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Rheology of concentrated suspensions of deformable elastic particles such as human erythrocytes.

New models for the viscosity of concentrated suspensions of deformable elastic particles are developed using the differential effective medium approach (DEMA). The models are capable of describing the rheological behavior of un-aggregated suspensions of human red blood cells (RBCs). With the increase in shear rate, a shear-thinning behavior is predicted similar to that observed in the case of un-aggregated suspensions of RBCs. A decrease in relative viscosity and an enhancement of shear-thinning behavior is predicted when either the particle rigidity (elastic modulus) is decreased or the continuous medium viscosity is increased. These predictions are similar to those observed in suspensions of human RBCs. The proposed models are evaluated using experimental data on normal and hardened human RBC suspensions in protein-free saline.

Blood Flow Velocity↗

Thin-layer chromatography-matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry using particle suspension matrices.

Particle suspension matrices have been successfully utilized for the analysis of tetracycline antibiotics by thin-layer chromatography-matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry (TLC-MALDI-TOF-MS). Particles of different materials and sizes have been investigated (Co-UFP, TiN, TiO2, Graphite and Silicon) by applying particle suspensions to eluted TLC plates. Mass spectra and mass chromatograms have been recorded directly from the TLC plates. Strong cationization by sodium and potassium was obtained in the positive ion mode, with [M+Na-NH3]+ ions being the predominant signals. The TLC-MALDI mass spectra recorded from graphite suspensions showed the lowest background noise and the highest peak intensities from the range of suspension matrices studied. The mass accuracy from graphite films was improved by adding the peptide Phe-Phe to the graphite suspensions. This allowed internal recalibration of the TLC-MALDI mass spectra acquired during a run. One major potential advantage of TLC-MALDI-TOF-MS has been demonstrated in the analysis of chlortetracycline and tetracycline in a mixture of oxytetracycline, chlortetracycline, tetracycline and minocycline. Examination of the TLC plate prior to MALDI analysis showed only an unresolved spot for chlortetracycline and tetracycline. However by investigation of the MALDI mass spectra and plotting of single ion chromatograms separate peaks for chlortetracycline and tetracycline could be obtained.

Anti-Bacterial Agents↗

Consolidation behavior in sedimentation of TiO(2) suspensions in the presence of electrolytes.

The consolidation of TiO(2) suspensions (anatase and rutile) due to gravity sedimentation in the presence of electrolytes has been investigated as a function of pH. Sodium and barium nitrate were used as flocculating electrolytes. The particle interaction was related to the zeta potential and the thickness of the electrical double layer, kappa(-1), by utilizing the repulsive barrier in the classical DLVO theory. The stability of the suspensions was represented as the average final solids content of the sediment cake, phi(fin). The batch sedimentation process was followed by scanning the sample cell with X-rays, from which the solids content and the particle size were calculated. Generally, dense sediments, with phi(fin) up to volume fractions of 0.5, were found for stable suspensions. Flocculated suspensions produced sediments with low phi(fin). The phi(fin) was observed to increase linearly with increasing repulsive barrier. However, at pH values only slightly higher than the isoelectric point (pH(iep)) the phi(fin) remained low until it returned to linearity at a pH much higher than pH(iep). This was attributed to the stronger affinity of sodium than of nitrate for the particle surface, which may be explained by the higher negative hydration energy of sodium. The stronger affinity of sodium was also shown as unsymmetrical distribution of phi(fin) around pH(iep), with stronger flocculation at pH>pH(iep). The interpretation of phi(fin) as a function of the repulsive barrier (or kappa(-1)) also made it possible to distinguish between the adsorption mechanisms of ions from solution. Addition of electrolyte at a fixed low and high pH (surface positively and negatively charged, respectively) clearly showed the specificity in adsorption and consequent flocculation of the barium ion from the indifferent nitrate. Sodium was, however, again observed to flocculate the TiO(2) suspensions slightly more strongly than nitrate.

