La albúmina como marcador pronóstico en el implante de válvula aórtica percutánea / Albumin as a prognostic marker in the percutaneous aortic valve replacement

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[Bisalbuminemia: A Rare Variant of Albumin]. / Bisalbuminémia: Uma Variante Rara da Albumina.

INTRODUCTION: Bisalbuminemia is a qualitative disorder of albumin and it is defined by the coexistence in the same individual of two types of serum albumin with different electrophoretic mobility. There are two forms: hereditary and permanent, or acquired and transient. CASE REPORT: Girl, 17-years-old, referenced to the hospital consult after incidental finding of bisalbuminemia detected in plasma protein electrophoresis performed within the investigation of diminished muscular tone in the lower limbs. Physical examination was normal. Secondary causes of bisalbuminemia were excluded. Later, it was confirmed the same disorder in plasma protein electrophoresis performed to her 14-years-old brother and mother. DISCUSSION: We describe a rare case of hereditary bisalbuminemia in a portuguese family. In general, this condition shows no pathological significance, however it is of interest to the clinicians the knowledge of this analytic change for better orientation of their patients.

Introdução: A bisalbuminémia é uma alteração qualitativa da albumina e define-se pela coexistência no mesmo indivíduo de dois tipos de albumina sérica com mobilidade eletroforética diferente. Existem duas formas: hereditária e permanente ou adquirida e transitória. Caso Clínico: Adolescente, sexo feminino, 17 anos, referenciada à consulta hospitalar por achado incidental de bisalbuminémia detetada na eletroforese de proteínas plasmáticas, realizada em contexto de noção de diminuição da força dos membros inferiores. O exame objetivo não apresentava alterações. Foi excluída causa secundária de bisalbuminémia. Posteriormente, confirmou-se a mesma alteração em eletroforese de proteínas plasmáticas realizada ao irmão de 14 anos e à mãe. Discussão: Descrevemos um caso raro de bisalbuminémia hereditária numa família portuguesa. Em geral não apresenta significado patológico, no entanto tem interesse para o clínico o conhecimento desta alteração analítica para melhor orientar e esclarecer os seus doentes.

Evaluation of dietary stevioside supplementation on anti-human serum albumin immunoglobulin G, Alpha-1-glycoprotein, body weight and thyroid hormones in broiler chickens.

Sixty male broiler chickens fed a diet supplemented with 130 mg/kg stevioside (S group) or an unsupplemented diet (C group) from day 1 of age onwards. On day 21 of age, ten birds from either the S (SH) or C (CH) group were injected subcutaneously with 100 µg human serum albumin (HSA) and ten others from either S (SP) or C (CP) group injected with 100 µl phosphate-buffered saline (PBS) in the same way. There were no significant effect of supplementation nor interaction with age on average body weights, T(3) and T(4) concentrations of non-injected chickens. After the primary immunization, α(1) -glycoprotein concentrations increased in all treatment groups except the CP group, and were significantly higher in the CH group in relation to the other groups. Fourteen and 18 days after the primary immunization, HSA injected chickens of both dietary treatments had significantly higher anti-HSA immunoglobulin G (IgG) levels than their PBS injected controls. No effect of stevioside supplementation was observed for IgG level. In conclusion, dietary stevioside inclusion can attenuate the pro-inflammatory response after stimulation of the innate immune response in broiler chickens.

Tuning the serum persistence of human serum albumin domain III:diabody fusion proteins.

The long circulation persistence of human serum albumin (HSA) is enabled by its domain III (DIII) interaction with the neonatal Fc receptor (FcRn). A protein scaffold based on HSA DIII was designed. To modify the serum half life of the scaffold, residues H535, H510, and H464 were individually mutated to alanine. HSA DIII wild type (WT) and variants were fused to the anti-carcinoembryonic antigen (CEA) T84.66 diabody (Db), radiolabeled with (124)I and injected into xenografted athymic mice for serial PET/CT imaging. All proteins targeted the CEA-positive tumor. The mean residence times (MRT) of the proteins, calculated by quantifying blood activity from the PET images, were: Db-DIII WT (56.7 h), H535A (25 h), H510A (20 h), H464A (17 h), compared with Db (2.9 h). Biodistribution confirmed the order of blood clearance from slow to fast: Db-DIII WT > H535A > H510A > H464A > Db with 4.0, 2.0, 1.8, 1.6 and 0.08 %ID/g of remaining blood activity at 51 h, respectively. This study demonstrates that attenuating the DIII-FcRn interaction provides a way of controlling the pharmacokinetics of the entire Db-DIII fusion protein without compromising tumor targeting. H464 appears to be most crucial for FcRn binding (greatest reduction in MRT), followed by H510 and H535. By mutating the DIII scaffold, we can dial serum kinetics for imaging or therapy applications.

Influence of hypoalbuminemia or hyperalbuminemia on the serum anion gap.

