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PubMed1997

The melanin biosynthesis genes of Alternaria alternata can restore pathogenicity of the melanin-deficient mutants of Magnaporthe grisea.

The phytopathogenic fungi Magnaporthe grisea and Alternaria alternata produce melanin via the polyketide biosynthesis, and both fungi form melanized colonies. However, the site of melanin deposition and the role of melanin in pathogenicity differ between these two fungi. M. grisea accumulates melanin in appressoria, and their melanization is essential for host penetration. On the other hand, A. alternata produces colorless appressoria, and melanin is not relevant to host penetration. We examined whether the melanin biosynthesis genes of A. alternata could complement the melanin-deficient mutations of M. grisea. Melanin-deficient, nonpathogenic mutants of M. grisea, albino (Alb-), rosy (Rsy-), and buff (Buf-), were successfully transformed with a cosmid clone pMRB1 that carries melanin biosynthesis genes ALM, BRM1, and BRM2 of A. alternata. This transformation restored the melanin synthesis of the Alb- and Buf- mutants, but not that of the Rsy- mutant. The melanin-restored transformants regained mycelial melanization, appressorium melanization, and pathogenicity to rice. Further, transformation of Alb- and Buf- mutants with subcloned ALM and BRM2 genes, respectively, also produced melanin-restored transformants. These results indicate that the Alternaria genes ALM and BRM2 can restore pathogenicity to the mutants Alb- and Buf-, respectively, due to their function during appressorium development in M. grisea.

Alternaria↗
PubMed1997

Experimental subarachnoid hemorrhage in rats: effect of intravenous alpha-alpha diaspirin crosslinked hemoglobin on hypoperfusion and neuronal death.

BACKGROUND: Hemodilution with diaspirin crosslinked hemoglobin (DCLHb) ameliorates occlusive cerebral ischemia. However, subarachnoid hemoglobin has been implicated as a cause of cerebral hypoperfusion. The effect of intravenous DCLHb on cerebral perfusion and neuronal death after experimental subarachnoid hemorrhage was evaluated. METHODS: Rats (n = 48) were anesthetized with isoflurane and subarachnoid hemorrhage was induced by injecting 0.3 ml of autologous blood into the cistema magna. Each animal received one of the following regimens: Control, no hematocrit manipulation; DCLHb, hematocrit concentration decreased to 30% with DCLHb; or Alb, hematocrit concentration decreased to 30% with human serum albumin. The experiments had two parts, A and B. In part A, after 20 min, cerebral blood flow (CBF) was assessed with 14C-iodoantipyrine autoradiography. In part B, after 96 h, in separate animals, the number of dead neurons was determined in predetermined coronal sections by hematoxylin and eosin staining. RESULTS: Cerebral blood flow was greater for the DCLHb group than for the control group; and CBF was greater for the Alb group than the other two groups (P < 0.05). In one section, CBF was 45.5 +/- 10.9 ml x 100 g(-1) x min(-1) (mean +/- SD) for the control group, 95.3 +/- 16.6 ml x 100 g(-1) x min(-1) for the DCLHb group, and 138.1 +/- 18.7 ml x 100 g(-1) x min(-1) for the Alb group. The number of dead neurons was less in the Alb group (611 +/- 84) than in the control group (1,097 +/- 211), and was less in the DCLHb group (305 +/- 38) than in the other two groups (P < 0.05). CONCLUSIONS: These data support a hypothesis that hemodilution decreases hypoperfusion and neuronal death after subarachnoid hemorrhage. The data do not support the notion that intravascular molecular hemoglobin has an adverse effect on brain injury after subarachnoid hemorrhage.

Animals↗
PubMed1983

Resuscitation in hypovolemia and shock: a prospective study of hydroxyethyl starch and albumin.

In a prospective study comprising 50 patients, we evaluated the hemodynamic, pulmonary, renal and coagulation changes after resuscitation with 2 colloidal fluids, 6% hydroxyethyl starch (HES) and 5% albumin (ALB). Twenty-five patients studied in each group were well matched for age, clinical presentation, presence of shock and type of surgical procedures. A standard fluid challenge with 500 ml of either solution significantly (p less than 0.01) increased pulmonary artery wedge pressure (WP), mean arterial pressure (MAP) and left ventricular stroke work index (LVSWI) and decreased systemic vascular resistance index (SVRI). Increases in LVSWI of 43% to 68% over baseline in HES patients compared favorably to 15-22% increases in ALB patients. The cardiopulmonary variables at 12 and 24 h were comparable in both groups. Improvement in cardiac function was also reflected by better tissue perfusion as judged by reduction in arterial lactate from 2.9 to 1.5 mM/L (ALB) and 2.6 to 1.4 mM/L (HES). Increased O2 delivery and reduced O2 extraction without significant deterioration of PaO2 or alveolar-arterial O2 gradient were observed with stabilization of circulation. Clinical bleeding due to colloid resuscitation was not documented and renal function was not affected significantly by either fluid. It seems that HES may offer a cost-effective alternative to ALB for patients requiring colloid resuscitation.

Aged↗
PubMed2002

Pharmacokinetics and protein adduct formation of the pharmacologically active acyl glucuronide metabolite of mycophenolic acid in pediatric renal transplant recipients.

The acyl glucuronide metabolite (AcMPAG) of mycophenolic acid (MPA) has been found to possess both immunosuppressive and pro-inflammatory activity in vitro. In this study its pharmacokinetics were determined in pediatric renal transplant recipients receiving cyclosporine, steroids, and mycophenolate mofetil. Twelve-hour concentration-time profiles for AcMPAG, MPA, and the phenolic glucuronide (MPAG) were determined by high-performance liquid chromatography (HPLC) in the initial (1-3 wk; n = 16) and stable (3-12 mo; n = 22) phases after transplantation. In addition, the formation of covalent adducts between AcMPAG and plasma albumin (AcMPAG-Alb) was investigated using Western Blot analysis. AcMPAG-AUC(12h) showed significant (p < 0.05) correlations with MPA-AUC(12h) (r = 0.78) and MPAG-AUC(12h) (r = 0.78). In molar equivalents the median AcMPAG-AUC(12h) was 10.3% (range, 4.6%-45.5%) of MPA-AUC(12h). Values (median [range]) of AcMPAG-AUC(12h) (10.1 [3.30-30.1] mg.h/L), AcMPAG-C(0) (0.48 [0.08-1.43] mg/L), and AcMPAG-C(max) (1.95 [0.88-5.35] mg/L) were significantly (p < 0.05) higher in the stable phase than in the initial phase: 3.54 [2.07-20.0] mg.h/L for AUC(12h); 0.25 [<0.04-0.97] mg/L for C(0), and 1.12 [0.32-2.44] mg/L for C(max). The increases in the AcMPAG pharmacokinetic variables were paralleled by significant increases in the corresponding MPA variables. In addition, a strong negative correlation (r = -0.69; p < 0.05) was found between AcMPAG concentrations and the creatinine clearance. AcMPAG-Alb adducts were detected in all patient samples. They showed considerable interindividual variation and increased significantly with time from the initial phase to the stable phase. AcMPAG-Alb correlated significantly (p < 0.05) with AcMPAG-AUC(12h) (r = 0.70) and plasma albumin (r = 0.40). AcMPAG plasma concentrations are dependent on renal function, MPA disposition, and glucuronidation. The pharmacokinetics of AcMPAG is characterized by broad interindividual variation. In some patients AcMPAG may significantly contribute to the immunosuppression during mycophenolate mofetil therapy. AcMPAG-Alb adduct formation may serve as a marker for extended AcMPAG exposure. The association of AcMPAG with adverse effects must be further investigated.

Administration, Oral↗
PubMed2006

Prognostic factors for patients with spinal metastases from lung cancer.

