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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to excessive salt and water retention, hypertension often becomes refractory in patients undergoing peritoneal dialysis (PD). Management of high blood pressure (BP) appears to be of particular importance in such patients because of its substantial impact on the patients' prognosis. However, attempts to control hypertension in PD patients have not been successful in most cases. In this regard, the present study aimed to address the adequacy of current antihypertensive therapy for PD patients. A new antihypertensive strategy expected to improve the outcome was tested on the assumption that treatment with either angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) in the evening together with alpha1-blocker at bed time and long-acting Ca channel blocker (CCB) in the morning might ameliorate BP control associated with morning hypertension. Enrolled in the present study were 40 patients whose BP was evaluated by both office and home measurement. Due to an emerging concern about morning hypertension, home BP measured early in the morning was used for the analysis. Each patient was categorized into the following four groups in accordance with office and home BP: well-controlled, poorly-controlled, white-coat and masked (opposite to white-coat), hypertension. After the observation period, 28 patients with refractory hypertension were allocated to intensive antihypertensive therapy in which ARB or ACE-I previously prescribed in the morning or daytime was shifted to the night. In addition, alpha1-blocker was given at bed time. Furthermore, long-acting CCB and diuretics were shifted to the morning. The patients were then followed up for 4-6 months. The results were as follows: 1) Of the total number of 40 PD patients, systolic hypertension was noted in 50% of cases by office BP and in 80% by home BP. The former was less frequent than the latter (p=0.0047, n=40). Similarly, diastolic hypertension was noted in 20% by office BP and in 45% by home BP. The former was less frequent than the latter (p=0.0045, n=40 by McNemar's analysis). The distribution of BP control categories was well-controlled in 11%, poorly-controlled in 42%, masked hypertension in 39% and white-coat hypertension in 8% when determined by systolic BP. The distribution was well-controlled in 45%, poorly-controlled in 13%, masked hypertension in 34% and white-coat hypertension in 8% of cases when determined by diastolic BP. 2) In 28 patients subjected to the intensive therapy, the control category of systolic BP was changed from 11 to 37% in well-controlled cases, from 42 to 30% in poorly-controlled cases, from 39 to 26% in masked hypertension cases and from 8 to 7% in white-coat hypertension cases. The shift in categories in both poorly-controlled and masked hypertension cases to the better category (well-controlled), was statistically significant (p=0.001, by Wilcoxon's signed rank test). Similarly, the control category of diastolic BP was changed from 45 to 43% in well-controlled cases, from 13 to 15% in poorly-controlled cases, from 34 to 32% in masked hypertension cases and from 8 to 10% in white-coat hypertension cases. There was a tendency for the prevalence of poorly-controlled and masked hypertension to improve to the well-controlled category in response to intensive therapy (p=0.0625, by Wilcoxon's signed rank test). 3) The plasma concentration of plasminogen activator inhibitor (PAI-1)/tissue plasminogen activator (t-PA) complex (total PAI-1 complex) was significantly decreased after intensive therapy (17.3+/-7.8 ng/ml vs. 13.5+/-4.6 ng/ml, n=28, p<0.01 by paired t-test). In contrast, the plasma concentration of t-PA was unchanged even after intensive therapy (4.8+/-3.9 ng/ml vs. 6.2+/-2.9 ng/ml, n=28, ns). These data suggest that home BP obtained in the morning is a useful measure for evaluating morning hypertension in PD patients, most of whom have refractory hypertension categorized as either poorly-controlled or masked hypertension. Intensive treatment with ACE-I/ARB given in the evening along with alpha1-blocker at bed time combined with a diuretic and/or long-acting CCB in the morning is efficacious in controlling the BP of patients with refractory hypertension in PD patients. The link between the reduction in plasma total PAI-1 levels and the intensive therapy may suggest that this therapeutic strategy could prevent thrombotic events associated with morning hypertension in patients on PD.
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PMID:[Antihypertensive therapy for refractory morning hypertension in patients on peritoneal dialysis]. 1575 62

