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Biomedical subjects

R T Riley

Publications and source records attributed to R T Riley.

82 records · Page 5Linked to original sources

Penetration of aflatoxins through isolated human epidermis.

The purpose of this study was to determine if aflatoxin B1 (AFB1) could penetrate through isolated human epidermis (stratum corneum plus viable epidermis). [14C]AFB1 (7.5-9.3 micrograms) was applied to the stratum corneum of epidermal disks mounted in Teflon diffusion cells. [14C]AFB1 penetrated chemically unaltered through the isolated epidermis. Chloroform-extractable radioactivity accounted for 82.5 +/- 3.7% of the total penetrating radioactivity in the receptor fluid of the diffusion cells. The rate of penetration was very slow when experiments were conducted under nonoccluded conditions, but was approximately 40 times greater under conditions of occlusion. The maximum velocity of penetration was 0.63 +/- 0.71 and 27.31 +/- 10.15 pmol/h under conditions of exposure to ambient conditions and occlusion, respectively. Penetration after 46 h was less than 0.05% and 3.41% of the applied dose under nonoccluded and occluded conditions, respectively. Total recovery expressed as a percentage of the applied radioactivity was 98.6 +/- 6.4%.

Aflatoxin B1↗

Increased accumulation of the lipophilic cation tetraphenylphosphonium+ by cyclopiazonic acid-treated renal epithelial cells.

Pig kidney renal epithelial cells (LLC-PK1) in culture were used to determine the effects of cyclopiazonic acid (CPA) on the uptake of the transmembrane potential probe, [3H]tetraphenylphosphonium bromide (TPP+). CPA had a significant stimulatory effect on TPP+ accumulation, which occurred in a dose-related manner. TPP+ accumulation in the presence of CPA was significantly reduced by high-potassium media (HK) and carbonylcyanide m-chlorophenylhydrazone (CCCP), but neither HK nor the protonophore CCCP, could completely abolish the stimulatory effect of CPA. The apparent transmembrane potential difference (delta psi), calculated based on the difference in accumulation of TPP+ in low-potassium and HK media, ranged from -55.9 to -85.7 mV for control cells and -89.4 to -109.0 mV for CPA-treated cells (20 mg CPA/I). The mechanism of CPA stimulation of TPP+ accumulation was not known. However, it was hypothesized that the effect could be a result of alterations in ion pumps or altered membrane permeability. The fact that the stimulatory effect could not be completely abolished by high potassium or CCCP suggested that there was some interaction between CPA and TPP+ or there were sites of TPP+ accumulation that were insensitive to K+ and H+ permeability.

Animals↗

Penetration of [3H]T-2 toxin through excised human and guinea-pig skin during exposure to [3H]T-2 toxin adsorbed to corn dust.

An in vitro test system was used to measure the penetration of [3H]T-2 toxin through human epidermis, human whole skin (isolated dermis and epidermis), and through guinea-pig whole skin. To simulate the conditions which occur when agricultural workers are exposed to corn dust contaminated with T-2 toxin, the epidermal surface of each skin preparation was dosed with [3H]T-2 toxin adsorbed onto corn dust. The applied dose was 3.27 to 4.75 mg of corn dust containing 18.2 ppm [3H]T-2 toxin. The rate of percutaneous penetration was determined by measuring the accumulation of radioactivity in the receptor fluid bathing the dermal side of the excised skin. The total penetrations (expressed as percentage dose) through isolated human epidermis, human whole skin and through isolated guinea-pig whole skin were 1.12 +/- 0.26% (mean +/- standard deviation), 0.33 +/- 0.07%, and 0.13 +/- 0.07% respectively. The radioactive compounds in the receptor fluid bathing the human whole skin corresponded to T-2 toxin (69%) and HT-2 toxin (25%), as determined by thin-layer chromatography. Thus T-2 toxin adsorbed onto corn dust can partition into and penetrate through excised human and guinea-pig skin.

Absorption↗

Age and growth-related changes in cyclopiazonic acid-potentiated lipophilic cation accumulation by cultured cells and binding to freeze-thaw lysed cells.

