A dietary embryo/fetal developmental toxicity study of arruva, an R,R-monatin salt isomer, in Crl:CD(SD) rats.

R,R-Monatin is an intensely sweet substance originally identified in the root bark of Sclerochiton ilicifolius. R,R-Monatin salt, commonly known as "arruva", has potential for use as a high-potency sweetener food ingredient. Previously, arruva was concluded to present no toxicologically relevant effects to Crl:CD(SD) rats and Crl:CD-1(ICR) mice fed up to 35,000 ppm arruva in the diet for 90 days. In the present study, groups of mated Sprague-Dawley rats (25 Crl:CD(SD) females/group) were exposed continuously to 0 (control), 15,000, 30,000, or 50,000 ppm arruva in the diet during gestation days 6-21. There were no fetal malformations or developmental variations that were attributable to arruva at any exposure level, nor were there any test article-related effects on intrauterine survival. Maternal toxicity, evidenced by lower mean body weights, body weight gains and feed efficiency, was observed at 50,000 ppm. A developmental effect, in the form of lower mean fetal body weight, was noted in the 50,000 ppm group in the presence of maternal toxicity. Therefore, the dietary no-observed-adverse-effect level (NOAEL) for maternal and embryo/fetal developmental toxicity of arruva in pregnant rats during gestation days 6-21 was 30,000 ppm (equivalent to 2564 mg/kg bw/day) based on reductions in maternal and fetal body weights.

A 90-day oral (dietary) toxicity study of arruva, an R, R-monatin salt isomer, in Crl:CD-1(ICR) mice.

R,R-Monatin [2R,4R- isomer of 2-hydroxy-2-(indol-3-ylmethyl)-4-aminoglutaric acid] is one of four natural constituent isomers in the root bark of Sclerochitin ilicifolius; and "arruva" is the common/usual name that is proposed to represent R,R-monatin salt forms, which have potential use as high potency sweetener food ingredients. In the present study, groups of male and female Crl:CD-1(ICR) mice were exposed to 0 (control), 5000, 10,000, 20,000, or 35,000ppm of arruva in the diet for 90days. There were no toxicologically relevant clinical or histopathological findings in any of the test article-treated groups. Significantly lower mean body weights and cumulative body weight gains were noted in the 35,000ppm group when compared to the control group. Mean body weights in the 35,000ppm group males and females were 9% and 7% less than the control group, respectively, at week 13. In the absence of observations associated with systemic toxicity and in consideration of the magnitude of body weight difference, these effects were not considered toxicologically significant. Based on the results of this study, the dietary no-observed-adverse-effect level (NOAEL) of arruva for 90days in male and female mice was 35,000ppm (equivalent to an exposure level of 5764 and 8013mg/kg bw/day, respectively).

A 90-day oral (dietary) toxicity study of the 2R,4R-isomer of monatin salt in Sprague-Dawley rats.

The root bark of Sclerochitin ilicifolius contains an intensely sweet substance analytically identified as isomers of 2-hydroxy-2-(indol-3-ylmethyl)-4-aminoglutaric acid and generically coined "monatin." Groups of male and female Crl:CD(SD) rats were fed 0 (control), 5000, 10,000, 20,000 or 35,000 ppm R,R-monatin salt in the diet for 90 days. There were no toxicologically relevant clinical or histopathological findings in any of the test article-treated groups. Significantly lower cumulative body weight gains were noted in the 35,000 ppm group. Mean body weights in the 35,000 ppm group males and females were 7% and 12% lower, respectively, than the control group at study week 13. In the absence of other observations associated with systemic toxicity and lower food consumption, the magnitude of the body weight difference in the 35,000 ppm group females relative to the control group exceeded 10%, which indicated attainment of a maximum tolerated dose (MTD) level. Based on the results of this study, and conservatively assuming the body weight observations at the MTD to be indicative of an adverse effect, the dietary no-observed-adverse-effect level (NOAEL) of R,R-monatin salt for 90 days was 20,000 ppm in female rats (approximately 1544 mg/kg bw/day) and 35,000 ppm in male rats (approximately 2368 mg/kg bw/day).

