Search PubMed⌕ Search

Biomedical subjects

J W Dailey

Publications and source records attributed to J W Dailey.

88 records · Page 5Linked to original sources
PubMed1978

Effects of adrenalectomy and adrenal steroids on norepinephrine synthesis and monamine oxidase activity.

Rat heart norepinephrine (NE) tunover was increased 6--10 days after bilateral adrenalectomy. This increase was prevented by administration of deoxycorticosterone acetate (DOCA) but not by either hydrocortisone or corticosterone. Blood pressure decreased following adrenalectomy. This decrease was prevented by DOCA, hydrocortisone and corticosterone. Monoamine oxidase (MAO) activity increased in the heart but not in the liver following adrenalectomy. DOCA prevented the increase in heart MAO activity whereas hydrocortisone and corticosterone were ineffective. In intact animals, heart and liver MAO activity were not changed by 5 days of cold exposure, a procedure which increases NE turnover. It is suggested that the increase in heart NE turnover may be related to the increase in MAO activity seen after adrenalectomy.

Adrenal Cortex Hormones↗
PubMed1978

Effects of maternally administered reserpine on the development of the cold stress response and its possible relation to adrenergic nervous system function.

Maternal administration of reserpine (100 microgram/kg/day) from day 8 of pregnancy until weaning of the pups produced no change in litter size, birth weight or weaning weight. At 70 to 80 days of age the offspring of reserpine treated dams were less able to maintain body temperature in response to cold stress with physical restraint. Similarly treated offspring exhibited a smaller rise in urinary free norepinephrine levels during the initial stages of cold exposure and they incorporated significantly less 14C from tyrosine into heart norepinephrine during acute cold exposure. No differences in incorporation of 14C into norepinephrine from tyrosine were evident when the animals were not subjected to cold stress. These data are consistent with the hypothesis that maternal administration of reserpine produces a permanent alteration in the ability of the offspring to respond to cold stress and that this deficit is related to an alteration in adrenergic nervous system development.

Animals↗
PubMed1977

The role of oxygen diffusivity in biochemical reactions.

It has been shown that increasing protein concentrations can decrease oxygen diffusion in 3 in vitro systems. We postulate that it is possible, and in some circumstances probable, that diffusion might be a rate limiting step in both in vitro and in vivo biological systems.

Animals↗
PubMedDate not supplied

The genetically epilepsy-prone rat (GEPR).

Two independently inbred strains of genetically epilepsy-prone rats (GEPRs) have been developed. GEPR-3s and GEPR-9s have moderate and severe degrees of seizure predisposition as well as expression, respectively. Seizure predisposition is a fundamental distinction between the normal and epileptic brain. Seizure predisposition in GEPRs and in humans with epilepsy includes spontaneous seizures and exaggerated seizure responsiveness and/or abnormally low thresholds to stimuli which also cause seizures in non-epileptic subjects. Activation of brainstem seizure circuitry by auditory input via the inferior colliculus causes electrographic and behavioral responses in GEPR-9s which replicates human generalized tonic/clonic seizures. Activation of brainstem seizure circuitry by input from forebrain seizure circuitry in GEPRs provides a newly discovered model of complex partial seizures with secondary generalization to tonic/clonic seizures. Thus, seizure predisposition in GEPRs offers a unique opportunity to study the human epilepsies that is not offered in studies of normal brain exposed to convulsant stimuli.

Animals↗
PubMedDate not supplied

Sex-specific distinctions in audiogenic convulsions exhibited by severe seizure genetically epilepsy-prone rats (GEPR-9s).

The severe seizure genetically epilepsy-prone rat (GEPR-9) is characterized by a broad-based seizure predisposition and is increasingly recognized as a useful model of epilepsy. When sound stimulated, members of the GEPR-9 colony exhibit complete tonic extensor convulsions. Female GEPR-9s appear to experience a higher frequency of more severe seizures than males when they are sound stimulated. The purpose of this report is to examine and document this observation. Convulsive behavior was evaluated in approximately 4400 GEPR-9s. Each of these animals was sound stimulated 3 times at weekly intervals. Audiogenic response score (ARS), latency to wild running and latency to convulsion were recorded for each animal in each of the 3 tests. For the first 2 weekly tests, females exhibited a significantly higher incidence of complete tonic convulsions, a significantly higher ARS and significantly shorter latencies to wild running and convulsions than did males. The significant differences in latencies persisted through the 3 tests, whereas an increase in the incidence of complete tonic convulsions among males led to a diminution of the differences between males and females in the other parameters. The possible underlying biochemical differences that are responsible for this sex difference in seizure severity are, as yet, unknown.

Acoustic Stimulation↗
PubMedDate not supplied

Audiogenic convulsions in moderate seizure genetically epilepsy-prone rats (GEPR-3s).

