Preparation and in vitro characterization of piroxicam enteric coated pellets using powder layering technique

The objective of this study was to develop piroxicam enteric coated pellets using nonpareil seeds by powder layering technique to minimize its gastrointestinal adverse effects. Inert seeds were prepared by incorporating sugar, Avicel PH 101 and lactose. The obtained cores were then treated by PVP 10 w/v % solution using centrifugal granulator (CF-granulator) and then coated with micronized piroxicam using HPMC solution (8 w/v %) as binder. The piroxicam pellets were finally coated with different polymers (Eudragit L30D-55, Eudragit L100, Eudragit NE30D, Acryleze, or mixture of Eudragits L30D-55 and NE30D) and plasticizers (triethyl citrate and polyethylene glycol 6000). Results showed that Eudragit L30D-55 with 3% weight gain accompanied with TEC produced suitable enteric coated pellets.     

Communicating side effect risks in a tamoxifen prophylaxis decision aid: The debiasing influence of pictographs

Objective

To experimentally test whether using pictographs (image matrices), incremental risk formats, and varied risk denominators would influence perceptions and comprehension of side effect risks in an online decision aid about prophylactic use of tamoxifen to prevent primary breast cancers.

Methods

We recruited 631 women with elevated breast cancer risk from two healthcare organizations. Participants saw tailored estimates of the risks of 5 side effects: endometrial cancer, blood clotting, cataracts, hormonal symptoms, and sexual problems. Presentation format was randomly varied in a three factor design: (A) risk information was displayed either in pictographs or numeric text; (B) presentations either reported total risks with and without tamoxifen or highlighted the incremental risk most relevant for decision making; and (C) risk estimates used 100 or 1000 person denominators. Primary outcome measures included risk perceptions and gist knowledge.

Results

Incremental risk formats consistently lowered perceived risk of side effects but resulted in low knowledge when displayed by numeric text only. Adding pictographs, however, produced significantly higher comprehension levels.

Conclusions

Pictographs make risk statistics easier to interpret, reducing biases associated with incremental risk presentations.

Practice implications

Including graphs in risk communications is essential to support an informed treatment decision-making process.     

CTLA-4 x Ig converts naive CD4+CD25- T cells into CD4+CD25+ regulatory T cells

CTLA-4 x Ig was originally designed as an immunosuppressive agent capable of interfering with the co-stimulation of T cells. In the present study, we demonstrate that CTLA-4 x Ig, in combination with TCR ligation, has the additional capacity to convert naive CD4+CD25- T cells into Foxp3+ regulatory T (T(reg)) cells, as well as to expand their numbers. The CD4+CD25+Foxp3+ T(reg) generated by CTLA-4 x Ig treatment in vitro potently suppress effector T cells. Extending this in vivo, we show that systemic administration of CTLA-4 x Ig increases the percentage of CD4+CD25(hi)Foxp3+ cells within mixed lymphocyte reaction-induced murine lymph nodes. Significantly, the in vitro conversion of naive CD4+CD25- T cells into T(reg) cells is antigen-presenting cell (APC) dependent. This finding, together with the further observation that this conversion can also be driven in vitro by an antibody that engages B7-2 ligand, suggests that CTLA-4 x Ig-driven T(reg) induction may be predicated upon active CTLA-4 x Ig to B7-2 signaling within APC, which elicits from them T(reg)-inducing potential. These findings extend CTLA-4 x Ig's functional repertoire, and at the same time, reinforce the concept that T cell anergy and active suppression are not entirely distinct processes and may be linked by some common molecular triggers.     

Structural characterization and physical properties of P2O5-CaO-Na2O-TiO2 glasses by Fourier transform infrared, Raman and solid-state magic angle spinning nuclear magnetic resonance spectroscopies

Phosphate-based glasses have been investigated for tissue engineering applications. This study details the properties and structural characterization of titanium ultra-phosphate glasses in the 55(P₂O₅)-30(CaO)-(25 − x)(Na₂O)-x(TiO₂) (0 ? x ? 5) system, which have been prepared via melt-quenching techniques. Structural characterization was achieved by a combination of X-ray diffraction (XRD), and solid-state nuclear magnetic resonance, Raman and Fourier transform infrared spectroscopies. Physical properties were also investigated using density, degradation and ion release studies; additionally, differential thermal analysis was used for thermal analysis of these glasses. The results show that with the addition of TiO₂ the density and glass transition temperature increased whereas the degradation and ion release properties are decreased. From XRD data, TiP₂O₇ and CaP₂O₆ were detected in 3 and 5 mol.% TiO₂-containing glasses. Magic angle spinning nuclear magnetic resonance results confirmed that as TiO₂ is incorporated into the glass; the amount of Q³ increases as the amount of Q² consequently decreases, indicating increasing polymerization of the phosphate network. Spectroscopy results also showed that the local structure of glasses changes with increasing TiO₂ content. As TiO₂ is incorporated into the glass, the phosphate connectivity increases, indicating that the addition of TiO₂ content correlates unequivocally with an increase in glass stability.     

Russell body gastritis: a case report

Russell body gastritis refers to the accumulation of plasma cells containing Russell bodies within the lamina propria. This report describes the first case of monoclonal Russell body gastritis without the previously reported associations.     

Structural Studies of Nicotinic Acetylcholine Receptors: Using Acetylcholine‐Binding Protein as a Structural Surrogate

Nicotinic acetylcholine receptors (nAChRs) are members of the pentameric ligand‐gated ion channel superfamily that play important roles in the control of neurotransmitter release in the central and peripheral nervous system. These receptors are important therapeutic targets for the development of drugs against a number of mental health disorders and for marketed smoking cessation aids. Unfortunately, drug discovery has been hampered by difficulties in obtaining sufficiently selective compounds. Together with functional complexity of the receptors, this has made it difficult to obtain drugs with sufficiently high‐target to off‐target affinity ratios. The recent and ongoing progress in structural studies holds promise to help understand structure–function relationships of nAChR drugs at the atomic level. This will undoubtedly lead to the design of more efficient drugs with fewer side effects. As a high‐resolution structure of a nAChR is yet to be determined, structural studies are to a large extent based on acetylcholine‐binding proteins (AChBPs) that despite low overall sequence identity display a high degree of conservation of overall structure and amino acids at the ligand‐binding site. Further, AChBPs reproduce relative binding affinities of ligands at nAChRs. Over the past decade, AChBPs have been used extensively as models for nAChRs and have aided the understanding of drug receptor interactions at nAChRs significantly.     

Impact of various culture conditions on ex vivo expansion of polyclonal T cells for adoptive immunotherapy

Currently, adoptive immunotherapy is considered as one of the leading treatments in cancer. Successful adoptive immunotherapy depends on producing large numbers of desired T cells ex vivo for infusion. This requires an effective protocol for maximum functional T‐cell expansion while keeping the time and costs to a minimum. Current T‐cell expansion protocols are diverse in their methodology, and a universal protocol of expansion is wanting. Also, new findings regarding T‐cell biology, signaling, and activation have reshaped the strategies of T‐cell propagation over the years, introducing new ways to expand T cells. Here, we reviewed different conditions for blood‐derived polyclonal T‐cell expansion so as to elucidate the influential factors of T‐cell expansion and their efficacy.