Boldine inhibits the alveolar bone resorption during ligature-induced periodontitis by modulating the Th17/Treg imbalance.

BACKGROUND: During periodontitis, tooth-supporting alveolar bone is resorbed when there is an increased expression of the pro-osteolytic factor termed receptor activator of nuclear factor κB ligand (RANKL), which is responsible for osteoclast differentiation and activation. In periodontitis-affected tissues, the imbalance between T-helper type-17 (Th17) and T-regulatory (Treg) lymphocyte activity favors this RANKL overexpression. In this context, immunotherapeutic strategies aimed at modulating this Th17/Treg imbalance could eventually arrest the RANKL-mediated alveolar bone loss. Boldine has been reported to protect from pathological bone loss during rheumatoid arthritis and osteoporosis, whose pathogenesis is associated with a Th17/Treg imbalance. However, the effect of boldine on alveolar bone resorption during periodontitis has not been elucidated yet. This study aimed to determine whether boldine inhibits alveolar bone resorption by modulating the Th17/Treg imbalance during periodontitis. METHODS: Mice with ligature-induced periodontitis were orally treated with boldine (10/20/40 mg/kg) for 15 consecutive days. Non-treated periodontitis-affected mice and non-ligated mice were used as controls. Alveolar bone loss was analyzed by micro-computed tomography and scanning electron microscopy. Osteoclasts were quantified by histological identification of tartrate-resistant acid phosphatase-positive cells. Production of RANKL and its competitive antagonist osteoprotegerin (OPG) were analyzed by ELISA, quantitative polymerase chain reaction (qPCR), and immunohistochemistry. The Th17 and Treg responses were analyzed by quantifying the T-cell frequency and number by flow cytometry. Also, the expression of their signature transcription factors and cytokines were quantified by qPCR. RESULTS: Boldine inhibited the alveolar bone resorption. Consistently, boldine caused a decrease in the osteoclast number and RANKL/OPG ratio in periodontal lesions. Besides, boldine reduced the Th17-lymphocyte detection and response and increased the Treg-lymphocyte detection and response in periodontitis-affected tissues. CONCLUSION: Boldine, administered orally, inhibited the alveolar bone resorption and modulated the Th17/Treg imbalance during experimental periodontitis.

Histologic and microbiological findings of the defunctionalized loop in sleeve gastrectomy with jejunal bypass.

BACKGROUND: Bariatric surgery produces anatomic changes in the digestive tract that can affect the intestinal microbiome and, in some cases, can cause small intestinal bacterial overgrowth. Since the inception of the sleeve gastrectomy with jejunal bypass (SGJB) in 2004, there has been discussion regarding the possible development of those complications associated with the now abandoned jejunoileal bypass (JIB) procedure. OBJECTIVES: The primary endpoint was to characterize the bacteriologic and histopathologic findings in the defunctionalized jejunal loop after the SGJB procedure and to analyze the liver profile. The secondary endpoint was to report SGJB conversions or reversions and to review the differences between SGJB and JIB. SETTING: Academic medical center. METHODS: We conducted a prospective study of patients who underwent laparoscopy for any reason, having previously had an SGJB. A 5-cm segment at the proximal end of the excluded limb was resected. Luminal liquid and tissue samples were taken from this segment for aerobic and anaerobic cultures, and pathologic examination of the bowel wall was performed to evaluate trophism and signs of chronic inflammation. Other variables were liver function and pre- and postoperative status. Finally, we retrospectively reviewed the causes of revisional surgery in the prospective database. RESULTS: Eleven patients underwent laparoscopy. The median time after SGJB was 14 months (range, 10-144 months). There were no complications from the procedure. Eight (72.7%) of the procedures were cholecystectomies. None of the patients showed histologic alterations or signs of chronic infection. The liquid and tissue cultures were negative. The liver tests and the laparoscopic morphology of the liver were normal in all patients, except in 1 with previously documented liver cirrhosis. The number of SGJB revisions was 19 of 1074 (1.8 %), and all of them were converted to Roux-en-Y gastric bypass for severe gastroesophageal reflux. CONCLUSIONS: In this study, we were unable to demonstrate the presence of symptoms or histologic alterations that would suggest that patients undergoing SGJB develop small intestinal bacterial overgrowth in the short- and medium-term follow-up, unlike those who have undergone JIB. The study constitutes an initial step toward establishing what happens to the defunctionalized jejunal limb as a result of this surgical technique.

Variation of the alkaloid content of Peumus boldus (boldo).

Eighteen alkaloids were detected in the bark, leaves, wood and roots of Peumus boldus, including traces of secoboldine, N-methylsecoboldine (boldine methine), glaucine and norreticuline, not reported previously as constituents of this species. Using appropriate standards, we quantified thirteen of them by UHPLC-MS/MS. Boldine was dominant in the bark, and laurolitsine in wood and roots. The alkaloid composition of the leaves, determined for 130 individually identified trees, classified by age and sex, was highly variable, where N-methyllaurotetanine, laurotetanine, coclaurine and in some cases isocorydine predominated, but not boldine.