Effects of sodium hyaluronate and carboxymethylcellulose membrane on collagen and fibroblast formation in bowel suture healing: experimental study in rats.
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PURPOSE: To analyze the effects of sodium hyaluronate and carboxymethylcellulose membrane on collagen and fibroblast formation in bowel suture healing in rats. METHODS: 48 male Wistar rats, weighing 250 to 343g, were randomized into two groups: group I--bowel suture without applying a biologically absorbable membrane and group II--bowel suture with application of an absorbable membrane. The two groups were divided into subgroups of 3, 14 and 30 days of observation, with 8 rats in each subgroup. All were sacrificed after the end of the observation period. RESULTS: No morbidity or mortality was observed during the experiment. The amounts of collagen in group I were 23.4%, 72.1% and 67.6% and in group II were 22.5%, 52.5% and 51.6%, for the subgroups of 3, 14 and 30 days, respectively. Comparison between groups showed that the 14-day (p = 0.0013) and 30-day (p = 0.0587) subgroups had significant variance, with larger collagen zones in animals in which the membrane was not applied. However, with regard to fibroblasts, group I had 2%, 13% and 8% and group II had 2%, 10% and 8%, for the 3-day (p = 1.0), 14-day (p = 0.3184) and 30-day (p = 0.5995) subgroups, respectively, showing no significant variance. CONCLUSION: The use of the biologically absorbable membrane cause a decrease in collagen formation, while not altering the number of fibroblasts, in bowel suture healing in rats, without increased morbidity and mortality. (+info)
Effect of carbon source on the cellulosomal subpopulations of Clostridium cellulovorans.
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Clostridium cellulovorans produces a cellulase enzyme complex called the cellulosome. When cells were grown on different carbon substrates such as Avicel, pectin, xylan, or a mixture of all three, the subunit composition of the cellulosomal subpopulations and their enzymic activities varied significantly. Fractionation of the cellulosomes (7-11 fractions) indicated that the cellulosome population was heterogeneous, although the composition of the scaffolding protein CbpA, endoglucanase EngE and cellobiohydrolase ExgS was relatively constant. One of the cellulosomal fractions with the greatest endoglucanase activity also showed the highest or second highest cellulase activity under all growth conditions tested. The cellulosomal fractions produced from cells grown on a mixture of carbon substrates showed the greatest cellulase activity and contained CbpA, EngE/EngK, ExgS/EngH and EngL. High xylanase activity in cellulose, pectin and mixed carbon-grown cells was detected with a specific cellulosomal fraction which had relatively larger amounts of XynB, XynA and unknown proteins (35-45 kDa). These results in toto indicate that the assembly of cellulosomes occurs in a non-random fashion. (+info)
Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects.
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We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment. (+info)
Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy.
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PURPOSE: For chemotherapy to act synergistically and safely with radiation against high-grade gliomas, drugs must pass the endothelial junctions of the blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood-brain barrier (BBB) to cause toxicity to normal brain. The objective of this study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during a course of radiotherapy of high-grade gliomas. PATIENTS AND METHODS: Sixteen patients with grade 3 or 4 supratentorial malignant glioma receiving conformal radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) uptake index was analyzed with respect to the tumor and RT dose received. RESULTS: In the nonenhanced tumor region, contrast uptake increased significantly after the receipt of approximately 10 Gy (P < .01), and reached a maximum after the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor region, contrast uptake decreased over the course of RT and became significant after completion of RT in patients without progressive disease. The healthy brain showed only nonsignificant changes during and after irradiation. CONCLUSION: Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced tumor region but not in the remaining brain during the course of RT, suggesting opening of the BTB. This finding suggests that the effect of conformal radiation is more selective on the BTB than the BBB, and there may be a window extending from 1 week after the initiation of radiotherapy to 1 month after the completion of treatment during which a pharmaceutical agent has maximum access to high-grade gliomas. (+info)
Activity and regulation of alpha interferon in respiratory syncytial virus and human metapneumovirus experimental infections.
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Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause a similar spectrum of respiratory infections in humans. Classified within the Paramyxoviridae family, Pneumovirinae subfamily, RSV and hMPV present a significant degree of divergence in genome constellation, organization, and protein sequences. RSV has been reported to be a poor inducer of alpha/beta interferons (IFN-alpha/beta) and partially resistant to its antiviral activity. The nature of the innate immune response to hMPV is currently unknown. Herein, an experimental mouse model was used to investigate the interplay between RSV and hMPV infections and IFN-alpha in the airways. RSV-infected BALB/c mice treated intranasally with either poly-ICLC, a potent inducer of IFN-alpha, or directly with recombinant IFN-alpha showed significantly reduced lung viral titers, inflammation, and clinical disease than untreated controls. However, RSV was significantly less sensitive to the antiviral activity of IFN-alpha than hMPV. Similarly, when the ability to directly induce IFN-alpha production was assessed, RSV was clearly a weaker inducer of IFN-alpha than hMPV, as shown by both kinetics and the absolute amount of IFN-alpha secreted into the bronchoalveolar lavage. To further investigate the putative inhibitory effect of these viruses on IFN-alpha production, mice were infected for 48 h prior to treatment with poly-ICLC or a specific Toll-like receptor 9 ligand, CpG oligodeoxynucleotides. Strikingly, both poly-ICLC- and CpG-mediated IFN-alpha production was abrogated by either RSV or MPV infection. These results suggest that a complex interplay between virus-specific and host-mediated responses regulates IFN-alpha in the lung during infection by members of the Pneumovirinae family. (+info)
Permeation enhancement of ketoprofen using a supersaturated system with antinucleant polymers.
