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PubMedDate not supplied

[Value of ascitic lipids and sero-ascitic gradient of albumin in the differential diagnosis of ascites].

In order to compare its diagnostic value in the differentiation between malignant and hepatic ascites, we analysed the ascitic fluid concentrations of cholesterol (Ct) and triglycerides (Tg) and the serum-ascites albumin gradient (S-A alb grad) in 58 patients--forty one with chronic liver disease (CLD) and 17 with malignancy. In CLD group the mean values +/- SD for Ct (27.1 +/- 20.1 mg/dl), Tg (34.2 +/- 33.8 mg/dl) and S-A alb grad (1.9 +/- 0.6 g/dl) were significantly different from those obtained in malignant ascites (Ct 103.1 +/- 45.1 mg/dl; Tg 62.1 +/- 43.0 mg/dl; S-A alb grad 0.5 +/- 0.4 g/dl) (p less than 0.001 for all parameters). Application of the cutoff concentrations given in the literature revealed the following results: Ct-Sensitivity (Se) 82.4%, Specificity (Sp) 85.4%, Efficiency (E) 84.5%; Tg-Se 29.4%, Sp 95.1%, E 75.9%; S-A alb grad- Se 88.2%, Sp 97.6%, E 94.8%. The exclusion of the 4 patients with massive hepatic metastasis from malignant group by ultrasound or computer tomography gave an efficiency of 87.0% for Ct, 88.9% for Tg and 98.1% for S-A alb grad. We conclude that: 1) S-A alb grad is the best analysed parameter in the discrimination between malignant and hepatic ascites, 2) the combination with non-invasive imaging methods increases its diagnostic value.

Albumins↗
PubMed1979

Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study.

The effects of hemodynamic resuscitation with protein-containing or balanced salt solution were studied prospectively in 29 patients undergoing abdominal aortic surgery. Blood loss was replaced with packed red cells and extracellular volume with either Ringer's Lactate (RL) or 5% albumin in Ringer's lactate (ALB). Fluids were given to maintain the pulmonary capillary wedge pressure (PCWP) equal to or within 5 torr above preoperative (PO) levels, the cardiac output (CO) equal to or greater than preoperative values, and the urine output at least 50 ml/hr. Serum colloid osmotic pressure (COP), CO, PCWP, the gradient between COP and PCWP (COP-PCWP), and intrapulmonary shunt (Qs/Qt) were measured PO, intraoperatively (IO), and daily for 3 days. The measured variables were similar PO in both groups. Operation time, estimated blood loss, and transfusions were similar. Total fluids received for resuscitation (day of operation) was 11.3 +/- 0.8 liters (RL) and 6.2 +/- 0.4 liters (ALB). Fluid balance at the end of resuscitation was 8.4 +/- 0.8 liters (RL) and 3.4 +/- 0.5 liters (ALB). Maximum decrease in COP was 40% (P less than 0.001) in the RL group and was insignificant in the ALB group. The COP-PCWP decreased from 11 +/- 1 to 2 +/- 1 in RL (P less than 0.001) and insignificantly in ALB. Qs/Qt increased slightly in both groups following operation but was not different between groups. Fluid balance, total fluid infused, sodium balance, total sodium infused, COP, or COP-PCWP did not significantly correlate with Qs/Qt. Two patients in the ALB group experienced pulmonary edema associated with normal COPs and elevated PCWPs. There were no cases of pulmonary edema associated with low COPs and normal PCWPs in the crystalloid group. These data seriously question the necessity to maintain COP by using protein-containing solutions during acute hemodynamic resuscitation. When titrated to physiological end points, even large volumes of balanced salt solutions are tolerated well.

Albumins↗
PubMedDate not supplied

[Respiratory permeability studies by clearance of an aerosol solute and bronchoalveolar lavage in interstitial pneumopathies].

