Ultrafiltrate Of Plasma Research Articles

The hepatocyte growth factor/scatter factor (HGF/SF) receptor, met, transduces a morphogenetic signal in renal glomerular fibromuscular mesangial cells

Previous studies have demonstrated that hepatocyte growth factor/scatter factor (HGF/SF) is secreted by mesenchymal cells and that it elicits motility, morphogenesis and proliferation of epithelia expressing the met receptor. We now report that HGF/SF may act as an autocrine factor in fibromuscular renal mesangial cells. These cells mechanically support glomerular endothelia, control the rate of plasma ultrafiltration and are implicated in the pathogenesis of a variety of chronic renal diseases. We detected met protein in the vascular stalk of metanephric glomeruli and in the mature mesangium. Mesangial lines from a mouse transgenic for a temperature-sensitive simian virus 40 T antigen expressed met mRNA and protein, and recombinant HGF/SF phosphorylated the met receptor tyrosine kinase. Cells were immortal in the permissive condition and HGF/SF enhanced proliferation in a defined medium. In the absence of the immortalising protein, division ceased and recombinant HGF/SF caused multipolar cells to become bipolar. The factor diminished stress fibres, their focal contacts and immunostaining for extracellular fibronectin, hence suggesting reduced substratum adhesion and enhanced motility. Mesangial lines also expressed HGF/SF mRNA and secreted bioactive factor; immunocytochemistry showed both ligand and receptor in individual cells. HGF/SF blocking antibody aggregated the cells, suggesting that mesangial-derived factor affects basal cell conformation in an autocrine manner. We conclude that mesangial cells express both HGF/SF and met, and the factor induces morphogenesis of cultured mesangial cells. Therefore HGF/SF may have an autocrine role in mesangial biology but further studies are now required to investigate the potential importance of the factor in vivo.

Factors Affecting Bicarbonate Transfer with Bicarbonate-Containing CAPD Solution

To evaluate bicarbonate fluxes across the peritoneal membrane and bicarbonate gain in patients treated with continuous ambulatory peritoneal dialysis (CAPD) using dialysis solutions with different bicarbonate concentrations. Ninety-seven exchanges, using different dwell times and glucose and bicarbonate concentrations were performed in 43 stable CAPD patients. Dialysate effluent bicarbonate concentration and volumes were measured at different dwell times. Net dialytic bicarbonate gain was calculated. Patients' acid-base status was determined at the middle of the dwell. In prolonged dwells (6-12 hours) the dialysate effluent bicarbonate concentration correlated with arterial plasma bicarbonate concentration (F = 129, p < 0.0001), but not with ultrafiltration rate or dialysis solution bicarbonate concentration. In 4-hour dwells, effluent bicarbonate concentration correlated with both plasma bicarbonate concentration and ultrafiltration rate (F = 32.52, p < 0.0001 and F = 4.4, p < 0.05, respectively). The effluent bicarbonate concentration may be predicted from the patient's plasma bicarbonate concentration and net ultrafiltration rate for either a 4-hour or prolonged (6-12 hours) dwell time. Net bicarbonate gain by the patient correlated with ultrafiltration rate, plasma bicarbonate, and dialysis solution bicarbonate concentration (F = 100.56, p < 0.0001 at 4 hours and F = 108.08, p < 0.0001 at 6-12 hours), with the ultrafiltration rate being the predominant parameter. The effluent bicarbonate concentration is related to plasma bicarbonate concentration, with ultrafiltration playing a marginal role only during short dwells. However, the ultrafiltration rate has a profound effect on net patient bicarbonate gain. Multiple linear regression analysis allows the prediction of the effect of acid-base status, ultrafiltration, dwell time, and dialysis solution bicarbonate content on net patient bicarbonate gain. It seems that bicarbonate content in the CAPD dialysis solution should be progressively increased with increasing solution osmolality.