STUDY DESIGN: We conducted a retrospective study to identify prognostic factors of patients with spinal metastases from lung cancer. OBJECTIVE: To provide clinical data with strong association to the prognosis and to propose criteria determining indication of operation for spinal metastases. SUMMARY OF BACKGROUND DATA: To make a proper selection of patients for whom surgery is indicated, forecasting short-time survival after spinal metastases is very important. In the past, there has been no report of prognostic factors of patients with such metastases from this cancer. METHODS: This study included 114 patients with spinal metastases of lung cancer. Tumors were histologically categorized as non-small cell lung cancer (NSCLC) in 94 patients and small cell lung cancer (SCLC) in 20 patients. We investigated prognostic factors after spinal metastases using Cox comparative hazard model and a preoperative prognostic score proposed by Tokuhashi. We also investigated the patients who underwent operation for spinal metastases from lung cancer in our hospital. RESULTS: Multivariate analysis showed that the significant prognostic factors for survival after spinal metastases from NSCLC were performance status (PS), Ca, Alb. Among SCLC patients, Ca, Alb, and a history of chemotherapy were significant (P < 0.05) in univariate analysis. The score of Tokuhashi was not correlative to the survival period. Among the operated patients, postoperative PS was significant for the period of postoperative survival. CONCLUSION: PS, Ca, and Alb in NSCLC and Ca, Alb, and a history of chemotherapy in SCLC are useful for determining an indication of operation for spinal metastases from lung cancer.

Activities of Daily Living↗
PubMed2003

Recombinant human growth hormone increases thyroid hormone-binding sites in recovering severely burned children.

Thyroxine (T4), Tri-iodothyronine (T3), and total serum protein levels are reduced in severely burned children. T4 and T3 are carried on serum transport proteins via thyroid hormone-binding sites (THBS). Treatment of bums with recombinant human growth hormone (rhGH) increases albumin (Alb) and prealbumin (PreAlb), which bind nearly 30% of circulating T4 and T3. This study investigated the effect of rhGH on THBS sites in burned children. Records of 11 acutely burned children with a total body surface area burned >40% who were randomized to either a daily subcutaneous injection of rhGH at 0.05 mg/kg/day or placebo for 6 months after discharge from hospital were reviewed. Thyroxine uptake percentage (TU%), Total T4 levels (TT4), free thyroxine index, Alb and PreAlb, and height and weight measurements taken at discharge and 6 months later were compared in both groups. In the six children who received rhGH, mean TU% had decreased from 41 +/- 1 to 33 +/- 1% by 6 months postdischarge, (P < 0.001), mean TT4 increased from 5.8 +/- 0.3 to 8.1 +/- 0.8 microg/dL, (P < 0.02), mean Alb increased from 2.0 +/- (0.6) to 3.5 +/- (0.1) g/dL (P < 0.0001), and mean PreAlb increased from 8.7 +/- 0.7 to 16.5 +/- 2.1 mg/dL, (P < 0.006). There were no significant changes in the five children in the placebo (control group), and height and weight did not significantly change in either group. rhGH significantly increases THBS in severely burned children, possibly through increases in serum Alb and PreAlb. The increases in circulating thyroxine observed in this group may be involved in the attenuation of growth arrest.

Blood Glucose↗
PubMed2004

Resuscitation from hemorrhagic shock with MalPEG-albumin: comparison with MalPEG-hemoglobin.

Our aim was to determine the efficacy of polyethylene glycol-conjugated human albumin (MalPEG-Alb) in restoring circulatory volume after 1 h of hemorrhagic shock. Experiments were performed in the awake condition in the hamster skin fold preparation. Microhemodynamic parameters and tissue Po2 were assessed with intravital microscopy and the use of the phosphorescence quenching technique. One hour after shock induction by withdrawal of 50% of the blood volume, animals were resuscitated with MalPEG-Alb (n = 6). Systemic and microhemodynamic parameters following resuscitation were identical to those obtained with the same protocol using MalPEG-Hb (1). However, parameters related to microvascular oxygen distribution were significantly lower in the MalPEG-Alb group compared with the previous data from the MalPEG-Hb group in that tissue oxygen partial pressure was 5 +/- 2 mmHg (vs. 8 +/- 3 mmHg, P < 0.05), oxygen delivery was reduced to 60 +/- 27% (P < 0.05), and oxygen consumption was reduced to 69 +/- 28% (P < 0.05). Both molecules were matched in composition (4.2 g/dL) and surface chemistry. MalPEG-Alb colloid osmotic pressure was 37 mmHg (vs. 49 mmHg for MalPEG-Hb), and viscosity was 2.7 cP (vs. 2.5 cP for MalPEG-Hb). The present results show that both solutions are efficacious plasma expanders and that the hemoglobin-based solution provides improved oxygen distribution and tissue Po2 in the hamster chamber model.

Animals↗
PubMed2005

Early difference in tissue pH and microvascular hemodynamics in hemorrhagic shock resuscitation using polyethylene glycol-albumin- and hydroxyethyl starch-based plasma expanders.

The hamster chamber window model was subjected to hemorrhagic shock by the withdrawal of 50% of blood volume (BV). BV was restored 1 h after hemorrhage with a single volume infusion (resuscitation) of 25% BV with polyethylene glycol (PEG)-conjugated bovine serum albumin (Alb) and hydroxyethyl starch (HES). Hemorrhage, shock, and resuscitation were monitored continuously in terms of mean arterial pressure (MAP), microvascular blood flow, capillary perfusion, and tissue pH. Blood samples for laboratory parameters were taken at baseline, shock, and resuscitation. Intravascular and tissue pO2 were assessed after resuscitation, and microvascular oxygen supply and extraction were calculated and corrected for pH effect on hemoglobin saturation. Resuscitation with PEG-Alb restored systemic and microvascular parameters up to the end of the observation period (90 min). HES was identical to PEG-Alb resuscitation during the initial 10 to 15 min, but was not sustained subsequently. The trend of recovery in MAP for HES persisted beyond the time when both function capillary density and tissue pH decreased, thus MAP was not indicative of early microvascular dysfunction. Hemoglobin oxygen saturation estimation showed a significant pH dependence. However, oxygen-dependant parameters corrected for pH varied less than 10% from uncorrected data. Early differences found at the microvascular levels suggest that decisions to amend end-result of resuscitation may be short and on the order of minutes. Furthermore, PEG-Alb appears to provide early and long-term sustained systemic and microvascular recovery when used to restitute perfusion and metabolic conditions after resuscitation from hemorrhagic shock.

Animals↗
PubMed2004

Natural selection drives altitudinal divergence at the albumin locus in deer mice, Peromyscus maniculatus.

In populations that are distributed across steep environmental gradients, the potential for local adaptation is largely determined by the spatial scale of fitness variation relative to dispersal distance. Since altitudinal gradients are generally characterized by dramatic ecological transitions over relatively short linear distances, adaptive divergence across such gradients will typically require especially strong selection to counterbalance the homogenizing effect of gene flow. Here we report the results of a study that was designed to test for evidence of adaptive divergence across an altitudinal gradient in a natural population of deer mice, Peromyscus maniculatus. We conducted a multilocus survey of allozyme variation across a steep altitudinal gradient in the southern Rocky Mountains that spanned several distinct biomes, from prairie grassland to alpine tundra. As a control for the effects of altitude, we also surveyed the same loci in mice sampled along a latitudinal transect through the prairie grassland that ran perpendicular to the east-west altitudinal transect. We used a coalescent-based simulation model to identify loci that deviated from neutral expectations, and we then assessed whether locus-specific patterns of variation were nonrandom with respect to altitude. Results indicated that the albumin locus (Alb) reflects a history of diversifying selection across the altitudinal gradient. This conclusion is supported by two main lines of evidence: (1) Alb was characterized by levels of divergence across the altitudinal transect that exceeded neutral expectations in two consecutive years of sampling (in contrast to the spatial pattern of variation across the latitudinal transect), and (2) levels of divergence at the Alb locus exhibited a positive association with altitudinal distance in both years (in contrast to the pattern observed at unlinked loci). We conclude that clinal variation at the Alb locus reflects a balance between gene flow and diversifying selection that results from elevational changes in fitness rankings among alternative genotypes.

