The effect of black barberry hydroalcoholic extract on immune mediators in patients with active rheumatoid arthritis: A randomized, double-blind, controlled clinical trial.

Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. In this trial, we aimed to investigate the Immunomodulatory effect of hydroalcoholic extract of black barberry on immune mediators in patients with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled clinical trial, 80 women with active RA were randomly assigned into two groups of two capsules, each containing 1,000 mg black barberry extract (n = 40) or maltodextrin placebo (n = 40) daily for 12 weeks. Demographic indices, physical activity, dietary intake, and disease activity were investigated using suitable questionnaires. Concentration of cytokines IL-2, IL-4, IL-10, and IL-17 in blood sample were measured using PBMC method. Statistical analysis was performed using SPSS (version 22). At baseline, there were no differences between the two groups in terms of demographic indices, physical activity, and dietary intake (p > .05). Black barberry supplementation reduced the severity of RA. It showed no significant effect on IL-2 and IL-4 cytokines (p > .05). IL-17 levels decreased significantly after the intervention within the black barberry group, while IL-10 had a significant increase in this group (p < .05). Barberry extract may reduce inflammatory and increase anti-inflammatory cytokines in RA, and stimulates the immune response by increasing Th2 production.

The effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active rheumatoid arthritis: A randomized, double-blind, placebo-controlled clinical trial.

Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Our study aimed to determine the effect of saffron supplement on clinical outcomes and metabolic profiles in patients with active RA. In this randomized, double-blind, placebo-controlled trial, 66 women older than 18 years old received 100 mg/day either saffron supplement in the intervention group (n = 33) or matched placebo in the placebo group (n = 33) for a period of 12 weeks. Sixty-one patients (30 in the control and 31 in the saffron group) remained for the final analysis. No adverse effects were reported by the patients. Saffron supplementation significantly decreased the number of tender (-1.38 ± 1.66 vs. 0.10 ± 0.40, p < .001) and swollen (-2.12 ± 2.34 vs. 0.63 ± 2.79, p < .001) joints, pain intensity based on visual analogue scale (-18.36 ± 15.07 vs. -2.33 ± 5.04), p < .001), and disease activity score (DAS28) (-0.75 ± 0.67 vs. 0.26 ± 0.77, p < .001) at the end of intervention between the two groups and in saffron group compared with baseline values. Physician Global Assessment (p = .002) and erythrocyte sedimentation rate were significantly improved after intervention (24.06 ± 12.66 vs. 32.00 ± 14.75, p = 0.028). High-sensitivity C-reactive protein reduced at the end of the intervention in the saffron group compared with baseline values (12.00 ± 7.40 vs. 8.82 ± 7.930, p = .004). Tumor necrosis factor alpha, interferon gamma, and malondialdehyde were decreased, and total antioxidant capacity were increased, but their differences between the two groups were not significant (p > .05). According to the results, saffron supplements could positively and significantly improve clinical outcomes in RA patients.

Effects of Plasma Proteins on the Transport and Surface Characteristics of Polysulfone/Polyethersulfone and Asymmetric Cellulose Triacetate High Flux Dialyzers.

Blood-membrane interactions can have a large impact on the performance of hemodialysis membranes, particularly for high flux membranes in which the membrane itself provides very low resistance to solute transport. The objective of this study was to examine the effects of exposure to serum on the solute clearance and convective sieving characteristics of high flux polysulfone (Optiflux F250NR), polyethersulfone (ELISIO-25H), and asymmetric cellulose triacetate (SOLACEA-25H) hemodialyzers using both vitamin B12 and a range of polydisperse dextrans. Zeta potential measurements were used to obtain additional insights into the changes in membrane surface properties. Exposure to serum in a simulated dialysis session caused a significant reduction in both solute clearance and sieving coefficients for the polysulfone/polyethersulfone dialyzers, particularly for the larger molecular weight solutes. In contrast, the transport characteristics of the asymmetric cellulose triacetate dialyzers were almost unchanged after exposure to serum. The zeta potential of the cellulose triacetate membrane became slightly more negative after exposure to serum, consistent with an adsorbed protein layer composed largely of albumin. The net result is that the asymmetric cellulose triacetate dialyzer had dramatically higher clearance of the larger dextrans after exposure to serum, with the clearance and sieving coefficient for a 10 kDa molecular weight dextran being more than an order of magnitude greater than that of the polysulfone/polyethersulfone membranes. These results provide important insights into the expected clinical performance of these high flux dialyzers.

Transport Characteristics of Asymmetric Cellulose Triacetate Hemodialysis Membranes.

