Quantitative genetic architecture of parasite-induced cataract in rainbow trout, Oncorhynchus mykiss.

Parasites impose costs on their hosts. The capability to fight against them is of great advantage, but may also be traded off with other traits. Although often observed at the phenotypic level, our knowledge of the extent to which such trade-offs are genetically determined is relatively poor. We tested this possibility with a farmed rainbow trout population suffering from natural Diplostomum spp. infections that cause cataracts in fish. We estimated the heritability of cataract severity and examined phenotypic and genetic correlations between cataract and a set of performance traits measured three times during a 3-year rearing period. A cataract score was used as an indicator of the host's capability to resist and/or tolerate the parasite. Our results showed moderate heritability for the cataract. Nevertheless, we found no evidence for a genetic or phenotypic trade-off between parasite resistance/tolerance and the measured performance traits. Initial body weight was not correlated with the cataract score. Phenotypic and genetic correlations of cataract severity with body mass and condition measured in the second and third year were strongly negative, indicating reduced growth and condition in fish with a high cataract score. The reduced body size and condition in cataract-bearing fish were probably reflected in the phenotypic association between a high cataract score and delayed maturity age in females. Put together, our study did not provide evidence of genetic or phenotypic trade-offs between Diplostomum resistance/tolerance and a number of performance traits. Therefore, selection for lessened Diplostomum-caused cataracts is unlikely to have a negative impact on the studied performance traits.

The effect of beta-glucan on the glycemic and insulin index.

OBJECTIVE: To determine the effects of oat products with increasing beta-glucan content on the glycemic (GI) and insulin indexes (II) of oat products, and to establish the effect of physical properties of beta-glucan on these physiological responses. DESIGN: Test group (n=10) randomly attended to three glucose tolerance tests and glycemic response tests for four oat bran products. SETTINGS: Functional Foods Forum and the Department of Food Chemistry, University of Turku, and the Department of Food Technology, University of Helsinki. SUBJECTS: One male and nine female volunteers were recruited from university students and staff, and all completed the study. INTERVENTIONS: GI and II of different products were calculated for each subject using the average of parallel glucose tolerance tests and the subsequent glycemic/insulinemic responses for each product. Average indexes for products were calculated according to the individual data. RESULTS: The glycemic responses to oat products with increasing amounts of beta-glucan had lower peak values than the reference glucose load. The amount of extractable beta-glucan had a high correlation between the glycemic and insulinemic response. CONCLUSION: In addition to the total amount of beta-glucan in oat products, the amount of extractable beta-glucan in oat products explains the magnitude of the decrease in glycemic responses to carbohydrate products.

Interleukin-8 immunoreactivity in the skin of healthy subjects and patients with palmoplantar pustulosis and psoriasis.

Previous studies have shown that neutrophil-activating peptide 1/interleukin-8 (IL-8) is present in psoriatic scales and to a lesser extent in normal human epidermis. A panel of monoclonal antibodies and polyclonal antisera raised against IL-8 was used to localize IL-8 with immunoperoxidase techniques in non-lesional and lesional skin of patients with psoriasis and palmo-plantar pustulosis (PPP), and in corresponding sites from healthy subjects. Intracellular IL-8 immunoreactivity was found in all epidermal cell layers in biopsies of healthy subjects and in non-lesional and lesional skin in both PPP and psoriasis. The most intense immunolabeling was regularly found in the basal cell layer. Intercellular epidermal IL-8 immunolabeling was regularly detected in lesional biopsies in PPP and psoriasis, but not in healthy subjects or non-lesional skin in PPP and psoriasis. No intercellular immunolabeling was detected after successful treatment of lesional skin. The majority of cells along the eccrine sweat glands, dermal mononuclear cell infiltrates, and endothelial cells were IL-8 immunoreactive in all biopsies studied. The present study suggests that IL-8, its precursor form, or, alternatively, a degradation product is present in normal human epidermis.

Membrane and cytosolic interleukin-1 alpha and beta in normal human epidermal cells: variability of epitope exposure in immunohistochemistry.

Previous studies have shown that interleukin-1 (IL-1) is present in normal human epidermis. However, with immunohistochemical techniques, epidermal IL-1 immunoreactivity has been found in only a limited number of epidermal cells. In the present study, we show that both IL-1 alpha and beta immunoreactivities can be detected in all epidermal cell layers, provided optimal processing of tissue samples is used. The use of isolated epidermal cells showed that keratinocytes at various stages of maturation display both membrane-associated and cytosolic IL-1 alpha and beta immunoreactivities. After protease treatment of tissue sections, the IL-1 beta immunoreactivity of the granular cell layer was enhanced by some antibodies used, whereas in the other cell layers it was clearly lower. We a) suggest a different cellular localization, processing, and/or binding to subcellular structures of IL-1 during the differentiation process of human keratinocytes and b) outline the technical difficulties in any immunohistologic approach to IL-1 status in diseased skin.

Salmeterol/fluticasone propionate (50/100 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in children with asthma.

