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Cell interior is extremely congested with tightly packed biological macromolecules that exerts macromolecular crowding effect, influencing biophysical properties of proteins. To have a deeper insight into it we studied consequences of crowding on aggregation susceptibility and structural stability of α-chymotrypsinogen-A, pro-enzyme of serine protease family, upon addition of co-solvent reported to exert stress on polypeptides crafting favourable conditions for aggregation. Hexafluoropropan-2-ol (HFIP), a fluorinated alcohol caused structural disruption at 5% v/v unveiled by reduced intrinsic intensity and blue shifted ANS spectra. Significantly enhanced, red-shifted ThT and Congo red spectra sustained conformational changes concomitant with aggregation. FTIR and CD results confirmed transition of native structure to non-native extended, cross-linked beta-sheets. Transmission electron micrographs visibly exhibited incidence of amorphous aggregates. Macromolecular crowding, typically mimicked by concentrated solutions of dextran 70, was noticeably witnessed to defend conformational stability under denaturing condition. The native structure was retained maximally in presence of 100 mg/ml followed by 200 and 300 mg/ml dextran indicating concentration dependent deceleration of aggregate formation. It can be established that explicit consideration of crowding effects using relevant range of inert crowding agents must be a requisite for presumptions on intracellular conformational behaviour of proteins deduced from in vitro experiments.

Cell interiors are extremely congested with biological macromolecules exerting crowding effect, influencing various physiognomies of protein life. Present work deals with effect of crowding on folding behaviour of haemoglobin (Hb) under glycating conditions. Macromolecular crowding was mimicked by concentrated solutions of dextran 70. Hb with 0.2 M fructose and ribose was incubated separately for 96 h in dilute and crowded solution to analyse conformational changes. Reduced intrinsic and ANS fluorescence, decreased Soret absorbance, enhanced turbidity, browning of protein, red shift in ThT and Congo red spectra significantly unveiled protein aggregation. FTIR and CD results revealed transition from α-helix to β-sheets confirming aggregation. Transmission electron microscopy exhibited incidence of aggregates. Macromolecular crowding was witnessed to defend conformational stability of native Hb under stress condition at 100 mg/ml dextran, noticeably indicating deceleration of aggregation. Stabilising effect of crowding was marginally better in fructosylated Hb than with ribose due to difference in their glycation potential. Contrarily, in over-crowded solution where dextran concentration was 500 mg/ml, heightened aggregation was perceived implying concentration dependant, dual nature of macromolecular crowding. The novelty of this study lies in idea of considering macromolecular crowding as a key player in regulation of protein stability which was safely ignored previously.

Dextran 70 and its building block (glucose) has been used as macromolecular crowder and osmolyte, respectively. The difference in size and structure of both made us inquisitive to measure stability of lysozyme in the presence of their mixture. The effects of mixture of a fixed dextran 70 concentration (300 mg/ml) containing different concentrations of glucose and vice versa, were studied. It was observed that Tm (the midpoint of denaturation curve) and △GDo (standard Gibbs free energy change at 25 °C) of lysozyme increase with the increasing concentration of dextran 70 and glucose alone and their mixture. We asked a question whether the effect of synthetic crowding agent on the stability of protein is due to the property of its monomer or due to the crowder. In this study, we observed that both dextran and its monomer stabilize the protein by same mechanism which is volume exclusion. The stabilization arises due to change in in the entropy of unfolding, while there is insignificant change in enthalpy of the protein with increasing concentration of the co-solute. Furthermore, the efficacy of stabilization by glucose increases in the crowded environment, when the concentration of dextran 70 is more than 200 mg/ml in the mixture.

The role of crowding agents on structure and activities of heme proteins has been established. Analysis of kinetic and thermodynamic parameters measured for CO-dissociation reaction of natively-folded carbonmonoxycytochrome c (NCO) and carbonmonoxymyoglobin (MbCO) at different [GdnHCl] or [Urea] in the presence of crowding agents (dextran 40, dextran 70 and ficoll 70) demonstrate that (i) at low denaturant concentrations, crowder presence enhances the denaturant-mediated restricted dynamics of NCO and MbCO, and (ii) at higher denaturant concentrations, large scale unfolding-fluctuations dominate the dynamics and inclusion of crowder counteracts the structural-fluctuations causing the unfolding of proteins. Thermodynamic analysis of thermal and urea-unfolding curves of cytochrome c (Cyt c) and myoglobin (Mb) measured at different [GdnHCl] in presence of crowding agents reveals that crowder presence counterbalances and strengthens the destabilizing action of GdnHCl on stability of Cyt c and Mb, respectively. This study further demonstrates that the size, shape and concentration of crowding agent modulate the effect of crowder on denaturant-mediated dynamics and thermodynamic stability of heme proteins.

Purpose: This study aimed to compare the efficacy of two sustained-release formulation of artificial tear drops. Patients and methods: This is a randomized patient-masked clinical trial, a total 88 patients into two group A (n = 41; with single dose of artificial tear, containing dextran 70, 1 mg/ml and hypromellose, 3 mg/ml hydroxypropyl methylcellulose (HPMC) and group B (n = 47; with multidose of artificial tear, containing 0.3 g HPMC and 0.1 g of dextran 70, with 0.01% benzalkonium chloride (BAK) as preservative) were completed the study. The ocular surface disease index (OSDI) questionnaire, tear break up time (TBUT), corneal and conjunctival staining and Schirmer test, were performed. Repeated measures ANOVA was used to assess the differences among the two products. A p-value less than 0.05 was considered significant. Results: The mean of age of the participants in the Group A and B was 44.08 ± 6.29 (range, 33–58 years) years and 45.83 ± 8.42 (31–60 years), respectively. In comparing two groups before the intervention, the OSDI scores, the TBUT scores, the conjunctival and corneal staining scores and the Schirmer scores did not show statistically significant differences (p = 0.339, p = 0.640, p = 0.334, p = 0.807 and p = 0.676, respectively). After 4 weeks, the OSDI scores, conjunctival and corneal staining scores showed improvement in compare to those before the intervention (p

Biological macromolecules are known to evolve and function under crowded intracellular environments that comprises of a wealth of soluble and insoluble macromolecules like proteins, nucleic acids, ribosomes and carbohydrates etc. Crowded environment is known to result in altered biological properties including thermodynamic, structural and functional aspect of macromolecules as compared to the macromolecules present in our commonly used experimental dilute buffers. In this study, we have investigated the effect of Dextran 70 on the thermodynamic and structural properties of three different proteins (Ribonuclease-A, lysozyme and holo α-lactalbumin) at different pH values. We discovered that Dextran 70 has a protein-independent effect in terms of protein stability and structure.

The paper presents results of a study of dynamics of dextran transportation through a synthetic membrane separating the system made of the infusion liquid and water. Changes in the optical density on both sides of the membrane permit the application of the sensitive method of optical interference for analysis of changes in the solution concentration, determination of the dextran molecule radius and the parameters characterising the membrane permeability. The membrane pore size was estimated under a scanning electron microscope.

Introduction: Our lab has developed a novel strategy for intestinal preservation involving the intraluminal delivery of a nutrient-rich preservation solution. The aim of this study was to compare the effectiveness of two impermeant agents for use in our solution: Dextran 70 (D70; Mw = 70 kDa) and Hydroxyethyl starch (HES; Mw = 2200 kDa). Methods: Rat intestines were procured, including an intravascular flush with University of Wisconsin solution followed by a ‘backtable’ intraluminal flush with: UW solution (group 1, UW), or an amino acid-based nutrient-rich preservation solution (AA solution) containing either 5% D70 (group 2, AA-D70) or HES (group 3, AA-HES). Tissue samples (n = 6) were taken at 2, 4, 8, and 12 h cold storage; histology, energetic, end-product, and oxidative parameters were assessed. In separate groups (n = 4), D70 and HES were fluorescently labeled with fluorescein isothiocyanate (FITC) in order to directly observe mucosal penetration of the starch and dextran. Results: Over the 12 h storage time-course, direct visualization of the fluorescently labeled D70 showed penetration of the mucosal layer as early as 2 h and progressively continued to do so throughout the 12 h period. In contrast, HES did not cross the mucosal barrier and remained captive within the lumen. As time of storage progressed, grade of injury increased in all groups, however, at 4 and 12 h the AA-HES treated tissues exhibited significantly less injury compared to UW and AA-D70, P < 0.05. AA-HES group showed on moderate villus clefting (median grade 2; P < 0.05) while the AA-D70 group exhibited complete villus denudation (grade 4) and the UW group had extensive injury into the regenerative cryptal regions (grade 6). Metabolic parameters revealed a preferential maintenance of ATP and Energy Charge; increases in lactate, alanine and ammonium supported the involvement of aerobic and anaerobic pathways for energy production. Conclusion: The results of this study challenge the idea that oncotic support is not a fundamental requirement of static organ storage. Furthermore, our data suggests that HES is an effective oncotic agent for use in our intraluminal nutrient-rich preservation solution, while Dextran 70 is not.

Objective Death and severe morbidity after subarachnoid hemorrhage (SAH) are mainly caused by global cerebral ischemia through increased intracranial pressure (ICP) and decreased cerebral blood flow (CBF). We have recently demonstrated neuroprotective effects of small volume resuscitation (7.5% saline in combination with 6% dextran 70) in an animal model of SAH, leading to normalization of increased ICP, reduced morphological damage and improved neurological recovery. In the present study, we compared the concept of small volume resuscitation represented by two clinically licenced hypertonic–hyperoncotic saline solutions with the routinely used hyperosmotic agent–mannitol–and investigated their effects on ICP, CBF, neurological recovery and morphological damage after SAH in rats. Methods 60 dextran-resistant Wistar rats were subjected to SAH by an endovascular filament. ICP, MABP (mean arterial blood pressure) and bilateral local CBF were continuously recorded. All animals were randomly assigned to four groups: (I) NaCl 0.9% (4 ml/kg bw), (II) 7.5% NaCl + 6% dextran 70 (4 ml/kg bw), (III) 7.2% NaCl + HES 200,000 (4 ml/kg bw) and (IV) 20% mannitol (9.33 ml/kg bw) given 30 min after SAH. Neurological deficits were assessed on days 1, 3 and 7 after SAH. The morphological damage was evaluated on day 7 after SAH. Results The induction of SAH resulted in an immediate ICP increase to 46.6 ± 3.2 mm Hg (mean ± S.E.M.) and 29.6 ± 1.3 (mean ± S.E.M.) mm Hg 90 min post-SAH. While a treatment with both hypertonic saline solutions (II, III) decreased ICP as well as the 20% mannitol solution, only the group treated with hypertonic saline and dextran 70 (II) showed an increase of ipsilateral CBF for 20 min after the infusion and significantly more surviving neurons in the motorcortex and caudoputamen. Mortality was reduced from 60% (I) and 73% (III and IV), respectively, to 40% in group II. Conclusion Of all hypertonic solutions investigated, small volume resuscitation with NaCl 7.5% in combination with 6% dextran 70 evolved to be most effective in terms of reducing the initial harmful sequelae of SAH, leading to lowered ICP and less morphological damage after SAH in the rat.

BACKGROUND: Plasma substitutes such as hydroxyethyl starch (HES) and various dextrans may compromise the haemostatic system, thereby causing potentially dangerous bleeding. Whilst several mechanisms have been advanced to explain the nature of the coagulopathy induced by this colloid, there has been comparably little interest in devising ways to optimize haemostasis after a relative colloid overdose.METHODS: Real-time whole blood (WB) clot formation profiles were recorded using a thrombelastographic method employing activation with tissue factor. The coagulation tracings were transformed into dynamic velocity profiles of WB clot formation. WB from healthy individuals (n=20) was exposed to haemodilution of approximately 55% with isotonic saline, HES 200/0.5, HES 130/0.4, and dextran 70, respectively. Possible modalities for improvement of the induced coagulopathy were explored, in particular ex vivo addition of a fibrinogen concentrate.RESULTS: WB coagulation profiles changed significantly with decreased clot strength, and a compromised propagation phase of clot formation. The duration of the initiation phase of WB coagulation was unchanged. No statistical differences were detected amongst the HES solutions and dextran 70. However, dextran 70 returned a more suppressed clot development and strength compared with the HES solutions. Ex vivo haemostatic addition of washed platelets (75 x 10(9) litre(-1)) and factor VIII (0.6 IU ml(-1)) produced insignificant changes in clot initiation, propagation, and in the clot strength. In contrast, ex vivo addition of a fibrinogen concentrate (1 g litre(-1)) improved the coagulopathy induced by all of the three individual plasma expanders tested.CONCLUSION: Coagulopathy induced by haemodilution with either HES 200/0.5, HES 130/0.4, and dextran 70 may be improved by fibrinogen supplementation.

The intrinsically unstructured protein, reduced and carboxyamidated RNase T1 (TCAM) was used to determine the degree to which macromolecular crowding agents increase the equilibrium constant for folding. TCAM is not catalytically active in an aqueous assay system alone, but becomes catalytically active on addition of 400 mg/ml dextran 70. The activity observed accounts for approximately 16% of the total available TCAM in solution. We interpret this result to mean that 16% of the TCAM becomes folded protein in the presence of the 400 mg/ml dextran 70, and this translates into an approximately five-fold increase in the equilibrium constant for folding. Sarcosine-induced folding of TCAM was performed in the presence of 0, 100, 200 and 300 mg/ml dextran 70, and apparent deltaG(o)(N-D) values determined from the linear extrapolation method provide an estimated 22% folded TCAM formed in the limit of zero sarcosine concentration and in presence of 400 mg/ml dextran 70. The increase in TCAM folding equilibrium constant using this method of determination is approximately 7.5-fold. Overall, the results indicate that macromolecular crowding agents are only modestly effective in promoting folding of this intrinsically unstructured protein.

Poly n-butyl cyanoacrylate has been used in the synthesis of nanoparticles by dispersion polymerisation in aqueous media. Following establishment of a thermometric procedure for assessment of monomer reactivity, the relationships between monomer-polymer conversion reactions and particle development at various pH values was investigated. Particle size was measured during the synthesis process using a laser diffraction technique and final particle character was assessed by scanning electron microscopy. Optimum conditions for particle production were a dispersion medium of pH 2.5 at a temperature of 65 degrees C, with dextran 70 used as a steric stabiliser. In the presence of dextran, following a period of equilibration, colloidally stable particles form, but in the absence of dextran particles are colloidally unstable and rapidly coalesce. Measurement of molecular weight changes through the synthesis process show an upward shift consistent with the initial formation of oligomers, which then further polymerise through a re-initiation re-polymerisation process until an equilibrium molecular weight is reached.

The in vitro immunosuppressive activity of a conjugate of methylprednisolone (MP) with dextran 70 kDa (DEX-MPS) was tested using the lymphocyte proliferation assay after stimulation of lymphocytes with concanavalin A (Con-A). Blood and spleen lymphocytes, isolated from drug-free male Sprague–Dawley rats, were used in the assay. First, the optimum concentration of Con-A for stimulation of lymphocytes was determined. The inhibition of the lymphocyte proliferation was then tested in the presence of 0.25, 0.5, 1.0, 2.5, 5.0, 10, 20, and 50 nM concentrations (MP equivalent) of DEX-MPS or free MP. The maximum stimulation of lymphocytes with Con-A was observed at mitogen concentrations of 2.5 and 10 μg/ml for the spleen and blood lymphocytes, respectively. For free MP, sigmoidal relationships were observed between the effect (% inhibition of lymphocyte proliferation) and the logarithm of MP concentration. Additionally, the maximum inhibitory effect (Imax) and MP concentration producing half of Imax (IC50) were, respectively, 98% and 1.38 nM for the blood and 86% and 3.1 nM for the spleen lymphocytes. For MP conjugated to dextran, the response–log concentration curves were substantially shifted to the right with IC50 values of 40 and 52 nM for the blood and spleen lymphocytes, respectively. It is concluded that compared with free MP, the steroid attached to dextran has minimal immunosuppressive activity. Therefore, to be effective in vivo, DEX-MPS should release MP in the body.