Two methods of assessing the permeability of the respiratory epithelium have been compared: the ratio of serum albumin concentration to bronchoalveolar albumin (BA/S Alb) and the clearance of the aerosolized 99mTc-diethylene-triamine-penta-acetic acid (Tc-DTPA). The study population consisted of a control group of 21 normal subjects (group C1) in whom BA/S Alb was determined, a control group of 26 normal subjects (group C2) in whom the clearance of Tc-DTPA was measured and a group of 27 patients with interstitial lung disease including 20 with sarcoidosis (group PI) in whom both BA/S Alb and the clearance of Tc-DTPA were measured. BA/S Alb was higher in group PI (3.55 +/- 2.44 mg X g-1) than in group C1 (0.67 +/- 0.31 mg X g-1; p less than 0.001). The clearance of Tc-DTPA was higher in group PI (3.64 +/- 4.05% X min-1) than in group C2 (1.18 +/- 0.31% X min-1; p less than 0.01). BA/S Alb value exceeded the normal value of 1.33 mg X g-1 in 23 of the 27 patients, but the clearance of Tc-DTPA exceeded the normal value of 1.82% X min-1 in 15 of the 27 patients (X2 = 6.4; p less than 0.02). No correlation has been observed between BA/S Alb and the clearance of Tc-DTPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Membrane Permeability↗
PubMedDate not supplied

The relation between nutritional state and quality of life in surgical patients.

OBJECTIVE: To explore the relationship between nutritional status and quality of life in a group of patients in a surgical department. DESIGN: Prospective open study. SETTINGS: Department of Surgery, University Hospital, Linköping, Sweden. SUBJECTS: The patients (n = 199) included 89 females and 110 males, mean age 59 years. INTERVENTIONS: The nutritional status was assessed by the percentage weight loss (% WL), weight index (WI), arm muscle circumference (AMC), triceps skin fold thickness (TSF), serum-albumin (Alb) and serum-prealbumin (p-Alb) concentration. Malnutrition was classified as three or more abnormal values and the overall frequency was 35%. The quality of life was assessed by a self-administered rating form with a life-domain rating part and a well-being rating part. In the current statistical analysis, the nutritional status and its different nutritional markers were tested for significant associations with the life-domain ratings (n = 7) and wellbeing scales (n = 11). RESULTS: There were significant relations between malnutrition according to nutritional assessment (p < 0.001), % WL (p < 0.005-0.001), Alb (p < 0.05-0.001), p-Alb (p < 0.01-0.001) and quality of life in all life domains except for the social network sphere. The anthropometric variables AMC and TSF showed no association with life domain ratings. As to the wellbeing ratings, an even stronger and more consistent relation were seen between a malnourished state (p < 0.01-0.001), % WL (p < 0.01-0.001), WI (p < 0.01-0.001), Alb (p < 0.01-0.001) and p-Alb (p < 0.05-0.001). AMC and TSF were not linked to the wellbeing ratings. CONCLUSIONS: In summary, there was a close association between malnutrition and impaired quality of life.

Adult↗
PubMed1994

Cellular structures involved in albumin interaction with preadipocytes in various stages of adipogenesis, in vitro.

Albumin is the major carrier of long chain free fatty acids, that are known to be heavily utilized by fat cells. To investigate the cellular structures involved in the interaction of albumin with preadipocytes, precursor fat cells isolated from rat epididymal fat pads were cultured in Dulbecco's modified Eagle's medium supplemented with 5% fetal calf serum and antibiotics. Cell differentiation was induced by 1.7 nM insulin added to the culture medium. The ensuing cells in various stages of differentiation were incubated with albumin, alone or bearing oleic acid, adsorbed to 5 nm gold particles (Alb-Au or Alb-OA-Au) for 10 min at 37 degrees C. As control, polyethyleneglycol-gold and IgG-gold complexes were used in same conditions. After extensive washing, the cell monolayer was fixed in 2.5% glutaraldehyde, and processed for electron microscopy. Examination of thin sections and morphometric analysis showed that: a) in the process of adipogenesis induced in vitro four cell types were simultaneously present: fibroblast-like cells (F), early adipocytes (EA), adipocytes (A) and aged adipocytes (AA); b) upon incubation with Alb-Au, the probe labelled preferentially coated pits and coated vesicles and only some uncoated vesicles; in time the tracer was found in endosomes, occasionally, multivesicular bodies and lysosome-like structures. The binding and uptake was dependent on the stage of cell differentiation, being less pronounced in fibroblast-like cells and increased in later stages (A and AA); c) Alb-OA-Au labelled the same structural features like the Alb-Au (i.e. coated pits and vesicles); however, the binding to the cell membrane was fourfold higher than that of Alb-Au in F and EA stages and was maintained at the same level in A and AA stages; d) control probes were taken up only by adipocytes and aged adipocytes, cells that express a strong phagocytic function for all tracers used. These results indicated that albumin bound to gold and especially albumin-bearing fatty acids-gold, bind preferentially to coated pits and vesicles of preadipocytes. Further internalization of albumin-gold particles seems to be non-specific, since both the probes and the controls adsorbed to gold were delivered to the same endosomal-lysosomal compartment.

