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Biomedical subjects

J B Long

Publications and source records attributed to J B Long.

At least 73 records · Page 4Linked to original sources
PubMed1985

Endogenous anticonvulsant substance in rat cerebrospinal fluid after a generalized seizure.

Cerebrospinal fluid taken from rats subjected to electroshock-induced seizures and injected into the cerebral ventricles of rats that had not been shocked increased the seizure threshold of the recipients. The anticonvulsant activity of the donor cerebrospinal fluid was antagonized by opioid antagonists and enhanced by peptidase inhibitors. These results suggest the existence of an endogenous anticonvulsant substance in rat cerebrospinal fluid, possibly opioid in nature, which is activated as a consequence of a seizure and which may play a critical role in postseizure inhibition.

Animals↗
PubMed1985

Endogenous opioid systems: physiological role in the self-limitation of seizures.

Immediately following a seizure, the severity of subsequent seizures is significantly reduced. The involvement of endogenous opioid systems as a physiological regulator of this postseizure inhibition was studied in rats using repeated maximal electroshock (MES) seizures. Both the opiate antagonist (-)-naloxone and morphine tolerance abolished the progressive seizure protection associated with repeated MES. We propose that endogenous opioids, activated by a prior seizure, provide a central homeostatic inhibitory mechanism which may be responsible for the initiation of a postictal refractory state in the epileptic.

Animals↗
PubMed1985

Blood-brain barrier: endogenous modulation by adrenal-cortical function.

The blood-brain barrier restricts the passage of molecules from the blood to the brain. The permeability of the barrier to iodine-125-labeled bovine serum albumin was examined in rats that had undergone adrenalectomy, adrenal demedullation, and corticosterone replacement. Adrenalectomy, but not adrenal demedullation, increased the permeability of brain tissue to the isotopically labeled macromolecule; corticosterone replacement reversed this effect. These results indicate that the blood-brain barrier may be hormonally regulated; that is, the pituitary-adrenal axis may physiologically modulate the permeability of the brain microvasculature to macromolecules.

Adrenal Cortex↗
PubMed1985

An improved method for the analysis of sister-chromatid exchange in vivo.

A single injection method of halogenated nucleosides for analysis in vivo of SCE is reported. Halogenated nucleosides were suspended in plant oils, such as peanut oil, and injected into mice subcutaneously. When the dosage of halogenated nucleosides reached 500 mg/kg, satisfactory differential sister chromatid staining of bone marrow cells was obtained. This technique was simple, neither special equipment nor surgical procedure was needed, and the dosage of halogenated nucleosides was relatively low.

Aflatoxin B1↗
PubMed1985

Results of revascularization and amputation in severe lower extremity ischemia: a five-year clinical experience.

Aggressive revascularization of the ischemic lower extremity in atherosclerotic occlusive disease by femoropopliteal (FP) and femorotibial (FT) bypass or profundaplasty (P), as indicated, has been advocated by some authors for all patients. Others have recommended primary amputation, particularly for tibial occlusive disease. To clarify this clinical dilemma, we reviewed the results of 547 procedures performed during the last 5 years: revascularization in 375 (69%) instances and below-knee amputation (BKA) in 172 (31%) cases. Bypass procedures were used in 246 cases: FP in 155 (64%) and FT in 91 (37%). Reversed autogenous saphenous vein (ASV) was used preferentially in 125 (51%) cases, whereas polytetrafluoroethylene (PTFE) was used in 121 (49%) cases. P was performed in 129 instances accompanied by inflow procedures in 92 (71%) of these cases. Cumulative limb salvage (LS) exceeded bypass patency in all categories and resulted in 2- and 5-year LS rates of 83% and 81% for FP with the use of ASV and 52% and 35% for PTFE. The LS rate for FT was 53% and 47%, respectively, for ASV and 20% and 15% for PTFE. Rest pain was successfully relieved by P in 99 cases (77%), whereas healing occurred in only 51% of cases with tissue loss. The perioperative mortality rate for revascularization was 3%; 42% of the group died during follow-up, death usually resulting from complications of atherosclerosis. Of the 172 BKAs, primary healing occurred in 80%, but the perioperative mortality rate was 13%. FP and FT bypasses are preferred procedures if ASV is available, whereas use of PTFE should be limited to FP bypasses only. Rest pain is relieved by P but tissue loss should prompt consideration for bypass. BKA should be considered in cases of severe tibial disease only in the absence of a suitable ASV, as the perioperative mortality rate is high and ultimate rehabilitation (64%) is limited.

