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nOur objective was to confirm the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients. We conducted a 36-week confirmatory study, consisting of 12-week pre-observation period followed by 24-week treatment period. Patients received placebo or edaravone i.v. infusion over 60 min for the first 14 days in cycle 1, and for 10 of the first 14 days during cycles 2 to 6. The efficacy primary endpoint was changed in the revised ALS functional rating scale (ALSFRS-R) scores during the 24-week treatment. Patients were treated with placebo (n = 104) and edaravone (n = 102). Changes in ALSFRS-R during the 24-week treatment were −6.35 ± 0.84 in the placebo group (n = 99) and −5.70 ± 0.85 in the edaravone group (n = 100), with a difference of 0.65 ± 0.78 (p = 0.411). Adverse events amounted to 88.5% (92/104) in the placebo group and 89.2% (91/102) in the edaravone group. In conclusion, the reduction of ALSFRS-R was smaller in the edaravone group than in the placebo group, but efficacy of edaravone for treatment of ALS was not demonstrated. Levels and frequencies of reported adverse events were similar in the two groups.

The present study is the first to report the hypocholesterolemic effect of chitosan on humans. When 3-6 g/day of chitosan was given in the diet to 8 healthy males, total serum cholesterol significantly decreased, and when the ingestion was stopped, the value increased to the level before ingestion. Serum HDL-cholesterol was increased significantly by the ingestion of chitosan. The excreted amounts of primary bile acids, cholic acid and chenodeoxycholic acid, into the feces was significantly increased by the ingestion of chitosan, and the amount of cholic acid excretion decreased significantly after the ingestion was stopped. These facts suggest that chitosan combined bile acids in the digestive tract, and that the combined product was excreted into the feces. This, in turn, deceased the resorption of bile acids, so that the cholesterol poool in the body was decreased and the level of serum chrolesterol consequently decreased.Chitin is a polysaccharide contained in the cuticle of Crustacea and insects, and in the cell walls of some kinds of mold. Chitosan is the general name for the dilute acid-soluble group of deacetylated chitin. The chemical structure of chitosan is similar to that of cellulose in dietary fiber. Chitosan is not hydrolyzable by the digestive enzymes in humans, so it can be classed as one of the dietary fibers of animal origin. However, it is a cationic polymer having an amino group in its chemical structure, which is a characteristic greatly different from those of other dietary fibers.Many functions of chitosan attributable to its amino group are known. Among them, the most noticeable is its hypocholesterolemic effect,l -6) and several studies on its mechanism have been reported. 5, 7) According to these reports, it has been said that chitosan is .dissolved in the digestive tract under acidic conditions, combines bile acid with its ion-exchanging function, and excretes the combined bile acid outside the body; consequently, it decreases the cholesterol pool in the body. However, all of these studies on the hypocholesterolemic effect of chitosan so far reported have used animals,1-6) and there is no report on a study of the effects on humans. Moreover, data for elucidating the mechanism were obtained mostly by in vitro studies,7) and the proposed mechanism based upon animal studies is not entirely clear.The present study is the first to report the hypocholesterolemic effect of chitosan on humans. The results obtained are particularly useful for the effect of chitosan on the metabolism of serum cholesterol and its possible mechanism of action.. Materials and MethodsTest subjects. This study was performed in conformity with the spirit of the "Declaration of Helsinki". The test subjects were 8 healthy male volunteers between 20 and 23 years of age, who were informed of the details of the aims, contents and methods of the study, and after giving their consent, decided to participate in the study of their own free will. All of them were university studuents, and Table I shows the background factors f...

Application of IR Tracking substantially reduced the geometric error caused by respiratory motion; however, an intrafractional error due to baseline drift of >3 mm was occasionally observed. To compensate for EBD, the authors recommend checking the target and IR marker positions constantly and updating the 4D model several times during a treatment session.

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress may be one of the major mechanisms involved. In vitro and in vivo data of edaravone suggest that it may possess broad free radical scavenging activity and protect neurons, glia, and vascular endothelial cells against oxidative stress. During the 1980s and 1990s, edaravone was developed for the treatment of acute ischemic stroke. In 2001, a clinical program in ALS was initiated and five clinical studies were conducted in Japan. Phase III studies were designed to rapidly evaluate (within a 24-week double-blind study window) functional changes using the Revised ALS Functional Rating Scale (ALSFRS-R) as a primary endpoint. The study populations were selected according to these considerations and were further refined as the studies proceeded. Although the first phase III study did not meet its primary endpoint, post-hoc analyses showed an apparent effect of edaravone, when additional patient inclusion criteria defined by ALSFRS-R score, pulmonary function, certainty of ALS diagnosis, and duration of disease were applied. This population was hypothesized not only to have retained broad functionality and normal respiratory function at study baseline but also to be likely to show measurable disease progression over 24 weeks. A second confirmatory phase III study applying these refinements in patient selection was prospectively designed and successfully documented a statistically significant difference between the edaravone and placebo groups in the ALSFRS-R primary endpoint. This paper describes and reviews data pertinent to the potential mechanism of action of edaravone, and reviews the development history of edaravone for the treatment of ALS.