***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The present study set out to define the possible effect of reduced glutathione ( GSH ) , the substrate of glutathione peroxidase ( GSH-Px ) , a free radical inactivating enzyme , in amyotrophic lateral sclerosis ( ALS ) . Thirty-two patients affected by definite ALS seen in our institution between August 1993 and July 1994 were admitted to the study . The effect of GSH was studied in an open , crossover , r and omized study . GSH was given at the dose of 600 mg each day intramuscularly for 12 weeks . The patients , taken sequentially , were r and omly assigned to two groups . The first group received the drug while the second received only symptomatic therapies for 12 weeks . After a week of wash-out , the second group received GSH and the first only symptomatic therapies for 12 weeks . The rate of progression of the diseases was compared in the two groups . Clinical evaluation included manual test for muscle strength , Norris scale , bulbar scale , and forced vital capacity ( FVC ) percent . No significant difference was found in the progression of ALS in the two periods , although a slight slowing of the disease progression rate was found during the period of treatment , probably related to the open design of the study . Our data do not show any significant effect of reduced glutathione in modifying the progression of ALS.SommarioLo scopo del lavoro è stato definire il possibile effetto del glutatione ridotto ( GSH ) , il substrato della glutatione perossidasi ( GSH-Px ) , un enzima inattivatore dei radicali liberi , nella sclerosi laterale amiotrofica ( SLA ) . Sono stati ammessi nello studio 32 pazienti affetti da SLA definita visitati nel nostro Istituto dall'agosto 1993 a luglio 1995 . L'effetto del GSH è stato studiato in uno studio in aperto , crossover , r and omizzato . Il GSH è stato somministrato alla dose di 600 mg per via intramuscolare per 12 settimane . I pazienti sono stati assegnati a caso , secondo l'ordine di visita , a due gruppi . Per le prime 12 settimane il primo gruppo ha ricevuto il farmaco e il secondo solo terapie sintomatiche . Dopo un wash-out di una settimana , il secondo gruppo ha ricevuto il GSH e il primo solo terapie sintomatiche per altre 12  settimane . È stata confrontata la velocità di progressione dei sintomi nei due gruppi . La valutazione clinica comprendeva test manuali per la forza muscolare , la scala di Norris , una scala bulbare e la capacità vitale forzata ( FVC ) . Non è stata trovata alcuna differenza significativa nella velocità di progressione della SLA nei due periodi , anche se è stato osservato un lieve rallentamento nella velocità di progressione durante il perrodo di trattamento , forse dovuto al disegno in aperto dello studio . I nostri dati non dimostrano alcun effetto significativo del glutatione ridotto nel modificare la progressione della SLA Nutritional etiology of amyotrophic lateral sclerosis ( ALS ) , and other motor neuron disorders , can not be ignored even though many trials of nutritional therapy have not , thus far , yielded any benefit to the sufferers . Possibly the nutrients available , or the dosages used , have not been adequate to the circumstances ; perhaps an as-yet-unknown nutrient is deficient , poorly absorbed or under-utilized Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease , we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis ( ALS ) to examine whether it might modify the progression of the disease . Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months . Patients with familial ALS , pure progressive bulbar palsy , primary lateral sclerosis or progressive muscle atrophy were excluded ; a total of 111 patients were recruited . Fifty-three patients were r and omly assigned to receive the drug ( selegiline 10 mg/day orally for 6 months ) and the remaining 58 were considered ALS  controls . Mortality was similar in the two groups ( 4 and 5 patients respectively ) , though the difference was not statistically significant . Among the survivors , mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found . The results did not change when the data were related to age , duration and characteristics of onset of the disease . The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups . Our data do not show any significant effect of selegiline in modifying the progression of ALS BACKGROUND Amyotrophic lateral sclerosis ( ALS ) is a progressive disease with no effective treatment . In an initial study , riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients . We have carried out a double-blind , placebo-controlled , multicentre study to confirm those findings and to assess drug efficacy at different doses . METHODS 959 patients with clinical ly probable or definite ALS of less than 5 years ' duration were r and omly assigned treatment with placebo or 50 mg , 100 mg , or 200 mg riluzole daily ; r and omisation was stratified by centre and site of disease onset ( bulbar or limb ) . The primary outcome was survival without a tracheostomy . Secondary outcomes were rates of change in functional measures ( muscle strength , functional status , respiratory function , patient 's assessment s of fasciculation , cramps , stiffness , and tiredness ) . The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat . Drug-effect on survival was assessed before ( log-rank test ) and after adjustment for known prognostic factors ( Cox 's model ) . FINDINGS At the end of the study , after median follow-up of 18 months , 122 ( 50.4 % ) placebo-treated patients and 134 ( 56.8 % ) of those who received 100 mg/day riluzole were alive without tracheostomy ( unadjusted risk 0.79 , p = 0.076 ; adjusted risk 0.65 , p = 0.002 ) . In the groups receiving 50 mg and 200 mg riluzole daily , 131 ( 55.3 % ) and 141 ( 57.8 % ) patients were alive without tracheostomy ( relative to placebo 50 mg adjusted risk 0.76 , p = 0.04 ; 200 mg 0.61 , p = 0.0004 ) . There was a significant inverse dose response in risk of death . No functional scale discriminated between the treatment groups . The most common adverse reactions were asthenia , dizziness , gastrointestinal