Chronic kidney disease (CKD) leads to an 18-fold increase in cardiovascular complications not fully explained by traditional risk factors. Levels of renalase, a recently discovered oxidase that metabolizes catecholamines, are decreased in CKD. Here we show that renalase deficiency in a mouse knockout model causes increased plasma catecholamine levels and hypertension. Plasma blood urea nitrogen, creatinine, and aldosterone were unaffected. However, knockout mice had normal systolic function and mild ventricular hypertrophy but tolerated cardiac ischemia poorly and developed myocardial necrosis threefold more severe than that found in wild-type mice. Treatment with recombinant renalase completely rescued the cardiac phenotype. To gain insight into the mechanisms mediating this cardioprotective effect, we tested if gene deletion affected nitrate and glutathione metabolism, but found no differences between hearts of knockout and wild-type mice. The ratio of oxidized (NAD) to reduced (NADH) nicotinamide adenine dinucleotide in cardiac tissue, however, was significantly decreased in the hearts of renalase knockout mice, as was plasma NADH oxidase activity. In vitro studies confirmed that renalase metabolizes NADH and catecholamines. Thus, renalase plays an important role in cardiovascular pathology and its replacement may reduce cardiac complications in renalase-deficient states such as CKD.

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OBJECTIVES:Oral health in Down syndrome children has some peculiar aspects that must be considered in the follow-up of these patients. This study focuses on characterizing the environmental and host factors associated with dental caries in Portuguese children with and without Down syndrome.METHODS:A sibling-matched, population-based, cross-sectional survey was performed.RESULTS:Down syndrome children presented a significantly greater percentage of children without caries, 78% vs. 58% of non-Down syndrome siblings. This difference in the DMFT index (number of decayed, missing and filled teeth) essentially reflects data obtained from treated teeth, for which 91% of children with Down syndrome had never had a tooth treated vs. 67% of siblings. This result was statistically significant, whereas results for decayed and lost teeth did not differ between Down syndrome children and their unaffected siblings. Additionally, in Down syndrome children, a delayed eruption of the second molar occurs. Down syndrome children and their siblings have similar oral hygiene habits, but a higher percentage of Down syndrome children visit a dentist before the age of three years, in comparison to their siblings. Bruxism was also more common in Down syndrome children compared to their siblings.CONCLUSIONS:Our results show that Portuguese children with Down syndrome have lower caries rates than children without Down syndrome. This reduced prevalence may be associated with the parents' greater concern about oral health care in Down syndrome children, resulting in their taking them sooner to visit a dentist, as well as to a higher bruxism prevalence and delayed tooth eruption.

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Oral microbiota is one of the most complex and diverse microbial communities in the human body. In the present study, we aimed to characterize oral fungi biodiversity and stability over time in a group of healthy participants with good oral health. Oral health and oral fungal microbiota were evaluated in 40 healthy individuals. A follow-up of 10 participants was carried out 28 weeks and 30 weeks after the first sampling. Oral rinse was collected and incubated in a fungal selective medium at 25ºC and 37ºC for 7 days. Fungi were identified based on macro- and microscopic morphology. API/ID32C was used for yeast identification, and molecular techniques were used to identify the most prevalent nonidentified moulds, mainly by sequencing 18S and internally transcribed spacer regions. Moulds were recovered from all participants and yeast from 92.5%. The most frequently isolated fungi were Candida spp., Rhodotorula spp., Penicillium spp., Aspergillus spp., and Cladosporium spp. The oral fungal community presented a high interindividual variability, but the frequency and quantification of each fungal taxon was constant over the 30-week observation period, showing a consistent intraindividual stability over time. The intraindividual stability opposed to interindividual variability may suggest a common and a variable group of fungi in the oral cavity.