Amputation, Surgical↗
PubMed1985

Asymptomatic carotid disease.

The advent of noninvasive screening tests has allowed the identification of an increasing number of patients with asymptomatic carotid stenoses. The management of these patients must be individualized, as the preferred method of therapy has not been established. Such a solution ultimately requires a prospective randomized trial to define the natural history of these lesions and to clearly establish if surgical therapy has a role. Currently, there is a Veterans Administration Cooperative Study underway which will attempt to fill the existing information gap. Specifically being examined is the relationship between subsequent cerebrovascular symptoms and the degree of stenosis, progression of stenosis, contralateral disease and non-carotid operation. This study will not be completed for five years, so that other, current guidelines must be sought. It is essential that any surgeon considering prophylactic carotid endarterectomy demonstrate combined morbidity and mortality figures of less than 3 per cent. The patients being considered must also be an acceptable cardiac risk, as myocardial infarction represents the most common postoperative complication. Until prospective data is available, with a detailed analysis of the degree of stenosis, presence of ulceration and ultimate clinical course, the surgeon undertaking prophylactic endarterectomy must carefully screen his patients and concentrate on groups at high risk. This is especially important as more data on the significant incidence (10 to 15 per cent) of carotid restenosis becomes available. The results of three studies (34, 36, 69) suggest that those patients with hemodynamically significant stenoses, identified noninvasively by OPG techniques, are at a greater risk for cerebral ischemic events than those patients without significant stenoses. In addition, an observed incidence of stroke of 17.5 per cent and an indicence of TIAs of 33 per cent in patients with disease progression demonstrated by OPG-K/CPA. The work of another researcher (71) suggests that patients with carotid stenoses can be observed until symptoms develop or until the stenosis progresses to greater than 80 per cent.(ABSTRACT TRUNCATED AT 400 WORDS)

Arterial Occlusive Diseases↗
PubMed1985

Opioids and neuropeptides: mechanisms in circulatory shock.

Endogenous opioid systems are activated in stressful situations such as circulatory shock. The opiate antagonist naloxone improves cardiovascular function in several models of shock caused by endotoxemia, hypovolemia, anaphylaxis, and spinal trauma. The ergotropic neuropeptide, thyrotropin-releasing hormone, in supraphysiological doses, also improves cardiovascular function in these shock models, but this effect does not result from action at the opiate receptor. For both these agents a central nervous system (CNS) site of action has been partially characterized. A variety of neuropeptides, including the opioids, seem capable of modulating autonomic function through their CNS actions. In addition, they may play a role in peripheral integration and transmission of autonomic nervous activity by actions at the ganglia and/or at nerve endings. Some neuropeptides also have direct autacoid effects on cells, including those of the microvasculature. This raises new questions concerning possible peripheral functions of neuropeptides during circulatory shock, and the nature of their interactions with other potential shock mediators such as monokines and arachidonic acid derivatives.

Adrenal Glands↗
PubMed1984

Possible involvement of serotonergic neurotransmission in neurotensin but not morphine analgesia.