ABSTRACT: It is well known that light transmission through blood is the most widely utilized method for the study of erythrocyte aggregation. The curves obtained had been considered empirically as exponential functions. In consequence, the process becomes characterized by an only parameter that varies with all the process factors without discrimination. In the present paper a mathematical model for RBC aggregation process is deduced in accordance with von Smoluchowski's theory about the kinetics of colloidal particles agglomeration. The equation fitted the experimental pattern of the RBC suspension optical transmittance closely and contained two parameters that estimate the most important characteristics of the aggregation process separately, i.e., (1) average size of rouleaux at equilibrium and (2) aggregation rate. The evaluation of the method was assessed by some factors affecting erythrocyte aggregation, such as temperature, plasma dilutions, Dextran 500, Dextran 70 and PVP 360, at different media concentrations, cellular membrane alteration by the alkylating agent TCEA, and decrease of medium osmolarity. Results were interpreted considering the process characteristics estimated by the parameters, and there were also compared with similar studies carried out by other authors with other methods. This analysis allowed us to conclude that the equation proposed is reliable and useful to study erythrocyte aggregation.

Since the first descriptions of the use of 7.5% hypertonic saline for resuscitation of haemorrhage in 1980, there has been substantial animal research and clinical evaluation of small volume resuscitation. Most interest has focused on combined hyperosmotic and hyperoncotic colloid formulations. Infused hyperosmotic NaCl rapidly expands plasma volume, while the hyperoncotic colloid sustains the volume expansion. Other contributing factors to the efficacy of these solutions are increased cardiac effectiveness and peripheral vasodilation. The most often studied solution, 7.5% NaCl/6% dextran 70, offers promise to reduce the mortality of traumatic hypotension and head injury when used as an initial treatment. Future hyperosmotic-hyperoncotic formulations with different solutes may provide specific beneficial pharmacological properties in addition to the established cardiovascular effects of hyperosmolarity. A particularly promising formulation might be a combination solution of an oxygen carrier colloid, for example, haemoglobin, and a hyperosmotic crystalloid.

Dextran solutions are favored distending media for many hysteroscopic procedures because they are easy to administer, distribute uniformly within the uterine cavity, and are relatively nontoxic. We present the case of a 26-year-old woman who developed hypotension, noncardiogenic pulmonary edema, and hemorrhagic diathesis following hysteroscopie surgery with 32% dextran 70. A medical literature review indicates that following hysteroscopie surgery in which dextran solution has been used, “dextran syndrome” has been diagnosed in some patients. This syndrome is characterized by acute hypotension, hypoxia, coagulopathy, and anemia. We speculate on the pathogenesis of this condition and offer recommendations on how to evaluate and treat this rare dextran-related complication.

Background. Peritoneal adhesions continue to be a significant cause of postoperative complications. Elucidating the origin of these adhesions has been hampered by the lack of a reproducible animal model. The purpose of this study was to create a standardized model in which a single, specific adhesion, could be objectively measured. With this model the kinetics of adhesion formation were then evaluated. A variety of peotential antiadhesive agents were then tested and compared. Methods. In this study a reproducible, quantitative rat model was developed that used uniform defects on the peritoneal wall and cecal surface. The resulting adhesions were subsequently scored, and their strength was measured with a tensiometer. An evaluation of the kinetics of peritoneal adhesion formation was obtained by using a timed removal of silicone elastomer sheeting held between the two injured surfaces. The following antiadhesive agents were evaluated: Ringer's lactate solution; dextran 70 (32%); modified carboxymethylcellulose (1.0% and 2.0%); an absorbable barrier of specially knitted material composed of oxidized regenerated cellulose; fibrin sealant; silicone elastomer film; and expanded polytetrafluoroethylene membrane. Results. Evaluation of the kinetics of peritoneal adhesion formation indicated that the susceptibility for adhesion formation was significantly decreased or eliminated after the first 36 hours. Evaluation of antiadhesion agents indicated that the magnitude of adhesion prevention was directly proportional to the agent's ability to remain at the site of injury during the critical period of adhesion formation. Permanent barriers (silicone elastomer film, expanded polytetrafluoroethylene membrane) provided the greatest antiadhesion effect but were not believed to be ideal agents because they remained at the site of injury well after the critical period of adhesion formation. The incidence of adhesion formation for the other agents was as follows: control, (34 of 34), Ringer's lactate (12 of 12), absorbable barrier of knitted cellulose (10 of 10), 32% dextran 70 (8 of 12), 1% carboxymethylcellulose (6 of 12), fibrin sealant (4 of 9), and 2% carboxymethylcellulose (4 of 12). Conclusions. The efficacy of antiadhesion agents appears to be related to the agent's viscosity, ability to coat the wound surface, and residence time at the site of injury. In this rat model an agent that remained on the injured surfaces for at least 36 hours after injury appeared to be more effective in reducing adhesion formation than an agent with a shorter residence time.

Experiments have shown that secondary fluid flows within the extra-capillary space (ECS) of hollow fiber bioreactors (HFBRs) can lead to the downstream polarization of cells and growth factors and subsequent reductions in reactor productivity. Recent model studies and experimental investigations of this system have demonstrated further that the polarization of ECS solutes can be reduced through increased loading of bovine serum albumin within the ECS, which leads to a concomitant reduction in solute convection via osmotic pressure effects. The following study extends previous models of HFBR hydrodynamics to include the effect of multiple solute species on the transient distribution of ECS solutes. The model is then used to study the relative effectiveness of dextran 500, dextran 70, hydroxyethylstarch 120, and bovine serum albumin, as well as periodic switching of the fiber lumen flow direction, in eliminating solute polarization. The high molecular weight additives are found to be more effective than flow switching in reducing polarization, particularly when the membranes display permeabilities characteristic of some polysulfone fibers (i.e. 6 × 10 −13 m).

BACKGROUND: Previous studies deinonstrated that intravenous contrast medium (CM), as used in contrast enhanced computed tomography, aggravater the impairment of pancreatic microcirculation (PM) characteristic of severe pancreatitis and increases necrosis and mortality in necrotizing pancreatitis (NP) in rats. This study evaluates the use of isovolemic hemodilution, which can enhance the microcirculation in revere pancreatitis, for preventing CM-induced injury. METHODS: NP war induced in 30 dextran-tolerant Wistar rats by intraductal glycodeoxycholic acid and intravenous cerulein for 6 hours. PM war quantified by intravital microscopy using fluorescein isothiocyanate labeled erythrocytes. Bared on previous results, areas with low blood flow (

Thirty-six ewes and 19 does were randomly assigned to control (15 ewes and 9 does) or treatment groups (21 ewes and 10 does). Ventral midline laparotomy was performed 6–8 d after dl of estrus. Number of corpora lutea (CL) and oocytes/embryos were recorded and compared. Treated animals received 500 ml 6% dextran 70 intra-abdominally following uterine flushing. Control animals received 500 ml 0.9% NaCl irrigation solution. At the time of the second laparotomy, degree and extent of adhesion formation were assessed and scored on a scale of 0 to 3, and CL and embryos/oocytes were counted and compared. There was no difference in adhesion scores between control and dextran-treated groups for ewes (P ⩾ 0.61) or does (P ⩾ 0.43). Number of live embryos at the second surgery in control ewes was higher than in dextran-treated ewes (P

An in vivo experimental venous thrombosis model based on endothelial damage and flow reduction was used to investigate the effect of low molecular weight heparin (LMWH) alone and in combination with dextran and the effect of surgical and endothelial trauma on thrombus formation, formation of occlusive thrombi and thrombus weights. Five groups with 15 rabbits in each were studied. Two groups received dalteparin (50 anti-Xa IU/kg i.v.) before surgical trauma or after, during the endothelial trauma and two groups received dalteparin (50 anti-Xa IU/kg i.v.) with dextran 70 (1 g/kg i.v.) before surgical trauma or after, during the endothelial trauma. Compared to a control group (saline) all treatment regimes reduced significantly the frequency of thrombosis and occlusive thrombi as well as thrombus weights. No significant difference was observed between the identical treatment groups when the substances were introduced before respective after surgical trauma. It is concluded from the present study that thromboprophylaxis with LMWH in this particular in vivo model, given before or after surgical trauma is equally effective. Dextran has a certain augmenting thromboprophylactic effect when added to LMWH in this model.

The cardiovascular changes during epidural caesarean delivery were studied, using a non-invasive cardiac output monitor (BoMed NCCOM3-R7). Two different regimens were used to control hypotension (A = 15 ml/kg of 3% dextran 70, B = 7.5 ml/kg of 3% dextran 70 followed by an infusion of 17.5 mg of ephedrine). Cardiac index (CI) and heart rate (HR) increased after delivery and oxytocin administration (P0.001) and maximum values were recorded 1-1.5 min after administration of oxytocin. The maximum increase in CI was 76% (A) and 117% (B), in HR 42% (A) and 56% (B), and in SI 23% (A) and 47% (B) compared with values before anaesthesia. The increase in cardiac output after delivery was greater than that measured previously, which might be because impedance cardiac output is a continuous method. It is also suggested that the most pronounced changes are augmented by the use of a bolus injection of 10 units oxytocin i.v.

Forty-one patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g for each 1000 ml of ascites removed) (group I=20 patients) or paracentesis with albumin (6 g for each 1000 ml of ascites) (group II=21 patients). The basal clinical features, laboratory data, and plasma renin activity were similar in both groups. The volume of ascites removed was 12.9 ± 4.4 and 10.9 ± 3.7 liters in group I and II, respectively (n.s.). No significant changes were observed in liver and renal function tests, KPTT, platelet count, factor VIII, serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups, except for a decrease in bilirubin in group I and a transient increase of serum albumin in group II. Four patients developed complications in each group, mainly hyponatremia, while one patient in each group developed renal impairment. One patient from group I died with hepatic encephalopathy. Moreover, the probability of survival and readmission to the hospital because of tense ascites were similar in both groups of patients during the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient treated. These results indicate that repeated large volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites. However, due to its reduced cost, paracentesis with Dextran 70 may be considered the treatment of choice in cirrhotic patients with tense ascites without liver cancer and renal failure.

