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PubMed2005

An extremely high dose of losartan affords superior renoprotection in the remnant model.

BACKGROUND: Rats subjected to 5/6 renal ablation (NX) exhibit large renal amounts of angiotensin II (Ang II) and of its main receptor, AT-1R. At previously used doses, AT-1R blockers (ARB) offer only partial renal protection. A possible explanation for this limited effect is that these doses are insufficient to block most of the abnormally expressed AT-1R. We investigated whether extremely high doses of the ARB, losartan (L), offer better protection than conventional doses in the NX model. METHODS: Thirty days after NX, tail-cuff pressure (TCP), albuminuria (U(alb)V, mg/day), glomerulosclerosis index (GSI), fractional interstitial area (%INT), and macrophage infiltration (MO) were evaluated in a separate group (NX(pre)). The remaining rats were then subdivided among 4 groups: NX+V, receiving vehicle; NX+L50, treated with L, at the "conventional" dose of 50 mg/kg/day; NX+L500, receiving L, 500 mg/kg/day; and NX+HH, receiving hydrochlorothiazide and hydralazine to lower blood pressure to a similar extent as in group L500. RESULTS: After a month of treatment, blood pressure and renal vascular resistance were lowest in group L500. Glomerular pressure was lowered by a similar extent by L50 and L500, while GFR was similar among groups. U(alb)V, TCP, and renal injury were only partially reduced by L50 120 days after renal ablation. By contrast, L500 arrested renal inflammation and glomerular/interstitial injury at pretreatment levels, and promoted regression of hypertension and U(alb)V, causing no apparent untoward effects. CONCLUSION: The renal protection afforded by ARB in NX is dose dependent. Maximal protection may require doses several fold higher than those currently employed.

Albuminuria↗
PubMed2005

Relevance of immunological variables in neuroborreliosis and multiple sclerosis.

OBJECTIVES: The aims were to investigate the frequency of intrathecal synthesis of specific antibodies against measles (M), rubella (R) and varicella zoster (Z) viruses (MRZ reaction) as a diagnostic marker between multiple sclerosis (MS) and neuroborreliosis (NB) groups and to postulate the most typical cerebrospinal fluid (CSF) variables profile of these entities. METHODS: Three cohorts of patients were investigated: MS (n = 42), NB (n = 27) and other neurological diseases (OND) (n = 15). Measles, rubella, varicella zoster and borrelia-specific IgG antibodies were measured by ELISA, Q(alb) (CSF/serum albumin ratio) as a marker of blood-CSF barrier function and specific antibody indices (AI) were calculated according to relevant formulae. IgG oligoclonal bands (OB) were detected by isoelectric focusing and immunoenzymatic staining. RESULTS: Eighty-eight percent of MS patients had positive MRZ reaction and 26.2% had positive anti-borrelia AI. Eighty-nine percent of NB patients had positive anti-borrelia AI and two patients had individually anti-measles and rubella positive AI. MS-CSF variables profile included the presence of IgG OB in 81%, elevated Q(alb) in 31% and normal cell count in 66.7%. Of NB patients IgG OB were positive in 74%, elevated Q(alb) in 81.5% and normal cell count in 7.4%. CONCLUSION: MRZ reaction was proved as statistically significant marker in differential diagnosis between MS and NB. Typical CSF variables profile of these two entities is highly supportive, especially when MRZ is included.

Antigens, Bacterial↗
PubMed1979

Changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins during early infancy. Studies in healthy fullterm, small-for-gestational age and preterm infants aged 7 to 240 days.

