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Biomedical subjects

J Will

Publications and source records attributed to J Will.

15 recordsLinked to original sources
PubMed2007

Effect of different gamma-irradiation doses on cytotoxicity and material properties of porous polyether-urethane polymer.

Biomaterials respond to sterilization methods differently. Steam sterilization might decrease the performance of thermoplastic polyether-urethane (TPU); however, the effect of different gamma-radiation doses on this polymer is contradictory in present literature. The purpose of this study was to investigate the differences between irradiative doses in comparison with steam sterilization on a porous TPU scaffold produced by a new processing method. No significant differences in the surface chemical structure were found with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis when comparing with the sterilization methods. The molecular weight (M(w)) had a net increase from 11.5 +/- 0.039 to 13.2 +/- 0.072 kDa by gamma-sterilization from 10 to 60 kGy. The samples that were irradiated (>60 kGy) had also an increase in polydispersity index (PDI; 1.45 +/- 0.007) in comparison with the nonsterile ones (1.31 +/- 0.017), which indicate branching. Liquid chromatography/mass spectroscopy (LC/MS) analysis showed that there was a correlation between the concentration of the breakdown product, methyl dianiline, and cytotoxicity. The concentration of this compound was found to be four times higher in steam-sterilized sample (1.3 +/- 0.01 ppb) compared with that of the polymer sample gamma-sterilized at 10 kGy (0.3 +/- 0.01 ppb). The cytotoxicity of TPU was found to decrease with higher radiation doses, and was significantly higher for the steam-sterilized samples. It is recommended that TPU produced with the described foaming method should be sterilized by gamma-irradiation at 25 kGy or higher doses.

Biocompatible Materials↗
PubMed2006

A novel processing method for injection-molded polyether-urethane scaffolds. Part 1: processing.

A large-scale scaffold processing method with injection molding has been successfully developed. Water was used as afoaming agent for the new technique. NaCl was used as a porogen to achieve an open-cell structure. Organic solvents, which are common foaming agents for polyurethane, where not used. Toxic remains in the polymer were therefore prevented. Pore size and porosity was adjustable through process parameters. A parameter study showed that an increase in injection pressure, plasticize speed, cylinder, and mold temperature raised the mean pore diameter. The porosity also could be mended by the cylinder and mold temperature, in addition to NaCl concentration. It was possible to produce scaffolds with a porosity of 64 +/- 3%, a pore size distribution from 30-450 microm, and a mean pore diameter of 270 +/- 90 microm. The interconnective pores were found to lie between 5 and 58 microm.

Biocompatible Materials↗
PubMed2005

Biostability of polyether-urethane scaffolds: a comparison of two novel processing methods and the effect of higher gamma-irradiation dose.

This article deals with enzyme-induced biodegradation behavior of thermoplastic polyether-urethane (TPU). Porous scaffolds were processed by a new foaming method applied in hot pressing and injection molding. The scaffolds were subsequently gamma sterilized. The samples were incubated with cholesterol esterase (CE) for 28 days to simulate an enzymatic degradation order to assess polymer biostability. The main focus of degradation products was the most toxic one: methylene dianiline (MDA). LC/MS was used to separate the breakdown products and to identify possible MDA amounts. The results showed that (a) the hot-pressed sample released an MDA amount almost twice as large (0.26 ng +/- 0.008) as that of the injection-molded samples (0.15 ng +/- 0.003) after incubation with enzyme activity in the physiological range, and (b) a tenfold increase in CE activity revealed considerably higher MDA amounts (7540.0 ng +/- 0.004). This enzyme concentration is physiologically unlikely, however, but may occur for extreme high inflammation behavior. Even for extremely high levels of CE enzyme, the scaffold will not discharge MDA above toxic levels. The injection-molded samples sterilized at 25 kGy seem to represent the most promising processing method. Therefore, the new injection-molding foaming process of polyether-urethane can be considered appropriate for use as a biomaterial.

Animals↗
PubMed2004

Water as foaming agent for open cell polyurethane structures.