Adipocytes↗
PubMedDate not supplied

Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children.

The relative contribution of, and possible mechanism of interaction between, aflatoxin and hepatitis B virus (HBV) in the development of primary hepatocellular carcinoma can be better investigated now that markers of individual exposure to both factors are available. In this study, blood samples were collected over a 1-month period from 117 children aged 3 to 4 years, resident in Kuntair or Kerr Cherno in the Upper Niumi District of The Gambia. Samples were analyzed for aflatoxin-albumin (AF-alb) adducts, markers of HBV infection, liver enzymes [serum alanine aminotransferase (ALT)] as markers of liver damage, and glutathione S-transferase M1 genotype. All but two children showed detectable serum AF-alb with levels ranging from 2.2 to 250.4 pg aflatoxin B1-lysine equivalent/mg albumin. There was a significant positive correlation between AF-alb and ALT (r = 0.4; P < 0.001). HBV carriers showed moderately higher levels of AF-alb than noncarriers but the difference was not statistically significant and the association between AF-alb and ALT was unchanged when the HBV carriers were excluded from the analysis, suggesting that factors other than HBV infection contributed to the association. The null glutathione S-transferase M1 genotype was infrequent (17.7%) in this population and was not associated with any difference in AF-alb adduct levels compared to glutathione S-transferase M1-positive individuals. However, the percentage of individuals with the null genotype varied significantly between ethnic groups with 32.1% in Fula, 8.8% in Mandinka, and 13.3% in Wollof.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxins↗
PubMed1993

[Studies on urinary apolipoprotein H in diabetics].

In order to elucidate the diagnostic significance of urinary apolipoprotein H (apo H), known as beta 2-glycoprotein I, urinary apo H levels were measured by a non-competitive enzyme immunoassay in diabetics without hypertension and Albustix-positive proteinuria. The relationships between urinary apo H levels and urinary albumin (Alb) levels as well as clinical profiles in diabetics were investigated. The mean urinary apo H level in 45 diabetics was 264.2 +/- 189.5 micrograms/g.cr, and significantly higher than that in 41 healthy subjects (120.6 +/- 84.8 micrograms/g.cr, p < 0.01). Diabetics were classified into three groups based on urinary Alb levels; 17 group I patients with normoalbuminuria (U-Alb < 15mg/g.cr), 12 group II patients, whose urinary Alb levels were in between normo- and microalbuminuria (15 < or = U-Alb < 30mg/g.cr) and 16 group III patients with microalbuminuria (30 < U-Alb < or = 300mg/g.cr). The mean urinary apo H level in group I patients, who were regarded as without nephropathy, was 199.2 +/- 109.0 micrograms/g.cr, significantly higher than that in normal subjects (p < 0.01). The mean urinary apo H levels in group II and III were 271.4 +/- 177.1 and 327.8 +/- 246.1 micrograms/g.cr, respectively. These values were also higher than in normal subjects (both of p < 0.01). Urinary apo H levels correlated positively with urinary levels of glycosaminoglycan (r = 0.382, n = 45, p < 0.01), which was regarded as an indicator of the anion loss from glomerular basement membrane to urine, and with urinary N-acetyl-beta-D-glucosaminidase activities (r = 0.378, n = 37, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1997

Protective effect of exogenous transferrin against hyperoxia: a study on premature rabbits.