Serum concentrations of thyrotropin (TSH), thyroxine (T4), triiodothyronine (T3), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were determined in 492 blood samples from 127 fullterm (FT), 91 small-for-gestational age (SGA) and 88 preterm (PT) healthy infants aged 7 to 240 days. Serum T4 decreased about 20% during the first month of life. In infants aged 7--49 days, serum T4 concentrations were significantly lower in SGA than in FT infants, and even lower values were found in PT infants. Serum T3 increased 50--70% reaching maximal values by 50--79 days of life. Serum T3 levels were higher in FT than in SGA infants throughout the observation period. In PT infants serum T3 increased from low values to levels which exceeded those of SGA and FT infants by 120--240 days of life. Serum TSH level did not change with age and was less than or equal to 5 mU/l in all infants. Serum TBG values were high compared to normal adult values and did not change significantly with age. Comparable serum TBG values were found in FT, SGA and PT infants. Serum TBPA increased with age. Serum TBPA increased gradually in FT infants. In SGA infants serum TBPA increased from low values to levels which by 120--240 days of life exceeded those of PT and FT infants. In PT infants a decrease in serum TBPA appeared before the rise commenced. Serum Alb increased gradually in FT, SGA and PT infants during the observation period. Serum Alb in PT infants aged 30--119 days was lower than those in FT infants with similar ages. These physiological changes in serum concentrations of thyroid hormones and hormone-binding proteins during early infancy should be considered when interpreting thyroid function tests in infants with various maturity.

Age Factors↗
PubMed1987

Orosomucoid as one of the serum components contributing to normal capillary permselectivity in rat skeletal muscle.

The effects of human serum orosomucoid (normal serum concentration 0.7-1.0 g l-1) on capillary permeability were investigated in 12 isolated maximally vasodilated rat hindquarters perfused with bovine serum albumin (50 g l-1) in modified Tyrode. Measurements were made of capillary filtration coefficient (CFC), permeability surface area product (PS) for vitamin B12 and isogravimetric clearance of radiolabelled albumin (Cl alb). The results were compared with those obtained using perfusates without addition of orosomucoid ('albumin group') or perfusates containing horse serum ('serum group'). Clearance of albumin was almost four-fold higher in the albumin than in the serum group, 0.0895 +/- 0.0066 (n = 12) and 0.0252 +/- 0.016 ml min-1 per 100 g (n = 18), respectively, while intermediate Cl alb values were obtained with human orosomucoid in the perfusate (greater than 0.1 g l-1), 0.0436 +/- 0.0034 ml min-1 per 100 g) (n = 8). These changes in Cl alb were not accompanied by any differences in CFC or PS. We conclude that orosomucoid is one of the components in serum (besides albumin) needed for the maintenance of normal permselectivity of the capillary walls of rat skeletal muscle. Alternatively, human orosomucoid is structurally related to other substances exerting this 'serum effect'.

Animals↗
PubMed2005

Superoxide dismutase mimetic preserves the glomerular capillary permeability barrier to protein.

Overproduction of superoxide (O2*) occurs in glomerular disease and may overwhelm the capacity of superoxide dismutase (SOD), thereby intensifying oxidant injury by O2* and related radical species that disrupt the glomerular capillary permeability barrier to protein. We examined the efficacy of the SOD mimetic tempol in preserving glomerular permeability to protein using 1) a rat model of glomerular immune injury induced by an antiglomerular basement membrane antibody (anti-GBM), and 2) isolated rat glomeruli in which injury was induced by the cytokine tumor necrosis factor-alpha (TNFalpha). To induce glomerular immune injury, rats received anti-GBM using a protocol that results in prominent infiltration of glomeruli by macrophages and in which macrophage-derived TNFalpha has been shown to mediate albuminuria. To increase glomerular capillary permeability to albumin (P(alb)) ex vivo, isolated glomeruli were incubated with TNFalpha at concentrations (0.5-4.0 microg/ml) known to stimulate O2* production. Increments in P(alb) were detected by measuring changes in glomerular volume in response to an applied oncotic gradient. Significant increases in the urine excretion of albumin and F(2alpha)-isoprostane were observed in rats with glomerular immune injury without a significant change in systolic blood pressure. Tempol treatment significantly reduced urine isoprostane and albumin excretion. In isolated glomeruli, TNFalpha increased P(alb) and tempol abrogated this effect, both in a dose-dependent manner. These observations indicate that SOD mimetics can preserve the glomerular permeability barrier to protein under conditions of oxidative stress from O2* production.

Animals↗
PubMed1983

Use of total cholesterol/albumin ratio as an alternative to high density lipoprotein cholesterol measurement.

