Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients

Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B and T cells with a secondary long-term reconstruction of the immune system. This study provides evidence of CLD’s immunomodulatory role in peripheral blood mononuclear cells (PBMCs) harvested from 40 patients with untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion from PBMCs isolated by density gradient centrifugation with Ficoll–Paque using xMAP technology on a FlexMap 3D analyzer with a highly sensitive multiplex immunoassay kit. The PBMC secretory profile was evaluated with and without CLD exposure. PBMCs isolated from patients with RRMS for ≤12 months had significantly higher IL-4 but significantly lower IFN-γ and TNF-α secretion after CLD exposure. PBMCs isolated from patients with RRMS for >12 months had altered inflammatory ratios toward an anti-inflammatory profile and increased IL-4 but decreased TNF-α secretion after CLD exposure. CLD induced nonsignificant changes in IL-17 secretion in both RRMS groups. Our findings reaffirm CLD’s immunomodulatory effect that induces an anti-inflammatory phenotype.     

Thermal stability of catechin and epicatechin upon disaccharides addition

Influence of sucrose and trehalose addition on epimerisation and thermal degradation of catechin and epicatechin have been studied. Sucrose addition accelerated epimerisation of catechin and epicatechin at 80 and 100 °C. Addition of trehalose had protective effect on epimerisation of catechin and epicatechin. Considering thermal degradation, it was confirmed that thermal degradation of catechin and epicatechin follows the first‐order kinetics. Increasing the temperature causes shorter half‐lives of catechin and epicatechin. Addition of sucrose had negative effect on catechin stability. However, in samples with epicatechin, sucrose impact was temperature dependent. Trehalose addition had positive impact on preventing catechin and epicatechin degradation almost doubling the half‐life of studied compounds. Data presented in this study could help to predict chemical conversions of investigated phenolics in various food systems and to prolong their shelf life in thermally processed foods.     

Microwave-Assisted,Base-Catalyzed Synthesis of Fatty Acid Methyl Esters from Seeds and Fish Oil Supplements

Growing health awareness has resulted in the increased use of dietary supplements derived from plants and marine sources, leaving consumers unsure of their best options. There were three objectives of the present study. The first was to design and evaluate an efficient derivatization procedure. The second was to perform a comparative analysis of liquid oils and their corresponding capsules of hemp, chia, and flax seeds. The final objective was to determine the fatty acid (FA) composition of six fish oil products and compare it to the one provided on the label. For the FA profiling, we implemented two efficient, one-step, sustainable methods with high percentage recovery for the synthesis of FA methyl esters (FAME), which use base catalysis and microwave-assisted heating. Our results found no difference in nutritional value between liquid oils and capsules of the seed supplements, with flaxseed and chia offering a higher, beneficial n-3:n-6 ratio compared to hemp oil. Four of the fish oils analyzed contained significantly less eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than their reported label, and the other two not only agreed with the manufacturers' declaration but were able to fulfill the daily adequate intake (AI) with fewer capsules.     

Computer assisted education in health economics for medical advisers

A computer-based distance learning study aid on health economics (HELP) for medical advisers was developed from an existing paper course using a user-centred, prototyping approach. We illustrate and discuss this approach. The prototypes were iteratively tested and refined with potential users. The initial prototype was used for market research which included a survey of medical and pharmaceutical advisers. Results from the market research established the study aid's feasibility. The design of the study aid was guided by the market research and by application of an architectural analysis and design framework. HELP was designed in the form of an electronic, frame-based book with self-tests and navigational facilities that permit additional exploration. On-line journal articles were included for users' reference. The strategy adopted for delivery of the new course consists of presenting the computer study aid together with the paper course. The authoring shell that was developed is generically reusable for other courses with other teaching and learning strategies.     

Managed care: a call for strategic management in the dental office

Strategic management of any business will enable it to prosper in challenging times of change. Strategic planning is not characteristically found only in large corporations. Indeed, small business, such as solo private practices, can gain much from the process. The successful practice is one that is proactive rather than reactive; it has learned to become the beneficiary of change, rather than its victim.     

Insights Into Molecular Interaction of Antitumor Drug Mitoxantrone With Anionic Surfactant Sodium Dodecyl Sulfate at Different Temperatures

A study of the interaction of antitumor drug mitoxantrone with anionic surfactant sodium dodecyl sulfate (SDS) has been carried out by UV–Vis absorption spectroscopy at submicellar and micellar surfactant concentrations, pH 7.4 and 10, and over a temperature range of 293.15–323.15 K. The variation of the monomer drug absorbance as a function of SDS concentration indicates, at pH 7.4 and all investigated temperatures, two definite processes: process I in the submicellar range, attributed to the electrostatic interaction between mitoxantrone and SDS monomers; and process II in the micellar range, when the drug is incorporated into SDS micelles in monomer form. At pH 10, the results have indicated only the process II at micellar SDS concentrations. The monomer absorbance changes occurring as a result of the interactions between mitoxantrone and SDS were rationalized in terms of binding constant, micelle/water partition coefficient, and the corresponding thermodynamic parameters for binding and partitioning processes. Thermodynamic parameters indicate that at pH 7.4 both binding process of mitoxantrone to SDS and partition process of mitoxantrone between micellar and bulk aqueous phases are spontaneous and enthalpy controlled, while at pH 10 both processes are spontaneous and entropy controlled.     

In Vitro Photodynamic Activity of N‐Methylated and N‐Oxidised Tripyridyl Porphyrins with Long Alkyl Chains and Their Inhibitory Activity in Sphingolipid Metabolism

A series of N‐methylated and N‐oxidised tripyridyl porphyrins were synthesised, characterised, and their PDT activity was studied with six cell lines. All the tested porphyrins with a long alkyl chain, except one, were more efficient for PDT than an N‐methylated hydrophilic porphyrin and N‐oxidised porphyrin without the long alkyl chain. Generally, N‐methylated tripyridyl porphyrins were more active than those N‐oxidised, but IC₅₀ values for phototoxicity of two N‐oxides, named TOPyP3‐C₁₇H₃₃O and TOPyP3‐C₁₇H₃₅ , were still in the nanomolar concentration range for most of the tested cell lines. However, TOPyP3‐C₁₇H₃₅ did not show phototoxicity on human foreskin fibroblast cells. Two methylated amphiphilic porphyrins, named TMPyP3‐C₁₇H₃₃ and TMPyP4‐C₁₇H_{35 ,} showed significant dark toxicity, whereas none of the oxidopyridyl porphyrins were toxic without light activation. The selected photosensitisers were shown to be apoptosis inducers, and had inhibitory effects on the clonogenic growth of HCT116 and HeLa cells. All three N‐methylated amphiphilic porphyrins significantly reduced the migratory potential of HCT116 cells. Porphyrins TMPyP3‐C₁₇H₃₅ and TOPyP3‐C₁₇H₃₅ reduced the activity of acid ceramidase, whereas TOPyP3‐C₁₇H₃₃O had a significant inhibitory effect on sphingosine kinase 1 activity in HeLa cells. Compounds with this dual activity were shown to be the most promising photosensitisers, with potential to treat invasive cancers.