A twelve-week, four-arm, randomized, double-blind, placebo-controlled, phase 2 prospective clinical trial to evaluate the efficacy and safety of an anthroposophic multimodal treatment on chronic pain in outpatients with postpolio syndrome.

INTRODUCTION: Chronic pain and fatigue are the main symptoms of postpoliomyelitis syndrome (PPS). This study aimed to evaluate the efficacy and safety of an anthroposophic multimodal treatment for chronic pain in PPS outpatients. METHODS: A twelve-week, four-arm, randomized, double-blind, placebo-controlled, phase 2 prospective clinical trial was designed to compare four groups (n = 48): groups A and B received daily active experimental transdermal gel (ETG) or placebo gel (PTG), respectively; groups C and D received weekly external therapies, art therapies, and neurofunctional reorganization, plus either daily ETG or PTG, respectively. The pain symptoms were evaluated through a visual analogue scale (VAS), the McGill questionnaire, and thermography. Quality of life and resilience were evaluated by the WHOQOL-BREF and Antonovsky sense of coherence questionnaires applied at baseline and after the interventions. RESULTS: No related adverse events occurred, and 10% of the patients reports dysphagia improvement. In the groups C and D, pain reduction was statistically significant in both the placebo group (p = .02, d = 1.315) and in the ETG (p = .005, d = 2.035). However, following the week-to-week evolution of pain with the concomitant use of the ETG, this significant pain reduction occurred earlier from the 4th week and continued to decrease (p = .016, d = 1.369). In the group that received the complete multimodal treatment, the greatest significant benefit in increasing quality of life occurred in the physical domain and elevation in resilience with an emphasis on meaning and comprehension domains. CONCLUSIONS: The anthroposophic multimodal treatment group presented both safety and efficacy as an analgesic in the groups that received the nonpharmacological therapies, much earlier when associated with the ETG. The multimodal approach corresponded to the pattern of better efficacy for both pain reduction and improvement in quality of life and resilience.

Pregnancy and the apoptotic pathway in experimental melanoma.

Pregnancy-associated melanoma is defined as melanoma diagnosed during pregnancy or within 1 year of delivery. The association of pregnancy with melanoma is well known, but its underlying molecular mechanisms of association are poorly understood. The aim was to assess the expression of apoptosis-related genes in melanoma tumors during pregnancy in an attempt to elucidate the molecular mechanisms underlying apoptosis-driven activation of melanoma cells in this period. Mice were allocated across two experimental groups (nonpregnant and pregnant) and implanted with the melanoma cell line BF16-F10. Tumor tissue was collected for RNA extraction and purification, and gene expression was quantified using the mouse apoptosis RT2ProfilerTM PCR array. Different intracellular apoptotic pathways were activated (positively or negatively) by pregnancy in tumor cells: intrinsic (21.5%), extrinsic (32%), caspase (14%), apoptosis (21.5%), and caspase-activated DNase (11%). The proportion of upregulated genes for each of these pathways was 100, 30, 50, 17, and 0%, respectively. MetaCore software was then used to analyze gene ontology processes and pathways by building networks. Among the gene ontology processes, the majority of differentiated genes were related to the apoptotic process. The main pathway activated by pregnancy was the intrinsic one (genes Api-5, Bcl2-L1, Birc-2, Birc-3, Bok, and Trp53bp2). Pregnancy activates the intrinsic apoptosis pathway to stimulate caspases 7 and 9, but the final balance is inhibition of apoptosis mechanisms. In mice, pregnancy cannot promote or worsen melanoma.