In a study of apparently healthy males, we noted a correlation between serum albumin and high density lipoprotein cholesterol (HDL-C) (r = 0.32, p less than 0.001). We then correlated the total cholesterol:albumin ratio (TC:Alb) with the TC:HDL-C ratio (r = 0.89, p less than 0.001). We used the TC:Alb ratio to determine whether this was better than TC by itself in predicting whether an individual had a TC:HDL-C ratio of less than or greater than or equal to 5. The ratio performed better than TC and correctly classified 89% of individuals (66% with TC) (p less than 0.001). Since measurements of TC and Alb are routinely available on multichannel analysers, use of this ratio would provide a less expensive alternative to HDL-C measurement.

Adult↗
PubMed1999

Reduced concentrations of HIV-RNA and TNF-alpha coexist in CSF of AIDS patients with progressive multifocal leukoencephalopathy.

OBJECTIVES: To confirm reduced human immunodeficiency virus type-1 (HIV-1) burden in the CSF of patients with progressive multifocal leukoencephalopathy (PML) and to verify whether this viral load coincides with the absence of inflammatory changes in the CSF. METHODS: Paired CSF and plasma samples from 17 patients with PML, 26 with non-PML cerebral opportunistic infections, nine with HIV-1 leukoencephalopathy (HIVE), and 12 neurologically asymptomatic AIDS patients were subjected to HIV-RNA titration. Tumour necrosis factor (TNF)-alpha was also measured and the CSF albumin: serum albumin ratio (Q(Alb)) was calculated. RESULTS: The CSF HIV-1 burden of patients with PML did not differ from that of neurologically asymptomatic patients (p=0.21), but was significantly lower than CSF burden of the remaining patients (non-PML opportunistic infections, p<0.001; HIVE, p<0.001). Q(Alb) was normal for all neurologically asymptomatic patients, for 86.6% patients with PML, and 62.5% patients with HIVE (p=0.09). Q(Alb) was altered in 91.6% patients with non-PML opportunistic infections. TNF-alpha in CSF was higher in patients with non-PML opportunistic infections (p<0.001) and those with HIVE (p<0.001) than in patients with PML who consistently had TNF-alpha concentrations<10 pg/ml. CONCLUSIONS: These results, while indicating a reduced HIV replication in CSF of patients with PML which might serve as a disease marker, emphasise the increased CSF HIV-RNA concentration in patients with HIVE and patients with non-PML opportunistic infections. Low concentrations of HIV-RNA in CSF coincide with reduced TNF-alpha concentrations, possibly due to particular features of PML compared with other opportunistic infections as it develops without detectable inflammatory changes in the CSF.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Assessment of renal dysfunction in workers previously exposed to mercury vapour at a chloralkali plant.

Urinary albumin concentration (U-alb) and N-acetyl-beta-D-glucosaminidase (U-NAG) and glomerular basement membrane antibodies (a-GBMs) in serum samples were measured in 77 chloralkali workers previously exposed to mercury (Hg) vapour and 53 age matched referents. The exposure ceased on average 12.3 (range 1-35) years before the study. The mean exposure time was 7.9 (range 1.1-36.2) years. The mean yearly urinary Hg concentration (U-Hg) was 531 nmol/l. The concentrations of the urinary isoenzymes NAG A (U-NAG A) and NAG B (U-NAG B) were determined in 30 highly exposed subjects and 30 referents. No differences in U-alb or U-NAG, U-NAG A, or U-NAG B were found between the groups. Higher concentrations of a-GBMs were found among subjects who stopped exposure a short time before the study, but there was no association between a-GBMs and U-alb. The U-NAG and U-NAG A were negatively correlated with storage time. The results may suggest that microalbuminuria and enzymuria reported in subjects with ongoing exposure to Hg vapour are reversible in most instances.

Acetylglucosaminidase↗
PubMed1990

Macromolecular transport in canine coronary microvasculature.