disorders , and rises in liver enzyme activities ; they were commonest with the 200 mg dose . INTERPRETATION Overall , efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio . This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS In this paper we present results from a double blind cross over trial with deprenyl , a selective and irreversible monoamine oxidase-B ( MAO-B ) inhibitor , in 10 patients suffering from amyotrophic lateral sclerosis . The patients were r and omised in such a way that half of the patients started with the active drug and half with the placebo treatment . Each patient was given 10 mg deprenyl ( eldepryl , 10 mg tablets ) per day for 12 weeks and then placebo for the same length of time . There was a drug free period of 12 weeks between the courses . The neurological status of the patients were evaluated every six weeks by using Norris , spinal and bulbar scores and it was observed that all cases deteriorated in their clinical status during the 36 weeks of the controlled study . MAO-B activity in blood platelets was completely inhibited during treatment with deprenyl . In the preliminary analysis performed so far , no obvious retardation in the progress of the disease could be observed with deprenyl treatment BACKGROUND The cause of amyotrophic lateral sclerosis ( ALS ) is not known , and there is no effective treatment . Cell death may be caused by oxidative damage . Selegiline hydrochloride ( Eldepryl ) is a monoamine oxidase-B inhibitor with antioxidant properties . OBJECTIVE To determine if selegiline affects the clinical course of patients with ALS . DESIGN Six-month , double-blind , placebo-controlled study of 133 patients with classical ALS and symptoms for less than 3 years . The primary end point to indicate effectiveness was the rate of change of the Appel ALS total score , an index of disease severity that incorporates strength and function in limbs , respiratory function , and bulbar function . RESULTS Of the 133 patients , 67 were r and omized to receive selegiline and 66 to receive placebo . One hundred four patients ( 53 in the selegiline group and 51 in the placebo group ) completed the 6-month trial . Both groups were comparable for baseline characteristics and mean Appel ALS total score ( 70.5 points for the selegiline group and 70.6 for the placebo group ) . There was no difference in the rate of progression as measured by the Appel ALS total score , showing an average increase of 22 points in 6 months . The monthly rate of change was 3.4 for the selegiline group and 3.5 for the placebo group . There was 1 adverse reaction : worsening depression . Seven patients died during the study ( 4 in the selegiline group and 3 in the placebo group ) . CONCLUSION Selegiline treatment had no significant effect on the rate of clinical progression or outcome of ALS Oxidative stress may contribute to the pathogenesis of amyotrophic lateral sclerosis ( ALS ) . We therefore examined prospect ively whether individuals who regularly use supplements of the antioxidant vitamins E and C  have a lower risk of ALS than nonusers . The study population comprised 957,740 individuals 30 years of age or older participating in the American Cancer Society 's Cancer Prevention Study II . Information on vitamin use was collected at time of recruitment in 1982 ; participants then were followed up for ALS deaths from 1989 through 1998 via linkage with the National Death Index . During the follow‐up , we documented 525 deaths from ALS . Regular use of vitamin E supplements was associated with a lower risk of dying of ALS . The age‐ and smoking‐adjusted relative risk was 0.99 ( 95 % confidence interval [ CI ] , 0.69–1.41 ) among occasional users , 0.59 ( 95 % CI , 0.36–0.96 ) in regular users for less than 10 years , and 0.38 ( 95 % CI , 0.16–0.92 ) in regular users for 10 years or more as compared with nonusers of vitamin E ( p for trend = 0.004 ) . In contrast , no significant associations were found for use of vitamin C or multivitamins . These results suggest that vitamin E supplementation could have a role in ALS prevention . Ann Neurol Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis ( ALS ) by an array of antioxidants and added other drugs to the regimen whenever a patient reported deterioration . Our customary prescription sequence was N-acetylcysteine ( NAC ) ; vitamins C and E ; N-acetylmethionine ( NAM ) ; and dithiothreitol ( DTT ) or its isomer dithioerythritol ( DTE ) .  Patients with a history of heavy exposure to metal were also given meso 2,3-dimercaptosuccinic acid ( DMSA ) . NAC , NAM , DTT , and DTE were administered by subcutaneous injection or by mouth or by both routes , the other vitamins and DMSA by mouth alone . The hospital pharmacy supplied NAC and NAM injections fluid as 100 ml bottles of 5.0 and 5.85 % solutions , respectively . DTT was delivered in special double-walled capsules of 200 mg . DTT/DTE injection fluid was added to the NAC and NAM bottles , the final DTT/DTE concentrations never exceeding 0.5 % . DMSA was provided in 250 mg capsules . All of the 36 patients used NAC and DTT/DTE ; 29 also used vitamins C and E ; 21 also used NAM ; and 7 also used DMSA , DMSA , NAM , vitamins C and E were tolerated well . In many patients , DTT , DTE , NAC and NAM induced pain , redness and swelling at the injection sites in that order of decreasing frequency . DTT and DTE did often and NAC did sometimes cause gastric pain , nausea and other abdominal discomfort . Comparison of survival in the treated group and in a cohort of untreated historical controls , disclosed a median survival of 3.4 years ( 95 % confidence interval : 3.0 - 4.2 ) in the treated and of 2.8 ( 95 % confidence interval 2.2 - 3.1 ) years in 
    Output:
    
No significant effect on the primary outcome measure was observed in a meta analysis of all antioxidants combined .
No significant differences were demonstrated in any of the secondary outcome measures .
In the opinion of the review ers , there is insufficient evidence of efficacy of individual  antioxidants  , or antioxidants in general , in the treatment of people with amyotrophic lateral sclerosis .