The moderate seizure genetically epilepsy-prone rat (GEPR-3) typically exhibits a generalized clonic convulsion upon acoustical stimulation. The purpose of this report is to document sex-specific distinctions in the seizure characteristics as well as the effect of prior seizure experience on sensitivity to acoustically induced seizures in members of the GEPR-3 colony. Convulsive behavior was evaluated in approximately 3300 GEPR-3s. Each of these animals was stimulated with sound 3 times at weekly intervals. Audiogenic response score (ARS), latency to the onset of wild running and latency to convulsion were recorded for each animal in each of 3 tests given at 1 week intervals. Statistical analysis revealed that compared to their male littermates, females exhibited significantly shorter latencies to onset of running and convulsion for the last of the 3 weekly tests. Also, in both sexes, a significantly higher incidence of clonic convulsions, an increase in audiogenic response scores and a reduction in latencies to running and convulsion were observed in each succeeding audiogenic stimulation test. The mechanism of this increased seizure facilitation with prior seizure experience may have at least some similarity to that of kindling. The factors responsible for sex-specific distinctions in seizure severity are unknown at the present time.

Acoustic Stimulation↗
PubMedDate not supplied

Ontogeny of sound-induced seizures in the genetically epilepsy-prone rat.

Seizure responsiveness of the adult genetically epilepsy-prone rat (GEPR) is well documented. Much less is known about the ontogeny to seizure activity in the GEPR. In the present study, members of the moderate seizure (GEPR-3) and severe seizure (GEPR-9) colonies were tested for susceptibility to sound-induced seizures at 11 different ages ranging from 13 to 45 days post partum. Running episodes first appeared in GEPR-3s at 15 days post partum. Clonic seizures first appeared in GEPR-3s and GEPR-9s at 15 and 16 days post partum, respectively. Seizure incidence reached 100% by post partum day 21 in both colonies. GEPR-3s exhibited a 100% incidence of their characteristic clonic seizure at day 21. GEPR-9s exhibited a 77.3% incidence of clonic seizure and a 22.7% incidence of their adult characteristic tonic seizure at day 21. Tonic seizures first appeared in GEPR-9s at day 18 and increased in incidence over time reaching 100% by day 45. Two unexpected findings occurred in GEPR-3s. First, secondary rearing seizures were detected in all GEPR-3s exhibiting clonic seizures between day 16 and 21. Second, GEPR-3s exhibited a transient susceptibility between 19 and 27 days post partum to the more severe tonic seizures characteristic of adult GEPR-9s. Peak incidence of tonic seizures in GEPR-3s was 70%, occurring at day 23. The adult GEPR-3 pattern of 100% incidence of clonic seizures was restored by day 45.

Acoustic Stimulation↗
PubMedDate not supplied

Neurobiology of seizure predisposition in the genetically epilepsy-prone rat.

Seizure predisposition in the genetically epilepsy-prone rat (GEPR) is innately determined and these animals exhibit consistent and reproducible convulsive patterns. This epilepsy model is made up of 2 independently derived colonies of animals with each exhibiting a characteristic convulsive pattern. In response to a standardized acoustic stimulus, GEPR-3s exhibit moderate or clonic convulsions and GEPR-9s exhibit more severe tonic extensor convulsions. Besides exhibiting convulsions in response to sound stimulation, some GEPRs experience spontaneous and hyperthermic seizures. They are also abnormally sensitive to a number of seizure provoking stimuli that produce seizures in normal animals. The neurochemical basis for the seizure predisposition in GEPRs is increasingly well understood. Abnormalities in central nervous system norepinephrine and serotonin are widespread and may play a prominent role in regulation of seizures in the GEPR. Amino acid neurotransmitter systems are less well defined in the GEPR but abnormalities exist and may be, along with other documented deficiencies, responsible in part for the seizure predisposition that is characteristic of GEPRs.

Acoustic Stimulation↗
PubMedDate not supplied

Non-pulsatile circulatory support in 90 cases.

Survival after cardiac arrest is reportably less than 10%; after cardiogenic shock it is less than 50%; and in failure to wean post-cardiotomy (even with centrifugal pumps in several large series) it is only 11-21%. The authors' experience with non-pulsatile circulatory support in 90 consecutive cases from 1986-91 has shown improved survival. The emergent cardiopulmonary bypass system (CPS) was used in 67 of the 90 patients, with 65 patients resuscitated, 34 (51%) weaned, and 19 (28%) transferred to other cardiovascular support therapies. Of the patients weaned or transferred, 34 (51%) survived > 24 hr, and 21 (31%) survived > 30 days. In the current series, 108 major cardiovascular procedures were done during or after CPS implementation. An in-house trained nursing team working with surgeons and perfusionists contributed to early implementation of the CPS and the subsequent improved survival. The BioMedicus centrifugal pump (VAD) was used predominantly for post-cardiotomy failure to wean in 16 patients and as a bridge to transplant in 7 patients. Fourteen patients (61%) were weaned or transplanted. Of these 14 patients, 11 (48%) survived > 30 days. Non-pulsatile circulatory support devices are relatively inexpensive and available to most hospitals. With careful patient selection and early implementation, one can expect survival of 37% of patients who would otherwise not survive.

Assisted Circulation↗
PubMedDate not supplied

Indices of noradrenergic function in the central nervous system of seizure-naive genetically epilepsy-prone rats.

