Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In experiments in which blood was cross-circulating in rats, the blood pressure of the recipient dropped while that of the donor rose, following the increase of the circulating blood volume, produced by infusion either of saline or blood. The phenomenon was almost imperceptible when binephrectomized animals were used. In experiments in which the blood-bathed organ technique was used, prostaglandin-like substances were detected, released during the rise of the blood pressure, produced by the same stimulus (the expansion), in anaesthetized rats. A significant difference was found between the prostaglandin-like substances detected using the blood-bathed organ technique, in normal rats (5.387 ng per ml of blood plus or minus 0.288 = SEM) and those detected in binephrectomized rats (3.202 ng per ml of blood plus or minus 0.330, p smaller than 0.025). The biologically active substances detected in 25 ml of blood collected during expansion, while the assay organs showed a prostaglandin-like activity, were found to have the chromatographic behaviour and the bioassay properties of PGA, PGE and PGF series. A great quantity of the biologically active substances, having the chromatographic behaviour and the bioassay properties of PGA, PGS and PGF was detected in the rat renal medulla. Sufficient quantities of the released prostaglandin-like substances could escape the pulmonary vascular bed in this species of animal. It was concluded that a great quantity of the released prostaglandin-like substances came from the kidney and their release by this particular mechanism suggested that they play an important homeostatic role on the blood pressure, blood volume, and sodium and water balance regulation.
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PMID:[Origin, nature, role and fate of prostaglandins liberated during the expansion of intravascular space in the anesthetized rat]. 109 32

The role of prostaglandins in blood pressure regulation was studied in normal rats and in animals with renal artery constriction. The effects of chronic inhibition of prostaglandin (PG) synthesis on arterial pressure were observed, and renal medullary PG synthesis was measured in vitro. The prostaglandin synthetase inhibitor indomethacin was given in a dose of 2 mg/kg/day by mouth to one of two groups of male Wistar rats with a unilateral renal artery constriction and the other kidney untouched, and to one of two sham-clipped groups. Systolic blood pressures were higher in indomethacin-treated clipped rats than in non-indomethacin-treated clipped animals, and at 18 days averaged 188 mm Hg (plus or minus SEM 5.9, n = 36) and 162 mm Hg (plus or minus SEM 7.6, n = 34), respectively (P less than 0.005 for data pooled from two experiments). Indomethacin did not affect pressures of sham-clipped animals treated for 40 days. Analysis of PG synthesis by gas-liquid chromatography in renal medullary slices incubated for 30 minutes in Krebs-Henseleit buffer showed: (1) 40% suppression of PGE synthesis in hypertensive animals (P less than 0.001): (2) no differences between clipped and untouched kidneys; (3) chronic indomethacin treatment did not affect PGE synthesis in the in vitro buffer system; and (4) no PGA synthesis was detected. In a further experiment in which medullary slices were incubated in plasma of rats treated with equivalent doses of indomethacin, PGE synthesis was suppressed by 35%. The experiments support the concept that prostaglandins modulate pressor mechanisms which come into play when renal blood flow is drastically reduced. The effects could be mediated by PG synthesis in the kidney and/or in other systemic vascular beds.
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PMID:Renal prostaglandin synthesis in the Goldblatt hypertensive rat. 113 85

Microdissection of acellular rat renal cortex with pepsin was carried out to investigate the morphological substructure of glomerular basement membrane (GBM) by high resolution SEM. Renal cortical blocks (less than 5 mm3) from adult male Sprague Dawley rats were rendered acellular by sequential detergent extraction and digested up to 184 hrs with 5 mg/ml pepsin (185 U/mg) in 0.5 M acetic acid (pH 2) at 10-15 degrees C. Samples were conventionally prepared for SEM, and observed at original magnifications of 500-100,000 diameters. At low magnifications (500-5,000x), acellular GBM surfaces appeared smooth at all digestion times. At higher magnifications (50,000-100,000x), control GBM surfaces were finely granular. Granule diameter ranged from 20-80 nm, with most between 30-40 nm. Pepsin digestion did not affect average granule size. Beginning at 44 hrs of digestion, intrinsic fibrillar structures comprised of linear arrays of 20-40 nm granules were observed on/in GBM surfaces. At later incubation times, this component of GBM became more extensive. At 160 hrs, the fibrillar arrays frequently bifurcated and showed distinctive "forked" termini, some of which comprised two sides of a triangle (120-150 nm on a side). Fork "handles" (310-350 nm in length) radiated from each angle of the triangle. These sometimes terminated in large granules (approximately 100 nm in diameter), two of which appeared to connect fibrillar arrays end-to-end. Together with other arrays, the interconnected triangles appeared to comprise a three-dimensional meshwork extending into the GBM and possibly providing support for, its granular components.
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PMID:High resolution SEM analysis of acellular glomerular basement membrane following pepsin digestion: intrinsic fibrillar structures. 213 83

