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Endothelial dysfunction (impaired vasodilation, prothrombotic, proinflammatory and prooxidant states) is involved in the development of cardiovascular diseases (atherosclerosis, hypertension, heart failure, stroke) and vascular complications of diabetes mellitus. Reduced production of endothelium-derived relaxing factors, increased release of endothelium-derived constricting factors, prothrombotic molecules and inflammatory mediators, upregulation of growth factors and adhesion molecules play a crucial role in the development and progression of endothelial dysfunction. Phytochemicals belonging to different chemical classes (alkaloids, flavonoids, isoflavonoids, phenolic acids, terpenoids) were reported to prevent and/or reverse endothelial dysfunction in different experimental models. Many of them showed a multitarget activity which is a great advantage in tackling endothelial dysfunction and thereby, they may serve as lead compounds for novel drug development. Salvianolic acid B, caffeic, chlorogenic, ferulic and rosmarinic acids, resveratrol, luteolin are only some examples of phytochemicals modulating multiple mechanisms associated with endothelial dysfunction. Obviously, extensive clinical trials are needed to confirm the efficacy of phytochemicals in improving endothelial function and also their safety. In addition, formulation strategies to enhance bioavailability and afford an endothelium-targeted delivery should be explored.

Oligomeric proanthocyanidins are among the most widely distributed polyphenols in the plant kingdom, being endowed with antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, antitumor and cardioprotective activities. Since oligomeric proanthocyanidins are found in limited amounts in plants and plant-derived products, there is a great need for efficient separation methodologies that can supply analytical quality standards or sufficient material for further bioassays. By efficiently providing a good molar mass distribution of oligomeric proanthocyanidins according to their degree of polymerization, Sephadex LH is the most used sorbent in column chromatography, together with other size exclusion polymers, such as Toyopearl, Diaion, MCI gel CHP or Amberlite. Combination of normal and reversed-phase high pressure liquid chromatography can significantly reduce the total number of chromatographic steps required to obtain high purity oligomeric proanthocyanidins, whereas hydrophilic interaction liquid chromatography on Diol phases can yield proanthocyanidins with a higher degree of polymerization. By lacking a solid support, countercurrent separations can solve issues related to irreversible adsorption, giving higher recoveries, low sample denaturation and a facile scale-up from analytical to industrial production. By taking advantage of the complementarity of all these chromatographic techniques, high-purity oligomeric proanthocyanidin fractions or individual compounds can be obtained on a large scale in a reduced number of separation steps.

Glibenclamide and lipoic acid are two drugs frequently recommended for the management of diabetes mellitus, and so, the development of a new formulation containing both substances has a great benefit in terms of efficiency and compliance, acting also as a multi-target drug system. Accordingly, the aim of this study was the formulation and physicochemicalcharacterization of new polymeric systems based on chitosan (CS) in whose matrix were encapsulated glibenclamide (Gly) and lipoic acid (LA). The polymeric systems were prepared as microparticles (CS&ndash, Gly, CS&ndash, LA, and CS&ndash, Gly&ndash, LA) through ionic gelation method, using pentasodium tripolyphosphate (TPP) as crosslinking agent. The polymeric systems obtained were characterized in terms of particle size and morphology, IR spectroscopy, entrapment efficiency and drug loading, swelling degree, and therelease of the active substances from the chitosan matrix. The polymeric systems obtained were stable systems, the presence of glibenclamide and lipoic acid into the polymer matrix were proved by IR spectroscopy. The entrapment efficiency was 94.66% for Gly and 39.68% for LA. The developed polymeric systems proved a favorable swelling degree and drug release profile, the percentage of release being 88.68% for LA and 75.17% for Gly from CS&ndash, LA systems.

Ethnopharmacological relevance Crataegus leaves, flowers and fruits have been traditionally used to improve blood circulation, numerous preclinical and clinical studies supporting the cardiovascular benefits of Crataegus preparations. In this respect, there is very limited data on Crataegus pentagyna; in addition, the chemical profile of this species is still incompletely elucidated. Aim of the study The objective of this study was to examine the cardiovascular benefits of Crataegus pentagyna Waldst. et Kit. ex Willd. (small-flowered black hawthorn, Rosaceae) extracts (leaf, flower and fruit ethyl acetate extracts) and the underlying mechanisms. We hypothesized that C. pentagyna extracts might exert vasodilatory effects and inhibit arginase activity due, in large part, to their polyphenolic constituents. Materials and methods C. pentagyna extracts induced-relaxation and the mechanisms involved were studied ex vivo in isolated aortic rings from Sprague-Dawley rats. The inhibitory effects on bovine liver arginase I were assessed by an in vitro assay. Metabolite profiling of C. pentagyna extracts was performed and the most endothelium- and nitric oxide synthase-dependent; flower extract additionally reduced Ca2+ entry and, to a lesser extent, Ca2+ release from the sarcoplasmic reticulum. C. pentagyna proved to be an important source of arginase inhibitors with potential benefits in endothelial dysfunction that remains to be explored.

