Probing insulin's secondary structure after entrapment into alginate/chitosan nanoparticles.

The aim of the present study was to probe the structural integrity of insulin after being entrapped into chitosan/alginate nanoparticles produced by ionotropic polyelectrolyte pre-gelation. By manipulating the alginate:chitosan mass ratio and the pH during nanoparticle production, desired nanoparticles with a mean size of 850 (+/-88)nm and insulin association efficiency of 81 (+/-2)% were obtained. Insulin secondary structure was assessed by Fourier transform infrared (FTIR) and circular dichroism (CD) after entrapment into nanoparticles and after release from the particles under gastrointestinal simulated conditions. FTIR second-derivative spectra and area-overlap compared to an insulin standard confirmed that no significant conformational changes of insulin occurred in terms of alpha-helix and beta-sheet content. Far-UV-CD spectra corroborated the preservation of insulin structure during the nanoparticle production procedure. The presented nanoparticulate system is a promising carrier for insulin oral delivery since it preserves insulin structure and therefore also, potentially, its bioactivity.     

Influence of mattress characteristics on house dust mite allergen concentration

BACKGROUND: Exposure to a high level of house dust mite allergens (HDMAs) is considered as a risk factor for HDM sensitization and development of asthma in genetically disposed people. Mattresses are one of the most important sources of HDMA in people's living environment. OBJECTIVE: The aim of this study was to evaluate the association between mattress characteristics and HDMA concentrations on mattresses. METHODS: Dust samples of mattress surfaces were taken to evaluate the level of Der p 1 allergen. All participants filled in a questionnaire about the type of mattress, the type of covering (upper layer) of the mattress, dwelling characteristics and cleaning habits. Humidity and temperature of the bedroom were measured at the time of dust sampling. RESULTS: One hundred and sixty-eight questionnaires were filled in. Synthetic upper layer of the mattress was associated with a higher level of Der p 1 compared with cotton upper layer (2.6 vs. 0.8 microg/g Der p 1). Moreover, higher relative humidity (RH) was associated with significant higher concentrations and density of Der p 1. CONCLUSIONS: Two factors were associated with lower levels of Der p 1 found on mattresses, namely: a cotton upper layer of the mattress compared with a layer of synthetic material and lower RH at the time of sampling. As far as we know, the association between type of upper layer and concentration of Der p 1 has not been described before and could lead to the formulation of practical advices in order to reduce HDMA concentrations on mattresses.     

Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon.

1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus

In this report, we examine the functional significance of the molecular microheterogeneity of alpha-fetoprotein (AFP). In doing so, we have taken the direct approach of purifying the naturally occurring isomeric forms of fetal-derived AFP using a preparative anion exchange column linked to an automated fast protein liquid chromatography (FPLC) system followed by parallel testing of each isolated molecular variant for in vitro immunoregulatory activity. The data obtained demonstrate the presence of seven distinct variants of AFP as defined by their retention volumes on FPLC elution profiles, by their pIs on analytical IEF gels, and by Western blot analysis. Molecular mass determination by SDS-PAGE showed each isomer to be equivalent in size to 69,000-dalton native unfractionated AFP molecules. All the immunosuppressive activity of AFP was localized to a single variant representing only 6% of the total composition of native AFP. The immunoregulating isomer termed AFP-1 was the least acidic of the seven isolated variants with a pI of 5.1 and displayed a sialic acid content of 1 mol/mol of protein. The inhibitory activity of AFP-1 could be readily measured on T cell-dependent antibody synthesis, Con A-induced stimulation of Lyt-1+23- thymocyte DNA synthesis, and lymphokine-activated NK cell activity. All other isomers were without effect in these test systems. The immunosuppressive AFP-1 isomer also displayed the strongest growth-promoting influence on cultured bone marrow lymphocytes. There was no correlation between functional activity and degree of expression of sialic acid residues on the AFP molecules. These findings demonstrate that the immunoregulating function of AFP is confined to a distinct and relatively small subpopulation of native AFP molecules and should therefore contribute to the resolution of outstanding questions regarding the structure/function relationship of this onco-fetal glycoprotein.     

Iowa's High School High Tech Goes to College Program: Preparing Students with Mild Disabilities for Careers in Technology

This paper describes an innovative approach to preparing high school students with mild disabilities for challenging careers in high tech industries, called High School High Tech (HSHT). Iowa's HSHT Goes to College program has three central elements, each of which is discussed in this paper: High School Preparation—assisting students in identifying a suitable high tech career goal; Higher Education Preparation and Supports—assisting students in selecting college/training programs that match their career goal, and in successfully completing their postsecondary programs; Workforce Entry Assistance—linking students with employers and launching their high tech careers. The paper concludes with a presentation of outcomes to date and recommendations for program enhancements. The information presented here is intended to assist education and rehabilitation professionals interested in establishing similar efforts across the nation.     

Five‐Year Follow‐up After Sacral Neuromodulation: Single Center Experience

Objective. We studied long‐term clinical efficacy of sacral neuromodulation (SNM) therapy in patients with refractory urgency incontinence (UI), urgency/frequency (UF) and voiding difficulty (VD), together with urodynamic data at baseline and six   months postimplant. Materials and Methods. Twenty‐two patients were implanted with a neurostimulator after a positive response to a percutaneous nerve evaluation test defined as a greater than 50% improvement in symptoms. Results. At five‐year follow‐up, the number of incontinent episodes and pad usage per day decreased significantly in 10 out of 15 UI patients. Two of five UF patients were successfully treated with SNM; the number of daily voids for all UF patients decreased from 25 to 19 and average voided volume increased from 98 to 212 mL. One of the two VD patients was able to void to completion. Mean first sensation of filling at the six‐month urodynamic investigation for the UI and UF patients increased from 78 to 241 mL and 141 to 232 mL, respectively, and the maximum bladder capacity increased from 292 to 352 mL and 223 to 318 mL, respectively. Five of 22 patients underwent device explant and one patient still has an inactive stimulator implanted. Conclusion. SNM is an effective treatment modality that offers sustained clinical benefit in the majority of patients with refractory UI, UF, and VD that do not respond to other, more conservative therapies.