The problem of moisture in polymer processing is known to any polymer engineer, as air bubbles may be formed. Hence granulates are generally dried prior to manufacturing. This study tried to develop a novel processing methods for scaffolds with controlled moisture content in thermoplastic polyurethane. The common foaming agents for polyurethane are organic solvents, whose residues remaining in the scaffold may be harmful to adherent cells, protein growth factors or nearby tissues. Water was used as a foaming agent and NaCl was used as porogens to achieve an open-cell structure. The polyether-polyurethane samples were processed in a heated press, and achieved a porosity of 64%. The pore size ranged between 50 and 500 microm. Human fibroblasts adhered and proliferate in the scaffold. A non-toxic production process was developed to manufacture a porous structure with a thermoplastic polyether-polyurethane. The process enables a mass-production of samples with adjustable pore size and porosity. In contrast to an existing method (solvent casting), the processing of the samples was not limited by its thickness. The process parameters, which attribute mostly to the pore building, were filling volume, temperature, NaCl-concentration and water-uptake rate.

Air↗
PubMed2001

Nutrition and physical activity interventions to reduce cardiovascular disease risk in health care settings: a quantitative review with a focus on women.

The authors conducted a quantitative literature review of the impact of 32 diet and physical activity (PA) interventions delivered in health care settings on cardiovascular disease risk factors. Intervention effects were relatively modest but statistically significant for PA, body mass index or weight, dietary fat, blood pressure, and total and low-density lipoprotein serum cholesterol. Intervention effects were generally larger for samples with a mean age >50 years and for studies with <6 months follow-up. Type of comparison group, type of intervention, and use of a behavior theory did not have a consistent impact on intervention effects. Few studies focused on persons of color, although the results from these studies are promising.

Age Distribution↗
PubMed1998

Minimal molecular determinants of substrates for recognition by the intestinal peptide transporter.

Proton-dependent electrogenic transporters for di- and tripeptides have been identified in bacteria, fungi, plants, and mammalian cells. They all show sequence-independent transport of all possible di- and tripeptides as well as of a variety of peptidomimetics. We used the mammalian intestinal peptide transporter PEPT1 as a model to define the molecular basis for its multisubstrate specificity. By employing computational analysis of possible substrate conformations in combination with transport assays using transgenic yeast cells and Xenopus laevis oocytes expressing PEPT1, the minimal structural requirements for substrate binding and transport were determined. Based on a series of medium chain fatty acids bearing an amino group as a head group (omega-amino fatty acids, omega-AFA), we show that electrogenic transport by PEPT1 requires as a minimum the two ionized head groups separated by at least four methylene groups. Consequently, a > 500 pm < 630 pm distance between the two charged centers (carboxylic carbon and amino nitrogen) is sufficient for substrate recognition and transport. Removal of either the amino group or the carboxyl group in omega-AFA maintained the affinity of the compound for interaction with the transporter but abolished the capability for electrogenic transport. Additional groups in the omega-AFA backbone that provide more hydrogen bonding sites appear to increase substrate affinity but are not essential. The information provided here does (a) explain the capability of the peptide carrier for sequence-independent transport of thousands of different substrates and (b) set the molecular basis for a rational drug design to increase the absorption of peptide-based drugs mediated by PEPT1.

Amino Acids↗
PubMed1998

Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications.

Delta-aminolevulinic acid (ALA) is the precursor of porphyrin synthesis and has been recently used in vitro and in clinical studies as an endogenous photosensitizer for photodynamic therapy in the treatment of various tumors. For this purpose, ALA is given topically, systemically, or orally. When administered by the oral route, it shows excellent intestinal absorption. ALA is also efficiently reabsorbed in the renal proximal tubule after glomerular filtration. However, the pathways and mechanisms for its transmembrane transport into epithelial cells of intestine and kidney are unknown. Here we demonstrate that ALA uses the intestinal and renal apical peptide transporters for entering into epithelial cells. Kinetics and characteristics of ALA transport were determined in Xenopus laevis ooyctes and Pichia pastoris yeast cells expressing either the cloned intestinal peptide transporter PEPT1 or the renal form PEPT2. By using radiolabeled ALA and electrophysiological techniques in these heterologous expression systems, we established that: (a) PEPT1 and PEPT2 translocate 3H-ALA by saturable and pH-dependent transport mechanisms, (b) that ALA and di-/tripeptides, but not GABA or related amino acids, compete at the same substrate-binding site of the carriers, and (c) that ALA transport is electrogenic in nature as a consequence of H+/ALA cotransport. Reverse transcriptase-PCR analysis performed with specific primers for PEPT1 and PEPT2 in rabbit tissues demonstrates that, in particular, the PEPT2 mRNA is expressed in a variety of other tissues including lung, brain, and mammary gland, which have been shown to accumulate ALA. This suggests that these tissues could take up the porphyrin precusor via expressed peptide transporters, providing the endogenous photosensitizers for efficient photodynamic therapy.

