Effects of differentiation on purinergic and neurotensin-mediated calcium signaling in human HT-29 colon cancer cells.

Calcium signaling is a key regulator of processes important in differentiation. In colon cancer cells differentiation is associated with altered expression of specific isoforms of calcium pumps of the endoplasmic reticulum and the plasma membrane, suggesting that differentiation of colon cancer cells is associated with a major remodeling of calcium homeostasis. Purinergic and neurotensin receptor activation are known regulators of cytosolic free Ca(2+) levels in colon cancer cells. This study aimed to assess changes in cytosolic free Ca(2+) levels in response to ATP and neurotensin with differentiation induced by sodium butyrate or culturing post-confluence. Parameters assessed included peak cytosolic free Ca(2+) level after activation; time to reach peak cytosolic free Ca(2+) and the EC50 of dose response curves. Our results demonstrate that differentiation of HT-29 colon cancer cells is associated with a remodeling of both ATP and neurotensin mediated Ca(2+) signaling. Neurotensin-mediated calcium signaling appeared more sensitive to differentiation than ATP-mediated Ca(2+) signaling.

Salmonella Typhi and Plasmodium falciparum co-infection in a 12-year old girl with haemoglobin E trait from a non-malarious area in Bangladesh.

A 12-year old girl from Uttar Badda, Dhaka, Bangladesh, was admitted to the Dhaka Hospital of ICDDR,B, with a 23-day history of fever and diarrhoea. After admission, she was treated for culture-proven Salmonella Typhi-associated infection and was discovered to be heterozygous for haemoglobin E. Despite treatment with appropriate antibiotics, the patient's condition did not improve, prompting further investigation, which revealed malaria due to Plasmodium falciparum. Dhaka is considered a malaria-free zone, and the patient denied recent travel outside Dhaka. Subsequently, the patient recovered fully on antimalarial therapy.

Metal-organic-frameworks for biomedical applications in drug delivery, and as MRI contrast agents.

The metal-organic-frameworks (MOFs) materials are increasingly gaining attraction to utilise into biomedical applications. MOFs are playing a major role to harnessing dual or multiple modalities in therapeutics and diagnostics. MOFs are mostly devised for particular biomedical application by post-synthetic functionalization or modification using variety of polymers, bio-ligands, and silica coating processes. This article presents a brief overview of two particular areas of biomedical applications where a broad range of MOFs have been used: (1) variety of drug delivery including intracellular drug delivery systems using the MOFs-based carriers; and, (2) development of MOFs-based contrast agents for magnetic resonance image enhancement. Biocompatibility, bio-toxicity, tissue responses, cell viability, cellular uptakes, and, how the effects of size, shape, structural, and morphological properties of the MOFs impact on the utilities in drug delivery and as MRI contrast agents, are discussed. Perspectives, insights and critical reflections into a range of aspects, and future outlook are illustrated. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1184-1194, 2017.

The Controlled Release of Drugs and Bioactive Compounds from Mesoporous Silica Nanoparticles.

In recent period of time the mesoporous silica nanoparticles (MSNs) have been extensively utilised in controlled release (CR) applications. This burgeoning research is favoured because of the unique characteristics of the MSNs such as, ordered and homogenous pore network, high surface area and pore volumes, silanol-containing surfaces, and relatively low toxic in nature. However, for an effective targeted drug delivery, these materials offer numerous challenges such as, to reduce the complications and toxicity and avoid any undesired interactions of the MSNs with the untargeted healthy cells and membranes. A range of concepts and techniques have been implied to overcome these challenges. This article presents an overview on the recent research advancements in CR of drugs and bioactive compounds from the MSNs. Based on the past researches that took place over the last 15 years, the article illustrates three particular areas: 1) unmodified MSNs, 2) modified MSNs, and 3) biocompatibility, bio-toxicity, tissue responses and cellular uptakes of the MSNs. The three encompassed areas of research describe enormous diversities and complexities which span the aspects of complex designs and syntheses, types of silica materials being used, drug loadings, types of drug used, and ranges of biological evaluations of the MSNs. Perspectives and insights are presented into a range of aspects such as, syntheses, characterisations, functionalisation and incorporations of biomacromolecules into the MSNs; drug loadings and drug release kinetics; biological evaluations such as, biocompatibility, bio-toxicity and intracellular drug delivery; and, the effects of size, shape, morphology, structural and textural properties of the MSNs.

The controlled release of bioactive compounds from lignin and lignin-based biopolymer matrices.

