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.
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.
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.
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.
High-level, plasmid-based, transferable vancomycin resistance is documented in a community-associated MRSA organism. The vancomycin-resistant strain caused a serious bloodstream infection in a ...patient in Brazil.
Since the description in 2002 of the
vanA
gene cluster in MRSA as the mechanism of high-level vancomycin resistance, 13 isolates have been reported in the United States,
1
,
2
with others reported in India
3
and Iran.
4
Enterococcus faecalis
and
E. faecium
have been implicated as the donors of the vancomycin resistance genes.
5
,
6
The VRSA isolates were recovered from patients with soft-tissue or skin infections, and multilocus sequence typing has shown that 12 U.S. VRSA isolates belong to clonal complex 5 (including ST5, ST85, ST231, and ST371)
1
and that the 13th isolate belongs to clonal complex 30. Clonal complex 5 . . .
Aim
To provide a comprehensive evidence‐based assessment of the anatomical variations of the left colic artery (LCA).
Method
A thorough systematic search of the literature up until 1 April 2019 was ...conducted on the electronic databases PubMed, SCOPUS and Web of Science (WOS) to identify studies eligible for inclusion. Data were extracted and pooled into a meta‐analysis using the Metafor package in R. The primary outcomes of interest were the absence of the LCA and the anatomical variants of its origin. The secondary outcomes were the distance (mean ± SD) between the origin of the inferior mesenteric artery (OIMA) and the origin of the left colic artery (OLCA).
Results
A total of 19 studies (n = 2040 patients) were included. The pooled prevalence estimate (PPE) of LCA absence was 1.2% (95% CI 0.0–3.6%). Across participants with either a Type I or Type II LCA, the PPE of a Type I LCA was 49.0% (95% CI 40.2–57.8%). The PPE of a Type II LCA was therefore 51.0%. The pooled mean distance from the OIMA to the OLCA was 40.41 mm (95 CI% 38.69–42.12 mm). The pooled mean length of a Type I LCA was 39.12 mm (95% CI 36.70–41.53 mm) while the pooled mean length of a Type IIa and Type IIb LCA was 41.43 mm (95% CI 36.90–43.27 mm) and 39.64 mm (95% CI 37.68–41.59 mm), respectively.
Conclusion
Although the absence of the LCA is a rare occurrence (PPE 1.2%), it may be associated with an important risk of anastomotic leakage as a result of insufficient vascularization of the proximal colonic conduit. It is also necessary to distinguish variants I and II of Latarjet, the frequency of which is identical, with division of the LCA being technically more straightforward in variant I of Latarjet. Surgeons should be aware that technical difficulties are likely to be more common with variant II of Latarjet, as LCA ligation may be more difficult due to its close proximity to the inferior mesenteric vein (IMV).
Objective
Through years, interest in quality of life (QoL) among patients affected by vestibular schwannoma (VS) has increased. The expansion of the indications for endoscopic ear surgery allowed the ...development of the transcanal transpromontorial surgery (TTS) for VS removal. The objective of the present study was to assess QoL in a cohort of VS patients operated on by translabyrinthine (TL), retrosigmoid (RS) and TTS approach.
Methods
The study was conducted on 111 patients who underwent surgery for VS between January 2017 and January 2020 at two different institutions. Patients fulfilled three questionnaires during follow-up: Glasgow Benefit Inventory, Depression Anxiety Stress Scales-21 and Penn Acoustic Neuroma Quality-Of-Life. The association between sex, age, date of surgery, tumor size, post-operative facial nerve (FN) function and QoL outcomes was assessed.
Results
An overall subjective impairment was demonstrated in all groups. Age, Koos staging and FN functions were associated to distinct QoL outcomes.
Conclusions
QoL decreases in patients surgically treated for VS. The TTS may allow improved scores in many domains, confirming to be a subjectively well-tolerated technique.