BACKGROUND: Conflicting data exist as to what extent hypoalbuminemia reduces the anion gap; estimates range from 1.5 to 2.5 mM per g/dL decrease in serum albumin. METHODS: We measured serum albumin, total protein, and electrolyte concentrations in 5328 consecutive patients aged 1 month to 102 years. Most patients (3750; 70%) had a normal albumin, but 1158 had hypoalbuminemia (< or =3.4 g/dL); 420 had hyperalbuminemia (> or =4.7 g/dL). Relationships between serum albumin or total protein and the anion gap were analyzed by linear regression. RESULTS: 309 (27%) hypoalbuminemic patients had a decreased anion gap, and 257 hyperalbuminemic patients (61%) had an increased anion gap. Among the entire group of 5328 patients, there were highly significant correlations between either serum albumin or total protein and the anion gap (P < 0.001). The slope of the regression for albumin versus anion gap was 2.3 mM per g/dL. Using this slope, anion gap could be adjusted for abnormal serum albumin levels: anion gap(adjusted) =anion gap + 2.3 (4-albumin). The initial assessment of an anion gap as being increased, normal, or decreased changed in 44% of the patients with hypo- or hyperalbuminemia once anion gap had been adjusted with this formula. CONCLUSIONS: Before considering whether a disorder associated with an increased or decreased anion gap is present, the anion gap should be first adjusted for abnormal serum albumin concentrations. Our data suggest that physicians use 2.3 times the change in serum albumin, whereas those of Figge et al suggest 2.5; either approach gives similar results.

Intermediate formation at lower urea concentration in 'B' isomer of human serum albumin: a case study using domain specific ligands.

The urea-induced unfolding of 'N' isomer (occurring at pH 7.0) and 'B' isomer (occurring at pH 9.0) of human serum albumin was studied by fluorescence and circular dichroism spectroscopic measurements. Urea-induced destabilization in different domains of both the isomers was monitored by using domain specific ligands, hemin (domain-I), chloroform, bilirubin (domain-II), and diazepam (domain-III). Urea-induced denaturation of N and B isomers of HSA showed a two-step, three-state transition with accumulation of intermediates around 4.8-5.2M and 3.0-3.4M urea concentrations, respectively. During first transition (0-4.8M urea for N isomer and 0-3.0M urea for B isomer) a continuous decrease in diazepam binding suggested major conformational changes in domain-III prior to intermediate formation. On the other hand, binding of hemin, a ligand for domain-IB and chloroform, whose binding site is located in domain-IIA remains unchanged up to 5.0M urea for N isomer and 3.0M urea for B isomer. Similarly, fluorescence intensity of Trp-214 that resides in domain-IIA remained unchanged up to the above-said urea concentrations and decreased thereafter. Absence of any decrease in hemin binding, chloroform binding, and Trp-214 fluorescence suggested the non-involvement of domain-IB and domain-IIA in intermediate formation. A significant increase in bilirubin binding prior to intermediate formation showed favorable conformational rearrangement in bilirubin binding cavity formed by loop 4 of domain-IB and loop 3 of domain-IIA. Further, a nearly complete abolishment of bilirubin binding to both isomers around 7.0M and 6.0M urea concentrations, respectively, indicated complete separation of domain-I from domain-II from each other. From these observations it can be concluded that N to B transition of human serum albumin shifted the intermediate formation towards lower urea concentration (3.0-3.4M urea for B isomer as against 4.8-5.2M urea for N isomer). Further both the intermediates were found to possess similar alpha-helical (approximately 39%) content and ligand binding properties.

Phthalic anhydride allergy: development and characterization of optimized hapten-carrier conjugates for improved diagnosis.

BACKGROUND: At present the diagnosis of IgE-mediated hypersensitivity to phthalic anhydride (PA) is based on conjugates that are not characterized or standardized. The aim of this study was to develop optimized and molecularly characterized PA conjugates that can be used to improve the diagnosis of PA-allergy. METHODS: The PA conjugates were synthesized and the number of haptens bound on a carrier protein was estimated by matrix-assisted laser desorption/ionization time of light (MALDI-TOF) mass spectrometry. The ability of conjugates to bind IgE and IgG antibodies was measured by enzyme-linked immunosorbent assay (ELISA). Reactivity of the conjugates in vivo was evaluated by skin prick testing. RESULTS: The most active IgE-binding conjugates had a PA : HSA molar ratio of 80 : 1. In the optimal conjugates the average numbers of PA haptens per carrier molecule of human serum albumin (HSA) were 14-16. In ELISA, all 13 patients and none of the 20 controls had IgE antibodies to optimized PA conjugate. The sensitivity and specificity of the ELISA was comparable to commercial CAP RAST. PA conjugates elicited positive test results in skin prick testing showing that conjugates are immunologically active also in vivo. CONCLUSIONS: These results indicate that optimized and molecularly characterized PA-HSA conjugates can be used both in vitro and in vivo assays to improve the diagnosis of PA allergy.

Species-dependency in chiral-drug recognition of serum albumin studied by chromatographic methods.