A new method to prepare PLA/CMP (poly-L-lactide/calcium metaphosphate) composite scaffolds was developed for effective bone tissue engineering. This novel sintering method is composed of pressing the mixture of PLA, CMP, and salt particles at 150 MPa for 3 min followed by heat treatment at 210 degrees C for 30 min. The scaffolds had a homogeneously interconnected porous structure without a skin layer, and they exhibited a narrower pore size distribution and higher mechanical strength in comparison with scaffolds made by a solvent casting method. The scaffolds were seeded by osteoblasts and cultured in vitro or implanted into nude mice subcutaneously for up to 5 weeks. The number of cells attached to and proliferated on the scaffolds at both in vitro and in vivo was in the order of; PLA by novel sintering < PLA/CMP by solvent casting < PLA/CMP by novel sintering. In addition, the alkaline phosphatase activity of and calcium deposition in the scaffolds explanted from mice were enhanced significantly for the scaffolds by novel sintering compared to them by solvent casting. The in vitro results agreed well with the in vivo data. Such a superior characteristic of the novel sintering method should have resulted from the fact that the CMP particles could contact directly with cells/tissues to stimulate the cell proliferation and osteogenic differentiation, while the CMP particles would be coated by polymers and hindered to interact with cells/tissues in the case of a solvent casting method. As the novel sintering method does not use any solvents it offers another advantage to avoid problems associated with solvent residue.
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PMID:A poly(lactic acid)/calcium metaphosphate composite for bone tissue engineering. 1591 59

Previous studies have suggested that thrombin interacts with integrins in endothelial cells through its RGD (Arg-187, Gly-188, Asp-189) sequence. All existing crystal structures of thrombin show that most of this sequence is buried under the 220-loop and therefore interaction via RGD implies either partial unfolding of the enzyme or its proteolytic digestion. Here, we demonstrate that surface-absorbed thrombin promotes attachment and migration of endothelial cells through interaction with alpha(v)beta(3) and alpha(5)beta(1) integrins. Using site-directed mutants of thrombin we prove that this effect is mediated by the RGD sequence and does not require catalytic activity. The effect is abrogated when residues of the RGD sequence are mutated to Ala and is not observed with proteases like trypsin and tissue-type plasminogen activator, unless the RGD sequence is introduced at position 187-189. The potent inhibitor hirudin does not abrogate the effect, suggesting that thrombin functions through its RGD sequence in a non-canonical conformation. A 1.9-Angstroms resolution crystal structure of free thrombin grown in the presence of high salt (400 mm KCl) shows two molecules in the asymmetric unit, one of which assumes an unprecedented conformation with the autolysis loop shifted 20 Angstroms away from its canonical position, the 220-loop entirely disordered, and the RGD sequence exposed to the solvent.
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PMID:Thrombin functions through its RGD sequence in a non-canonical conformation. 1599 37

The aim of this work was to investigate the role of HLB of emulsifier as well as volume of the internal aqueous phase (W(1)) and presence of salt in the external aqueous phase (W(2)) on the morphology, size and encapsulation efficiency of poly(D,L-lactide) microspheres containing naltrexone HCl. PLA microparticles containing naltrexone HCl, an effective opiate antagonist, were prepared by a water-in-oil-in-water emulsification-solvent evaporation procedure. One of the five different emulsifiers: span 80, span 20, tween 85, tween 80 and tween 20, with HLB values from 4-17 were added to W(1). Presence of emulsifier in W(1) resulted in smaller particles with a more dense and uniform internal structure. Incorporation of span 80 (HLB 4.3, suitable for W/O emulsions) yield the highest encapsulation efficiency. Increasing the HLB value to 8 or 11 (span 20 or tween 85) decreased the efficiency of naltrexone HCl-loading. HLB values higher than 15 (tween 80 or tween 20) increased encapsulation efficiency unexpectedly, which could be attributed to migration of these emulsifiers to the O/W(2) interface and modifying the surface properties of microparticles. Increasing the internal water phase volume from 0.2-1.8 ml resulted in larger particle size with poor encapsulation efficiency. Addition of 10% w/w NaCl to the W(2) changed the surface morphology of microspheres from a porous form to a smooth surface. It was shown that, by selecting the appropriate HLB value of emulsifier in W(1), addition of salt to W(2) and controlling the volume of W(1), one can control the encapsulation efficiency, size and morphology of microspheres.
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PMID:Effect of surfactant HLB and different formulation variables on the properties of poly-D,L-lactide microspheres of naltrexone prepared by double emulsion technique. 1601

