RESUMO
BACKGROUND: Multiple studies have reported that cannabis administration in multiple sclerosis patients is associated with decreased symptom severity. This study was conducted to evaluate the prevalence of cannabis abuse in multiple sclerosis cases and to evaluate the effect of cannabis on serum cytokines in such cases. Patients and Methods. A total of 150 multiple sclerosis cases along with 150 healthy controls were included during the study period. All cases were subjected to history taking, neurological examination, and routine investigations. Cases were asked about cannabis intake which was confirmed by a urine test. Serum cytokines including IL-1, IL-2, IL-4, IL-10, IL-12, IL-17, IL-22, IFN-γ, IFN-ß1, and TNF-α were ordered for all cases and controls. RESULTS: Twenty-eight cases were cannabis abusers (MS/cannabis group, 18.67%). The remaining 122 cases represented the MS group. There was no significant difference between the three groups regarding age, disease duration, or MS type. Male gender was more predominant in the MS/cannabis group, and the number of relapses was significantly lower in the same group. Fifteen cases (53.6%) reported that their symptoms were improved by cannabis. Proinflammatory cytokines were significantly elevated in the MS group compared to the MS/cannabis and control groups. Additionally, anti-inflammatory cytokines had significantly lower values in the MS group compared to the MS/cannabis and control groups. Most clinical symptoms were significantly improved in the MS/cannabis group compared to the MS group apart from sexual dysfunction, bladder symptoms, and visual disturbances. Mild side effects of cannabis were also reported. CONCLUSION: Cannabis may have a positive impact on the cytokine and clinical profiles in cases with multiple sclerosis.
RESUMO
Sulfonic acid analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene, 1) as well as seven novel and two reported analogues of 6-(ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinic acid (NEt-TMN) were synthesized and assessed for selective retinoid X receptor (RXR) agonism. Compound 1 is FDA-approved for treatment of cutaneous T-cell lymphoma (CTCL); however, 1 can provoke side effects by impacting RXR-dependent receptor pathways. All of the analogues in this study were evaluated for their potential to bind RXR through modeling and then assayed in an RXR-RXR mammalian-2-hybrid (M2H) system and in RXR-responsive element (RXRE)-mediated transcriptional experiments. The EC50 profiles for these unique analogues and their analogous effectiveness to inhibit proliferation in CTCL cells relative to 1 suggest that these compounds possess similar or even enhanced therapeutic potential. Several compounds also displayed more selective RXR activation with minimal cross-signaling of the retinoic acid receptor. These results suggest that modifications of potent RXR agonists such as NEt-TMN can lead to improved biological selectivity and potency compared with the known therapeutic.