Journal Article↗

Organ culture of human lymphoid tissue. II. Marked differences in cytokine production and proliferation between slice and suspension cultures of human spleen.

Recently, we have established a method for the culture of human spleen slices in vitro. The procedure allows thin slices (200-350 microns) of human spleen to be cultured for up to 7 days. Using this method, we have previously established that unstimulated spleen slices spontaneously synthesize and secrete considerably higher levels of immunoglobulin than suspension cultures of the same tissue run in parallel. In this study, we report that there are also marked differences in the cytokine secretion profile between slices and suspensions and in their proliferative response. In brief, control and PHA-stimulated spleen slices secrete high levels of IL-1 beta, IL-6, IL-8 and IL-11 while the levels found in suspension supernatants are appreciably lower. By way of contrast, high levels of IL-2, IL-4, IL-10 and TNF alpha are found in suspension culture supernatants following PHA stimulation while the response in slice cultures is extremely low. These differences are also reflected in the results obtained at the cellular (intracellular cytokine) level. Additional studies reveal that spontaneous immunoglobulin production observed in spleen slices can be inhibited by the addition of specific antibodies to IL-1 beta, IL-6 and TNF alpha and that the bulk of the IL-6 and IL-1 beta detected in culture supernatants represents de novo synthesis. Finally, the background and mitogen-stimulated proliferative response of tissue slices is meagre compared with that observed in spleen suspensions suggesting that proliferation in the former is held under strict control. Collectively, we believe that the tissue slice procedure described provides us with a system for studying integrated events in lymphoid tissues in vitro and evaluating immunomodulatory substances of potential clinical importance.

Adolescent↗

Modified Pereyra bladder neck suspension: 10-year mean followup using outcomes analysis in 125 patients.

PURPOSE: We attempt to determine the long-term success rate of the modified Pereyra bladder neck suspension, identify preoperative factors predictive of long-term outcome, and investigate the influence of method and length of followup on reported continence status after modified Pereyra bladder neck suspension. MATERIALS AND METHODS: The charts of 177 patients who underwent modified Pereyra bladder neck suspension at our institution more than 5 years ago were reviewed. An attempt was made to contact all patients either by mail or telephone to complete a patient survey questionnaire. RESULTS: Of 177 patients 125 (71%) completed the patient survey with a mean followup of 9.8 years. At survey followup 20% of the patients reported no incontinence of any type and 51% reported stress urinary incontinence with or without urge incontinence. Of the patients 71% reported significant improvement in the incontinence and 73% were satisfied with the results of the procedure. No accurate preoperative predictors of long-term outcome were identified. The method and length of followup had significant impact on reported continence status after modified Pereyra bladder neck suspension. CONCLUSIONS: This long-term study using outcomes analysis reveals a high rate of recurrent stress incontinence after modified Pereyra bladder neck suspension. However, most patients maintain significant subjective improvement and remain satisfied with the results of the operation.

Female↗

Needle suspension procedures for female incontinence.

In the past, needle suspensions were considered a viable option to treat female stress urinary incontinence. There have been many modifications since the first needle suspension over 40 years ago. Despite these modifications, the long-term outcome data does not support the efficacy of needle suspension procedures, with only a 67% cure/dry rate at > 48 months. The long-term results are much more efficacious with the sling procedure (83%), as well as with retropubic suspensions (84%). Needle suspensions have historical significance, but because of the poor long-term results, they currently have a limited role in the management of stress urinary incontinence.

Female↗

In-use testing of extemporaneously prepared suspensions of second generation non-nucleoside reversed transcriptase inhibitors in support of phase I clinical studies.

