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Hydroxypropylmethylcellulose, viscosity, and plasma cholesterol control.

The mechanism for the lowering of plasma cholesterol by water-soluble nonstarch polysaccharides (NSP) could involve alteration of intestinal viscosity leading to attenuated fat and steroid digestion and absorption. Alternatively, there may be direct inhibition of hepatic cholesterol synthesis by short-chain fatty acids produced by large bowel bacterial fermentation. A synthetic NSP, hydroxypropylmethylcellulose (HPMC), has been shown to lower plasma low-density lipoprotein (LDL) cholesterol in humans. This polysaccharide is not fermented by the large bowel microflora and has been shown to lower the plasma and liver cholesterol in hamsters, with no change noted in hepatic sterol synthesis. In further studies with hamsters, a linear relationship has been identified between plasma cholesterol and the logarithm of hydroxymethylcellulose viscosity. Only a relatively small increment in viscosity was necessary to achieve a maximal effect, suggesting that intestinal digestion may be quite sensitive to increased NSP intake.

Animals↗

Composition and viscosity of interstitial fluid of rabbits.

Open-ended plastic tubes were used as capsules for obtaining interstitial fluid from rabbits. The capsule was a 2.5 cm long plastic tube with an inner diameter of 6 mm. Three small incisions were made in the dorsal mid-line of the anaesthetized rabbit; two capsules were inserted into each incision. A sample of capsular fluid was obtained 6 weeks later by inserting a hypodermic needle through the skin. The volume of fluid obtained from the capsule was sufficient for the analysis of total protein, albumin, albumin:globulin ratio, colloid osmotic pressure and the fluid viscosity. Despite the significantly lower total protein, albumin, globulin and colloid pressure of intracapsular fluid compared with plasma, the intracapsular fluid was found to have a greater viscosity. It is our opinion that the increased viscosity of the intracapsular fluid is due to the presence of a high molecular weight substance other than albumin and globulin, possibly hyaluronan.

Animals↗

The viscosity of mammalian nerve axoplasm measured by electron spin resonance.

1. The microviscosity of the axoplasm of can sciatic nerve was determined by an in vitro electron spin resonance (e.s.r.) method using the spin label tempone. To identify the spin label signal as one arising only from within the axoplasm, Ni2+ was used as a line broadening agent. In one series of experiments in nerves with sheath intact the Ni2+ ion was shown to eliminate the tempone signal arising from the surface water, and in another series of experiments, with the sheath slit, to eliminate the signal from the extracellular space as well. 2. A microviscosity of less than 5 centipoise (cP), i.e. 5x that of water, was determined for the axoplasm. Changes in the viscosity of the nerve axoplasm as a function of temperature over a range of 38 degrees down to 2 degrees C were seen to follow closely the viscosity change found for a water solution. 3. The microviscosity of nerve axoplasm and its change with temperature were related to axoplasmic transport of material in nerve fibres. The results were used to exclude a large increase in viscosity at low temperatures as the cause for the cold-block of fast axoplasmic transport.

Animals↗

Effect of isoniazid on the protoplasmic viscosity in Mycobacterium tuberculosis.

The effect of isoniazid on the protoplasmic viscosity in the H37Ra strain of Mycobacterium tuberculosis was determined by using electron spin resonance spectroscopy and a small spin label tempone (2,2,6,6-tetramethylpiperidone-N-oxyl radical). Isoniazid (0.5 mug/ml) caused the internal cellular viscosity to increase gradually over the first 15 h of exposure from a rotational correlation time value (T(c)) of 2.4 x 10(-10) to 3.4 x 10(10) s and then decrease linearly to the control level after 27 h. These results could be interpreted to mean that isoniazid allows a continued and normal synthesis of the protoplasmic components while the rate of increase in the cell volume is reduced. A degradative process may begin after the initial 15-h exposure time, which would cause the reduction in the internal viscosity.

Cytoplasm↗

Reduction of cell lysate viscosity during processing of poly(3-hydroxyalkanoates) by chromosomal integration of the staphylococcal nuclease gene in Pseudomonas putida.