A luteotropic role for prostaglandins (PGs) during the luteal phase of the menstrual cycle of rhesus monkeys was suggested by the observation that intraluteal infusion of a PG synthesis inhibitor caused premature luteolysis. This study was designed to identify PGs that promote luteal function in primates. First, the effects of various PGs on progesterone (P) production by macaque luteal cells were examined in vitro. Collagenase-dispersed luteal cells from midluteal phase of the menstrual cycle (Day 6-7 after the estimated surge of LH, n = 3) were incubated with 0-5,000 ng/ml PGE2, PGD, 6 beta PGI1 (a stable analogue of PGI2), PGA2, or PGF2 alpha alone or with hCG (100 ng/ml). PGE2, PGD2, and 6 beta PGI1 alone stimulated (p less than 0.05) P production to a similar extent (2- to 3-fold over basal) as hCG alone, whereas PGA2 and PGF2 alpha alone had no effect on P production. Stimulation (p less than 0.05) of P synthesis by PGE2, PGD2, and 6 beta PGI1 in combination with hCG was similar to that of hCG alone. Whereas PGA2 inhibited gonadotropin-induced P production (p less than 0.05), that in the presence of PGF2 alpha plus hCG tended (p = 0.05) to remain elevated. Second, the effects of various PGs on P production during chronic infusion into the CL were studied in vivo. Saline with or without 0.1% BSA (n = 12), PGE2 (300 ng/h; n = 4), PGD2 (300 ng/h; n = 4), 6 beta PGI1 (500 ng/h; n = 3), PGA2 (300 ng/h; n = 4), or PGF2 alpha (10 ng/h; n = 8) was infused via osmotic minipump beginning at midluteal phase (Days 5-8 after the estimated LH surge) until menses. In addition, the same dose of PGE, PGD, PGI, or PGA was infused in combination with PGF2 alpha (n = 3-4/group) for 7 days. P levels over 5 days preceding treatment were not different among groups. In 5 of 8 monkeys receiving PGF2 alpha alone, P declined to less than 0.5 ng/ml within 72 h after initiation of infusion and was lower (p less than 0.05) than controls. The length of the luteal phase in PGF2 alpha-infused monkeys was shortened (12.3 +/- 0.9 days; mean +/- SEM, n = 8; p less than 0.05) compared to controls (15.8 +/- 0.5). Intraluteal infusion of PGE, PGD, PGI, or PGA alone did not affect patterns of circulating P or luteal phase length.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intraluteal infusions of prostaglandins of the E, D, I, and A series prevent PGF2 alpha-induced, but not spontaneous, luteal regression in rhesus monkeys. 227 32

The effect of the H2 agonist impromidine, gastrin 1-17 (G1-17), pentagastrin, and the M1 agonist McN-A-343 on pepsin secretion in the acid-inhibited totally isolated, vascularly perfused rat stomach was studied. Omeprazole produced a 97-98% inhibition of stimulated acid outputs. Base-line pepsin output after omeprazole was 712 +/- 278 micrograms/h (mean +/- SEM) and, after stimulation with impromidine, 1528 +/- 164 micrograms/h; G1-17, 1520 +/- 180 micrograms/h; and pentagastrin, 2063 +/- 605 micrograms/h. Output after McN-A-343 was 534 +/- 69 micrograms/h. Pepsin secretion after impromidine, G1-17, and pentagastrin was significantly (p less than 0.01) higher than base-line output. McN-A-343 had no significant effect on pepsin output in this model. Pepsin secretion after impromidine, G1-17, and pentagastrin was considerably lower than found in the same model with uninhibited acid output. This could be caused by decreased tubular 'washout' after acid inhibition, and, accordingly, no conclusions can be drawn as to the possible stimulatory effect of acid on pepsin secretion. However, the present study indicates that pepsin secretion can be stimulated directly by impromidine and (penta)gastrin without concomitant acidification of the gastric glands.
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PMID:Stimulated pepsin secretion after omeprazole-induced acid suppression in the totally isolated, vascularly perfused rat stomach. 243 47

Gastric fistula rats (n = 79) were either left as unstressed (fistula closed) controls or gastric secretion, microcirculation (MBF), mucosal stress ulcers were studied in secretory rats subjected to zero (= freely movements allowed), mild, severe restraint stress for 8 h. In all rats gastrin in portal vein and aorta was measured in addition after discontinuation of either protocol. Acid secretion and MBF are progressively reduced by increasing stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Pepsin and sodium are elevated with severe, acid concentration with mild stress. Serum gastrin (controls - aorta 53+/- SEM 5, portal vein 73 +/- 9 pg/ml) rises sharply in portal and systemic blood with institution of acid diversion via the outside (zero stress - 136 +/- 21, 398 +/- 98 pg/ml), but declines with increasing stress (severe stress - 82 +/- 16, 101 +/- 27 pg/ml) despite otherwise identical experimental conditions. It is concluded that (1) acid secretion rate and MBF are lowered by stress, but stress ulcers are associated with either increased acidity (mild stress) or peptic activity (severe stress) of gastric juice in the absence of elevated gastrin, (2) enhanced sodium fluxes via gastric lumen and lower acid suggest disruption if mucosal barrier by severe stress, and (3) restraint stress ulcers may be the expression of a combination of disturbances, mainly of metabolic and endocrine nature.
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PMID:Gastric secretion, mucosal erosions and porto-systemic gastrin gradients as influenced by different degrees of stress in the rat. 732 53