AIMS: The objective of this study was to compare the transport characteristics of highly asymmetric cellulose triacetate (ATA™) membranes with that of both symmetric cellulose triacetate and asymmetric polysulfone membranes. METHODS: Data were obtained for solute clearance and sieving coefficients of vitamin B12 and a range of polydisperse dextrans using ATA™ SOLACEA-25H and Optiflux F250NR polysulfone dialyzers. Results for these, and the CT190 symmetric cellulose triacetate dialyzer, were analyzed using available membrane transport models. RESULTS: The ATA™ had the largest solute clearance, although the homogeneous CT190 dialyzer had the highest sieving coefficients. These differences were a direct result of the differences in the underlying membrane morphology, with the asymmetric ATA™ membrane providing much higher diffusive transport rates (and thus higher solute clearance). CONCLUSIONS: These results demonstrate the importance of membrane morphology on dialyzer transport and provide important insights into the effective clinical performance observed with the highly asymmetric ATA™ dialyzers.

Efficiency of ultrafiltration/diafiltration in removing organic and elemental process equipment related leachables from biological therapeutics.

In the production of biological therapeutics such as monoclonal antibodies (mAbs), ultrafiltration and diafiltration (UF/DF) are widely regarded as effective downstream processing steps capable of removing process equipment related leachables (PERLs) introduced upstream of the UF/DF step. However, clearance data available in the literature are limited to species with low partition coefficients (log P) such as buffer ions, hydrophilic organic compounds, and some metal ions. Additional data for a wide range of PERLs including hydrophobic compounds and elemental impurities are needed to establish meaningful, comprehensive safety risk assessments. Herein, we report the results from studies investigating the clearance of seven different organic PERLs representing a wide range of characteristics (i.e., log P (-0.3 to 18)), and four model elements with different chemical properties spiked into a mAb formulation at 10 ppm and analyzed during clearance using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-photodiode-array-mass spectrometry (LC-PDA-MS), and inductively coupled plasma mass spectrometry (ICP-MS). The clearance data showed ideal clearance and sieving of spiked organic PERLs with log P < 4, partial clearance of PERLs with 4 < log P < 9, and poor clearance of highly hydrophobic PERLs (log P > 9) after nine diafiltration volumes (DVs). Supplemental clearance studies on seven additional PERLs present at much lower concentration levels (0.1-1.5 ppm) in the mAb formulation upstream of UF/DF and three PERLs associated with the tangential flow filtration (TFF) equipment also demonstrated the similar correlations between log P and % clearance. For model elements, the findings suggest that UF/DF in general provides ideal clearance for elements. Evidence showed that the UF/DF process does not only help mitigate leachables risk from PERLs introduced upstream of UF/DF, but also from the TFF operation itself as all three TFF-related PERLs were effectively cleared. Overall, the UF/DF clearance presented in this work demonstrated whereas highly hydrophobic PERLs and elements that exist as charged species, particularly transition metal ions, may not be as effectively cleared and thus warrant further risk assessment; hydrophilic and some hydrophobic PERLs (log P < 4) are indeed well-cleared and thus present a lower overall safety risk.

Effect of electrostatic interactions on the ultrafiltration behavior of charged bacterial capsular polysaccharides.

Charged polysaccharides are used in the food industry, as cosmetics, and as vaccines. The viscosity, thermodynamics, and hydrodynamic properties of these charged polysaccharides are known to be strongly dependent on the solution ionic strength because of both inter- and intramolecular electrostatic interactions. The goal of this work was to quantitatively describe the effect of these electrostatic interactions on the ultrafiltration behavior of several charged capsular polysaccharides obtained from Streptococcus pneumoniae and used in the production of Pneumococcus vaccines. Ultrafiltration data were obtained using various Biomax™ polyethersulfone membranes with different nominal molecular weight cutoffs. Polysaccharide transmission decreased with decreasing ionic strength primarily because of the expansion of the charged polysaccharide associated with intramolecular electrostatic repulsion. Data were in good agreement with a simple theoretical model based on solute partitioning in porous membranes, with the effective size of the different polysaccharide serotypes evaluated using size exclusion chromatography at the same ionic conditions. These results provide fundamental insights and practical guidelines for exploiting the effects of electrostatic interactions during the ultrafiltration of charged polysaccharides. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1531-1538, 2016.

Effects of solution conditions on characteristics and size exclusion chromatography of pneumococcal polysaccharides and conjugate vaccines.

Molecular properties of bacterial polysaccharides and protein-polysaccharide conjugates play an important role in the efficiency and immunogenicity of the final vaccine product. Size exclusion chromatography (SEC) is commonly used to analyze and characterize biopolymers, including capsular polysaccharides. The objective of this work was to determine the effects of solution ionic strength and pH on the SEC retention of several capsular polysaccharides from S. pneumoniae bacteria in their native and conjugated forms. The retention time of the charged polysaccharides increased with increasing ionic strength and decreasing pH due to compaction of the polysaccharides associated with a reduction in the intramolecular electrostatic interactions. The calculated radius of gyration was in good agreement with model calculations based on the worm-like chain model accounting for the increase in chain stiffness and excluded volume of the charged polysaccharide at low ionic strength. These results provide important insights into the effects of solution ionic strength on physical properties and SEC behavior of capsular polysaccharides and their corresponding conjugates.