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California↗
Biomedical subjects
W E Smith
Publications and source records attributed to W E Smith.
Ascorbic acid, glutathione and synthetic antioxidants prevent the oxidation of vitamin E in platelets.
An earlier report from this laboratory showed that tocopherol in human platelets is oxidized when the platelets are incubated in vitro in Tyrode medium with arachidonate (or other oxidants). Arachidonate is a more potent oxidizing agent in 50 mM potassium phosphate buffer at pH 7.4 with 0.1 mM ethylenediaminetetraacetic acid (EDTA) than in Tyrode medium. Forty to fifty percent of total platelet tocopherol was oxidized upon incubation with 40-50 microM arachidonate in the phosphate-buffered medium. The tocopherol oxidation took place within 15 min after the addition of arachidonate. Preincubation of platelets with ascorbate blocked the oxidation of tocopherol. This is one of the first direct in vitro demonstrations of the vitamin E-sparing action of vitamin C in media containing biological cellular material. Other compounds which blocked the oxidation of platelet tocopherol were ascorbyl palmitate, propyl gallate, butylated hydroxytoluene, hydroquinone and glutathione. If ascorbate or glutathione was added after the tocopherol was oxidized to the quinone there was no reversal of the oxidation.
Adult↗
Free radical pathology in chronic arterial disease.
The generation of toxic oxygen metabolites is more usually associated with inflammation. However, pathological free radical reactions can cause tissue damage by adversely affecting prostacyclin (PGI2) synthesis allowing initiation of coagulation. We have assessed changes in the red cell defence to toxic oxygen metabolite generation, viz measurement of glutathione concentration (GSH) and superoxide dismutase activity (SOD). GSH and SOD were measured in 20 patients with peripheral arterial disease, 22 patients with vasculitis, and 11 patients with angina, and compared to 17 matched controls. The 53 subjects with arterial disease had significantly lower SOD levels: in contrast GSH levels were significantly higher. Extracellularly plasma thiol levels (PSH) were low and caeruloplasmin (Cp) levels were high. We suggest that free radical pathology exists not only in inflammatory vascular disease but also in atherosclerosis.
Angina Pectoris↗
Captopril: a free radical scavenger.
The use of captopril in heart failure and hypertension is becoming increasingly accepted. Captopril has a sulphydryl group in its molecular structure. We wondered if this might confer free radical scavenging activity on the drug and have investigated this in an in vitro system. Results show that captopril is a free radical scavenger and we suggest that this action might be relevant in its use in heart failure and other vascular diseases.
Angiotensin-Converting Enzyme Inhibitors↗
Free radicals and Graves' disease: the effects of therapy.
Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH) and superoxide dismutase (SOD) activity were measured in 30 patients with newly diagnosed Graves' disease (GD). Compared to control subjects (C) PSH and SOD were significantly reduced (C vs GD, 507 vs 449 mumol/l, P less than 0.01; 2.1 vs 1.6 mumol/l, P less than 0.01 respectively) and LSH was significantly raised (C vs GD 181 vs 298 mumol/l). Treatment with carbimazole produced a significant rise in LSH and SOD. Propylthiouracil (PTU) treatment raised LSH levels but 131I treatment produced no significant change. All four parameters are involved in different ways in oxygen metabolism and together provide an indication of oxidative stress across the red-cell membrane. In addition LSH is a general radical scavenger and SOD a specific O2- scavenger. In Graves' disease the increased oxidative stress and increased general radical scavenging may result from raised free-radical activity. These changes, which have not previously been reported in Graves' patients, were modified by antithyroid drug therapy, but it is not clear whether this is a direct or indirect effect.
Adult↗
Cellular response to oxidative stress at sulfhydryl group receptor sites on the erythrocyte membrane.
Ellman's reagent was used to induce an oxidative stimulus on the exofacial membrane sulfhydryl groups of the human erythrocyte. Thiol-disulfide exchange occurring extracellularly was monitored using resonance Raman spectroscopy, and intracellular changes were observed by 1H spin echo nuclear magnetic resonance spectroscopy of the intact cell. The stimulus caused oxidation and depletion of the glutathione pool, which was followed at higher concentrations of Ellman's reagent by a depletion of intracellular ergothioneine levels. Larger changes are induced intracellularly than would be expected from the stoichiometry of the reaction at the exofacial surface. A mechanism is proposed which links exofacial sulfhydryl receptor sites via the transport proteins to spectrin and glutathione. The consequences for the cellular redox balance of an extracellular stimulus of this type are discussed.
Blood Glucose↗
Doxorubicin-induced altered glycolytic patterns in the leukemic cell studied by proton spin echo NMR.
1H spin echo NMR of the leukemic cell line J-lll is reported. Phosphorylcholine, phosphorylcreatine, lactate and mobile triglyceride are identified as constituents of the cytosolic pool in the intact and viable cells. The concentration of cells in the NMR tube is high (approx. 10(9) in 0.4 ml) and as a result the available oxygen is restricted, making the NMR experiment a plausible in vitro tumour model in which kinetics in the living cell can be probed in a non-invasive manner. Treatment with pharmacological concentrations of the drug doxorubicin produced immediate enhanced anaerobic glycolysis and eventual cell death.