We hypothesized that an increase in plasma iron binding capacity would decrease the generation of oxygen radicals and of lipid peroxides. To test this hypothesis, we studied whether supplementation of transferrin (TF) in premature rabbits would modify the degree of hyperoxic lung injury. Animals, delivered prematurely at 29 days of gestation (term 31 days), were randomized and given either 0.5 g/kg of albumin (Alb) (n = 116) or 0.5 g/kg of iron-free TF (n = 132) intravenously within 2 hours after birth. Another group was randomized to receive saline (n = 15), or either 0.35 g/kg (n = 12) or 0.70 g/kg of iron-free TF (n = 8). After exposure to a 100% oxygen environment for 2 or 4 days, the animals were killed, and plasma and bronchoalveolar lavage (BAL) fluid was recovered. Infusion of TF caused a dose-dependent increase in the concentration of TF and an increase in the unsaturated iron-binding capacity. Administration of TF at birth increased the gradient of TF between serum and alveolar epithelial lining fluid on day 4, suggesting decreased alveolar-capillary permeability. BAL fluid and plasma from TF-supplemented animals contained less lipid peroxidation products and more inhibitor of lipid peroxidation than BAL fluid or plasma from Alb-treated animals. In TF-treated animals, the recovery of protein in BAL fluid (TF group, 1.26 +/- 0.07 mg; Alb group, 1.78 +/- 0.10 mg; P = 0.02) and the water content of the extravascular lung tissue (TF group, 78.5 +/- 1.4%; Alb group, 83.2 +/- 1.3%; P = 0.05) were lower than in Alb-treated animals. We propose that supplementation of iron-free TF decreases iron-catalyzed redox reactions and may decrease hyperoxic lung injury in the premature.

Analysis of Variance↗
PubMed1995

Kinetic modelling of liposome degradation in peritoneal macrophages.

The objective of this study was to quantify and model the degradation process of liposomes in peritoneal macrophages (PMs). Iodinated albumin (125I-alb) was chosen to be the marker of liposome degradation. The time course of the degradation of free 125I-alb after pinocytosis by PMs followed first-order kinetics with a half-life of 23 min. The degradation of liposomally encapsulated 125I-alb was also quantified. Kinetic modelling of liposome degradation indicated the existence of two kinetically different processes, one with a half-life of 13 min and the other with a half-life of 7.5 h. Comparing the degradation of liposomal and free 125I-alb suggested that 125I-alb was delivered to lysosomes much faster through phagocytosis than pinocytosis. These results indicate that the intracellular degradation kinetics of pinosomes and phagosomes is different. This method can quantify the rate and extent of liposomal degradation in macrophages and provide kinetic information on the intracellular destiny of liposomally encapsulated compounds.

Albumins↗
PubMed1987

Value of nutritional parameters in the prediction of postoperative complications in elective gastrointestinal surgery.

The following nutritional parameters were assessed in 117 patients before major gastrointestinal surgery: percentage recent weight loss: percentage ideal body weight; tricipital skinfold; arm muscular area; grip strength dynamometry; serum albumin (ALB); serum transferrin (TFN); delayed hypersensitivity skin tests (DH); total lymphocyte count; prognostic nutritional index (PNI) and clinical assessment of malnutrition. Comparing the results in patients without complications (n = 99) with those in patients with complications (n = 18) and the results in patients who survived (n = 109) with those who died (n = 8), we found that only ALB, DH, TFN and PNI showed significant differences in both comparisons. Correlations of complications with combined parameters was made by multiple linear regression analysis; a modified PNI (mPNI), including these three single variables, has emerged. Considering its risk values, the nutritional parameters showed the following sensitivity and specificity, respectively: ALB less than 3.2 g/dl (72 and 71 per cent), anergy (67 and 64 per cent), TFN less than 205 mg/dl (67 and 55 per cent) and mPNI less than 20 (72 and 70 per cent). Using Bayes' theorems, ALB, DH and calculated indices showed the same predictive capacity and we conclude that single or multiple association of nutritional parameters have no additive effect. To predict complications of nutritional origin it seems only necessary to consider ALB, taking into account the type of operation and the normal duration of postoperative hospital stay without oral intake.

