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Glomerular filtration barrier in aminoglycoside-induced nephrotoxic acute renal failure.

To elucidate the role of the glomerular filtration barrier in the development of nephrotoxic acute renal failure, we produced acute renal failure in rats with either gentamicin or tobramycin. Both drugs evoked changes in the glomerular capillary endothelium. Gentamicin administration resulted in a dose-related decrease in the diameter, density and area of endothelial fenestrae, which was considerably more pronounced than those observed with tobramycin. Prolonged, high-dose gentamicin administration caused a decrease in creatinine clearance, an increase in plasma renin activity and a corresponding decrease in the area available for filtration. These changes reverted with continued drug administration. These results support the notion that morphological alterations in the filtration barrier are responsible for the decrease in filtration observed in acute renal failure. The changes may be at least in part mediated by the renin-angiotensin system.

Acute Kidney Injury↗

Effect of saline infusions on intrarenal distribution of glomerular filtrate and proximal reabsorption in the dog.

The effect of acute extracellular volume expansion with saline on the intrarenal distribution of glomerular filtrate, was studied in dogs utilizing micropuncture techniques in which samples were obtained by both recollection and from new tubules. Recollection was examined in seven dogs during continuous hydropenia and in five dogs during continuous saline diuresis. Recollection was associated with an increase in nephron flow rate of 8% during hydropenia and 27% during saline diuresis. In addition, during continuous saline diuresis, shortened transit times and lowered intratubular pressures were recorded in previously punctured tubules. Despite increased tubular flow, fractional reabsorption was unchanged. Nephron glomerular filtration rates (gfr) were measured during hydropenia and then after acute volume expansion in 10 dogs. In the repunctured tubules gfr rose 38% more than total glomerular filtration rate (GFR). In contrast, when new tubules were punctured during volume expansion, nephron gfr and total GFR changed proportionately. The disproportionate rise in nephron gfr after volume expansion noted with the recollection technique appears to be artifactual when contrasted to micropuncture of new tubules. With acute volume expansion, fractional reabsorption decreased 15% in recollected samples and 16% in newly sampled tubules. Increased nephron gfr cannot account for the fall in fractional reabsorption. It is concluded that in dogs, saline diuresis is not associated with redistribution of filtrate from deep to superficial nephrons, and that the fall in proximal fractional reabsorption is caused by diminished absolute reabsorption.

Animals↗

Canine systemic lupus erythematosus. Transmission of serologic abnormalities by cell-free filtrates.

The presence of viruses was sought in a colony of dogs bred from parents with systemic lupus crythematosus (SLE). Cell-free filtrates prepared from the spleens of these animals were injected into newborn dogs, mice, and rats. The canine recipients developed antinuclear antibody (ANA) and positive lupus erythematosus (LE) cell tests: ANA and, in some cases, antinative DNA antibodies were produced by the murine recipients: no abnormalities were detected in the rats. Serial passage of spleen cells or cell-free filtrates of spleen tissue in syngeneic mice reduced the time required for appearance of ANA from 9 to 4 mo. Some murine recipients of the canine filtrate developed malignant lymphomas. Murine leukemia viruses were identified in these tumors by electron microscopic, virologic, and serologic technics. These neoplasms, but not other tumors known to contain murine leukemia viruses, were associated with the production of ANA. Puppies inoculated with the canine filtrate-induced mouse lymphoma developed ANA and positive LE cell tests within 4 mo. THE RESULTS WERE INTERPRETED TO INDICATE THE PRESENCE IN CANINE SLE OF A VIRUS CAPABLE OF: (a) inducing the serologic abnormalities of SLE in normal dogs and mice: (b) activating latent murine leukemia viruses: and (c) spreading by both horizonal and vertical routes.

Animals↗

Skin flow the venoarteriolar response and capillary filtration in diabetics. A 3-year follow-up.

Resting skin blood flow (RF) and the venoarteriolar response (VAR = the vasoconstrictor response on standing) have been studied in 100 patients with diabetic neuropathy, in 100 diabetics without neuropathy, and in 100 normal subjects by laser Doppler flowmetry. Capillary filtration was also studied with strain gauge plethysmography. The authors followed up these patients by evaluating their microcirculation again after three years. At the beginning of the study in patients with neuropathy, RF and capillary filtration were increased. The VAR and the microangiopathy index (MI = VAR/RF) were reduced in all diabetics, to a greater extent to those with neuropathy. After three years the authors observed an increase in capillary filtration associated with a further impairment in VAR and MI, suggesting progression of microangiopathy in both groups of diabetics. These results suggest that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in neuropathics. Increased skin blood flow and capillary filtration and the impaired venoarteriolar response cause edema and may contribute to the thickening of capillary basement membranes and the progressive evolution of diabetic microangiopathy.