This article presents the perspectives on the lignin-based controlled release (CR) of bioactive materials which are based on the researches that took place over the last three decades. It encompasses three broad spectra of observations: CR formulations with mixed-matrix of lignin; CR formulations with modified lignin; and the lignin-based CR formulation modelling. The article covers a range of bioactive materials aimed for agricultural utilisations viz. herbicides, pesticides, insecticides and fertilisers for their controlled release studies, which were formulated either with lignin or lignin-based biopolymers. The inherent complexities, structural heterogeneities, and the presence of myriad range of functionalities in the lignin structure make it difficult to understand and explaining the underlying CR behaviour and process. In conjunction to this issue, the fundamental aspects of the synthetic and biocompatible polymer-based drug controlled release process are presented, and correlated with the lignin-based CR research. The articulation of this correlation and the overview presented in this article may be complemented of the future lignin-based CR research gaining better insights, reflections, and understanding. A recommended approach on the lignin depolymerisation is suggested to fragmenting the lignin, which may be tailored further using the re-polymerisation or other synthetic approaches. Thus it may allow more control with flexibilities and improved properties of the modified lignin materials, and help achieve the desired CR outcomes.

Mass uptake study of the diffusion of water and SBF into poly(2-hydroxyethyl methacrylate-co-tetrahydrofurfuryl methacrylate) containing aspirin or vitamin B12.

The ingress of water and Kokubo simulated body fluid (SBF) into poly(2-hydroxyethyl methacrylate) (PHEMA), and its co-polymers with tetrahydrofurduryl methacrylate (THFMA), loaded with either one of two model drugs, vitamin B12 or aspirin, was studied by mass uptake over the temperature range 298-318 K. The polymers were studied as cylinders and were loaded with either 5 wt% or 10 wt% of the drugs. From DSC studies it was observed that vitamin B12 behaved as a physical cross-linker restricting chain segmental mobility, and so had a small anti-plasticisation effect on PHEMA and the co-polymers rich in HEMA, but almost no effect on the Tg of co-polymers rich in THFMA. On the other hand, aspirin exhibited a plasticising effect on PHEMA and the co-polymers. All of the polymers were found to absorb water and SBF according to a Fickian diffusion mechanism. The polymers were all found to swell to a greater extent in SBF than in water, which was attributed to the presence of Tris buffer in the SBF. The sorptions of the two penetrants were found to follow Fickian kinetics in all cases and the diffusion coefficients at 310 K for SBF were found to be smaller than those for water, except for the polymers containing aspirin where the diffusion coefficients were higher than for the other systems. For example, for sorption into PHEMA the diffusion coefficient for water was 1.41 x 10(-11) m2/s and for SBF was 0.79 x 10(-11) m2/s, but in the presence of 5 wt% aspirin the corresponding values were 1.27 x 10(-11) m2/s and 1.25 x 10(-11) m2/s, respectively. The corresponding values for PHEMA loaded with 5 wt% B12 were 1.25 x 10(-11) m2/s and 0.74 x 10(-11) m2/s, respectively.

NMR imaging of the diffusion of water at 37 degrees C into Poly(2-hydroxyethyl methacrylate) containing aspirin or vitamin B(12).

The ingress of water into poly(2-hydroxyethyl methacrylate), PHEMA, loaded with either one of two model drugs, vitamin B(12) or aspirin, was studied at 37 degrees C using three-dimensional NMR imaging. PHEMA was loaded with 5 and 10 wt % of the drugs. From the imaging profiles, it was observed that incorporation of vitamin B(12) into PHEMA resulted in enhanced crack formation on sorption of water and the crack healing behind the diffusion front was slower than for PHEMA without added drug. This was accounted for by the anti-plasticization of PHEMA by vitamin B(12). Crack formation was inhibited in the PHEMA-aspirin systems because of the plasticizing effect of the aspirin on the PHEMA matrix. All of the polymers were found to absorb water according to an underlying Fickian diffusion mechanism. For PHEMA loaded with 5 wt % of aspirin or vitamin B(12), the best values of the water diffusion coefficients were both found to be 1.3 +/- 0.1 x 10(-11) m(2) s(-1) at 37 degrees C, while the values for the polymer loaded with 10 wt % of the drugs were slightly higher, 1.5 +/- 0.1 x 10(-11) m(2) s(-1).

NMR imaging of the diffusion of water at 310 K into semi-IPNs of PEM and poly(HEMA-co-THFMA) with and without chlorhexidine diacetate.

Magnetic resonance imaging has been used to monitor the diffusion of water at 310 K into a series of semi-IPNs of poly(ethyl methacrylate), PEM, and copolymers of 2-hydroxyethyl methacrylate, HEMA, and tetrahydrofurfuryl methacrylate, THFMA. The diffusion was found to be well described by a Fickian kinetic model in the early stages of the water sorption process, and the diffusion coefficients were found to be slightly smaller than those for the copolymers of HEMA and THFMA, P(HEMA-co-THFMA), containing the same mole fraction of HEMA in the matrix. A second stage sorption process was identified in the later stage of water sorption by the PEM/PTHFMA semi-IPN and for the systems containing a P(HEMA-co-THFMA) component with a mole fraction HEMA of 0.6 or less. This was characterized by the presence of water near the surface of the cylinders with a longer NMR T(2) relaxation time, which would be characteristic of mobile water, such as water present in large pores or surface fissures. The presence of the drug chlorhexidine in the polymer matrixes at a concentration of 5.625 wt % was found not to modify the properties significantly, but the diffusion coefficients for the water sorption were systematically smaller when the drug was present.