Preferential uptake of a water-soluble phthalocyanine by atherosclerotic plaques in rabbits

This study is the first demonstration of preferential accumulation of a water soluble phthalocyanine dye in atheromatous plaques in the rabbit. Two groups of rabbits with diet-induced atheromatous plaques were killed 4 and 24 h following intravenous administration of copper phthalocyanine tetrasulfonate. Uptake of the dye by plaque-containing and normal appearing aortae was evaluated macroscopically and quantitatively by extraction of the dye from the tissues. The concentration of the dye in the atheromatous plaques was 2.6 and 1.7 times higher than in the normal vessel wall at 4 and 24 h, respectively. The concentration of the dye in normal appearing aortae in the 2 study groups was similar to that of aortae of control rabbits which were fed a normal diet and exposed to the dye for the same time periods. We conclude that copper phthalocyanine accumulates preferentially in atheromatous plaques in rabbits. These findings provide a basis for the utilization of phthalocyanines for plaque identification and for photodynamic therapy of atherosclerosis.     

Dialysis in Israel, 1989-2005--time trends and international comparisons.

BACKGROUND: A universal increase in the incidence of renal replacement therapy (RRT) was reported in developed countries during the 1990s, especially among the elderly and diabetic patients. We studied trends in RRT incidence and mortality in Israel between 1989 and 2001-2005. METHODS: The end-stage renal disease (ESRD) registry holds data on all RRT patients in Israel. Age-adjusted incidence rate ratios (RRs) were estimated comparing 2001-2005 with 1989. We compared incidence data between Israel and elsewhere using standardized incidence ratios (SIRs). Survival analysis was conducted by the Kaplan-Meier method and Cox's proportional hazards regression was used to compare survival of diabetic with non-diabetic ESRD patients. RESULTS: The mean incidence rates per million population increased from 99 in 1989-1991 to 179 in 2003-2005. In 2000, Israel was the second leading country for incidence of RRT. Age-adjusted incidence rates increased by 67% [95% confidence interval (CI): 49-87%], from 1989 to 2001, but the trend was attenuated between 2002 and 2005. The increase in incidence was positively associated with age, the largest increase being among the elderly aged > or = 75 years (RR: 3.18, 95%CI: 2.72-3.70). Diabetes accounted for 41% of RRT in 2001 vs only 19% in 1989. There was no increase in 1-year survival between the beginning and the end of the study period. Patients with diabetes-associated RRT had 57% increased risk of 1-year mortality (adjusted HR: 1.57 95% CI: 1.51-1.63). CONCLUSIONS: Despite a similar proportion of RRT attributed to diabetes in Israel and other countries, the age-adjusted incidence in Israel is considerably higher than most countries.     

Surgical technique for the treatment of radial wrist pain.

Chronic radial wrist pain with no radiographic evidence of scapholunate instability or other wrist disease can be difficult to diagnose and treat. Our purpose was to evaluate the results of an operation to treat chronic radial or periscaphoid wrist pain that has failed to respond to conservative treatment. We examined the scapholunate ligament and performed a dorsal capsulodesis. One hundred-and-two patients were reviewed retrospectively. Casenotes were available for 88 patients. Function, pain, range of movement (ROM), and grip and pinch strengths were evaluated. Twenty (23%) of the patients were found to have a scapholunate ligament tear of 0-30%, 55 (61%) had a tear of 30%-60%, and 14 (16%) had a tear of 60%-100%. Mean postoperative grip strength was 29.5 kg (80% of the normal side). Postoperative range of movement was significantly limited in flexion compared with the normal side. All patients returned to their previous employment. Seventy (80%) of the patients described improvement in pain and function. Twenty-two (25%) required further operation on the same wrist. This procedure may be indicated in patients with chronic radial wrist pain and no overt instability that is resistant to conservative treatment. It has minimal morbidity and gives good results.     

The role of NO synthases in arginine-dependent small intestinal and colonic carcinogenesis

Arginine is catabolized by NOS2 and other nitric oxide synthases to form nitric oxide. We evaluated the roles of dietary arginine and Nos2 in Apc-dependent intestinal tumorigenesis in Min mice with and without a functional Nos2 gene. NOS2 protein was expressed only in intestinal tissues of Apc(Min/+) Nos2+/+ mice. NOS3 expression was higher in intestinal tissues of mice lacking Nos2, mainly in the small intestine. When diet was supplemented with arginine (0.2% and 2% in drinking water), lack of Nos2 results in decreased tumorigenesis in both small intestine and colon. In Nos2 knockout mice, supplemental arginine (up to 2%) caused a decrease in small intestinal tumor number and size. The arginine-dependent decrease was associated with an increase in nitrotyrosine formation and apoptosis in the region of intestinal stem cells. Mice expressing Nos2 did not show these changes. These mice did, however, show an arginine-dependent increase in colon tumor number and incidence, while no effect on apoptosis was seen. These changes were associated with increased nitrotyrosine formation in epithelial cells. Mice lacking Nos2 did not show changes in tumorigenesis or nitrotyrosine formation, while demonstrating an arginine-dependent increase in apoptosis. These data suggest that Nos2 and dietary arginine have significant effects on intestinal and colonic tumorigenesis in Min mice. In both tissues, loss of Nos2 is associated with decreased tumorigenesis when mice are supplemented with dietary arginine. In the small intestine, Nos2 prevents the arginine-induced decrease in tumor number and size, which is associated with NOS3 expression and increased apoptosis. In the colon, Nos2 is required for the arginine-induced increase in tumor number and incidence.