Composition of interstitial fluid

In several previous experiments to determine the composition of interstitial fluid, the results varied depending on the collecting technique, and the electrolyte concentrations differed from those of a hypothetical ultrafiltrate of plasma. In our approach, since a change of position from standing to supine is accompanied by hemodilution with interstitial fluid, we used the changes in hematocrit and composition of plasma in 20 subjects before and after lying down to calculate the composition of added interstitial fluid. The estimated protein concentration was 20.6 g/L, and the concentrations of total calcium and magnesium were low, in accord with a lower concentration of protein-bound calcium and magnesium. The activity of free cations was also lower, in agreement with a Donnan equilibrium potential of 1 mV across the endothelium. The concentration of leukocytes and platelets decreased according to the hemodilution, implying no escape or mobilization of these elements.

Nitric Oxide Synthase Inhibition in Spontaneously Hypertensive Rats

To investigate the prolonged effects of nitric oxide inhibition on systemic, renal, and glomerular hemodynamics, the effects of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on cardiac index, renal micropuncture results, urinary excretion, and histology were obtained in 20-week-old male spontaneously hypertensive rats (SHR) that were divided into two groups: untreated and L-NAME-treated (50 mg/L), each followed for 3 weeks. Cardiac index and effective renal plasma flow decreased (P < .01) in L-NAME-treated SHR, exhibiting a positive correlation (r = .816; P < .0001). Single-nephron plasma flow (123 +/- 8 versus 80 +/- 12 nL/min per gram; P < .01) and ultrafiltration coefficient (P < .05) were also reduced in L-NAME-treated SHR versus controls. Most notably, the L-NAME-treated SHR had increased afferent (4.4 +/- 0.3 versus 9.5 +/- 1.3 U; P < .01) and efferent (1.4 +/- 0.1 versus 2.7 +/- 0.3 U; P < .01) glomerular arteriolar resistances versus controls. These functional changes were associated with significantly altered afferent arteriolar (P < .001) and glomerular (P < .005) histological injury scores accompanied by marked proteinuria (P < .001). Because of the intense afferent glomerular artery constriction and lesser increase in efferent glomerular arteriolar resistance associated with reduced single-nephron plasma flow, glomerular capillary pressure did not increase in the L-NAME-treated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Parameter estimation in six numerical models of transperitoneal transport of potassium in patients undergoing peritoneal dialysis

The mechanisms of transperitoneal potassium transport during peritoneal dialysis were evaluated by validation of different mathematical models. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. Experimental results were obtained from 26 non-diabetic patients undergoing peritoneal dialysis. The validation procedure demonstrated that models including both diffusive and non-lymphatic convective solute transport were superior to the other models. Lymphatic convective solute transport was not identifiable. Furthermore, it was demonstrated experimentally that the equilibrium distribution of potassium between plasma water and dialysate did not differ from a Donnan equilibrium, although the precondition of the Donnan equilibrium was not fulfilled, i.e. the volumes on each side of the membrane were not constant and dialysate was not an ultrafiltrate of plasma.

Role of nitric oxide in renal hemodynamic abnormalities of cyclosporin nephrotoxicity

To evaluate the participation of nitric oxide (NO) in chronic cyclosporin A (CsA) nephrotoxicity, the glomerular hemodynamic response to NO inhibition with N-nitro-L-arginine-methyl-ester (NAME) and stimulation of NO production with L-arginine was studied in uninephrectomized rats. Chronic CsA administration produced renal vasoconstriction, characterized by increased afferent (AR) and efferent (ER) resistances, decrease of glomerular plasma flow (QA) and ultrafiltration coefficient (Kf) that resulted in a 53% fall of single-nephron glomerular filtration rate (SNGFR). NAME infusion in vehicle group (V) elevated mean arterial pressure (MAP), AR and ER, reduced qA and Kf, and increased glomerular capillary pressure (PGC), resulting in a 28.9% fall of SNGFR. In the CsA group, NAME also increased MAP, but renal vasoconstriction was more intense; a greater rise of AR lowered PGC (P < 0.05 vs. V) further decreasing SNGFR by 38.9%. In control rats, L-arginine infusion induced a vasodilatory response of AR and ER, and elevation of QA and Kf, which resulted in a 72.6% increase in SNGFR. In the CsA group, greater vasodilation was observed and SNGFR rose by 114.9%. NO2-/NO3- urinary excretion was similar in CsA and V groups, and it was not modified by NAME in either group, but it increased five- to sixfold during L-arginine infusion in both groups. In conclusion, in CsA nephrotoxicity NO production seems to be normal and the ability of the renal endothelium to produce NO is maintained. Therefore renal vasoconstriction associated with CsA is not mediated by NO deficiency, although NO appears to attenuate it.

Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder.

Consistent with previous studies, elevated free intracellular calcium ion concentrations ([Ca2+]i) were found in blood platelets and lymphocytes of patients with mania and bipolar depression. Incubation with an ultrafiltrate of plasma from patients with bipolar illness had no effect on intracellular calcium ion concentration in platelets from normal subjects, suggesting that elevated [Ca2+]i is not due to a circulating factor. As was true in an earlier study of the effect of lithium on platelets, incubation with therapeutic levels of carbamazepine lowered [Ca2+]i in lymphocytes from affectively ill patients but not controls. Increased [Ca2+]i in peripheral cells may reflect a diffuse change in cellular homeostasis and may contribute to mixtures as well as rapid alternations of activity of affective, behavioral and physiologic systems in bipolar illness. Correction of the abnormality may at least be a marker of a relevant therapeutic action if it is not the action itself.

Evaluation of methotrexate tissue exposure by in situ microdialysis in a rat model.

The feasibility of using a microdialysis technique to obtain pharmacokinetic data on tissue exposure to methotrexate (MTX) was investigated. Microdialysis probes were implanted in the jugular vein, femoral muscle, and liver of anesthetized male Wistar rats. MTX (100 mg/kg) was given as a bolus injection through an indwelling venous catheter, and blood samples were obtained through a second venous access and by microdialysis for a total of 6 h. Heparinized plasma, ultrafiltered plasma, and microdialysis effluent from tissue and venous probes were analyzed by high-performance liquid chromatography. Centrifugal ultrafiltration of rat plasma spiked in vitro with MTX (1-100 microM) revealed a mean binding to plasma proteins of 21%. In vitro microdialysis of this spiked plasma resulted in 23% relative recovery of the unbound fraction. In rats receiving MTX, plasma protein binding was 23% and the relative drug recovery as assessed with venous microdialysis probes was 18%. Plotting of unbound (i.e., ultrafiltrate) MTX concentrations in the blood against venous microdialysis perfusate values in the blood gave a good linear correlation with a coefficient of correlation (r2) of 0.98. There was also a linear correlation between the total MTX concentrations in venous blood and the drug levels in microdialysis samples from muscle and liver (r2 = 0.93 and 0.74, respectively). Area under the curve estimations were consistent with an MTX exposure of 30% and 46% for the muscle and liver as compared with the circulation. The present study demonstrates that the microdialysis technique can provide reproducible data on tissue exposure to MTX in an animal model and indicates that the methodology is adaptable to clinical settings.

Concentration polarization formation in ultrafiltration of blood and plasma

This paper describes a technique for investigating the kinetics of concentration polarization formation in ultrafiltration of bovine blood, plasma and albumin (BSA) solutions using polysulfone hollow fiber membranes of 30000 Da cut-off. The mebrane is submitted to step pressure changes while monitoring the variation of instantaneous permeate flux. When the pressure is suddenly raised from an unpolarized regime to a high polarization one, the permeate flux reaches a peak in 4 ot 7 sec and decays back to its equilibrium level in 2 min, for blood and plasma, and in less than 1 min, for albumin solution. With blood, the apparent filtration resistance (neglecting osotic pressure) reaches its maximum of 6 × 10 13 m −1 when 200 ml of blood has been filtered (on a 0.65 m 2 membrane). The red cell contribution to this resistance is about 20%. The filtration resistance is higher with plasma than with albumin, at the same protein concentration. In the initial buildup of concentration polarization the resistance increases linearly with albumin mass carried towards the membrane, with a rate independent of concentratiion. Nevertheless, the final resistance at equilibrium increases with increasing albumin concentration. The time for complete reversal of concentration polarization is estimated by repeating pressure increments, while increasing the time interval between two increments, until the permeate peak following the pressure step reaches its maximum. This time is found to be of the order of 12 sec for BSA solutions.

Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa.

Reactive oxygen species (ROS) can be detected in the semen of 40% of infertile men, whereas none is detected in semen from normal men. The ROS detected in semen are a reflection of the imbalance between ROS production and degradation. The aim of the present study was to determine whether a lowered scavenging capacity or an increased production of ROS was responsible for the ROS detected in semen samples from infertile men. Two activities were investigated: (1) catalase-like activity, which is responsible for the degradation of H2O2 and (2) superoxide dismutase-like (SOD-like) activity which is responsible for the degradation of .O2-. Catalase-like and SOD-like activities were found in whole seminal plasma, in dialyzed seminal plasma (> 12 kD), in an ultrafiltrate of seminal plasma (< 5 kD) and in spermatozoa. There was no significant difference in the SOD-like activities measured in spermatozoa, or in seminal plasma (whole or fractionated) from samples that did or did not produce ROS. SOD-like activity originated mostly from the high molecular weight components of seminal plasma. However, the catalase-like activity of whole seminal plasma and of spermatozoa was significantly greater (P = 0.01) in those samples that produced ROS as compared to those that did not. The catalase-like activity in dialyzed seminal plasma, and an ultrafiltrate of seminal plasma from semen samples that did or did not produce ROS were not statistically different. The catalase-like activity of the seminal plasma originated equally from high and low molecular weight components.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of antibiotics in natural and experimental superficial compartments in animals and humans.

Transcapillary exchange of antibiotics and other small molecules is diffusion driven and occurs in the capillary beds of the tissues. Small polar molecules are ionized at physiological pH and diffusion is pore-mediated. More lipophilic substances can also leave capillaries by the transcellular route. Splanchnic tissues have fenestrated capillary walls while somatic tissues have mainly micropores in their capillary walls. Under normal physiological conditions the ratio of capillary surface area to volume of fluid present (SA/V) is very large (> 100) and the rate of exchange of substances between capillaries, interstitial fluid and tissue fluid is extremely rapid. The structure of the interstitial space or ground substance, linking the capillary to the tissue cells, is designed to regulate the exchange of water, albumen and other solutes between the plasma and tissues. Interstitial space fluid (tissue fluid) is not simply an ultrafiltrate of plasma and has a specific chemical imbalance with plasma. Some antibiotics bind to serum albumen and it is claimed that this impairs their ability to penetrate into tissue fluids. However, the reduced concentration of albumen in the tissue fluid, relative to the plasma, is the main reason why percentage tissue penetration data based on total levels present are misleading and perpetuate the misconception that highly bound antibiotics (> 80%) have a reduced penetration potential. The majority of infections are localized in extracellular fluid. Several models have been developed to sample serially the extracellular compartment. They have yielded diverse concentration/time profiles even for the same antibiotic at similar sites (skin and subcutaneous tissues). It has been shown that the various profiles are a direct consequence of compartment SA/V, which can range from > 100 to < 10. In the preclinical situation, the blister model has proven popular and reproducible but it should be remembered that the delayed profile seen is an artefact of blister geometry (SA/V < 10). On the evidence available it is likely that bacterial infections, in the presence of acute inflammation, will enhance the rate of entry of agents, while the reverse is true in areas of chronic inflammation where pathological barriers are already in place.