Endovascular repair of traumatic pseudoaneurysm by uncovered self-expandable stenting with or without transstent coiling of the aneurysm cavity.

Various surgical options for internal carotid or subclavian artery pseudoaneurysm repair have been reported; however, in general they have resulted in poor outcomes with high morbidity and mortality rates. Recently, these open surgical procedures have been partly replaced by percutaneous transluminal placement of endovascular devices. We evaluated the potential for using flexible self-expanding uncovered stents with or without coiling to treat extracranial internal carotid, subclavian and other peripheral artery posttraumatic pseudoaneurysm. Three patients with posttraumatic pseudoaneurysm were treated by stent deployment and coiling (two cases) of the aneurysm cavity. In one case, a 5.0 x 47 mm Wallstent (Boston Scientific) was positioned to span the neck of the 9 x 5 mm size pseudoaneurysm (left internal carotid artery) and deployed. Angiography demonstrated complete occlusion of the pseudoaneurysm without coiling. In the second patient, a 5.0 x 31 mm Wallstent (Boston Scientific) was positioned to span the neck of the 9 x 7 mm size pseudoaneurysm (right internal carotid artery) and deployed. A total of six coils (Guglielmi Detachable Coils, Boston Scientific) were deployed into the pseudoaneurysm cavity until it was completely obliterated. In the third case, an 8.0 x 80 mm SMART (Cordis) stent was advanced over the wire, positioned to span the neck of the 10 x 7 mm size pseudoaneurysm of the left subclavian artery, and deployed. Fourteen 40 x 0.5 mm Trufill (Cordis) pushable coils were deployed into the pseudoaneurysm cavity until it was completely obliterated. At long-term follow-up (6-9 months), all patients were asymptomatic without flow into the aneurysm cavity by Duplex ultrasound. We conclude that uncovered endovascular flexible self-expanding stent placement with transstent coil embolization of the pseudoaneurysm cavity is a promising new technique to treat posttraumatic pseudoaneurysm vascular disease by minimally invasive methods, while preserving the patency of the vessel and side branches.

Successful treatment of coronary artery perforation in an abciximab-treated patient by microcoil embolization.

We describe a case of type 2 coronary artery perforation in a 73-year-old man undergoing coronary artery rotablation and stenting with abciximab therapy. The coronary artery perforation was successfully treated by coil embolization with Trufill pushable coils made from platinum alloy and synthetic fibers to promote maximum thrombogenicity.

Cardiogenic Shock.

In the setting of acute myocardial infarction, the timely recognition and treatment of cardiogenic shock are essential in reducing the incidence of death. Patients with cardiogenic shock should be treated aggressively with a combination of pharmacologic agents and mechanical support devices to achieve stabilization. Once stabilization has been achieved, the ultimate goal should be the restoration of flow in the infarct-related artery. This is best achieved with angioplasty or bypass surgery. In those centers not equipped for these procedures, thrombolysis should be performed, and the patient should then be transferred to a higher-level facility.

Fluorescent light photosensitivity in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of fluorescent light toxicity in patients with systemic lupus erythematosus (SLE). METHODS: SLE patients were polled about their symptomatic responses to sunlight and cool white fluorescent light. Photometry was used to determine the levels of ultraviolet (UV) emissions from fluorescent lamps. RESULTS: Thirteen of 30 photosensitive SLE patients described increases in disease activity following exposure to unshielded fluorescent lamps. Photometry indicated that these lamps emit substantial levels of UV-B (280-320 nm) radiation, which is toxic to patients with SLE. Standard acrylic diffusers absorbed this radiation, and their use was associated with almost no patient-reported problems. CONCLUSION: Fluorescent lamps, emitting UV-B radiation, induce disease activity in photosensitive SLE patients. Standard acrylic diffusers absorb UV-B radiation and appear to be protective against induction of disease activity with the use of fluorescent lamps.