METHOD: α-tocopherol monoester of MFA (TMMA) and α-tocopherol di-ester of MFA (TDMA) were synthesized by esterification reaction and were subjected to various in vivo characterizations.
RESULTS: Masking of the carboxylate group of MFA with the proposed pro-moieties significantly (p<0.05) delayed the onset of tonic-clonic seizure in mice. Besides, the intraperitoneal administration of TMMA and TDMA in mice produced significantly (p<0.05) stronger anti-inflammatory effects in the carrageenan-induced paw edema test and greater anti-nociceptive effect in the acetic acid-induced writhing test than MFA at an equimolar dose of 20 mg/kg. Treatment with TMMA and TDMA caused a significant (p<0.05) inhibition of pain at 1st and 2nd phases of formalin-induced licking test in mice, whereas treatment with MFA inhibited the 2nd phase only. Pretreatment with naloxone and flumazenil significantly (p<0.05) reversed the anti-nociceptive effect of MFA, TMMA and TDMA in the acetic acid-induced writhing test. In addition, treatment with TMMA and TDMA caused significantly (p<0.05) a higher inhibition of pain in the glutamate-induced licking response in mice than MFA.
CONCLUSION: Masking the carboxylate moiety of MFA by α-tocopherol and α-tocopherol acetate has a great potential for reducing CNS toxicity, enhancing the therapeutic efficacy and altering the mode of anti-nociceptive action.
OBJECTIVES: To assess the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) for diabetic cystoid macular oedema (CMO).
SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 12 January 2015.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs investigating the effects of topically applied NSAIDs in the treatment of people with diabetic CMO aged 18 years of age or over.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and screened all available titles and abstracts for inclusion. There were no discrepancies and we did not have to contact trial investigators for missing data.
MAIN RESULTS: We did not identify any RCTs matching the inclusion criteria for this review.
AUTHORS' CONCLUSIONS: The review did not identify any RCTs investigating the effects of topical NSAIDs in the treatment of diabetic CMO. Most of the studies identified through the electronic searches had been conducted to analyse the effect of topical NSAIDs for pseudophakic CMO.In the absence of high quality evidence, clinicians need to use their clinical judgement and other low level evidence, such as observational non-randomised trials, to decide whether to use topical NSAIDs in cases of diabetic CMO.More research is needed to better understand the cause of this condition and its pathophysiology. This systematic review has identified the need for well designed, adequately powered RCTs to assess possible beneficial and adverse effects of topical NSAIDs in people with diabetic CMO. Future trials should aim to include a large sample size with an adequate follow-up period of up to one year.
METHODS: This comparative pilot study consists of 40 diabetic patients with diabetic macular oedema. The patients were randomized into two groups using envelope technique sampling procedure. Treatment for diabetic macular oedema was based on the printed envelope technique selected for every patient. Twenty patients were assigned for IVTA group (one injection of IVTA) and another 20 patients for LASER group (one laser session). Main outcome measures were mean BCVA and mean MEI at three months post treatment. The MEI was quantified using Heidelberg Retinal Tomography II.
RESULTS: The mean difference for BCVA at baseline [IVTA: 0.935 (0.223), LASER: 0.795 (0.315)] and at three months post treatment [IVTA: 0.405 (0.224), LASER: 0.525 (0.289)] between IVTA and LASER group was not statistically significant (p = 0.113 and p = 0.151 respectively). The mean difference for MEI at baseline [IVTA: 2.539 (0.914), LASER: 2.139 (0.577)] and at three months post treatment [IVTA: 1.753 (0.614), LASER: 1.711 (0.472)] between IVTA and LASER group was also not statistically significant (p = 0.106 and p = 0.811 respectively).
CONCLUSIONS: IVTA demonstrates good outcome comparable to laser photocoagulation as a primary treatment for diabetic macular oedema at three months post treatment.
TRIAL REGISTRATION: ISRCTN05040192 (http://www.controlled-trial.com).