Human Pleural Effusions Are Rich in Matrix Metalloproteinases

We identified and characterized type IV collagenase and gelatinase activity in pleural fluid from 32 patients. The capacity to substantially degrade type IV collagen was demonstrated in every pleural sample. Comparable results were also noted for the degradation of a radiolabeled gelatin substrate. Gelatin gel zymography of the pleural fluids revealed two prominent zones of lysis at 66 kDa and 92 kDa. These were identified by specific polyclonal antibodies as human matrix metalloproteinases MMP-2 and MMP-9. The concentration of MMP-2 in pleural fluid, as measured by enzyme-linked immunoassay, averaged 1,622 ng/ml whereas those of MMP-9 were 210 ng/ml. Substrate degradation activity was compared in both serum and pleural fluid from three patients and found to be similar. In serum this enzymatic activity was primarily due to MMP-9 whereas in pleural fluid, the predominant gelatinase was MMP-2. This was confirmed by immunoassay that showed that MMP-2 levels were two to five times higher in pleural fluid than in serum. We conclude that substantial amounts of MMP-2 and, to a lesser degree, MMP-9 are present in pleural effusions. The bioactivity and the immunoactivity of these enzymes did not help to distinguish among pleural fluids characterized as transudates, nonmalignant exudates, or malignant exudates. The differences in the distribution of these enzymes in pleural fluid and blood suggest that their presence is not due simply to the ultrafiltration of plasma, but rather to synthesis by the resident cells at the pleural surfaces.

Ultrafiltrate Analysis Confirms the Specificity of the Selected Method for Plasma Ammonia Determination

The specificity of the direct enzymatic determination of plasma ammonia has hitherto not been unequivocally confirmed, because a suitable comparison method was lacking. Therefore a method variant was elaborated, which includes ultrafiltration to eliminate the high-molecular-mass components regarded as potential sources of unspecificity in the direct measurement procedure according to Rattliff, C.R. & Hall, F. F. (Select. Meth. Clin. Chem. 9, 85-90 (1982)). As the distribution of ammonia during plasma ultrafiltration is markedly influenced by pH and protein concentration, plasma pH is adjusted to 5.5 where the distribution ratio is 1 and nearly independent of actual protein concentration. Acidification significantly diminishes the spontaneous increase of ammonia in plasma at 2-4 degrees C, and the plasma ultrafiltrate is virtually stable. Taking into consideration the slow ammonia formation during sample preparation, excellent agreement was found between ammonia concentrations measured in plasma and in plasma ultrafiltrate, using samples with an apparently normal matrix (n = 30), dysproteinaemia (n = 32) or paraproteinaemia (n = 8). Our data show that the protein matrix of the sample does not cause significant unspecificity in the direct "endpoint" procedure for ammonia determination nor does it affect imprecision. In samples with added bilirubin (up to 252 mumol/l), haemolysate (haemoglobin up to 3.87 g/l) or lipid emulsion (triacylglycerol up to 3.86 mmol/l) ammonia values determined directly in plasma differed maximally by 4% from ultrafiltrate values. A simplified procedure for the ultrafiltration of plasma may be used routinely in clinical service in cases of grossly icteric, haemolytic or turbid samples.

プリン，ピリミジン代謝の研究（1）

A reversed-phase high-performance liquid-chromatography method for determining simultaneous quantitation of purine-pyrimidine metabolites, allopurinol and oxipurinol in plasma and urine samples was studied. Separation was optimal with phosphate buffer (10 mmol/l, pH 5.0) containing 1% methanol as an eluent and mu Bondapak C18 as a column. An isocratic separation of a standard mixture of 13 compounds was achieved within 40 minutes with adequate reproducibilities (coefficient of variation: 2.49% for 1.63 mumol/l orotidin-0.12% for 50 mumol/l uridine). A simple ultrafiltration of plasma yielded quantitative recoveries (uric acid: 101.7-107.5%, hypoxanthine: 90.4-102.8%, xanthine: 95.9-99.5%, oxipurinol: 104.4-107.1%, allopurinol: 97.4-103.4%). Compounds were identified by their retention times, absorbance ratios, co-elution with standards and enzymic shifts. In addition to the above compounds, simultaneous quantitation of pseudouridine, uridine, adenine and inosine in the plasma would be possible under the same conditions.