Aminolevulinic Acid↗
PubMed1990

Doxacurium and mivacurium do not trigger malignant hyperthermia in susceptible swine.

The role of succinylcholine in the precipitation of malignant hyperthermia (MH) necessitates the testing of new neuromuscular relaxants for their ability to trigger MH in MH-susceptible swine before general human use. We tested doxacurium and mivacurium, two new nondepolarizing bis-benzylisoquinolinium neuromuscular relaxants, at ED95 and at four times ED95 doses in swine previously documented to be MH-susceptible. In none of the 16 animals was MH triggered after administration of these relaxants, whereas all animals developed fatal MH after administration of halothane or halothane plus succinylcholine. Muscle biopsy specimens taken before administration of the relaxant confirmed that all animals had increased sensitivity to halothane, caffeine, or both. Thus, we conclude that doxacurium and mivacurium are not triggering agents of malignant hyperthermia in MH-susceptible swine.

Animals↗
PubMed1980

Thalamonal, droperidol and fentanyl in induced hypovolaemic shock in the conscious dog.

Previous studies had shown that Thalamonal exerts a protective activity against hypovolaemic shock in experimental animals as well as in patients. The purpose of the present study was to make a long-term evaluation of the value of single doses of Thalamonal fentanyl and droperidol as shock-protecting agents in conscious dogs which received no replacement of blood loss. The study was conducted in 20 animals in which devices were implanted for measuring heart rate, arterial and venous blood pressure, left ventricular and left atrial blood pressure. The dogs were divided into 4 groups, receiving 20 ml of an i.v. injection containing either 0.025 mg/kg fentanyl, 0.625 mg/kg droperidol, 0.25 ml/kg Thalamonal (0.625 mg/kg droperidol + 0.0125 mg/kg fentanyl), or saline. Thalamonal allowed a 100 per cent survival of the dogs, one of the 5 animals survived in the droperidol group, whereas fentanyl and saline were completely ineffective. As a possible mechanism of action the interruption of the vicious sequence of blood loss, vasoconstriction and circulatory arrest at a peripheral and/or central level is discussed. The hypothesis of intracorporeal blood volume correction under the influence of Thalamonal as an anti-vasoconstrictor seems to be logical but needs further investigation.

Animals↗
PubMed1978

The effect of glucagon on the pulmonary transvascular fluid filtration rate.

Administration of glucagon has been shown to decrease pulmonary vascular resistance, but its primary site of action is undetermined. Whether this is on the arterial or venous side of the capillary would be reflected in the microvascular hydrostatic pressure. We used the pulmonary flow of lymph, a sensitive index of the transvascular fluid filtration rate, to monitor the microvascular hydrostatic pressure. Eight unanesthetized sheep with a surgically created long-term fistula for monitoring pulmonary lymph were given a 3-mg bolus of glucagon after a baseline period. We found no change in pulmonary arterial or left atrial pressures but noted a significant increase in cardiac output and a decrease in pulmonary resistance. The flow of pulmonary lymph increased by 50 percent for 30 minutes after administration of glucagon, and the protein content of the lymph decreased by 15 percent, indicating a large increase in the microvascular hydrostatic pressure. From these data, we calculated a decrease in arterial resistance from 60 percent to 30 percent of the total and, subsequently, an increase of 6 cm H2O in the microvascular hydrostatic pressure. Administration of glucagon, therefore, decreases the arterial resistance while increasing microvascular pressure in the process.

Animals↗