Study on enhanced lymphatic tracing of isosulfan blue injection by influence of osmotic pressure on lymphatic exposure

Isosulfan blue (IB) is being used as a lymphatic tracer has been approved by the FDA in 1981. This study aimed at improving lymphatic exposure of IB injection by osmotic pressure regulation to achieve step-by step lymphatic tracing. First, IB injection with appropriate osmotic pressure, stability, and suitable pH was prepared. Next, the lymphatic tracing ability of different osmotic pressure was studied to determine the blue-stained state of IB in three-level lymph nodes after subcutaneous administration. Furthermore, pharmacokinetics of lymphatic drainage, lymph node uptake, and plasma concentration was investigate to explore the improving law of the lymphatic tracing by osmotic pressure, and combined with tissue irritation to determine the optimal osmotic pressure. At last, the tissue distribution in mice of IB injection which had the property of optimal osmotic pressure was investigated. The results showed that increasing osmotic pressure could significantly reduce injection site retention and increase IB concentration of lymph node. The lymph nodes could be obviously blue-stained by IB injection which had 938?mmol/kg osmotic pressure and would not cause inflammatory reaction and blood exposure. The tissue distribution study suggested that IB injection which had 938?mmol/kg osmotic pressure was mainly distributed into gallbladder and duodenum that verified the reports that 90% IB was excreted through the feces through biliary excretion. In conclusion, this study provides the basic study to improve lymphatic exposure of IB injection by regulate the osmotic pressure and have the potential to be the helpful guidance for the elective lymph node dissection.     

Osmotic stress on nitrification in an airlift bioreactor

The effect of osmotic pressure on nitrification was studied in a lab-scale internal-loop airlift-nitrifying reactor. The reactor slowly adapted to the escalating osmotic pressure during 270 days operation. The conditions were reversed to the initial stage upon full inhibition of the process. Keeping influent ammonium concentration constant at 420 mg N L(-1) and hydraulic retention time at 20.7h, with gradual increase in osmotic pressure from 4.3 to 18.8x10(5) Pa by adding sodium sulphate, the ammonium removal efficiencies of the nitrifying bioreactor were maintained at 93-100%. Further increase in osmotic pressure up to 19.2x10(5) Pa resulted in drop of the ammonium conversion to 69.2%. The osmotic pressure caused abrupt inhibition of nitrification without any alarm and the critical osmotic pressure value causing inhibition remained between 18.8 and 19.2x10(5) Pa. Nitrite oxidizers were found more sensitive to osmotic stress as compared with ammonia oxidizers, leading to nitrite accumulation up to 61.7% in the reactor. The performance of bioreactor recovered gradually upon lowering the osmotic pressure. Scanning and transmission electron microscopy indicated that osmotic stress resulted in simplification of the nitrifying bacterial populations in the activated sludge as the cellular size reduced; the inner membrane became thinner and some unknown inclusions appeared within the cells. The microbial morphology and cellular structure restored upon relieving the osmotic pressure. Addition of potassium relieved the effect of osmotic pressure upon nitrification. Results demonstrate that the nitrifying reactor possesses the potential to treat ammonium-rich brines after acclimatization.     

Experiment on formulation and drug release behavior of porosity asymmetric membrane capsules in vitro

Porosity asymmetric membrane capsules were prepared to study the relationship between the capsule formulation and drug release. Cellulose acetate (CA) and pore formers were used in the capsule shell formulation as the main semipermeable membrane material. The capsules were permeable to both water and dissolved solutes. Using sparingly soluble drug acetaminophen as a model, cumulative release was calculated. The slope of the release profile from the distilled water had good relationship with the concentration of the pore formers F68. The release of acetaminophen was independent to the pH, osmotic pressure of dissolution medium, but influenced by intensity of agitation. When the concentration of pore former was low, zero-order release behavior was observed within 24?h which was consistent with Fickian diffusion model. When the concentration of pore former was high, however, Higuchi model release was found which is caused by Fickian diffusion and osmotic pressure release. With scanning electron microscope (SEM), the surface structure and cross-section of the capsule shell were also studied before and after drug delivery. With simple preparation and broad scope of drug application, porosity asymmetric membrane capsules can give desired drug extended release and show more convenience than controlled tablets with laser drilling.     