Adult↗

Acute airsacculitis in turkeys inoculated with cell-free culture filtrate of Pasteurella multocida.

Twenty-six female and 26 male turkeys, inoculated into the caudal thoracic air sacs with cell-free culture filtrate of Pasteurella multocida strain R44/6, were examined from 0 to 6 hours post-inoculation and compared with 26 female and 26 male sham-inoculated control turkeys given brain-heart-infusion broth. The air sac reacted rapidly with exudation of heterophils. Microscopically, low numbers of heterophils were present within air sac blood vessels and also perivascularly by 0.5 hour after inoculation. These became more numerous by 1.5 and 3 hours post-inoculation. By 6 hours post-inoculation, there was severe swelling of air sac epithelial and mesothelial cells and thickening of the air sac by proteinaceous fluid and heterophils. Ultrastructurally, mesothelial and air sac epithelial cells were vacuolated, and interdigitating processes of epithelial cells were separated. Microscopically, in control turkeys, rare heterophils were present perivascularly at 1.5, 3, and 6 hours after inoculation. Ultrastructurally, all features were normal. In turkeys given cell-free culture filtrate, total cell counts in air sac lavage fluids increased markedly by 3 hours post-inoculation in which heterophils predominated (greater than 97%). There were only slight increases in cell counts of air sac lavages from control turkeys. The circulating blood heterophil cell count dropped transiently at 1.5 hours post-inoculation, followed by a return to normal 3 hours after inoculation, and by heterophilia by 6 hours post-inoculation in turkeys given either cell-free culture filtrate or brain-heart-infusion broth. These results indicate cell-free culture filtrate of P. multocida induces hematologic, cytologic, and morphologic changes indistinguishable from those induced by cultures of P. multocida.

Acute Disease↗

Erbium filtration for dose reduction in dental radiography.

Previous work has suggested that rare-earth filtration of diagnostic X rays is an effective means of dose reduction in radiology. Erbium (atomic number 68) is particularly promising in this respect. The effects on the X-ray beam and surface dose of the addition of 0.1 mm of erbium foil to the conventional filtration of a GE1000 dental X-ray set were investigated. Filtration by 0.1 mm of erbium produced a beam of narrower spectrum, greater penetration but lower intensity than that filtered conventionally by aluminium alone. The overall dose reduction achieved in dental radiography was greater than 30% between 65 and 85 kVp with a maximum dose reduction of 42% at 65 kVp. The question of the cost-effectiveness of erbium filtration as a radiation protection measure is also addressed.

Erbium↗

The use of the anti-Acholeplasma activities of Streptomyces culture filtrates for the screening of new antibiotics.

A screening method for new antimicrobial agents from streptomyces culture filtrates was developed. Three different types of test organisms were used for determining the antimicrobial activities of the culture filtrates: they were (a) an antibacterial activity test against Staphylococcus aureus, (b) an antimycoplasmal activity test against Acholeplasma laidlawii, and (c) a cytotoxicity test against HeLa-S3 cells. The active filtrates showing antimicrobial spectra (anticellogram) which did not match those of known antimicrobial agents were used for further purification to obtain new antimicrobial agents. Of these screening methods, antimycoplasmal activity against Acholeplasma laidawii was the most sensitive for discriminating new compounds contained in the filtrates of known antibiotics.

Acholeplasma laidlawii↗

An improved filtration rate for measuring red cell deformability.