Coronary vascular osmotic reflection coefficients (sigma dS) for total protein, albumin (Alb), immunoglobulin (Ig)G, and IgM were determined in the anesthetized dog. Myocardial lymph was collected from the anterior interventricular lymphatic trunk, and the sigma dS estimated from filtration rate-independent lymph-to-plasma protein concentration ratios (CL/CPS). Lymph flows of at least 12 times base line were needed to produce filtration rate-independent CL/CPS, and these were achieved in 9 of 12 experiments. In these nine experiments, sigma dS for total protein, Alb, IgG, and IgM were, respectively, 0.67 +/- 0.02 (SE), 0.59 +/- 0.05, 0.70 +/- 0.03, and 0.87 +/- 0.01. The data were fitted to a model that showed that transvascular fluid and solute flux could be described by two populations of pores. A large pore system with an equivalent radius of 235 A was responsible for 39% of the transvascular volume flow. A small pore system less than 53 A accounted for the remaining flow. In a second group of experiments (n = 8), 60 min of ischemia decreased the sigma dS to 0.27 +/- 0.03, 0.07 +/- 0.05, 0.22 +/- 0.03, and 0.69 +/- 0.04 for total protein, Alb, IgG, and IgM, respectively. A single population of pores of 220 A could describe the entire transvascular volume flow. These results indicate that coronary vascular protein permeability is moderately high and can be increased significantly by ischemia.

Animals↗
PubMed1997

Assessment of protein permeability in normal human systemic circulation.

Vascular permeability to oncotic agents is an important determinant of transvascular fluid flux (J) and systemic fluid balance. In this study, a technique was developed to measure protein reflection coefficients (omega) for albumin (Alb), immunoglobulin (Ig) G, and IgM in the intact human systemic circulation to evaluate the role of vascular protein permeability in health and disease. A mathematical model was developed to calculate omega in the forearm circulation from changes in venous hematocrit and protein concentration that occur during edema formation. Assumptions required for the model were validated in an initial set of experiments in normal subjects when edema was induced by inflating a pneumatic cuff on the upper arm. A second series of experiments assessed omega for Alb, IgG, and IgM in men (n = 7) and in women in the follicular (n = 5) and luteal (n = 4) phases of the menstrual cycle. There was an increasing trend in omega with molecular size in aggregated subjects [omega Alb = 0.81 +/- 0.12 (SE), omega IgG = 0.88 +/- 0.12, omega IgM = 0.92 +/- 0.18; P = 0.088]. These values were consistent with those obtained with in vitro preparations. omega values were lower in women in the luteal than in the follicular phase (P = 0.047). We conclude that the assumptions required for this model can be achieved in the intact forearm circulation and that there are menstrual phase-related differences in vascular protein permeability in normal women.

Adult↗
PubMed2000

Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury.

Apocynin (4-hydroxy-3-methoxy-acetophenone) inhibits NADPH oxidase in activated polymorphonuclear (PMN) leukocytes, preventing the generation of reactive oxygen species. To determine if apocynin attenuates ischemia-reperfusion lung injury, we examined the effects of apocynin (0.03, 0.3, and 3 mM) in isolated in situ sheep lungs. In diluent-treated lungs, reperfusion with blood (180 min) after 30 min of ischemia (ventilation 28% O(2), 5% CO(2)) caused leukocyte sequestration in the lung and increased vascular permeability [reflection coefficient for albumin (sigma(alb)) 0.47 +/- 0.10, filtration coefficient (K(f)) 0.14 +/- 0.03 g. min(-1). mmHg(-1). 100 g(-1)] compared with nonreperfused lungs (sigma(alb) 0.77 +/- 0. 03, K(f) 0.03 +/- 0.01 g. min(-1). mmHg(-1). 100 g(-1); P < 0.05). Apocynin attenuated the increased protein permeability at 0.3 and 3 mM (sigma(alb) 0.69 +/- 0.05 and 0.91 +/- 0.03, respectively, P < 0. 05); K(f) was decreased by 3 mM apocynin (0.05 +/- 0.01 g. min(-1). mmHg(-1). 100 g(-1), P < 0.05). Diphenyleneiodonium (DPI, 5 microM), a structurally unrelated inhibitor of NADPH oxidase, worsened injury (K(f) 0.32 +/- 0.07 g. min(-1). mmHg(-1). 100 g(-1), P < 0.05). Neither apocynin nor DPI affected leukocyte sequestration. Apocynin and DPI inhibited whole blood chemiluminescence and isolated PMN leukocyte-induced resazurin reduction, confirming NADPH oxidase inhibition. Apocynin inhibited pulmonary artery hypertension and perfusate concentrations of cyclooxygenase metabolites, including thromboxane B(2). The cyclooxygenase inhibitor indomethacin had no effect on the increased vascular permeability, suggesting that cyclooxygenase inhibition was not the explanation for the apocynin results. Apocynin prevented ischemia-reperfusion lung injury, but the mechanism of protection remains unclear.

