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[Effect of dopamine combined with norepinephrine on the renal function in patients with septic shock].

OBJECTIVE: To investigate the effects of dopamine and norepinephrine on the renal function in the patients with septic shock. METHODS: Eighty-seven patients with septic shock were divided into three groups (group A, B, C) according to the biggest infusing rate of norepinephrine, with the infusing rate of 0.5 - 0.9, 1.0 - 1.5, 1.6 - 2.0 microg x kg(-1) x min(-1), respectively. Mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB) and urine beta(2)-microglobulin (Ubeta(2)-MG) as well as APACHE III score in all the patients were detected. RESULTS: Before anti-shock therapy was given, hypotension, tachycardia and oliguria occurred in all the 87 patients, and CRE, BUN, U-ALB, Ubeta(2)-MG and APACHE III score were abnormal in most cases. With the anti-shock therapy, MAP, HR, urine output and BUN, CRE in all patients returned to normal levels gradually, and U-ALB, Ubeta(2)-MG levels and APACHE III score also restored but still remained abnormal. CONCLUSIONS: The first aim of treating septic shock should be restoring the organ blood supply, and based on volume resuscitation, dopamine, noradrenaline and other vasoactive drugs could be combined to maintain circulatory stability.

APACHE↗

Urine protein excretion and swimming events.

To determine total urinary protein, albumin (ALB), and beta 2-microglobulin (beta 2m) excretion rates in relation to different speeds, 12 males were studied while swimming distances of 100, 600, and 2,000 m at maximal speed. Venous blood lactate concentrations rose to 16.1, 11.6, and 4.5 mmol.l-1 after the 100, 600, and 2,000 m events, while plasma volumes were reduced by 11.3, 7.7, and 5.5%, respectively. ALB urine excretion increased to 110-120 micrograms.min-1 after the 100 and 600 m swims and to 56 micrograms.min-1 after 2,000 m (resting values: 9 micrograms.min-1). In the meantime, the beta 2m excretion rate increased 21 and 10 times the resting values, respectively, for the two shorter swims, with no change for the longer one. Progressive plasma volume reduction was associated with the increase of the protein excretion rate. As evidenced by the creatinine clearance, the glomerular filtration rate did not change for the 100 m swim but dropped by 23 and 35% for the 600 and 2,000 m ones, respectively. On the other hand, the ALB clearance increases were elevated for the three swims, while the beta 2m clearance increases were inversely related to the swimming speeds. The data showed a relationship between the rate of protein excretion and the speed of the swim, and the reduction of plasma volume. The findings could indicate a renal glomerular alteration, with an additional dysfunction of the tubular reabsorption process when the exercise load is high during swimming events.

Albuminuria↗

The rat vitamin D binding protein (Gc-globulin) gene. Structural analysis, functional and evolutionary correlations.

The complete rat vitamin D binding protein (DBP) gene has been cloned and characterized. Genomic mapping suggests that there is only one copy of this gene in the haploid genome. The gene spans 35 kilobase pairs and contains 13 exons. All exons, exon/intron borders, and 2196 base pairs of 5'-flanking region have been sequenced. The transcription cap site, determined by primer extension analysis, is 62 base pairs upstream from the start of translation and predicts that an unusual TGTAAA motif may serve as a surrogate TATA. The promoter region contains about 50% nucleotide sequence similarity to the corresponding region of the partially characterized human DBP gene and is uniquely interrupted by a repetitive element. Although lacking in overall sequence similarity to the albumin (ALB) and alpha-fetoprotein (AFP) genes, the 5'-flanking region of the DBP gene contains a number of conserved segments which may correspond to critical proximal promoter elements in this gene family. The location of the introns in the coding region of the DBP gene is highly conserved when compared with the ALB and AFP genes. Detailed comparison of exon size and content confirms the previous prediction that the smaller size of the DBP protein results from loss of internal exons 12 and 13 from the DBP progenitor gene during its evolutionary divergence from ALB and AFP.

Amino Acid Sequence↗

The role of serum proteins in acid-base equilibria.

