Nifedipine as a therapeutic modality for raynaud's phenomenon

Eight patients with Raynaud's phenomenon were entered into a double-blind crossover study of nifedipine versus placebo, with 7 patients undergoing finger pleth-ysmography before and after sublingual nifedipine ad-ministration. While receiving nifedipine, all patients reported decreased frequency and severity of attacks, and 4 of 5 had digital ulcer healing. Total finger blood flow increased in 5 of 6 patients after treatment with sublingual nifedipine. This preliminary study indicates that nifedipine may be a useful agent for treatment of digital vasospasm.     

Complete remission of a mesenteric fibromatosis after taking sulindac

We report the case of a 22-year-old-man having a familial adenomatous polyposis coli treated by total colectomy with ileo-rectal anastomosis. Two years after the operation, an asymptomatic mesenteric fibromatosis appeared which was nonresectable due to mesenteric vessels infiltration. Nine years later, sulindac therapy was started for residual polyps in the rectal stump. This treatment was taken intermittently, during periods of 1 to 8 months, for 6 years. After 4 years of treatment, the tumor was no longer palpable. Four years after sulindac discontinuation, the patient was operated on for suspicion of intestinal adhesion. The mesenteric fibromatosis had completely disappeared and mesenteric vessels were free. This complete macroscopic regression of a desmoid tumor after sulindac therapy emphasizes again the interest of this treatment for mesenteric fibromatosis.     

Repeated Multimodality Ablative Therapies for Oligorecurrent Pulmonary Metastatic Disease

Stereotactic body radiotherapy (SBRT) and percutaneous thermal ablation (TA) are alternatives to surgery for the management of pulmonary oligometastases. In this collaborative work, we retrospectively analyzed patients who had undergone iterative focal ablative treatments of pulmonary oligometastases. We hypothesized that repeated ablative therapies could benefit patients with consecutive oligometastatic relapses. Patients treated with SBRT and/or TA for pulmonary oligometastases in two French academic centers between October 2011 and November 2016 were included. A total of 102 patients with 198 lesions were included; 45 patients (44.1%) received repeated focal treatments at the pulmonary site for an oligorecurrent disease (the “multiple courses” group). Median follow-up was 22.5 months. The 3-year overall survival rates of patients who had a single treatment sequence (the “single course” group) versus the “multiple courses” were 73.9% and 78.8%, respectively, which was not a statistically significant difference (p = 0.860). The 3-year systemic therapy-free survival tended to be longer in the “multiple courses” group (50.4%) than in the “single course” group (44.7%) (p = 0.081). Tolerance of repeated treatments was excellent with only one grade 4 toxicity. Thereby, multimodality repeated ablative therapy is effective in patients with pulmonary oligorecurrent metastases. This strategy may delay the use of more toxic systemic therapy.     

Influence of orthodontic appliance type on salivary parameters during treatment

ObjectivesTo evaluate the effect of orthodontic appliances on physicochemical, biochemical, and oxidative stress changes in salivary parameters during treatment.Materials and MethodsA cohort study was conducted with 112 healthy patients. Salivary samples were taken at baseline, 1 month, and 9 months after placement of the orthodontic appliances used in treatment.ResultsA statistically significant difference was observed in certain examined salivary parameters, including enzymes, electrolytes, and oxidative stress markers.ConclusionsThe use of aligners had a lower prevalence of disturbing salivary parameters. Orthodontist must consider these changes to prevent the occurrence of white spot lesions.     

Murine Recombinant Angiotensin-Converting Enzyme 2: Effect on Angiotensin II-Dependent Hypertension and Distinctive Angiotensin-Converting Enzyme 2 Inhibitor Characteristics on Rodent and Human Angiotensin-Converting Enzyme 2

A newly produced murine recombinant angiotensin (Ang)-converting enzyme 2 (ACE2) was characterized in vivo and in vitro. The effects of available ACE2 inhibitors (MLN-4760 and 2 conformational variants of DX600, linear and cyclic) were also examined. When murine ACE2 was given to mice for 4 weeks, a marked increase in serum ACE2 activity was sustainable. In acute studies, mouse ACE2 (1 mg/kg) obliterated hypertension induced by Ang II infusion by rapidly decreasing plasma Ang II. These effects were blocked by MLN-4760 but not by either form of DX600. In vitro, conversion from Ang II to Ang-(1-7) by mouse ACE2 was blocked by MLN-4760 (10(-6) m) but not by either form of DX600 (10(-5) m). Quantitative analysis of multiple Ang peptides in plasma ex vivo revealed formation of Ang-(1-9) from Ang I by human but not by mouse ACE2. Both human and mouse ACE2 led to the dissipation of Ang II with formation of Ang (1-7). By contrast, mouse ACE2-driven Ang-(1-7) formation from Ang II was blocked by MLN-4760 but not by either linear or cyclic DX600. In conclusion, sustained elevations in serum ACE2 activity can be accomplished with murine ACE2 administration, thereby providing a strategy for ACE2 amplification in chronic studies using rodent models of hypertension and cardiovascular disease. Human but not mouse ACE2 degrades Ang I to form Ang-(1-9). There are also species differences regarding rodent and human ACE2 inhibition by known inhibitors such that MLN-4760 inhibits both human and mouse ACE2, whereas DX600 only blocks human ACE2 activity.