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Biomedical subjects

D E Richardson

Publications and source records attributed to D E Richardson.

At least 19 recordsLinked to original sources
PubMed2001

Mechanism of sulfide oxidations by peroxymonocarbonate.

A detailed mechanism for the oxidation of aryl sulfides by peroxymonocarbonate ion in cosolvent/water media is described. Kinetic studies were performed to characterize the transition state, including a Hammett correlation and variation of solvent composition. The results are consistent with a charge-separated transition state relative to the reactants, with an increase of positive charge on the sulfur following nucleophilic attack of the sulfide at the electrophilic oxygen of peroxymonocarbonate. In addition, an average solvent isotope effect of 1.5 +/- 0.2 for most aryl sulfide oxidations is consistent with proton transfer in the transition state of the rate-determining step. Activation parameters for oxidation of ethyl phenyl sulfide in tert-butyl alcohol/water are reported. From the pH dependence of oxidation rates and (13)C NMR equilibrium experiments, the estimated pK(a) of peroxymonocarbonate was found to be approximately 10.6.

Journal Article↗
PubMed2001

Frontal sinus osteoma associated with cerebral abscess formation: a case report.

BACKGROUND: Osteomas of the paranasal sinuses rarely lead to intracranial manifestations. We present an unusual case of a frontal sinus osteoma leading to intracerebral abscess formation. CASE DESCRIPTION: A 51-year-old Hispanic man presented with increasing frontal headaches, new onset seizure, lethargy, global dysphasia, and unilateral hemiparesis. CSF studies demonstrated mild pleocytosis. Neuroradiological studies revealed an opacity filling the left frontal sinus, as well as a ring-enhancing mass with surrounding edema in the left frontal lobe. The patient was surgically treated with a left frontal osteoplastic craniotomy and removal of the abscess and bony mass. Intraoperative cultures were positive for Streptococcus pneumoniae. Pathology revealed bony tumor consistent with osteoma. The patient's neurological status improved to baseline after surgery. CONCLUSION: The frontal sinus osteoma was associated with rapid development of a frontal lobe abscess, requiring emergent surgical debridement. Although rare, intracerebral manifestations should be considered and expected as a cause of new neurological deficits in the presence of paranasal sinus osteoma.

Brain Abscess↗
PubMed2000

Lateral tegmental field neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge.

Neurons in the lateral tegmental field (FTL) has been previously reported to have activity only minimally correlated (< 1% of neurons tested) with the 10-Hz rhythm of the slow wave of the sympathetic nerve discharge. We report here that 10% of the neurons recently tested in the FTL could be shown to correlate with the 10-Hz rhythm. The neuron-to-nerve coherence is weaker than in other medullary areas, but is nonetheless significant.

Animals↗
PubMed1997

Neurons of the rostral para-ambiguual field have activity correlated to the 10-Hz rhythm in sympathetic nerve discharge of urethane-anesthetized cat.

Using the techniques of time domain correlation (mid-signal spike-triggered averaging) and frequency domain correlation (neuron-to-nerve coherence), 24% (54) of a sample of 229 neurons of the rostral para-ambiguual field have shown to have activity correlated to the 8- to 13-Hz rhythm in the inferior cardiac sympathetic nerve discharge (SND) of urethane-anesthetized cat. This correlation existed in both baroreceptor-innervated and -denervated animals. Of the correlated neurons, 37% (20) were non-rhythmically firing and displayed flat autospectra, while 63% (34) fired rhythmically and contained well-defined peaks in their autospectra. The group firing rate of these neurons was 4.3 +/- 0.4 spikes/s, indicating that they are not pacemaker neurons for the 10-Hz SND rhythm. The group time of firing of these neurons to the next peak of the SND slow wave was 52 +/- 4 ms. Correlation of the activity of medullary neurons with the 8-13-Hz rhythm of the SND was previously claimed only for rostral ventrolateral medulla, caudal raphe, and rostral caudal ventrolateral medulla. This present finding suggests that this behavior may be more widely spread throughout the medulla.

Anesthetics, Intravenous↗
PubMed1997

The depression system: preliminary studies.

The learned helplessness paradigm was used to test the notion that lesions of a theatrical depression system in the rat will produce antidepression similar to antidepressive medication. Lateral brain stem lesions were effective in producing antidepression and unilateral lesions were as effective as bilateral lesions. Ibotenic acid lesions were not effective, indicating that the effective target site was in a fiber tract and not a cell nucleus.

Animals↗
PubMed1995

Sympathetically-mediated cardiovascular responses induced by neurochemical microinjection in the brainstem lateral tegmental field of cat.

This study examines sympathetically-mediated cardiovascular responses arising from microinjections of AMPA and kynurenic acid in the medullary lateral tegmental field (LTF). The resulting behavior, which is predominantly inhibitory, is nearly identical to that reported for the para-ambiguual area lying just lateral to the LTF, and suggests that the two regions may share other cardiovascular control functions.

Animals↗
PubMed1995

Deep brain stimulation for the relief of chronic pain.