In order to follow the filtration of a red cell suspension with time, the filtration technique described (1) has been modified. The red cell suspension is filtered through a polycarbonate membrane filter (pore diameter 5 micron) under gravitational force. The filtrate is collected in a plastic tube connected to an isometric transducer, the output of which is registered on a chart recorder. The linear part of the curve obtained is used to calculate the slope and the relative filterability (RF) ie the ratio of the rate of flow of the red cell suspension to the rate of flow of the suspending medium. The reproducibility of the technique is demonstrated by a less than 5% coefficient of variation in one blood sample less than 5% interobserver variation and a weekly variation from the same donor of less than 5%. The fast filtration rate of a highly diluted red cell suspension (0.5-1%) may be followed with this technique, taking the first 15 seconds to calculate it. The technique has proved useful in detecting differences in red cell deformability in connective tissue disorders (Scleroderma, Raynaud's phenomenon) also between stored and freshly prepared red cell suspension and its improvement by drugs (pentoxifylline, dipyridamole).

Dipyridamole↗

[Culture filtrate of Aspergillus fumigatus and its cytotoxic activity against leukocytes].

Aspergillosis has become the biggest cause of death among mycoses in Japan. The main causative agent is Aspergillus fumigatus and its virulence factors have been variously investigated, yet much remains to be clarified. We recently found that the culture filtrate of A. fumigatus has potent anti-leukocyte activity. It seriously damages macrophages and hampers the function of polymorphonuclear neutrophils. The filtrate is also active in vivo: when injected intraperitoneally, the culture filtrate lowered the survival of mice infected with A. fumigatus. This activity becomes overt within 24 hours of culture of the fungus. Although the mechanism of pathogenicity of A. fumigatus is believed to be somewhat complex, we suggest the activities shown in the culture filtrate may play a crucial role in the development of the infection.

Animals↗

[The inhibitory effect of tissue plasminogen activator combined with 5-fluorouracil polyphase liposome on the scar formation in experimental filtration surgery].

OBJECTIVE: To study the effect of tissue plasminogen activator (t-PA) in combination with 5-fluorouracil (5-Fu) polyphase liposome on the prevention of scar formation in filtration surgery. METHODS: Bilateral trabeculectomy filtering procedures were performed on 16 New Zealand white rabbits. The rabbits were divided into 4 groups of four rabbits each. In a randomized fashion, the first group received intracameral normal saline (0.1 ml) immediately following surgery and subconjunctival injection of 0.2 ml polyphase liposome (no drug) every 4 days serving as the control. The second group received intracameral t-PA 25 micrograms (0.1 ml) immediately following surgery. The third group received subconjunctival 5-Fu polyphase liposome 5 mg immediately after the procedures of filtration surgery and then every four days for another three injections. The fourth group received both intracameral t-PA 25 micrograms and subconjunctival 5-Fu polyphase liposome as in the third group. All eyes of the four groups were enucleated two weeks after the operation. RESULTS: Two weeks after the surgery, the average intraocular pressure demonstrated a significant decrease in the third and fourth groups (P < 0.05), but did not show a significant decrease (P > 0.05) in the control and the second groups, as compared with the average preoperative intraocular pressure correspondingly. Morphometric analysis of the area of fibrosis from histopathological sections demonstrated a significant decrease of episcleral fibrosis in the three drug-treated groups as compared with the control group. Moreover, the area of fibrosis in the fourth group was the least among the three drug-treated groups. Analysis of variance of 2 x 2 factorial design showed that t-PA and 5-Fu polyphase liposome had synergetic effect on the inhibition in all of the drug-treated eyes. CONCLUSION: Postoperatively, the inhibitory effect of intracameral t-PA combined with subconjunctival 5-Fu polyphase liposome on the scar formation in filtration surgery is more prominent than that of t-PA or 5-Fu used alone. They had synergetic effect on the inhibition of scar formation in filtration surgery.

Animals↗

Temporary vena caval filtration. Preliminary clinical experience with removable vena caval filters.

Removable vena caval devices look attractive in order to prevent pulmonary embolism (PE) in high risk patients when anticoagulant therapy has to be discontinued for periods shorter than 14 days. We describe our preliminary experience about 10 consecutive patients. All patients were anticoagulated for recent venous thromboembolism and the indication of vena caval filtration was mainly a short-term contraindication to anticoagulation due to surgery (8 cases) or delivery (1 case). Gunther Tulip retrievable vena caval device was used. No clinical manifestation of PE occurred during the filtration period. No thrombosis was detected at the insertion site, nor was any filter thrombosis found at the time of retrieval. Eight out of ten filters were easily retrieved through internal jugular vein. In one patient, filter could not be removed due to device tilting; in two patients, permanent filtration was secondarily requested. These results suggest that temporary vena caval filtration is efficient and safe for preventing pulmonary embolism during a short-term discontinuation of anticoagulant therapy in high risk patients.