DPC 961 and 963 are two of a series of prospective second generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) being considered for the treatment of HIV infections. The 'powder in a bottle' approach was used for drug administration for Phase I clinical studies. This new approach consists of compounding the active drug as a suspension or solution at the clinical site immediately before dosing. Prior to clinical use, studies were conducted to determine the compatibility of the drugs with the suspending agent, the recovery of the drugs using the administration procedure and the dissolution profile of the suspensions. The stability of the DPC 961 and 963 in the dosing formulation was followed over a 24-h period using a stability indicating HPLC method. In addition, the dissolution profiles of the suspensions were established for future comparison with solid dosage forms. Although the two drugs have very similar chemical structures, they clearly exhibited different behaviors in liquid/liquid extraction and dissolution experiments. These differences could be related to the physical characteristics of the powders, such as particle size and surface area. The results of the in-use testing of the suspension showed adequate recovery of the drugs from the bottle at two drug levels. The stability of DPC 961 and 963 in the suspending agent was sufficient for constitution and administration of the suspensions at the clinical site.

Anti-HIV Agents↗

Mechanical properties of bovine aortic endothelial cells in suspension studied by ultrasonic interferometry.

OBJECTIVE: Cell adhesion phenomenon has been extensively studied in the last decade and was shown to be mediated by specialized molecules and driven by physical forces. Cohesion of the vessel wall cells is also dependent on adhesion molecules but less is known about the physical forces involved. To investigate endothelial cell/endothelial cell interaction from a mechanical point of view, we have used an ultrasonic interferometry device, named EchoCell, which has been previously designed to study red blood cell-red bood cell (RBC-RBC) interaction. METHODS: Bovine aortic endothelial (BAE) cells were cultured, detached, then suspended in buffer and their mechanical and geometrical properties studied with the EchoCell system. The ultrasonic apparatus measures both the accumulation rate of cells in suspension on a solid plate and the acoustical impedances of the suspension and the sediment. RESULTS: In suspension, BAE exhibited, in our experimental conditions (3x10(6) cells per ml), a spherical size evaluated by calculation at a mean radius of 7+/-2 microm. Moreover, no BAE aggregation occurred at the concentrations used. The acoustical impedance of the BAE suspensions calculated from all the samples studied, in the cell concentration range from 1.5x10(6) to 6x10(6) cells per ml, was 1.52x10(6) Rayl (kg m(-2) s(-1)). Furthermore, the acoustical impedance of the cell sediment was found to be independent on the initial cell suspension concentration and equal to 1.63x10(6) Rayl (kg m(-2) s(-1)). Estimation of the volume fraction of BAE inside the sediment allows to evaluate the ultrasonic velocity and the elastic bulk modulus of cells. CONCLUSION: The ultrasonic interferometry method appears particularly interesting to study geometrical and mechanical (acoustical impedance, sound velocity, elastic bulk modulus) properties of BAE cells.

Animals↗

[188Re]Rhenium sulfide suspension: a potential radiopharmaceutical for tumor treatment following intra-tumor injection.

Intralesional therapy has been shown to be an effective treatment for tumors. In this study, the suitability of [188Re]rhenium sulfide suspension for tumor treatment following intra-tumor injection was evaluated. The [188Re]rhenium sulfide suspension was radiolabeled with 188Re with a radiochemical yield of more than 96%. In vitro stability studies revealed that more than 99% of the 188Re remained in sulfide form over a 3-day period. After ultrasonication for 5 or 10 min, the main particle size was 1-5 microm. Two [188Re]rhenium sulfide suspensions ultrasonicated for 5 and 10 min, respectively, were injected into separate group of tumor-bearing mice that were killed after specified times to compare the retention of 188Re in tumors and the leakage to different organs by periods and organs removed to gamma counting. The mean retention percentages of 188Re in tumors injected with suspension ultrasonicated for 5 (or 10) min were as follows: 1 h, 90.5 +/- 7.7% (83.1 +/- 13.7%); 24 h, 92.2 +/- 8.6% (83.9 +/- 9.8%); 48 h, 88.3 +/- 10.9% (80.2 +/- 3.8%); and 72 h, 91.5 +/- 7.6% (78.8 +/- 3.0%). Tumor-inhibiting ratio was 96.5%. These results demonstrated that [188Re]rhenium sulfide suspension is an effective radiopharmaceutical for tumor treatment by intralesional therapy.