Adult↗
PubMed2001

Lactose as a carrier in dry powder formulations: the influence of surface characteristics on drug delivery.

The aim of the study was to investigate the interdependence of carrier particle size, surface treatment of the carrier, and inclusion of fines on the drug delivery from dry power inhaler formulations. Two size fractions (< 63 and 63-90 microm) of alpha-lactose monohydrate were subjected to treatment with 95% (v/v) ethanol to introduce small asperities or cavities onto the otherwise smooth surface without substantially changing the particle shape. After blending with albuterol sulfate [ALB; volume median diameter (VMD), 1.9 microm; geometric standard deviation (GSD), 1.5], the solvent-treated lactose produced a fine particle fraction (FPF; < 6.18 microm) and dispersibility of the drug that was significantly (ANOVA p < 0.01) lower than that which resulted from formulations containing untreated lactose of a similar size fraction, after aerosolization at 60 L min(-1) via a Rotahaler. The two size fractions of the treated lactose resulted in similar deposition profiles of ALB. The effects of such surface asperities or cavities of lactose were offset by introducing a small amount (5% w/w) of smaller-sized lactose (5-10 microm) to the powder formulations. The fine lactose increased the FPF and dispersibility of ALB to such a level that all lactose batches, regardless of particle size or whether solvent treated, produced a similar fraction of aerosolized ALB. The inclusion of recrystallized needle lactose (5-15 microm) was superior to micronized lactose in improving the aerosolization of ALB. The findings of this study indicate that the presence and characteristics of the finer fraction of lactose carrier particles dominate over the particle size and surface smoothness of the carrier particles in determining dispersion and deaggregation of drugs from dry powder formulations for inhalation.

Chemistry, Pharmaceutical↗
PubMed1996

Tandem arrangement of the human serum albumin multigene family in the sub-centromeric region of 4q: evolution and chromosomal direction of transcription.

The albumin gene family is comprised of four genes encoding: serum albumin (ALB), alpha-fetoprotein (AFP), alpha-albumin (ALF), and vitamin D-binding protein (DBP; also known as GC). The genes are regulated developmentally, expressed in the liver, and the proteins are secreted into the bloodstream. The GC gene, and the tandemly linked ALB and AFP genes, have been previously localized to human chromosome 4q11-13. Using techniques of fluorescence in situ hybridization to chromatin fibres, chromosome walking and DNA sequencing of genomic clones, we now report on the chromosomal location of the ALF gene and the organization of the entire gene family. The four genes are tandemly linked in the 4q sub-centromeric region: 5'ALB-5'AFP-5'ALF-5'GC3'-centromere, and hence are transcribed in the same, centromere-bound, direction. The linear arrangement of the four genes along the chromosome is not correlated with their temporal expression in the human ontogeny. It appears that GC is very close (and may be the gene proximal) to the centromere. The linear chromosomal arrangement of the four genes and the structural differences between them are congruent with the following evolutionary divergence of the gene family. Starting with the first duplication of an ancestral progenitor gene, a single evolutionary line led to the contemporary GC, leaving ALB/AFP/ALF on the other line of descent. The second duplication occurred in this ALB lineage, giving rise to ALB and the AFP/ALF progenitor, and the third, most recent one, gave rise to the AFP-ALF pair.

Albumins↗
PubMed2002

Similar permeability responses to nitric oxide synthase inhibitors of venules from three animal species.

