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R Sundberg

Publications and source records attributed to R Sundberg.

At least 19 recordsLinked to original sources

On-line capillary electrophoresis with mass spectrometry detection for the analysis of carbohydrates after derivatization with 8-aminonaphthalene-1,3,6-trisulfonic acid.

Capillary electrophoresis (CE) with mass spectrometry (MS) detection is an ideal tool for analytical use, which combines a nano quantity assay with mass determination. Carbohydrate analysis has always been a challenge because of the inherent structural complexity and the lack of a chromophore, unless derivatization is used. Here we use the derivatization of carbohydrates with a fluorophore, 8-aminonaphthalene-1,3,6-trisulfonic acid (ANTS). This chromophore has two advantages, first, it facilitates UV and fluorescence detection and, second, it introduces negative charge to the analyte, which enhances zone electrophoretic separation. In this study, CE combined with negative ion electrospray MS (ESI-MS) was evaluated for the on-line analysis of ANTS labeled carbohydrates and cellulose fragments. The CE system was connected to the MS by a sheath-liquid electrospray arrangement. The ANTS reagent and Dextrin-15, which contains oligomers of maltose, were used as model samples for ESI-MS optimization in flow-injection-MS and CE-MS modes, respectively. Various sheath-liquid compositions regarding organic modifier (isopropanol, methanol, or acetonitrile) and electrolyte (acetic acid-formic acid, ammonium acetate, or triethylamine) were studied. The response as well as the analyte charge state distribution was found to be dependent on the composition and the orifice voltage. Low-pH conditions with isopropanol as organic modifier were sensitive, stable, and the most favorable for analysis.

Carbohydrates↗

Comparison of confidence procedures for type I censored exponential lifetimes.

In the model of type I censored exponential lifetimes, coverage probabilities are compared for a number of confidence interval constructions proposed in literature. The coverage probabilities are calculated exactly for sample sizes up to 50 and for different degrees of censoring and different degrees of intended confidence. If not only a fair two-sided coverage is desired, but also fair one-sided coverages, only few methods are quite satisfactory. A likelihood-based interval and a third root transformation to normality work almost perfectly, but the chi 2-based method that is perfect under no censoring and under type II censoring can also be advocated.

Confidence Intervals↗

The distribution of the maximum likelihood estimator in up-and-down experiments for quantal dose-response data.

Standard maximum likelihood logistic or probit regression has been used in biopharmaceutical practice for inference about tolerance threshold distributions in situations where subjects (patients) have been allocated doses according to an up-and-down design. For example, a steeper dose-response curve than expected was reported in one such study. This article demonstrates that the maximum likelihood estimator systematically and considerably exaggerates the regression parameter with moderately large sample sizes. Thus a probable explanation for finding a steeper curve than expected is the method used to analyze the experiment, that is, the bias in the maximum likelihood estimator. An additional consequence of this bias is that the mean/median/ED50 are estimated with a misleading precision. In particular, confidence intervals are much too narrow. As a conclusion, we warn against conventional logistic or probit regression in combination with up-and-down designs.

Animals↗

Protective effects of the lazaroid U74500A and lidoflazine on liver preservation with UW solution.

The effect of adding a 21-aminosteroid, U74500A, and a Ca2+ antagonist, lidoflazine, alone and together to UW solution was assessed in a rat liver preservation model. Following preservation, the livers were reperfused using a closed circuit, and the release of hepatocellular enzymes (ASAT, ALAT, and LDH) into the perfusate was determined with increasing time. Both drugs reduced the amount of enzymes lost from the liver. The combination of the two drugs was better than either drug alone. These data suggest that both agents may be of value in organ preservation for clinical liver transplantation.

Adenosine↗

A new dextran 40-based solution for liver preservation.

UW solution is at present the most efficient solution for preservation of livers for transplantation. We have developed an alternative solution based on dextran instead of hydroxyethyl starch and without raffinose, allopurinol, magnesium sulfate, insulin, penicillin, or dexamethasone, which all are used in UW solution. In addition, 62.5 mM potassium in UW solution is replaced with sodium. We tested this new solution for liver preservation using the isolated perfused rabbit liver. We found that livers preserved in the UW solution for 24 or 48 hr lost 11.6 +/- 2.6% and 16.8 +/- 2.0% of the prepreservation weight, respectively, as a sign of organ shrinkage (P less than 0.001). In contrast, no change in liver weight was observed after preservation in the new dextran-based solution. Similarly, no change in total tissue water of the rat liver slices was seen after preservation in the new solution. Furthermore, livers preserved for 24 hr in the UW solution or the new solution produced the same amount of bile as unpreserved livers. However, after preservation in the UW solution for 48 hr, bile production was reduced by 65% (P less than 0.05). In contrast, livers preserved for 48 hr in the new solution showed no reduction in bile production. We conclude that our new solution significantly improves long-term liver preservation, and with this modified solution, 48-hr preservation may be safe.

Adenosine↗

The functional effects of suppression of hypothermia-induced cell swelling in liver preservation by cold storage.

