Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0267964 (PAA)
 2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two weak poly(acid)s, poly(acrylic acid) (PAA) and poly(N-acryloyl-glycine) (P1), were graft-copolymerized onto porous cellulose membrane and their protonation behavior in aqueous media was studied by potentiometric techniques. Comparison with the corresponding free polymers in solution showed the same basicity constants during the protonation of ionized carboxyl groups, and the large potentiometric hysteresis loops observed for the grafts were indicative of specific interactions with the cellulose substrate. This was confirmed by FT-IR spectroscopic analysis at low pH. The polymeric membrane system, containing immobilized glucose oxidase, was synthesized for the purpose of insulin delivery in response to glucose concentration. The porosity of the membrane was controlled by the charge-state conformations of the grafted chains. The formation of gluconic acid in the presence of glucose caused a drop in pH which led to neutralization of the negatively charged carboxyl groups. The decrease in electrostatic repulsion caused the extended macromolecular chain to assume a coil-like form and opened the membrane pores to insulin.
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PMID:An insulin-releasing system responsive to glucose: thermodynamic evaluation of permeability properties. 175 61

1. In order to observe and compare the withdrawal phenomena which follow treatment with the beta-adrenoceptor blocking drugs, bopindolol (with partial agonist activity PAA) and atenolol (without PAA), two groups of six normal volunteers were studied before, during and after 16 days drug administration. 2. Measurements of plasma levels of cortisol, prolactin, insulin, noradrenaline, adrenaline, glucose and potassium were made during a pre-treatment baseline period, on maximum dose and for 21 days after drug withdrawal. Isoprenaline infusions were given to determine sensitivity of heart rate responses and haemodynamic changes measured in response to physiological manoeuvres. 3. Following atenolol withdrawal the results show hormonal evidence of adrenergic overactivity in the form of elevation of plasma cortisol, insulin and glucose levels. After bopindolol withdrawal there was, in contrast, an overshoot of plasma prolactin and a persistent elevation of plasma potassium and adrenaline post-isoprenaline. 4. The hormonal changes which follow withdrawal of atenolol and bopindolol are associated with haemodynamic changes reported elsewhere (Walden et al., 1990). 5. These observations provide confirmatory evidence of a post beta-adrenoceptor blockade withdrawal syndrome which differs between the two drugs studied and this may reflect the properties of the drugs, in particular the PAA of bopindolol.
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PMID:Withdrawal phenomena after atenolol and bopindolol: hormonal changes in normal volunteers. 198 17

The aim of the present study was to test whether proinsulin autoantibodies (IgG-PAA), insulin autoantibodies (IgG-IAA), and islet cell antibodies (ICA) may be used to identify subjects at risk for Type 1 diabetes. Pre-diabetic sera from 18 individuals who later developed diabetes were tested. Results were compared with 18 age-, sex-, and HLA-DR-matched non-diabetic control subjects from families with Type 1 diabetes. At a mean of 2.4 yr before the onset of diabetes, ICA were found in 13 patients (vs 0 control subjects, p less than 0.001), ELISA-determined IgG-IAA in 8 patients (vs 1 control subject, p less than 0.05) and ELISA-determined IgG-PAA in 4 patients (vs 2 control subjects, NS). ELISA-determined IgG-PAA do not appear to be useful predictors of the future development of Type 1 diabetes.
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PMID:Antibodies to proinsulin and insulin as predictive markers of type 1 diabetes. 214 83

Antibodies reacting with proinsulin but not with insulin determinants have been observed recently in Type I diabetes. We describe here that ELISA-determined proinsulin autoantibodies (IgG-PAA) also occur in first-degree relatives of IDDM patients (38/513, 7.4% vs 1.9% in controls, P less than 0.025). In contrast to insulin autoantibodies (IgG-IAA) and islet cell antibodies (ICA) no association with HLA type was found. Furthermore, IgG-PAA occur independently of IgG-IAA and ICA. We conclude that the humoral autoimmune response to proinsulin determinants is under separate genetic control.
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PMID:Proinsulin autoantibodies: association with type I diabetes but not with islet cell antibodies, insulin autoantibodies or HLA-DR type. 225 25

The author present a review of contemporary views on the pathogenesis of type I diabetes, in particular with regard to recent research of European and non-European diabetelogical departments. In the aetiopathogenesis attention is drawn to genetic influences, external factor and stimuli, the importance of some virus groups (Picornidae, Mengo 2T virus, Coxsackie B5, cytomegaloviruses, congenital rubeola syndrome etc.). Special attention is paid to the autoimmune theory of type I diabetes, the importance of different types of anti- beta-cell antibodies, insulin antibodies, antibodies against protein 64-KD of the islets, pro-insulin antibody PAA, and other stimuli and interferences (oxidation stress, non-enzymatic glycosylation etc.). As to treatment, the author mentions immunosuppressive treatment (cyclosporin A, azathioprine, prednisone) and transplantation of the pancreas. The author presents his own experience with a group of 2040 diabetics; in a group of 253 juvenile diabetics he followed-up the development of micro- and macroangiopathic complications in the course of 25 years. He proved an increase of so-called late diabetic complications in particular vascular ones along with the lengthening period of diabetes, with advancing age during its clinical manifestation. In the conclusion the author draws attention to the importance of multi-centre studies and new laboratory techniques.
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PMID:[New findings in type I diabetes]. 813 Nov 77

Conjugation of proteins to copolymers from poly(acrylic acid) grafted onto PEO-PPO-PEO backbone (Pluronic-PAA) following adsorption of the conjugates onto hydrophobic surfaces is reported. Insulin-Pluronic-PAA conjugates show negligible internalization of insulin into human uterine smooth muscle cells as well as enhancement of mitogenic activity. Glucose-induced release of glycated albumin complexed with a Pluronic-PAA-concanavalin conjugate and adsorbed onto polystyrene nanospheres may provide a model for a glucose-responsive protein delivery system or a heterogeneous diagnostic device.
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PMID:Bioactive surfaces via immobilization of self-assembling polymers onto hydrophobic materials. 1041 66

