Implant exudate leucocyte response to anti-inflammatory drug treatment

Implantation of artificial materials elicits a local inflammatory response. In this study a chamber model technique, allowing sampling of the inflammatory exudate for further analysis in vitro, was used. Male Sprague-Dawley rats were injected daily with two different anti-inflammatory drugs, betamethasone and indomethacin, and the local cellular response was compared with a control group. The retrieved exudate was evaluated with respect to the number of leucocytes, cell viability, differential counts and serum-opsonized zymosan stimulated chemiluminescence (CL). In all groups the majority of cells were polymorphonuclear granulocytes (PMNGs). Betamethasone and high-dose indomethacin (1.92 mg kg^-1 body weight day^-1) treatment caused a marked reduction in the number of accumulated leucocytes 6 days after implantation. A substantial inhibition of the CL response was observed 6 days after treatment with betamethasone (4.23 mg kg^-1 body weight day^-1). An increased CL responsiveness was observed after 24 h with low-dose indomethacin (0.03 mg kg^-1 body weight day^-1) and after 6 days with high-dose indomethacin (1.92 mg kg^-1 body weight day^-1) treatment. In summary, depending on the anti-inflammatory drug treatment, dose and time after implant surgery, either an inhibition or stimulation of leucocyte accumulation and activation was observed. This study shows the possibilities of sampling the inflammatory exudate adjacent to a biomaterial implanted in vivo. This chamber model may be useful for the analysis of the inflammatory reaction around an implanted biomaterial during pharmacological treatment.     

Incidence of neoplasms in ages 0-19 y in parts of Sweden with high 137Cs fallout after the Chernobyl accident

An experiment was conducted to elucidate the origin of tetraploids (2n = 4x = 44) of Paragonimus westermani that occur together with diploid (2n = 2x = 22) and triploid (2n = 3x = 33) types in Liaoning Province, the People's Republic of China. Metacercariae of the diploid type, obtained from Hyogo Prefecture, Japan, and those of the triploid type from Tsushima, Nagasaki Prefecture, Japan, were mixed and inoculated into dogs and cats. The following results were obtained. The flukes were found in pairs within cysts in random combinations of 2x + 2x, 2x + 3x, and 3x + 3x (7:15:7). Oocytes in the oviduct were at stages from diplotene to metaphase. In a triploid fluke encysted with a diploid fluke, the primary oocytes were intruded by sperms from the diploid fluke. In the primary oocytes of diploid as well as triploid flukes, from diplotene to diakinesis, the homologues of the nucleolar chromosomes were heteromorphic as far as the size of the short arm was concerned. This implies that the triploid is an autotriploid generated in an ancestral diploid population that was polymorphic for the nucleolar chromosome.     

Structural features of an arabinan fragment isolated from the water-soluble fraction of dehulled rapeseed

A water-soluble polysaccharide fraction was prepared from dehulled rapeseed meal (winter rapeseed variety Casino). Further purification yielded two major fractions having a high content of arabinose and galactose residues, with Ara/Gal ratios of 5.4 (G1) and 1.8 (G2). The Ara/Gal ratio of the high molecular weight fraction G1 was stable over the whole gel filtration peak, indicating that the arabinose and galactose residues are part of the same polysaccharide. The high molecular weight fraction G1 was studied further by methylation analysis and several NMR techniques. Structural studies showed G1 to consist mainly of arabian fragments, which have terminal alpha-L-arabinofuranosyl groups with anomeric carbons bound (1-->5) (A) or (1-->2) (B), and 2,5-substituted arabinosyl residues with anomeric carbons bound (1-->5) (D) or (1-->2) (C) to adjacent arabinosyl residues. The A:B:C:D ratios were 2:1:1:1 according to results from NMR and methylation analysis.     