Poly(3-hydroxyalkanoates) (PHAs) are biodegradable thermoplastics which are accumulated by many bacterial species in the form of intracellular granules and which are thought to serve as reserves of carbon and energy. Pseudomonas putida accumulates a polyester, composed of medium-side-chain 3-hydroxyalkanoic acids, which has excellent film-forming properties. Industrial processing of PHA involves purification of the PHA granules from high-cell-density cultures. After the fermentation process, cells are lysed by homogenization and PHA granules are purified by chemical treatment and repeated washings to yield a PHA latex. Unfortunately, the liberation of chromosomal DNA during lysis causes a dramatic increase in viscosity, which is problematic in the subsequent purification steps. Reduction of the viscosity is generally achieved by the supplementation of commercially available nuclease preparations or by heat treatment; however, both procedures add substantial costs to the process. As a solution to this problem, a nuclease-encoding gene from Staphylococcus aureus was integrated into the genomes of several PHA producers. Staphylococcal nuclease is readily expressed in PHA-producing Pseudomonas strains and is directed to the periplasm, and occasionally to the culture medium, without affecting PHA production or strain stability. During downstream processing, the viscosity of the lysate from a nuclease-integrated Pseudomonas strain was reduced to a level similar to that observed for the wild-type strain after treatment with commercial nuclease. The nuclease gene was also functionally integrated into the chromosomes of other PHA producers, including Ralstonia eutropha.

Culture Media↗

Extracellular polysaccharide from the black yeast NRRL Y-6272: improved methods for preparing a high-viscosity, pigment-free product.

When the extracellular polysaccharide from the black yeast NRRL Y-6272, composed of two parts N-acetyl-D-glucosamine and one part N-acetyl-D-glucosaminuronic acid, is isolated at maximum culture viscosity, adhering black pigment gives the polysaccharide preparations a gray-to-black appearance. Precipitation of the polysaccharide from cell-free culture supernatants with either ethanol of hexadecyltrimethylammonium bromide failed to remove the pigment. Various other methods were therefore tried for obtaining a high-viscosity polysaccharide product free of pigment. By systematically varying ingredients of defined and semidefined media, an improved medium was found that not only gave polysaccharide preparations of increased viscosity, but also increased yield. A key ingredient in this medium is L-asparagine. Also, adding autoclaved bovine serum albumin or egg albumin to this medium at the time of inoculation allowed a pigment-free polysaccharide to be isolated by standard procedures. None of several other proteins of synthetic polyamides tested were as effective as bovine serum albumin or egg albumin. In an alternate approach, pink mutants obtained by irradiation of the parent black strain with ultraviolet light, apparently produce the same extracellular polysaccharide free of any pigment but in lower yields or inferior in quality.

Acetylglucosamine↗

Effect of viscosity on bacterial motility.

The behavior of a number of motile flagellated bacteria toward viscosity characteristics of their fluid environments was observed. All showed an increase in velocity (micrometers per second) in more viscous solutions. Velocity reached a maximum at a characteristic value, however, and thereafter decreased with higher viscosities. Peritrichously flagellated bacteria had maximum velocities at higher viscosities than polarly flagellated bacteria. Effects of temperature, and possible utilization of chemical constituents in the viscous solutions, were studied and found to be negligible factors under the experimental conditions used. Different agents produced the same phenomenon, thus indicating that there probably were no chemically induced metabolic effects. Loss of available water and the possibility of a variable energy supply to the flagellar propulsive system were considered but are believed minimal. Theoretically derived thermodynamic equations were utilized and suggest that the conformation of the flagellar helix affects efficiency of propulsion. Such a relationship between helix waveform and velocity was experimentally observed with Thiospirillum jenese.

Bacillus megaterium↗

Viscosity and retinal vein thrombosis.

Whole-blood and plasma viscosity with haematological and biochemical investigations were measured in 44 patients with retinal vein occlusion. The patients were subdivided on the basis of fluorescein angiographic findings into: 1. Those with large areas of capillary non-perfusion. 2. Those with small areas of capillary non-perfusion. 3. Those with an intact capillary pattern. Capillary non-perfusion in retinal vein occlusion is associated with a higher morbidity owing to the complications of retinal neovascularization. Significantly higher values of whole-blood viscosity, packed cell volume, and yield stress have been found in patients with capillary non-perfusion than in those without. These differences may be of critical importance during the episode of retinal vein occlusion and suggest an aetiological factor in the development of capillary non-perfusion. Higher whole-blood and plasma viscosity values and plasma fibrinogen levels have also been shown in the whole retinal vein occlusion group compared with a control group of 30 individuals. These differences may be a factor in the development of retinal vein occlusion but their precise role is difficult to evaluate. Further biochemical investigations in the vein occlusion group supported the strong association with arterial disease and suggested a higher incidence of biochemical abnormalities in those patients with capillary non-perfusion.