Promotion of lymphocyte blastogenesis by hemodialysate of chronic renal failure.

Effects of hemodialysate of patients with chronic renal failure (CRF) on blastogenesis of human peripheral blood lymphocytes in the presence of concanavalin A or phytohemagglutinin was investigated. Hemodialysates from 11 CRF patients significantly promoted lymphocyte blastogenesis when compared with control dialysis fluids (p less than 0.01). The strongest activity (39% promotion of the lymphocyte blastogenesis) was observed with a hemodialysate obtained at 0.5 h after beginning dialysis. The activity decreased thereafter. On the contrary, the blastogenesis-promoting activity in plasma decreased significantly after hemodialysis (p less than 0.01, n = 11). To further confirm the presence of low-molecular-weight factor(s) in CRF, ultrafiltration of plasma obtained from CRF and healthy subjects was conducted using a membrane filter with a molecular cutoff of 3,000 D. The filtrate of CRF plasma significantly promoted lymphocyte blastogenesis when compared to that of healthy subjects (p less than 0.01). Heat treatment (100 degrees C, 40 min) did not abolish the activity of the hemodialysate. None of the drugs taken by the patients nor creatinine accumulated in CRF promoted the lymphocyte blastogenesis. Chromatographic analysis of a hemodialysate demonstrated several peaks which were absent in the control dialysis fluid. These results showed the presence of a novel lymphocyte-stimulating factor(s) in CRF, which is heat stable and has a low molecular weight (less than 3,000 D).

Factors affecting inorganic mercury transport and toxicity in the isolated perfused proximal tubule.

The effects of cysteine (80 microM), glutathione (80 microM), rabbit albumin (100 microM), and an ultrafiltrate of rabbit plasma on the toxicity and transport of inorganic mercury (Hg2+; 18.4 microM) in isolated perfused S1, S2, and S3 segments of the renal proximal tubule from the rabbit were studied. Cellular and tubular injuries were assessed qualitatively by light microscopy observations and quantitatively by the tubular leak of the volume marker 3H-glucose. The lumen-to-bath transport of inorganic mercury was assessed by measuring both the rate of disappearance of inorganic mercury from the luminal fluid and the rate of appearance of inorganic mercury in the bath. When glutathione was added to the perfusate containing the inorganic mercury, no signs of epithelial cell necrosis or injury were detected in any of the three segments of the proximal tubule. There was also an absence of or a decrease in cellular injury in the epithelium of the same tubular segments when either cysteine or the ultrafiltrate was present in the perfusate. However, when rabbit albumin and inorganic mercury were present in the perfusate, severe degenerative and necrotic changes occurred very rapidly in the epithelium of all three segments of the proximal tubule. In almost every instance where glutathione, cysteine, or the plasma ultrafiltrate were present in the perfusate, the disappearance flux of inorganic mercury from the tubular lumen into the tubular epithelium was lowered. It was concluded that glutathione, cysteine, and the ultrafiltrate of rabbit plasma provide isolated perfused S1, S2, and S3 segments of the proximal tubule varying degrees of protection from the toxic effects of inorganic mercury. This protection appears to be related to a decrease in the movement of inorganic mercury across the luminal membrane of the tubular epithelial cells.

Ion chromatographic determination of plasma oxalate in healthy subjects, in patients with chronic renal failure and in cases of hyperoxaluric syndromes

An ion chromatographic procedure for the determination of plasma oxalate is proposed, in which the ultrafiltered sample is injected into an ion-chromatographic system. Sample processing appears effective in avoiding spontaneous oxalogenesis. Sensitivity (down to 1.0 μmol/1) allows determinations in normal and pathological samples; recoveries from plasma ultrafiltration are 94.6 ± 11.7%. Protein binding was investigated and precautions to improve recoveries from plasma ultrafiltation are proposed. The technique is simple to perform and rapid enough to be useful for routine purposes. Plasma oxalate concentrations from healthy controls averaged 6.75 ± 26.2 μmol/1 (mean ± S.D. n = 18); samples from patients with primary hyperoxaluria and chronic renal failure undergoing regular dialysis were also analysed and some of the data obtained are reported and discussed.