Ultrafine poly (D, L-lactide) (PLA) fibers with diameter less than 200 nm produced by electrospinning were studied to obtain tissue restoration resembling extracellular matrix. Scanning electron microscopy was used to observe the fiber morphology. Results showed that the solvent was the critical factor to determine the formation of the electrospun PLA fibers. Compared with acetone, N,N-dimethylformamide (DMF) was a better solvent for PLA to electrospin. Entrance of an organic salt, triethylbenzylammonium chlorate, led to a great increase of the conductivity of PLA/DMF solutions, so that the average fiber diameter of the electrospun PLA fibers decreased dramatically from 500 nm to 100-200 nm. The addition of surfactant, Span-80, did not improve the fiber morphology but formed beaded fiber web.
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PMID:[Electrospinning and morphology of ultrafine poly (D, L-lactide) fibers]. 1642 11

To test the hypothesis that NO contributes to effects of angiotensin-converting enzyme inhibitors on fibrinolysis, fibrinolytic balance was assessed in 17 normal subjects during placebo and after randomized, double-blind 4-week treatment with the NO precursor L-arginine (3 g TID), ramipril (10 mg QD), or L-arginine+ramipril. Neither L-arginine nor ramipril alone affected basal plasminogen activator inhibitor-1 or tissue-type plasminogen activator (t-PA) antigen in these salt-replete subjects in whom plasma renin activity was suppressed (mean+/-SD 0.7+/-0.5 ng angiotensin I/mL per hour). In contrast, L-arginine+ramipril reduced morning plasminogen activator inhibitor-1 antigen (10.8+/-9.5 ng/mL) and the molar ratio of plasminogen activator inhibitor-1:t-PA (2.3+/-1.6) compared with placebo (13.5+/-10.8 ng/mL, P=0.006; ratio 2.9+/-2.1, P=0.015) or ramipril alone (15.2+/-13.2 ng/mL, P=0.009; ratio 3.7+/-3.3, P=0.005). L-arginine and ramipril synergistically increased d-dimers (23.1+/-31.5, 29.7+/-50.0, 35.1+/-50.0, and 57.1+/-144.8 ng/mL during placebo, L-arginine, ramipril, and L-arginine+ramipril, respectively; P<0.05 for L-arginine+ramipril versus any other group). During ramipril, the NO synthase inhibitor L-NG-nitro-arginine-methyl-ester (2 mg/kg) significantly increased plasminogen activator inhibitor-antigen after 2 hours (from 9.4+/-8.6 ng/mL during vehicle to 13.5+/-11.0 ng/mL during L-NG-nitro-arginine-methyl-ester; P=0.020), consistent with an effect on expression but rapidly increased t-PA activity (from 0.4+/-0.3 to 0.5+/-0.4 IU/mL; P=0.031), consistent with an effect on release. Both effects of L-NG-nitro-arginine-methyl-ester were reversed by L-arginine. During angiotensin-converting enzyme inhibition, endogenous NO decreases plasminogen activator inhibitor-1 antigen and improves fibrinolytic balance in normotensive salt-replete subjects.
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PMID:Endogenous NO regulates plasminogen activator inhibitor-1 during angiotensin-converting enzyme inhibition. 1643 54

Phospholipases A(2) (PLA(2)) play an important role for the production of lysophospholipids. Presently they are mainly obtained from porcine or bovine pancreas but these mammalian sources are not accepted in several fields of application. To make accessible a non-mammalian PLA(2) to industrial application, synthetic genes encoding PLA(2) from honey bee (Apis mellifera) with modified N-termini were constructed and expressed in Escherichia coli. While expression of the gene with an N-terminal leader sequence to direct the protein into the periplasm failed, four variants with slightly modified N-termini (I1A-PLA(2), I1V-PLA(2), His(6)-tagged PLA(2) and PLA(2) still containing the start methionine) were successfully expressed. In all cases, the PLA(2) variants were produced as inclusion bodies. Their protein content amounted to 26-35% of total cell protein. The optimized renaturation procedure and subsequent purification by cation-exchange chromatography yielded pure active enzymes in yields of 4-11 mg L(-1). The recombinant PLA(2) variants showed activities, far-UV CD and fluorescence spectra similar to the glycosylated PLA(2) isolated from the venom glands of honey bee (bv-PLA(2)). The thermodynamic stabilities of the recombinant enzymes calculated from the transition curves of guanidine hydrochloride induced unfolding were also nearly identical to the stability of bv-PLA(2). For the variant I1A-PLA(2) high-cell density fermentation in 10 L-scale using mineral salt medium was shown to increase the volumetric enzyme yield considerably.
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PMID:Production of synthetically created phospholipase A(2) variants with industrial impact. 1731 11

