This study presents a comprehensive view of the histological and functional status of the prostate of adult rat offspring of mothers subjected to gestational diabetes induced by alloxan. The ventral prostate of male adult offspring of diabetic (DP) or normal (CP) mothers was evaluated for collagen fibres, cell death, fibroblasts, smooth muscle cells, cell proliferation, matrix metalloproteinases (MMPs), androgen receptors (AR), transforming growth factor β1 (TGFβ-1), catalase and total antioxidant activity. The prostates of DP animals were lower in weight than those of the CP group. The DP group also exhibited hyperglycaemia and hypotestosteronemia, higher cell proliferation and AR expression, a reduction in α-actin (possibly interfering with the reproductive function of the prostate), and enhanced activity of MMP-2, although the absolute content of MMP-2 was lower in this group. These findings were associated with increased TGFβ-1 and decreased collagen distribution. The prostates of DP rats additionally exhibited reductions in catalase and total antioxidant activity. Thus, rats developing in a diabetic intrauterine environment have glycaemic and hormonal changes that impact on the structure and physiology of the prostate in adulthood. The increased AR expression possibly leads to elevated cell proliferation. Stromal remodelling was characterized by enhanced activity of MMP-2 and collagen degradation, even with increased TGFβ-1 activation. These changes associated with increased oxidative stress might interfere with tissue architecture and glandular homeostasis.

BackgroundThere is evidence that pharmacological interventions, including biologic therapies, can improve inflammation, disease activity and function in inflammatory rheumatic and musculoskeletal diseases (I-RMDs), and fatigue has increasingly been included as a secondary outcome of I-RMDs clinical trials. However, no systematic review (SR) has established the evidence for the pharmacological management of fatigue in people with I-RMD [1,2].ObjectivesTo identify the best evidence on the efficacy of pharmacological interventions in reducing fatigue in people with I-RMDs and to summarise their safety in the identified studies to inform EULAR recommendations for the management of fatigue in people with I-RMD.MethodsSystematic review of adults with I-RMD conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Assessment of risk of bias, data extraction, and synthesis performed by two reviewers independently. Data pooled in statistical meta-analyses.ResultsFrom a total of 4,150 records, 454 were selected for full-text review, 105 fulfilled the inclusion criteria, and 19 RCTs were included in meta-analyses. Adalimumab was superior to placebo in reducing fatigue at 52 and 12 weeks (wk) in rheumatoid arthritis (RA) (mean difference [MD]=-2.25, p=0.03; MD=-3.03, p<0.001; respectively) and psoriatic arthritis (MD=-3.16, p=0.26). Golimumab (24wk: MD=-5.27, p<0.001), baricitinib (24wk: MD=-4.06, p<0.001), sarilumab (24wk: MD=-3.15, p<0.001), tocilizumab (24wk: MD=-3.69, p<0.001) and tofacitinib (12wk: MD=-4.44, p<0.001) were also superior to placebo in reducing fatigue in RA. A dose/effect relationship was observed for sarilumab, tocilizumab and tofacitinib. In spondyloarthritis, secukinumab was superior to placebo in reducing fatigue at 16wk (MD=-4.15, p<0.001), with a dose/effect relationship also observed (Figure 1). The narrative results of the RCTs not included in the meta-analysis indicated that several other pharmacological interventions were efficacious in reducing fatigue, with reassuring safety results.ConclusionPharmacological interventions are efficacious and safe for the management of fatigue in people with I-RMD.References[1]Almeida C, Choy EH, Hewlett S, et al. Biologic interventions for fatigue in rheumatoid arthritis.The Cochrane database of systematic reviews. 2016;2016:Cd008334.[2]Choy EH. Effect of biologics and targeted synthetic disease-modifying anti-rheumatic drugs on fatigue in rheumatoid arthritis.Rheumatology. 2019;58:v51-v5.Figure 1.The summary of the meta-analyses, PsA: Psoriatic arthritis, RA: Rheumatoid arthritis, SpA: Spondyloarthritis, wk: weeksAcknowledgementsB Farisogullari and E Santos contributed equally to the manuscript.Disclosure of InterestsBayram Farisogullari: None declared, Eduardo Santos: None declared, Emma Dures: None declared, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB.