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Renal failure associated with the use of dextran-40.

A typical case of dextran-40 associated acute renal failure is presented. In this patient a single plasma exchange was successful in considerably lowering the plasma dextran concentration. At the same time the elevated plasma oncotic pressure was reduced to normal values. Diuresis returned within 12 h. Several possible explanations of the mechanism of renal failure associated with the use of dextran-40 are discussed. While the mechanism of dextran-associated renal failure remains unsolved, plasma exchange seems to be effective therapy.

Acute Kidney Injury↗

[Effect of low molecular dextran on maternal microrheologic parameters, fetal heart rate and transcutaneous fetal oxygen partial pressure in labor].

The results from animal experimental research have shown that the infusion of dextran 40 increased the uterine blood flow mainly by decreasing the vascular resistance and by this improving the oxygen supply to the fetus. Dextran 40 given in a dosage of 50 ml/min within 10 minutes to 11 pregnant women during parturition showed that the fetal blood PO2 increased if the PO2 before infusion was low and decreased if the PO2 before infusion was high. Therefore the question enhanced if the reduced maternal oxygen capacity results in a reduction of fetal PO2 (tcPo2) too. After informed consent 10 healthy pregnant women at term with a normal pregnancy got an infusion of 500 ml dextran 40 during 30 minutes. The following maternal parameters were measured: heart rate, mean arterial blood pressure, intrauterine pressure and transcutaneous carbon dioxide tension (tcPCO2). Maternal microrheological parameters before and after infusion of dextran 40 were estimated as following: plasma viscosity, erythrocyte aggregation, serum osmolality, colloid osmotic pressure, hemoglobin and haematocrit. The mothers were laying in the side position and their ventilation was controlled by tcPco2 (Dräger, Lübeck). The following fetal parameters were registered: basal fetal heart rate, transcutaneous fetal oxygen partial pressure (tcPo2) and the umbilical cord blood gases. After rupture of the fetal membranes and at a cervix dilatation of about 5-7 cm a tcPo2 electrode (Dräger, Lübeck) was fixed at the fetal scalp with an acrylate glue (Histoacryl) and by this fetal tcPo2 and its "flow" registered.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Localization of proliferating cells in lymphatic tissues triggered by dextran sulfate.

Mice were injected with dextran sulfate in the presence or absence of various amounts of sheep red blood cells. The incorporation of thymidine into the proliferating cells of spleen, lymph nodes and thymus was investigated using autoradiographic and histologic techniques. Dextran sulfate triggered selective proliferation of cells localized in the marginal zone of the white pulp of the spleen. The uptake of colloid carbon particles was also enhanced by dextran sulfate in this area of the spleen. The results are consistent with the suggestion that dextran sulfate triggers proliferation of non-thymus-derived cells probably a sub-population of B-lymphocytes and activates phagocytic cells.

Animals↗

Similarity of the structure of ferritin and iron . dextran (imferon) determined by extended X-ray absorption fine structure analysis.

Ferritin, a natural complex of iron oxide encased in protein, and iron . dextran, a synthetic complex of iron oxide coated with dextran, have the similar properties of maintaining high concentrations of iron in solution at physiological pH and releasing iron relatively slowly in vivo. Extended x-ray absorption fine structure (EX-AFS) analysis was performed on each complex and compared to see if the structures of the iron cores were similar. The results obtained from the extended x-ray absorption fine structure technique show that the near-neighbor environment around the average iron atom in ferritin and iron . dextran is identical, within experimental uncertainty, for the first three shells. The similarity of the iron cores in both complexes may explain the similarity of iron release in vivo. Ferritin has a protein coat which is composed of 24 subunits arranged in a hollow sphere with six channels through which the iron may move during deposition and release. However, little is known about the requirements of the protein structure in ferritin for the maintenance of high concentrations of iron in a soluble, nontoxic form or about the role of the protein in the release of iron from ferritin. The results suggest that iron . dextran will be a useful model compound in studies of the relation of the iron core and protein in ferritin to function.

Dextrans↗

Binding constants of NZB myeloma antidextrans for dextrans and isomaltose oligosaccharides determined by affinity electrophoresis.

Association constants of dextrans (Ka) and oligosaccharides (Kia) from NZB myeloma antidextrans (PC3858 and PC3936) were studied by affinity electrophoresis. With linear dextrans or with those with a low degree of branching, Ka ranged from 2.7 X 10(3) to 5.4 X 10(4) ml/g for PC3858 and from 1.3 X 10(4) to 2.6 X 10(5) ml/g for PC3936. Completely linear alpha-(1 leads to 6)-linked dextrans, LD7 and D3, showed relatively high affinities for the two NZB antidextrans. With oligosaccharides, the Kia value increased as the number oa alpha-(1 leads to 6)-linked glycosyl residues increased. Isomaltoheptaose (IM7) showed the highest Kia (1.9 X 10(4) M-1 for PC3858 and 1.63 X 10(4) M-1 for PC3936), whereas isomaltose (IM2) had the lowest Kia (2.36 X 10(2)M-1 for PC3858 and 1.32 X 10(2)M-1 for PC3936). Pullulan and glycogen showed very weak affinity for PC3936, but they did not react at all with PC3858. These findings indicate that NZB myeloma antidextrans, PC3858 and PC3936, are specific for internal chains of alpha-(1 leads to 6)-linked dextrans. Data on the precision with which Ka and Kia can be determined are presented.

Animals↗

[Long term tolerance of highly dosed infusions of hydroxylethylstarch and dextran 60 in normovolemic rabbits].

Normovolemic rabbits were administered 50 ml of 6% hydroxyethyl starch in saline, 6% dextran 60 in saline solutions 5 days a week over a period of 3 weeks. Only 2 rabbits of the hydroxyethyl starch or the dextran treated series and 4 rabbits of the saline series survived 3 weeks. In all 3 series large amounts of fluid in the serous cavities and edema of the lungs due to the overload of fluid have been observed. Severe hydropic changes were found in the liver and kidneys of the hydroxyethyl starch and dextran treated series, but not after prolonged administration of saline alone. According to the findings presented there is no difference between the effects due to the prolonged administration of extremely high doses of hydroxyethyl starch and dextran 60.

Animals↗

[The antistreptolysin reaction with and without dextran sulfate addition in various diseases].

It is reported on the results of determinations of the antistreptolysin titre in patients with infectious hepatitis, renal and essential hypertension, mitral stenosis, acute tonsillitis, scarlet fever, rheumatic fever as well as rheumatoid arthritis according to the usual and the dextran sulphate absorption method in altogether 739 patients. Here as in a former publication in 1,700 normal persons partly considerable significant differences between the antistreptolysin titre with and without dextran sulphate were found. The two techniques are discussed, also the influence of the beta-lipoproteins with their proportion of phosphatide on the result of the antistreptolysin titre. It is possible to absorb beta-lipoproteins and perhaps also phosphatides with the help of the addition of dextran sulphate. The present investigations show unequivocally that the absorption the dextran sulphate is a necessary demand which saves the clinician from diagnostic and therapeutic errors. The antistreptolysin reaction is to be regarded only as one constituent for the clinical diagnosis and must not be overvalued in its importance.

Antigen-Antibody Reactions↗

Disposition and pharmacokinetics of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate, in the rat.

The disposition and pharmacokinetics of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMCD), following iv bolus administration was studied in rats. Three types of MMCD, conjugates with dextran of molecular weights of 10,000, 70,000, and 500,000, were tested and disposition of carrier dextran and MMC was determined by 14C radioactivity counting and bioassay, respectively. Radioactivity was accumulated in the reticuloendothelial system such as the liver, spleen, and lymph nodes after injection of all three types of 14C-MMCD, but not in the lung, heart, and muscle. Renal distribution of 14C-MMCD varied with the molecular size of the carrier. After injection of cold MMCD, plasma concentrations of MMC in the free and conjugated forms were determined separately on the bases of bioassay. Similar sustained plasma levels of MMC were detected regardless of the carrier size although the concentration-time profiles of MMCD varied with the size of dextran. These plasma concentration data were fitted to a compartment model including a first order conversion process from MMCD to MMC in the central and peripheral compartments of MMCD. Kinetical analysis revealed that MMCD acts as a reservoir of MMC which behaves characteristically as a macromolecule while supplying active MMC in the body.

Animals↗

Prevention of postoperative thromboembolism by dextran 70 or low-dose heparin.

The efficacy of intravenous infusion of dextran 70 or subcutaneous administration of low-dose heparin in preventing postoperative thromboembolic complications has been investigated in a prospective randomized trial. During part 1 of the study, 232 patients over the age of 40 years who were undergoing major gynecologic surgery underwent a complete test protocol. The 125I fibrinogen uptake test (FUT) was used for the diagnosis of deep vein thrombosis (DVT) in 117 patients in the dextran and 115 patients in the heparin group. Heparin was significantly more effective than dextran for reducing DVT (P less than .001). During part 2 of the study no FUT was done but the incidence of clinical and fatal pulmonary embolism (PE) and the number of complications were studied. Of 444 patients (parts 1 and 2) 1 fatal and 2 nonfatal pulmonary emboli were diagnosed. All the emboli occurred in the dextran group. The benefit: hazard ratio appeared to favor heparin for the prophylaxis of DVT.

Adult↗

The effect of dextran 70 on the structure of plasma-derived fibrin gels.