Adaptation, Physiological↗
PubMed1988

High susceptibility of an analbuminemic congenic strain of rats with an F344 genetic background to induced bladder cancer and its possible mechanism.

The susceptibility of an analbuminemic congenic strain of rats (F344-alb) originating from the F344 strain to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. F344-alb rats were found to be highly susceptible to induction of urinary bladder cancers. The incidences of bladder cancers in F344-alb and F344 rats were 94% (15/16) and 31% (5/16) in males and 100% (16/16) and 19% (3/16) in females. The bladder weights of these rats, including tumors, were 307 +/- 294 mg, 123 +/- 26 mg, 183 +/- 80 mg and 93 +/- 11 mg, respectively. Administration of 0.05%, 0.1% and 0.3% BBN in the drinking water for 2 weeks resulted in greater increases in the bladder content of N-butyl-N-(3-carboxypropyl)nitrosamine in F344-alb rats than in F344 rats. This increase was prevented by the presence of rat albumin.

Animals↗
PubMed1995

Comparative plasma and tissue pharmacokinetics and drug residue profiles of different chemotherapeutants in fowls and rabbits.

Blood and tissue pharmacokinetics and drug residue profiles of six chemotherapeutants were studied. Ceftriaxone (CEF), intravenously at 50 mg/kg, sulfamonomethoxine (SMM) and sulfaquinoxaline (SQ), orally at 200 mg/kg, and olaquindox (OLA), orally at 50 mg/kg, were administered to young broilers. Penicillin (PEN), intramuscularly at 200,000 U/kg, and albendazole (ALB), orally at 20 mg/kg, were given to rabbits. For each drug, 13-18 groups (n = 5-10 individuals/group) of the dosed animals were killed at different post-dosing times. Drug and/or metabolite concentrations in plasma, liver, kidney, heart, lung, and muscle tissues were analysed by HPLC procedures. Multi-exponential kinetic models were fitted to the observed tissue concentration-time data by applying a non-linear least-squares regression computer program. Tissue half-life, peak tissue concentration, and time of peak tissue concentration were determined. Half-life of CEF, SMM, SQ, OLA, PEN, ALB, and two metabolites of ALB (sulfoxide and sulfone) in various tissues ranged 0.6-1.4, 4.7-9.0, 4.5-18.9, 1.8-3.1, 0.9-3.0, 3.4-9.6, 5.0-16.1 and 7.4-12.2 h. The times required for CEF, SMM, SQ, OLA, PEN, and ALB residue concentrations to decline to 0.1 microgram/g in various tissues ranged from 5.0-11.6, 70.0-110.5, 114.0-179.8, 21.3-30.3, 4.1-24.8 and 47.8-84.4 h. Drug kinetic characteristics in tissues differed significantly from those in plasma, and also varied from tissue to tissue. It is necessary, therefore, to evaluate tissue kinetics when designing dosage regimens in tissue infection chemotherapy with these drugs. Knowledge of tissue kinetics is also important in predicting and controlling drug residues in edible tissues of food-producing animals.

Administration, Oral↗
PubMed1998

Assay for detecting IgE and IgG antibodies against Candida albicans cell-wall mannan.

In the present study, we assayed mannan-specific IgE and IgG antibodies in samples of serum isolated from blood collected from adult patients with bronchial asthma, using a liquid-phase method with a polysaccharide, mannan (Mn), purified from Candida albicans (C. alb), and investigated the relationships of allergenicity among a crude extract of C. alb, purified Mn, and acid protease (AP), The correlations between the titers of anti-Mn A and anti-Mn B IgE and IgG were very strong, and the levels of inhibition of anti-Mn A IgE and IgG reactions by Mn A and Mn B were almost identical. Although no common allergenicity was observed between Mn A and AP because there was no correlation between the titers of anti-Mn A and anti-AP IgE, and no inhibition of the anti-Mn A IgE reaction by AP, both antigens were found to exist in crude C. alb. The level of inhibition of anti-crude C. alb IgG reaction by Mn A or Mn B was about 60%. Approximately 70% inhibition of the anti-Mn A IgE reaction was observed for eight different fungal allergen extracts, but no inhibition was observed for 11 of the other fungal allergen extracts tested. The above results indicate that common antigenicity was observed between Mn A and Mn B in the human IgE and IgG antibody production system, and the cross-allergenicity observed among some fungi was considered to be the result of the common antigenicity of Mn isoforms.

