Producing shape-engineered alginate particles using viscoplastic fluids.

Non-spherical hydrogel particles are of fundamental interest and can find use in a variety of applications ranging from pharmaceuticals to biomedical to food. Here, we report a new method that leverages the yield stress property of viscoplastic fluids to synthesize shape-engineered alginate particles. By dripping an aqueous viscoplastic solution composed of sodium alginate and a yield-stress material into an ionic gelation bath, droplets are controllably deformed and crosslinked, producing a wide assortment of shapes. We find that by tuning the yield stress of the solution and the nozzle tip orientation, a range of shapes from symmetric and near-spherical, to asymmetric and anisotropic (e.g., egg-, rice grain-, arc-, ring-, snail shell-, tear-, and tadpole-like) can be produced. We explain our observations using scaling analysis of the forces exerted on the droplet at different stages of particle production. We show that the main factors that determine the degree of droplet deformation during bath entry and the final appearance of the alginate particles are the initial shape of the droplets, the timescales of the viscoplastic fluid relaxation versus the crosslinking reaction, and the physico-chemical properties of the yield-stress material.

Gelation under stress: impact of shear flow on the formation and mechanical properties of methylcellulose hydrogels.

We demonstrate that small unidirectional applied-stresses during temperature-induced gelation dramatically change the gel temperature and the resulting mechanical properties and structure of aqueous methylcellulose (MC), a material that forms a brittle gel with a fibrillar microstructure at elevated temperatures. Applied stress makes gelation more difficult, evidenced by an increased gelation temperature, and weakens mechanical properties of the hot gel, evidenced by a decreased elastic modulus and decreased apparent failure stress. In extreme cases, formation of a fully percolated polymer network is inhibited and a soft granular yield-stress fluid is formed. We quantify the effects of the applied stress using a filament-based mechanical model to relate the measured properties to the structural features of the fibril network. The dramatic changes in the gel temperature and hot gel properties give more design freedom to processing-dependent rheology, but could be detrimental to coating applications where gravitational stress during gelation is unavoidable.

Control of Drug-Excipient Particle Attributes with Droplet Microfluidic-based Extractive Solidification Enables Improved Powder Rheology.

PURPOSE: Industrial implementation of continuous oral solid dosage form manufacturing has been impeded by the poor powder flow properties of many active pharmaceutical ingredients (APIs). Microfluidic droplet-based particle synthesis is an emerging particle engineering technique that enables the production of neat or composite microparticles with precise control over key attributes that affect powder flowability, such as particle size distribution, particle morphology, composition, and the API's polymorphic form. However, the powder properties of these microparticles have not been well-studied due to the limited mass throughputs of available platforms. In this work, we produce spherical API and API-composite microparticles at high mass throughputs, enabling characterization and comparison of the bulk powder flow properties of these materials and greater understanding of how particle-scale attributes correlate with powder rheology. METHODS: A multi-channel emulsification device and an extractive droplet-based method are harnessed to synthesize spherical API and API-excipient particles of artemether. As-received API and API crystallized in the absence of droplet confinement are used as control cases. Particle attributes are characterized for each material and correlated with a comprehensive series of powder rheology tests. RESULTS: The droplet-based processed artemether particles are observed to be more flowable, less cohesive, and less compressible than conventionally synthesized artemether powder. Co-processing the API with polycaprolactone to produce composite microparticles reduces the friction of the powder on stainless steel, a common equipment material. CONCLUSIONS: Droplet-based extractive solidification is an attractive particle engineering technique for improving powder processing and may aid in the implementation of continuous solid dosage form manufacturing.

Development of eco-friendly, self-cleaning, antibacterial membrane for the elimination of chromium (VI) from tannery wastewater.

Hydrophobic polyvinylidene fluoride membrane was reformed to the hydrophilic membrane by incorporating synthesized titanium dioxide nanoparticles using Cajanus cajan seed extract. Spectroscopic and microscopic techniques characterized the composite membrane. The X-ray diffraction confirms the anatase phase of titanium dioxide nanoparticles of crystalline size 15.89 nm. The effect of titanium dioxide concentration on the thermodynamical and rheological properties on the polyvinylidene fluoride casting solution was investigated by the triangle phase diagram and viscosity measurement. It was concluded that titanium dioxide introduction caused thermodynamic enhancement, but the impact of rheological hinderance was higher at high concentrations. The polyvinylidene fluoride/titanium dioxide membranes were used as a bi-functional membrane to evaluate the rejection of chromium (VI) from wastewater; then, they were applied as sunlight-active catalyst membrane to reduce the concentrated chromium (VI) to chromium (III) by reduction. It was concluded that at 0.02 wt% of titanium dioxide, the maximum rejection of 85.59% and a% reduction of 92% was achieved with enhanced flux.