Deep brain stimulation analgesia is an effective method of treating otherwise intractable chronic pain, with few side-effects, and long-term good or better results in 50% to 80% of patients, depending on etiology and stimulation site. In general, the best results are in deafferentation pain with internal capsule stimulation and somatic pain with periventricular stimulation.

Brain↗
PubMed1993

Cardiovascular sympathoinhibitory neurons form an extended longitudinal column in cat lateral medulla.

A search for vasomotor depressor sites in the lateral medullary brainstem of anesthetized cat using microinjections of AMPA has delineated a longitudinal column of sympathoinhibitory neurons consisting of the rostral depressor area, the caudal ventrolateral medulla, and a new intermediate depressor area. Systematic blockade of these three subregions with bilateral microinjections of kynurenic acid indicates a uniform involvement of the entire column with sympathetic baroreflex, but a slightly greater involvement of the anterior portion, over the posterior, with regulation of cardiovascular tone.

Animals↗
PubMed1992

Cranioplasty using gentamicin-loaded acrylic cement: a test of neurotoxicity.

Cranioplasty represents a formidable challenge for neuro-surgeons, with a significant morbidity from both early and late wound infections. Polymethylmethacrylate (PMMA) is one of the most widely used materials in this setting. Despite the advantages of this material, such as ease of handling and inert biochemical properties, it is still a foreign body that is prone to infection. We present an animal model using a gentamicin-impregnated PMMA patch to assess the neurotoxicity as well as the efficacy of using this as an alternative material to lessen the infectious morbidity in this clinical setting. In part two of our experiment, we used a PMMA patch of similar weight and surface area in a physiological saline solution to determine the rate of gentamicin elution from the patch. The results obtained appear promising with no evidence of neurotoxicity and warrant further study to assess the clinical efficacy of PMMA in this setting.

Animals↗
PubMed1991

A sympathoinhibitory area in cat rostral medulla: its role in cardiovascular tone regulation and baroreflex.

We have found a medullary vasodepressor area in cat centered 3 mm rostral to the obex and just lateral to the compact division of the ambiguus nucleus. The area is compact, extending at most 1 mm in any direction. Microinjection of L-glutamate into this rostral depressor area (RDA) elicited acute hypotension and bradycardia. These responses were not reduced by either peripheral atropine blockade or bilateral vagotomy, but they were nearly abolished by peripheral phentolamine/propranolol blockade or high cervical cord transection. Bilateral reversible blockade of the RDA by local microinjection of the neuronal hyperpolarizing agent muscimol yielded chronic hypertension and tachycardia. Sympathetically mediated baroreflex, observed as a bradycardic response to a peripherally administered phenylephrine bolus in atropinized animals, was partially (50%) abolished during this same blockade. We conclude that the RDA contains sympathoinhibitory cells which are involved in the regulation of cardiovascular tone and in the expression of the sympathetic component of baroreflex.

Animals↗
PubMed1990

Central stimulation-induced analgesia in humans--modulation by endogenous opioid peptides.

Stimulation of the endogenous opiate system produced relief of somatosensory induced pain states. Stimulation of the nonopiate system can control pain from somatosensory causes as well as damage to the nervous system. Neither of these systems in themselves are rewarding or produce self-stimulation in humans, who have free choice of whether to use stimulation or not, except to reduce discomfort. Lack of pain in general produces lack of use of the stimulation system. Apparently, the descending opiate system for somatosensory pain control involves descending norepinephrine and serotonin pathways at an intermediate step through the dorsolateral funiculus of the cord. Enhancement of the opiate system can be produced by administration of L-Tryptophan and L-Dopa due to precursor loading of serotonin and norepinephrine. The endogenous opiate system, when activated by electrical stimulation, usually produces excellent control of somatosensory induced pain, but often is not effective for centrally produced pain. Stimulation of areas that produce analgesia that are nonopiate-dependent are usually more effective in reducing pain from damage to the nervous system itself than the opiate-dependent system, but this is sometimes the converse. While cross tolerance to morphine from electrical stimulation of the endogenous opiate system exists in animals, it does not seem to be a problem clinically as the abstinence syndrome and tolerance have not been a problem in humans.

Analgesia↗
PubMed1988

Platinum(II) binding to metallothioneins.

The reaction of equine renal metallothionein (MT) with excess K2PtCl4 at pH 2 results in a polymeric adduct containing 17 +/- 2 mol Pt/mol MT. A monomeric adduct containing 7 mol Pt/mol MT is obtained at neutral pH. Rates of reaction of Pt7MT with DTNB and iodoacetic acid are consistent with Pt2+ to cysteine thiolate coordination, and the extent of reaction in both cases is 11 +/- 2 mol cys/mol MT. Adducts from the reaction of K2PtCl4 with apoMT chemically modified at the N-terminal methionine residue, Cd7MT, and native MT are also reported. A structural model of Pt7MT is proposed in which the square planar tetrathiolate Pt(II) unit is incorporated into a three-metal beta cluster. Implications for the metabolism of platinum anticancer drugs are discussed.

