Nanoparticle delivery of grape seed-derived proanthocyanidins to airway epithelial cells dampens oxidative stress and inflammation.

BACKGROUND: Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins. METHODS: Plain, 6-coumarin (6-Coum), DiR- and GSE-loaded SLN were produced with the melt-emulsion method. Physicochemical characterization of all prepared SLN was determined by photon correlation spectroscopy and laser Doppler anemometry. MTT assay (spectrophotometry) and propidium iodide (PI) assay (cytofluorimetry) were used to assess cell viability. Flow cytometry coupled with cell imaging was performed for assessing apoptosis and necrosis by Annexin V/7-AAD staining (plain SLE), cell internalization (6-Coum-SLN) and reactive oxygen species (ROS) production (SLN-GSE). NF-κB nuclear translocation was studied by immunofluorescence. In vivo bio-imaging was used to assess lung deposition and persistence of aerosolized DiR-loaded SLN. RESULTS: Plain SLN were not cytotoxic when incubated with H441 airway epithelial cells, as judged by both PI and MTT assays as well as by apoptosis/necrosis evaluation. 6-Coum-loaded SLN were taken up by H441 cells in a dose-dependent fashion and persisted into cells at detectable levels up to 16 days. SLN were detected in mice lungs up to 6 days. SLN-GSE possessed 243 nm as mean diameter, were negatively charged, and stable in size at 37 °C in Simulated Lung Fluid up to 48 h and at 4 °C in double distilled water up to 2 months. The content of SLN in proanthocyanidins remained unvaried up to 2 months. GSE-loaded SLN determined a significant reduction in ROS production when added 24-72 h before the stimulation with hydrogen peroxide. Interestingly, while at 24 h free GSE determined a higher decrease of ROS production than SLN-GSE, the contrary was seen at 48 and 72 h. Similar results were observed for NF-κB nuclear translocation. CONCLUSIONS: SLN are a biocompatible drug delivery system for natural anti-oxidants obtained from grape seed in a model of oxidative stress in airway epithelial cells. They feature stability and long-term persistence inside cells where they release proanthocyanidins. These results could pave the way to novel anti-oxidant and anti-inflammatory therapies for chronic respiratory diseases.

Postoperative infections after cytoreductive surgery and HIPEC for peritoneal carcinomatosis: proposal and results from a prospective protocol study of prevention, surveillance and treatment.

The incidence of infectious complications due to several contributory causes is particularly elevated and life-threatening in patients undergoing peritonectomy and HIPEC procedure for peritoneal carcinomatosis. Following a previous experience, we started a prospective protocol study of preoperative screening, perioperative prophylaxis and postoperative surveillance and treatment. A total of 111 patients with peritoneal carcinomatosis of various origin underwent CRS with HIPEC between April 2004 and December 2012. The group was divided into a pilot group of 30 patients (04/04 to 05/08) and a main group of 81 patients (06/08 to 12/12). Overall postoperative morbidity rate was 44%, with 35.8% of symptomatic infections. No post-operative mortality was observed. Microorganisms were isolated in 24 patients (80.0%) in the first group and 54 (66.7%) in the second. They were symptomatic in 18 cases (75.0%) and 25 (46.3%) cases respectively. In addition, 7 invasive candidosis were recorded (25.9%). Colon resection (P = 0.01) and duration of surgery (P = 0.0008) were associated with infection at logistic regression model. Concerning symptomatic infections, only Infection Risk Index (P = 0.009) showed significance at multivariate analysis. Despite a significant incidence of infectious complications, establishment of a prevention, surveillance and treatment protocol lead to a zero mortality rate in the observed patients of our experience. Owing to the obtained results, we suggest the use of a standardized protocol for the prevention, monitoring and treatment in all patients enrolled for cytoreductive surgery and HIPEC.

Environmental efficiency of alternative dairy systems: a productive efficiency approach.