Embedded droplet printing in yield-stress fluids.

Microfluidic tools and techniques for manipulating fluid droplets have become core to many scientific and technological fields. Despite the plethora of existing approaches to fluidic manipulation, non-Newtonian fluid phenomena are rarely taken advantage of. Here we introduce embedded droplet printing-a system and methods for the generation, trapping, and processing of fluid droplets within yield-stress fluids, materials that exhibit extreme shear thinning. This technique allows for the manipulation of droplets under conditions that are simply unattainable with conventional microfluidic methods, namely the elimination of exterior influences including convection and solid boundaries. Because of this, we believe embedded droplet printing approaches an ideal for the experimentation, processing, or observation of many samples in an "absolutely quiescent" state, while also removing some troublesome aspects of microfluidics including the use of surfactants and the complexity of device manufacturing. We characterize a model material system to understand the process of droplet generation inside yield-stress fluids and develop a nascent set of archetypal operations that can be performed with embedded droplet printing. With these principles and tools, we demonstrate the benefits and versatility of our method, applying it toward the diverse applications of pharmaceutical crystallization, microbatch chemical reactions, and biological assays.

The Use of Prophylactic Somatostatin Therapy Following Pancreaticoduodenectomy: A Meta-analysis of Randomised Controlled Trials.

BACKGROUND: Prophylactic administration of somatostatin analogues (SA) to reduce the incidence of post-operative pancreatic fistula (POPF) remains contentious. This meta-analysis evaluated its impact on outcomes following pancreaticoduodenectomy (PD). METHODS: The EMBASE, MEDLINE and Cochrane databases were searched for randomised controlled trials (RCTs) investigating prophylactic SA following PD. Comparative effects were summarised as odds ratio and weighted mean difference based on an intention to treat. Quantitative pooling of the effect sizes was derived using the random-effects model. MAIN RESULTS: Twelve RCTs were included involving 1615 patients [SA-treated group (n = 820) and control group (n = 795)]. The SA used included somatostatin-14, pasireotide, vapreotide and octreotide. Pooling of the data showed no significant benefit of its use for the primary outcome measure of all grades of POPF, odds ratio (OR) 0.73 [95% confidence interval (CI), 0.51-1.05, p = 0.09] and clinically relevant POPF, OR 0.48 [95% CI, 0.22-1.06, p = 0.07]. There were no benefits in the secondary outcome measures of delayed gastric emptying, OR 0.98 [95% CI, 0.57-1.69, p = 0.94]; infected abdominal collections, OR 0.80 [95% CI, 0.44-1.43, p = 0.80]; reoperation rates, OR 1.24 [95% CI, 0.73-2.13, p = 0.42]; duration of hospital stay, - 0.23 [95% CI - .59 to 1.13, p = 0.74]; and mortality, 1.78 [95% CI, 0.94-3.39, p = 0.08]. CONCLUSION: SA did not improve the post-operative outcomes following PD, including reducing the incidence of POPF. The routine administration of SA cannot be recommended following PD.

Acid-Triggered, Acid-Generating, and Self-Amplifying Degradable Polymers.

We describe the 3-iodopropyl acetal moiety as a simple cleavable unit that undergoes acid catalyzed hydrolysis to liberate HI (p Ka ∼ -10) and acrolein stoichiometrically. Integrating this unit into linear and network polymers gives a class of macromolecules that undergo a new mechanism of degradation with an acid amplified, sigmoidal rate. This trigger-responsive self-amplified degradable polymer undergoes accelerated rate of degradation and agent release.

Dynamic Remodeling of Covalent Networks via Ring-Opening Metathesis Polymerization.

Reversible transformations in bulk polymers offer numerous possibilities for materials remodeling and reprocessing. While reversible systems based on dynamic covalent chemistry such as the Diels-Alder reaction and transesterification have been intensively studied to enable local bond dissociation and formation, reports regarding the reversion from bulk network polymers to monomers are rare. Herein, we report a reversibly polymerizable system based on ring-opening metathesis polymerization of cyclopentene derivatives in the bulk state. The network polymer is thermodynamically stable and mechanically robust at room temperature and readily depolymerizes at elevated temperatures to yield liquid monomers that are repolymerized to cross-linked polymers by simply cooling to room temperature. This reversible process was characterized by differential scanning calorimetry and rheological tests.