Animals↗

Imaging of anisotropic cellulose suspensions using environmental scanning electron microscopy.

The effect of concentration on anisotropic phase behavior of acid-hydrolyzed cellulose suspensions has been examined using conventional polarizing microscopy and the novel technique of environmental scanning electron microscopy (ESEM). Microcrystalline cellulose dispersed in water formed biphasic suspensions in a narrow concentration range, 4-12 wt % for a suspension pH of 4, where the upper and lower phases were isotropic and anisotropic (chiral nematic), respectively. It is known from previous work that within the biphasic regime total suspension concentration affects only the volume fractions of the two phases, not phase concentration or interfacial packing. As the total suspension concentration surpassed the upper critical limit (c), however, a single anisotropic phase of increasing concentration was observed. It was evident from polarizing microscopy that the chiral nematic pitch of the anisotropic phase decreased with increasing concentration, which has been attributed to a reduction in the electrostatic double layer thickness of the individual rods, thus increasing intermolecular interactions. Chiral nematic textures were also visible using ESEM. This technique has the advantage of studying individual rod orientation within the liquid crystalline phase as it permits the high resolution of electron microscopy to be applied to hydrated samples in their natural state. To our knowledge this is the first time such lyotropic systems have been observed using electron microscopy.

Anisotropy↗

Scale-up of breast cancer stem cell aggregate cultures to suspension bioreactors.

It has been hypothesized that breast tumor formation results from the activity of a scarce population of cells known as Breast Cancer Stem Cells (BrCSCs) and that the development of effective breast cancer therapies may therefore ultimately rely upon the ability to effectively target these cells for eradication. The scarcity of BrCSCs in vivo severely compromises research on these populations, as analyses are restricted to those requiring small cell numbers, and has become a major impediment to the development of therapeutic strategies against breast cancer. Through the culture of murine tissue aggregates containing a population of BrCSCs, this study demonstrates the ability of propagating this scarce population in a controlled and reproducible manner, within suspension bioreactors. A rigorous theoretical framework has been developed in order to understand and characterize the implications of oxygen mass transfer within aggregates upon scale-up and thereby provide a foundation for the scale-up of aggregate cultures. A two-factor, two-level factorial experimental design was also performed in order to assess the effects of inoculation density and hydrodynamic shear upon cell yield. We discovered that the culture of the murine aggregates in a relatively low shear environment (tau(max) = 0.20 Pa) and inoculated at 3.50 x 10(4) cells/mL resulted in the best yields for the range of conditions investigated in suspension bioreactors. A detailed study on the oxygen uptake kinetics of the aggregates also revealed that the uptake rates were not significantly affected by mass transfer limitations, as uptake rates of aggregate cultures were found to be comparable to those observed in single cell cultures. Cells propagated in a process controlled 500 mL suspension bioreactor resulted in growth kinetics that were comparable to those observed in 125 mL bioreactors. Doubling times in the 500 mL vessel were found to be 23.9 h and attained a maximum cell density of 1.20 x 10(6) cells/mL. After enumerating the number of BrCSCs, this resulted in an approximately 20-fold increase in BrCSC numbers in batch suspension cultures. With greater attention being applied to BrCSCs, their propagation in suspension bioreactors makes available experimental avenues that are not currently accessible and may thereby enable the development of more effective therapeutic drugs for the treatment of breast cancer.