PLLA, PLA-PEG and PLGA porous scaffolds with pore size ranging from 100 to 250 microm and porosity over 85% were fabricated by a solution-casting/salt-leaching method. The porous structure and porosity of the scaffold were mainly dependent on volume fraction and size of the porogens of NaCl particles. The effects of the polymeric materials on the cell culture behavior and bone formation in vitro in their scaffolds were studied. In vitro cell culture in the scaffolds of the three polymers demonstrated that mesenchymal stem cells (MSCs) had a good adhesion and spread. The composite matrixes cultured for several days possessed preliminary functions of tissue-engineering bone, with signs of the calcium knur formation and the expression of osteocalcin and collagen I in mRNA, especially that of PLA-PEG and PLGA. These cell-loaded porous scaffolds showed effective repair of mandibular defect of rabbits in vivo. Contrastive experiments demonstrated that the MSCs/PLGA scaffold owned better ability facilitating for the MSCs proliferation, differentiation and defect repair. These composite scaffolds can be a potential effective tool for treating mandibular and other bone defects.
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PMID:Repair of mandibular defects using MSCs-seeded biodegradable polyester porous scaffolds. 1755 Jun 55

In this work, three-dimensional porous composite scaffolds, based on poly(epsilon-caprolactone) (PCL), were fabricated through the combination of a filament winding technique and a phase inversion/salt leaching process. Sodium chloride crystals were used as the porogen agent, and poly(lactic acid) (PLA) fibers and calcium phosphates as reinforcement. The aim of the current work is to assess the effective synergistic role of bioactive particles (i.e. alpha-tricalcium phosphates (alpha-TCP)) and PLA fibers on the morphology and mechanical response of the final scaffold. Morphological investigations performed on fiber-reinforced composite scaffolds with different PCL/alpha-TCP volume ratios (0%, 13%, 20% and 26%) show a high porosity degree (ca. 80%), pore interconnection and a homogeneous distribution of pores within the scaffold. More specifically, a bimodal pore size distribution was observed. This comprised microporosity (pores with radii ranging from 0.1 to 10 microm, which were strictly related to solvent extraction) and macroporosity (pores with radii from 10 to 300 microm, which were ascribable to the leaching of porogen elements). Static compressive tests showed that the effect of alpha-TCP on the mechanical response was to increase the elastic modulus up to a maximum value of 2.21+/-0.24 MPa, depending on the concentration of alpha-TCP added. This effect may be explained through the interaction of calcium-deficient hydroxyapatite crystals, formed as a consequence of a hydrolysis reaction of alpha-TCP, and the fiber-reinforced polymer matrix. The correct balance between chemical composition and spatial organization of reinforcement systems allows the attainment of an ideal compromise between mechanical response and bioactive potential, facilitating the development of composite scaffolds for bone tissue engineering applications.
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PMID:The synergic effect of polylactide fiber and calcium phosphate particle reinforcement in poly epsilon-caprolactone-based composite scaffolds. 1857 87

Chondroitin-4-sulfate was oversulfated using chlorosulfonic acid-pyridine complex and was isolated as the sodium salt. A comparison of the infrared analysis of the native (N-2) and oversulfated (S-2) compounds showed that the two spectra were identical except for a new peak in S-2 at 825 cm corresponding to the equatorial C-6 position of galactosamine. There was a 2.7-fold increase of sulfate content in S-2 and a generation of a significant anticoagulant activity as measured by doubling of the prothrombin time of normal citrated human plasma using 7.5 microg, while N-2 was inactive even at 2,000 microg. The result of the in-vitro studies of the activation of glutamic plasminogen by tissue plasminogen activator (t-PA) or by high-molecular-weight urokinase using 0.05 mol/l Tris buffer (pH 7.35) containing a physiological concentration of NaCl (0.9%) showed that 28.6 microg/ml S-2 enhanced the activation by three-fold to four-fold by t-PA or by urokinase, while the same concentrations of N-2 or unfractionated heparin gave less than 30% enhancement of t-PA and no enhancement of urokinase. The mechanism of enhancement by S-2 was investigated by dilution studies. The results showed that S-2 interacted with both urokinase or t-PA and glutamic plasminogen favoring a template model, while N-2 or unfractionated heparin interacted only with t-PA.
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PMID:Effect of oversulfation on the chemical and biological properties of chondroitin-4-sulfate. 1868 30


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