The present study investigated the effects of Cornus mas, Sorbus aucuparia and Viburnum opulus fruit extracts on arginase activity and arterial vasodilation. V. opulus fruit extract exerted the highest vasorelaxant activity in phenylephrine precontracted rat aortic rings (EC50 = 6.31 ± 1.61 μg/mL) and a significant inhibition of arginase (IC50 = 71.02 ± 3.06 μg/mL). By contrast, S. aucuparia and C. mas fruit extracts showed no important anti-arginase activity and a significantly weaker activity in the rat aortic rings relaxation assay (EC50 = 100.9 ± 11.63 and 78.52 ± 8.59 μg/mL, respectively). For all extracts, the main mechanism of vasodilation was proven to be endothelium-dependent. HPLC-ESI-Q-TOF-MS/MS studies revealed a very complex metabolite profiling in all three extracts with chlorogenic acid accounting for 30.89, 0.72 and 2.03 mg/g in V. opulus, C. mas and S. aucuparia fruit extracts, respectively. All extracts were declared non-toxic in the brine shrimp acute toxicity test. Our study highlights potential benefits of V. opulus fruit extract in diseases associated with endothelial dysfunction and impaired vasodilation.

A polyphenol-rich diet protects against chronic pathologies by modulating numerous physiological processes, such as cellular redox potential, enzymatic activity, cell proliferation and signaling transduction pathways. However, polyphenols have a low oral bioavailability mainly due to an extensive biotransformation mediated by phase I and phase II reactions in enterocytes and liver but also by gut microbiota. Despite low oral bioavailability, most polyphenols proved significant biological effects which brought into attention the low bioavailability/high bioactivity paradox. In recent years, polyphenol metabolites have attracted great interest as many of them showed similar or higher intrinsic biological effects in comparison to the parent compounds. There is a huge body of literature reporting on the biological functions of polyphenol metabolites generated by phase I and phase II metabolic reactions and gut microbiota-mediated biotransformation. In this respect, the review highlights the pharmacokinetic fate of the major dietary polyphenols (resveratrol, curcumin, quercetin, rutin, genistein, daidzein, ellagitannins, proanthocyanidins) in order to further address the efficacy of biometabolites as compared to parent molecules. The present work strongly supports the contribution of metabolites to the health benefits of polyphenols, thus offering a better perspective in understanding the role played by dietary polyphenols in human health.

Gram-negative bacteria cause infections that are difficult to treat due to the emergence of multidrug resistance. This review summarizes the current status of the studies investigating the capacity of essential oils and their components to modulate antibiotic activity against Gram-negative bacteria. Synergistic interactions are particularly discussed with reference to possible mechanisms by which essential oil constituents interact with antibiotics. Special emphasis is given to essential oils and volatile compounds that inhibit efflux pumps, thus reversing drug resistance in Gram-negative bacteria. In addition, indifference and antagonism between essential oils/volatile compounds and conventional antibiotics have also been reported. Overall, this literature review reveals that essential oils and their purified components enhance the efficacy of antibiotics against Gram-negative bacteria, being promising candidates for the development of new effective formulations against Gram-negative bacteria.

Background: Vaginal masses are an uncommon finding in well-woman gynecologic examinations. The differential diagnosis includes cysts, leiomyomata, ectopic ureteroceles, infected granuloma, and malignancy. Case: A 74-year-old woman with a history of mantle cell lymphoma was referred for vaginal prolapse. Examination revealed a vaginal mass, with MRI confirming 3 masses. Fine needle aspiration confirmed metastatic mantle cell lymphoma which later regressed with radiation therapy. Conclusion: Although vaginal masses are often rare and incidental findings during routine gynecologic examinations, a comprehensive differential diagnosis is required to avoid delays in treatment. Fine needle aspiration should be included as part of the arsenal of diagnostic tools because of its low cost and the ease with which it can be performed in a clinical setting.

To estimate whether prophylactic antibiotics at the time of repair of third- or fourth-degree perineal tears after vaginal delivery prevent wound infection and breakdown.This was a prospective, randomized, placebo-controlled study. Patients who sustained third- or fourth-degree perineal tears after a vaginal delivery were recruited for the study. Each patient was given a single intravenous dose of a second-generation cephalosporin (cefotetan or cefoxitin) or placebo before repair of third- or fourth-degree perineal tears. Obstetricians and patients were blinded to study drug. The perineum was inspected for evidence of infection or breakdown at discharge from the hospital and at 2 weeks postpartum. Primary end points were gross disruption or purulent discharge at site of perineal repair by 2 weeks postpartum.One hundred forty-seven patients were recruited for the study. Of these, 83 patients received placebo and 64 patients received antibiotics. Forty patients (27.2%) did not return for their 2-week appointment. Of the patients seen at 2 weeks postpartum, 4 of 49 (8.2%) patients who received antibiotics and 14 of 58 (24.1%) patients who received placebo developed a perineal wound complication (P=.037). There were no differences between groups in parity, incidence of diabetes, operative delivery, or third-degree compared with fourth-degree lacerations.By 2 weeks postpartum, patients who received prophylactic antibiotics at the time of third- or fourth-degree laceration repair had a lower rate of perineal wound complications than patients who received placebo.ClinicalTrials.gov, www.clincaltrials.gov, NCT00186082.I.

Vaginal masses are an uncommon finding in well-woman gynecologic examinations. The differential diagnosis includes cysts, leiomyomata, ectopic ureteroceles, infected granuloma, and malignancy.A 74-year-old woman with a history of mantle cell lymphoma was referred for vaginal prolapse. Examination revealed a vaginal mass, with MRI confirming 3 masses. Fine needle aspiration confirmed metastatic mantle cell lymphoma which later regressed with radiation therapy.Although vaginal masses are often rare and incidental findings during routine gynecologic examinations, a comprehensive differential diagnosis is required to avoid delays in treatment. Fine needle aspiration should be included as part of the arsenal of diagnostic tools because of its low cost and the ease with which it can be performed in a clinical setting.