In a prospective randomized study heptest, thrombinantithrombin complexes (TAT), D-dimer, and t-PA:ag were analysed pre-and postoperatively in 206 consecutive patients undergoing hip arthroplasty during thromboprophylaxis with either a LMW heparin (Enoxaparin) or Dextran 70. Deep vein thrombosis (DVT) developed in 6 of 102 (6%) Enoxaparin and in 21 of 104 (20%) Dextran patients diagnosed by bilateral phlebography. In the Enoxaparin group heptest showed a significant increase from the pre- to the postoperative level opposed to a significant decrease in the Dextran group. Postoperative levels of TAT, D-dimer, and t-PA:ag were significantly increased in both groups, however, TAT was significantly higher in patients in the Dextran group than in the Enoxaparin patients. D-dimer was significantly higher in Dextran patients with DVT postoperatively compared with patients without DVT. No differences concerning TAT or t-PA:ag were observed between patients with and without DVT in any of the groups.

The effects of desmopressin and dextran on haemostasis and fibrinolysis were studied in four healthy volunteers. Both drugs were compared to placebo, each volunteer being subject to four experiments. Dextran 70 (30 g i.v.) moderately decreased VIII:C and vWF:Ag and slightly increased antithrombin III, also when haemodilution and diurnal variation were considered. Desmopressin (0.3 γ/kg BW i.v.), alone as well as in combination with dextran, increased VIII:C, vWF:Ag, protein C and tPA and decreased PAI-1. The combination of desmopressin and dextran stimulated coagulation and fibrinolysis and might be of relevance to surgical blood loss as well as to postoperative thromboembolism.

Owing to the low rate of association of polar drugs, such as amikacin sulphate, to hydrophobic carriers, e.g. poly(alkylcyanoacrylate) nanoparticles, several procedures have been investigated to improve the drug carrier capacity. The greatest improvement was noted with the covalent reaction between the drug and the suspension agent dextran 70, attached to the particle surface. The antibacterial activity in this case was dramatically reduced, however. The addition of sodium lauryl sulphate to the polymerisation medium reduced the hydrosolubility of the drug, improving its incorporation into the nanoparticles. The study of the sorption behaviour of amikacin sulphate onto freeze-dried nanoparticles, prepared either using a surfactant (Synperonic F 68) or a suspension agent (dextran 70), shows preferrable results in the former case. The presence of drug in the polymerisation medium drastically increased the mean particle size, destabilising the nanoparticles at the highest concentration assayed (20 mg/ml). Less drug was adsorbed onto these particles at a later stage, which seems to be due to their larger size compared to non-loaded nanoparticles. Moreover, the drug-polymer association mechanism, investigated by zeta-potential studies, appears to be an electrostatic interaction, in keeping with the observed reduction of particle surface charge after adsorption of amikacin. Finally, the modification of the polymer molecular weight in the formulations developed was investigated.

Surgical adjuvants are commonly employed to reduce the frequency of postoperative adhesion development after reproductive pelvic surgery. The ability of indomethacin, promethazine, dexamethasone, Intralipid, progesterone, and heparin to reduce adhesion formation in combination with INTERCEED(TC7) (Johnson and Johnson Medical, Inc., New Brunswick, NJ), an absorbable barrier that alone reduces adhesion formation, was examined in a rabbit uterine horn model. A significant reduction in adhesion formation was only observed with the combination of INTERCEED(TC7) plus heparin. In additional studies, heparin delivery by intraperitoneal (IP) lavage, intravenous injection, or intra-abdominal instillation failed to demonstrate efficacy. Similarly, heparin delivery with other barriers or IP instillates (carboxymethylcellulose or 32% Dextran 70) failed to reduce adhesion formation. We conclude that INTERCEED(TC7) can be efficaciously utilized as a carrier to deliver heparin to traumatized surfaces, thereby reducing adhesion formation.

We have studied haemodilution and cardiovascular responses to i.v. hydration with either 3% dextran 70 (Dx70) or Ringer's acetate using a non-invasive cardiac output monitor (BoMed NCCOM3-R7) in 40 healthy parturients undergoing Caesarean section under extradural anaesthesia. Haemodilution was more pronounced, and central venous pressure, mean arterial pressure and cardiac index maintained at greater values, after treatment with Dx70. Colloid osmotic pressures (COP) decreased by 1.7 mm Hg after loading with 3% Dx70, and by 5.6 mm Hg in mothers treated with Ringer's acetate (P less than 0.001). The transthoracic fluid index decreased more after hydration with Ringer's acetate (P less than 0.001), indicating an increase in lung water. In spite of these maternal changes, there were no differences in neonatal bioimpedance or values of haemoglobin, PCV, albumin and COP in umbilical cord blood, and only one case of respiratory distress. We conclude that colloids may be preferable to crystalloids for circulatory preload for extradural Caesarean section, as greater haemodynamic stability was maintained and increases in lung water avoided.

Intraperitoneal administration of sodium tolmetin-hyaluronic acid reduced the formation of adhesions at early postsurgical time points. In addition, at 6, 48, 72, and 96 hr following surgery, there was a significant reduction in the number of red blood cells (RBC) recovered from peritoneal lavage. This effect was not the result of fluid or viscous solution in the peritoneal cavity since intraperitoneal administration of Ringer's lactate or Hyskon (a 32% solution of Dextran 70) did not affect RBC recovery. In contrast, the influx of leukocytes into the peritoneal cavity was elevated at 12 hr after surgery, but suppressed at 96 hr. These data may suggest a mechanism by which sodium tolmetin in hyaluronic acid reduced adhesion formation.