A special class of hydrophobically modified polyelectrolytes was studied wherein poly(acrylic acid) (PAA) was conjugated with Pluronic F127 NF surfactant. The Pluronic-PAA copolymer solutions form gels at low concentrations when exposed to bodytemperature. Such gels possess enhanced retention in topical applications. Circular dichroism spectra indicate that tertiary structures of human insulin, haemoglobin, and albumin were stabilized in solutions of Pluronic-PAA. Aggregation of insulin in gelled solutions of Pluronic-PAA was impeded as demonstrated in shaking tests. The presence of Pluronic-PAA hindered the insulin degradation by alpha-chymotrypsin by at least 7-fold. Extraction of calcium ions from trypsin by Pluronic-PAA led to the dramatic changes in the tertiary structure and total loss of enzymatic activity, suggesting that Pluronic-PAA could inhibit tryptic degradation of proteins.
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PMID:Interactions among proteins and hydrophobically modified polyelectrolytes. 1134 72

The aim of this study was to develop a peroral mucoadhesive microparticulate delivery system for peptide drugs. Microparticles containing either the mucoadhesive polymer poly(acrylic acid)-cysteine (PAA-Cys) or unmodified PAA, 15% insulin used as model peptide drug and 0, 30, 50 and 70% Eudragit RS (MP-RS0, MP-RS30, MP-RS50 and MP-RS70) were prepared by the emulsification solvent evaporation technique. Particle size distribution, release of incorporated insulin, mucoadhesive and swelling properties were examined. During preparation inter- and intramolecular cross-linking occurred, which could be quantified by the amount of disulfide bonds within the resulting particles; this was determined to be 69.2% of the total amount of thiol groups. This cross-linking led to a higher stability of the particles. Microparticles were spherical displaying a rough surface. The particle diameter was in the range of 1-110 microm in the following rank order beginning with the largest: MP-RS30>MP-RS50>MP-RS70=MP-RS0. The higher the ratio of Eudragit RS in the microparticles, the more prolonged was the release of insulin. In the case of MP-RS70, a sustained release over a time period of at least 60 min was achieved. Mucoadhesive properties and the capacity of water uptake followed the rank order: MP-RS0>MP-RS30>MP-RS50>MP-RS70. Compared to particles comprising unmodified PAA, the mucoadhesive properties of the thiolated microparticulate systems were up to 14-fold improved. According to these results PAA-Cys-Eudragit RS microparticles might be a promising tool for the peroral administration of peptide drugs.
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PMID:Thiomers: development and in vitro evaluation of a peroral microparticulate peptide delivery system. 1501 73

The aim of this work was develop a new combined radioligand-binding assay (RBA-combi) for the rapid and simultaneous determination of two autoimmunity markers, GADA and PAA, known to be differentially distributed in young and in some adult diabetic patients. The methodology was applied to sera from 85 young type 1 and 98 adult-onset diabetic patients with different marker profiles and insulin requirements, and to 53 normal control sera. Among type 1 diabetes sera used as autoimmunity controls, 100% of those with at least one positive marker by single methods and 17.7% of those with double negative markers were positive by RBA-combi (RBA-combi+). Among sera from adult-onset diabetes, 100% of those PAA+ (GADA+ or GADA-), 92.3% of GADA+/PAA-, and 1.3% of GADA-/PAA- were RBA-combi+. In conclusion, the new RBA-combi allowed the simultaneous detection of GADA and PAA markers with acceptable performance. Moreover, 16 out of 18 (88.9%) of adult patients RBA-combi+ evolved to insulin requirement, suggesting that this test is a valuable tool for assessing autoimmune processes associated to future impairment of insulin secretion.
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PMID:Single-tube test for autoantibodies to glutamic acid decarboxylase and proinsulin as first-line screening for autoimmunity in adult-onset diabetic patients. 1550 88

The purpose of this study was to develop an oral thiomer-based microparticulate delivery system for insulin by ionic gelation. The microparticulate matrix consisted of either poly(acrylic acid)-cysteine (PAA-Cys) and alginate-cysteine (Alg-Cys) or the corresponding unmodified polymers (PAA, Alg). Two different viscosities of alginates were provided for the study, low and medium. Three different types of microparticles were prepared via ionic gelation with calcium (Alg, AlgPAA and AlgPAA-Cys) and their different properties evaluated in-vitro (particle size and shape, drug loading and release profile, swelling and stability). The mean particle size of all formulations ranged from 400 to 600 microm, revealing the lowest for thiolated microparticles. SEM micrographs showed different morphological profiles for the three different types of microparticles. Encapsulation efficiency of insulin increased within the following rank order: Alg (15%) < AlgPAA (40%) < AlgPAA-Cys (65%). Alginate and AlgPAA microparticles displayed a burst release after 30 min, whereas the thiolated particles achieved a controlled release of insulin over 3 h. The swelling ratio was pH dependent: in simulated intestinal fluid microparticles exhibited a much higher water uptake compared with simulated gastric fluid. Due to the formation of intraparticulate disulfide bonds during the preparation process, thiolated particles revealed a higher stability. It was also observed that the viscosity of the two alginates used had no influence on the properties of the particles. According to these results AlgPAA-Cys microparticles obtained by ionic gelation and stabilized via disulfide bonds might be an alternative tool for the oral administration of therapeutic peptides.
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PMID:Oral peptide delivery: in-vitro evaluation of thiolated alginate/poly(acrylic acid) microparticles. 1788 89


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