Our laboratory has investigated hepatocyte transplantation using biodegradable polymer matrices as an alternative treatment to end-stage liver disease. One of the major limitations has been the insufficient survival of an adequate mass of transplanted cells. This study investigates a novel method of dynamic seeding and culture of hepatocytes in a flow perfusion system. In experiment I, hepatocytes were flow-seeded onto PGA scaffolds and cultured in a flow perfusion system for 24 h. Overall metabolic activity and distribution of cells were assessed by their ability to reduce MTT. DNA quantification was used to determine the number of cells attached. Culture medium was analyzed for albumin content. In Experiment II, hepatocyte/polymer constructs were cultured in a perfusion system for 2 and 7 days. The constructs were examined by SEM and histology. Culture medium was analyzed for albumin. In experiment I, an average of 4.4 X 10(6) cells attached to the scaffolds by DNA quantification. Cells maintained a high metabolic activity and secreted albumin at a rate of 13 pg/cell/day. In experiment II, SEM demonstrated successful attachment of hepatocytes on the scaffolds after 2 and 7 days. Cells appeared healthy on histology and maintained a high rate of albumin secretion through day 7. Hepatocytes can be dynamically seeded onto biodegradable polymers and survive with a high rate of albumin synthesis in the flow perfusion culture system.
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PMID:Dynamic seeding and in vitro culture of hepatocytes in a flow perfusion system. 1094 Nov 99

Gamma-poly(glutamic acid) (gamma-PGA), a hydrophilic and biodegradable polymer, was chosen to modify chitosan matrices to produce a gamma-PGA/chitosan composite biomaterial. Three types of both dense and porous composite matrices containing different amounts of gamma-PGA were fabricated. Chitosan and gamma-PGA matrices were also prepared as controls. Fluorescence staining indicated that chitosan and gamma-PGA were evenly distributed in the composite matrices. SEM micrographs showed that an interconnected porous structure with a pore size of 30-100 microm was present in all porous matrices except the gamma-PGA ones. By increasing the percentage of gamma-PGA from 0% to 20%, the swelling ratio of the matrices was enhanced from 1.6 to 3.2. Similarly, the contact angle of the matrices decreased from 113 degrees to 94 degrees . These data suggested that the surface hydrophilicity, water absorption rate, and swelling ratio were improved by adding gamma-PGA to the matrices. Additionally, the mechanical strength of the porous gamma-PGA/chitosan matrices was about 25-50%, higher than that of the unmodified chitosan matrices. The composite matrices were also examined and found to be an appropriate environment for cell attachment and proliferation. The cell density on the 20% gamma-PGA-modified matrices was almost triple that on the unmodified chitosan matrices on day 5. In summary, the gamma-PGA/chitosan composite matrices, due to their better hydrophilic, cytocompatible, and mechanical properties, are very promising biomaterials for tissue engineering applications.
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PMID:Preparation of gamma-PGA/chitosan composite tissue engineering matrices. 1587 66

Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(d,l-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760+/-210 nm. The average Young's modulus of electrospun PLGA nanofibers was 42+/-26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1-4 weeks at a density of 2 x 10(6)cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells.
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PMID:Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. 1701 Apr 25

Pepsin (EC 3.4.4.1) from porcine stomach mucosa caused depolymerization of a chitosan sample (a copolymer of glucosamine and N-acetylglucosamine linked by beta-1-4-glycosidic bonds). N-terminal sequence and zymogram analyses confirmed dual (proteolytic and chitosanolytic) activities of pepsin. Optimum depolymerization occurred at pH 5.0 and 45 degrees C with an activity of 4.98 U. Low molecular weight chitosan (LMWC), the major depolymerization product, was obtained in a yield of 75-82%, the degree of polymerization of which depended on reaction time. The LMWC showed a nearly 10-14-fold decrease in the molecular mass as compared to native chitosan, which was also confirmed by GPC and HPLC analyses. IR and 13C NMR spectra indicated a decrease in the degree of acetylation (DA, approximately 13.4-18.8%) as compared to native chitosan (approximately 25.7%), which was in accordance with the CD analysis. Native chitosan had a crystallinity index (CrI) of approximately 70%, whereas there was a decrease in the CrI of LMWC (approximately 61%). The latter showed a better bactericidal activity toward both Bacillus cereus and Escherichia coli, which was more toward the former. The bactericidal activity was essentially due to the lytic and not static effect of LMWC, as evidenced by the pore formation on the bacterial cell surface when observed under SEM. This study suggests the possible use of pepsin in place of chitosanase, which is expensive and unavailable in bulk quantities for the production of LMWC of desired molecular mass that has diversified applications in various fields.
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PMID:Low molecular weight chitosan--preparation with the aid of pepsin, characterization, and its bactericidal activity. 1725 86


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