Measurements of fiber mass-length ratios and fibrin gel elastic modulus as a function of dextran 70 concentration are reported for fibrin gels derived from human plasma. Dextran 70 at 0.1 mg/ml produces a 50% reduction in the storage modulus of fibrin gels obtained from human plasma diluted 1:10 with saline. Since the fibrin fiber diameter increases as only a weak function of the dextran 70 concentration, the lower elastic modulus most likely results from a reduction in network branch points. Aprotinin is also shown to modulate the dextran effect.

Aprotinin↗

Water-soluble, dextran-linked retinal: preparation, vitamin A-like activity in rats, and effects on melanoma cells.

A new, water-soluble, polymer-linked form of retinal was synthesized and tested for its ability to support the growth of vitamin A-deficient noninbred Holtzman rats and to inhibit the proliferation of melanoma cells in culture. Retinal was conjugated to the hydrazide of carboxymethyldextran in the presence of alpha-and beta-cyclodextrins. The aqueous solutions of the product contained between 200 and 1,000 micrograms retinal/ml as opposed to the low water solubility (< 0.01 micrograms/ml) of retinal itself. The retinal-dextran complex, although barely resorbed from the gastrointestinal tract, supported the growth of rats fed a vitamin A-deficient diet when administered ip at 2.3 mumol of retinal equivalent/kg body weight. Retinal and the retinal-dextran complex exhibited differential cytotoxicity toward S91 melanoma cells and caused cell lysis at 10 and 500 microM (retinal residue), respectively. At noncytotoxic doses both free retinal and its dextran-linked derivative reduced the cell proliferation rate in a time- and dose-dependent fashion with median inhibitory doses of 1 and 4 microM (retinal residue), respectively. These data demonstrated that the water-soluble retinal-dextran complex retained certain biologic activities of retinal and was less cytotoxic.

Animals↗

The dextrans--clinical data.

The use of dextrans in clinical practice are mainly based on the following effects: 1. Plasma volume effects 2. Flow Promotion 3. Antithrombotic effects. The dextrans are the only plasma volume substitute with the antithrombotic effect but this discussion will only deal with their effects on plasma volume and flow. The effect on plasma volume--the colloid supported intravascular volume--can be calculated as ml of water held in circulation per gram circulating colloid--for dextran 70 around 20 ml/g, for albumin 18 ml/g and for plasma protein 12-13 ml/g. After infusion of a plasma volume substitute the volume effect depends on dose injected, molecular weight distribution, rate of disappearance from the intravascular department mainly via the kidneys. The clinical experience of a reliable plasma volume expansion can be demonstrated in animal experiments comparing different infusion fluids. The effect on erythrocyte aggregation depends on kind of substance and molecular weight distribution. The flow promoting effect is mainly due to restoration of plasma volume but also related to hemodilution and aggregation. The vasoconstriction seen in shock can be counteracted essentially with colloid supported plasma volume expansion. The supposed influence of the dextrans on the kidney function in some clinical cases has been investigated experimentally.

Blood Circulation↗

Selective inhibition of RNase H by dextran.

Ordinarily, ribonuclease H hydrolyzes poly(rA) . poly(dT) and phiX174DNA-RNA at equal rates. Here we show that in the presence of dextran, the degradation of poly(rA) . poly(dT) is inhibited, while that of phi 174DNA-RNA is not. A similar inhibition by sucrose is found to be due to trace contamination of dextran in the sucrose. Ribose, deoxyribose, and a number of other saccharides fail to inhibit RNase H. In experiments where the two substrates are presented in the presence of the inhibitor, the kinetics indicates that both molecules are recognized by the enzyme, but only the phi X174DNA-RNA is degraded. That is, dextran does not interfere with the recognition site, but rather blocks hydrolysis. It is proposed that the ability of dextran to confer selectivity toward different substrates reveals a potential regulatory mechanism for RNase H activity which may represent a control step in the initiation of DNA synthesis.

Dextrans↗

Genetics of the alpha 1,6-dextran response: expression of the QUPC52 idiotype in different inbred and congenic strains of mice.

Antibodies to dextran B512 were raised in various strains of mice and were assayed by a radioimmunoassay procedure. Idiotypic antibodies to the IgA(k) dextran B512 binding myeloma proteins QUPC52 and W3129 of BALB/c origin were prepared in rabbits. After adsorption each antiserum was specific for the immunizing myeloma protein and did not react with hundreds of other myeloma proteins; nonetheless, antibodies to dextran B512 from various strains of mice cross-reacted in these test systems. Of the 2 idiotypes tested, the W3129 idiotype was more universally expressed in different strains of mice. The QUPC52 idiotype was the predominant idiotype in BALB/c anti-dextran B512 antibodies and was found in only a few other inbred strains. Using a battery of congenic and inbred strains, it was shown that the QUPC52 idiotype was controlled by genes linked to the Igh complex locus (chromosome 12) and to the Ig kappa complex locus (chromosome 6). The W3129 idiotype was found in a number of stocks of mice in the genus Mus recently isolated from the wild. The QUPC52 idiotype thus far was found only in inbred mice.