We use a new spherical accretion recipe tested on
N
-body simulations to measure the observed mass accretion rate (MAR) of 129 clusters in the Cluster Infall Regions in the Sloan Digital Sky Survey ...(CIRS) and in the Hectospec Cluster Survey (HeCS). The observed clusters cover the redshift range of 0.01 <
z
< 0.30 and the mass range of ∼10
14
− 10
15
h
−1
M
⊙
. Based on three-dimensional mass profiles of simulated clusters reaching beyond the virial radius, our recipe returns MARs that agree with MARs based on merger trees. We adopt this recipe to estimate the MAR of real clusters based on measurements of the mass profile out to ∼3
R
200
. We use the caustic method to measure the mass profiles to these large radii. We demonstrate the validity of our estimates by applying the same approach to a set of mock redshift surveys of a sample of 2000 simulated clusters with a median mass of
M
200
= 10
14
h
−1
M
⊙
as well as a sample of 50 simulated clusters with a median mass of
M
200
= 10
15
h
−1
M
⊙
: the median MARs based on the caustic mass profiles of the simulated clusters are unbiased and agree within 19% with the median MARs based on the real mass profile of the clusters. The MAR of the CIRS and HeCS clusters increases with the mass and the redshift of the accreting cluster, which is in excellent agreement with the growth of clusters in the ΛCDM model.
Mitotic microtubule (MT)-targeting drugs are widely used to treat cancer. The GTPase Ran regulates multiple processes, including mitotic spindle assembly, spindle pole formation and MT dynamics; Ran ...activity is therefore essential to formation of a functional mitotic apparatus. The RanBP1 protein, which binds Ran and regulates its interaction with effectors, is overexpressed in many cancer types. Several observations indicate that RanBP1 contributes to regulate the function of the mitotic apparatus: RanBP1 inactivation yields hyperstable MTs and induces apoptosis during mitosis, reminiscent of the effects of the MT-stabilizing drug taxol. Here we have investigated the influence of RanBP1 on spontaneous and taxol-induced apoptosis in transformed cells. We report that RanBP1 downregulation by RNA interference activates apoptosis in several transformed cell lines regardless of their p53 status, but not in the caspase-3-defective MCF-7 breast cancer cell line. Furthermore, RanBP1-interfered cells show an increased apoptotic response to taxol compared to their counterpart with normal or high RanBP1 levels, and this response is caspase-3 dependent. These results indicate that RanBP1 can modulate the outcome of MT-targeting therapeutic protocols.
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In this study, novel polymeric nanoparticles (NPs) were developed and their potential as carriers for beclomethasone dipropionate (BDP) into the lung after aerosolization was ...demonstrated by in vivo studies in mice. In particular, these NPs were obtained starting from two polyaspartamide-based copolymers which were synthesized by chemical reaction of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) and its pegylated derivative (PHEA-PEG2000) with poly(lactic acid) (PLA). To obtain nanosized particles, the high pressure homogenization (HPH)—solvent evaporation method was followed by using an organic phase containing both PHEA-PLA and PHEA-PEG2000-PLA (at a weight ratio equal to 1:1), lactose as cryoprotectant and no surfactant was adopted. PHEA-PLA/PHEA-PEG2000-PLA NPs were characterized by a quite spherical shape, ζ potential slightly negative, and size lower than 50 and 200nm, respectively, for empty and BDP-loaded NPs. In vivo biodistribution of BDP and its metabolites in various lung compartments, i.e. bronchoalveolar lavage fluid (BALF), alveolar macrophages (MPG) obtained from BALF, and lung tissue, was carried out at 3h post-administration in mice by aerosolization of BDP-loaded NPs or free BDP (commercial formulation, Clenil®) at the dose of 0.5mg/kg BDP. Results demonstrated that BDP entrapped into NPs reached all analyzed lung compartments and were internalized by both alveolar MPG and respiratory epithelial cells, and detected amounts were comparable to those of Clenil-treated mice. Moreover, the entrapment into NPs protects the drug from the enzymatic hydrolysis, allowing a significant lower amount of beclomethasone (BOH) into the lung tissue and BALF than that obtained after Clenil administration.
About half of the ATLAS pixel modules have been assembled with the Selex indium bump bonding process. The requirements of the ATLAS Insertable B-Layer (IBL) detector ask for larger and thinner chips, ...two critical parameters for bonding processes. We report on the research and development carried on with Selex to produce modules with 100 mu m thick and 18.8 x 20.2mm super(2) area read out chips bonded with indium bumps.
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