Adult↗

Influence of age, systemic blood pressure, smoking, and blood viscosity on orbital blood velocities.

The influence of multiple systemic factors upon the blood velocities obtained from the orbital circulations was investigated. The velocities obtained by colour Doppler imaging from the ophthalmic artery, central retinal artery, and vein from 95 ophthalmologically healthy volunteers were analyzed. The effects of age, systemic blood pressure, and smoking habit were examined. In 24 volunteers blood viscosity was also measured and its relation with blood velocity assessed. Age was weakly negatively correlated with the blood velocities in the ophthalmic artery and weakly positively correlated with resistance to flow in the retinal circulation. Systolic blood pressure showed a positive correlation with the peak systolic velocities in the arteries while cigarette smoking was associated with lower ophthalmic artery velocities. Increased haematocrit and viscosity were positively correlated with resistance to flow proximal to the ophthalmic artery and red cell rigidity negatively correlated with the pulsatility of flow in the retinal vein. These results help to identify the roles of systemic conditions in the ocular circulation. The influence of blood viscosity on retinal venous flow may be relevant to the pathogenetic mechanisms of conditions such as central retinal vein occlusion.

Age Factors↗

Beneficial effect of fish oil on blood viscosity in peripheral vascular disease.

Reports suggest that the low incidence of ischaemic heart disease in Greenlandic Eskimos is related to the effect of a diet rich in eicosapentaenoic acid on platelet reactivity and plasma lipid concentrations. A double blind randomised investigation was therefore conducted of the effects on blood viscosity of dietary supplementation with an oil rich in this fatty acid (1.8 g/day, given as fish oil) and an eicosapentaenoic acid poor oil (as corn/olive oil) in patients with peripheral arterial disease. A statistically significant reduction in whole blood viscosity was observed at seven weeks in those patients receiving the eicosapentaenoic acid rich oil. No changes in plasma viscosity, haemoglobin concentration, packed cell volume, or platelet count were seen. A significant fall in plasma triglyceride concentration was also noted only in the patients receiving oil rich in eicosapentaenoic acid; plasma concentrations of cholesterol and high density lipoprotein cholesterol were unchanged. It is concluded that rheological changes that result from a diet rich in eicosapentaenoic acid may contribute to the suggested protective effects of such a diet against arterial disease and that such changes are of potential therapeutic importance in established arterial disease.

Aged↗

Increases in platelet and red cell counts, blood viscosity, and arterial pressure during mild surface cooling: factors in mortality from coronary and cerebral thrombosis in winter.

Six hours of mild surface cooling in moving air at 24 degrees C with little fall in core temperature (0.4 degree C) increased the packed cell volume by 7% and increased the platelet count and usually the mean platelet volume to produce a 15% increase in the fraction of plasma volume occupied by platelets. Little of these increases occurred in the first hour. Whole blood viscosity increased by 21%; plasma viscosity usually increased, and arterial pressure rose on average from 126/69 to 138/87 mm Hg. Plasma cholesterol concentration increased, in both high and low density lipoprotein fractions, but values of total lipoprotein and lipoprotein fractions were unchanged. The increases in platelets, red cells, and viscosity associated with normal thermoregulatory adjustments to mild surface cooling provide a probable explanation for rapid increases in coronary and cerebral thrombosis in cold weather. The raised arterial pressure and possibly cholesterol concentration may contribute to slower components of the increased thrombosis.

Adolescent↗

Higher viscosity participates in the regulation of coronary flow via nitric oxide and indomethacin-sensitive contracting factor.