In a previous study (1) we demonstrated that increased tetraphenylphosphonium (TPP) uptake by renal epithelial cells (LLC-PK1) exposed to the fungal metabolite cyclopiazonic acid (CPA) was not a result of hyperpolarization across the plasma membrane even though CPA-potentiated TPP uptake could be totally inhibited by the depolarizing agent carbonylcyanide-m-chlorophenylhydrazone (CCCP). We now demonstrate that CPA potentiates TPP accumulation by proliferating skeletal muscle (L6) and LLC-PK1 cells but not by nonproliferating primary rat hepatocytes. In LLC-PK1 cells, CPA-potentiated TPP accumulation is observed in cells at all ages. In L6 cells, CPA-potentiated TPP accumulation is maximal soon after subculturing, and as the cells age they become less sensitive to CPA until TPP accumulation by CPA-treated cells approaches that of untreated cells. The temporal change in sensitivity of L6 cells to CPA may be related to biochemical and/or metabolic changes which occur as the cells age in culture. Hepatocytes, LLC-PK1 cells, and L6 cells permeabilized by freeze-thaw lysis, all exhibit CPA-potentiated TPP partitioning, even in the presence of CCCP. This result indicates that both TPP and CPA must have access to the intracellular space in order for potentiated TPP partitioning to be observed. We hypothesize that the site of interaction between CPA and TPP is intracellular and probably associated with the cytoplasmic side of the plasma membrane and possibly the mitochondria.

Animals↗

Subchronic toxicity of fumonisin B1 to male and female rats.

Fumonisins are a class of mycotoxins produced by Fusarium moniliforme and other Fusarium spp. These compounds are widely distributed in corn. Equine leukoencephalomalacia, pulmonary oedema in swine, and nephrotoxicity, hepatotoxicity and liver cancer in male rats, all of which are caused by toxic F. moniliforme, have been experimentally reproduced using fumisin B1 (FB1) (ca 90-94% purity). To investigate the effect of purified (> or = 99% purity) FB1, to compare the effects of FB1 in males and females, and to obtain dose-response information for FB1, three rats per sex were fed diets containing 0, 15, 50 or 150 FB1 for 4 weeks. Serum chemical, organ weight and histopathological evidence showed that 150 mg/kg FB1 was hepatotoxic in both sexes. Nephrosis was found in males fed > or = 15 mg/kg and females fed > or = 50 mg/kg FB1. Altered sphingolipid profiles, specifically increased free sphinganine concentrations and increased sphinganine:sphinogosine ratios, were found in the liver, kidney, serum and urine of FB1-fed rats. These findings support the hypothesis that in vivo toxicity caused by fumonisins may result from altered sphingolipid metabolism.

Animals↗

Antecedents of the people and organizational aspects of medical informatics: review of the literature.

People and organizational issues are critical in both implementing medical informatics systems and in dealing with the altered organizations that new systems often create. The people and organizational issues area--like medical informatics itself--is a blend of many disciplines. The academic disciplines of psychology, sociology, social psychology, social anthropology, organizational behavior and organizational development, management, and cognitive sciences are rich with research with significant potential to ease the introduction and on-going use of information technology in today's complex health systems. These academic areas contribute research data and core information for better understanding of such issues as the importance of and processes for creating future direction; managing a complex change process; effective strategies for involving individuals and groups in the informatics effort; and effectively managing the altered organization. This article reviews the behavioral and business referent disciplines that can potentially contribute to improved implementations and on-going management of change in the medical informatics arena.

Attitude to Computers↗

Managing change: an overview.

As increasingly powerful informatics systems are designed, developed, and implemented, they inevitably affect larger, more heterogeneous groups of people and more organizational areas. In turn, the major challenges to system success are often more behavioral than technical. Successfully introducing such systems into complex health care organizations requires an effective blend of good technical and good organizational skills. People who have low psychological ownership in a system and who vigorously resist its implementation can bring a "technically best" system to its knees. However, effective leadership can sharply reduce the behavioral resistance to change-including to new technologies-to achieve a more rapid and productive introduction of informatics technology. This paper looks at four major areas-why information system failures occur, the core theories supporting change management, the practical applications of change management, and the change management efforts in informatics.

Consumer Behavior↗