Design of yield-stress fluids: a rheology-to-structure inverse problem.

We present a paradigm for the design of yield-stress fluids, using six archetypal materials for demonstration. By applying concepts of engineering design, we outline a materials design paradigm that includes (i) morphological organization based on jammed versus networked microstructures, (ii) collected scaling laws for predictive design, (iii) low-dimensional descriptions of function-valued flow data, (iv) consideration of secondary properties including viscous behavior, and (v) a strategy for material concept synthesis based on the juxtaposition of microstructures. By explicitly specifying these design strategies, we seek to create an ontology and database for the engineering of yield-stress fluids. Our proposed design strategy increases the likelihood of finding an optimal material and prevents design fixation by considering multiple material classes to achieve a desired rheological performance. This flips the typical structure-to-rheology analysis to become the inverse: rheology-to-structure with multiple possible materials as solutions.

Effect of pure and oxidized cholesterol-rich diets on some biochemical parameters in rats.

The present study was undertaken to evaluate the peroxidative damage and hypercholesterolemia induced in male Wistar albino rats by diets enriched either with 1% oxidized cholesterol (OC) (containing 49.8% of cholesterol oxidation products) or pure cholesterol (PC). The damage caused by the OC diet was revealed by a significant rise in red blood cell hemolysis, increased tissue lipid peroxidation and elevated aspartate amino transferase activity as compared with control and PC diets. Liver glutathione-S-transferase activity was decreased by both OC (P < 0.01) and PC (P < 0.05) diets, but glutathione was observed to be decreased only by the OC diet. Plasma triacylglycerol and cholesterol were increased significantly with both the OC and PC diets. Liver cholesterol and triacylglycerol were increased significantly with the OC diet only. These results indicate that the oxidative damage caused by the OC diet is much more pronounced than that caused by the PC diet.

Environmental risk factors for rheumatoid arthritis.

In this review we examine the association between rheumatoid arthritis (RA) and exposure to silica and other environmental toxicants. We performed a series of meta-analyses of peer-reviewed studies, using 10 studies for silica, and 5 studies for other exposures published between 1986 and 2001. Before the meta-analyses, all studies were reviewed and evaluated for heterogeneity and publication bias. We detected a significant heterogeneity among studies on silica and calculated a combined estimator of relative risk (RR), using the random effect model. Most studies reported consistent elevation in the risk of RA with exposure to silica. The combined RR for silica exposure was 3.43 195% confidence interval (95% CI) 2.25-5.22] for all studies, and 4.45 (95% CI 2.24-8.86) for male cohorts. The combined RR for male farmers was 1.40 [95% CI 1.18-1.66] and was 1.29 [95% CI 0.84-1.97] for pesticide exposure. The combined RR for hair dressers was 1.52 [95% CI 1.04-2.20]. The findings of this study suggest a significant elevation in the risk of RA from exposure to silica. Further studies assessing the dose-response effect would greatly aid in determining whether the observed association is causal.

Effect of coffee oil and its unsaponifiable fraction on plasma cholesterol level in female rats.

The present study was conducted to identify the cholesterol-raising factor in coffee oil besides the other two well-known diterpenes, cafestol and kahweol. Female rats fed coffee oil for 4 weeks showed significantly higher level of plasma cholesterol (P < 0.01) and triacylglycerols (P < 0.01). Feeding unsaponifiable lipids of coffee oil caused significant decrease in plasma cholesterol; however, increase in triacylglycerol was observed. Rats given beta-sitosterol showed increase in plasma triacylglecerol and decrease in cholesterol levels, an effect similar to that observed with unsaponifiable lipids. beta-sitosterol is the major constituent of unsaponifiable lipids of the coffee oil. These results show that cafestol and kahweol diterpene alcohols are not the only cholesterol-raising factors in coffee oil.

Nucleic acid-8-methoxypsoralen crosslinks bind monoclonal anti-Z-DNA antibody.

Native calf thymus DNA and poly(dA-dT).poly(dA-dT) were photo-adducted with 8-methoxypsoralen and characterized by thermal denaturation (Tm) and hydroxyapatite column chromatography. The data demonstrated the formation of interstrand photo-crosslinks. It has been shown by competition ELISA and band shift assays that crosslinked species of DNA-8-MOP and poly(dA-dT)-8-MOP photoadducts recognize previously defined monoclonal anti-Z-DNA antibody (Z22). The results indicate the possible presence of Z- or Z-like epitopes on nucleic acid-8-MOP crosslinks as Z22 antibody does not recognize other nucleic acid conformations. These studies also point out that conformational changes in DNA arising from the photo-addition could induce antibodies to DNA or could cause autoimmune disease.

