Hibiscus Sabdariffa L. Flowers and Olea Europea L. Leaves Extract-Based Formulation for Hypertension Care: In Vitro Efficacy and Toxicological Profile

Olea europaea L. leaves extract (Oe) and Hybiscus sabdariffa L. flowers extract (Hs) have calcium antagonistic properties. Aim of this work was to study the cardiovascular effects of Pres Phytum(\uae), a nutraceutical formulation containing a mixture of the two extracts and the excipients, and investigate its possible off-target effects, using in vitro biological assays on guinea pig isolated organs. Cardiovascular effects were assessed using guinea pig atria and aorta. The effects of Pres Phytum on spontaneous gastrointestinal, urinary, and respiratory tracts smooth muscle contractility were evaluated. Pres Phytum exerted a vasorelaxant effect (IC50\u2009=\u20092.38\u2009mg/mL) and a negative chronotropic effect (IC50\u2009=\u20091.04\u2009mg/mL) at concentrations lower than those producing smooth muscle spontaneous contractility alterations in the other organs. Compared to Pres Phytum, the mixture did not exert negative inotropic activity, while it maintained a negative chronotropic efficacy (IC50\u2009=\u20091.04\u2009mg/mL). These experimental data suggest a possible nutraceutical use of this food supplement for the management of preclinical hypertension

Strategic reprogramming of implantable cardiac monitors reduces the false-positive remote alert burden in a nurse-led service

Aims Implantable cardiac monitors (ICMs) can generate false-positive (FP) alerts. Although these devices have an extended programmability, there are no recommendations on their optimization to reduce not-relevant activations. We tested a strategic programming optimization guide based on the type of FP and investigated the safety and feasibility of the nurse-led insertion of ICMs with a long-sensing vector. Methods and results Consecutive patients implanted by trained nurses with long-sensing vector ICM were enrolled in a 1-month observational stage (Phase A). Patients who had >= 10 FP episodes underwent ICM reprogramming based on the predefined guide and were followed for an additional month (Phase B). A total of 78 patients had successful ICM insertion by nurses with a mean R wave amplitude of 0.96 +/- 0.43 mV and an 86% P wave visibility. Only one patient reported a significant device-related issue, and nurse-delivered ICM was generally well accepted by the patients. During Phase A, 11 patients (14%) generated most of FP (3,627/3,849; 94%) and underwent ICM reprogramming. In the following month (Phase B), five patients (45%) were free from FP and six (55%) transmitted 57 FP alerts (98% reduction compared with Phase A). The median number of FP per patient was significantly reduced after reprogramming [195 (interquartile range, 50-311) vs. one (0-10), P = 0.0002]. Conclusion A strategic reprogramming of ICM in those patients with a high FP alert burden reduces the volume of erroneous activations with potential benefits for the remote monitoring service. No concerns were raised regarding nurse-led insertion of ICMs with a long-sensing vector

Antiinflammatory Effect of Phytosterols in Experimental Murine Colitis Model: Prevention, Induction, Remission Study

Phytosterols, besides hypocholesterolemic effect, present anti-inflammatory properties. Little information is available about their efficacy in Inflammatory Bowel Disease (IBD). Therefore, we have evaluated the effect of a mixture of phytosterols on prevention/induction/remission in a murine experimental model of colitis. Phytosterols were administered x os before, during and after colitis induction with Dextran Sodium Sulfate (DSS) in mice. Disease Activity Index (DAI), colon length, histopathology score, 18F-FDG microPET, oxidative stress in the intestinal tissue (ileum and colon) and gallbladder ileum and colon spontaneous and carbachol (CCh) induced motility, plasma lipids and plasma, liver and biliary bile acids (BA) were evaluated. A similar longitudinal study was performed in a DSS colitis control group. Mice treated with DSS developed severe colitis as shown by DAI, colon length, histopathology score, 18F-FDG microPET, oxidative stress. Both spontaneous and induced ileal and colonic motility were severely disturbed. The same was observed with gallbladder. DSS colitis resulted in an increase in plasma cholesterol, and a modification of the BA pattern. Phytosterols feeding did not prevent colitis onset but significantly reduced the severity of the disease and improved clinical and histological remission. It had strong antioxidant effects, almost restored colon, ileal and gallbladder motility. Plasmatic levels of cholesterol were also reduced. DSS induced a modification in the BA pattern consistent with an increase in the intestinal BA deconjugating bacteria, prevented by phytosterols. Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects

Assessment of acute colitis and evaluation of the response to Ph. Oxydative stress.

<p>MDA equivalents in ileum (A) and colon homogenates (B) White bars refer to CD and black bars refer to Ph treatment in the prevention, induction and remission period. In both ileum and colon, a strong oxidative stress is observed in the CD group in the induction phase, shown by a significant increase in MDA equivalents, prevented by Ph treatment (n = 4, *<i>P</i><.001). The increase is significantly higher than in the prevention and remission phases (n = 4, *<i>P</i><.001). C. Coenzyme Q₉ levels in colon homogenate measured by HPLC. The ubiquinone content is not significantly different in all experimental conditions. Each tissue was analyzed in triplicate. Statistical analysis was performed by one way ANOVA test.</p

Gallbladder Spontaneous and Induced motility.

<p>Amplitude (A) and Frequency (B) of spontaneous phasic contractions and (C) response to CCh and Atropine in mice gallbladder. Data are mean ± SEM values (<i>n</i> = 3–5) (*<i>P</i>>.01) (**<i>P</i>>.05).</p

Plasma, liver and biliary BA.

<p>A. Plasma free and taurine-conjugated BA. B. Biliary BA. C. Liver BA. BA were evaluated after 14 days either Ph or CD and at the end of the study (day38). Since the CD group from day 0 to day 14 went on assuming the same usual commercial diet as before, day 14 was considered as the control value with respect to Ph. Plasma, liver and bile were collected from the same animal. The results were expressed as mean ± SD (n = 3–4 animals) CA: cholic acid; CDCA: chenodeoxycholic acid; DCA: deoxycholic acid; LCA: lithocholic acid; UDCA: ursodeoxycholic acid; muCA: muricholic acid; T-: Taurine conjugated-.</p

Parameters investigated for the evaluation of the Disease Activity Index.

<p>Parameters investigated for the evaluation of the Disease Activity Index.</p

Assessment of acute colitis and evaluation of the response to Ph. Histology.

<p>Prevention: normal ileum (Left) and colon (Right) in CD and Ph mice. (H&E,4x). Induction: colonic sections from ileum and colon from CD and Ph. The ileum is normal in both groups. Colon. Upper panel. Left: mucosal ulceration with linfoplasmacytic and neutrophils infiltrate extending to the entire mucosa (H&E, 20 x). Right: cryptic abscess (H&E, 10 x). Lower panel: colonic sections from Ph mice at the end of the induction period. Left: The mucosa and sub-mucosa show a moderate inflammatory infiltrate with lymphocytes and neutrophils (H&E, 10 x). Right: follicular inflammation. (H&E, 10 x). Remission. Upper panel: colonic mucosa specimens. Left: inflammatory infiltrate (H&E, 4x). Right: inflammatory infiltrate with lymphocytes and neutrophils (H&E, 20 x). Lower panel: colonic mucosa specimens. Left: minimal focal lymphocytes infiltration (H&E, 4x). The same at higher magnification (H&E, 10x).</p