Potential bio-functional properties of Citrus aurantium L. leaf: chemical composition, antiviral activity on herpes simplex virus type-1, antiproliferative effects on human lung and colon cancer cells and oxidative protection.

This study examined the antioxidant, anticancer and antiviral properties of the methanolic extracts from bigarade (Citrus aurantium L.) leaves at two development stages. Ferulic acid, naringin and naringenin were the principal phenolic components of young and old leaves. The highest total antioxidant capacity was obtained in young leaf extracts (YLE). These latter also exhibited the highest antiradical DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) activities, while the highest iron chelating and reducing power activities were observed in old leaf extracts (OLE). The potent anticancer activity was observed in YLE for human lung carcinoma (A-549) and in OLE for colon adenocarcinoma (DLD-1) cells. YLE showed the highest virucidal effects as compared to OLE and the positive control acyclovir against herpes simplex virus type-1 (HSV-1) propagation in Vero cells during the absorption and replication periods. The young and old leaves might be a source of natural antioxidants and protective agents against oxidative damage.

Phytochemical analysis, antioxidant, anticancer and anti-inflammatory activities of Lycium europaeum fruits.

Lycium europaeum is used as a medicinal herb in many countries. In this study, cyclohexane, dichloromethane, ethyl acetate, methanol and water were used as solvents in the extraction of L. europaeum fruits. The contents of total phenolics, total flavonoids, total tannins and condensed tannins as well as the biological activities of these extracts were investigated using various in vitro and ex vivo assays. Results showed that all solvent extracts of L. europaeum had no anticancer activity against cancerous (A-549 and DLD-1) and non-cancerous (WS-1) human cells. Methanol and ethyl acetate were the most effective solvent for extraction of phenolic compounds and also exhibited the highest antioxidant and anti-inflammatory activities. The methanol extract of L. europaeum fruits was the richest in phenolic compounds with the predominance of ferulic acid, catechin and narengin. These results supported the use of L. europaeum fruit as natural source of bioactive compound for pharmaceutical applications.

The impact of new partial AUC parameters for evaluating the bioequivalence of prolonged-release formulations.

To demonstrate bioequivalence (BE) between two prolonged-release (PR) drug formulations, single dose studies under fasting and fed state as well as at least one steady-state study are currently required by the European Medicines Agency (EMA). Recently, however, there have been debates regarding the relevance of steady-state studies. New requirements in single-dose investigations have also been suggested by the EMA to address the absence of a parameter that can adequately assess the equivalence of the shape of the curves. In the draft guideline issued in 2013, new partial area under the curve (pAUC) pharmacokinetic (PK) parameters were introduced to that effect. In light of these potential changes, there is a need of supportive clinical evidence to evaluate the impact of pAUCs on the evaluation of BE between PR formulations. In this retrospective analysis, it was investigated whether the newly defined parameters were associated with an increase in discriminatory ability or a change in variability compared to the conventional PK parameters. Among the single dose studies that met the requirements already in place, 20% were found unable to meet the EMA's new requirements in regards to the pAUC PK parameters. When pairing fasting and fed studies for a same formulation, the failure rate increased to 40%. In some cases, due to the high variability of these parameters, an increase of the sample size would be required to prove BE. In other cases however, the pAUC parameters demonstrated a robust ability to detect differences between the shapes of the curves of PR formulations. The present analysis should help to better understand the impact of the upcoming changes in European regulations on PR formulations and in the design of future BE studies.

Small bowel capsule endoscopy for management of Crohn's disease: a retrospective tertiary care centre experience.

BACKGROUND: The role of small bowel capsule endoscopy in the management of established Crohn's disease is uncertain. METHODS: A retrospective study of small bowel capsule endoscopy tests performed in a referral centre from 2008 to 2011; 77 tests were performed in patients with known Crohn's disease. Six patients were excluded due to capsule test retention. Patients were classified into 4 indication groups: unexplained anaemia (G1, n = 6); discrepancy between clinical symptoms and morphology (G2, n = 25), full assessment of Crohn's disease location (G3, n = 37) and evaluation of mucosal healing (G4, n = 3). RESULTS: Twenty-seven (38%) patients had no lesions, 32 (45%) moderate and 12 (17%) severe lesions. Endoscopic lesions were found in 4/6 (67%) G1 patients, 11/25 (44%) G2 and 28/37 (76%) G3 (p < 0.03). Three months after endoscopy was performed, 38/71 patients experienced a change in their treatment that was significantly associated with the severity of endoscopic lesions and with test indications; in 60%, 20% and 58% of patients from G1, G2 and G3, respectively (p < 0.01). CONCLUSION: Small bowel capsule endoscopy resulted in management changes in the majority of patients with established Crohn's disease.

