Rapid induction of functional and morphological continuity between severed ends of mammalian or earthworm myelinated axons.
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The inability to rapidly restore the loss of function that results from severance (cutting or crushing) of PNS and CNS axons is a severe clinical problem. As a novel strategy to help alleviate this problem, we have developed in vitro procedures using Ca2+-free solutions of polyethylene glycol (PEG solutions), which within minutes induce functional and morphological continuity (PEG-induced fusion) between the cut or crushed ends of myelinated sciatic or spinal axons in rats. Using a PEG-based hydrogel that binds to connective tissue to provide mechanical strength at the lesion site and is nontoxic to nerve tissues in earthworms and mammals, we have also developed in vivo procedures that permanently maintain earthworm myelinated medial giant axons whose functional and morphological integrity has been restored by PEG-induced fusion after axonal severance. In all these in vitro or in vivo procedures, the success of PEG-induced fusion of sciatic or spinal axons and myelinated medial giant axons is measured by the restored conduction of action potentials through the lesion site, the presence of intact axonal profiles in electron micrographs taken at the lesion site, and/or the intra-axonal diffusion of fluorescent dyes across the lesion site. These and other data suggest that the application of polymeric fusiogens (such as our PEG solutions), possibly combined with a tissue adherent (such as our PEG hydrogels), could lead to in vivo treatments that rapidly and permanently repair cut or crushed axons in the PNS and CNS of adult mammals, including humans. (+info)
New biodegradable hydrogels based on a photocrosslinkable modified polyaspartamide: synthesis and characterization.
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alpha,beta-Poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA), a synthetic water-soluble biocompatible polymer, was derivatized with glycidyl methacrylate (GMA), in order to introduce in its structure chemical residues having double bonds and ester groups. The obtained copolymer (PHG) contained 29 mol% of GMA residues. PHG aqueous solutions at various concentrations ranging from 30 to 70 mg/ml were exposed to a source of UV rays at lambda 254 nm in the presence or in the absence of N,N'-methylenebisacrylamide (BIS); the formation of compact gel phases was observed beginning from 50 mg/ml. The obtained networks were characterized by FT-IR spectrophotometry and swelling measurements which evidenced the high affinity of PHG hydrogels towards aqueous media at different pH values. In vitro chemical or enzymatic hydrolysis studies suggested that the prepared samples undergo a partial degradation both at pH 1 and pH 10 and after incubation with enzymes such as esterase, pepsin and alpha-chymotrypsin. Finally, the effect of irradiation time on the yield and the properties of these hydrogels was investigated and the sol fractions coming from irradiated samples, properly purified, were characterized by FT-IR and 1H-NMR analyses. (+info)
Activities of a nitrofurazone-containing urinary catheter and a silver hydrogel catheter against multidrug-resistant bacteria characteristic of catheter-associated urinary tract infection.
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The in vitro inhibitory activity of a nitrofurazone-coated urinary catheter (NFC) against 86 recently obtained susceptible and multidrug-resistant (MDR) clinical isolates of Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus faecium, which are species implicated in catheter-associated urinary tract infection and which traditionally have been susceptible to nitrofuran derivatives, was determined using an agar diffusion assay. In a subset of these strains, the activity of the NFC was compared with that of a silver hydrogel urinary catheter (SHC), and the durability of each catheter's inhibitory activity was assessed during serial daily transfers of catheter segments to fresh culture plates. Except for vancomycin-resistant E. faecium, the NFC was active against all isolates tested and showed comparable inhibition zones with susceptible and MDR strains of each species. In contrast, the SHC inhibited only certain staphylococci (P < 0.01 versus the NFC), and among these strains, the SHC produced smaller inhibition zones than did the NFC (P < 0.01). Inhibition was evident for up to 5 days with the NFC, but for only 1 day (if at all) with the SHC (P < 0.01). These data document that, for most genera which traditionally have been susceptible to nitrofuran derivatives, the NFC remains active against contemporary MDR isolates. They also demonstrate that the in vitro antibacterial activity of the NFC is markedly superior to that of the SHC in several respects. Thus, the NFC shows promise for clinical use in the current era of MDR bacteria. (+info)
A new model of chronic cardiac ischemia in rabbits.
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Chronic cardiac ischemia has mainly been studied in large species such as pigs or dogs. Little research has been performed using small species such as rabbits. In the present study, 1-3 wk after implantation of a novel device (ameroid) on the circumflex coronary artery of New Zealand White rabbits, vessel patency was evaluated by coronary angiography, corrosion cast, and radiolabeled microspheres. Coronary angiograms showed, after 21 days, either total occlusion or severe stenosis in seven of eight arteries, which was confirmed by corrosion casts. The ameroid group had less blood flow in the epicardial (-62%) and endocardial (-54%) layers of the ischemic area compared with sham-operated rabbits (P < 0.05). Blood flow increased in the ischemic area compared with day 0 during acute occlusion, suggesting that progressive coronary occlusion initiated the growth of de novo collateral vessels. Thus we have developed a new model of chronic cardiac ischemia in rabbits with documented progressive coronary stenosis and occlusion that is suitable to test various therapeutic angiogenesis strategies. (+info)
Effectiveness of wound care products in the transmission of acoustic energy.
