Improvement of resveratrol permeation through sublingual mucosa: Chemical permeation enhancers versus spray drying technique to obtain fast-disintegrating sublingual mini-tablets

Resveratrol (RSV) is a natural polyphenol with several interesting broad-spectrum pharmacological properties. However, it is characterized by poor oral bioavailability, extensive first-pass effect metabolism and low stability. Indeed, RSV could benefit from the advantage of the sublingual route of administration. In this view, RSV attitudes to crossing the porcine sublingual mucosa were evaluated and promoted both by six different chemical permeation enhancers (CPEs) as well as by preparing four innovative fast-disintegrating sublingual mini-tablets by spray drying followed by direct compression. Since RSV by itself exhibits a low permeation aptitude, this could be significantly enhanced by the use of CPEs as well as by embedding RSV in a spray-dried powder to be compressed in order to prepare fast-disintegrating mini-tablets. The most promising observed CPEs (menthol, lysine and urea) were then inserted into the most promising spray-dried excipients’ compositions (RSV-B and RSV-C), thus preparing CPE-loaded mini-tablets. However, this procedure leads to unsatisfactory results which preclude the possibility of merging the two proposed approaches. Finally, the best spray-dried composition (RSV-B) was further evaluated by SEM, FTIR, XRD and disintegration as well as dissolution behavior to prove its effectiveness as a sublingual fast-disintegrating formulation

Lipid nanocarriers-loaded nanocomposite as a suitable platform to release antibacterial and antioxidant agents for immediate dental implant placement restorative treatment

Immediate implant placement is a single-stage restorative approach for missing teeth widely used to overcome the ridge remodeling process occurring after dental extractions. The success of this procedure relies on opportune osseointegration in the surrounding tissues. To support this process, a multifunctional nanocomposite, to be applied in the fresh post-extraction socket, was here designed, prepared, and characterized. This formulation consists of quercetin (QRC)-loaded nanostructured lipid carriers (NLCs) entrapped in a chitosan-based solid matrix containing ciprofloxacin (CPX). QRC-NLCs were prepared by homogenization followed by high-frequency sonication, and thereafter this dispersion was trapped in a chitosan-based CPX-loaded gel, obtaining the nanocomposite powder (BioQ-CPX) by lyophilization. BioQ-CPX displayed desirable properties such as high porosity (94.1 ± 0.5%), drug amounts (2.1% QRC and 3.5% CPX). and low swelling index (100%). Moreover, the mechanism of drug release from BioQ-CPX and their ability to be accumulated in the target tissue were in vitro and ex vivo elucidated, also by applying mathematical models. When trapped into the nanocomposite, QRC stressed under UV light exposure (50 W) was shown to maintain its antioxidant power, and CPX and QRC under natural light were stable over nine months. Finally, both the measured antioxidant power and the antimicrobial and antibiofilm properties on Staphylococcus aureus demonstrated that BioQ-CPX could be a promising platform to support the single-stage dental restorative treatment

Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level

Background: The methylotrophic, Crabtree-negative yeast Pichia pastoris is widely used as a heterologous protein production host. Strong inducible promoters derived from methanol utilization genes or constitutive glycolytic promoters are typically used to drive gene expression. Notably, genes involved in methanol utilization are not only repressed by the presence of glucose, but also by glycerol. This unusual regulatory behavior prompted us to study the regulation of carbon substrate utilization in different bioprocess conditions on a genome wide scale. Results: We performed microarray analysis on the total mRNA population as well as mRNA that had been fractionated according to ribosome occupancy. Translationally quiescent mRNAs were defined as being associated with single ribosomes (monosomes) and highly-translated mRNAs with multiple ribosomes (polysomes). We found that despite their lower growth rates, global translation was most active in methanol-grown P. pastoris cells, followed by excess glycerol- or glucose-grown cells. Transcript-specific translational responses were found to be minimal, while extensive transcriptional regulation was observed for cells grown on different carbon sources. Due to their respiratory metabolism, cells grown in excess glucose or glycerol had very similar expression profiles. Genes subject to glucose repression were mainly involved in the metabolism of alternative carbon sources including the control of glycerol uptake and metabolism. Peroxisomal and methanol utilization genes were confirmed to be subject to carbon substrate repression in excess glucose or glycerol, but were found to be strongly de-repressed in limiting glucose-conditions (as are often applied in fed batch cultivations) in addition to induction by methanol. Conclusions: P. pastoris cells grown in excess glycerol or glucose have similar transcript profiles in contrast to S. cerevisiae cells, in which the transcriptional response to these carbon sources is very different. The main response to different growth conditions in P. pastoris is transcriptional; translational regulation was not transcript-specific. The high proportion of mRNAs associated with polysomes in methanol-grown cells is a major finding of this study; it reveals that high productivity during methanol induction is directly linked to the growth condition and not only to promoter strength

