10 research outputs found

    Modified VEGF-A with improved angiogenic properties

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    The present invention is directed to methods and compositions for making and using chimeric polypeptides that comprise a VEGFR-2 ligand. The chimeric molecules of the present invention retain VEGFR-2 binding activity and an enhanced angiogenic activity as compared to native VEGF-A

    Disturbed Keratinocyte Differentiation in Transgenic Mice and Organotypic Keratinocyte Cultures as a Result of Spermidine/Spermine N1-Acetyltransferase Overexpression

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    Overexpression of the rate-limiting enzyme in polyamine catabolism spermidine/spermine N1-acetyltransferase (SSAT) in transgenic (Tg) mouse leads to accumulation of putrescine in the skin and permanent hair loss at the age of 3 wk. The hair follicles of these mice are replaced by dermal cysts and epidermal utriculi. Increased putrescine production is also seen in hyperproliferative cutaneous disorders such as in psoriasis. These disorders are characterized by delayed onset of epidermal differentiation characterized as reduced expression of terminal differentiation markers such as cytokeratins 1/10, and filaggrin and persisting expression of basal cell cytokeratins 5/14 in the suprabasal layers. The use of these markers in immunohistological analysis of SSAT Tg skin clearly showed signs of disturbed differentiation. To exclude the possibility that changes in differentiation originated from underlying connective tissue, we introduced SSAT gene into an established rat epidermal cell line. Organotypic cultures derived from the transfected cells displayed similar changes in their differentiation pattern as keratinocytes in Tg skin. The role of accumulated putrescine in cutaneous changes of SSAT Tg mice was verified by an experiment in which putrescine level was reduced by systemic putrescine biosynthesis inhibition. The putrescine reduction was sufficient to alleviate the cutaneous changes to such an extent that distinct hair regrowth could be seen. These results suggest that the cutaneous changes of SSAT Tg animals are due to disorders of the keratinocyte differentiation. Moreover, they strengthen the view that the proper regulation of polyamine metabolism plays an important role in the keratinocyte maturation

    Mean (95% confidence interval) for selected HRV indices at rest before (pre), and after 21 weeks of training (post) in the endurance, strength, combined strength and endurance training, and control group.

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    <p>HR, heart rate; SDNN, standard deviation of NN intervals; HFP, high frequency power; LFP low frequency power; LFP/HFP, ratio between LFP and HFP; CI<sub>1–5</sub>, complexity index of multiscale entropy analysis over the scales of 1 to 5. Statistically significant changes were not observed.</p

    Heart rate and heart rate dynamics during steady state exercise.

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    <p>Heart rate (HR, A), standard deviation of NN intervals (SDNN, B), high frequency power (HFP, C) and HR complexity index for the scales 1 to 2 (CI<sub>1–2</sub>, D) measured at baseline (0) and after 10 and 21 weeks of endurance (E), strength (S) or combined strength and endurance training (SE) and in the control group (C). *significant change (P<0.05) compared to the baseline, **P<0.01, ***P<0.001.</p

    Individual and the mean changes in the HR complexity index.

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    <p>The index for the scales 1 to 2 (CI<sub>1–2</sub>) was measured during steady state exercise at baseline (pre) and after 21 weeks in the endurance training (E), combined strength and endurance training (SE), strength training (S) and the control (C) group. **significant change (P<0.01) compared to the baseline.</p

    Heart rate dynamics after combined strength and endurance training in middle-aged women: Heterogeneity of responses.

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    The loss of complexity in physiological systems may be a dynamical biomarker of aging and disease. In this study the effects of combined strength and endurance training compared with those of endurance training or strength training alone on heart rate (HR) complexity and traditional HR variability indices were examined in middle-aged women. 90 previously untrained female volunteers between the age of 40 and 65 years completed a 21 week progressive training period of either strength training, endurance training or their combination, or served as controls. Continuous HR time series were obtained during supine rest and submaximal steady state exercise. The complexity of HR dynamics was assessed using multiscale entropy analysis. In addition, standard time and frequency domain measures were also computed. Endurance training led to increases in HR complexity and selected time and frequency domain measures of HR variability (P<0.01) when measured during exercise. Combined strength and endurance training or strength training alone did not produce significant changes in HR dynamics. Inter-subject heterogeneity of responses was particularly noticeable in the combined training group. At supine rest, no training-induced changes in HR parameters were observed in any of the groups. The present findings emphasize the potential utility of endurance training in increasing the complex variability of HR in middle-aged women. Further studies are needed to explore the combined endurance and strength training adaptations and possible gender and age related factors, as well as other mechanisms, that may mediate the effects of different training regimens on HR dynamics.peerReviewe
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