Antigenicity of poly(dA-dT) . poly(dA-dT) photocrosslinked with 8-methoxypsoralen.

We report the formation of photocrosslink (diad-duct) between duplex poly(dA-dT) and 8-methoxypsoralen inferred on the basis of UV and fluorescence characteristics, Tm, nuclease S1 digestibility, and hydroxyapatite column chromatography. The photocrosslink was highly immunogenic inducing high titer antibodies in goat. The affinity constant of antigen-antibody interaction quantitated by precipitin titration was found to be 2.71 x 10(9) M-1, calculated by Langmuir isotherm plot. These antibodies were highly specific showing recognition of almost exclusively of nucleic acid-furocoumarin photoadducts and could be used as a probe to detect and quantitate DNA modified with furocoumarins in health and disease. Antibodies against poly(dA-dT)-furocoumarin photocrosslink might be a better probe because of repeated A-T sequences on the immunogen.

Antigen binding specificity of antibodies against 8-methoxypsoralen photoadducted DNA.

The photoadduct between native DNA and 8-methoxypsoralen was characterized on the basis of UV and fluorescence characteristics, Tm, nuclease S 1 digestibility and hydroxyapatite column chromatography. Approximately 80% of photoadduct has at least one diadduct (crosslink) per DNA molecule and only thymine was modified to the extent of 69%. The photo-crosslink was highly immunogenic inducing antibodies having apparent association constant of 1.3 x 10(-9)M. The immune IgG was highly specific towards nucleic acid-furocoumarin crosslink site without appreciable recognition of B-conformation or nucleic acid bases. The antibodies could be used as probe to detect and quantitate nucleic acid modified with furocoumarins in health and disease.

Native DNA fragments photocrosslinked to psoralen binds to anti-B and anti-Z DNA antibodies.

Calf thymus DNA fragments of varying size (100-600 bp) were covalently linked to psoralen in the presence of 365 nm UV light. The crosslinked species were separated from the monoadducts by hydroxyapatite column chromatography. The DNA-psoralen crosslink showed binding with naturally occurring anti-DNA autoantibodies. This was substantiated by the recognition of affinity purified IgG by DNA-psoralen crosslinks of varying DNA size. The photo-crosslinks exhibited considerable recognition of both monoclonal and polyclonal anti-Z-DNA antibodies in inhibition ELISA and band shift assay.

Enzyme activity of glucose-6-phosphate dehydrogenase-deficient Malaysian neonates during the first 10 days of life.

OBJECTIVE: The objective of this study was to determine the degree of severity of enzyme deficiency in glucose-6-phosphate dehydrogenase (G6PD)-deficient Malaysian neonates as part of an effort to identify risk factors associated with severe hyperbilirubinaemia in G6PD-deficient infants. METHODOLOGY: During this study, enzyme activity was measured in 53/59 (89.8%) hospital-diagnosed G6PD-deficient neonates (34 Malays, 12 Chinese, and seven other ethnic groups) born consecutively in the Kuala Lumpur Maternity Hospital. All neonates, except one, were males. RESULTS: The mean level of enzyme activity of the 52 males G6PD-deficient neonates (0.47 iu/g Hb, 95% confidence intervals: 0.37, 0.57) was less than 10% of that of normal Malaysian male neonates. The enzyme activity of the only female G6PD-deficient infant, at 1.11 iu/g Hb, was 12.5% of the mean G6PD enzyme activity of normal females. CONCLUSION: Our results showed that G6PD deficiency in Malaysian neonates predominantly affects males and is usually severe.

Autoantibodies-like antigen binding characteristics of induced antibodies against polylysine-polyglutamate complex.

Rabbits immunized with polylysine-polyglutamate complex induced high titer antibodies. The immune IgG exhibited high degree of specificity towards the immunogen. In a competition assay, nDNA, heat denatured DNA and total buffalo thymus RNA were inhibitory. An appreciable binding with polyglutamate, poly(rG).poly(dC) poly(dG).poly(dC), cardiolipin, poly(dA-dU). Poly(dA-dU) and Z- or Z-like conformations demonstrates the polyspecificity of induced antibodies. The immunological specificity of induced antibodies was comparable to autoantibodies derived from SLE. The results might be of some help in understanding the etiology of autoimmune process.