Animals↗

Potential of enzymatic kinetic resolution using solid substrates suspension: improved yield, productivity, substrate concentration, and recovery

In the literature the enzymatic kinetic resolution of a suspension of a solid substrate has largely been treated as a conventional kinetic resolution of a fully dissolved substrate. In this paper it is shown that this type of kinetic resolution is different in several important aspects. Quantitative models are developed for two types of such suspension processes. These models are used to compare the merits of these processes with the conventional kinetic resolution process where fully dissolved substrate is used. In the suspension processes the liquid phase concentration of substrate enantiomer that should be converted can be kept close to the maximum value, i.e., the solubility, when process conditions are properly chosen, whereas in a conventional process this concentration gradually decreases. Calculations show that this leads to a productivity that is about 6-fold higher in the suspension processes. Also, for enzymes with a low enantioselectivity, a severalfold increase in yield of remaining enantiopure substrate is predicted compared to the conventional kinetic resolution of dissolved enantiomers. Other potential advantages of using suspension reactions are that the initial substrate concentration may be higher (up to 25% (w/w)) and that the desired remaining substrate may be recovered by simply filtering off the solid crystals. Experimental evidence that these merits can be exploited is only partly given, using the few available examples from the literature.

Journal Article↗

Antibacterial activity of fullerene water suspensions: effects of preparation method and particle size.

Fullerene research in biological systems has been hindered by the compound's relative insolubility in water. However, C60 molecules can be made to aggregate, forming stable fullerene water suspensions (FWS) whose properties differ from those of bulk solid C60. There are many different protocols for making FWS. This paper explores four of these methods and establishes the antibacterial activity of each resulting suspension, including a suspension made without intermediary solvents. The aggregates in each polydisperse suspension were separated by size using differential centrifugation and tested for antibacterial activity using Bacillus subtilis as a test organism. All suspensions exhibited relatively strong antibacterial activity. Fractions containing smaller aggregates had greater antibacterial activity, although the increase in toxicity was disproportionately higher than the associated increase in putative surface area. This suggests the need for improved understanding of the behavior of FWS towards organisms and in the environment to determine how C60 can be safely used and disposed.

Anti-Bacterial Agents↗

Heat-induced phenomena in soy protein suspensions. Rheometric data and theoretical interpretation.

Heat-induced aggregation of soy proteins in aqueous suspensions was studied through cone and plate rheometry for two different heating conditions. The rheometric data obtained covered the temperature range from 20 degrees C (stable colloidal suspension) to approximately 90 degrees C (onset of network formation). Calorimetric data for the soy protein samples were also obtained to evaluate the degree of protein denaturation in the rheometric cell. Heat-induced transitions in soy globulins, such as dissociation, denaturation, and aggregation, were analyzed in relation to the rheological response of the suspension. The viscosity of the stable colloidal suspension satisfies the Cross model. A viscosity equation for the aggregating suspension was also derived by considering the fractal structure of the particle clusters and the Brownian aggregation mechanism. This equation is suitable to describe the experimental viscosity data.

Calorimetry↗

Chain photoreduction of CCl3F in TiO2 suspensions: enhancement induced by O2.

Trichlorofluoromethane (CFC 11) was photoreduced in aqueous suspensions of TiO2 particles containing HCO2- ions and air. Dissolved O2 inhibited the reaction during an induction period that preceded the rapid formation of chloride ions. Reaction rates were higher in systems containing O2 as compared to analogous reactions that occurred in anaerobic suspensions. High photonic efficiencies of Cl- formation (> or =15) were achieved using suspensions with pH > or = 5. As was the case for studies with air-free suspensions, reactions are best described using a photoinitiated chain mechanism that produced CHCl2F and Cl- during the propagation steps. The enhanced yields obtained in the presence of air are attributed to the removal by O2 of electrons trapped in the oxide, which are converted first into H2O2 and then into reducing radicals that participate in the chain process. Enhanced yields of Freon photoreduction were also observed during illumination of air-free suspensions containing hydrogen peroxide, which were interpreted using a similar mechanism.

Journal Article↗

Gas-solid coexistence in highly charged colloidal suspensions.

