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Biomedical subjects

R J Richards

Publications and source records attributed to R J Richards.

At least 37 records · Page 2Linked to original sources
PubMed1999

Bioreactivity of carbon black and diesel exhaust particles to primary Clara and type II epithelial cell cultures.

OBJECTIVES: To begin to elucidate the mechanisms of particle toxicity to the lung, the bioreactivity of four carbon black (CB) and diesel exhaust particles ((DEPs), a surrogate for particulate matter of aerodynamic diameter < 10 microns (PM10), were examined with primary cultures of Clara and type II epithelial cells. METHODS: The particles were extensively characterised by surface chemistry, size, and aggregation properties. Toxicity of the particles was assessed by determining cell attachment to an extracellular matrix substratum. RESULTS: The spherulite size range for the particles ranged from 50, 40, 20, 20, and 30 nm for CB1-4 and DEPs. All particle samples had different surface chemical compositions. CB1 was the least toxic to Clara (170 micrograms) and type II cells (150 micrograms) and CB4 was the most toxic (55 micrograms and 23 micrograms respectively). DEPs stored for 2 weeks were equally toxic to both epithelial cell types (27-28 micrograms). DEPs became progressively less toxic to type II cells with time of storage. Both primary epithelial cell types internalised the particles in culture. CONCLUSIONS: Bioreactivity was found to be related to CB particle spherulite size and hence surface area: the smaller the particle and larger the surface area, the more toxic the particles. Also, CB particles with the most complicated surface chemistry were the most bioreactive. Freshly prepared DEPs were equally toxic to type II and Clara cells and they became progressively less toxic to the type II cells with time. With all CB and DEPs, the primary epithelial cells internalised the particles, although this was noted most in cells of low functional competence.

Animals↗
PubMed1998

The response of lung epithelium to well characterised fine particles.

Diesel particles form a large component of the fine particle fraction (PM10) in urban air in the UK. During pollution episodes small increases in PM10 have been linked to detrimental health effects. The comparative toxicological effects of diesel exhaust and other well-characterised particles (carbon black, amorphous and crystalline silica) on rat respiratory epithelium were investigated in the present study. The effects of small masses of particles (1 mg) delivered by intratracheal instillation were monitored by changes in components of lavage fluid. Respirable, crystalline quartz, produced significant increases in lung permeability, persistent surface inflammation, progressive increases in pulmonary surfactant and activities of epithelial marker enzymes up to 12 weeks after primary exposure. Ultrafine amorphous silica did not induce progressive effects but it promoted initial epithelial damage with permeability changes and these regressed with time after exposure. By contrast, ultrafine/fine carbon black had little, if any, effect on lung permeability, epithelial markers or inflammation, despite being given at a dose which readily translocated the epithelium and which has been reported to induce inflammation. Similarly, diesel exhaust particles produced only minimal changes in lavage components, although they were smaller individual particles and differed in surface chemistry from carbon black. It is concluded that diesel exhaust particles are less damaging to respiratory epithelium than silicon dioxide and that the surface chemistry of a particle is more important than ultrafine size in explaining its biological reactivity.

Air Pollutants↗
PubMed1997

Using threshold analysis to improve medical decisions.

Physicians can improve their medical decision making by considering the risk-benefit ratio, characteristics of a diagnostic test, and the probability of disease. Several threshold values of probability were defined. The treatment threshold is used when a diagnostic test is not being considered. If the probability of disease is greater than the treatment threshold, then treatment should be administered. If a test is being considered, then the test threshold and the test-treatment threshold should be used to determine if testing is indicated. If the probability of disease is less than the test threshold, then no treatment and no testing are the preferred options. If the probability of disease is greater than the test-treatment threshold, then treatment without testing is preferred. If the probability of disease lies between the test and test-treatment thresholds, the test should be performed.

Decision Support Techniques↗
PubMed1997

Extracellular biotransformation potential in mouse airways.

