The permeability of large molecular weight solutes following particle delivery to air-interfaced cells that model the respiratory mucosa.

The transepithelial transport rates of compounds after deposition as aerosolised particles onto respiratory cell layers and allowing dissolution in the cell surface secretions has not been reported in a comprehensive manner to date. Here, the twin-stage impinger (TSI) was used to deposit potentially respirable particles (aerodynamically <6.4 microm) of varying molecular weight dextrans labelled with fluorescein isothiocyanate (FITC-dex) onto Calu-3 cells, a model of the bronchial epithelium. The TSI functioned as a particle size segregator, with >96% of the deposited particles being geometrically <6.4 microm (as measured by microscopy) and the particles being deposited discretely with a uniform distribution. Cell layers tolerated particle deposition at an air flow of 60 L/min. A small reduction in transepithelial electrical resistance (TER) of <10% occurred initially, but the original TER was recovered within 10 min and there was no significant effect on apparent permeability (P(app)) of FITC-dex 4 over 4 h. Interleukin 8 (IL-8) secretion in the apical and basolateral directions over 24 h was not increased by exposure to the TSI and particle deposition. The rate of FITC-dex 4 (4 kDa) transport across the cell layer after deposition and dissolution of the particles in the cell surface secretions was approximately 20-fold higher (P<0.05) than if applied as a solution. The volume of cell surface secretions was estimated by tracer dilution (3.44+/-1.90 microl, mean+/-SEM) and this value was used to calculate the P(app) of compound once deposited as a particle. The Papp value was found to be similar to that obtained when the compound was applied in solution (P<0.05). Thus, the increased transport rate was attributable to the differences in donor chamber solute concentration rather than any change in the permeability of the cell layer itself. Following particle deposition, transport of FITC-dex with molecular weights between 4 and 70 kDa correlated well (r(2)=0.918) with reported in vivo canine pulmonary clearance after intratracheal instillation of dextrans of similar molecular weight. The use of the TSI and the Calu-3 cell line for the assessment of compound dissolution and transport rates after particle deposition may allow more realistic analyses to be made with respect to the in vivo situation.

Pulmonary antioxidants exert differential protective effects against urban and industrial particulate matter.

This investigation focuses on the application of an in vitro assay in elucidating the role of lung lining fluid antioxidants in the protection against inhaled particles, and to compare the toxicities of different airborne particulate matter (PM), PM10, collections from South Wales, UK. PM collections from both urban and industrial sites caused 50% oxidative degradation of DNA in vitro at concentrations as low as 12.9 +/- 2.1 microg ml(-1) and 4.9 0.9 mg ml-1 respectively. The primary source of this bioreactivity was found to be the soluble fraction of both particle collections. The coarser PM(10-2.5) fraction also showed greater oxidative bioreactivity than the PM(2.5-0.1) in both cases. When repeated in the presence of a low molecular weight fraction of fresh pulmonary lavage fluid, as well as in artificial lung lining fluid (200 microM urate, glutathione and ascorbate), the DNA damage was significantly reduced in all cases (P < 0.05). The antioxidants exerted a greater effect on the industrial samples than on the urban samples, and on the PM(10-2.5) fractions than on the PM(2.5-0.1) fractions, supporting the previous findings that respirable PM and urban samples contain fewer free radical sources than inhalable PM and industrial samples.

Collaborative working with specific speech & language disorder in mainstream education.

Children with specific speech and language disorders are part of a special needs population whose educational and therapeutic needs have been provided for in a variety of settings over the last fifty years. Changes have been implemented in response to a range of legislation. This has also had implications for the delivery and type of provision of the children's education and therapy. The National Health Service and local education authorities (LEAs) have had to respond to legislation and continue to provide for the full range of specific speech and language disorders. This paper will outline how therapeutic input has had to adapt to the changing educational context. Changes in delivery have necessitated a redefinement of roles and adjustments in collaborative working.

Geographic distance and contact between middle-aged children and their parents: the effects of social class over 20 years.

This research derives and tests hypotheses from two alternative conceptual models: the modified extended family model, and the changing family constraints model, which takes into account recent changes in work and family life. The hypotheses address social class differences in geographic distance and contact frequency between middle-aged children and their parents over time. Simultaneous probit models are used to analyze distance and contact as jointly determined outcomes with data from the USC Longitudinal Study of Generations and Mental Health. Results from these analyses indicate that children's 1971 educational aspirations and social class positions predict 1991 distance and contact between generations. Parents who have lower 1991 incomes, however, live farther from children and talk with them on the telephone less frequently than higher-income parents. Thus, the effects of early social class position support the modified extended family model, whereas the effects of current social class position support the changing family constraints model.

Fish oil increases peripheral capillary blood cell velocity in humans.

Fish oils containing n-3 fatty acids have been shown in humans to decrease platelet aggregation in vitro, lower plasma triglycerides, and to increase bleeding time. The in vivo effects of fish oils on microcirculatory blood flow in humans has not been studied to date. Twenty-one male subjects were randomly assigned to either olive oil (n = 10) or fish oil (n = 11) supplemented groups to determine the effects of these oils on capillary blood flow velocity (CBV) in the nailfold area. The subjects were given the oils for three weeks (1.5 g oil/10 kg b.wt./day) in a single blind study design. In addition to CBV plasma lipid profiles, blood viscosity, blood pressure and platelet and erythrocyte fatty acids were also determined prior to and after the dietary intervention. Fish oil supplementation significantly increased CBV, by 1.75-fold (0.144 +/- 0.069 to 0.253 +/- 0.147 mm/s). The olive oil group remained unchanged. Increased levels of n-3 fatty acids were noted in platelets and erythrocytes of the fish compared to olive oil-supplemented groups. Blood viscosity was unaltered in both groups, however, blood pressure in the olive oil supplemented group was significantly decreased. Plasma triglycerides were significantly decreased in the fish oil supplemented group. These observations suggest that increases in CBV after fish oil supplementation are due to changes in vascular tone and not to alterations in blood pressure or blood viscosity.