Toxicological Risks of the Cobalt-Chromium Alloys in Dentistry: A Systematic Review.

Background: The toxicological risk of Co-Cr dental alloys is actually a sensitive subject with the European regulatory changes, namely regulation (EU) 2017/745 and annex VI to the CLP regulation (EC) 1972/2008. Objectives: The objective of this review is to conduct a rigorous analysis of the cytocompatibility of cobalt-chromium (Co-Cr) dental alloys. Considering various parameters such as cytotoxicity, type IV hypersensitivity reaction, sensitization, and irritation, we investigated evidence of toxicity of Co-Cr in human dental applications. Data sources: Specific search strategies were performed in three electronic databases, namely Medline, Embase, and Web of Science, using a main restriction in the search regarding the publication date (1995-2022). Study selection: Out of a total of 836 articles, only 21 studies were selected and analyzed according to PRISMA methodology. Results: Among them, 10 in vitro studies using human samples and 11 in vivo studies on human patients were distinguished. Most of the in vitro studies confirmed that Co-Cr alloys have a good cytocompatibility compared to Ni alloys. Regarding the in vivo studies, it appeared that Co-Cr could rarely cause sensitization, irritation, and allergic reactions. Reactions were mainly observed for people allergic to Co or Cr. Nevertheless, titanium-based materials showed better results. Conclusions: This study proposes a new state of the art on Co-Cr dental alloys and will thus be very useful for carrying out additional studies. Relevance: This review will help practitioners in their daily clinical choice.

Seasonal variability of vitamin D status in patients with inflammatory bowel disease - A retrospective cohort study.

OBJECTIVES: Vitamin D deficiency predicts unfavorable disease outcomes in inflammatory bowel disease. Endogenous vitamin D synthesis is affected by seasonal factors including sunlight exposure, raising the question whether seasonality determines the risk of vitamin D deficiency and may mask other clinical risk factors. METHODS: Univariable and multiple regression analyses were performed in a retrospective cohort of 384 patients to determine risk factors for vitamin D deficiency. Since the observed 25-hydroxyvitamin D [25(OH)D] concentrations followed a sinusoidal pattern over the year, all 25(OH)D concentrations were normalized for the predicted variability of the respective day of analysis based on a sinusoidal regression analysis of 25(OH)D test results obtained in more than 86,000 control serum samples. RESULTS: Vitamin D deficiency was highly prevalent in patients with Crohn's disease or ulcerative colitis (63% and 55%, respectively) and associated with winter/spring seasons. After normalization of 25(OH)D concentrations for the day of analysis, vitamin D deficiency was associated with histories of complications related to inflammatory bowel disease, surgery, smoking and ongoing diarrhea while initial disease manifestation during adulthood, ongoing vitamin D supplementation and diagnosis of ulcerative colitis vs. Crohn's disease appeared to be protective. Multiple regression analyses revealed that vitamin D deficiency was associated with disease activity in Crohn's disease and anemia in ulcerative colitis patients. Only few deficient patients achieved sufficient 25(OH)D concentrations over time. However, increasing 25(OH)D concentrations correlated with improved Crohn's disease activity. CONCLUSIONS: Vitamin D deficiency was highly prevalent in patients with Crohn's disease and ulcerative colitis and dependent on the season of the year. Following normalization for seasonality by sinusoidal regression analysis, vitamin D deficiency was found to be associated with parameters of complicated disease course while increasing 25(OH)D concentrations over time correlated with reduced activity of Crohn's disease.

Vitamin D Inhibits Pro-Inflammatory T Cell Function in Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Dysregulated T cell responses contribute to the pathogenesis of inflammatory bowel disease [IBD]. Because vitamin D [vitD] deficiency is a risk factor for adverse disease outcomes, we aimed to characterize the impact of vitD on intestinal and peripheral T cell profiles. METHODS: T cells were isolated from peripheral blood and intestinal biopsies of IBD patients, incubated with vitD and characterized by flow cytometry. To translate these in vitro findings to the clinic, serum vitD concentrations and clinical outcomes were correlated with T cell phenotype and function in a prospective patient cohort. RESULTS: Incubation of peripheral and intestinal T cells with 1,25(OH)2-vitD resulted in strongly reduced frequencies of pro-inflammatory CD4+ and CD8+ T cells producing interferon γ [IFNγ], interleukin-17 [IL-17], IL-22, IL-9 and tumour necrosis factor [TNF]. Univariable analysis of 200 IBD patients revealed associations of vitD deficiency with non-compliant vitD intake, season of the year and anaemia in Crohn's disease [CD] as well as disease activity in ulcerative colitis [UC]. Ex vivo immunophenotyping revealed that CD4+ and CD8+ T cell subsets were not substantially altered in vitD-deficient vs vitD-sufficient patients while regulatory T cell frequencies were reduced in UC and non-smoking CD patients with vitD deficiency. However, normalization of serum vitD concentrations in previously deficient CD patients resulted in significantly reduced frequencies of CD4+ T cells producing IFNγ, IL-17 and IL-22. CONCLUSION: vitD exerts profound anti-inflammatory effects on peripheral and intestinal CD4+ and CD8+ T cells of IBD patients in vitro and inhibits TH1 and TH17 cytokine production in CD patients in vivo.