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R Gniadecki

Publications and source records attributed to R Gniadecki.

45 records · Page 3Linked to original sources
PubMed1994

Inhibition of glucocorticoid-induced epidermal and dermal atrophy with KH 1060--a potent 20-epi analogue of 1,25-dihydroxyvitamin D3.

1. The possibility of preventing and treating glucocorticoid-induced skin atrophy with KH 1060 (the potent 20-epi-22-oxa-24a-homo-26,27-dimethyl analogue of 1,25-dihydroxyvitamin D3) was examined in a hairless mouse model. 2. KH 1060 (0.625-6.25 pmol cm-2 of skin) applied topically for 7 days together with 2.5 nmol cm-2 betamethasone-17-valerate prevented, in a concentration-dependent manner, the development of epidermal, dermal and total skin thinning caused by the glucocorticoid. The effect of KH 1060 on the epidermis occurred at a lower dose than on the dermis, and at doses above 1.25 pmol cm-2 KH 1060 caused epidermal hyperplasia. 3. KH 1060 (2.5 pmol cm-2) prevented the development of betamethasone-associated skin atrophy in mice during a long-term (4 weeks) treatment, and reversed established cutaneous glucocorticoid atrophy. 4. Radiolabelling experiments with [35S]-sulphate and [3H]-proline in vivo revealed that KH 1060 stimulated the synthesis of sulphated glycosaminoglycans and hydroxyproline in skin treated with betamethasone. 5. These findings strongly suggest that KH 1060 prevents and reverses glucocorticoid-induced skin atrophy by stimulating epidermal proliferation and enhancing synthesis of extracellular matrix in the dermis.

Animals↗
PubMed1994

Enhancement of the granulation tissue formation in hairless mice by a potent vitamin D receptor agonist--KH 1060.

KH 1060 is a 20-epi analogue of 1,25-dihydroxyvitamin D3 and a potent agonist of the vitamin D receptor. Our recent finding that it stimulates glycosaminoglycan synthesis and transforming growth factor-beta 1 (TGF-beta 1) expression in normal skin provided a rationale for investigating its influence on the process of wound healing. Normal and betamethasone-impaired granulation tissue formation was studied in a polytetrafluoroethylene dead space model in hairless mice. The application of KH 1060 increased the indexes of fibroplasia and cellularity ([3H]thymidine incorporation and DNA concentration) of the betamethasone-impaired granulation tissue. Collagen production and deposition, measured as hydroxyproline synthesis and concentration in the granulation tissue, were also increased. The effect of KH 1060 on normal connective tissue repair was less pronounced; DNA and hydroxyproline concentrations in granulation tissue were unchanged. KH 1060 strongly stimulated the expression of TGF-beta 1 in betamethasone-impaired granulation tissue. Thus, it effectively reversed the deleterious effect of betamethasone on granulation tissue. The hyperproliferative response to this vitamin D analogue might be related to the direct stimulation of the vitamin D receptors in the granulation tissue, while the increased collagen synthesis and deposition was probably caused indirectly, via stimulation of TGF-beta 1.

Animals↗
PubMed1994

A vitamin D analogue KH 1060 activates the protein kinase C-c-fos signalling pathway to stimulate epidermal proliferation in murine skin.

The cellular signalling pathways of a potent 20-epi-22-oxa vitamin D3 analogue (KH 1060) were examined in vivo in a hairless mouse model. Seventy two hours after a single topical application of KH 1060 a thickening of the epidermis (from 24.8 +/- 1.2 microns at 0.01 pmol/cm2 KH 1060 to 124.2 +/- 6 microns at 5 pmol/cm2 KH 1060, P < 0.001) was elicited due to epidermal hyperproliferation. This effect could be blocked by topical 2.5 mumol/cm2 sphingosine, an inhibitor of protein kinase C. Two hours after topical application of 2.5 pmol/cm2 KH 1060 a translocation of protein kinase C activity from cytoplasm to the membrane fractions was observed. Moreover, using a reverse-transcription polymerase chain reaction technique, a transient upregulation of c-fos gene expression was seen 2 hours after topical treatment with KH 1060. The expression of c-fos was dependent on protein kinase C activation, since after pretreatment with the protein kinase C blocker sphingosine, c-fos messenger RNA was not detected. These findings strongly suggest that KH 1060 stimulates epidermal growth through activation of the protein kinase C-c-fos signalling axis in vivo.

Animals↗
PubMed1994

Skin mechanical properties present adaptation to man's upright position. In vivo studies of young and aged individuals.

In tall animals dependent tissues are stiffer to prevent oedema formation in the upright posture, but whether the same adaptation is operating in man is not known. Skin elasticity and distensibility were measured in vivo in 18 young and 15 aged individuals in the morning before getting up (baseline) and 12 h later. In young individuals skin was stiffer (less distensible) and less elastic in the acral parts of the extremities (ankle, forearm). In the evening distensibility and elasticity of the skin increased. In aged individuals skin was less elastic and no diurnal variability in elasticity and distensibility was detected. We propose that these unique mechanical properties of the acral skin reflect a major role of the integument in the protection against the gravitational stress and the development of the postural oedema. Altered skin mechanical properties may contribute to the poor compensation for gravitational stress in elderly.

Adaptation, Physiological↗
PubMed1994

Microvascular reactions to postural changes in patients with sickle cell anaemia.

Normal microcirculation of the lower extremity is characterized by the venoarteriolar vasoconstriction reflex and the disappearance of vasomotion in the dependent position. Patients with sickle cell disease are prone to develop ischemic leg ulcers at an early age. Dysfunction of the microcirculation might promote the development of leg ulcers in patients with sickle cell disease. Using laser Doppler equipment we have studied the changes of blood flux in the skin overlying the medial malleolus after leg lowering. Contrary to the normal physiological situation seen in our control persons, the venoarteriolar reflex was abolished and vasomotion preserved in the dependent position of the leg in both patients. We conclude that this may represent an adaptation to the dependent position in sickle cell disease.

Adolescent↗
PubMed1994

Impairment of the postural venoarteriolar reflex in aged individuals.

The venoarteriolar vasoconstriction reflex plays a major role in the prevention of leg oedema in the upright position in man. We studied the venoarteriolar vasoconstriction reflex with laser Doppler flowmetry in young (21 subjects, age 17-27) and very old (20 subjects, age 75-100) healthy volunteers. In the group of young volunteers, after lowering of the lower extremity 50 cm below the heart level, cutaneous blood flux decreased to 16.6% of the baseline, whereas in the group of old persons the venoarteriolar reflex was impaired and the flux decreased only to 29.2%. The difference between the two groups was statistically significant (p < 0.001). These results may explain the increased prevalence of postural oedema in old people.

Adolescent↗
PubMed1992

Alterations of skin microcirculatory rhythmic oscillations in different positions of the lower extremity.

Microcirculatory vasomotion is considered to be an important mechanism promoting and facilitating the transfer of blood cells through skin capillaries. Since skin vulnerability of the leg is closely associated with gravitational factors and skin micro-circulation, we investigated by a laser Doppler apparatus influence of postural changes on skin blood flow oscillations in lower limbs of healthy volunteers. Our data show a marked decrease in microcirculatory oscillation amplitudes at a frequency 7.6 (+/- 0.6) min-1 after lowering the leg. This could be reversed by the application of compressive bandage. Our study points toward a potentially important mechanism of microcirculatory impairment during orthostasis.

Adult↗