Acetophenones↗
PubMed2006

Protective effects of S-nitrosoalbumin on lung injury induced by hypoxia-reoxygenation in mouse model of sickle cell disease.

Nitric oxide (NO) is a potential new therapeutic agent for sickle cell disease (SCD). We investigated the effects of NO donor on hypoxia-induced acute lung injury that occurs when transgenic sickle cell SAD mice are exposed to chronic hypoxia, a model for lung vasoocclusive sickle cell events. In wild-type and SAD mice, intraperitoneal injection of S-nitrosoalbumin (NO-Alb) produced no significant hematologic changes under room air conditions, whereas it induced mild temporary hypotension and inhibition of platelet aggregation. NO-Alb administration (300 mg/kg ip twice a day, equivalent to 7.5 microM NO) in wild-type and SAD mice exposed to 46 h of hypoxia (8% oxygen) followed by 2 h of normoxia resulted in 1) reduction of the hypoxia-induced increase in blood neutrophil count, 2) prevention of hypoxia-induced increased IL-6 and IL-1beta levels in bronchoalveolar lavage, 3) reduction of the lung injury induced by hypoxia-reoxygenation, 4) prevention of thrombus formation, and 5) prevention of hypoxia-induced increase of lung matrix metalloproteinase-9 gene expression. These effects provide new insights into the possible use of NO-Alb in the treatment of acute lung injury in SCD.

Anemia, Sickle Cell↗
PubMed1992

Changes in permeability of dog tracheal epithelium in response to hydrostatic pressure.

We tested the hypothesis that, in asthma, the airway epithelial damage and leakage of blood proteins into the lumen are the result of edema and raised submucosal hydrostatic pressure. Sheets of dog tracheal epithelium were mounted in Ussing chambers, and the effects of transepithelial hydrostatic pressure differences (delta P) on conductance (G), [3H]mannitol flux (Jman), and fluorescein isothiocyanate-albumin flux (Jalb) were determined. delta P values of 20 cmH2O directed from the mucosal to submucosal side of the tissue (m----s) had no significant effects on G, Jman, Jalb, or tissue ultrastructure. delta Ps----m caused increases in conductance (G) with a maximal effect at approximately 20 cmH2O. delta Ps----m of 20 cmH2O significantly (P less than 0.05) increased G (4.3 +/- 0.6 to 10.6 +/- 1.6 mS/cm2), Jman s----m (18 +/- 5 to 411 +/- 54 nmol.cm-2.h-1), J(alb)s----m (0.3 +/- 0.1 to 6.0 +/- 2.0 micrograms.cm-2.h-1), and J(alb)m----s (0.7 +/- 0.3 to 1.8 +/- 0.4 micrograms.cm-2.h-1). Jman m----s was not affected. On removal of delta P, G and Jman s----m returned to preexposure values, though J(alb)s----m remained slightly elevated at 1.1 +/- 0.3 micrograms.cm-2.h-1. Morphologically, delta Ps----m caused dilation of lateral intercellular spaces, disruption of tight junctions, and submucosal edema. The large increases in s----m fluxes of albumin and mannitol are consistent with bulk flow of fluid toward the lumen via the areas of epithelial damage.

Animals↗
PubMed1992

Arginine augments neither albuminuria nor albumin synthesis caused by high-protein diets in nephrosis.

