Differences in motility pattern between human buccal fibroblasts and periodontal and skin fibroblasts

Migration of fibroblasts from surrounding normal tissue into the wound bed is an important requirement for successful wound healing. This study investigated the motility pattern of buccal, periodontal and skin fibroblasts to determine whether differences in the wound healing efficiency at these sites can be explained by differences in the motile behavior of their respective fibroblast populations. The migratory characteristics were studied in a two-dimensional culture system. The migration of single cells was time-lapse video recorded at intervals of 15 min for a period of 6 h using a computer-assisted microscope work-station. For evaluation of cell morphology, cell contours were recognized semiautomatically and used for determination of cell area, cell spreading and number and length of processes. We found that the cellular displacement of the buccal fibroblasts was only approximately 50% of the cellular displacement of periodontal and skin fibroblasts. The decreased cellular displacement of the buccal fibroblasts was found to be due to both lower cellular speed and less persistence in direction. The buccal fibroblasts also displayed smaller areas and longer processes. The differences in cellular morphology and motility pattern amongst the three fibroblast types could not be explained by differences in secretion of extracellular matrix components and are therefore believed to reflect phenotypic differences amongst fibroblast subpopulations.     

Corneal autofluorescence in relation to permeability of the blood-aqueous barrier in diabetic patients with clinically significant macular edema and in an age-matched control group

PURPOSE: Corneal autofluorescence is related to advanced glycation end products formed by glucose that reaches the cornea via the aqueous humour. The aim of the study was to examine the influence on autofluorescence of changes in permeability of the blood aqueous barrier. METHODS: Corneal autofluorescence was measured in 50 diabetic patients with clinically significant macular edema and in 28 age-matched control subjects. Permeability of the blood aqueous barrier was assessed using the diffusion coefficient of fluorescein. RESULTS: Corneal autofluorescence was higher in diabetic subjects than in the control group, mean (SD) at an excitation wavelength of 458 nm was 41.2 ng f-eq/ml (11.7) in diabetic patients and 26.5 ng f-eq/ml (7.3) in the control group, p < 0.001. The mean permeability of the blood aqueous barrier, Kd(F), was 492.0.10(-6) min(-1 )in the diabetic patients and 484.2. 10(-6) min(-1)in the control group. There was no association between permeability of the blood aqueous barrier and corneal autofluorescence, p = 0.99 for the diabetic patients and p = 0.15 for the control group (458 nm). CONCLUSIONS: Corneal autofluorescence was unaffected by permeability of the blood aqueous barrier suggesting that formation of advanced glycation products is limited by other factors than the concentration of glucose in the aqueous humour, or that other factors unrelated to nonenzymatic glycation of stromal proteins are involved.     

(S)-2-Amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid,a potent and selective agonist at the GluR5 subtype of ionotropic glutamate receptors. Synthesis,modeling, and molecular pharmacology

We have previously described (RS)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid (4-AHCP) as a highly effective agonist at non-N-methyl-d-aspartate (non-NMDA) glutamate (Glu) receptors in vivo, which is more potent than (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) but inactive at NMDA receptors. However, 4-AHCP was found to be much weaker than AMPA as an inhibitor of [(3)H]AMPA binding and to have limited effect in a [(3)H]kainic acid binding assay using rat cortical membranes. To shed light on the mechanism(s) underlying this quite enigmatic pharmacological profile of 4-AHCP, we have now developed a synthesis of (S)-4-AHCP (6) and (R)-4-AHCP (7). At cloned metabotropic Glu receptors mGluR1alpha (group I), mGluR2 (group II), and mGluR4a (group III), neither 6 nor 7 showed significant agonist or antagonist effects. The stereoisomer 6, but not 7, activated cloned AMPA receptor subunits GluR1o, GluR3o, and GluR4o with EC(50) values in the range 4.5-15 microM and the coexpressed kainate-preferring subunits GluR6 + KA2 (EC(50) = 6.4 microM). Compound 6, but not 7, proved to be a very potent agonist (EC(50) = 0.13 microM) at the kainate-preferring GluR5 subunit, equipotent with (S)-2-amino-3-(5-tert-butyl-3-hydroxyisothiazol-4-yl)propionic acid [(S)-Thio-ATPA, 4] and almost 4 times more potent than (S)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionic acid [(S)-ATPA, 3]. Compound 6 thus represents a new structural class of GluR5 agonists. Molecular modeling and docking to a crystal structure of the extracellular binding domain of the AMPA subunit GluR2 has enabled identification of the probable active conformation and binding mode of 6. We are able to rationalize the observed selectivities by comparing the docking of 4 and 6 to subtype constructs, i.e., a crystal structure of the extracellular binding domain of GluR2 and a homology model of GluR5.     