Experiment on formulation and drug release behavior of porosity asymmetric membrane capsules in vitro

Porosity asymmetric membrane capsules were prepared to study the relationship between the capsule formulation and drug release. Cellulose acetate (CA) and pore formers were used in the capsule shell formulation as the main semipermeable membrane material. The capsules were permeable to both water and dissolved solutes. Using sparingly soluble drug acetaminophen as a model, cumulative release was calculated. The slope of the release profile from the distilled water had good relationship with the concentration of the pore formers F68. The release of acetaminophen was independent to the pH, osmotic pressure of dissolution medium, but influenced by intensity of agitation. When the concentration of pore former was low, zero-order release behavior was observed within 24?h which was consistent with Fickian diffusion model. When the concentration of pore former was high, however, Higuchi model release was found which is caused by Fickian diffusion and osmotic pressure release. With scanning electron microscope (SEM), the surface structure and cross-section of the capsule shell were also studied before and after drug delivery. With simple preparation and broad scope of drug application, porosity asymmetric membrane capsules can give desired drug extended release and show more convenience than controlled tablets with laser drilling.     

Wet process-induced phase-transited drug delivery system: a means for achieving osmotic, controlled, and level A IVIVC for poorly water-soluble drug

A phase-transited, nondisintegrating, controlled release, asymmetric membrane capsular system for poorly water-soluble model drug flurbiprofen was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. Asymmetric membrane capsules (AMCs) were prepared using fabricated glass mold pins through wet phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. In vitro release studies for all the prepared formulations were carried out (n = 6). Statistical test was applied for in vitro drug release at p > .05. Predicted in vivo concentration from in vitro release data closely matched the minimum effective concentration (in vivo) level achieved by the drug from its release through phase-transited AMC in rabbits for the first hour. The drug release was found to be independent of the pH but dependent on the osmotic pressure of the dissolution medium. In vivo pharmacokinetic studies showed level A correlation (R(2) > .99) with 42.84% relative bioavailability compared to immediate release tablet of flurbiprofen. Excellent correlation achieved suggested that the in vivo performance of the AMCs could be accurately predicted from their in vitro release profile.     

Wet Process-Induced Phase-Transited Drug Delivery System: A Means for Achieving Osmotic,Controlled, and Level A IVIVC for Poorly Water-Soluble Drug

A phase-transited, nondisintegrating, controlled release, asymmetric membrane capsular system for poorly water-soluble model drug flurbiprofen was developed and evaluated both in vitro and in vivo for osmotic and controlled release of the drug. Asymmetric membrane capsules (AMCs) were prepared using fabricated glass mold pins through wet phase inversion process. Effect of varying osmotic pressure of the dissolution medium on drug release was studied. Membrane characterization by scanning electron microscopy showed an outer dense region with less pores and an inner porous region for the prepared asymmetric membrane. In vitro release studies for all the prepared formulations were carried out (n = 6). Statistical test was applied for in vitro drug release at p > .05. Predicted in vivo concentration from in vitro release data closely matched the minimum effective concentration (in vivo) level achieved by the drug from its release through phase-transited AMC in rabbits for the first hour. The drug release was found to be independent of the pH but dependent on the osmotic pressure of the dissolution medium. In vivo pharmacokinetic studies showed level A correlation (R² > .99) with 42.84% relative bioavailability compared to immediate release tablet of flurbiprofen. Excellent correlation achieved suggested that the in vivo performance of the AMCs could be accurately predicted from their in vitro release profile.     

Theory of the osmotic pressure of dilute mixtures of3He in liquid4He at low temperatures

The osmotic pressure of dilute mixtures of³He in liquid⁴He is calculated and compared with experiment. One parameter, which is a measure of the difference between the mean potential energy of³He atoms and⁴He atoms in the mixture is determined from the experiments, and good agreement is obtained with the measured values of as a function of concentration and temperature. It is shown that the osmotic pressure does not provide any accurate information about the effective interaction between³He atoms. A comparison with earlier calculations of the osmotic pressure and of the³He chemical potential is made.Work performed under the auspices of U.S. Atomic Energy Commission.     

Solute transfer in fluid flow in permeable tubes with application to flow in glomerular capillaries

Summary A mathematical model for solute transfer in an ultrafiltering glomerular capillary has been proposed. The solute transfer, by diffusion and convection, within and across the tube wall has been considered. Effects due to the presence of red cells are neglected and the blood is assumed to be Newtonian fluid with constant viscosity. The rate of fluid movement at the wall is assumed to be proportional to the difference between the net hydrostatic and osmotic forces — Starling's law. The velocity and concentration profiles, at different positions along the axis, the axial distribution of hydrostatic and osmotic pressures and the total solute clearance have been obtained. It is found that the osmotic pressure has relatively greater influence on capillary mass transfer than the hydrostatic pressure. Radial concentration gradients of considerable order have been observed, particularly near the entrance portion of the tube. The radial concentration gradient increases with ultrafiltration parameter and decreases, as the diffusion coefficient increases. The influence of transmittance coefficient (solute wall permeability coefficient) is found to be predominant at higher ultrafiltration rates (higher concentration difference across the membrane). The generalized nature of the present model has been illustrated by obtaining some of the existing results as the particular cases of this model. Using relevant data, the physiological implications of some of the obtained results have been briefly discussed.     

