Rapamycin limits the growth of established experimental abdominal aortic aneurysms.

OBJECTIVES: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease affecting 4-8% of men older than 60 years. No pharmacologic strategies limit disease progression, aneurysm rupture, or aneurysm-related death. We examined the ability of rapamycin to limit the progression of established experimental AAAs. METHODS: AAAs were created in 10-12-week-old male C57BL/6J mice via the porcine pancreatic elastase (PPE) infusion method. Beginning 4 days after PPE infusion, mice were treated with rapamycin (5 mg/kg/day) or an equal volume of vehicle for 10 days. AAA progression was monitored by serial ultrasound examination. Aortae were harvested for histological analyses at sacrifice. RESULTS: Three days after PPE infusion, prior to vehicle or rapamycin treatment, aneurysms were enlarging at an equal rate between groups. In the rapamycin group, treatment reduced aortic enlargement by 38%, and 53% at 3 and 10 days, respectively. On histological analysis, medial elastin and smooth muscle cell populations were relatively preserved in the rapamycin group. Rapamycin treatment also reduced mural macrophage density and neoangiogenesis. CONCLUSION: Rapamycin limits the progression of established experimental aneurysms, increasing the translational potential of mechanistic target of rapamycin-related AAA inhibition strategies.

Synthesis of (+)-Turmeronol A, an Inhibitor of Soybean Lipoxygenase, and (+)-ar-Turmerone.

Syntheses of optically pure turmeronol A and turmerone were achieved in a simple manner starting from ethyl (R)-3-hydroxybutanoate (4) of 100% e.e. The key step was the displacement of the chiral tosylate (6) with an organocopper reagent.

Cimetidine-mediated augmentation of lymphocyte responses to phytohemagglutinin in gastric cancer patients.

The effect of cimetidine, a histamine type 2 receptor antagonist, on lymphocyte responses to phytohemagglutinin (PHA) was studied in 58 gastric cancer patients. Cimetidine significantly enhanced lymphocyte responses to PHA in certain gastric cancer patients. The degree of enhancement was associated with tumor load. A significant inverse correlation was observed between the degree of enhancement and that of the original lymphocyte responses to PHA. The degree of enhancement significantly correlated with the proportions of OKT3 and OKT8 positive cells. A determination of the degree of enhancement in selected gastric cancer patients revealed it to fall to a low level after a certain period following curative gastric resection. These data appear to favor the in vivo therapeutic administration of cimetidine to advanced gastric cancer patients.

[Clinical experience with cefoxitin in the surgical field].

Cefoxitin (CFX) was administered to 49 hospitalized patients in the surgical field, and the following results were obtained: Clinical results of the 12 patients with surgical infections were excellent in 1 patient, good in 10, and poor in 1, with the efficacy rate of 91.7%. CFX was also administered to 37 patients for prophylaxis of postoperative infections, and the clinical efficacy rate was 91.7%. No side effects were seen besides mild eruption in 1 patient. The above results indicate that CFX is exceeding useful in surgical field.

Effects of oral befunolol on heart rate and systolic blood pressure during submaximal exercise in man.

For the purpose of determining exercise intensity required for evaluating the effect of beta-blocking agents, the multi-stage treadmill exercise was carried out up to intensity of 85% of maximal oxygen intake (VO2max) after administration of beta-blocking agents in 7 healthy men. To obtain a stable dose response in the inhibitory effect of beta-blocking agents on heart rate (HR) and systolic blood pressure (S-BP), the exercise intensity more than 65% of VO2max (75% of maximal heart rate) was needed. In order to evaluate the effect of befunolol (BFE), a submaximal treadmill exercise of 75% of the age adjusted predicted maximal heart rate was loaded in 6 healthy men at 1.5, 4, and 8 hours following a single oral administration of 10 mg, 20 mg or 40 mg of BFE and 20 mg or 40 mg of propranolol. Simultaneously, the plasma concentration of BFE was determined 1.5, 4, 6 and 8 hours after the administration of BFE at each dose. In human serum, BFE was detected together with its metabolite, revealing a significant correlation between BFE and metabolite (r = 0.94, p < 0.001). Almost a certain rate of metabolite (4--5 times) was detected against BFE. As for the biological half life, it was 1.79 +/- 0.13 hours with BFE and 3.67 +/- 1.33 hours with metabolite. The inhibitory effect of BFE on HR and S-BP during exercise exhibited a dose response with the oral dose and its plasma concentration, and was almost twice as much as that of propranolol at the same dose. Accordingly, the myocardial oxygen consumption which may be represented as rate pressure product was inhibited twice as much as propranolol. BFE is characteristic of its more rapid elimination of its effect compared to the other beta-blocking agents. The decrease in the inhibitory effect of BFE or HR during exercise was about 1.8 times quicker than that of propranolol.

Immunofluorescence study of wild rabies virus and antibody.

A concentrate of wild rabies antibody was prepared from hyperimmune serums of three dogs refractory to wild rabies. The animals resisted repeated intramuscular injections of large doses of wild rabies virus in emulsions of whole brain, in emulsions of submaxillary salivary glands, and in emulsified mixtures of brain and submaxillary glands taken from naturally rabid dogs. The antibody was conjugated with fluorochrome and then absorbed by a procedure that gave "cell-free" working solutions of fluorescent antibody. The procedure entailed parallel absorption steps with minced pathological canine submaxillary glands from (1) naturally rabid dogs (these glands contained specific, undegraded, natural antigens of live wild rabies virus plus nonspecific substances and antigens) and (2) nonrabid dogs from a rabies endemic region (these glands contained nonspecific substances and antigens). Extracts from submaxillary glands of the three naturally rabid dogs and one nonrabid dog were stained with a cell-free solution of the fluorescent antibody. The glands of the rabid dogs contained fluorescent aggregates of intense green spherical and filamentous particles. When nonfluorescent canine hyperimmune serum was incubated with rabies-containing submaxillary extract, the rabies antigens were quenched. When nonfluorescent equine fixed virus antiserum was incubated with such extracts, the aggregates still retained bright fluorescence.