Statins are mainstream therapy in the treatment and prevention of cardiovascular disease through inhibitory effects on cholesterol synthesis. However, statins' beneficial effects in cardiovascular disease may also be attributable to their role as anti-inflammatory mediators. Here, we investigated the effects of simvastatin treatment on expression levels of interleukin (IL) 1β in both patient with hyperlipidemia and healthy human peripheral blood mononuclear cells (PBMCs) using cholesterol crystals (CC), a cardiovascular pathogenic stimulus for activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Cholesterol crystal-induced NLRP3 inflammasome activation was used to trigger maturation and release of IL-1β in PBMCs. Specifically, isolated PBMCs from patients with hyperlipidemia at baseline and following 8 weeks of in vivo treatment with simvastatin (10-20 mg) daily were stimulated with lipopolysaccharide (LPS; 100 ng/mL) for 3 hours to induce proIL-Iβ expression followed by CC (2 mg/mL) stimulation for further 18 hours to activate the NLRP3 inflammasome complex to induce maturation/activation of IL-1β. Peripheral blood mononuclear cells were also isolated from healthy donors and stimulated in vitro with simvastatin (50, 25, 5, and 2 µmol/L) prior to stimulation with LPS and CC as described above. The effects of simvastatin treatment on levels of IL-1β expression were determined by enzyme-linked immunosorbent assay and western blot. Both in vitro and in vivo treatments with simvastatin led to a significant reduction in the levels of expression of IL-1β in response to stimulation with CC. Simvastatin inhibits the expression and activation of IL-1β induced by CC in PBMCs, which may contribute to its protective role in patients with cardiovascular disease.
Vocally disruptive behavior (VDB) is a common and particularly difficult symptom to manage in dementia. VDB is usually considered collectively with agitation and aggression as a component of behavioral and psychological symptoms in dementia and is therefore poorly understood as an individual symptom. A review of the literature is described where VDB as a challenging behavior has been individually examined as a symptom. A case of VDB occurring in patient with dementia is described where the patient’s repetitive vocalizations responded to treatment with pregabalin. This has not been previously reported in the literature. The prevalence of VDB, the factors associated with it and the current management guidelines for clinicians are outlined with a review of the drug treatment strategies for VDB. Pregabalin with its unique pharmacological profile and excellent tolerability should be considered as a possible treatment for VDB where drug treatment is indicated.
Approximately 25% of people with quiescent inflammatory bowel disease (IBD) have symptoms caused by a functional gastrointestinal disorder (FGID). The pathophysiology of FGIDs in IBD is multifactorial. The gut–brain axis plays an important role as a bidirectional pathway with reciprocal gastrointestinal and psychological symptoms. Other factors include altered gastrointestinal motility, microbiome dysbiosis, medication use, prior surgery, impaired intestinal permeability, immune-system activation, and visceral hypersensitivity. As both IBD and certain FGIDs can have similar symptoms, it can be difficult to determine which disorder is the precipitant of symptoms. However, a prompt diagnosis of an overlapping FGID helps avoid unnecessary corticosteroid use and escalations of IBD treatment. Despite their prevalence, there have been very few randomized controlled trials conducted on therapeutic interventions for overlapping FGIDs in IBD. Therefore, management usually follows those interventions recommended for FGIDs, with certain adaptations made to allow for an altered gastrointestinal anatomy and functioning, caused by IBD.
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