Stereoselective binding of benzodiazepine and coumarin drugs to serum albumin from human and six mammalian species were studied by chiral chromatographic techniques. The applied methods were affinity chromatography on the albumins immobilized on Sepharose 4B, high-performance liquid chromatography (HPLC) separation on columns based on human serum albumin (HSA) and bovine serum albumin (BSA), and chiral HPLC analysis of ultrafiltrates of solutions containing the racemic drug and the native protein. Substantial differences in preferred configurations and conformations were detected among the species. The binding stereoselectivity of the 2,3-benzodiazepine drug, tofisopam, in human, is opposite to that in all other species. In the binding of 1,4-benzodiazepines, dog albumin is very similar to HSA. Highly preferred binding of (S)-phenprocoumon was found with dog albumin.

Familial dysalbuminemic hypertriiodothyroninemia in a Japanese kindred.

A 56-year-old Japanese housewife had been diagnosed as having Graves' disease and was treated with methimazole. When she was referred to our hospital, the serum T3 level was high irrespective of high TSH level. High serum T3 levels were also observed in two out of her three sisters. Electrophoresis revealed that binding of 125I-T3 to serum albumin was markedly increased whereas the binding of 125I-T4 to serum albumin was slightly increased in the three sisters whose serum T3 levels were high. These data indicate that the presence of an albumin variant is the cause of hypertriiodothyroninemia in this family.

Genetic variants showing apparent hot-spots in the human serum albumin gene.

The molecular defects of three different slow-migrating genetic variants of human serum albumin, albumins Kamloops (formerly RIH), Stirling and Amsterdam, previously characterized only by electrophoretic and dye-binding studies, are now reported. Two of them are proalbumin variants: sequential analysis of the purified whole proteins has established the mutation responsible for albumin Kamloops as -1Arg-->Gln, and for albumin Stirling as -2Arg-->His. A Glu-->Lys substitution in position 570 of the mature albumin molecule was determined in albumin Amsterdam by sequential analysis of two abnormal tryptic fragments. The three alloalbumins are caused by single-base changes all of which seem to represent hot-spots in the albumin gene. The possible functional consequences of the presence of a circulating alloalbumin are discussed.

[Genetic variants of human albumin: structural characterization of allotypes used as references for electrophoretic classification]. / Variants génétiques de l'albumine humaine: caractérisation structurale des allotypes utilisés comme références dans la classification électrophorétique.

Eight different types of genetic variants of albumin are observed in the French population. The analysis of electrophoretic patterns of sera containing these variants, performed a three different pHs (8.6, 5.0 and 6.9) after addition of a reference protein (transferrin), allows the identification each variant by a quantitative estimation of its relative mobilities. The accuracy and reproducibility of the technique make it a useful reference method, commonly employed for studying European variants. The samples used as references for five genetic variant types, proalbumins Christchurch and Lille, albumins Vanves, B and Reading, were subjected to sequence analysis to determine the nature and localization of their structural change. Together with the mutations of albumins Gent and Roma previously described, the data presented here make available seven reference specimens for which the structural changes are characterized out of the eight variants known to exist in France.

Human albumin variants. Nomenclature of allotypes observed in Europe and quantitative estimation of their relative mobilities.

In order to clarify the actual nomenclature of the albumin allotypes in French and Italian populations we compared the samples collected in our laboratory to those kindly supplied by Dr. Porta (Italy) with reference to albumin variants classified in starch gel electrophoresis using three buffer systems by Weitkamp. The inherited human albumin variants can be classified on the basis of their relative mobilities on cellulose acetate electrophoresis compatively to human transferrin mobility. The relative mobility of each variant can be expressed by the following ratio: migration distance of the variant versus migration distance of the normal albumin where zero represents the transferrin mobility. Using three buffers system at pH 8.6, 5.0 and 6.9, it is possible to distinguish some albumin variants having a same mobility at alkaline pH and different mobilities at acidic pH. In the european area, eleven albumin variants are distinguishable on the basis of their relative mobilities at different pH: four Fast moving variants: Gent, Vanves (a new variant described here), Reading and CN/BL, and seven Slow moving variants: MI/MI Slow, GE/CT, SO/BS (or D type), Pollibauer, Gainesville, Roma and B type. Thirty-six sera from unrelated subjects with genetic bisalbuminemia were analyzed in our laboratory. Their distribution was as follows: B type (22), Pollibauer (9), SO/BS (2), Gainesville (1), Gent (1) and Vanves type (1). The frequency of bisalbuminemia was 0.35 per 1,000 in a population of 19,949 blood donors.

[Bisalbuminemia (author's transl)]. / Bisalbuminemia.

A general review of bisalbuminemia is presented. Besides congenital bisalbuminemia there is an acquired form of bisalbuminemia that appears following treatment with high dosis of penicillin and cephalosporin, or in cases of acute pancreatitis after the development of a pancreatic pseudocyst. There is one type of abnormal albumin that migrates faster than normal albumin (rapid variant) and another type that is slower (slow variant). Different subtypes of each one have been recognized. There is no immunological difference between normal albumin and the variants. From a clinical point of view, bisalbuminemia per se does not cause any observable alterations. This is an important finding, however, because of the possibility that some physiologic or pharmacologic substances may not be bound to the abnormal variants as well as to normal albumin. When bisalbuminemia appears following an episode of pancreatitis it may be indicative of a pancreatic pseudocyst.