***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: OBJECTIVE To evaluate the efficacy and safety of alpha-lipoic acid given intravenously , followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy . RESEARCH DESIGN AND METHODS In a multicenter r and omized double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy [ ALADIN ] III Study ) , 509 out patients were r and omly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by 600 mg alpha-lipoic acid three times a day orally for 6 months ( A-A ; n = 167 ) ; 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( A-P ; n = 174 ) ; and placebo once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( P-P ; n = 168 ) . Outcome measures included the Total Symptom Score ( TSS ) for neuropathic symptoms ( pain , burning , paresthesias , and numbness ) in the feet , and the Neuropathy Impairment Score ( NIS ) . Data analysis was based on the intention to treat . RESULTS No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline . The TSS in the feet decreased from baseline to day 19 ( median [ range ] ) by -3.7 ( -12.6 to 5.0 ) points in the group given alpha-lipoic acid intravenously and by -3.0 ( -12.3 to 8.0 ) points in the placebo group ( P = 0.447 ) , but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group ( 85.6 [ 0 - 219 ] vs. 95.9 [ 5.5 - 220 ] ) ; P = 0.033 ) . After 7 months , the changes in the TSS from baseline were not significantly different between the three groups studied , which could be due to increasing intercenter variability in the TSS during the trial . The NIS decreased after 19 days by -4.34+/-0.35 points ( mean + /- SEM ) in A-A and A-P and -3.49+/-0.58 points in P-P ( P = 0.02 for alpha-lipoic acid versus placebo ) and after 7 months by -5.82+/-0.73 points in A-A , -5.76+/-0.69 points in A-P , and -4.37+/-0.83 points in P-P ( P = 0.09 for A-A vs. P-P ) . The rates of adverse events were not different between the groups throughout the study . CONCLUSIONS These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid , followed by a 6-month oral treatment , had no effect on neuropathic symptoms distinguishable from placebo to a clinical ly meaningful degree , possibly due to increasing intercenter variability in symptom scoring during the study . However , this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions . Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy BACKGROUND QR-333 , a topical compound that contains quercetin , a flavonoid with aldose reductase inhibitor effects , ascorbyl palmitate , and vitamin D(3 ) , was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms . This proof-of-principle study assessed the efficacy and safety of QR-333 against placebo in a small cohort of patients with diabetic neuropathy . METHODS This r and omized , placebo-controlled , double-blind trial included 34 men and women ( 21 - 71 years of age ) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo ( 2:1 ratio ) , three times daily for 4 weeks , to each foot where symptoms were experienced . Five-point scales were used to determine changes from baseline to endpoint in symptoms and quality of life ( efficacy ) . Safety was assessed through concomitant medications , adverse events , laboratory evaluations , and physical examinations . RESULTS QR-333 reduced the severity of numbness , jolting pain , and irritation from baseline values . Improvements were also seen in overall and specific quality -of-life measures .  QR-333 was well tolerated .  Eleven patients in the  QR-333 group reported 23 adverse events ( all mild or moderate ) ; 4 in the placebo group reported 5 events ( all moderate ) . One patient who applied QR-333 noted a pricking sensation twice , the only adverse event considered possibly related to study treatment . CONCLUSIONS From this preliminary safety study , it appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy and improve quality of life . These findings warrant further investigation of this topical compound Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus ( HIV ) patients under dideoxynucleoside therapy  , benefits only partially from medical therapy , and often leads to drug discontinuation . Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism , eventually related to a reduction of mitochondrial DNA content , and interference with nerve growth factor activity . Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions . Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation . The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients . Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period .  