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BACKGROUND AND PURPOSE: Ultrasound is often recommended in the treatment of people with partial and full-thickness wounds. Many treatments are performed over a hydrogel sheet or semipermeable film dressing. The purpose of this in vitro study was to examine the effectiveness of 4 hydrogels (Nu-Gel, ClearSite, Aquasorb Border, and CarraDres) and 4 film dressings (CarraSmart Film, J&J Bioclusive, Tegaderm, and Opsite Flexigrid) in ultrasound transmission. METHODS: The amount of sound energy transmitted through each product and interposed pig tissue was measured using an oscilloscope to display the intensity of sound energy delivered by the transducer. Five intensities at a frequency of 3.3 MHz were studied. RESULTS: Results were expressed as the mean ((SD) percentage of voltage transmitted compared with a gel baseline. Nu-Gel was the most efficient hydrogel (77.2%(4.6%), followed by ClearSite (72.0%(2.2%), Aquasorb Border (45.3%(2.1%), and CarraDres (42.8%(5.9%). The 4 film dressings, in order of efficiency, were CarraSmart Film (60.5%(4.4%), J&J Bioclusive (53.2%(2.4%), Tegaderm (47.1%(2.3%), and Opsite Flexigrid (31.5%(4.0%). CONCLUSION AND DISCUSSION: Transmissivity of wound care products used to deliver acoustic energy during ultrasound treatment of wounds varies greatly among dressing products. We believe that clinicians can use our findings as a part of the clinical reasoning process that they use to select an optimal wound dressing. (+info)
Novel materials to enhance keratoprosthesis integration.
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BACKGROUND: The successful integration of keratoprostheses (KPros) within the cornea depends in part on peripheral host keratocyte adhesion to anchor the implant in place and prevent epithelial downgrowth. The following study incorporated different acrylate co-monomers with poly(hydroxyethyl methacrylate) (p(HEMA)) and measured the suitability of these materials as potential skirt materials in terms of their ability to enhance keratocyte adhesion to p(HEMA). METHODS: p(HEMA) hydrogels incorporating varying amounts of the acrylate co-monomers methacrylic acid (MA), 2-(dimethylamino)ethyl methacrylate (DEM), or phenoxyethyl methacrylate (PEM) were formed by free radical polymerisation. Keratocytes were seeded onto discs of each material and incubated at 37 degrees C for 72 hours. Assays for viable cell adhesion were carried out. A viability/cytotoxicity assay using solutions of calcein-AM (0.5 mM) and ethidium homodimer-1 (EthD-1) (0.5 microM) were used to measure viable and non-viable cell adhesion, respectively. An ATP assay was also used to quantify cell adhesion in terms of the amount of ATP present following lysis of adherent cells. RESULTS: The viability/cytotoxicity assays indicated that the incorporation of 15 mol% of the co-monomer PEM or of 20 mol% DEM increased cell adhesion to p(HEMA) by at least four times. The ATP assays confirmed the results for PEM but absorption of ATP to the DEM containing hydrogel indicated that the assay was not a suitable measure of cell adhesion to this material. CONCLUSIONS: The properties of p(HEMA) may be moderated to enhance keratocyte adhesion by the incorporation of PEM or DEM suggesting that these may be suitable materials for use in the further development of a novel KPro skirt material. (+info)
Self-assembled peptide fibers from valylvaline bola-amphiphiles by a parallel beta-sheet network.
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A series of dipeptide-based bola-amphiphiles, bis(N-alpha-amide-L-valyl-L-valine) 1, n-alkane dicarboxylate (n=4-12), have been synthesized. The bola-amphiphiles with n=4 and 6 self-assembled to form crystalline solids in water, whereas those with n=7-12 produced peptide fibers. FT-IR spectroscopy and X-ray diffraction patterns revealed that the peptide fibers have parallel-type beta-sheet networks between the valylvaline units. FT-IR deconvolution study of carboxyl regions indicated that these crystalline solids and peptide fibers are stabilized by interlayer bifurcated and intralayer lateral hydrogen-bond networks between the end carboxylic acid groups, respectively. (+info)
Transbuccal delivery of acyclovir (II): feasibility, system design, and in vitro permeation studies.
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PURPOSE: To design a buccal mucoadhesive system for systemic delivery of acyclovir using a novel mucoadhesive, copolymers of acrylic acid and poly(ethylene glycol), and to determine the feasibility of transbuccal delivery of acyclovir using this system. METHODS: The buccal delivery system was prepared using an adhesive, a copolymer of acrylic acid and poly(ethylene glycol) monomethylether monomethacrylate, and an impermeable membrane to prevent excessive washout by saliva and to attain unidirectional release. Acyclovir was loaded into the copolymer film prior to lamination of backing material. In vitro drug release studies were conducted in isotonic McIlvaine buffer solution. Buccal permeation of acyclovir was investigated using porcine buccal mucosa with side-by-side flow through diffusion cells at 37;C. Acyclovir was quantified using HPLC. RESULTS: Buccal permeation of acyclovir from the mucoadhesive delivery system was controlled for up to 20 hours with a time lag (t(lag)) of 10.4 hours and a steady state flux of 144.2 microg/cm(2)/h. With the incorporation of NaGC into the system t(lag) was shortened to 5.6 hours with an enhanced steady state flux of 758.7 microg/cm(2)/h. Sustained delivery of acyclovir across bucccal mucosa using this mucoadhesive system was maintained for up to 22 hours. CONCLUSIONS: The mucoadhesive system of P(AA-co-PEG) was shown to be a good candidate for controlled oral mucosal delivery of acyclovir. Buccal delivery of acyclovir was proven feasible based on in vitro permeation studies. (+info)