Antibiotic prophylaxis in total hip arthroplasty: effects of antibiotic prophylaxis systemically and in bone cement on the revision rate of 22,170 primary hip replacements followed 0-14 years in the Norwegian Arthroplasty Register

We studied the effects of antibiotic prophylaxis, systemically and in bone cement, on the revision rate of cemented total hip arthroplasties (THAs) in data from the Norwegian Arthroplasty Register during the period 1987-2001. To have comparable groups, only THAs performed because of primary osteoarthritis, using cemented implants with documented good results, and high-viscosity cement were included. If systemic antibiotic prophylaxis had been given, only operations with cephalosporin or penicillin were selected. Cox-estimated survival relative revision risks (RR) are presented with adjustment for differences among groups in gender, age, cement brand, type of systemic antibiotic prophylaxis, type of prosthesis, type of operating room, and duration of the operation. Of 22,170 THAs studied, 696 THAs (3.1%) were revised, 440 (2.0%) for aseptic loosening and 102 (0.5%) for deep infection. We found the lowest risk of revision when the antibiotic prophylaxis was given both systemically and in the cement (15,676 THAs). Compared to this combined regime, patients who received antibiotic prophylaxis only systemically (5,960 THAs) had a 1.4 times higher revision rate with all reasons for revision as endpoint (p = 0.001), 1.3 times higher with aseptic loosening (p = 0.02) and 1.8 times higher with infection as the endpoint (p = 0.01). With the combined antibiotic regime, the results were better if antibiotics were given 4 times on the day of surgery (2,194 THAs), as compared to once (1,424 THAs) (p < 0.001), twice (2,680 THAs) (p < 0.001), or 3 times (5,522 THAs) (p = 0.02). Those who received systemic prophylaxis a single day 1, 2 or 3 times, as compared to 4 times, had a revision rate 1.8-3.5 times higher with all reasons for revision as endpoint, 1.5-3.1 times higher with aseptic loosening, and 2.7-6.8 times higher with infection. When we compared systemic prophylaxis 4 times in 1 day, no further improvement resulted in those given systemic prophylaxis for 2 days (1,928 THAs) or 3 days (717 THAs). In a subset of data including only the Charnley prosthesis, we obtained similar results. This observational study shows that the best results were recorded when antibiotic prophylaxis was given both systemically and in the bone cement, and if the systemic antibiotic was given 4 times on the day of surgery.     

The influence of genetic factors on physical functioning and exercise in second half of life

During the past decades, a number of studies of families and twins in particular have assessed the relative contribution of genetic and environmental factors to traits reflecting various aspects of physical functioning: maximal O2 uptake, muscular endurance, muscular strength, muscle cross sectional area, flexibility, and trainability. Although the estimate of the size of the genetic component differs between the various studies, they point towards a moderate to substantial genetic influence on these phenotypes. Most of the studies have used only young and healthy study subjects, although in recent years phenotypes of particular importance to the elderly and the oldest-old (e.g., activities-of-daily living abilities) have also been shown to have substantial genetic component. Furthermore, behavioural studies have also revealed a genetic contribution to the disposition to level of leisure time physical activity. At present, there is still a few association studies on specific genetic variants, and the results have either been inconsistent or failed to show an association with physical functioning. Therefore, the mechanisms through which the genetic influence is expressed, is still an enigma. Here, we summarise the evidence currently available for a genetic influence on physical functioning and disposition to leisure time physical activity with a focus on recent Danish twin data.     

Gadolinium-enhanced magnetic resonance imaging predicts response to methylprednisolone in multiple sclerosis

Oral high-dose methylprednisolone treatment is efficacious in acute optic neuritis (ON) and attacks of multiple sclerosis (MS). The responses to treatment in subgroups of patients participating in two randomized, controlled trials were assessed. Fifty-eight patients with ON and 51 patients with attacks of MS were treated with placebo or oral methylprednisolone (500 mg daily for five days with a 10-day tapering period). A gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) scan was obtained at baseline in 66 patients, and 29 patients underwent repeated MRI studies. Seventy-four patients underwent lumbar puncture before treatment. The odds ratio (OR) of improvement after methylprednisolone treatment (a one point change in the visual function system score of the Kurtzke Expanded Disability Status Scale (EDSS) in ON or in the EDSS score in attacks of MS) was higher in patients with enhancing lesions on baseline MRI (one week: OR 15, P = 0.02; eight weeks: OR 4.6, P = 0.02). Methylprednisolone treatment suppressed Gd-enhancement after one week (P < 0.001) and three weeks (P = 0.001). Cerebrospinal fluid measures of intrathecal inflammation correlated with the area of Gd-enhancement but did not correlate as closely with the treatment response as did the results of Gd-enhanced MRI. These findings suggest that the resolution of intrathecal inflammation as assessed by Gd-enhanced MRI is a major effect of oral high-dose methylprednisolone.