Serum proteins act as weak acids and participate in acid-base balance. Their effects are imprecisely quantified; in particular, the roles of albumin and globulins need reevaluation. We approached the problem in three steps. First, in artificial solutions resembling serum but with human serum albumin as the only protein moiety, we varied the strong ion difference (SID), partial pressure of carbon dioxide (Pco2) and the concentration of albumin [( Alb]) and fixed the concentration of inorganic phosphate [( Pi]). We measured pH and derived the charges on albumin. Second, extending the work of Stewart (Stewart PA. How to understand acid-base. A quantitative acid-base primer for biology and medicine. New York: Elsevier, 1981:1-286), we developed a mathematical model that solves for pH and for the charges on albumin as functions of SID, Pco2, [Pi], and [Alb]. The calculated values fit the observed values well; that is, the model describes well the behavior of these solutions over a wide range of simulated complex acid-base disturbances. Finally, in human serum samples containing both albumin and globulins, we varied SID, Pco2, and total protein concentration [( TP]); we fixed [Pi] and then measured pH and derived the charges on proteins as above. When we applied to these data the computer model developed for albumin alone, the calculated pH and derived charges on albumin values agreed well with the observed pH and derived charges on proteins. We conclude first that human serum globulins play a negligible role in acid-base equilibria, and second, that in normal human serum at pH 7.40 with [TP] = 7 and [Alb] = 4.3 gm/dl, the charges attributed to proteins are approximately 12 mEq/L; this is substantially less than the value of approximately 17 mEq/L given by many contemporary texts, based on work of van Slyke et al. (van Slyke DD, Hastings AB, Hiller A, Sendroy J Jr. Studies of gas and electrolyte equilibria in blood. XIV. Amounts of alkali bound by serum albumin and globulin. J Biol Chem 1928;79:769-80). These findings should be considered when evaluating acid-base balance in patients with abnormal serum albumin concentration, for example, when interpreting values of the anion gap.

Acid-Base Equilibrium↗

Human embryonic liver cell differentiation. I. Changes in specific mRNA synthesis correlates with parameters signaling oncologic alterations.

When incubated in preconditioned medium, i.e. spent media from the hepatocellular carcinoma (PLC/PRF/5) cell cultures, human embryonic liver (HEL) cells differentiate and acquire oncologic phenotypes. This is caused by transcriptional alterations in fetal gene expression. This occurs when hepatocytes are proliferating rapidly and secreting alpha fetoprotein (AFP), and later when the quiescent state is reached with secretion of albumin (ALB). The present studies examined the parameters signaling oncologic transformation during liver cell differentiation in the conditioned medium. mRNAs coding for AFP, ALB and HBsAg were isolated from HEL, adult liver cells (ADLC) and from PLC/PRF/5 cells, respectively. cDNA molecules complementary to these polysomal mRNA molecules were constructed and labeled with 32P. These tracers were used to quantitate changes in cellular mRNA X AFP, mRNA X ALB and mRNA X HBsAg directly by DNA molecular hybridization during HEL cells cultivation in the preconditioned medium. Under these conditions, the changes in cellular mRNA X HBsAg and mRNA X AFP correlated with an increased tumorigenicity in athymic Nu/Nu mice, membrane galactosyltransferase and phospho-tyrosine kinase activities.

Albumins↗

[Changes in protein in bile excretion from rat liver inoculated with BERH-2 hepatoma].

Rocket immunoelectrophoresis was used to assay the change in alpha fetoprotein (AFP) and albumin (Alb) in bile of rats 10 to 14 days after intrahepatic or intraperitoneal inoculation of BERH-2 hepatoma. The bile was collected from the common bile duct cannula. Total protein was determined by the Lowry method. The results showed that the excretion of total protein and Alb was reduced to 54% and 24% of the control in the intrahepatic group, and 65% and 56% of the control in the intraperitoneal group. Bile-AFP can be detected in rats in both groups and its concentration increased gradually during the tumor progression. In the hepatic group, the bile-AFP content per gram of tumor tissue was 29% of that in the intraperitoneal group. It suggests that decreased excretion of AFP, Alb and total protein in bile of rat bearing tumor in the liver be related to local obstruction of excretion by the tumor mass leading to constriction of biliary canaliculi.

Albumins↗

A prospective randomized study of hydroxyethyl starch, albumin, and lactated Ringer's solution as priming fluid for cardiopulmonary bypass.