Is the Donnan effect sufficient to explain swelling in brain tissue slices?

Brain tissue swelling is a dangerous consequence of traumatic injury and is associated with raised intracranial pressure and restricted blood flow. We consider the mechanical effects that drive swelling of brain tissue slices in an ionic solution bath, motivated by recent experimental results that showed that the volume change of tissue slices depends on the ionic concentration of the bathing solution. This result was attributed to the presence of large charged molecules that induce ion concentration gradients to ensure electroneutrality (the Donnan effect), leading to osmotic pressures and water accumulation. We use a mathematical triphasic model for soft tissue to characterize the underlying processes that could lead to the volume changes observed experimentally. We suggest that swelling is caused by an osmotic pressure increase driven by both non-permeating solutes released by necrotic cells, in addition to the Donnan effect. Both effects are necessary to explain the dependence of the tissue slice volume on the ionic bath concentration that was observed experimentally.     

Calculations of static properties of spin-polarized3He-4He mixtures

The theory of dilute mixtures of³He in⁴He that have been polarized by a strong magnetic field is developed. The interaction between the quasiparticles is taken to be constant, an approximation valid at low temperatures. The polarization of the mixture depends on the strength of the interaction. The internal energy, the specific heat, the osmotic pressure, and the velocity of second sound are also calculated. The specific heat is relatively insensitive to the interaction, but it does change significantly with magnetic field. The osmotic pressure is more sensitive to the effects of the interaction for some³He concentrations and temperatures. The velocity of second sound behaves qualitatively like the osmotic pressure. The measurement of these quantities as a function of temperature and magnetic field is discussed with a view to obtaining the strength of the interaction between quasiparticles.     

Fast membrane osmometer as alternative to freezing point and vapor pressure osmometry

Osmometry is an essential technique for solution analysis and the investigation of chemical and biological phenomena. Commercially available osmometers rely on the measurements of freezing point, vapor pressure, and osmotic pressure of solutions. Although vapor pressure osmometry (VPO) and freezing point osmometry (FPO) can perform rapid and inexpensive measurements, they are indirect techniques, which rely on thermodynamic assumptions, which limit their applicability. While membrane osmometry (MO) provides a potentially unlimited direct measurement of osmotic pressure and solution osmolality, the conventional technique is often time-consuming and difficult to operate. In the present work, a novel membrane osmometer is presented. The instrument significantly reduces the conventional MO measurement time and is not subject to the limitations of VPO and FPO. For this paper, the osmotic pressure of aqueous sucrose solutions was collected in a molality range 0-5.5, by way of demonstration of the new instrument. When compared with data found in the literature, the experimental data were generally in good agreement. However, differences among results from the three techniques were observed.     

渗透压循环加卸载作用下页岩渗透率演化规律研究

为研究页岩在渗透压循环加卸载作用下渗透率演化规律,利用改进的脉冲衰减气体渗透率测量装置对页岩进行不同围压、不同渗透压循环加卸载试验。试验结果表明:初始围压的大小会影响页岩的初始渗透率,初始围压越大初始渗透率越小;在定围压循环加卸载渗透压的过程中,渗透率随着渗透压的加载而增大,随着渗透压的卸载而减小;在同一渗透压加卸载循环中,加载阶段和卸载阶段的渗透率曲线不重合,且卸载阶段渗透率曲线位于加载阶段渗透率曲线的上方;对渗透率随渗透压循环加卸载的变化关系进行拟合,拟合结果符合二次函数关系,相关系数大于95%。     

The pivotal role of sodium balance in control of blood pressure in dialysis patients

In hemodialysis patients, as in patients with normal kidney function, sodium balance is the major determinant of changes in extracellular volume, and extracellular volume is an important determinant of blood pressure. The osmotic thresholds for thirst and ADH release are normal in kidney failure; pre‐dialysis serum sodium concentration shows a high index of individuality in oliguric hemodialysis patients. Non‐osmotic storage of sodium in vascular walls may also amplify the volume‐sensitivity of blood pressure. The variable relationship between volume removal and change in blood pressure described in clinical studies reflects a state of permanent volume expansion in those whose blood pressure does not fall, or rises, during dialysis, whereas those whose blood pressure falls during dialysis are those who approach normovolemia. Rigorous control of extracellular volume often results in perfect blood pressure control, but may be difficult to achieve safely other than with long, slow dialysis combined with dietary salt restriction.     