The aim of this study was to compare the efficacy and safety in children of salmeterol (50 microg twice daily) plus fluticasone propionate (100 microg twice daily) when delivered together via a single Diskus inhaler (Seretide; combination therapy) or concurrently using two separate Diskus inhalers (concurrent therapy). In a multicenter, randomized, double-blind, double-dummy, parallel-group study, 257 children with reversible airways obstruction who remained symptomatic on inhaled corticosteroids (200-500 microg daily) alone were randomized to combination or concurrent therapy for 12 weeks. Efficacy was assessed by measuring daily peak expiratory flow (PEF), symptom scores, and rescue salbutamol use. In addition, lung function tests were performed at each clinic visit. Safety assessments included monitoring of adverse events and morning serum cortisol concentrations. The primary efficacy parameter (mean morning PEF) increased during treatment in both groups; adjusted mean changes were 33 and 28 L/min for the combination and concurrent therapies, respectively. The 90% confidence interval for the difference in mean morning PEF between treatment groups was within the +15 L/min criterion for clinical equivalence. Similarly, there were improvements in pulmonary function, symptom score, and rescue salbutamol use during treatment in both groups, with no significant differences between the combination and concurrent therapy groups for any of these secondary efficacy parameters. Both treatment regimens were well-tolerated and had comparable adverse event profiles. Mean morning serum cortisol levels increased similarly in both groups during the study. In conclusion, salmeterol and fluticasone propionate therapy given as a new combination product is as safe and effective in children with asthma as the same drugs given concurrently via separate inhalers.

Regulation of interleukin-1 beta production by glucocorticoids in human monocytes: the mechanism of action depends on the activation signal.

Glucocorticoids are known to downregulate interleukin-1 beta production in monocytic cells by two different mechanims: direct inhibition of the gene transcription and destabilization of the preformed interleukin-1 beta mRNA. Now we have examined the effect of the nature of the monocyte activating signal on these two inhibitory mechanims. When human monocytes were preincubated with dexamethasone for 1 hour and then stimulated either with bacterial lipopolysaccharide or phorbol myristate, it was found that dexamethasone inhibited the lipopolysaccharide-induced interleukin-1 beta protein production, but the phorbol myristate-induced production was increased 3-10 fold. This difference was also seen at the mRNA level. When dexamethasone was added to the cultures 3 hours after the stimulators, it clearly decreased the interleukin-1 beta mRNA levels regardless of the stimulator used (although the effect was clearly weaker on the PMA-induced mRNA). Thus these data suggest that the phorbol myristate-induced signal (prolonged protein kinase C activation?) cannot be inhibited by prior incubation with dexamethasone and it also protects the induced mRNA for the degradative action of dexamethasone.

Interleukin 1 immunoreactivity in sebaceous glands.

Interleukin 1 (IL-1) immunoreactivity in sebaceous glands was studied in paraffin sections of normal human skin. A panel of antibodies against IL-1 alpha and beta was tested using an immunoperoxidase labelling method. All the antibodies showed a similar specific labelling pattern: both glandular and ductal cells were immunoreactive for both IL-1 alpha and beta, provided optimal tissue fixation was used.

Signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone.

Previous studies have shown that IL-8 gene expression is enhanced by various stimuli, which induce different signal transduction pathways. A lipopolysaccharide (LPS)-induced pathway has been reported to be inhibited by glucocorticoids in monocytes. We have now examined the effect of dexamethasone on the LPS-induced and other signal transduction pathways leading to the production of IL-8 by human monocytes. Dexamethasone inhibited the production of IL-8 stimulated with a cyclic adenosine monophosphate analog or LPS. In contrast, dexamethasone had no significant effect on a phorbol ester (PMA)-stimulated IL-8 production. These results suggest that the signal transduction pathways leading to the production of IL-8 by human monocytes are differentially regulated by dexamethasone.

Immunohistochemical identification of interleukin I alpha and beta in human eccrine sweat-gland apparatus.

Bouin-fixed paraffin sections or acetone-fixed cryostat sections were labelled with the avidin-biotin complex (ABC) or peroxidase-antiperoxidase (PAP) method using three monoclonal antibodies (MAbs) and two polyclonal antisera to human recombinant interleukin I beta (IL-I beta) and three polyclonal antisera to human recombinant interleukin I alpha (IL-I alpha). In the secretory coil both IL-alpha and beta were detected in the clear, but not in the dark cells. Both luminal and basal cells of the coiled and straight ducts expressed IL-I alpha and beta, the IL-I labelling being more intense in the luminal cells. IL-I was not usually detected in the initial portion of the intraepidermal eccrine sweat duct, whereas intense labelling was seen in the upper part including through the stratum corneum. In skin biopsies of the palm, taken after exercise, there was only faint IL-I labelling of the secretory cells, whereas the luminal cells of the dermal ducts showed intense labelling for both IL-I alpha and beta. In the acrosyringium, exercise did not alter the pattern for IL-I alpha and beta, except that in the palm, some of the antibodies to IL-I beta produced a more intense immunolabelling of the acrosyringeal cells. This study identifies a distinct and similar distribution of the two forms of IL-I throughout the eccrine sweat-gland apparatus and indicates that part of the IL-I epidermal pool originates from the sweat.