Few studies have reported on the association of viscosity with coronary circulation. We evaluated the change in coronary flow after dextran was added to a perfusion solution to increase viscosity in isolated rat hearts. We also measured NOx- production induced by the change in shear stress in the coronary effluent, as a marker of NO synthesis. The baseline coronary flow was not influenced by the presence of either the cyclooxygenase inhibitor indomethacin, the thromboxane A2 (TXA2)-prostaglandin H2 (PGH2) receptor antagonist ONO-3708, or the TXA2 synthase inhibitor OKY-046. After exposure to solution containing 0.5% dextran, the coronary flow first decreased and then gradually increased until 10 min. The initial decrease in coronary flow was inhibited by indomethacin, ONO-3708, and OKY-046 individually. The gradual increase was completely inhibited by the NO inhibitor L-NAME, but not by indomethacin or ONO-3708. OKY-046 partially inhibited the increase. NOx- levels in the effluent were higher after the dextran solution was administered, and the increased NOx- levels were inhibited by L-NAME. The increased NOx- levels were not inhibited by inhibitors of the cyclooxygenase pathway. It appears that a higher viscosity of perfusion solution induced a gradual increase in NO production and was associated with increased production of indomethacin-sensitive contracting factor.

Animals↗

Alteration of the erythrocyte ultrastructure and blood viscosity by morphine.

The effects of acute morphine administration on intact erythrocytes and on their flow properties were studied by measuring the mean cell volume, cell geometry, and whole blood and plasma viscosities. Morphine caused a small (2-7%) increase in mean cell volume. Changes in cell geometry were found to be time dependent and most pronounced in concave portions of the red cells. Whole body viscosity was found to decrease upon morphine treatment; this may be due in part to a concurrent decrease in plasma viscosity.

Animals↗

Flow birefringence, stress optical rule and rheology of four micellar solutions with the same low shear viscosity.

The flow birefringence and the rheological properties of four viscoelastic solutions having nearly the same zero shear viscosity and subjected to shear flows are investigated in the linear and non-linear domains. The surfactant used for the samples is the cetyltrimethylammonium chloride in water at the concentration of 100 mmol/l with an organic salt, the sodium salicylate. The low shear viscosity curve versus the salt concentration is non-monotonic and has two maxima separated by a minimum forming four domains in which the salt concentration is chosen. For the two solutions belonging to the inner branch, i.e. between the two maxima, a simple Maxwellian behaviour is observed and shear banding occurs as confirmed by the flow birefringence pictures. Contrary to the results of P. Fisher (1996) where the unstable flow regime is restricted to the first decreasing part of the low shear viscosity curve of a cetylpyridinium chloride solution, we show that shear banding exits in a wider domain of the salt concentration.

Birefringence↗

Intracellular elasticity and viscosity in the body, leading, and trailing regions of locomoting neutrophils.

To investigate the mechanisms underlying pseudopod protrusion in locomoting neutrophils, we measured the intracellular stiffness and viscosity in the leading region, main body, and trailing region from displacements of oscillating intracellular granules driven with an optical trap. Experiments were done in control conditions and after treatment with cytochalasin D or nocodazole. We found 1) in the body and trailing region, the granules divided into a "fixed" population (too stiff to measure) and a "free" population (easily oscillated; fixed fraction 65%, free fraction 35%). By contrast, the fixed fraction in the leading region was <5%. 2) In the body and trailing region, there was no difference in stiffness or viscosity, but both were sharply lower in the leading region (respectively, 20-fold and 5-fold). 3) Neither cytochalasin D nor nocodazole caused a decrease in stiffness, but both treatments markedly reduced the fixed fraction in the body and trailing region to <20% and <40%, respectively. These observations suggest a discrete lattice structure in the body and trailing region and suggest that the developing pseudopod has a core that is more fluidlike, in the sense of a much lower viscosity and an almost total loss of stiffness. This is consistent with the contraction/solation hypothesis of pseudopodial formation.

Cell Movement↗

Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions.