The purpose of this study is to determine whether the antinociceptive properties of morphine and neurotensin (NT) are dependent upon central serotonergic neurotransmission. To this end, we studied the effects of morphine (10 mg/kg i.p.) and NT (30 micrograms i.c.v.) on the turnover of 5-hydroxytryptamine (5-HT) in 8 microdissected nuclei of adult rat brain: n. septalis lateralis (LS); n. tractus diagonalis (DB); n. amygdaloideus centralis (AG); posterior medial forebrain bundle (MFB); periaqueductal gray (PAG); n. raphe dorsalis (DR); n. centralis superior (NCS); and n. raphe magnus (RM). The systemic administration of morphine did not alter rates of 5-hydroxytryptophan (5-HTP) biosynthesis in any of the nuclei examined, although concentrations of serotonin were increased by 24% in the RM. In contrast, the central administration of neurotensin significantly decreased the rate of 5-HTP biosynthesis in the posterior MFB. The central administration of NT was accompanied by increased levels of serotonin in the DB, DR, and RM and by decreased serotonin levels in the MFB and PAG. In a complementary series of experiments, the effect of depletion of central 5-HT stores on the antinociceptive properties of both morphine and NT was determined. p-Chlorophenylalanine (PCPA, 325 mg/kg, i.p.) decreased whole brain 5-HT levels by 87%, but had no effect upon the increase in hot plate latencies induced by morphine. Conversely, although without significant antinociceptive properties of its own, PCPA markedly potentiated the antinociceptive effects of NT.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1984

ICI 174864, a putative delta opioid antagonist, reverses endotoxemic hypotension: pretreatment with dynorphin 1-13, A kappa agonist, blocks this action.

The putative delta opioid receptor antagonist ICI 174864 (3 mg/kg, i.v.) significantly reversed endotoxic shock hypotension at a dose which lacked significant pressor actions in normotensive, non-endotoxemic rats. In contrast, dynorphin 1-13, when administered either before (0.1 or 1.0 mg/kg, i.v.) or following (1.0 mg/kg, i.v.) injection of endotoxin, failed to alter the course of ensuing circulatory shock. Additionally, pretreatment with dynorphin 1-13 prevented the subsequent reversal of endotoxemic hypotension by ICI 174864. It is concluded that: 1) delta opioid receptors mediate the endogenous opioid component of endotoxic shock hypotension; and 2) functional interactions occur between ligands for mu, delta, and kappa opioid receptor subtypes, which may predict potential interactions with a common macromolecular opioid receptor complex.

Animals↗
PubMed1984

The assessment of skin blood flow in peripheral vascular disease by laser Doppler velocimetry.

The helium-neon laser Doppler (LD) is designed to measure skin blood flow velocity (SBFV). Flow velocity and pulse wave amplitude are expressed in millivolts (mv) relative to a zero-flow reference. The authors have reviewed their initial experience in ten persons (20 limbs) without peripheral vascular disease (PVD, group I) and nine patients (12 limbs) with severe PVD (group II). The finger, palm, great toe, and forehead had a significantly (P less than 0.05) greater flow velocity than the plantar and dorsal foot, distal and proximal leg, thigh, chest, arm, and forearm. Baseline and hyperemic SBFV, measured at the great toe, were compared in groups I and II. In group I, the baseline SBFV (mv, mean +/- standard error of the mean (SEM] in the great toe was 197 +/- 38 compared with 67 +/- 12 in group-II patients (P less than 0.05). The pulse wave amplitude (mv, mean +/- SEM) was 77 +/- 14 in group I and 5.4 +/- 1.1 in group II (P less than 0.05). The time to maximal hyperemic response (seconds, mean +/- SEM) in group I was 18 +/- 1.5 compared with 150 +/- 14 in group II (P less than 0.05). LD is a sensitive indicator of changes in SBFV, allowing differentiation between normal persons and patients with PVD. The LD tracing in patients with PVD is characterized by a baseline SBFV that is significantly less than normal and also by the attenuation or absence of pulse waves. The diagnostic accuracy is enhanced by the use of reactive hyperemia.

Adult↗
PubMed1983

Effects of castration and adrenalectomy on in vitro rates of tryptophan hydroxylation and levels of serotonin in microdissected brain nuclei of adult male rats.

