Osteoarthritis is primarily characterized by areas of destruction of articular cartilage and by synovitis. Articular damage and synovitis are secondary to local increase of pro-inflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha), enzymes with proteolytic activity (matrix metalloproteinases), and enzymes with pro-inflammatory activity (cyclooxygenase-2 and nitric oxide synthase-2). Enhanced expression of these proteins in chondrocytes and in synovial membrane appears associated to the activation and nuclear translocation of nuclear factor-kappaB (NF-kappaB). Chondroitin sulfate (CS) prevents joint space narrowing and reduces joint swelling and effusion. To produce these effects, CS elicits an anti-inflammatory effect at the chondral and synovial levels. CS and its disaccharides reduce NF-kappaB nuclear translocation, probably by diminishing extracellular signal-regulated kinase1/2, p38mitogen-activated protein kinase and c-Jun N-terminal kinase activation. This review discusses the evidence supporting that CS pleiotropic effects in chondrocytes and synoviocytes are primarily due to a common mechanism, e.g., the inhibition of NF-kappaB nuclear translocation.

Inflammatory reactions (IRs), both infectious and aseptic, downregulate numerous enzymes of cytochrome P450 (CYP) and ATP-binding cassette transporters. The mechanism involves proinflammatory cytokines and activation of transcription factors, nuclear factor-κB, CCAAT-enhancer-binding protein-β and c-myc, which bind to negative regulatory elements and/or impede the binding of nuclear receptors to promoter elements. Downregulation of CYP enzymes and transporters modulates the kinetics of a drug, resulting in increased plasma and tissue concentrations of the drug and enhanced effect and/or toxicity. Clinical trials have shown that IRs increase the risk of myocardial infarction and stroke. In this article, we speculate that IRs downregulate cardiac and vascular CYP enzymes (CYP2C8/9 and CYP2J2) responsible for the formation of vasorelaxant products. Patients with IRs should be advised that the risk of drug adverse effects and of cardiovascular diseases is increased; therefore, the benefit-risk ratio and use of drugs with narrow therapeutic index should be revaluated, as well as the conditions precipitating cardiovascular events.

Did universities benefit from the pandemic? Some did receive more funding than usual. We use vector autoregressive models to forecast both enrollment and public subsidies in a jurisdiction where public funding depends mostly on enrollment. Using unemployment as an established proxy for the impact of recessions on enrollment, we show that the recent COVID pandemic increases pressure on public subsidies. Further, we use our forecasts to decompose the current subsidies between long-term subsidies, recession induced subsidies, and additional funding. We find that the subsidies given during the pandemic were higher than what a typical recession would command for 8 universities out of 18.

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