The hamster window chamber model was used to study systemic and microvascular hemodynamic responses to extreme hemodilution with low- and high-viscosity plasma expanders (LVPE and HVPE, respectively) to determine whether plasma viscosity is a factor in homeostasis during extreme anemic conditions. Moderated hemodilution was induced by two isovolemic steps performed with 6% 70-kDa dextran until systemic hematocrit (Hct) was reduced to 18% (level 2). In a third isovolemic step, hemodilution with LVPE (6% 70-kDa dextran, 2.8 cP) or HVPE (6% 500-kDa dextran, 5.9 cP) reduced Hct to 11%. Systemic parameters, cardiac output (CO), organ flow distribution, microhemodynamics, and functional capillary density, were measured after each exchange dilution. Fluorescent-labeled microspheres were used to measure organ (brain, heart, kidney, liver, lung, and spleen) and window chamber blood flow. Final blood and plasma viscosities after the entire protocol were 2.1 and 1.4 cP, respectively, for LVPE and 2.8 and 2.2 cP, respectively, for HVPE (baseline = 4.2 and 1.2 cP, respectively). HVPE significantly elevated mean arterial pressure and CO compared with LVPE but did not increase vascular resistance. Functional capillary density was significantly higher for HVPE [87% (SD 7) of baseline] than for LVPE [42% (SD 11) of baseline]. Increases in mean arterial blood pressure, CO, and shear stress-mediated factors could be responsible for maintaining organ and microvascular perfusion after exchange with HVPE compared with LVPE. Microhemodynamic data corresponded to microsphere-measured perfusion data in vital organs.

Anemia↗

Paradoxical hypotension following increased hematocrit and blood viscosity.

Hematocrit (Hct) of awake hamsters and CD-1 mice was acutely increased by isovolemic exchange transfusion of packed red blood cells (RBCs) to assess the relation between Hct and blood pressure. Increasing Hct 7-13% of baseline decreased mean arterial blood pressure (MAP) by 13 mmHg. Increasing Hct above 19% reversed this trend and caused MAP to rise above baseline. This relationship is described by a parabolic function (R2 = 0.57 and P < 0.05). Hamsters pretreated with the nitric oxide (NO) synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and endothelial NOS-deficient mice showed no change in MAP when Hct was increased by <19%. Nitrate/nitrite plasma levels of Hct-augmented hamsters increased relative to control and L-NAME treated animals. The blood pressure effect was stable 2 h after exchange transfusion. These findings suggest that increasing Hct increases blood viscosity, shear stress, and NO production, leading to vasodilation and mild hypotension. This was corroborated by measuring A1 arteriolar diameters (55.0 +/- 21.5 microm) and blood flow in the hamster window chamber preparation, which showed statistically significant increased vessel diameter (1.04 +/- 0.1 relative to baseline) and microcirculatory blood flow (1.39 +/- 0.68 relative to baseline) after exchange transfusion with packed RBCs. Larger increases of Hct (>19% of baseline) led blood viscosity to increase >50%, overwhelming the NO effect through a significant viscosity-dependent increase in vascular resistance, causing MAP to rise above baseline values.

Animals↗

Hematology, viscosity, and respiratory functions of whole blood of the lesser mouse deer, Tragulus javanicus.

Blood samples from the lesser mouse deer were examined for hematology, viscosity, oxygen dissociation curve, and magnitude of the Bohr effect. Red corpuscle dimensions, determined under oil immersion with an ocular micrometer, averaged 2.2 micron while the cell counts averaged 53 million/micronl blood, and the packed cell volume averaged 31.2%. Blood hemoglobin concentration averaged 11.2 g/100 ml and the calculated mean cell hemoglobin concentration was 38 g/100 ml. The relative viscosity of the mouse deer plasma was 1.97 and increased in a nonlinear manner with hematocrit to 100 at 80% packed cell volume. Oxygen-hemoglobin equilibrium curves, determined with a mixing technique at 37 degrees C and 10, 36 and 71 Torr PCO2, have the same configuration observed in blood from mammals in general. The P50 of the mouse deer blood at pH = 7.40 is 34 Torr and the Bohr effect (deltalog P50/deltapH) is -0.483. The mouse deer have blood hematocrits which are well below the hematocrits observed in mammals with larger erythrocytes, but similar to the blood hematocrits observed in other mammals with small erythrocytes. We suggest that the low hematocrit is an adaptation which circumvents the hemodynamic problems associated with a high blood viscosity and that, in the mouse deer, the expected concomitantly low total blood hemoglobin concentration is compensated by a higher than average mean cell hemoglobin concentration.

Animals↗