Allergens↗
PubMed1988

Alpha fetoprotein and albumin gene transcripts are detected in distinct cell populations of the brain and kidney of the developing rat.

We report the cellular localization of alpha-fetoprotein (AFP) and albumin (ALB) gene transcripts in rat kidney and brain as detected by in situ hybridization on tissue sections with [35S]-labelled alpha-fetoprotein and albumin cDNA probes. Both types of mRNA were present in distinct cell populations of the developing kidney and brain. In the kidney, both gene transcripts were distributed over all developing tubular cells in the 20-day-old fetus. During the first 3 weeks of life, a gradual decrease in the expression of AFP and ALB mRNA was apparent, the rate of decrease being greater on proximal tubules than on the other tubular cells. From the 4th week onwards, a weak signal for both mRNAs persisted in the majority of the tubular cells. In the brain, all neuronal cells expressed both genes. Transcript cellular distribution was mainly cytoplasmic during fetal and early postnatal life and became predominantly nuclear at 3, 4 and 5 weeks, suggesting that posttranscriptional mechanisms are involved in the control of AFP and ALB gene expression at these stages. In the adult brain no significant signal was recorded thereafter. Coexpression of AFP and ALB transcripts by specific cell types, together with their gradual disappearance concomitant with postnatal organ maturation, suggests a possible role for these proteins in terminal differentiation processes of tubular and neuronal cells.

Aging↗
PubMed2007

Advanced-glycation end products (AGEs) derived from glycated albumin suppress early beta1-adrenergic preconditioning.

Ischemic heart disease in diabetic patients might be linked to the accumulation of advanced-glycation end products (AGEs). In ischemic rat hearts, expression of receptor for AGEs and its ligands is significantly enhanced and involved in cardiac ischemia/reperfusion (I/R) injury even in the absence of diabetes. It has recently been reported that diabetic human myocardium cannot be protected by preconditioning. In this context, our hypothesis was that beta1-adrenergic preconditioning might be altered in the presence of AGEs. Using an isolated non-working rat heart model, this study investigated the effect of AGEs on cardioprotection induced by transient beta1-adrenoceptor (beta1-AR) stimulation with xamoterol (Xa). After 6-hydroxydopamine (6-OHDA) pre-treatment and a 20-min stabilization period, hearts were perfused at constant pressure for 20 min, then subjected to 40 min of global ischemia and 30 min of reperfusion (I/R, Ctrl); and exposed to 0.01 microm Xa for 5 min framed with or without 15.2 microm albumin (Alb) or glycated albumin (Gly Alb). The main endpoints were the mean coronary flow (MCF), the left ventricular end-diastolic pressure (LVEDP), rate-pressure product (RPP) and creatine kinase (CK) release and necrosis area. XA induced an increase in the MCF after I/R (t = 85 min), a protective effect on the LVEDP, an improvement in RPP, a decrease of CK release during reperfusion and a reduction of necrotic area. The beneficial effects induced by Xa during reperfusion were suppressed by the administration of Gly Alb during Xa infusion, whereas Alb did not hamper Xa-induced protection. These results suggest that AGEs suppress the cardioprotection resulting from the activation of beta1-ARs and thus might contribute to cardiovascular damages seen in diabetic patients.

Adrenergic beta-1 Receptor Agonists↗
PubMed1979

Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants.

Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels were found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in fullterm, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was even lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.

Birth Weight↗
PubMed1997

Interstitial exclusion of macromolecules studied by graded centrifugation of rat tail tendon.

