Beta-cryptoxanthin from citrus juices: assessment of bioaccessibility using an in vitro digestion/Caco-2 cell culture model

Beta-Cryptoxanthin (beta-CX), a provitaminic carotenoid of potential interest for health, is found principally in Citrus fruit in both free and esterified forms. Little is known about the intestinal absorption of beta-CX especially with regard to the esterified forms. The aim of this study was to evaluate the absorption of free and esterified beta-CX using simulated digestion coupled with the Caco-2 model. Bioaccessibility was investigated by measuring the transfer of carotenoids from different citrus juices into micelles using an in vitro digestion system. Then, carotenoid uptake was evaluated by adding carotenoid-rich micelles (from the in vitro digestion) or synthetic micelles (made from synthetic lipids and carotenoids purified from citrus juice) to human intestinal cells (Caco-2 TC7 clone). Our results showed that beta-cryptoxanthin esters (beta-CXE) were partially hydrolysed during the in vitro digestion. The bioaccessibility of free beta-CX measured was significantly higher (40 (SD 1.05) %) than that of beta-carotene (30 (SD 1.9) %) and beta-CXE (16 (SD 1.5) %). In the same way, the incorporation of free beta-CX (27 (SD 1.01) %) into synthetic micelles exceeded (P<0.05) that of beta-carotene (10 (SD 0.7) %) and beta-CXE (8.8 (SD 0.4) %). In the case of micelles from in vitro digestion, the uptake of beta-carotene, free beta-CX and beta-CXE forms by Caco-2 cells was 14.3 (SD 1.8), 3.9 (SD 1.3), and 0.7 (SD 0.08) % respectively. These results showed a preferential uptake by Caco-2 cells of beta-carotene and free beta-CX compared with the two esters of beta-CX.     

Differential effect of dietary antioxidant classes (carotenoids, polyphenols, vitamins C and E) on lutein absorption

Lutein is assumed to protect the human retina from blue light and oxidative stress and diminish the incidence of age-related macular degeneration. This antioxidant is commonly ingested with other dietary antioxidants. The aim of the present study was to assess whether the main dietary antioxidants, i.e. carotenoids, polyphenols and vitamins C and E, affect lutein absorption. We measured the effect of adding a mixture of antioxidants (500 mg vitamin C, 67 mg (100 IU) vitamin E and 1 g polyphenols) to a lutein-containing meal (18 mg) on the postprandial lutein response in the chylomicron-rich fraction in eight healthy men. Lutein response was weakest (-23 %; P=0 x 07) after ingestion of the meal containing antioxidants (21 x 9 (sem 4 x 6) v. 28 x 4 (sem 7 x 2) nmol x h/l). To assess the effect of each class of antioxidants and potential interactions, we subsequently evaluated the effect of various combinations of antioxidants on lutein uptake by human intestinal Caco-2 TC-7 cells. A full factorial design showed that both a mixture of polyphenols (gallic acid, caffeic acid, (+)-catechin and naringenin) and a mixture of carotenoids (lycopene plus beta-carotene) significantly (P<0 x 05) impaired lutein uptake by (-10 to-30 %), while vitamins C and E had no significant effect. Subsequent experiments showed that the aglycone flavanone naringenin was the only polyphenol responsible for the effect of the polyphenol mixture, and that the carotenoid effect was not carotenoid species-dependent. Taken together, the present results suggest that lutein absorption is not markedly affected by physiological concentrations of vitamins C and E but can be impaired by carotenoids and naringenin     

Moment-to-moment associations between negative affect,aberrant salience,and paranoia

Introduction: There is an ongoing debate about whether negative affect are consequences or triggers of paranoid thinking. It has also been suggested that aberrant salience is central to the development of delusions. This study modelled the moment-to-moment relationships between negative affect, aberrant salience, and paranoia in acute inpatients with psychosis.

Methods: Participants with active paranoid delusions were assessed using clinical rating scales and experience sampling method (ESM) over 14 days. ESM data were analysed using time-lagged multilevel regression modelling.

Results: Both negative affect and aberrant salience predicted an increase in paranoia at the next time point. Conversely, the level of paranoia did not predict subsequent changes in negative affect or aberrant salience. Negative affect predicted an increase in aberrant salience at the next time point, and vice versa.

Conclusions: Negative affect and aberrant salience appear to drive and exacerbate paranoia, rather than being merely the sequelae of the symptom. Our results suggest both direct and indirect (via aberrant salience) pathways from negative affect to paranoia.     

Multimodal <Emphasis Type="Italic">In Vivo</Emphasis> Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer

Purpose

Transgenic mice expressing the polyoma middle T oncoprotein (PyMT) in the mammary epithelium were explored by multimodal imaging to monitor longitudinally spontaneous tumor growth and response to chemotherapy.

Procedures

Positron emission tomography (PET) with 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) and 3'-deoxy-3'-[¹⁸F]fluorothymidine ([¹⁸F]FLT), single photon emission tomography (SPECT) with [^99mTc]TcO₄ ([^99mTc]TEC), X-ray computed tomography, and fluorescent confocal endomicroscopy (FCE) images were acquired during tumor progression in female PyMT mice. Imaging with [¹⁸F]FDG and [^99mTc]TEC was also performed in untreated, doxorubicin-treated, and docetaxel-treated PyMT mice. Total tumor volumes were quantified. Tumors were collected and macroscopic and histological examinations were performed.