Rates of 5-hydroxytryptophan (5-HTP) synthesis and levels of serotonin (5-HT) were measured in microdissected brain nuclei following castration or adrenalectomy of adult male rats. Fourteen days following gonadectomy, 5-HTP synthesis decreased in the nucleus raphe dorsalis (DR) and nucleus centralis superior (NCS), while levels of 5-HT were unchanged in the 7 brain nuclei examined. Administration of testosterone to castrated rats not only did not reverse the castration-induced decrease in 5-HTP synthesis in the DR and NCS, but also decreased 5-HT synthesis in the nucleus amygdaloideus centralis (AGC) and the nucleus septalis lateralis (LS). Following administration of testosterone, 5-HT levels were unchanged. 10 days following bilateral adrenalectomy, 5-HTP synthesis increased in the NCS and the median eminence. Levels of 5-HT increased only in the median eminence. The increased 5-HTP synthesis and 5-HT levels following adrenalectomy were not reversed by corticosterone administration. In addition, these selective changes in 5-HT metabolism did not result from hormonal effects on the availability of tryptophan to the brain. We conclude that there are subsets of serotonergic neurons in rat central nervous system which respond uniquely to removal of the gonads and adrenals. Furthermore, the dissociation between serum and brain tryptophan concentrations and changes in rates of 5-HTP synthesis argue against tryptophan availability as being a primary determinant of 5-HT biosynthesis and for a direct endocrine central nervous system interaction with serotonergic neurons.

5-Hydroxytryptophan↗
PubMed1983

Regional differences in the response of serotonergic neurons in rat CNS to drugs.

In vivo rates of 5-hydroxytryptophan accumulation (following administration of the decarboxylase inhibitor R04/4602/1) and levels of 5-HT in the nucleus raphe dorsalis (DR), nucleus centralis superior (NCS), nucleus septalis lateralis (LS), nucleus suprachiasmaticus (SCN), nucleus hypothalamicus anterior (AH), and nucleus amygdaloideus centralis (AG) were determined following administration of fluoxetine, 5-methoxy-N,N-dimethyltryptamine, methiothepin, L-tryptophan and reserpine. Fluoxetine and 5-methoxy-N,N-dimethyltryptamine inhibited 5-hydroxytryptophan synthesis in all nuclei, although inhibition of synthesis in the DR was resistant to fluoxetine. Methiothepin inhibited 5-HT synthesis in the DR, NCS, LS and AG, but not in the SCN or AH. L-Tryptophan greatly increased 5HT synthesis in all areas, but this increase was not uniform, being fourfold greater in the NCS than in the LS. Reserpine, while greatly depleting 5HT did not increase 5-hydroxytryptophan synthesis in any nucleus. In no region could changes in brain tryptophan account for the observed drug effects on serotonin metabolism. We conclude that not all CNS serotonergic structures respond to the same drug in a uniform manner.

5-Hydroxytryptophan↗
PubMed1982

A microassay for simultaneous measurement of in vivo rates of tryptophan hydroxylation and levels of serotonin in discrete brain nuclei.

A sensitive procedure for simultaneous determination of in vivo rates of tryptophan hydroxylation and levels of serotonin (5-HT) in discrete rat brain nuclei is described. Rates of tryptophan hydroxylation are estimated by 5-hydroxytryptophan (5-HTP) accumulation following l-aromatic amino acid decarboxylase inhibition by R04-4602/1. 5-HTP is separated from 5-HT by liquid cation exchange after which both 5-HTP and 5-HT are measured by a sensitive radioenzymatic assay. Following decarboxylase inhibition, 5-HTP accumulates over 30 min in 6 brain nuclei examined, with negligible levels of 5-HTP being measured in the absence of decarboxylase inhibition. 5-HT levels do not change significantly up to 45 min after decarboxylase inhibition. Comparison of rates of tryptophan hydroxylation determined in 12 different microdissected rat brain areas reveals a greater rate of 5-HT biosynthetic activity in raphe nuclei containing 5-HT cell bodies than in nuclei containing 5-HT terminals. Pretreatment with para-chlorophenylalanine markedly reduces both 5-HTP accumulation and 5-HT levels in the nucleus raphe dorsalis. With this procedure quantities as little as 10 pg of both 5-HTP and 5-HT can be measured, allowing estimation of in vivo serotonin biosynthesis in microgram quantities of brain tissue.

5-Hydroxytryptophan↗