Design of Porous Alginate Hydrogels by Sacrificial CaCO3 Templates: Pore Formation Mechanism

Fabrication of porous alginate hydrogels with a well‐controlled architecture useful for tissue engineering is still a challenge. Here, CaCO₃‐based templating is utilized to design stable alginate gels with controlled pore dimensions in the range of 5–50 μm. The mechanism of pore formation is studied considering two factors affecting the pore size: i) osmotic pressure generated during the dissolution of sacrificial CaCO₃ templates and ii) alginate gel network density. Osmotic pressure can achieve an upper limit of 100 MPa but does not affect the gel porosity. Additional osmotic pressure (range of kPa) induced by dextrans pre‐encapsulated into CaCO₃ vaterite is also insufficient for pore enlargement. Pore stability depends merely on the gel network density and on the number of crosslinking calcium ions provided locally per unit time; pores are collapsed when template dissolution is too slow or if there is insufficient alginate concentration (below 2%). Young's modulus indicates the soft nature of the prepared hydrogels (tens of kPa) applicable as soft porous scaffolds with a tuned internal structure.     

Monolithic Osmotic Tablet Containing Solid Dispersion of 10-hydroxycamptothecin

A novel monolithic osmotic tablet composed of solid dispersion of water-insoluble 10-hydroxycamptothecin (HCPT) was prepared. The tablet core was made of a suspending agent, polyethylene oxide, an osmotic agent, sodium chloride, and a solid dispersion consisting of polyethylene glycol 6000 and HCPT. Optimized formulation was able to deliver HCPT at the constant rate of 1.21 mg/hour for 12 hours with cumulative release above 90% in vitro, independent of environmental media and stirring rate, and the release rate is co-controlled by osmotic pressure, suspending effect, and drug solubility in solid dispersion. The monolithic osmotic tablet containing solid dispersion has great potential in the controlled delivery of water-insoluble drugs.     

Influences of Osmotic Agents in Diffusion Layer on Drug Release from Multilayer Coated Pellets

Nonpareil beads were coated with three different functional layers, namely inner chlorpheniramine maleate‐loaded hydroxypropylmethylcellulose (HPMC, 4 mPa · s) deposition layer, middle HPMC (400 mPa · s) diffusion layer, and outer polyacrylic polymer (Eudragit RS30D) retention layer. The osmotic agents, including sodium chloride, glycine, citric acid, and disodium hydrogen phosphate, were incorporated in different amounts into the diffusion layer and the influences on drug release were studied. The osmotic agent competed with HPMC for imbibed water and subsequently caused more water influx owing to the osmotic pressure gradient. An appropriate amount of osmotic agent in the diffusion layer was necessary to exert its effect on retarding drug release. The osmotic effect on drug release was compromised with pellets at a higher coating level of the diffusion layer due to the extensive swelling and rupture of coat. The release parameters, including dissolution T_50% and mean dissolution time, showed linear relationship with osmolalities of osmotic agents studied. The effect of the osmotic agent in the diffusion layer played an important role in determining the unique multiphase drug release profiles, particularly in the initial phase of dissolution, and reduced with depletion of the osmotic agent in the later phase of dissolution.     

Influences of osmotic agents in diffusion layer on drug release from multilayer coated pellets

Nonpareil beads were coated with three different functional layers, namely inner chlorpheniramine maleate-loaded hydroxypropylmethylcellulose (HPMC, 4 mPa · s) deposition layer, middle HPMC (400 mPa · s) diffusion layer, and outer polyacrylic polymer (Eudragit RS30D) retention layer. The osmotic agents, including sodium chloride, glycine, citric acid, and disodium hydrogen phosphate, were incorporated in different amounts into the diffusion layer and the influences on drug release were studied. The osmotic agent competed with HPMC for imbibed water and subsequently caused more water influx owing to the osmotic pressure gradient. An appropriate amount of osmotic agent in the diffusion layer was necessary to exert its effect on retarding drug release. The osmotic effect on drug release was compromised with pellets at a higher coating level of the diffusion layer due to the extensive swelling and rupture of coat. The release parameters, including dissolution T_50% and mean dissolution time, showed linear relationship with osmolalities of osmotic agents studied. The effect of the osmotic agent in the diffusion layer played an important role in determining the unique multiphase drug release profiles, particularly in the initial phase of dissolution, and reduced with depletion of the osmotic agent in the later phase of dissolution.     