Results

All PyMT mice developed multifocal tumors of the mammary epithelium that became palpable at 8 weeks of age (W8). Computed tomography (CT) detected tumors at W14, while a clear tumoral uptake of [^99mTc]TEC and [¹⁸F]FDG was present as early as W6 and W8, respectively. No contrast between mammary tumors and surrounding tissue was observed at any stage with [¹⁸F]FLT. FCE detected an angiogenic switch at W10. Lung metastases were not clearly evidenced by imaging. Doxorubicin and docetaxel treatments delayed tumor growth, as shown by [¹⁸F]FDG and [^99mTc]TEC, but tumor growth resumed upon treatment discontinuation. Tumor growth fitted an exponential model with time constant rates of 0.315, 0.145, and 0.212 week^?1 in untreated, doxorubicin, and docetaxel groups, respectively.

Conclusions

Molecular imaging of mammary tumors in PyMT is precocious, precise, and predictive. [¹⁸F]FDG-PET and [^99mTc]TEC SPECT monitor tumor response to chemotherapy.

     

Impact of tapered-cuff tracheal tube on microaspiration of gastric contents in intubated critically ill patients: a multicenter cluster-randomized cross-over controlled trial

Purpose

Studies on the impact of tapered-cuff tracheal tubes on rates of microaspiration and ventilator-associated pneumonia (VAP) in intubated patients have reported conflicting results. The aim of this study was to determine the influence of this shape of tracheal cuff on abundant microaspiration of gastric contents in critically ill patients.

Methods

All patients intubated in the intensive care unit (ICU) and requiring mechanical ventilation for at least 48 h were eligible for this multicenter cluster-randomized controlled cross-over open-label study. The primary outcome was abundant microaspiration of gastric contents, defined by the presence of pepsin at significant level in >30% of tracheal aspirates. Quantitative measurement of pepsin and salivary amylase was performed in all tracheal aspirates during the 48 h following enrollment.

Results

A total of 326 patients were enrolled in the ten participating ICUs (162 in the PVC tapered-cuff group and 164 in the standard-cuff group). Patient characteristics were similar in the two study groups. The proportion of patients with abundant microaspiration of gastric contents was 53.5% in the tapered-cuff and 51.0% in the standard-cuff group (odds ratio 1.14, 95% CI 0.72–1.82). While abundant microaspiration of oropharyngeal secretions was not significantly different (77.4 vs 68.6%, p = 0.095), the proportion of patients with tracheobronchial colonization was significantly lower (29.6 vs 43.3%, p = 0.01) in the tapered-cuff than in the standard-cuff group. No significant difference between the two groups was found for other secondary outcomes, including ventilator-associated events and VAP.

Conclusions

This trial showed no significant impact of tapered-cuff tracheal tubes on abundant microaspiration of gastric contents.

Trial registration

ClinicalTrials.gov, number NCT01948635.

     

The costs of septic syndromes in the intensive care unit and influence of hospital-acquired sepsis

Objective To document the costs and outcomes of the various forms of the septic syndromes [systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock), particularly those associated with infection acquired in an intensive care unit (ICU).Design Prospective data collection for all septic patients admitted to a medical ICU during a 1-year period. Costs were computed from the viewpoint of the hospital.Results Mean total hospital costs were €26,256, €35,185, and €27,083 for patients with sepsis, severe sepsis, and septic shock, respectively. Total costs varied slightly according to the site of infection and the severity of sepsis but were influenced mostly by its mode of acquisition: patients having sepsis associated with ICU-acquired infection incurred total costs about three times those of patients presenting with infection and sepsis on ICU admission (from €39,908 in patients with ICU acquired sepsis to €44,851 in patients with ICU-acquired septic shock). Stratifying patients by the presence of ICU-acquired infection also showed that a first episode of infection complicated by ICU-acquired sepsis incurred at least 2.5 times more costs than a single episode of sepsis.Conclusions In this series the medical costs of sepsis were not markedly influenced by its severity but by its mode of acquisition. Due to wide variations in ICU costs cost-effectiveness analyses of treatments for sepsis should document the case-mix of patients and the contribution to this of nosocomial infections.     

Cis variants identified in F508del complex alleles modulate CFTR channel rescue by small molecules

Molecules correcting the trafficking (correctors) and gating defects (potentiators) of the cystic fibrosis causing mutation c.1521_1523delCTT (p.Phe508del) begin to be a useful treatment for CF patients bearing p.Phe508del. This mutation has been identified in different genetic contexts, alone or in combination with variants in cis. Until now, 21 exonic variants in cis of p.Phe508del have been identified, albeit at a low frequency. The aim of this study was to evaluate their impact on the efficacy of CFTR‐directed corrector/potentiator therapy (Orkambi). The analysis by minigene showed that two out of 15 cis variants tested increased exon skipping (c.609C > T and c.2770G > A). Four cis variants were studied functionally in the absence of p.Phe508del, one of which was found to be deleterious for protein maturation c.1399C > T (p.Leu467Phe). In the presence of p.Phe508del, this variant was the only to prevent the response to Orkambi treatment. This study showed that some patients carrying p.Phe508del complex alleles are predicted to poorly respond to corrector/potentiator treatments. Our results underline the importance to validate treatment efficacy in the context of complex alleles.