Evaluation of the in vivo interaction of methyl tert-butyl ether with alpha2u-globulin in male F-344 rats.

Methyl tert-butyl ether (MTBE), a fuel additive blended into unleaded gasoline, decreases emissions of selected air pollutants. Exposure to MTBE causes a low incidence of renal tumors in male, but not female, F-344 rats. A number of chemicals that cause male rat-specific renal tumors also cause a syndrome unique to male rats referred to as alpha2u-globulin (alpha2u) nephropathy (alpha2u-N). Previous investigations have demonstrated that MTBE exposure induces a mild accumulation of alpha2u in male F-344 rats. The objective of the present study was to determine if MTBE, or a metabolite of MTBE, interacts with alpha2u in male rats administered MTBE orally. Eleven-week-old male and female F-344 rats were administered 750 mg [14C]MTBE/kg body wt or an equivalent volume of 10% emulphor orally for 4 consecutive days. Although [14C]MTBE-treated male rats exhibited a statistically significant increase in renal alpha2u concentration, the total radioactivity recovered was similar in kidney samples from [14C]MTBE-treated male and female rats. Further analysis of kidney cytosol prepared from [14C]MTBE-treated rats revealed that a slightly greater percentage of radioactivity coeluted on a G-25 gel filtration column with the total protein fraction from male rats than from female rats. Gel filtration (Sephadex G-75 column) and anion exchange chromatography, however, did not demonstrate any coelution of MTBE-derived radioactivity with the low-molecular-weight protein fraction or alpha2u fraction, respectively, in kidney cytosol prepared from [14C]MTBE-treated male or female rats. Further experimentation using a sealed vial equilibration system demonstrated that d-limonene oxide, a chemical with a high affinity for alpha2u, displaced MTBE in male, but not female, rat kidney samples following administration of MTBE. These findings provide indirect evidence that MTBE interacts with a male-specific protein such as alpha2u in male F-344 rats. Since the pathogenesis of alpha2u-N is dependent on the formation of a reversibly bound chemical-alpha2u complex, demonstration of an in vivo interaction of MTBE or one of its metabolites with alpha2u supports the alpha2u mechanism as a cause of MTBE-induced protein droplet nephropathy in male rats.

Methyl tert-butyl ether causes alpha2u-globulin nephropathy and enhanced renal cell proliferation in male Fischer-344 rats.

Methyl tert-butyl ether (MTBE), a fuel additive blended into unleaded gasoline to decrease carbon monoxide emissions, induces renal tumors in male, but not female, rats exposed by inhalation to > or =3000 ppm MTBE. A number of chemicals that induce male rat-specific renal tumors also cause a syndrome unique to male rats referred to as alpha2u-globulin nephropathy (alpha2u-N). The objective of the present study was to determine if MTBE induces an alpha2u-N and renal cell proliferation in male F-344 rats. Male and female F-344 rats were exposed to MTBE vapors of 0, 413, 1516, or 3013 ppm for 6 hr/day for 10 consecutive days. Significant proximal tubule necrosis and protein droplet accumulation were observed in kidneys from male rats exposed to 1516 and 3013 ppm MTBE. Significantly greater labeling indices were observed in all groups of MTBE-exposed male rats. alpha2u-Globulin immunoreactivity was present in and confined to protein droplets in male rat kidney. A mild dose-related increase in alpha2u concentration in the kidney, as measured by an enzyme-linked immunosorbent assay, was observed in male rats exposed to MTBE, with a statistically significant increase in alpha2u concentration in male rats exposed to 3013 ppm MTBE. There was a strong positive correlation (r = 0.994) with exposure concentration between cell proliferation and alpha2u concentration in male rat kidney. No significant differences were observed in female rats for any of these responses. Further analysis of kidney cytosol failed to demonstrate the accumulation of any protein besides alpha2u in MTBE-exposed male rat kidney. These findings demonstrate that MTBE causes a mild induction of alpha2u-N and enhanced renal cell proliferation in male, but not female, F-344 rats, suggesting a role for alpha2u-N in renal tumorigenesis.

Effects of pretreatment with ketoprofen and phenylbutazone on experimentally induced synovitis in horses.

