control of the sympathetic nervous system.

1. In addition to its effects at the renal tubules to influence water retention and at vascular smooth muscle to cause vasoconstriction, the hormone arginine vasopressin also appears to modulate cardiovascular reflex control of the sympathetic nervous system. Infusion or endogenous release of vasopressin results in enhanced baroreflex sympatho-inhibitory responses compared with other pressor agents. In addition, when changes in arterial pressure are imposed on an elevated background level of circulating vasopressin, due either to infusion or endogenous release, the arterial baroreflex response is shifted to lower pressures, and the maximum sympatho-excitation to a decrease in pressure is reduced. 2. Evidence suggests that vasopressin may influence cardiovascular reflex function at multiple sites. Nevertheless, the primary site involved in the effects of circulating vasopressin on baroreflex function appears to be in the central nervous system, specifically in the area postrema. Lesion of the area postrema abolishes the ability of circulating vasopressin to modulate arterial baroreflex and cardiopulmonary reflex function and electrical or chemical stimulation of this circumventricular organ mimics the effects of vasopressin. In addition, vasopressin has been shown to influence the activity of area postrema neurons in vivo and in vitro. Although not all studies agree, the effects of the area postrema and vasopressin on cardiovascular reflex function appear to be dependent on afferent input from peripheral baroreceptors. 3. Most evidence suggests that vasopressin exerts its effects on baroreflex function through a V1 vasopressin receptor mechanism. Systemic administration or microinjection into the area postrema of a specific V1 receptor antagonist abolishes the action of arginine vasopressin on arterial baroreflex and cardiopulmonary reflex control of the sympathetic nervous system. 4. The ability of vasopressin and the area postrema to influence baroreflex function appears to be dependent on an alpha 2-adrenoceptor mechanism at the level of the nucleus tractus solitarius (NTS). Blockade of alpha 2-adrenoceptors in the NTS abolishes the effects of vasopressin and the area postrema on the sympathetic nervous system. Facilitation of NTS processing of baroreceptor afferent inputs by the area postrema could contribute to the enhanced sympatho-inhibition and shift of the baroreflex curve to lower pressures during elevations in circulating vasopressin.

Afferent Pathways↗
PubMed1997

Administration of AVP to the area postrema alters response of NTS neurons to afferent inputs.

This study was designed to determine if arginine vasopressin (AVP) facilitates the response of nucleus of the solitary tract (NTS) neurons to baroreceptor input. In anesthetized sinoaortic-denervated vagotomized rabbits, AVP was intravenously infused (15 microg x kg(-1) x min(-1), 1 min) or microinjected into the area postrema (AP; 1 ng/nl, 10 nl). Extracellular recordings of evoked NTS neuronal responses to electrical stimulation of the aortic depressor nerve (ADN) or vagus nerve (1 Hz, 2-20 V, 0.05-0.6 ms) were evaluated before and after AVP administration. In neurons receiving input from the ADN (n = 19), 58% of them increased their responses after AVP (40.3 +/- 5.0 to 71.5 +/- 4,8%, P < 0.001). Similarly, in neurons activated by vagal stimulation (n = 22), 55% of them were facilitated during AVP administration (59.7 +/- 12.8 to 90.8 +/- 10.7%, P < 0.01). This action of AVP was independent of the mode of AVP administration, since either microinjection or venous infusion was effective in augmenting responses of NTS neurons to aortic/vagal stimulation. In an additional 37 spontaneous NTS neurons, AVP showed no effect on the mean baseline firing rate (8.9 +/- 1.3 vs. 9.6 +/- 1.3 spikes/s, P > 0.05), but increased neuronal activity in 54% of neurons (6.9 +/- 1.3 vs. 13.1 +/- 1.7 spikes/s, P < 0.01). In two rabbits pretreated with vasopressin antagonist (15 microg/kg iv), AVP failed to produce facilitatory effects (n = 8). The results of this study provide evidence in support of the hypothesis that circulating peptides modulate the arterial baroreflex via activation of neurons in the AP.

Afferent Pathways↗
PubMed1997

Modification of feed intake response to a beta 2-agonist by bovine somatotropin in lactating or dry dairy cows.

The aim of this experiment was to show whether growth hormone could increase the effect of the beta 2-adrenergic agonist clenbuterol on feed intake. Two groups of Holstein cows [lactating (n = 4) and dry (n = 4)] were used to rule out the possible effects of increased energy requirements on feed intake. Treatments were administered according to a crossover experimental design with two 13-d periods and an 8-d readjustment interval. Treatments consisted of daily injections of 40 mg of bST or a placebo. Moreover, clenbuterol (3.16 micrograms/kg of BW) or saline challenges were infused intravenously for 4 h either on d 8 or on d 11 of each period. The cows were offered a dehydrated total mixed diet for ad libitum intake for 4 h twice daily. For both groups of cows, clenbuterol reduced DMI on the experimental day only, and bST intensified the effects of clenbuterol on DMI, causing a sharper decrease in DMI over 2 d. This enhancement of clenbuterol activity modified certain metabolic parameters including higher lipid mobilization during infusion and higher glycogenolysis. For dry cows, the initial rate of eating was reduced under bST treatment alone. During early lactation, bST, either by itself or through increased beta 2-adrenergic stimulation may restrict the development of intake by dairy cows over a few weeks.

Adrenergic beta-Agonists↗
PubMed1996

Synaptic connections and interactions between area postrema and nucleus tractus solitarius.

The purpose of this study was to examine whether there are separate excitatory and inhibitory pathways from the area postrema (AP) to the nucleus tractus solitarius (NTS) and to examine the synaptic interactions between inputs from the AP and solitary tract (ST) on the NTS neurons. The following observations were made: (1) the predominant projections from the AP to the NTS were excitatory. Among the cells that had AP input, 90% of the cells (43/48) were excited by AP stimulation while 10% (5/48) of the cells were inhibited; (2) inputs from the AP and ST mainly summated occlusively on the NTS neurons, but at near threshold of discharge, the input from one source could facilitate the generation of action potentials induced by the other; and (3) single conditioning stimulation of the AP did not significantly inhibit the NTS neuronal response to ST stimulation, but stimulation of the AP with a train of high frequency stimuli inhibited the response of NTS neurons to ST stimulation and inhibited the evoked response to AP stimulation. The results of this study may help in the understanding of the modulatory role of the AP in the baroreflex and the integration process in the NTS.

Action Potentials↗
PubMed1996

Construction and characterization of an azurin analog for the purple copper site in cytochrome c oxidase.

A protein analog of a purple copper center has been constructed from a recombinant blue copper protein (Pseudomonas aeruginosa azurin) by replacing the loop containing the three ligands to the blue copper center with the corresponding loop of the CuA center in cytochrome c oxidase (COX) from Paracoccus denitrificans. The electronic absorption in the UV and visible region (UV-vis) and electron paramagnetic resonance (EPR) spectra of this analog are remarkably similar to those of the native CuA center in COX from Paracoccus denitrificans. The above spectra can be obtained upon addition of a mixture of Cu2+ and Cu+. Addition of Cu2+ only results in a UV-vis spectrum consisting of absorptions from both a purple copper center and a blue copper center. This spectrum can be converted to the spectrum of a pure purple copper by a prolonged incubation in the air, or by addition of excess ascorbate. The azurin mutant reported here is an example of an engineered purple copper center with the A480/A530 ratio greater than 1 and with no detectable hyperfines, similar to those of the CuA sites in COX of bovine heart and of Paracoccus denitrificans.

Amino Acid Sequence↗