Multicellular and aggregative behaviour of Salmonella typhimurium strains is controlled by mutations in the agfD promoter

To investigate the biochemical requirements for in vivo L-DOPA production by cells genetically modified ex vivo in a rat model of Parkinson's disease (PD), rat syngeneic 9L gliosarcoma and primary Fischer dermal fibroblasts (FDFs) were transduced with retroviral vectors encoding the human tyrosine hydroxylase 2 (hTH2) and human GTP cyclohydrolase I (hGTPCHI) cDNAs. As GTPCHI is a rate-limiting enzyme in the pathway for synthesis of the essential TH cofactor, tetrahydrobiopterin (BH4), only hTH2 and GTPCHI cotransduced cultured cells produced L-DOPA in the absence of added BH4. As striatal BH4 levels in 6-hydroxydopamine (6-OHDA)-lesioned rats are minimal, the effects of cotransduction with hTH2 and hGTPCHI on L-DOPA synthesis by striatal grafts of either 9L cells or FDFs in unilateral 6-OHDA-lesioned rats were tested. Microdialysis experiments showed that those subjects that received cells cotransduced with hTH2 and hGTPCHI produced significantly higher levels of L-DOPA than animals that received either hTH2 or untransduced cells. However, animals that received transduced FDF grafts showed a progressive loss of transgene expression until expression was undetectable 5 weeks after engraftment. In FDF-engrafted animals, no differential effect of hTH2 vs hTH2 + hGTPCHI transgene expression on apomorphine-induced rotation was observed. The differences in L-DOPA production found with cells transduced with hTH2 alone and those cotransduced with hTH2 and hGTPCHI show that BH4 is critical to the restoration of the capacity for L-DOPA production and that GTPCHI expression is an effective means of supplying BH4 in this rat model of PD.     

Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in transfected CHO cells without the concomitant administration of a Ca2+-mobilizing agent

In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3-PPP], also induced AA release, but with somewhat lower efficacy (maximal effect: 165%; EC50=91 nM). The AA-releasing effect of dopamine was counteracted by pertussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calcium from the medium, by the phospholipase A2 (PLA2) inhibitor, quinacrine, and by long-term pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, it was antagonized by the D2 antagonists, raclopride and (-)-sulpiride--but not by (+)-sulpiride--and absent in sham-transfected CHO cells devoid of D2 receptors. The results obtained contrast to the previous notion that dopamine and other D2 receptor agonists require the concomitant administration of calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimycin), thrombin, and TRH, to influence AA release from various cell lines.     

Identification of domains involved in superantigenicity of streptococcal pyrogenic exotoxin F (SpeF)

Coronary artery angioplasty or bypass is being performed for increasing numbers of patients in their seventh, eighth, ninth and even tenth decades of life. Because of the cost involved, justification for performing these procedures in the elderly has become a topic of daily discussion among those responsible for funding healthcare. Both silent and overt coronary artery disease (CAD) are more common in the population over 65 years of age. Because CAD in the elderly often presents in an atypical manner, diagnosis of the disease is frequently delayed. Partly because of the delayed diagnosis and partly because of cost considerations, coronary arterial bypass (CABG) is more often performed as an emergency procedure in the elderly with the results that both operative mortality and costs are increased over those observed in a younger population. Nevertheless, it is clear that performance of coronary revascularization procedures in the elderly can both prolong life and improve the quality of life beyond what can be achieved using alternative methods of treatment. Greater efforts directed toward detection of ischemic heart disease in the these patients and earlier, elective surgery could significantly reduce both the mortality and disability associated with CAD in the elderly.     

Determination of the molecular weight distribution of cellulose on calibrated gel columns

CMC samples obtained by gel filtration on a preparative scale were used to calibrate an agarose column. The relation between molecular weight and the peak elution volume for monodisperse samples were calculated as well as the relation between band broadening and the peak elution volume. In the calculations of the molecular weight distribution curves of the studied CMC samples, consideration was given to the variable band broadening by proper transformations of the experimental data, thus making it possible to obtain numerical solutions free from oscillations. The method admits a rapid determination of the molecular weight distribution of cellulose and related materials.     