Investigations of a novel self-emulsifying osmotic pump tablet containing carvedilol

Carvedilol has been made into a novel osmotic pump tablet which includes Gelucire 44/14, Lutrol F68, Transcutol P, silicon dioxide, mannitol, citric acid, and sodium hydrogen carbonate. The Self-emulsifying osmotic pump tablet (SEOPT) has two outstanding features. It could improve the bioavailability of carvedilol by self-emulsifying drug delivery system (SEDDS), control the release rate and make the plasma concentrations more stable by elementary osmotic pump tablet. The results of transmission electron microscope (TEM) and particle size assessment showed that the shape of the resultant emulsion was round and regular, the average diameter of the particles was 246 nm. Since the solubility of carvedilol was improved by the emulsion, the elementary SEOPT could guarantee a complete release of carvedilol under the osmotic pressure of mannitol. The cumulative release at 12 hr was 85.18%. Therefore the disadvantage that lipophilic drugs can not be released completely when prepared into elementary osmotic pump tablet was resolved. The results of Differential scanning calorimetry (DSC), Infrared spectroscopy (IR) and X-ray diffraction diffraction (XRD) proved that carvedilol was amorphous in the preparation. The relative bioavailability of carvedilol in beagle dogs was 156.78%. The plasma concentrations were more stable compared with that of commercially available tablet (Luode®). And the in vitro and in vivo correlation was good (r = 0.9725). Therefore, the elementary SEOPT developed in this paper might provide a new idea for preparing lipophilic drugs into osmotic pump tablet conveniently.     

Are liquid crystalline properties of nucleosomes involved in chromosome structure and dynamics?

Nucleosome core particles correspond to the structural units of eukaryotic chromatin. They are charged colloids, 101 Angstrom in diameter and 55 Angstrom in length, formed by the coiling of a 146/147 bp DNA fragment (50 nm) around the histone protein octamer. Solutions of these particles can be concentrated, under osmotic pressure, up to the concentrations found in the nuclei of living cells. In the presence of monovalent cations (Na(+)), nucleosomes self-assemble into crystalline or liquid crystalline phases. A lamello-columnar phase is observed at 'low salt' concentrations, while a two-dimensional hexagonal phase and a three-dimensional quasi-hexagonal phase form at 'high salt' concentrations. We followed the formation of these phases from the dilute isotropic solutions to the ordered phases by combining cryoelectron microscopy and X-ray diffraction analyses. The phase diagram is presented as a function of the monovalent salt concentration and applied osmotic pressure. An alternative method to condense nucleosomes is to induce their aggregation upon addition of divalent or multivalent cations (Mg(2+), spermidine(3+) and spermine(4+)). Ordered phases are also found in the aggregates. We also discuss whether these condensed phases of nucleosomes may be relevant from a biological point of view.     

Transport and fate of volatile organic chemicals in unsaturated, nonisothermal, salty porous media: 1. Theoretical development.

A wide variety of volatile organic chemicals (VOC) have been applied to agricultural land or buried in chemical waste sites. The fate of these chemicals depends upon several mechanisms such as sorption, degradation, and transport in liquid and gaseous phases. Understanding the transport mechanisms affecting the volatile chemicals can lead to better management strategies. A theory describing inorganic solute transport, water and heat transfer, and the fate and transport of VOC in porous media has been developed. This theory includes matric water pressure head, solution osmotic pressure head, gravity pressure head, temperature, inorganic solute concentration, and VOC concentration gradients as driving forces for heat and mass transfer. The effect of surface tension, as a function of VOC concentration and temperature, on the matric water pressure head is included. The VOC can be associated with gas, liquid, and solid phases of the porous media. The gas and liquid phases are mobile, but the solid phase is immobile. The transfer of VOC across the gas/liquid, liquid/solid, and gas/solid interfaces is included using sorption-equilibrium assumptions at the interfaces. The VOC can degrade. This degradation is described by a first-order decay rate. The theory can be used to predict spatial and temporal variations of water content, temperature, inorganic concentration and the total concentration of VOC within a porous medium. The concentration of VOC in each phase can be predicted also.