Bibliothek

Notizen: Elevated oestradiol concentrations during the follicular phase stimulate a surge in gonadotropin-releasing hormone (GnRH) and luteinising hormone (LH) concentrations, which leads to ovulation. Progesterone can block the oestradiol-induced GnRH/LH surge, but the mechanism that is involved is unclear. We examined the effect of progesterone on oestradiol-induced activation of cells within the ovine hypothalamus/preoptic area (POA) to determine: (i) in which regions progesterone acts to block the GnRH/LH surge and (ii) whether progesterone directly or indirectly prevents activation of oestradiol-responsive cells. Cellular activation was assessed by measuring the number of cells that expressed Fos (an immediate early gene). Exposure to increased oestradiol concentrations in the absence of progesterone (which normally stimulates a LH surge) did not cause any region-specific changes in hypothalamic Fos expression during the activation stage of the LH surge-induction process (Experiment 1). The same treatment significantly increased cellular activation within the POA, lateral septum (LS), and arcuate nucleus at the time of surge onset (Experiment 2). Concurrent exposure to increased oestradiol and progesterone concentrations during the activation stage of the surge-induction process (which normally blocks the LH surge) was associated with significantly reduced cellular activation within the ventromedial hypothalamus and anterior hypothalamic area, relative to the positive controls (oestradiol increment alone) and arcuate nucleus relative to the negative controls (no increment in oestradiol) during the activation stage (Experiment 1). At the time of surge onset (Experiment 2), exposure to progesterone during the activation period prevented the oestradiol-induced increase in cellular activation that occurred in the POA, LS and arcuate nucleus of the positive controls. These results demonstrated that oestradiol and progesterone induced differential region- and time-specific effects on cellular activation within the regions of the ovine brain that generate the preovulatory GnRH/LH surge. Moreover, the lack of cellular activation within the POA, LS and arcuate nucleus at the time of surge onset in animals exposed to progesterone during the activation stage is consistent with the hypothesis that progesterone can block the preovulatory surge by direct inhibition of oestradiol-induced cellular activation in these areas.

Notizen: We demonstrated that an epitope from the recombinant protective antigen (rPA) of Bacillus anthracis was presented by mature major histocompatibility complex class II (MHC-II) molecules, whereas an epitope from the recombinant virulent (rV) antigen of Yersinia pestis was presented by newly synthesized MHC-II. We addressed which endosomal compartments were involved in the antigen processing of each epitope. Bone-marrow-derived macrophages were subjected to subcellular fractionation; fractions were analysed for the expression of endosomal markers and used as a source of enzyme activity for the processing of rPA and rV antigens. The rPA epitope was productively processed by dense lysosomal fractions and light membrane fractions expressing early endosomal markers Rab5 and early endosomal antigen-1 as well as markers of antigen-presenting compartments (MHC-II, DM, DO and Ii chain). In contrast, the rV epitope was productively processed only by dense fractions with lysosomal activity. No productive antigen-processing activity was associated with fractions of intermediate density expressing Rab7 and Rab9, characteristic of late endosomes. The data suggest that endosomal compartments expressing Rab5 guanosine triphosphatase can productively process protein antigens for presentation by mature MHC class II molecules.

Notizen: Abstract –  We examine patterns in fish species assemblages in the Toxaway and Horsepasture rivers, two high elevation streams in North Carolina, USA. This region is noted for extreme topographical relief, high cumulative annual rainfall and many rare and endemic plants and animals. The study area encompasses a portion of the Blue Ridge Escarpment and the associated Brevard Fault Zone. We hypothesise that major waterfalls and cascade complexes have acted to limit invasion and colonisation by fishes from downstream. This hypothesis is supported by longitudinal fish assemblage patterns in our study streams. Fish species richness in Toxaway River increased from 4 to 23 between Lake Toxaway and Lake Jocassee, a distance of 10 river km. We found similar discontinuities in neighbouring Horsepasture River and Bearwallow Creek. We found no instances of species replacement along this elevation gradient, and the trend in increased diversity downstream showed discontinuities coincident with sharp elevation breaks. With regard to theories posited to explain community formation in headwater stream fish communities (especially in those characterised by high topographical relief), we suggest coloniser ‘access’ may be more important than other factors including competitive interactions.