Dietary protein independently modulates albuminuria (U(Alb)V) and albumin synthesis (AlbSyn) in nephrotic rats. While some amino acids are without effect on renal hemodynamics, arginine (Arg) augments renal blood flow and glomerular filtration rate, increases AlbSyn in tissue culture and isolated perfused livers, and could be one specific amino acid causing both decreased glomerular permselectivity and increased AlbSyn. Nephrotic rats were fed 10% casein (LP); 30% casein (HP); 30% casein with the inhibitor of nitric oxide (NO) synthesis N omega-nitro-L-arginine methyl ester (HP + L-NAME); 10% casein supplemented with Arg and amino acids that are Arg precursors of or are derived from Arg (proline, glutamate, and aspartate) in an amount in the increment between 10 and 30% casein (ArgAA); ArgAA supplemented with NH4 acetate to provide a diet isonitrogenous to 30% casein (ArgAA + NH4); or 10% casein plus an incomplete mixture of amino acids (Inc) containing the increment in histidine, phenylalanine, tryptophan, tyrosine, lysine, glycine, alanine, serine, threonine, cysteine, and methionine provided when the diet was changed from 10 to 30% casein. U(Alb)V increased significantly in HP and by a significantly greater amount in HP + L-NAME, but did not change in LP, ArgAA, or ArgAA + NH4. U(Alb)V tended to increase in Inc, was significantly greater than in LP or in ArgAA + NH4, but less than in HP. AlbSyn ([3H]phenylalanine incorporation) was no different in Inc than in HP, and was significantly greater than in either ArgAA + NH4 or LP. Increased AlbSyn results from increased ingestion of one or more of amino acids in Inc, but not from Arg or its precursors or products or from total dietary nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1988

Pulmonary microvascular response to LTB4: effects of perfusate composition.

We examined the effects of leukotriene B4 (LTB4) on pulmonary hemodynamics and vascular permeability using isolated perfused guinea pig lungs and cultured monolayers of pulmonary arterial endothelial cells. In lungs perfused with Ringer solution, containing 0.5 g/100 ml albumin (R-alb), LTB4 (4 micrograms) transiently increased pulmonary arterial pressure (Ppa) and capillary pressure (Pcap). Pulmonary edema developed within 70 min after LTB4 injection despite a normal Pcap. The LTB4 metabolite, 20-COOH-LTB4 (4 micrograms), did not induce hemodynamic and lung weight changes. In lungs perfused with autologous blood hematocrit = 12 +/- 1%; protein concentration = 1.5 +/- 0.2 g/100 ml), the increases in Ppa and Pcap were greater, and both pressures remained elevated. The lung weight did not increase in blood-perfused lungs. In lungs perfused with R-alb (1.5 g/100 ml albumin) to match the blood perfusate protein concentration, LTB4 induced similar hemodynamic changes as R-alb (0.5 g/100 ml) perfusate, but the additional albumin prevented the pulmonary edema. LTB4 (10(-11)-10(-6) M) with or without the addition of neutrophils to the monolayer did not increase endothelial 125I-albumin permeability. Therefore LTB4 induces pulmonary edema when the perfusate contains a low albumin concentration, but increasing the albumin concentration or adding blood cells prevents the edema. The edema is not due to increased endothelial permeability to protein and is independent of hemodynamic alterations. Protection at higher protein-concentration may be the result of LTB4 binding to albumin.

Animals↗
PubMed2001

Effect of lymphatic outflow pressure on lymphatic albumin transport in humans.