OBJECTIVE: To compare the analgesic and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAID), ketoprofen (2.20 and 3.63 mg/kg of body weight) and phenylbutazone (4.40 mg/kg), in an acute equine synovitis model. DESIGN: 4 groups of 6 horses received NSAID or saline solution in a randomized design. ANIMALS: 24 clinically normal mares and geldings. PROCEDURE: Left intercarpal joints were injected with sterile carrageenan to induce synovitis at the same time as IV administration of NSAID or saline solution. Clinical assessments were made and synovial fluid was withdrawn at 0, 1, 3, 6, 9, 12, 24, and 48 hours. RESULTS: The eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4, increased in synovial fluid after synovitis induction in all horses then returned to near baseline by 48 hours. All NSAID-treated horses had decreased PGE2, compared with saline-treated horses. This effect lasted longer in phenylbutazone-treated horses than in ketoprofen-treated horses. There were no treatment effects on leukotriene B4. In saline-treated animals, lameness, joint temperature, and synovial fluid volume, protein concentration, and nucleated cells increased 3 to 12 hours after induction, with marked reduction by 48 hours. Only phenylbutazone treatment reduced lameness, joint temperature, and synovial fluid volume. CONCLUSION: Phenylbutazone was more effective than ketoprofen in reducing lameness, joint temperature, synovial fluid volume, and synovial fluid PGE2. Results do not support lipoxygenase inhibition by either NSAID. CLINICAL RELEVANCE: This reversible model induced synovial fluid alterations similar to those observed in horses with septic arthritis. Results indicate that phenylbutazone may be more useful than ketoprofen in treating acute joint inflammation.

Electroretinogram and visual-evoked potential measurements in sheep.

Electroretinogram (ERG) and visual-evoked potential (VEP) recordings were taken from ten Suffolk-cross sheep. Stimuli for VEP were 1.5 flashes of white light/s; ERG stimuli were single flashes. The ERG measurements of the a and b wave latencies and a-to-b amplitude were measured between the lower eyelid and the vertex, with ground on the nuchal crest. The VEP after monocular stimulation were measured between the nuchal crest and the interorbital line, with ground on the vertex. Measurements consisted of the latencies to seven alternating positive and negative peaks P1, N1, P2, N2, P3, N3 and P4, and six amplitudes, P1-N1, N1-P2, P2-N2, N2-P3, P3-N3 and N3-P4. Average latencies for the a and b waves were 13.6 and 28.2 ms; the mean ab amplitude was 131.68 microV. Average latencies for the seven VEP peaks were 35.0, 43.1, 52.8, 64.1, 74.5, 90.4 and 112.2 ms. Mean amplitudes ranged from 3.90 to 8.29 microV.

Preparation for the twenty-first century: the educational challenge.

In this Presidential Address, I have presented 11 goals for our education programs that are essential to preparation for the twenty-first century. I strongly value the profession of physical therapy and the services we provide to this society. Most of all, I value our education programs and our academicians, without whose efforts none of us would be gathered here today. Early in this Address, I indicated my belief that our education programs have an awesome influence on this profession. But the goals proposed for the twenty-first century pose a challenge to all physical therapists. I make this challenge to academicians, clinical practitioners, educational institutions, and the APTA at all levels. It is imperative that we all join together to identify ways to support, strengthen, and improve our modes of professional education for the twenty-first century. We must do so in pursuit of the educational excellence that has been our consistent endeavor and hallmark for more than 68 years.

The role of endoscopic retrograde cholangiopancreatography injection training sessions for the gastroenterology nurse and associate.

Pancreatitis is a recognized serious complication of endoscopic retrograde cholangiopancreatography (ERCP). The pressure with which contrast media are injected may be a risk factor for developing pancreatitis. We, therefore, designed a study to determine if there were differences in pressures generated by experienced and inexperienced gastroenterology nurses and how much training would be required to instruct individuals to inject to a specific pressure. With the use of manometrically guided practice sessions, it was determined that inexperienced operators initially inject with significantly high pressure but can learn to inject accurately to a specific pressure as rapidly as experienced operators. Injection training sessions may be beneficial in minimizing the potential risk factor of hydrostatic pressure induced endoscopic retrograde cholangiopancreatography-associated pancreatitis.