Doxorubicin↗
Evidence that the catalytic differences of two structurally homologous forms of cytochrome P-450 relate to their heme environment.
Cytochromes P-450 PB3a and PB3b, which appear to be equivalent to forms b and e described by Ryan et al. [Ryan, D.E., Thomas, P.E., & Levin, W. (1982) Arch. Biochem. Biophys. 216, 272-288], have been shown to share 97% sequence homology [Suwa, Y., Mizukami, Y., Sogawa, K., & Fujii-Kuriyama, Y. (1985) J. Biol. Chem. 260, 7980-7984] yet exhibit an intriguing difference in enzymatic activity. Studies to establish the basis for this difference, including a development of the technique of surface-enhanced resonance Raman spectroscopy (SERRS), are reported. Studies on substrate binding, metabolism, and redox properties, as well as SERRS, indicate a significant difference in the heme environment of these two proteins. No significant difference in the interaction of the two proteins with P-450 reductase could be established. However, this interaction appeared sensitive to changes in ionic strength, suggesting ionic interactions are important in the functional coupling of these electron-transport components. A marked variation in the ratio of PB3a to PB3b activity in the metabolism of different substrates, which included a series of structurally similar resorufin analogues, provided further evidence that reductase coupling was not a critical factor. Therefore, the few amino acid differences observed between these proteins indicate sites that may be important in influencing the heme environment of these cytochrome P-450's.
Animals↗
Spin-echo 1H NMR detected response of ergothioneine to oxidative stress in the intact human erythrocyte.
Human erythrocytes were subjected to oxidative stress using arsenicals. The study is a model for thiol-related redox processes observed in the etiology of diseases such as rheumatoid arthritis. Spin-echo NMR spectroscopy of the living cell was used to monitor the cellular biochemistry. Oxidation of glutathione and the first demonstrated response of ergothioneine to a chemical stimulus in a cell were observed. The reversible nature of the ergothioneine response is interpreted as an environmental rather than a chemical change.
Arthritis, Rheumatoid↗
Resonance Raman spectroscopy of hemoglobin in intact cells: a probe of oxygen uptake by erythrocytes in rheumatoid arthritis.
Resonance Raman spectra from intact viable erythrocytes can be used to study oxygen uptake in solution. In addition to changes in the oxidation state marker (nu 4), other bands due to the porphyrin ring (nu 3) and vinyl modes indicate subtle changes at oxygen pressures close to where the T/R change occurs. A comparison of whole cell and lysate spectra indicates a partial denaturation of hemoglobin on lysis. A simple smear technique is used to measure spectra from rheumatoid and normal blood. Results indicate a faster but less complete uptake of oxygen in cells from patients with rheumatoid arthritis than is the case in normal cell populations.
Arthritis, Rheumatoid↗
The use of 1H spin echo NMR and HPLC to confirm doxorubicin induced depletion of glutathione in the intact HeLa cell.
The effects of doxorubicin on the cellular biochemistry of the HeLa cell using 1H spin echo nuclear magnetic resonance spectroscopy (NMR) of the intact and viable cell in conjunction with dual wavelength HPLC of cell lysates is reported. Directly dose-related changes were observed in lactate and reduced glutathione concentration. Doxorubicin induces a time-dependent depletion of the cytosolic pool of glutathione and a change in the glycolytic pattern of the cell. The glutathione depletion could be partially reversed by controlled pre-treatment of the cells with N-acetylcysteine and cysteine, the protection being linked to the intracellular concentration of the thiol.
Acetylcysteine↗
Do only the healthy intend to participate in worksite health promotion?
Few companies or organizations involved in health promotion have addressed the major question of whether they are reaching the employees with the greatest health needs or those who could benefit most from these efforts. The popular view that only individuals who are already physically fit and healthy participate in worksite wellness programs was critically examined. Data from 523 survey respondents at the University of Oregon were analyzed to determine whether employees differed on health-related characteristics and their interest in attending a worksite health promotion program. Comparisons between program participant "intenders" and "nonintenders" revealed that both groups had similar lifestyle habits, preventive health practices, and health status profiles. Significant differences were more related to age and perceptions about their physical and emotional health status. Implications for health risk reduction program planning in the work setting are discussed.
Attitude to Health↗
Linear estimation theory applied to the evaluation of a priori information and system optimization in coded-aperture imaging.
Linear estimation theory is developed in the context of object reconstruction from data obtained by a general shift-variant imaging system. The formalism adopts nonstationary first- and second-order statistics of the object and noise classes as priori information. In addition, a metric for system optimization that depends on the a priori information is presented. The role of this a priori information as derived from several different training sets is then studied with respect to reconstruction performance for various noise levels in the data, using a tomographic coded-aperture system as the model. In a separate experiment, a simple coded-aperture system is optimized to a particular object class, and the results are compared with those from an earlier optimization experiment.