Agriculture across the globe needs to produce "more with less." Productivity should be increased in a sustainable manner so that the environment is not further degraded, management practices are both socially acceptable and economically favorable, and future generations are not disadvantaged. The objective of this paper was to compare the environmental efficiency of 2 divergent strains of Holstein-Friesian cows across 2 contrasting dairy management systems (grazing and nongrazing) over multiple years and so expose any genetic × environment (G × E) interaction. The models were an extension of the traditional efficiency analysis to account for undesirable outputs (pollutants), and estimate efficiency measures that allow for the asymmetric treatment of desirable outputs (i.e., milk production) and undesirable outputs. Two types of models were estimated, one considering production inputs (land, nitrogen fertilizers, feed, and cows) and the other not, thus allowing the assessment of the effect of inputs by comparing efficiency values and rankings between models. Each model type had 2 versions, one including 2 types of pollutants (greenhouse gas emissions, nitrogen surplus) and the other 3 (greenhouse gas emissions, nitrogen surplus, and phosphorus surplus). Significant differences were found between efficiency scores among the systems. Results indicated no G × E interaction; however, even though the select genetic merit herd consuming a diet with a higher proportion of concentrated feeds was most efficient in the majority of models, cows of the same genetic merit on higher forage diets could be just as efficient. Efficiency scores for the low forage groups were less variable from year to year, which reflected the uniformity of purchased concentrate feeds. The results also indicate that inputs play an important role in the measurement of environmental efficiency of dairy systems and that animal health variables (incidence of udder health disorders and body condition score) have a significant effect on the environmental efficiency of each dairy system. We conclude that traditional narrow measures of performance may not always distinguish dairy farming systems best fitted to future requirements.

A relationship between the inhibition of heparan sulfate and chondroitin sulfate synthesis and the inhibition of molting by selenate in the hemipteran Rhodnius prolixus.

The insect Rhodnius prolixus synthesizes heparan sulfate and chondroitin sulfate after a blood meal containing [35S]-inorganic sulfate. A 40 to 80% inhibition of heparan sulfate synthesis was obtained when the meal was supplemented with 10(-5) and 10(-4) M sodium selenate respectively. Likewise an inhibition of the molting in the order of 30 to 60% was observed when the insects were fed with blood containing 10(-5) and 10(-4) M selenate respectively. The insects after a subsequent meal without selenate molted normally. Except for the inhibition of the ecdysis no gross physiological or morphological changes could be observed in the insects. Based on these and other findings the possible role of sulfated glycosaminoglycans in the control of cell growth is discussed.

Randomized placebo-controlled comparative study of nifedipine, verapamil and isosorbide dinitrate in the treatment of angina at rest.

Twenty-nine patients with angina at rest took part in a randomized placebo-controlled short-term study to assess the relative effectiveness of different dosages of nifedipine (N), verapamil (V) and isosorbide dinitrate (ISDN) versus placebo and to evaluate the antianginal effects of a sustained-release preparation of ISDN (sr), of N retard form (r) and of V retard form (r). The 29 patients were divided into 3 groups: the first group of patients (10 patients, group A) was treated with N 10 mg six times daily, V 80 mg three times daily and ISDN 10 mg six times daily; the second group of patients (9 patients, group B) was treated with N 20 mg six times daily, V 120 mg four times daily and ISDN 20 mg six times daily; the third group of patients (10 patients, group C) was treated with N r 20 mg four times daily, V r 120 mg three times daily and ISDN sr 40 mg four times daily. The daily frequency of ischaemic episodes (IE) was assessed by Holter monitoring. The effect of each drug on the mean frequency of IE was compared with the placebo using a one-way analysis of variance and the Newman-Keuls test. In group A, the mean daily frequency of IE per patient was 8.1 +/- 5.9 with the placebo, 1.4 +/- 1.9 with N (P less than 0.001; -82%), 4 +/- 3.6 with V (P: NS; -50%) and 4.3 +/- 3.6 with ISDN (P: NS; -46%). In group B it was 6.4 +/- 3.4 with the placebo, 0.5 +/- 1.6 with N (P less than 0.01; -91%), 0.3 +/- 0.5 with V (P less than 0.01; -95%) and 1.2 +/- 1 with ISDN (P less than 0.01; -82%). In group C it was 10.3 +/- 8.7 with the placebo, 0.7 +/- 1.6 with N r (P less than 0.01; -93%), 1 +/- 2.5 with V r (P less than 0.01; -90%) and 5.1 +/- 7.7 with ISDN sr (P: NS; -50%). In group A a reduction of 100% in the number of recorded IEs was achieved in 5/10 patients by using N, in none by V, and in 1/10 by ISDN. In group B, in 8/9 patients by N, in 6/9 by V and in 3/9 by ISDN. In group C, in 8/10 patients by both N r and V r in 4/10 patients by ISDN sr.(ABSTRACT TRUNCATED AT 400 WORDS)