The ideal priming fluid for cardiopulmonary bypass is not known. We designed a study to determine whether there are important differences in the clinical effects of hydroxyethyl starch versus albumin when used in priming fluid, and in the clinical effects of colloid versus crystalloid priming fluid. We prospectively randomized 83 adult patients undergoing coronary artery bypass or valve replacement. All patients were managed by standardized protocol, and they received one of three priming fluids for bypass: hydroxyethyl starch (HES), 26 patients; albumin (ALB), 28 patients, and lactated Ringer's solution (LRS), 29 patients. The groups were stratified by body weight and type of operation. We measured 41 variables relating to operative time factors, fluid balance, bleeding, and organ function (renal, cardiac, and pulmonary) at several time intervals. The LRS group had a significantly lower colloid osmotic pressure than the other two groups, and the HES group had a substantially higher blood viscosity. Although the prothrombin time was significantly lower in the LRS group (p less than 0.05), the differences were very small and not clinically important. The platelet count in the HES group was significantly lower than in the other two groups immediately after bypass, but it was not different by the time the patients left the operating room. There were no differences among the groups in chest tube drainage, blood bank usage, or fluid balance. Postoperatively, the pulmonary shunt fraction was significantly greater in the LRS group. Body weight increased more in the LRS than in the HES and ALB groups (p = 0.01). No adverse reaction to the prime solutions was noted. The differences between the HES and ALB groups--prothrombin time, platelet count, and blood viscosity--had no apparent clinical effects; thus, the two may be considered clinically equivalent. The greater somatic and pulmonary fluid accumulation in the LRS group suggests that colloid is preferable to crystalloid in priming fluid.

Albumins↗

[The nephrotoxicity of ionic and nonionic contrast media in urography. An evaluation with immunoenzyme technics and monoclonal antibodies].

The nephrotoxicity of ionic and nonionic contrast media (cm) was evaluated in 52 patients undergoing pyelography. The contrast media were i.v. injected in 30'. Urine samples were collected before, 2 and 48 hours after the injection. Urinary albumin (alb) and retinol binding protein (RBP) excretion was evaluated by immunoenzymatic methods; alb and RBP were considered as indicators of glomerular permeability and of tubular reabsorption, respectively. The urinary excretion of brush-border antigen of proximal tubule (BBA) was also measured, as an indicator of microtissue damage, by a sensitive double-antibody ELISA with monoclonal antibodies. The results demonstrate ionic cm to have greater functional effects than nonionic ones, as suggested by the increased urinary excretion of both alb and RBP. However, tubular damage seemed to be more severe with nonionic agents, as suggested by BBA excretion. Although toxic damage had little significance for the patients' health, long-term effects are not to be excluded.

Adult↗

Correlation of HbA1C, glycated serum proteins and albumin, and fructosamine with the 24-h glucose profile of insulin-dependent pregnant diabetics.

To assess the value of various methods for long-term follow-up of diabetic patients, we compared the concentrations of fructosamine in serum with those of various glycated proteins: hemoglobin (HbA1C), total serum proteins (G-prot), and albumin (G-alb), assayed in 30 pregnant insulin-dependent diabetics every two weeks after initial determination of a 24-h blood glucose profile. HbA1C correlated best with the 24-h glucose profile during the succeeding 10-35 days (r = 0.65-0.68, P less than 0.001). G-prot and G-alb correlated nearly as well as HbA1C 10-20 days after the glucose profile (r = 0.54-0.64, P less than 0.01-0.001), but only weakly after 25-35 days. Values for fructosamine did not correlate significantly with the glucose profile 10-35 days after it (r = 0.23-0.36). Evidently the fructosamine assay is not an adequate alternative to HbA1C, G-alb, or G-prot as an index to long-term control of blood glucose in such patients.

Blood Glucose↗

Urinary excretion of some proteins and enzymes during normal pregnancy.

Total protein (TP), albumin (Alb), transferrin (TRF), retinol-binding protein (RPB), N-acetyl-beta-glucosaminidase (NAG), alanine aminopeptidase (AAP), gamma-glutamyltransferase (GGT), and creatinine (Cr) were measured in random (untimed) urine samples from 29 nonpregnant women and from pregnant subjects (11 in the first trimester, 34 in the second, and 37 in the third). The excretion of TP, Alb, TRF, NAG, and AAP (relative to creatinine) and the RBP concentration were all higher (P less than or equal to 0.05) in the second and third trimesters compared with values for the nonpregnant controls. The GGT/Cr ratio was significantly higher only in the third trimester. The increase in low-molecular-mass proteins and tubular enzymes suggests that at least part of the increase in Alb, TRF, and TP results from decreased tubular reabsorption. We conclude that excretion of both high- and low-molecular-mass proteins is increased during pregnancy.

Adult↗

Serum prealbumin, retinol-binding protein, transferrin, and albumin levels in patients with large bowel cancer.

In a study of the levels of serum prealbumin (PALB), retinol-binding protein (RBP), transferrin (TF), and albumin (ALB) in patients with large bowel cancer, critical values were established as (g/liter): PALB, 0.15; RBP, 40 X 10(-3); TF, 2.0; and ALB, 30. Values consistently below these were taken as a sign of malnutrition. The proteins in this system were interrelated and tended to show a similar pattern of change. Metastatic colon cancer caused a relatively small decline of ALB compared to the mean in tumor-free patients. PALB was the most sensitive indicator of nutrition, and its levels and rates of change had a prognostic significance. A rapid fall of PALB often occurred 2--3 months prior to the patients's death; this preterminal phase in ambulant patients was frequently heralded by a progressive rise in the level of C-reactive protein in the absence of any obvious infection.

Carcinoembryonic Antigen↗

Characterization of a membrane-associated receptor from rat sinusoidal liver cells that binds formaldehyde-treated serum albumin.

When treated with formaldehyde, serum albumin is known to be taken up and degraded by sinusoidal liver cells via adsorptive endocytosis. The present study aimed at characterization and identification of the membrane-associated receptor on rat sinusoidal liver cells. Kinetic studies of binding of 125I-labeled formaldehyde-treated serum albumin (125I-f-Alb) with the membranes of sinusoidal liver cells demonstrated the presence of specific, high-affinity, saturable membrane-bound receptors with an apparent Kd = 8 micrograms of f-Alb/ml and the optimal pH at around 8.0. The 125I-f-Alb binding to the membranes was not inhibited by either native albumin, asialofetuin, methylamine-treated alpha 2-macroglobulin, mannan, or immune complexes. The binding process exhibited independence of calcium and susceptibility both to heat treatment and to destruction by proteases. The binding was inhibited by concanavalin A and the inhibition was effectively reversed by the presence of alpha-methyl-D-glucoside, a haptenic inhibitor for this lectin, indicating the glycoprotein nature of the receptor. The binding protein was extracted from the membrane preparations with octyl beta-D-glucopyranoside and immunoprecipitated by anti-ligand antibody as a complex with the ligand. Sodium dodecyl sulfate-gel electrophoresis of the immunoprecipitate revealed two polypeptide chains with molecular weights of approximately 53,000 and 30,000, respectively.

Animals↗

Urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)-nitrosamine in an analbuminemic congenic strain of rats with an ACI genetic background.

An analbuminemic congenic strain of rats originating from ACI (ACI-alb) rats was established. The rats were found to be highly susceptible to induction of urinary bladder cancer by N-butyl-N-(4-hydroxy-butyl)nitrosamine. Bladder cancers were observed in all male ACI-alb and normal ACI rats treated with the compound, but the average weight of the bladder including tumors was more in ACI-alb rats than in ACI rats (0.63 +/- 0.24 g and 0.18 +/- 0.05 g, respectively; ratio, 3.5:1).

Animals↗

Binding of immunoglobulin classes and subclasses to human neutrophils and eosinophils.

A comparative study of membrane expression of immunoglobin (Fc) receptors on human eosinophils and neutrophils has been undertaken using human IgG-1, IgG-2, IgG-3, IgG-4, IgA-1, IgA-2, IgM, IgD and IgE myeloma proteins. Sheep erythrocytes (E) coated with either human IgG-1, IgG-2, IgG-3 or IgG-4 myeloma proteins formed rosettes with human neutrophils and eosinophils. Proportionally more (1 1/2-2 times) rosettes were observed with neutrophils compared to eosinophils. In contrast, E-IgE bound to eosinophils (but not to neutrophils) to a degree that was comparable to E-IgG-1. Although IgG and IgE rosettes were inhibited by aggregates prepared from their corresponding myeloma protein there was no evidence that eosinophils and neutrophils have distinct receptors for IgG subclasses. Cells from four patients with hypereosinophilia were separated on density (metrizamide) gradients. The percentages of E-IgG-1 and E-IgE rosettes with normal- and light-density eosinophils were similar. Neutrophils, but not eosinophils, also bound significantly more E-IgA-1 and E-IgA-2 than the E-human albumin (E-Alb) control. In contrast, neutrophil and eosinophil rosette formation with E-IgM and E-IgD was not significantly different from E-Alb or E alone. These experiments indicate that human neutrophils and eosinophils bind homologous IgG subclass myeloma proteins, eosinophils, but not neutrophils, bind E-IgE with a similar avidity to that observed with E-IgG1, neutrophils, but not eosinophils, readily express demonstrable receptors for IgA-1 and IgA-2 and neither neutrophils nor eosinophils form E-IgM or E-IgD rosettes in greater numbers than the E-Alb controls.

Dose-Response Relationship, Immunologic↗

[Muscle strength in patients with gastrointestinal carcinoma--an important role of muscle strength as a nutritional parameter].

The relationship between nutritional status and muscle strength was examined in 73 patients with gastrointestinal carcinoma preoperatively. Nutritional status was assessed by measuring various nutritional parameters. Muscle strength was determined by measurements of %grip strength and respiratory muscle strength expressed as %maximal expiratory and inspiratory pressure (%MEP and %MIP). The results were as follows: %GS was significantly low in the patients who showed low values in body weight (%ideal body weight: %IBW), mid-arm muscle circumference (%AMC), serum albumin (Alb), serum prealbumin (PA), total peripheral lymphocyte count (TLC), and/or nutritional surgical risk index (NRI). %MEP was significantly low in the patients who showed low values in %IBW, %AMC, triceps skin fold, Alb, PA, retinol binding protein, NRI, and/or nutritional assessment index (NAI). %MIP was significantly low in the patients who showed low values in %IBW, %AMC, creatinine height index, Alb, PA, NRI, and/or NAI. %MEP and %MIP were significantly correlated with %GS. Preoperative %GS value was significantly low in the esophageal cancer patients with postoperative pulmonary complications. It was suggested that %GS was a simple and useful nutritional parameter for detecting depletion of the muscle mass and visceral proteins, for respiratory muscle strength, and for functional capacity of muscle.

Aged↗

Crystalloid versus colloid in fluid resuscitation of patients with severe pulmonary insufficiency.

Forty-six patients with severe pulmonary insufficiency were prospectively studied to compare the effects of resuscitation with either crystalloid or colloid. By random number, 26 patients received RL and 20 patients received 5 per cent ALB to maintain hemodynamic stability. Groups were comparable with respect to the cause of pulmonary insufficiency, age and sex. For the duration of the study and at 48 hours, there was no statistically significant difference between groups with respect to the following: cardiac index, colloid osmotic pressure (COP), pulmonary capillary wedge pressure (PCWP), COP-PCWP gradient, right and left ventricular stroke work indices, and amount of constant positive airway pressure required for treatment. Both groups had a significant improvement in intrapulmonary shunt (Qs/Qt) after 24 hours of treatment. The Qs/Qt in the ALB group was significantly lower than the RL group at the termination of the study, but this did not affect outcome. The RL group required more fluid than the ALB group, but the difference was not statistically significant. No clinical advantage was found for either solution in this study.

Adult↗

An immunohistochemical study of a series of plasma proteins in the early human conceptus.

A 20-day-old human conceptus was studied by the indirect immunoperoxidase technique for the presence of a series of plasma proteins: prealbumin (PA), albumin (ALB), alpha-fetoprotein (AFP), alpha 1-antitrypsin (A1AT), carcioembryonic antigen (CEA), immunoglobulin G (IgG), ferritin (FER), transferrin (TR), fetal haemoglobin (HbF), human chorionic gonadotropin (HCG), human placental lactogen (HPL) and pregnancy specific beta 1-glycoprotein (SP1). In the embryo only FER and TR were found. The yolk sac was positively stained for several proteins: PA, ALB, AFP, A1AT, IgG, FER, TR and HbF were demonstrated in the endodermal cells and PA, ALB, IgG and TR in the mesothelial cells. The syncytiotrophoblast of the chorionic villi were heavily stained for all the placental proteins. HCG and HPL were additionally demonstrated in the cytotrophoblast. The Hofbauer cells of the chorionic and villous stroma stained positively for A1AT and FER. TR appeared as a characteristic band on the apical surface of the syncytiotrophoblast. The findings indicate that the yolk sac is the principle source of some of the plasma proteins also in the very early conceptus and the assumption that the yolk sac is the functional antecedent of the liver is supported. The distribution of the various placental proteins is in accordance with the present knowledge that the syncytiotrophoblast is the major site of synthesis of these proteins. Finally correlation of functional aspects of embryonic structures and germ cell tumours is recommended.

Blood Proteins↗

Lysozyme and albumin radioimmunoassays. New techniques for the study of proteinuria.

To facilitate the study of mechanisms and patterns of proteinuria, radioimmunoassays for human lysozyme (LZM) and albumin (alb) were established to permit quantitation of physiologic amounts of these proteins in urine. Commercially available LZM and alb preparations were radiolabeled with I125, and single antibody, competitive protein binding assays were developed. Separation of free and antibody-bound radioprotein was achieved with 20 per cent polyethylene glycol. LZM and alb 24-hr excretion rates for 12 normal subjects were 7 to 64 microgram and 2.3 to 16.1 mg, respectively. Of 6 renal disease patients with undetectable urine LZM by bioassay, 5 were shown to have elevated LZM concentrations by radioimmunoassay. The ease of establishing and performing these assays and their reproducibility suggest that they may have clinical and investigative value.

Albumins↗