Gender analysis of moxifloxacin clinical trials

Purpose: To determine the inclusion of women and the sex-stratification of results in moxifloxacin Clinical Trials (CTs), and to establish whether these CTs considered issues that specifically affect women, such as pregnancy and use of hormonal therapies. Previous publications about women’s inclusion in CTs have not specifically studied therapeutic drugs. Although this type of drug is taken by men and women at a similar rate, adverse effects occur more frequently in the latter. Methods: We reviewed 158 published moxifloxacin trials on humans, retrieved from MedLine and the Cochrane Library (1998–2010), to determine whether they complied with the gender recommendations published by U.S. Food and Drug Administration Guideline. Results: Of a total of 80,417 subjects included in the moxifloxacin CTs, only 33.7% were women in phase I, in contrast to phase II, where women accounted for 45%, phase III, where they represented 38.3% and phase IV, where 51.3% were women. About 40.9% (n = 52) of trials were stratified by sex and 15.3% (n = 13) and 9% (n = 7) provided data by sex on efficacy and adverse effects, respectively. We found little information about the influence of issues that specifically affect women. Only 3 of the 59 journals that published the moxifloxacin CTs stated that authors should stratify their results by sex. Conclusions: Women are under-represented in the published moxifloxacin trials, and this trend is more marked in phase I, as they comprise a higher proportion in the other phases. Data by sex on efficacy and adverse effects are scarce in moxifloxacin trials. These facts, together with the lack of data on women-specific issues, suggest that the therapeutic drug moxifloxacin is only a partially evidence-based medicine.

Alterations in energy metabolism, neuroprotection and visual signal transduction in the retina of parkinsonian, MPTP-treated monkeys

Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ±1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTPinduced neuronal degeneration in the retina, in similarity to mechanisms thought to underlie neuronal death in the Parkinson’s diseased brain and neurodegenerative diseases of the retina proper.