Hamamelis virginiana L. extract presents antimicrobial and antibiofilm effects, absence of cytotoxicity, anti-inflammatory action, and potential to fight infections through the nitric oxide production by macrophages.

The potential of H. virginiana L. was evaluated against Candida spp. (C. albicans, C. dubliniensis, C. glabrata, C. guilliermondii, C. krusei, and C. tropicalis) and bacteria (Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus mutans). Effect on murine macrophages (RAW 264.7) was also evaluated with respect to cytotoxicity and production of cytokines (IL-1ß and TNF-α) and nitric oxide (NO). The most effective concentrations of the extract were determined by microdilution broth. These concentrations were analyzed on biofilms, after 5 min or 24 h exposure. Cytotoxicity was performed by MTT assay and quantification of cytokines and NO by ELISA and Griess reagent, respectively. The extract acted against the planktonic forms and provided significant reductions of all the microbial biofilms; besides, showed no cytotoxic effect, except at 100 mg/mL, after 24 h exposure. There was cytokine production; however, a modulatory effect was observed in groups exposed to lipopolysaccharide (LPS) from E. coli. NO production was similar or higher than the control group. Thus, H. virginiana L. extract showed antimicrobial and antibiofilm effects; absence of cytotoxicity for RAW 264.7; anti-inflammatory action; and potential to fight infections through the NO production.

Chromosomal microarray analyses from 5778 patients with neurodevelopmental disorders and congenital anomalies in Brazil.

Chromosomal microarray analysis (CMA) has been recommended and practiced routinely since 2010 both in the USA and Europe as the first-tier cytogenetic test for patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. However, in Brazil, the use of CMA is still limited, due to its high cost and complexity in integrating the results from both the private and public health systems. Although Brazil has one of the world's largest single-payer public healthcare systems, nearly all patients referred for CMA come from the private sector, resulting in only a small number of CMA studies in Brazilian cohorts. To date, this study is by far the largest Brazilian cohort (n = 5788) studied by CMA and is derived from a joint collaboration formed by the University of São Paulo and three private genetic diagnostic centers to investigate the genetic bases of neurodevelopmental disorders and congenital abnormalities. We identified 2,279 clinically relevant CNVs in 1886 patients, not including the 26 cases of UPD found. Among detected CNVs, the corresponding frequency of each category was 55.6% Pathogenic, 4.4% Likely Pathogenic and 40% VUS. The diagnostic yield, by taking into account Pathogenic, Likely Pathogenic and UPDs, was 19.7%. Since the rational for the classification is mostly based on Mendelian or highly penetrant variants, it was not surprising that a second event was detected in 26% of those cases of predisposition syndromes. Although it is common practice to investigate the inheritance of VUS in most laboratories around the world to determine the inheritance of the variant, our results indicate an extremely low cost-benefit of this approach, and strongly suggest that in cases of a limited budget, investigation of the parents of VUS carriers using CMA should not be prioritized.

Fluoxetine inhibits inflammatory response and bone loss in a rat model of ligature-induced periodontitis.

BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, has been found recently to possess anti-inflammatory properties. The present study investigates the effects of fluoxetine on inflammatory tissue destruction in a rat model of ligature-induced periodontal disease. METHODS: Thirty male Wistar rats were randomly assigned into three groups (n = 10 animals per group): 1) control rats (without ligature); 2) rats with ligature + placebo (saline; oral gavage); and 3) rats with ligature + fluoxetine (20 mg/kg/day in saline; oral gavage). Histologic analyses were performed on the furcation region and mesial aspect of mandibular first molars of rats sacrificed at 15 days after ligature-induced periodontal disease. Reverse transcription-polymerase chain reaction and zymography were performed to analyze the mRNA expression of interleukin (IL)-1ß, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase and the MMP-9 activity, respectively, in gingival tissues samples. RESULTS: Compared to the ligature + placebo group, alveolar bone loss was reduced in the fluoxetine group (P <0.05), and the amount of collagen fibers in the gingival tissue was maintained. Moreover, in gingival tissue sampled 3 days after ligature attachment, fluoxetine administration reduced IL-1ß and COX-2 mRNA expression. Fluoxetine downregulated MMP-9 activity, without affecting MMP-9 mRNA expression induced by ligature, compared to the ligature + placebo group (P <0.05). These data suggest that fluoxetine suppressed proinflammatory responses, as well as proteolytic enzyme activity, induced by ligature. CONCLUSION: In the present study, fluoxetine suppresses the inflammatory response and protects against periodontal bone resorption and destruction of collagen fibers, suggesting that fluoxetine can constitute a promising therapeutic approach for periodontal diseases.