Mass transport in a weakly stratified electrochemical cell

A study of natural convection in an electrochemical system with a Rayleigh number of the order 10¹⁰ is presented. Theoretical and experimental results for the unsteady behaviour of the concentration and velocity fields during electrolysis of an aqueous solution of a metal salt are given. The cell geometry is a vertical slot and the reaction kinetics is governed by a Butler-Volmer law. To reduce the effects of stratification, the flush mounted electrodes are located (symmetrically) in the middle parts of the vertical walls. It is demonstrated, both theoretically and experimentally, that a weak stratification develops after a short time, regardless of cell geometry, even in the central part of the cell. This stratification has a strong effect on the velocity field, which rapidly attains boundary layer character. Measured profiles of concentration and vertical velocity at and above the cathode are in good agreement with numerical predictions. For a constant cell voltage, numerical computations show that between the initial transient and the time when stronger stratification reaches the electrode area, the distribution of electric current is approximately steady.List of symbols a _i left hand side of equation system - b _i right hand side of equation system - c concentration (mol m^–3) - c dimensionless concentration - c _i concentration of species i' (mol m^–3) - c₀ initial cell concentration (300 mol m^–3) - c ₀ dimensionless initial cell concentration - c_wall concentration at electrode surface (mol m^–3) - dx increment solution vector in Newton's method - D _i diffusion coefficient of species i (m² s^–1) - D ₁ 0.38 × 10^–9 m² s^–1 - D ₂ 0.82 × 10^–9 m² s^–1 - D effective diffusion coefficient of the electrolyte (0.52 × 10^–9 m² s^–1) - _x unit vector in the vertical direction - _y unit vector in the horizontal direction - F Faraday's constant (96 487 A s mol^–1) - g acceleration of gravity (9.81 m s^–2) - i dummy referring to positive (i = 1) or negative (i = 2) ion - f current density (A m^–2) - f dimensionless current density - i₀ exchange current density (0.01 A m^–2) - J _ij Jacobian of system matrix - L length of electrode (0.03 m) - N _i transport flux density of ion i (mol m^–2 s^–1) - n unit normal vector - p pressure (Nm^–2) - p dimensionless pressure - R gas constant molar (8.31 J K^–1 mol^–1) - R _i residual of equation system - Ra Rayleigh number gL ³ c ₀/D (2.54 × 101¹⁰) - S _c Schmidt number /D (1730) - t time (s) - t dimensionless time - T temperature (293 K) - velocity vector (m s^–1) - dimensionless velocity vector - U characteristic velocity in the vertical direction - V _± potential of anode and cathode, respectively - x spatial coordinate in vertical direction (m) - x dimensionless spatial coordinate in vertical direction - x solution vector for c, and - y spatial coordinate in horizontal direction (m) - y dimensionless spatial coordinate in horizontal direction - z _i charge number of ion i Greek symbols symmetry factor of the electrode kinetics, 0.5 - volume expansion coefficient (1.24 × 10^–4 m³ mol^–1) - _s surface overpotential - constant in equation for the electric potential (–5.46) - _s diffusion layer thickness - scale of diffusion layer thickness - constant relating c/y to the Butler-Volmer law (0.00733) - kinematic viscosity (0.9 × 10^–6 m2 s^–1)     

Excluded volume effects in on‐ and off‐lattice reaction–diffusion models

Mathematical models are important tools to study the excluded volume effects on reaction–diffusion systems, which are known to play an important role inside living cells. Detailed microscopic simulations with off‐lattice Brownian dynamics become computationally expensive in crowded environments. In this study, the authors therefore investigate to which extent on‐lattice approximations, the so‐called cellular automata models, can be used to simulate reactions and diffusion in the presence of crowding molecules. They show that the diffusion is most severely slowed down in the off‐lattice model, since randomly distributed obstacles effectively exclude more volume than those ordered on an artificial grid. Crowded reaction rates can be both increased and decreased by the grid structure and it proves important to model the molecules with realistic sizes when excluded volume is taken into account. The grid artefacts increase with increasing crowder density and they conclude that the computationally more efficient on‐lattice simulations are accurate approximations only for low crowder densities.Inspec keywords: reaction‐diffusion systems, cellular biophysics, biodiffusion, Brownian motion, cellular automata, molecular biophysics, molecular configurationsOther keywords: crowder density, grid artefacts, grid structure, crowded reaction rates, artificial grid, randomly distributed obstacles, crowding molecules, cellular automata models, on‐lattice approximations, crowded environments, off‐lattice Brownian dynamics, detailed microscopic simulations, living cells, mathematical models, off‐lattice reaction‐diffusion models, on‐lattice reaction‐diffusion models, excluded volume effects