The influence of nitric oxide (NO) on microvascular permeability remains unclear. NO synthase (NOS) inhibitors have been reported to increase as well as to decrease permeability in different experimental models and animal species. We tested the hypothesis that NOS inhibitors influence venular permeability differently in amphibians and mammals. Permeability coefficients to albumin (P(alb)(s)) were measured on in situ mesenteric venules of the frog and rat and excised pig coronary venules before and after exposure to NOS inhibitors. Despite individual variability in magnitude of responses, NOS inhibitors resulted in a reduction in P(alb)(s) in each species. Superfusion with 10(-5) M N(G)-monomethyl-l-arginine (l-NMMA) reduced P(alb)(s) of frog mesenteric venules by 42% (from a median of 11.4 x 10(-7) cm s(-1), n = 12, P < 0.01) and by 67% in porcine coronary venules (from 12.5 x 10(-7) cm s(-1), n = 5, P < 0.05). The response was attenuated in rat mesenteric venules; 10(-4) M N(G)-nitro-l-arginine methyl ester (l-NAME) reduced P(alb)(s) by 23% (from 7.6 x 10(-7) cm s(-1), n = 9, P = 0.01). The inactive d-enantiomers of the NOS inhibitors were without effect on P(alb)(s) in each model. In pig venules, perfusion with blood modified the permeability responses to l-NMMA, suggesting that effects of NO on permeability are modified by one or more elements of blood. These data support a role of nitric oxide release on venular permeability to albumin that is conserved among the three animal species.

Albumins↗
PubMed1990

Expression patterns of mRNAs for alpha-fetoprotein and albumin in the developing rat: the ontogenesis of hepatocyte heterogeneity.

In developing and normal adult rat liver the expression patterns of the mRNAs for alpha-fetoprotein (AFP) and albumin (ALB) were analysed by in situ hybridization using specific 35S-labelled complementary DNA probes. In the developing liver AFP and ALB mRNA are found from embryonic day (ED) 11 and 12, respectively, onward. At ED 20 the first signs of a zonal distribution of these mRNAs across the liver lobule can be observed, AFP mRNA concentration being higher in the pericentral area and ALB mRNA concentration higher in the periportal area. This distribution pattern of reciprocal, overlapping gradients of mRNA can be clearly recognized in the neonatal period. In the adult liver AFP mRNA can no longer be detected and similar to the neonatal situation, ALB mRNA is expressed across the entire porto-central distance decreasing in concentration going from the portal to the central area. Transient extra-hepatic expression of AFP mRNA is found in the embryonic heart and in the epithelial lining of intestine and lung; furthermore, AFP and ALB mRNA are found to be transiently expressed in the developing renal tubules. Similar expression patterns have been observed for other liver-characteristic mRNAs (Moorman et al., 1990), suggesting that common regulatory factors are operative during development.

Albumins↗
PubMed1998

Albumin and hemoglobin adducts as biomarkers of exposure to styrene in fiberglass-reinforced-plastics workers.

OBJECTIVE: The purpose of this work was to compare levels of styrene-7,8-oxide (SO) adducts of albumin (Alb) and hemoglobin (Hb) with those of two urinary metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA), among workers exposed to styrene in the reinforced-plastics industry and in unexposed subjects. We also wished to determine whether cigarette smoking influenced adduct levels among these subjects. METHODS: A group of 22 male workers was selected on basis of an expectedly high level of exposure to styrene, and a group of 15 controls was selected from hospital blood donors and hospital staff. In the exposed group, MA and PGA were quantified by high-performance liquid chromatography (HPLC) analysis of urine samples collected prior to the work shift. The SO adducts were cleaved from cysteine residues by reaction with Raney nickel to give 1-phenylethanol (1-PE) and 2-phenylethanol (2-PE), which, after derivatization, were measured using gas chromatography-mass spectrometry (GC-MS) in the negative-chemical-ionization (NCI) mode. RESULTS: The estimated mean levels of MA and MA + PGA were 74 and 159 mg/g creatinine, respectively. Using the levels of urinary metabolites, an average styrene concentration of about 100 mg/m3 in the workplace air was estimated. The mean levels of 2-PE and 1-PE adducts in exposed workers were 2.84 and 0.60 nmol/g Alb and 5.44 and 0.43 nmol/g Hb, respectively. When subjects were stratified by level of urinary metabolites [zero (controls), low-level exposure (MA + PGA < or = 159 mg/g creatinine), and high-level exposure (MA + PGA > 159 mg/g creatinine)] and smoking status (smokers versus nonsmokers), a difference in Alb adduct levels was found among the groups (2-PE P = 0.002, I-PE P = 0.052). The difference in 2-PE-Alb levels was related to exposure category, to smoking status, and to their interaction. Correlations at or near a 0.05 level of significance were observed among the workers (n = 22) between individual levels of SO-protein adducts and MA + PGA (2-PE Alb, r = 0.54, 2-PE Hb, r = 0.40). CONCLUSION: Our data suggest that only exposure to relatively high levels of styrene allows a clear relationship to be detected between styrene exposure and SO adducts, due in part to the effects of cigarette consumption and to the high background levels of these adducts observed in unexposed subjects.