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Permeation enhancement of ketoprofen (KP) from supersaturated systems and the effects of antinucleant polymers on both stability and permeation of supersaturated KP were investigated using silicone membrane as a skin model. The supersaturation was prepared by the cosolvent technique with water and propylene glycol (PG). Saturated solubility of KP in water/PG cosolvent increased markedly with an increase in PG percentage. The time-profiles of the cumulative amount of released KP from supersaturated solutions through the membrane increased linearly, and this KP flux had a significant correlation with the degree of saturation (DS) in 80 : 20, 60 : 40, 50 : 50, and 40 : 60 (v/v) water/PG cosolvent systems. The influence of 1% solutions of antinucleant polymers, hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), and sodium carboxymethylcellulose (SCMC) on the DS and the stability of supersaturated KP was examined in 60 : 40 (v/v) water/PG cosolvent. The remaining DS for 24 h after mixing the solvents increased in the presence of HPMC and SCMC but not PVP. In the presence of SCMC, the physical stability of supersaturated KP was higher, however, the KP flux was lower than that in the control and in the presence of the other polymers. In conclusion, the supersaturation system can be applied to achieve higher transmembrane permeation of KP, and appropriate antinucleant polymers such as HPMC can optimize the physical stability and permeability of KP. (+info)
Formation of biocompatible nanoparticles by self-assembly of enzymatic hydrolysates of chitosan and carboxymethyl cellulose.
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A simple preparation method for biocompatible nanoparticles in high concentration (0.5 wt %) by self-assembly of chitosan and carboxymethyl cellulose hydrolysates was developed. Chitosan and carboxymethyl cellulose were hydrolyzed beforehand with chitosanase and cellulase respectively to make fragments having lower molecular weights. Nanoparticles were spontaneously formed only by mixing the two hydrolysate solutions. The particle size distribution was relatively narrow, about 200 nm in mean size. The mean particle size decreased from 226 nm to 165 nm with decreasing molecular weight of chitosan hydrolysate from 9.5 to 6.8 kDa. The mixing ratio of chitosan and carboxymethyl cellulose hydrolysates also affected particle size. Changes in particle size are discussed in relation to a possible mechanism of polyionic complexation. The chitosan-carboxymethyl cellulose nanoparticles were stably suspended over 1 week even under low pH (pH 3.0), high ionic strength (NaCl 1 M), or low temperature (4 degrees C) conditions. (+info)
Cell-associated pectinolytic and cellulolytic enzymes in Rhizobium leguminosarum biovar trifolii.
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The involvement of Rhizobium enzymes that degrade plant cell wall polymers has long been an unresolved question about the infection process in root nodule symbiosis. Here we report the production of enzymes from Rhizobium leguminosarum bv. trifolii that degrade carboxymethyl cellulose and polypectate model substrates with sensitive methods that reliably detect the enzyme activities: a double-layer plate assay, quantitation of reducing sugars with a bicinchoninate reagent, and activity gel electrophoresis-isoelectric focusing. Both enzyme activities were (i) produced commonly by diverse wild-type strains, (ii) cell bound with at least some of the activity associated with the cell envelope, and (iii) not changed appreciably by growth in the presence of the model substrates or a flavone that activates expression of nodulation (nod) genes on the resident symbiotic plasmid (pSym). Equivalent levels of carboxymethyl cellulase activity were found in wild-type strain ANU843 and its pSym-cured derivative, ANU845, consistent with previous results of Morales et al. (V. Morales, E. Martinez-Molina, and D. Hubbell, Plant Soil 80:407-415, 1984). However, polygalacturonase activity was lower in ANU845 and was not restored to wild-type levels in the recombinant derivative of pSym- ANU845 containing the common and host-specific nod genes within a 14-kb HindIII DNA fragment of pSym from ANU843 cloned on plasmid pRt032. Activity gel electrophoresis resolved three carboxymethyl cellulase isozymes of approximately 102, 56, and 33 kDa in cell extracts from ANU843. Isoelectric focusing activity gels revealed one ANU843 polygalacturonase isozyme with a pI of approximately 7.2. These studies show that R. leguminosarum bv. trifolii produces multiple enzymes that cleave glycosidic bonds in plant cell walls and that are cell bound. (+info)