Mechanical compression of cartilage and tendon has been shown to expel fluid both from collagen fibrils and from the extrafibrillar space. As reported previously, albumin (Alb) concentration and colloid osmotic pressure in tendon fluid (TF) expelled by repeated centrifugations fell progressively at increasing centrifugation force (G = 600, 2,400, and 13,100), suggesting either molecular sieving in compressed tendon or mobilization of protein-free (excluded) fluid. The present experiments, including analysis of 51Cr-EDTA, aprotinin (Ap), Alb, immunoglobulin G (IgG), and hyaluronan (hyaluronic acid; HA) with molecular weight (MW) ranging from 341 to 5 x 10(6), strongly favored the exclusion hypothesis; the fraction of Alb, IgG, and HA-free fluid (excluded) was already 0.23-0.36 in the first centrifugate, increasing to 0.73-0.82 in the third. The corresponding numbers were, respectively, 0.11 and 0.43 for Ap (MW 6,500), and 0 and 0.08 for 51Cr-EDTA. These data, combined with calculated exclusion by collagen fibrils, proteoglycans, and HA, indicated that the first centrifugate was mainly derived from the extrafibrillar space, with increasing addition of macromolecular free intrafibrillar fluid in the second and third centrifugates, with each space contributing about equally to the total centrifugate volume. The calculations also indicated that Alb-, IgG-, and Ap-free fluid was mobilized from extrafibrillar space by increasing overlap of excluded territories. An excess of HA in tendon compared with that estimated from centrifugate concentrations suggests a large bound or immobilized HA fraction.

Animals↗
PubMed1999

Plasma volume expansion with solutions of hemoglobin, albumin, and Ringer lactate in sheep.

We have measured plasma volume expansion (Evans blue and hematocrit changes) and hemodynamic responses in conscious hemorrhaged and normovolemic splenectomized sheep after a 30-min infusion of either 20 ml/kg of diaspirin cross-linked hemoglobin (DCLHb), 20 ml/kg of human albumin (Alb), or 60 ml/kg of a solution of Ringer lactate (RL). All regimens expanded blood volume and increased blood pressure and cardiac output after hemorrhage. However, only 15 +/- 3% of the infused volume of RL was evident as intravascular expansion 10-min postinfusion, compared with 67 +/- 16% and 139 +/- 139% for Alb and DCLHb, respectively. DCLHb infusions were associated with higher blood pressures and lower cardiac outputs compared with RL and Alb infusions, but the increased oxygen content of blood with DCLHb resulted in systemic delivery of oxygen similar to that of the other infusions. These differences in hemodynamics and vascular volume continued for 6 h, and at 24 h vascular volume and all hemodynamics were similar in all three groups. The better volume expansion with DCLHb may be due to greater mobilization of endogenous interstitial protein or reduced transcapillary loss as total intravascular endogenous plasma protein increased after infusion of DCLHb, whereas there was an apparent loss of endogenous intravascular protein after infusions of Alb and RL. Vasoconstriction by DCLHb is one mechanism that could lower blood-to-tissue transport of fluid and protein. In addition to its oxygen-carrying capacity and vasoactivity, DCLHb is associated with volume expansion properties out of proportion to its colloid osmotic pressure.

Animals↗
PubMed1993

Relationships among protein and albumin concentrations and oncotic pressure in nephrotic plasma.

We determined oncotic pressure (pi) by membrane osmometry and assayed total protein (TP) and albumin (Alb) concentrations in plasma of 102 nephrotic subjects and 27 healthy controls. All three quantities were markedly depressed in the nephrotic group. When plasma was serially diluted and concentrated, nephrotic but not control plasma also exhibited a highly variable change point in the nonlinear relationship between TP or Alb and pi. Absent a unique change point, we developed quadratic models which incorporated TP, Alb, and (TP x Alb) to prospectively predict pi in unperturbed plasma. The ability of the most successful quadratic model to predict pi in afferent or efferent arteriolar plasma was limited; the prediction errors reached 10 mmHg in nephrotic and 6 mmHg in control subjects. The nephrotic model coefficients also differed significantly from control and pointed to an important influence of nonalbumin proteins on pi in nephrotic plasma. Investigation of the intrinsic membrane properties of diseased glomerular capillary walls requires precise knowledge of pi. For this purpose we recommend that pi be directly determined by membrane osmometry rather than calculated from protein concentration(s).

Adolescent↗