Diagnostic Imaging↗
A comparison of the free radical scavenging activity of leukotrienes and prostaglandins.
The relative reactivity of leukotrienes and prostaglandins to free radicals and the superoxide ion generated by the photo oxidation of dianisidine have been assessed in vitro. Leukotrienes are effective general radical scavengers rather than superoxide scavengers, with the order of effectiveness LTD4 greater than LTC4 greater than LTB4. Prostaglandins are relatively unreactive. It is suggested that this susceptibility to free radical attack may be one reason for the formation of chemotactic agents from leukotrienes rather than prostaglandins and this may be one part of the mode of action of these compounds in chronic inflammation.
Dianisidine↗
Excellence in the management of clinical pharmacy services.
Differences in the management of clinical versus nonclinical pharmaceutical services, unique aspects of managing clinical services, and management challenges for the 1990s are described. In nonclinical practice, pharmacists are located in the central pharmacy and have limited contact with physicians and nurses; managers focus on drug procurement, distribution, and accountability. A clinical program takes pharmacists to the patient's bedside and into more inter-professional contact; the management of a clinical pharmacy service is measured by the benefits received by patients, physicians, and nurses and by the job satisfaction of the pharmacists. Management of a clinical program requires (1) recognition of the potential for drugs to cause harm and commitment to pharmacists' responsibility for ensuring appropriate clinical outcomes, (2) analysis of the hospital and how clinical services can best be provided there, (3) obtaining resources to establish or gain access to a drug information service, (4) developing resources and support for a pharmacokinetics service, (5) for a pharmacokinetics service, (5) designing efficient distribution systems supported by automated applications and an adequate technician staff, (6) developing a pharmacist staff that will gain physicians' and nurses' support for clinical programs, (7) developing an organized approach to keeping staff members up to date on new drugs and technology and assisting them in sharing this knowledge with physicians and nurses, (8) demanding and ensuring the quality of the clinical performance of each pharmacist, (9) documenting and evaluating the cost-effectiveness of services provided, and (10) recruiting and retaining good pharmacists and technicians.(ABSTRACT TRUNCATED AT 250 WORDS)
Attitude↗
A decade of experience with a clinical pharmacokinetics service.
The development, operation, and functions of the pharmacokinetics service at Memorial Medical Center of Long Beach (MMCLB) are described, and the data used to determine the quality and cost-effectiveness of the service are presented. Current functions of the pharmacokinetics service at MMCLB include making brief written comments about the interpretations of serum drug concentrations (SDCs) and oral recommendations to physicians on dosage adjustment; provision of written consultations with dosage recommendations; provision of drug information, education, and research; and development of drug dosing guidelines for the pharmacy and medical staff. During the 10-year existence of this service, costs have been justified on the basis of not only revenue generated by the service (in the form of "drug concentration scheduling" and "drug concentration evaluation" fees charged to patients) but also by cost savings resulting from the prevention of inappropriate, misleading, and potentially dangerous SDCs. An audit conducted in 1986 showed that the policy of having pharmacists schedule the sampling times for SDCs saves about $500,000 annually. Quality assurance has been documented by auditing compliance with and therapeutic effectiveness of dosing guidelines and by working with laboratory personnel to identify and prevent spurious SDC results and assay errors. The methods used by the pharmacokinetics service at MMCLB to document the benefits of the service have been vital in proving both its cost-effectiveness and its positive effect on patient care.
California↗
Sialolithiasis of the minor salivary glands.
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Adult↗
Surface enhanced resonance Raman scattering as a probe of the spin state of structurally related cytochromes P-450 from rat liver.
Surface enhanced resonance Raman scattering (SERRS) was observed from structurally related drug-induced rat liver cytochromes P-450 adsorbed on a silver colloid. Careful control of pH and the sequence of addition of components to the so1 is required to prevent protein denaturation at the surface due to conversion to P-450's biologically inactive form P-420 or haem loss. A low-spin P-450 (PB3a), a mixed low- and high-spin P-450 (PB3b) and a predominantly high-spin P-450 (MC1a) were investigated. Spectra recorded in the 1300-1700 cm-1 frequency region, containing the oxidation state marker v4 at 1375 cm-1 (Fe3+) and spin state markers v10 (1625 cm-1, high-spin; 1633 cm-1, low-spin) and v19 (1575 cm-1, high-spin; 1585 cm-1, low-spin) were used to differentiate between the spin states of the various forms of cytochrome P-450. As well as the established spin state marker bands, the intensity of a band at 1400 cm-1 appeared to depend on the high-spin content. Thus, with this method SERRS from silver colloids can be used to determine spin states of related cytochromes P-450 in dilute solution (10(-8)M) and may be of value in studies of protein-substrate interactions.
Animals↗