Rapid blood volume expansion is the goal in prehospital hemorrhage resuscitation. A comparison was made for fixed volume and uncontrolled hemorrhage between three fluid regimes: Ringer's lactate (RL), Macrodex ® (MD), or a small volume of a hyperosmotic solution (HSD, 7.5% NaCl/6% dextran 70) followed by RL. A mathematical model was developed to simulate blood volume restoration for these given hemorrhage and resuscitation situations. Model predictions for a fixed hemorrhage (35%) and reinfusion of each fluid regime (1 mL · min −1 · kg −1 ) were found to agree with hematocrit and osmolality changes from experiments on anesthetized rabbits. HSD gave the quickest volume expansion after the controlled hemorrhage, which is a useful experimental model; however, it is not realistic of many trauma injuries. The model suggests for severe uncontrolled hemorrhage that HSD/RL initially hastens the bleed, yet the blood volume expansion is still more effective than RL alone for the first 20 minutes, making it an effective prehospital expander for most urban trauma situations.

Thirty-two percent dextran 70 is a highly viscous polysaccharide liquid used for uterine distention during hysteroscopy. Although generally safe, this agent has been recognized recently to cause noncardiogenic pulmonary edema, renal insufficiency, and intravascular coagulopathy. We report a case of acute 32 percent dextran 70 embolization, associated with intravascular coagulopathy, bilateral lung infiltrates, and rhabdomyolysis, recognized initially by hemoptysis and pleuritic chest pain while the patient was in the recovery room following a hysteroscopic procedure. Pulmonary, anesthesiology, and critical care physicians should be aware of these potential complications of hysteroscopie surgery.

Anaphylactic reaction associated with hysteroscopy using 32% dextran-70 as a distending medium is a rare phenomenon. We report anaphylactic reaction associated with hysteroscopy using dextran that was delivered manually in three otherwise healthy women occurring within a 6-month period. The rapidity and pressure of dextran administered might facilitate intravascular absorption and predispose patients to this phenomenon.

We investigated the effect of progressive normovolemic hemodilution with Dextran 70 on subcutaneous tissue oxygen tension (PscO2) in canine random pattern flaps and in adjacent intact skin. PscO2 was measured polarographically in implanted oxygen-permeable Silastic catheters. The mean PscO2 of 5.7 kPa in intact subcutis at hematocrit (HCT) 40 was maintained or insignificantly improved during hemodilution to a HCT of 14. The mean flap PscO2 of 3.1 kPa at HCT 40 was maintained down to HCT 20. Most flap measuring sites exhibited a PscO2 improvement in an individual HCT range at some point during hemodilution. The increment in PscO2 tended to be relatively greater and to occur at lower Hct values in locations with more severe ischemia initially. Central hemodynamics were characterized by a lowered total peripheral resistance and an increased cardiac output, whereas systemic and pulmonary arterial blood pressures and central venous pressure remained essentially unchanged.

Whether colloid mixtures or exclusively electrolyte solutions should be preferred for treatment of burn shock has been a topic of discussion for many years. The burns unit in Copenhagen has run a randomized, controlled trial, during the 5-year period 1971-5, in which every even-numbered patient was treated with Dextran 70 and every odd-numbered patient with Ringer lactate. Each group comprised 86 patients. The manner in which the two patient groups respond to treatment is essentially different. The characteristic features of the Dextran group are the relatively small quantities of fluid and sodium administered, the moderate hourly diuresis, the lack of haemoconcentration and reduced sodium uresis during the days subsequent to institution of shock treatment. Patients treated with Ringer lactate, on the contrary, receive more fluid and sodium, the hourly diuresis will be larger, but in spite of this these patients tend to haemoconcentrate to a considerable degree. The sodium uresis is normal all the time. Thus, these two methods of treatment create entirely different pathophysiological conditions. The weight of the patients treated with Ringer lactate is significantly greater than that of those treated with Dextran 70, but there is no difference in the extent of the burn either in square metres or in the percentage of body surface burned. A comparison is therefore permissible. The 86 patients treated with Dextran 70 had a calculated mortality of 29·9 according to Bull and Fisher (1954) and an actual mortality of 18. The 86 patients treated with Ringer lactate had an expected mortality of 32·5 and an actual mortality of 16. No statistically significant difference in mortality is to be found between the two groups. The authors consequently conclude that Ringer lactate is to be preferred to Dextran 70 because it is simpler to dose; dosing instructions do not lead to misinterpretation, treatment rarely needs to be adjusted and it is practically impossible to give an overdose.

Progesterone (P) has been shown to have potent antiinflammatory and immunosuppressive properties. Previous reports have suggested that the use of P decreases postoperative adhesion formation. To further evaluate the role of pharmacologic doses of progestogens in adhesion prevention, 42 mature New Zealand White rabbits underwent standardized injuries to the uterine horns, fimbriae, and pelvic peritoneum and received one of six treatments. Group S had intraperitoneal placement of normal saline (0.9%); group H received intraperitoneal placement of 32% dextran 70; group IM-P received intramuscular P-in-oil 10days before and after laparotomy in addition to intraperitoneal saline; group IP-P had intraperitoneal placement of an aqueous P suspension; group DP received medroxyprogesterone acetate intraperitoneally; and group C received no intramuscular or intraperitoneal adhesion-prevention agents. The animals were sacrificed 6weeks after laparotomy, and the adhesions were scored. Intraperitoneal saline (group S) significantly reduced the amount of adhesions when compared with the control group (C) ( P P

Dextran given intravenously to two patients with mild von Willebrand's disease and two healthy controls impaired the factor VIII properties measured, i.e. it decreased the factor VIII-related antigen and the ristocetin co-factor activity. In the patients the variables fell from borderline to abnormally low levels accompanied by a prolongation of the bleeding time. Infusion of factor VIII concentrate reversed the dextran-induced impairment of factor VIII and the prolonged bleeding time. The findings lend support to the view that dextran induces a defective platelet function in vivo by interfering with the factor VIII molecular complex. They also show that patients with von Willebrand's disease should not be given dextran as it might potentiate their bleeding diathesis.