The effects of posture on the lymphatic outflow pressure and lymphatic return of albumin were examined in 10 volunteers. Lymph flow was stimulated with a bolus infusion of isotonic saline (0.9%, 12.6 ml/kg body wt) under four separate conditions: upright rest (Up), upright rest with lower body positive pressure (LBPP), supine rest (Sup), and supine rest with lower body negative pressure (LBNP). The increase in plasma albumin content (Delta Alb) during the 2 h after bolus saline infusion was greater in Up than in LBPP: 82.9 +/- 18.5 vs. -28.4 mg/kg body wt. Delta Alb was greater in LBNP than in Sup: 92.6 vs. -22.5 +/- 18.9 mg/kg body wt (P < 0.05). The greater Delta Alb in Up and Sup with LBNP were associated with a lower estimated lymphatic outflow pressure on the basis of the difference in central venous pressure (Delta CVP). During LBPP, CVP was increased compared with Up: 3.8 +/- 1.4 vs. -1.2 +/- 1.2 mmHg. During LBNP, CVP was reduced compared with Sup: -3.0 +/- 2.2 vs. 1.7 +/- 1.0 mmHg. The translocation of protein into the vascular space after bolus saline infusion reflects lymph return of protein and is higher in Up than in Sup. Modulation of CVP with LBPP or LBNP in Up and Sup, respectively, reversed the impact of posture on lymphatic outflow pressure. Thus posture-dependent changes in lymphatic protein transport are modulated by changes in CVP through its mechanical impact on lymphatic outflow pressure.

Adult↗
PubMed1999

Effects of protein meals on the urinary excretion of various plasma proteins in healthy subjects.

To examine whether hemodynamic changes in response to acute protein loadings with different protein sources cause increases in urinary excretion of plasma proteins in healthy subjects, urinary excretions of various plasma proteins with various molecular radii and isoelectric points, namely albumin (Alb), IgG, IgG4, ceruloplasmin (CRL), and alpha2-macroglobulin (A2), were measured in healthy subjects after ingestion of a beef meal or of a tuna fish meal. Significant increases in urinary excretions of the negatively charged IgG4 and CRL and of the neutrally charged IgG were found in parallel with enhanced creatinine clearances after each protein ingestion. These renal responses returned to basal levels 9 h after the test. This finding suggests that in healthy subjects, the increase in glomerular filtration rate after acute protein loading caused selective enhancement of urinary excretions of plasma proteins with a molecular radius of approximately 55 A (the radius of IgG, IgG4, and CRL), irrespective of the charge barrier of the glomerulus. The increases in these three plasma proteins may be induced by leakage via the shunt pathway in the glomerulus, as proposed earlier (see text). In contrast, increases in urinary excretions of A2 and Alb were not found. The former finding may be explained by the possibility that A2 would not pass through this pathway, since the molecular radius of A2 (88 A) is larger than that of IgG, although the latter finding may be partially explained by preferential renal tubular reabsorption of Alb.

Adult↗
PubMed1982

Effect of hypovolemic hypotension on plasma proteins and hepatic energy status in jaundiced rabbits.

Changes in plasma proteins and hematocrit (Ht) were studied in jaundiced rabbits subjected to hemorrhagic hypotension induced by the modified method of Wiggers and compared with changes in the hepatic energy status. At 48 h after common bile duct ligation, jaundiced rabbits showed hypoalbuminemia and a lower hepatic energy charge (EC), (ATP+1/2ADP)/(ATP+ADP+AMP). 30 min after induction of hypovolemic hypotension, in order to maintain a mean arterial pressure of 40 mm Hg, 86% of the blood collected in the reservoir (about 19% of the normal whole blood volume) had to be successively reinfused over a 2-hour period. Despite increases in Ht and plasma total protein (p-TP) occurring in parallel with the reinfusion, plasma albumin (p-Alb) and the ratio of p-Alb to plasma globulin (A/G) did not increase. On the other hand, in sham-operated rabbits small amounts of blood had to be frequently removed during the first hour (about 34% of the normal whole blood volume), and only 34% of it had to be reinfused over a 2-hour period. Despite removal of more blood and a concomitant decrease in Ht, p-Alb and A/G ratio were higher than in jaundiced rabbits. After marked decreases in EC and total adenine nucleotides (TAN) due to the initial blood loss, EC recovered somewhat and remained higher in sham-operated rabbits than in jaundiced rabbits, whereas TAN did not recover in either group. This seems to indicate that hemodilution functions effectively to maintain microcirculation following hemorrhagic hypotension in sham-operated rabbits, while in jaundiced rabbits a rapid breakdown of protective homeostatic mechanisms results in the earlier deterioration of the hepatic energy status.

Animals↗