Plasma ultrafiltration as cancer therapy.

Studies of cancer-related immunosuppression reveal the presence of low-molecular-weight (less than 10 kilodaltons) serum factors capable of in vitro lymphocyte suppression. Removal of suppressor factors by ultrafiltration (UF) prolongs survival in tumor-bearing rabbits. This study determined the prevalence of low-molecular-weight suppressor factors in patients with cancer and normal volunteers and evaluated safety and feasibility of UF in patients with cancer. Intact serum and serum ultrafiltrate from 32 patients with cancer and 24 normal volunteers was examined with mitogen-induced lymphocyte blastogenesis. Eleven (34%) of serum samples from patients with cancer suppressed blastogenesis, while ultrafiltrate was suppressive in 25 (78%). None of the ultrafiltrate from normal volunteers was suppressive. Six patients with cancer underwent UF in a phase I trial, completing 82 sessions. There were no therapy-related complications, and high-performance liquid chromatography showed significant (greater than 90%) posttreatment reduction in serum suppressor factors.

Controlling factors in hemofiltration

Ultrafiltration of bovine plasma and blood (hemofiltration) was performed in a dual-parallelmembrane test device over a wide range of hematocrits (0–85%), plasma protein concentrations (3–20 gm%), channel heights (0.022–0.073 cm) and flow rates. The plasma ultrafiltration data was used to determine film theory equation constants by regression techniques similar to that which had been done by others in the past. The ratios of hemofiltration to plasma ultrafiltration rates were then correlated by an independent analytical function of hematocrit, total protein concentration, and the superficial wall shear rate. The filtration flux ratio has a Fricke equation limit at low shear rates which would be below unity while a maximum filtration flux ratio greater than one was observed (and correlated) at high shear rates with hematocrits below 42%. The form of the hemofiltration correlation was also applied to previously published augmentation data in a pure shear field without plasma proteins. The design ramifications of the correlation include the determination of when addition augmentation methods are needed. The combination of both plasma ultrafiltration and hemofiltration correlations show how each variable affects and controls hemofiltration. The correlations are for small percentages of the incoming flow being filtered. For large flow fractions being filtered the correlations would have to be integrated along the axial length combined with mass balances. The hemofiltration equations can yield slightly lower fluxes at the lowest channel heights and slightly higher fluxes for the larger channel heights, presumably due to the Fahraeus—Lindqvist effect. The channel heights and shear rates utilized included conditions where this effect should be considerable as well as conditions where it should not be present. The regression techniques were applied to all the data.

Lacrimal fluid and electrolyte secretion: A review

Lacrimal gland fluid is an important component of the precorneal tear film. The rate of lacrimal gland fluid secretion is controlled primarily by parasympathetic innervation, and it is, apparently, modulated by sympathetic innervation. Lacrimal gland fluid is produced in two stages, secretion of a primary fluid which resembles an isotonic ultrafiltrate of plasma in the acinus-early intercalated duct region, and secretion of a KCl-rich fluid in subsequent ductal elements. Little is known about the electrolyte transport mechanisms of the ductal epithelia. Recent work using a variety of techniques, including tracer flux measurements, intracellular electrical recording, intracellular ion activity measurements, patch clamping, and analytical subcellular fractionation, supports a model for transcellular Cl-secretion in the acinus which involves Cl--selective channels in the apical plasma membrane and an array of Na+/H+ antiporters, Cl-/HCO3-antiporters, K+ channels, and Na,K-ATPase in the basal-lateral plasma membrane.