Arrhythmogenic right ventricular cardiomyopathy: severe structural alterations are associated with inflammation.

AIM: Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a rare cardiomyopathy associated with sudden cardiac death. It is characterised by a progressive right ventricle (RV) fibrofatty replacement, although biventricular replacement (BV) is also common. Inflammation believed to be a key player in disease progression and outcome. Our study investigates the relationship between the presence of inflammatory infiltrates in myocardium and the severity of structural heart alterations in ARVC. METHODS: Our study included eight control and 36 ARVC postmortem human heart samples. We performed macroscopic assessment and microscopic analysis for different inflammatory cell types. RESULTS: Fibrofatty replacement of RV was present in all our cases. Thirteen cases showed sole RV involvement (36.11%). Of these, only one showed inflammatory infiltrates (7.69%). Sixteen cases showed severe ARVC phenotypic forms characterised by BV involvement and right auricular (RA) fatty accumulation plus RV dilation (44.44%); eight of them also showed inflammatory infiltrates (50%). Immunohistochemical studies revealed ventricular multifocal inflammatory infiltrates, showing seven T-lymphocytes as the main infiltrate cell types. CONCLUSIONS: The presence of inflammatory infiltrates in ventricular myocardium of ARVC samples is associated with severe structural heart changes, indicating that an inflammatory process may be a modulator of severity in ARVC.

Successful treatment with adalimumab in a familial case of gastrointestinal Behcet's disease.

We present here two siblings with a history of recurrent oral and genital ulcers, neurological and gastrointestinal manifestations. The diagnosis of Behçet's disease in a context of familial aggregation was assumed. Facing repeated steroid-dependent flares and failure of maintenance therapies with colchicine and intolerance to pentoxifilline and disulone, adalimumab was started. Rapid response was observed in both patients, with clinical remission after induction therapy, which currently sustains under maintenance schedule. This case report suggests the effectiveness of adalimumab as first anti-TNFα in case of steroid-dependent/resistant gastrointestinal BD.

Antioxidant activity, inhibition of nitric oxide overproduction, and in vitro antiproliferative effect of maple sap and syrup from Acer saccharum.

Antioxidant activity, inhibition of nitric oxide (NO) overproduction, and antiproliferative effect of ethyl acetate extracts of maple sap and syrup from 30 producers were evaluated in regard to the period of harvest in three different regions of Québec, Canada. Oxygen radical absorbance capacity (ORAC) values of maple sap and syrup extracts are, respectively, 12 +/- 6 and 15 +/- 5 micromol of Trolox equivalents (TE)/mg. The antioxidant activity was also confirmed by a cell-based assay. The period of harvest has no statistically significant incidence on the antioxidant activity of both extracts. The antioxidant activity of pure maple syrup was also determined using the ORAC assay. Results indicate that the ORAC value of pure maple syrup (8 +/- 2 micromol of TE/mL) is lower than the ORAC value of blueberry juice (24 +/- 1 micromol of TE/mL) but comparable to the ORAC values of strawberry (10.7 +/- 0.4 micromol of TE/mL) and orange (10.8 +/- 0.5 micromol of TE/mL) juices. Maple sap and syrup extracts showed to significantly inhibit lipopolysaccharide-induced NO overproduction in RAW264.7 murine macrophages. Maple syrup extract was significantly more active than maple sap extract, suggesting that the transformation of maple sap into syrup increases NO inhibition activity. The highest NO inhibition induced by the maple syrup extracts was observed at the end of the season. Moreover, darker maple syrup was found to be more active than clear maple syrup, suggesting that some colored oxidized compounds could be responsible in part for the activity. Finally, maple syrup extracts (50% inhibitory concentration = 42 +/- 6 microg/mL) and pure maple syrup possess a selective in vitro antiproliferative activity against cancer cells.