It is known that cellular edema and functional impairment develop during anaerobic cold storage of organs. The extent of both is related to the storage time and the composition of the preservation solution used. We studied hypothermia-induced cell swelling and its effect on liver function after cold storage preservation with either Eurocollins (EC), a number of modified EC solutions in which glucose was replaced by various concentrations of raffinose, or UW solution. After 24 h storage, tissue swelling as determined by total tissue water (TTW) in rat liver tissue slices was most pronounced in slices incubated in Eurocollins, whereas the TTW was only moderately increased in slices stored in modified Eurocollins containing 90 to 120 mM raffinose. In contrast, slices incubated in UW solution had a TTW equal to normal rat liver tissue. Furthermore, intact rabbit livers preserved with Eurocollins had an increase in the whole organ weight, while there was no weight change after preservation with the modified solution containing 120 mM raffinose (M120). In contrast, a pronounced weight loss was observed after preservation with UW solution. After cold storage, the livers were reperfused for 2 h at 38 degrees C in an isolated perfusion circuit (IPL) with an acellular perfusate. Bile flow was significantly greater in livers preserved in M120 than in those preserved with the conventional Eurocollins. However, the bile flow in the livers stored in M120 was inferior to that in the livers preserved with UW solution, which in turn was equal to that in control livers. The release of alanine-aspartate-aminotransferase into the perfusate was higher in livers preserved with Eurocollins, with or without modification, than in the livers preserved with UW solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗

The function of a colloid in liver cold-storage preservation.

The value of colloid in preservation of the liver by cold storage has not yet been fully clarified. Therefore, we studied the effects of colloid on cell swelling, liver weight, and bile production after cold storage in rat liver tissue slices and isolated rabbit liver. In rat liver tissue slices cold-stored for 24 hr in UW solution, total tissue water (TTW) was the same as in the control freshly unpreserved tissue and omitting the colloid (hydroxyethyl starch) from the UW solution did not affect the TTW. However, after cold storage for 24 hr in Perfadex, TTW was markedly increased (by 100%, P less than 0.001). Omitting the colloid in this solution, dextran, or replacing it with hydroxyethyl starch, did not affect this increase in TTW. Thus, the hypothermia-induced cell swelling evident after preservation in Perfadex was not prevented by colloid. Rabbit liver cold-stored in UW solution for 24 hr lost 15.4 +/- 4.7% of weight, but omitting the colloid from UW solution decreased this weight loss to 3.1 +/- 3% (P less than 0.01). In contrast, rabbit livers cold-preserved in colloid-free Perfadex gained 23.3 +/- 5.7% in weight. Adding colloid, either dextran or hydroxyethyl starch, decreased significantly this weight gain, to 9 +/- 3.7% and 10.4 +/- 1.8%, respectively (P less than 0.01), probably as a result of colloid osmotic pressure, preventing the interstitial edema. Rabbit livers preserved for 24 hr in UW solution, with or without colloid, produced the same amount of bile as control unpreserved livers. In contrast, livers preserved in colloid-free Perfadex for 24 hr had a markedly impaired bile production (3.9 +/- 0.9 ml/100 g) as compared with control livers (15.5 +/- 2.6 ml/100 g, P less than 0.01). Colloid partially restored this impaired bile production, to 8 +/- 1.4 mg/100 g by dextran and to 8.5 +/- 1.7 ml/100 g by hydroxyethyl starch, respectively (P less than 0.01). Thus, although colloids do not prevent the hypothermia-induced cell swelling, they prevent the development of interstitial edema, and, hence, improve the liver function.

Adenosine↗

Improvement of liver preservation quality with UW solution by chlorpromazine pretreatment of the donor in an experimental model.

We investigated the effect of donor pretreatment with chlorpromazine (CPZ), in rabbit livers cold-stored in University of Wisconsin (UW) cold storage solution for 48 hr. Three groups of livers were investigated: livers flushed with Perfadex and immediately thereafter reperfused on an isolated circuit (controls), and livers cold stored in UW solution for 48 hr, with or without donor pretreatment with CPZ, 3 mg/kg. After preservation, reperfusion was performed in vitro, using an isolated circuit (IPL). The reperfusion medium consisted of an oxygenated Krebs-Henseleit bicarbonate solution supplemented with 5 mM glucose, 50 mg/L of streptomycin and penicillin G, and 3.5% Dextran 60 for oncotic support. Livers that were not pretreated with CPZ produced 5.3 +/- 1.2 ml bile/100 g (mean +/- SD) during 2 hr of IPL reperfusion. CPZ donor pretreatment significantly improved the bile flow to 17.1 +/- 6.9 ml (P less than 0.01, Wilcoxon). This figure was not different from that in control livers without a storage period (18.3 +/- 3.8 ml). Alanine aspartate aminotransferase (ASAT) released into the perfusate was measured, and levels were increasing during 2 hr of reperfusion. ASAT values were moderately increased in the preserved groups compared with controls (P less than 0.01), with no discernible differences between livers with and without CPZ pretreatment. It is concluded that CPZ pretreatment of the donor improves preservation quality, as evidenced by improved bile formation. The present results suggest that 48 hr cold storage in UW solution may be safe for clinical preservation, if donors are pretreated with chlorpromazine.

Adenosine↗