The aims of this study were to determine if freshly isolated bronchiolar Clara cells retained biotransformation potential and whether components of phase 1 and/or phase 2 metabolism were present in the extracellular lining fluid of the lung airways. Approximately 550 microliters of lavage fluid was obtained from the mouse lung, which had been totally perfused of blood in order to facilitate the isolation of Clara cells from the same animal. Samples of acellular lavage fluid and aliquots of purified Clara cells were frozen at -20 degrees C prior to analysis. minimum numbers of cells and lavage fluid volumes, pooled from 2 CD-1 mice, were assayed for ethoxycoumarin-O-deethylase, NADPH-dependent cytochrome c reductase, glutathione-S-transferase(s) and non-protein sulphydryls (mostly reduced glutathione). Isolated Clara cells retained a high activity/level of all these parameters confirming their functional status for subsequent studies of xenobiotic metabolism in vitro. Acellular lavage fluid, from all the healthy animals, also contained mono-oxygenase, reductase and transferase activities and high non-protein sulphydryl levels suggesting that phase 1 and 2 reactions with xenobiotics could take place in the extracellular environment of the lung. Clara cells are known to undergo apocrine secretion and this removal of the apical cap containing secretory granules and smooth endoplasmic reticulum could account for the airway biotransformation potential that was observed.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1997

Is a history of tonsillectomy associated with a decreased risk of Helicobacter pylori infection?

To determine the relation between a history of tonsillectomy and the prevalence of colonization by Helicobacter pylori (HP), we conducted an observational, cohort study at the University of Oklahoma Hospital over a 13-month period. Subjects under-going upper endoscopic evaluation and antral biopsies for HP at the University of Oklahoma Hospital formed the database. The indication of the endoscopy and biopsies was determined by the endoscopist. The antral biopsy specimens were tested for HP using a rapid urease test. We recorded the patient's name, age, gender, race, history of smoking, and history of appendectomy or tonsillectomy. One hundred nine subjects constituted our database. There was no difference in age, gender, or smoking between the HP+ (n = 37) and HP- (n = 72) groups. The ability to pay for healthcare through a third-payor party also was similar. The prevalence of prior tonsillectomy was 30.6% in HP- group versus 5.4% in HP+ group (p < 0.01). In contrast, the prevalence of prior appendectomy was 21.6% in HP+ group versus 23.6% in HP- group (p = not significant). Multiple regression was carried out to account for confounding variables. The model showed that only white race and tonsillectomy were significantly related to the presence of HP colonization. Both appendectomy and health insurance, which were the surrogate markers for access to healthcare and socioeconomic status, were insignificant. We conclude that a history of tonsillectomy is associated with decreased prevalence of HP colonization.

Appendectomy↗
PubMed1996

Putrescine uptake by alveolar epithelial cell monolayers exhibiting differing transepithelial electrical resistances.

Rat alveolar type II cells were isolated following elastase digestion and cultured on polycarbonate filters at various densities and in different media. Two days after seeding, the cells formed a monolayer on the filters which consisted predominantly of type II cells, these then de-differentiated to a alveolar type I-like cell monolayer by day 6. The seeding density and media utilized affected the transepithelial electrical resistance (TEER) generated by the monolayer. Only certain culture conditions allowed the production of a monolayer that mimics, putatively, the in vivo alveolar epithelium (TEER greater than 1000 omega cm2). Vmax and K(m) values for the uptake of putrescine by monolayers exhibiting low and high TEERs on day 6 were determined. The capacity of the putrescine uptake mechanisms was greater in cell monolayers exhibiting a high TEER than those exhibiting a low TEER, suggesting that the TEER does not only measure the "tightness" of the monolayer but contains an element representative of the viability of the cell monolayer. The selection of appropriate TEERs for cell culture investigations is discussed.

Biological Transport↗
PubMed1996

Gender difference in the concentration of the antioxidant uric acid in human nasal lavage.

The entire respiratory tract is continually exposed to a variety of oxidants, of which a large percentage may react within the nasal passages. In the secretions lining the human nasal cavity uric acid has been shown to be the only low molecular weight antioxidant present in abundance. Because this uric acid originates in the plasma, it is possible that factors affecting the levels of plasma uric acid will also alter the levels recovered in lavage fluids. Lavage fluid from 15 men (20-68 years) and 11 women (20-59 years) were collected using a modified Foley catheter which allowed each subject to supply a basal lavage (saline removed immediately after instillation) and an "accrued' lavage (saline left in situ for 5 min) from each nasal cavity. Lavage fluids were assayed for protein, lysozyme and uric acid. The levels of protein and lysozyme in the recovered fluids were found not to be affected by subject age or gender. Uric acid, however, was found to have a weak negative (r2 = -0.685 basal and -0.62 accrued) correlation with age in women, but no such correlation was noted in men. Also, the levels of uric acid in women (1.3 +/- 0.3 microM/L basal and 4.5 +/- 0.6 microM/L accrued) were found to be lower than those seen in men (3.1 +/- 0.6 microM/L basal and 8.4 +/- 1.3 microM/L accrued) (p = 0.0681 and 0.0394 respectively). It is concluded that women have lower levels of uric acid in lavage fluids than men, with subject age also possibly affecting lavage uric acid. It is also proposed that such factors which lead to decreased levels of uric acid may be related to individual sensitivity to inhaled oxidants such as ozone.