Quercetin-based nanocomposites as a tool to improve dental disease management

The restoration and prosthetic rehabilitation of missing teeth are commonly performed using dental implants, which are extremely effective and long-lasting techniques due to their osteointegration ability with the preimplant tissues. Quercetin is a phytoestrogen-like flavonoid well known for its several positive effects on human health, mostly linked to the anti-inflammatory, antioxidant, and antibacterial activities against both Gram-positive and Gram-negative bacteria. Moreover, many studies in dentistry and the maxillofacial fields have highlighted the positive effects of quercetin on osteogenesis, acting on osteoblast activity and angiogenetic process, and promoting soft and hard tissue regeneration. This review focuses on the role of quercetin on the healing and restoration of bony defects, considering the experimental findings of its application both in vitro and in vivo as a mere compound or in association with scaffolds and dental implants having functionalized surfaces

IFree: Design and evaluation of a pointing method for disabled users on mobile devices

We present the design and evaluation of a pointing method for disabled people, called iFree, which can run on mobile devices such as smartphones and tablets. The method is based on face recognition and supports target selection (click) in two different modes: by opening and closing the mouth (mouth click) and by making a sound (sound click).The method was experimented on a smartphone with 14 non-disabled participants in order to evaluate its performance and to compare the two above mentioned modes. In particular, we measured its performance using ISO 9241-411 standard task. The throughput grand mean was 0.86 bit/s. The sound click mode had a greater throughput and accuracy, a lower movement time and was preferred by participants

Study on the possibility to use the allochthonous bivalve mollusc Scapharca inaequivalvis (Bruguire) in the human alimentation.

A research was carried out in order to investigate from a chemical point of view about the possibility to use the Asiatic mollusc Scapharca inaequivalvis in the human alimentation. The chemical composition and the acidic profile were determined on a pool of samples collected aloang the coast of Marche region. The results showed a situation similar to that obtained on other bivalve molluscs

Congenital Milroy Oedema: a case report of a family

The authors describe the case of a newborn and their family with Nonne-Milroy disease (hereditary lymphedema type I), a genetic disease that is usually characterized by lymphedema, that most often affects the lower extremities or less frequently the back of the hands. We discuss etiology, inheritance pattern, differential diagnosis and follow-up

Combining Wireless Technology and Behavioral Economics to Engage Patients (WiBEEP) with cardiometabolic disease: a pilot study

Abstract Background The long-term management of cardiometabolic diseases, such as type 2 diabetes and hypertension, is complex and can be facilitated by supporting patient-directed behavioral changes. The concurrent application of wireless technology and personalized text messages (PTMs) based on behavioral economics in managing cardiometabolic diseases, although promising, has not been studied. The aim of this pilot study was to evaluate the feasibility and acceptability of the concurrent application of wireless home blood pressure (BP) monitoring (as an example of “automated hovering”) and PTMs (as an example of “nudging”) targeting pharmacotherapy and lifestyle habits in patients with cardiometabolic disease (type 2 diabetes and/or hypertension). Methods The Wireless Technology and Behavioral Economics to Engage Patients (WiBEEP) with cardiometabolic disease study was a single-arm, open-label, 7-week-long pilot study in 12 patients (mean age 58.5 years) with access to a mobile phone. The study took place at Tufts Medical Center (Boston, MA) between March and September 2017. All patients received PTMs; nine patients received wireless home BP monitoring. At baseline, patients completed questionnaires to learn about their health goals and to assess medication adherence; at the end of week 7, all patients completed questionnaires to evaluate the feasibility and acceptability of the intervention and assess medication adherence. Hemoglobin A1c was ascertained from data collected during routine clinical care in 7 patients with available data. Results The majority of patients reported the text messages to be easy to understand (88%) and appropriate in frequency (71%) and language (88%). All patients reported BP monitoring to be useful. Mean arterial pressure was lower at the end-of-study compared to baseline (− 3.4 mmHg [95% CI, − 5 to − 1.8]. Mean change in hemoglobin A1c was − 0.31% [95% CI, − 0.56 to − 0.06]. Conclusions Among patients with cardiometabolic disease, the combination of wireless BP monitoring and lifestyle-focused text messaging was feasible and acceptable. Larger studies will determine the long-term effectiveness of such an approach