Animals↗

Dextran and carrageenan evoke different inflammatory responses in rat with respect to composition of infiltrates and effect of indomethacin.

A study of the anti-inflammatory reaction after the injection of dextrans (60 mg) of various molecular weights (10,000-2,000,000) or carrageenan (0.5 mg) into the rat pleural cavity revealed two types of response. The dextrans induced within 30 min partial degranulation of mast cells and a rapid accumulation of fluid with little protein and a few neutrophils. This response was not suppressed by treatment with indomethacin. Carrageenan, in contrast, caused no mast cell degranulation, histamine release or early edema, but a progressive accumulation of a protein-rich exudate which contained large numbers of neutrophils. This response was inhibited by indomethacin. A commercial variety of dextran (mw 250,000) produced both types of response in which a rapid infiltration of protein-free fluid into the pleural cavity was followed by the appearance of protein and numerous neutrophils. The major plasma proteins were identified in exudates collected 4 hr after the injection of either carrageenan and the commercial dextran; in both cases, the numbers of neutrophils were related to the protein content of the exudate. The data suggest that inflammatory infiltrates may be formed through two distinct mechanisms: one associated with transudation of protein-free fluids, the other to exudation of plasma proteins and neutrophils. There are indications that these responses may involve different mediators.

Animals↗

Penicilloyl-dextran conjugates as reagents for skin testing in penicillin allergy.

A procedure for implanting amino groups in the dextran molecule is described. The aminated polymer prepared from a dextran sample with a molecular weight of 20,000 was found to contain approximately 16 amino groups per molecule. Similarly to polylysine, the aminated dextran may be penicilloylated by incubation with penicillin at high pH. The penicilloyl-dextran (P-Dex) conjugate prepared in this way was found to contain approximately 8 penicilloyl (PO) groups per molecule. P-Dex was found practically nonimmunogenic in rabbits and showed itself antigenically active in precipitin, passive hemagglutination and passive cutaneous anaphylaxis (PCA) tests performed with a PO specific antiserum. A good correlation was found between the skin tests performed parallelly with P-Dex and penicilloyl-polylysine (PPL) in four subjects with penicillin allergy.

Animals↗

New dextran derivatives. I. Nitrogen containing derivatives.

Three new derivatives of dextran were obtained: 3-morpholine-2-hydroxypropyl ether of dextran (I), hydroxamic acid of carboxymethyl dextran (II), and oxime of ketodextran (III). All the three derivatives exhibited low toxicity at parenteral administration to laboratory animals. (I) and (II) showed the capability of weakening the activity of tetanus and malignant edema toxins. Additionally, (I) showed immunotropic activity. Biological activity was observed when the derivative (I) had been obtained from dextran of the molecular weight 4000. At the molecular weight 20,000 the activity did not appear. Similarly, no activity was observed under oral administration.

Animals↗

Experimental pancreatitis: Effect of plasma and dextran on pancreatic blood flow.

In spite of extensive investigations, many aspects of the hemodynamic changes occurring in acute pancreatitis are understood poorly. A dog model was established in which continuous measurements of pancreatic arterial blood flow, cardiac output, and mean arterial blood pressure were made using electromagnetic flow probes and a pressure transducer, respectively. Pancreatitis was induced and the animals were monitored for 3 hours. In addition, control animals (group I) without pancreatitis also were done. All animals 50 ml of saline in the first hours. Three methods of therapy then were instituted in the dogs with pancreatitis and their effects were recorded. group I 6 dogs control animals no pancreatitis saline 50 ml/hr group II 10 dogs saline 50 ml/hr group III 6 dogs plasma 15 ml/kg over 45 min then saline 50 ml/hr group IV 10 dogs saline 50 ml and 1.5 ml/kg of dextran 40/hr These results confirm the observations made previously using a transillumination technique--that the pancreatic circulation rapidly reduces in acute pancreatitis. Administration of plasma produced a significant (P less than 0.05) but transient increase in the cardiac output and pancreatic blood flow; however, the blood pressure remained low. Dextran 40 minimally increased cardiac output, but it significantly improved the blood pressure and maintained the pancreatic blood flow. Low-dose, low-molecular weight dextran 40 appears to help to maintain pancreatic blood flow in acute pancreatitis. The possible mechanisms concerning the made of action of dextran 40 will be discussed.

Animals↗