Notizen: The effects were investigated of fruit maturity and duration of wetness on infection of apple fruits by Venturia inaequalis, and subsequent scab development. Incubation rate (inverse of median incubation period) increased linearly with increasing temperature (5–20°C) on detached 5-week-old fruits of cv. Royal Gala. Fruits were highly susceptible in the early stages of development, but became increasingly resistant as they matured. Inoculation of attached 12-week-old and detached near-mature fruits did not result in any lesions, while inoculation of attached 4-, 5-, 7- and 9-week-old fruits resulted in various levels of infection. Fruits of cv. Mondial Gala were more susceptible than those of cv. Cox's Orange Pippin. On cv. Mondial Gala, a wet period of 9 h resulted in ≈ 90% infection of 4-week-old fruits, but only 9% infection of 9-week-old fruits. Numbers of scab lesions on an apple generally followed a Neyman type A rather than a Poisson distribution, indicating a certain degree of aggregation of lesions on a fruit. A two-parameter generalization of the Poisson model described the observed incidence–density relationship well. A longer duration of wetness was required to result in a similar level of scab infection on old fruits to that on young fruits. On cv. Mondial Gala, wet periods of 9 and 32 h were required for ≈ 90% incidence of fruit scab on 4- and 7-week-old fruits, respectively. A mathematical model was developed to relate the incidence of fruit scab to duration of wetness and fruit maturity. The potential use of these results in practical disease management is discussed.

Notizen: Background  Atopic dermatitis (AD) is a common inflammatory allergic disease of children. The primary anti-inflammatory therapy is topical steroids. An effective treatment without the topical and systemic adverse effects of corticosteroids would be useful. Topical formulations of sodium cromoglicate have been researched in the past, but without consistent results. We report a trial of a new aqueous skin lotion of sodium cromoglicate (Altoderm) in children with AD.Objectives  To compare the efficacy, safety and acceptability of Altoderm lotion with a placebo control in the treatment of AD in children.Methods  A double-blind, controlled study in which children aged 2–12 years with AD were randomized to 12 weeks of treatment with a lotion containing 4% sodium cromoglicate (Altoderm) or the lotion base. To be included subjects had to have a SCORAD score of ≥ 25 and ≤ 60 at both of two clinic visits 14 days apart. Subjects continued using existing treatment which included emollients and topical steroids. The primary outcome was the change in the SCORAD score. The two groups were compared for the change in the SCORAD score from the second baseline visit to the visit after 12 weeks of treatment using an analysis of variance. Secondary outcome measures included parents' assessment of symptoms, usage of topical steroids recorded on daily diary cards, and final opinions of treatment by parent and clinician. Parents were asked about adverse effects at each clinic visit and the responses recorded.Results  Fifty-eight children were randomized to Altoderm and 56 to placebo and all were included in the intention-to-treat analysis. The mean ± SD SCORAD scores at baseline were 41·0 ± 9·0 (Altoderm) and 40·4 ± 8·73 (placebo). These scores were reduced after 12 weeks by 13·2 (36%) with Altoderm and by 7·6 (20%) with placebo. The difference of 5·6 (95% confidence interval 1·0–10·3) is statistically significant (P = 0·018). Diary card symptoms improved with both treatments but the improvement was greater in the Altoderm-treated patients. Topical steroid usage was reduced in both groups and was larger in the Altoderm-treated patients. The differences were statistically significant for the mean of all symptoms, the overall skin condition and use of topical steroids. Those for itching and sleep loss were not. Treatment-related adverse events were reported in 11 subjects (Altoderm seven, placebo four). Most of these referred to irritation, redness and burning at the site of application. There were four reports of erythema and pruritus (Altoderm three, placebo one), and three reports of application site burning (Altoderm two, placebo one). None was reported as severe or very severe.Conclusions  These results show a clinically useful benefit of this sodium cromoglicate lotion in children with moderately severe AD.