Twenty female pigs underwent laparotomy during which transection of both uterine horns and wedge resection of both ovaries were performed with a standard technique. Following the injuries a mixture of Spongostan and 32% dextran 70 was applied only to the lesions on the right side. Three weeks after surgery another laparotomy was performed and the degree of adhesion formation was recorded. A marked reduction in degree and extent of adhesions was observed on the treated side as compared with the control side. The possible advantages of a compound that can be applied locally and has hemostatic properties as well are discussed.

The small quantities of 7.5% hypertonic saline (HTS) in 6% Dextran 70 (DEX 70; Travenol Laboratories, Deerfield, IL) required to produce marked improvement in tissue perfusion may make it an ideal solution for the prehospital management of hypotensive trauma patients. This study shows that the initial treatment of porcine hemorrhagic shock with 7.5% HTS/6% DEX 70 results in significantly improved hemodynamics and higher survival rates than those seen in animals treated with normal saline. These results are very encouraging and dictate the need for evaluation in human trials.

The immunosuppressive and anti-inflammatory properties of progesterone (P) have been established. The authors investigated whether the intraperitoneal instillation of P would lessen postoperative adhesion formation in New Zealand white rabbits undergoing pelvic surgical procedures. In phase I, severe, peritoneal lesions were made in the right uterine horn (n = 48). Animals were randomized to receive equal volumes of either (1) Ringer's lactate (RL); (2) 32% dextran 70 (HY; Hyskon Division, Pharmacia, Piscataway, NJ); (3) 500 mg P in oil (PO); or (4) 500 mg aqueous P (PA) at initial laparotomy. In phase II, the distal right uterine horn, including the mesosalpinx, was excised and microsurgical anastomosis was accomplished (n = 45). Aqueous P was not used in phase II; otherwise, the same agents were tested. Six weeks later, the severity of the adhesions formed was graded. The mean adhesion scores for the RL and HY groups were low for the right side in both phases and did not differ (P greater than 0.05). In contrast, higher scores were observed in all the P groups, regardless of the P preparation used or the surgical procedure performed (P less than 0.05).

The pharmacokinetics and pharmacodynamics of albumin, hetastarch, pentastarch, and dextrans are determined by different factors. Albumin's effects are controlled by movement of the protein between the vascular and extravascular pools. The kinetics and dynamics of hetastarch and a new plasma expander, pentastarch, are controlled more by the extent of hydroxyethylation (ie, molar substitution) than by the molecular weight of the different fracions. Pentastarch, because of its lower molar substitution and molecular weight distribution, is eliminated from the body at a much faster rate than hetastarch. In contrast, dextran's duration of effect is controlled by the molecular weight of the different fractions. A review of the available data indicates that 6% hetastarch is comparable to 6% dextran 70 in duration of plasma volume expansion. Their effects last 12 to 24 hours in comparison with eight to 12 hours for 10% pentastarch and only four to six hours for 5% albumin. The amount of plasma volume expansion appears to be greatest with 10% pentastarch (100% to 150% of infused volume), followed by 6% dextran 70 (100% to 125%), 6% hetastarch (100%), and 5% albumin (80% to 100%).

Dextran 70 was infused into four healthy volunteers and one patient with mild von Willebrand's disease. Ex vivo thrombi formed in Chandler tubes exhibited clear structural changes after the infusion. The large platelet aggregates of the thrombus head had ceased to form. The changes were most pronounced 2–4 hours after the infusion. The thrombi from the von Willebrand patient had a different structure before infusion, indicating the importance of factor VIII for the cohesion of the platelet aggregates. The change in structure of the thrombi after the infusion coincided with an impairment of the function of factor VIII in the healthy volunteers as well as in the patient. On infusion i.v. of factor VIII concentrate to the von Willebrand patient the platelets regained their potential to aggregate and formed a thrombus head. The morphological changes may explain the increased lysability of thrombi after infusion of dextran.

Tubal abrasions were surgically induced in 25 rhesus monkeys following demonstration of tubal patency. Five monkeys received dexamethasone, promethazine, and ampicillin perioperatively, five received intraperitoneal 10% dextran 40, five received intraperitoneal 32% dextran 70, and 10 received no additional therapy. Fimbrial biopsies were obtained from two additional monkeys treated with 32% dextran 70 before and postoperatively on days 2, 5, and 7. Only those treated with 32% dextran 70 retained tubal patency and avoided development of adhesions, involving fimbria, omentum, ovary, uterus, and bladder. Histologic examination of fimbrial biopsies demonstrated sufficient epithelial repair to have occurred during the 5 days 32% dextran 70 remained in the pelvin cavity to prevent adhesion formation.