Adult↗
PubMed1996

Differential depletion of human respiratory tract antioxidants in response to ozone challenge.

The toxicity of ozone, the major component of photochemical smog, is related to its powerful oxidising ability, and many of its deleterious effects are mediated through free radical reactions. As the majority of ozone oxidation events are thought to be confined to the pulmonary epithelial lining fluid, we studied the interaction of ozone with a range of small molecular weight antioxidants found within this compartment: ascorbic acid (AH2), uric acid (UA), and reduced glutathione (GSH). Epithelial lining fluid obtained as bronchoalveolar lavage (BAL) fluid, was taken from 16 male subjects and the antioxidant concentrations determined for each subject. BAL fluid samples from nine of these subjects were then exposed, using an interfacial exposure system, to a range (50-1000 ppb) of ozone concentrations. Both AH2 and UA were consumed by ozone in a time and ozone concentration dependent manner, with mean consumption rates of 1.7 +/- 0.8 and 1.0 +/- 0.5 pmol L-1 s-1 ppb-1, respectively. Considerable intersubject variation was however observed. The individual rates of consumption for each antioxidant were significantly correlated with the respective initial antioxidant concentration. In contrast, although GSH was consumed at 50 ppb ozone, the rate of consumption did not change with increasing ozone concentration. We conclude that there is differential depletion of BAL fluid antioxidants, suggesting a reactivity hierarchy toward ozone in human ELF of AH2 > UA > > GSH.

Antioxidants↗
PubMed1996

Obesity-related hypertension: its physiological basis and pharmacological approaches to its treatment.

Obesity-related hypertension is a common pathological disorder that can occur at any age and in any sex or race. Some of the metabolic, endocrinologic, adrenergic, and hemodynamic changes associated with this condition are reversed, in part, by weight reduction, which coincidentally decreases blood pressure (BP) in obese hypertensive patients. However, a major problem for obese hypertensives is dietary noncompliance. Consequently, a pharmacologic approach to obesity-related hypertension that meets the specific requirements of this complex pathological condition should be recommended when the initial nonpharmacological approach falls. Diuretics and beta-adrenergic blocking agents have been shown to be effective in decreasing BP in obese hypertensives, but they also decrease insulin sensitivity and increase cholesterol and lipoprotein concentrations. Calcium channel blockers, alpha 1-adrenoreceptor blocking, and angiotensin-converting enzyme inhibitor agents may offer an efficient and safe antihypertensive approach in obese hypertensive patients.

Antihypertensive Agents↗
PubMed1995

Depletion of urate in human nasal lavage following in vitro ozone exposure.

Ozone, a strong oxidant present in summer smog, is thought to primarily react with antioxidant molecules found in the epithelial lining fluid of the respiratory tract. In humans, as much as 40% of inhaled ozone can be removed in the nasal cavity where the major extracellular antioxidant has been identified as uric acid. The present study was undertaken to examine urate/oxidant interactions in human nasal lavage fluid following in vitro exposure to ozone at concentrations relevant to the U.K. Lavage fluid was collected from 8 volunteers using a modified Foley catheter which permits prolonged contact of isotonic saline with the anterior nasal cavity. Nasal lavage samples in multiwell plates were exposed to ozone at concentrations of 50, 100 and 250 ppb. Samples were removed at intervals from 15 to 240 min following exposure and assayed for uric acid depletion. Uric acid concentrations in the nasal lavage were found to fall from 8.52 (time zero) to 3.99 microM, 0.05 and 0.07 microM after 240 min at 50, 100 and 250 ppb ozone respectively. At a non-environmentally relevant ozone concentration of 1000 ppb, uric acid was completely depleted after 60 min. Regression analysis showed a linear correlation between rate of loss of urate and ozone concentration (R2 = 0.97). A novel, non-invasive technique is described to investigate antioxidant compromise and its importance in individual subjects. We conclude that uric acid in nasal lavage samples is scavenged by ozone in a dose and time dependent manner.

Ascorbic Acid↗