Adult↗
PubMed2004

A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).

BACKGROUND: A previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years' treatment. METHODS: A multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study. RESULTS: There was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed. CONCLUSIONS: The present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.

Adult↗
PubMed1994

Transcapillary escape rate of albumin positively correlates with plasma albumin concentration in acute but not in chronic inflammatory disease.

The relationship among "negative" plasma acute-phase proteins (APP), ie, albumin, prealbumin, and transferrin, and "positive" APP, ie, C-reactive protein (CRP), fibrinogen, and orosomucoid, was investigated in patients with acute infectious disease (n = 8) and in patients with chronic malignant disease (n = 9). In addition, the transcapillary escape rate (TER) and outflux (J(alb)) of albumin were investigated using an intravenous injection of 2 microCi 125I-albumin. Interleukin-6 (IL-6) plasma concentrations were measured with an enzyme immunoassay. In the majority of patients, negative APP were decreased, whereas positive APP were increased. However, in patients with infectious disease, there were no significant correlations between any of the negative and positive APP. Also, in patients with infectious disease, TER was increased to 8.6 +/- 3.4%/h (mean +/- SD), and J(alb) to 114 +/- 60 mg/kg/h, compared with normal values of 4.3 +/- 2.6%/h and 108 +/- 7 mg/kg/h, respectively. Unexpectedly, there was a significant positive correlation between plasma albumin and both TER (r = .8279, P = .011) and J(alb) (r = .8683, P = .005). In patients with malignomas, significant correlations within negative and positive APP and inverse correlations between negative and positive APP resulted. Malignant disease induced only a slight elevation in TER (6.6 +/- 2.4%/h), J(alb) was within normal limits (92 +/- 35 mg/kg/h), and no correlations between plasma albumin concentrations and TER (r = -.0174, P = .97) or J(alb) (r = .4090, P = .27) were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1983

Induction of single-strand breaks plus alkali-labile bonds by N-nitrosoureas in rat tissues in vivo: ethylnitrosourea versus benzylnitrosourea.

Alkaline sucrose sedimentation procedures were used to quantitate the amount of single-strand breaks plus alkali-labile bonds (SSB + ALB) induced and repaired following a single intraperitoneal injection of the neurocarcinogen N-ethyl-N-nitrosourea (ENU) and its non-neurocarcinogenic analog N-benzyl-N-nitrosourea (BNU) in the brain, liver and kidney of female Sprague-Dawley rats. SSB + ALB were measured and used as an indicator of apurinic/apyrimidinic sites, phosphotriesters and in situ breaks. ENU induced a dose-dependent increase in the number of SSB + ALB at the doses studied (0, 0.39, 0.77, 1.54 mmoles/kg) in all 3 tissues. At 1 h postinjection with 0.77 mmoles/kg of these compounds there were 50-70% fewer breaks induced by BNU than ENU. The SSB + ALB induced by ENU persisted over a 7-day period, while those induced by BNU did not. Thus, these studies showed that 2 homologues of nitrosoureas, ENU and BNU, exhibited different potentials to induce and to persist SSB + ALB in vivo.

DNA↗