Aqueous suspensions of highly charged polystyrene particles with different volume fractions have been investigated for structural ordering and phase behavior using static light scattering (SLS) and confocal laser scanning microscope (CLSM). Under deionized conditions, suspensions of high-charge-density colloidal particles remained disordered whereas suspensions of relatively low charge density showed crystallization by exhibiting iridescence for the visible light. Though for the unaided eye crystallized suspensions appeared homogeneous, SLS measurements and CLSM observations have revealed their inhomogeneous nature in the form of the coexistence of voids with dense ordered regions. CLSM investigations on disordered suspensions showed their inhomogeneous nature in the form coexistence of voids with dense disordered (amorphous) regions. Our studies on highly charged colloids confirm the occurrence of gas-solid transition and are in accordance with predictions of Monte Carlo simulations using a pair-potential having a long-range attractive term [Mohanty, P. S.; Tata, B. V. R. J. Colloid Interface Sci. 2003, 264, 101]. On the basis of our experimental and simulation results, we argue that the reported reentrant disordered state [Yamanaka et al. Phys. Rev. Lett. 1998, 80, 5806 and Toyotama et al. Langmuir 2003, 19, 3236] in charged colloids observed at high charge densities is a gas-solid coexistence state.

Journal Article↗

Primary electroviscous effect in a dilute suspension of charged mercury drops.

The standard theory of the primary electroviscous effect in a dilute suspension of charged spherical rigid particles in an electrolyte solution (Watterson, I. G.; White, L. R. J. Chem. Soc., Faraday Trans. 2 1981, 77, 1115) is extended to cover the case of a dilute suspension of charged mercury drops of viscosity eta(d). A general expression for the effective viscosity or the electroviscous coefficient p of the suspension is derived. This expression tends to that for the case of rigid particles in the limit of eta(d) --> infinity. We also derive an approximate analytical viscosity expressions applicable to mercury drops carrying low zeta potentials at arbitrary kappaa (where kappa is the Debye-Hückel parameter and a is the drop radius) and to mercury drops as well as rigid spheres with arbitrary zeta potentials at large kappaa. It is shown that the large-kappaa expression of p for rigid particles predicts a maximum when plotted as a function of zeta potential. This result for rigid particles agrees with the exact numerical results of Watterson and White. It is also shown that in the limit of high zeta potential the effective viscosity of a suspension of mercury drops tends to that of uncharged rigid spheres given by Einstein's formula (Einstein, A. Ann. Phys. 1906, 19, 289), whereas in the opposite limit of low zeta potential the effective viscosity approaches that of a suspension of uncharged liquid drops derived by Taylor (Taylor, G. I. Proc. R. Soc. London, Ser. A 1932, 138, 41).

Electrochemistry↗

Use of sulfate reducing cell suspension bioreactors for the treatment of SO2 rich flue gases.

This paper describes a novel bioscrubber concept for biological flue gas desulfurization, based on the recycling of a cell suspension of sulfite/sulfate reducing bacteria between a scrubber and a sulfite/sulfate reducing hydrogen fed bioreactor. Hydrogen metabolism in sulfite/sulfate reducing cell suspensions was investigated using batch activity tests and by operating a completely stirred tank reactor (CSTR). The maximum specific hydrogenotrophic sulfite/sulfate reduction rate increased with 10% and 300%, respectively, by crushing granular inoculum sludge and by cultivation of this sludge as cell suspension in a CSTR. Operation of a sulfite fed CSTR (hydraulic retention time 4 days; pH 7.0; sulfite loading rate 0.5-1.5 g SO3(2-) l(-1) d(-1)) with hydrogen as electron donor showed that high (up to 1.6 g l(-1)) H2S concentrations can be obtained within 10 days of operation. H2S inhibition, however, limited the sulfite reducing capacity of the CSTR. Methane production by the cell suspension disappeared within 20 days reactor operation. The outcompetition of methanogens in excess of H2 can be attributed to CO2 limitation and/or to sulfite or sulfide toxicity. The use of cell suspensions opens perspectives for monolith or packed bed reactor configurations, which have a much lower pressure drop compared to air lift reactors, to supply H2 to sulfite/sulfate reducing bioreactors.

Bioreactors↗