Adult↗

[Comparative study of two methods for salvaging red blood cells: centrifugation techniques (cell-saver) versus filtration through a 100,000-dalton filter].

OBJECTIVES: Some loss of blood occurs during blood salvage. We hypothesized that plasmapheresis filtering would damage blood much less than centrifugation techniques do, thereby allowing more red blood cells to be transfused. MATERIAL AND METHODS: Laboratory study in which 16 units of whole donor blood were distributed randomly in two groups and processed either by a conventional "cell-saver" method or by hemofiltration using recirculation through a 100,000 dalton filter. We analysed hemoglobin, hematocrit, free hemoglobin, extracellular potassium, platelets, leukocytes, protein and albumin in whole blood before and after processing, and in the waste bag in each group. RESULTS: The recovery of hemoglobin and red blood cell volume was about 80% with both methods. More free plasma hemoglobin was found in the waste bag with the filtration technique. Hemolysis in processed blood was low, less than 0.1% in both groups. Platelet recovery with conventional centrifugation and filtration was 11 and 49%, respectively. Albumin, total protein and extra-cellular potassium were recovered at a rate of about 20% with the filtration technique, whereas recovery of these elements was minimal with the cell saver method. CONCLUSIONS: Both methods of autotransfusion caused moderate loss of red blood cells and low plasma levels of free hemoglobin in processed blood. Recovery of platelets, albumin, total protein and potassium was better with filtration than with the "cell-saver" method.

Blood Donors↗

Gel-filtrated fractions of alveolar bone extract contain factors promoting cell attachment and a mitogenic effect on periodontal ligament fibroblasts.

The purpose of this study was to investigate the effect of acetic acid-extracted bone proteins on human periodontal ligament fibroblasts (hPF) with respect to mitogenic and cell attachment promoting activity. Alveolar bone was harvested from healthy donors and subjected to 0.5 M acetic acid extraction, dialysis and lyophilization, and gel filtration. Promotion of cell attachment and stimulation of DNA synthesis by the crude extract and gel-filtrated fractions were studied in cultured hPE Many protein components, varying in molecular weight from 10-14 to 120 kDa, were detectable in 10% SDS-PAGE of the extract. Gel filtration of bone extract disclosed four fractions with molecular weights of 55, 34, 29 and 19-20 kDa. Both the 34 and 55 kDa fractions at a concentration of 5 microg/ml, but not the 29- or 19-20 kDa fractions, were found to promote cell attachment while only the 55 kDa fraction (5 microg/ml) stimulated DNA synthesis of hPF, Both mitogenic activity and the promotion of the cell attachment by gel-filtrated active fractions were resistant to thermal treatment (70 degrees C) and pH (4 to approximately 8) changes. These findings suggest that acetic acid extract of alveolar bone may contain components which are capable of modulating cell attachment and mitogenesis of hPF.

Acetic Acid↗

[Biosynthesis of the non-polyene antibiotic imbricin in the medium containing the producer culture filtrate].

Imbricin (macrolide nonpolyen antibiotic) biosynthesis conditions was investigated in the medium containing culture filtrate of its producer--Streptomyces imbricatus. It was demonstrated that filtrate contains some regulator substance affecting the antibiotic biosynthesis and metabolism processes of actinomycetes S. imbricatus. Maximum of regulator accumulation coincides with maximum of antibiotic biosynthesis, and amount of synthesized imbricin is proportional to the amount of the culture filtrate added to the medium. When low active mutant of S. imbricatus was grown in the medium with added regulator its activity achieved the control level. It was shown that stimulating activity of the producer's culture filtrate is not connected with pH changes or with supplement with some additional nutritional substrates.

Anti-Bacterial Agents↗

Gel-filtration of sickle erythrocytes: separation based on cell deformability.