Animals↗
PubMed1988

Pulmonary vascular responses to forebrain stimulation in the cat.

The effects of forebrain stimulation on the pulmonary vascular bed were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was raised to a high steady level, direct electrical stimulation of the forebrain elicited a biphasic change in lobar arterial pressure. The response was characterized by an initial transient increase in lobar arterial pressure that was followed by a prolonged secondary decrease in pressure. When a delay coil was added to the extracorporeal perfusion circuit, the secondary vasodilator response was separated into initial brief and delayed prolonged components, suggesting that it was mediated in part by the release of a humoral factor. The entire response to forebrain stimulation was abolished by cervical cord section or freezing. The initial constrictor response and early brief dilator response were not blocked by classic pharmacological blocking agents. The delayed humorally mediated vasodilator response was blocked by propranolol or ICI 118551, indicating that it was mediated by a circulating factor with beta 2-stimulating properties. The delayed vasodilator response was associated with a large increase in arterial epinephrine levels, and this rise in plasma epinephrine was not altered by propranolol. The present data suggest that electrical stimulation of the forebrain causes a prolonged pulmonary vasodilator response that is mediated by way of a descending pathway, which results in a large rise in arterial epinephrine levels.

Animals↗
PubMed1988

Zinc suppression of free radicals induced in cultures of rat hepatocytes by iron, t-butyl hydroperoxide, and 3-methylindole.

The effect of zinc on lipid peroxidation initiated by either ferric-nitrilotriacetate, t-butyl hydroperoxide, or 3-methylindole was studied using primary monolayer cultures of rat liver parenchymal cells. The malondialdehyde content of the cells and culture medium was used to estimate the extent of lipid peroxidation. As the zinc concentration of the culture medium was increased from 1 to 48 microM, peroxidation was diminished. Cellular zinc and metallothionein levels were proportionally increased by supplemental zinc. Zinc supplementation of the medium inhibited NADPH-cytochrome c reductase activity and stimulated glutathione peroxidase activity. The uptake of iron into the hepatocytes was significantly reduced as the level of zinc was raised, suggesting that zinc antagonizes uptake of chelated iron into isolated hepatocytes and in this way blocks iron-induced peroxidation. Furthermore, induction of metallothionein synthesis by zinc may contribute to the reduction in free radicals. Spectra from electron spin resonance studies, using phenylbutylnitrone as a spin-trapping reagent, demonstrated that free radical production was inversely related to the zinc concentration of the culture medium. Spin trap data suggest that metallothionein added to lysed cells in vitro decreases free radical production. Studies using the spin trap, 3,3,5,5-tetramethylpyrroline-N-oxide indicated that cumulatively the predominant radical present in the cultures was a phenyl radical with hydroperoxide or methylindole. Collectively, our data demonstrate that zinc inhibits free radical production and lipid peroxidation in cultured hepatocytes. The mode of action of zinc could occur via free radical scavenging by zinc-induced metallothionein and/or by processes related to cytochrome P-450 and glutathione peroxidase, since these were also found to be sensitive to zinc supplementation levels of the culture medium.

Animals↗
PubMed1987

Allosteric interactions in sipunculid and brachiopod hemerythrins.

Chemical and spectroscopic consequences of allosteric interactions for ligand binding to sipunculid (Phascolopsis gouldii) and brachiopod (Lingula reevii) hemerythrins (Hrs) have been investigated. Possible allosteric effectors for homotropic effects in sipunculid Hrs have been examined, but only reduction in ligand affinity is observed without cooperativity. In contrast to sipunculid Hr, L. reevii Hr binds O2 cooperatively in the pH range 7-8 and exhibits a Bohr effect. Spectroscopic comparisons of the sipunculid and brachiopod Hrs show no significant differences in the active site structures; therefore, modulation of oxygen affinity is attributable to effects linking the site to quaternary structural changes in the octamer. Oxygen equilibria can be fit with a conformational model incorporating a minimum of three states, tensed (T), relaxed (R), and an R-T hybrid. Resonance Raman spectra of L. reevii oxyHr show a shift in the peroxo stretching frequency when the pH is lowered from pH 7.7 (predominantly R oxyHr) to pH 6.3 (a mixture of R, T, and R-T hybrid), but P. gouldii Hr does not have a frequency shift under the same conditions. In contrast to hemoglobins, ligand binding to the deoxy and met forms is noncooperative for brachiopod (and sipunculid) Hrs. It is thus suggested that conformational changes in the protein are linked to the oxidation state change that accompanies oxygenation of the coupled binuclear iron site (deoxy [FeIIFeII]----oxy [FeIIIFeIII]). The total allosteric energy expended in oxygenation is about 1.4 kcal/mol, and such a shift is possible in the relaxed-tense conversion with relatively limited constraints of the iron coordination environment via the protein quaternary structure. The mechanism of cooperativity in the binuclear copper oxygen carrier hemocyanin is discussed in light of these results.

Allosteric Regulation↗