Norepinephrine concentrations and tyrosine hydroxylase activity were determined in the brains of moderate-seizure and severe-seizure genetically epilepsy-prone rats (GEPRs) and in nonepileptic control rats. Both moderate-seizure (GEPR-3) and severe-seizure (GEPR-9) animals had widespread abnormalities in brain norepinephrine concentrations. Abnormalities in tyrosine hydroxylase activity were restricted to the midbrain. The state of abnormal seizure susceptibility, but not severity, in the GEPR may be determined by noradrenergic deficits in the hypothalamus/thalamus. Both seizure severity and susceptibility may be determined by noradrenergic deficits in the telencephalon, midbrain, and pons-medulla. Seizure severity but not susceptibility may be determined by noradrenergic abnormalities in the cerebellum.

Animals↗
PubMedDate not supplied

Noradrenergic abnormalities in the central nervous system of seizure-naive genetically epilepsy-prone rats.

Norepinephrine (NE) concentrations were measured in 15 discrete areas of the central nervous system of two types of genetically epilepsy-prone rats (GEPRs) and in nonepileptic controls. Both moderate-seizure (GEPR-3) and severe-seizure (GEPR-9) animals had extensive abnormalities in brain NE concentration. Deficits of equal magnitude in GEPR-3s and GEPR-9s were found in the spinal cord, midbrain minus the inferior colliculus, inferior colliculus, hypothalamus, amygdala, hippocampus, occipital + parietal cortex, frontal cortex, and olfactory septum. Because both types of GEPRs share these deficits and share seizure susceptibility, we hypothesize that these areas are candidates for regulation of seizure susceptibility in GEPRs. In addition, because GEPR-9s have more severe seizures than GEPR-3s and because GEPR-9s had greater NE deficits in several brain areas (cerebellum, pons-medulla, thalamus, and possibly the temporal cortex and olfactory bulbs), we hypothesize that these areas may be important in regulation of seizure severity in GEPRs. All animals used in these experiments had been protected from seizure-provoking stimuli and were naive to seizures. Because the abnormalities in NE concentration were present in seizure-predisposed animals that were protected from seizures, we conclude that these abnormalities are important components of the seizure-predisposition characteristic of GEPRs and do not result from seizure experience.

Acoustic Stimulation↗
PubMedDate not supplied

Dietary sodium and potassium-induced transient changes in blood pressure and catecholamine excretion in the Sprague-Dawley rat.

When Sprague-Dawley derived rats were changed from a chow type diet to a moderately high sodium diet, rapid transient changes in blood pressure (BP) and catecholamine excretion were observed. After 1 dietary week, BP increased from 122 +/- .1 mm Hg to approximately 145 mm Hg (p less than 0.001), and there was a concomitant 20% reduction in urinary norepinephrine (UNEV) and epinephrine (UEV) excretion (p less than 0.05). Heart rates were reduced (p less than 0.05). These data suggest that sodium-induced increases in BP were initially associated with suppressed sympathetic nervous system activity. During dietary Weeks 2 and 3, some animals had a persistent moderate elevation in BP (BP less than or equal to 150 mm Hg), while others developed more severe increases. UNEV in moderately hypertensive animals returned to control levels during this period; but UEV and heart rates remained suppressed. UNEV in severely hypertensive animals exceeded (13% +/- 3%, p less than 0.05) that of controls. This increase coincided with their most severe hypertension (171 +/- 1 mm Hg, p less than 0.001). UE values and heart rate data indicate that systemic adrenergic tone was likely suppressed at this time and that the increased UNEV was renal in origin. By dietary Week 4, the BP of severely hypertensive animals had begun to fall, and indices of sympathetic nervous system tone were indistinguishable among all groups. Inclusion of a dietary potassium supplement ameliorated the development of hypertension only in those animals that became severely hypertensive, and appeared to prevent the early suppression of indices of sympathetic activity.

Animals↗
PubMedDate not supplied

Drug excretion in human breast milk: principles, pharmacokinetics and projected consequences.

The excretion of drugs in human breast milk is reviewed with regard to milk production, composition, feeding patterns and mechanisms of drug transfer into milk. Fundamental principles of breast milk excretion are used to construct a pharmacokinetic approach useful for the study of most drugs. An infant-modulated 3-compartment open model is proposed for drug distribution and elimination in the breast feeding woman. Milk/plasma drug concentration ratios are projected on the basis of pH partitioning. While some studies confirm these projections, other studies demonstrate a need to consider additional factors such as lipid solubility and protein binding characteristics of a drug in milk. Data are lacking for most drugs and hence dosing via milk or risk to the infant remains speculative. Very few pharmacokinetic studies of both milk and infant plasma were found. A review of selected drug classes cites available information as a basis for future studies. Few drugs are contraindicated in breast feeding women, but supportive data for either proscriptions or permissive statements are often lacking. A neglected but potentially serious infant risk--impaired behaviour and development--is discussed from the standpoint of emerging animal data. Conceptually valid and comprehensive studies on drug excretion in breast milk are needed if this valuable nutrient for infants is to be made available safely.

Absorption↗