Efficacy was evaluated by means of the modified Short Form McGill Pain Question naire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit . Mean pain intensity score was significantly reduced during the study , changing from 7.35 + /- 1.98 ( mean + /- SD ) at baseline to 5.80 + /- 2.63 at week 4 ( p = 0.0001 ) . Electrophysiological parameters did not significantly change between baseline and week 4 . In this study , acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity . On the contrary , no effect was noted on neurophysiological parameters BACKGROUND The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity . Because this neurotoxicity involves ROS production , we investigated the efficacy of mangafodipir , a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer . METHODS The effects of mangafodipir were examined in mice following treatment with oxaliplatin . Neurotoxicity , axon myelination , and advanced oxidized protein products ( AOPPs ) were monitored . In addition , we enrolled 23 cancer patients with grade ≥ 2 oxaliplatin-induced neuropathy in a phase II study , with 22 patients receiving i.v . mangafodipir following oxaliplatin .  Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir . RESULTS Mangafodipir  prevented motor and sensory dysfunction and demyelinating lesion formation . In mice , serum AOPPs decreased after 4 weeks of mangafodipir treatment . In 77 % of patients treated with oxaliplatin and mangafodipir  , neuropathy improved or stabilized after 4 cycles . After 8 cycles , neurotoxicity was down grade d to grade ≥ 2 in 6 of 7 patients . Prior to enrollment , patients received an average of 880 ± 239 mg/m2 oxaliplatin . Patients treated with mangafodipir  tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy . Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin . Serum AOPPs were lower in responders compared with those in nonresponders . CONCLUSION Our study suggests that mangafodipir can prevent and /or relieve oxaliplatin-induced neuropathy in cancer patients . Trial registration . Clinical trials.gov NCT00727922 . Funding . Université Paris Descartes , Ministère de la Recherche et de l'Enseignement Supérieur , and Assistance Publique-Hôpitaux de Paris Abstract Background and Objective : The management of diabetic neuropathy is still a challenge for physicians . The aim of this study was to assess the efficacy of a new combination of alpha lipoic acid and superoxide dismutase for the treatment of diabetic neuropathy . p ] Methods : The setting of this study was ambulatory ( outpatient ) care . A prospect i ve , non-r and omized , open-label study was conducted in 50 patients with diabetes mellitus and with a deficit in both motor and sensory nerve conduction . Treatment was with a new combination of alpha lipoic acid and superoxide dismutase ( ALA600SOD ® ) for 4 months  . Electroneurographic parameters and perceived pain were assessed at baseline and after treatment . Results : After 4 months of treatment , patients significantly ( p < 0.001 ) improved their electroneurographic parameters and their perception of pain . Best improvements were observed in sensory nerve conduction . Conclusion : The combination of two powerful antioxidant agents leads to improvement in both subjective and objective parameters in patients with diabetic neuropathy . New profitable directions for investigations are opened for a non-invasive treatment of diabetic neuropathy in the future Vascular dysfunction , including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus . Both pentoxifylline ( PF ) and pentosan polysulphate ( PPS ) are known to improve microcirculation . Antioxidant and antiproteinuric effects of PF are also known . In a placebo-controlled study , we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients . Patients in Verum group ( n = 77 ) received PF-PPS infusions ( 100–100 mg/day ) for 5 days . Control diabetics ( Placebo group ; n = 12 ) were given only saline infusions . Specialized cardiovascular autonomic reflex tests , vibration threshold values and urinary albumin excretion were assessed before and after therapy . In Verum group , autonomic score , indicating the severity of cardiac autonomic dysfunction , decreased after therapy ( p ≤ 0.001 ) . Of the reflexes , deep breath and h and grip tests also improved after therapy ( p ≤ 0.001 ) . Vibration threshold values , an indicator of the loss of sensory nerve function , were increased after therapy ( p ≤ 0.001 ) . Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group . Majority of patients had normalbuminuria , which was not affected by PF-PPS . In 
    Output:
    
Peripheral neuropathy is associated with an increase of reactive oxygen species and a decrease in endogenous antioxidants .
Genetic predisposition to oxidative damage may be a factor .
Antioxidant treatment is promising regarding treatment .
Though further research is necessary to better underst and the underlying mechanism , it is evident that oxidative stress is implicated in the pathogenesis of – or is at least systematic ally present in – PN