UNLABELLED: Filtration of red blood cells (RBC) through columns of pre-swollen agarose-based beads has been evaluated using cells from subjects with sickle cell disease. Elution profiles from these gels showed elution times close to normal controls for a large fraction of sickle erythrocytes and a prolonged elution time for a sub-population of these cells. Analysis of red blood cell deformability using a computerized micropore filtration system (CTA) indicated that the deformability of sickle red blood cells in the first fraction was similar to controls but that the last fraction contained a sub-population of rigid RBC. We thus conclude that sickle red blood cell separation in columns of agarose-based beads is based upon cell deformability. Gel filtration therefore appears to be an interesting tool for the study of red blood cells in a variety of disorders with sub-populations of rigid, abnormal cells, and seems especially suited for studies in various sickle cell diseases. KEYWORDS: Deformability, gel filtration, sickle cell disease, erythrocyte

Anemia, Sickle Cell↗

Microvascular fluid filtration capacity (Kf) assessed with cumulative small venous pressure steps and with various degrees of tilt.

Tilt procedures are frequently used to test central and peripheral cardio-vascular reflexes. We have previously used venous congestion strain gauge plethysmography for measurement of fluid filtration capacity (Kf) in human legs and have shown that, providing small cumulative venous congestion pressure steps are applied, venous congestion pressure can be increased to arterial diastolic pressure without activating peripheral vasoconstrictor mechanisms. We have also studied the effect of passive tilting on Kf and have shown that the procedure does not influence the measured value Kf indicating that passive tilting does not after the total surface area available for fluid filtration, but rather the blood flow in the microvessels of the tissue under study. In the present protocol we compared the fluid filtration (Jv) resulting from small (7-10 mmHg) cumulative pressure steps with those obtained by altering hydrostatic load with progressive increases and decreases of head down tilt of -8 degrees -15 degrees and -30 degrees, followed by a similar pattern of 15 degrees, 30 degrees and 70 degrees of head up tilt. The values of Jv obtained in response to these procedures were compared with those deduced from the relationship between fluid filtration and venous congestion pressure (Pcuff) obtained during the small cumulative pressure step protocol. It was reasoned that reflex activation, by the tilt induced pressure load, would cause a reduction in local blood flow and enhanced microvascular fluid extraction. The resulting local increase in colloid osmotic pressure would give rise to lower values of Jv than those predicted on the basis of the Kf slope.

Adult↗

Self-association of cytochrome b5 in aqueous solution. Gel filtration and ultracentirfugational studies.

The aggregation state of detergent-extracted cytochrome b5 was examined by gel filtration and sedimentation equilibrium ultracentrifugation. Both techniques indicated the presence of a mixture of monomer and octomer. The proportion of monomer was decreased as the buffer salt concentration was raised and was approximately 1 muM in 10 mM Tris acetate/0.1 mM EDTA. The monomeric cytochrome b5 was isolated by gel filtration and showed a decreased tendency to aggregate in dilute buffer, although its other physical properties were identical to those of the original cytochrome b5. The monomer was found to have a Stokes radius of approximately 26 A, as determined by classical gel filtration and by an equilibrium saturation method where the sample was monitored in the gel by measuring the absorbance of the gel column directly in a dual wavelength spectrophotometer. The gel filtration and ultracentrifugation data together with the studied on the monomeric cytochrome b5 suggest the octomer is not a rapid equilibrium with monomer and this observation should be taken into account in lipid binding experiments with cytochrome b5.

Animals↗

[Filtration of buffy coat-free erythrocyte suspensions in additive solution].

Buffy coat-free red cell concentrates in SAG-M (RCC) were produced by BAT system (leukocyte content 132 x 10(6)/RCC). They were stored for 4 weeks and filtered by Erypur Optima (E), Sepacell R 500 B (S) und PALL RC 50 TM (P). Leukocyte depletion was very effective (E: 0.56 x 10(6)/RCC; S: 0.36 x 10(6)/RCC; P: 0.55 x 10(6)/RCC) but hemolysis was remarkable (E: 301 +/- 195; S: 127 +/- 123; P: 368 +/- 256 mg/RCC). Therefore preparation of two RCC per filter was only acceptable with S. In S and P loss of red cells was tolerable (E: 90.5; S. 41.8; P: 38.2). In contrast, E should be rinsed with sodium chloride at the end of the preparation. In E and S filtration times were short without additional pressure (E: 6.6 min; S: 4.7 min; P: 20.3 min). We conclude from our results that the use of buffy coat-free red cell concentrates in additive solution considerably reduces the problems of filtration, e.g. storage interval, leukocyte reduction, hemolysis, filtration flow. Despite this, bedside filtration is not recommended because quality assurance is necessary.

Blood Component Transfusion↗