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Biomedical subjects

P Autio

Publications and source records attributed to P Autio.

17 recordsLinked to original sources
PubMed1996

Effects of an inhaled steroid (budesonide) on skin collagen synthesis of asthma patients in vivo.

Skin atrophy has been observed after prolonged use of inhaled corticosteroids. We therefore studied the effect of inhaled budesonide and nedocromil in patients with asthma on concentrations of procollagen propeptides in suction blister fluid reflecting skin collagen synthesis in vivo. Both types I and III procollagen propeptide concentrations decreased significantly after 6 wk of either 1,600 micro g/day (n=10) or 400 micro g/day (n=9) of inhaled budesonide but not in control subjects using inhaled nedocromil 16 mg/day (n=9). The reduction in mean propeptide concentrations ranged from 39 to 63%; the effects of the two budesonide doses did not differ significantly. Thus, even a low dose of inhaled corticosteroid represses skin collagen synthesis within a relatively short period.

Administration, Inhalation↗
PubMed1995

Influence of aging, localization, glucocorticoids and isotretinoin on matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) in suction blister fluids.

The expression of two matrix metalloproteases (MMPs), 72 kDa gelatinase (MMP-2) and 92 kDa gelatinase (MMP-9), was studied in suction blister fluids and serum using a zymographic method. Both of the enzymes were detectable in blister fluid and serum, but their expression varied. The MMP-2 levels in serum were only about half of the levels in blister fluid, while the level of MMP-9 was about the same in both serum and blister fluid. The overall level of MMP-2 in serum was much lower than the level of MMP-9 which was possibly derived from inflammatory cells. In subjects aged from 20 to 86 years, no marked changes were seen in the serum or blister fluid gelatinases. Interestingly, body site affected the level of MMP-9. The lowest level was recorded in fluid from blisters on the lower leg, in which the level was only about 19% of the level in fluid from blisters on the abdomen. The levels of MMP-2 and MMP-9 were not decreased by pharmacological doses of systemic prednisone or isotretinoin, which indicates that systemic glucocorticoid or retinoid treatment does not affect the basal levels of MMP-2 and MMP-9.

Adult↗
PubMed1995

Chronic UVB irradiation induces superoxide dismutase activity in human epidermis in vivo.

In order to study the effects of repeated UVB exposures on the epidermal antioxidant defence system, we obtained epidermis samples from male volunteers who were exposed to chronic UVB irradiation. Chronic UVB irradiation was shown to be accompanied by induction of epidermal superoxide dismutase (SOD) activity in vivo, while the activities of the other antioxidant enzymes were not significantly changed. The repeated exposure of the epidermis to UVB irradiation was not accompanied by accumulation of products of lipid peroxidation reactions. As superoxide dismutase is of major importance in scavenging the reactive oxygen species, the UVB-induced changes in SOD activity might provide the epidermis a way of defending itself against the effects of chronic UVB irradiation.

Adolescent↗
PubMed1995

Occupational respiratory and skin sensitization caused by polyfunctional aziridine hardener.

Polyfunctional aziridine (PFA) is increasingly used as a water-based crosslinker in two-component paints, paint primers, lacquers, topcoats and other protective coatings. The crosslinker is made by reacting multifunctional acrylic monomer with a highly reactive aziridine compound. Respiratory allergy or hypersensitivity from PFA has not been reported previously. During 1978-1991 we came across nine cases with hypersensitivity from PFA: two had allergic contact dermatitis (ACD), four had occupational asthma and three had both of them. Five of the patients were parquet layers, two were fibreboard painters, one was a spray painter and one was a salesman of PFA products. ACD was diagnosed by positive allergic patch test reactions with PFA in a dilution series in petrolatum: 0.32%-0.5% gave a 2(+)-3+ allergic reaction in the five cases with ACD but 0.1% gave only a weak reaction in one case, whereas the methacrylate patch test series was negative. The diagnosis of seven cases of occupational asthma due to PFA hardener was based on symptoms related to exposure to PFA hardener at work, and on positive provocation tests with PFA hardener. One had an immediate type reaction, one a had a dual reaction, and the others had late reactions. The positive reactions with the PFA hardener and the negative reactions with the acrylate compounds indicate that PFA caused ACD which is different from the previous reports in which acrylates present as impurities in the PFA hardener caused the sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Systemic glucocorticoids decrease the synthesis of type I and type III collagen in human skin in vivo, whereas isotretinoin treatment has little effect.

The effects of systemic glucocorticoid and isotretinoin treatments on type I and type III collagen synthesis in intact skin were investigated by measuring the carboxyterminal and aminoterminal propeptides of type I procollagen, and the aminoterminal propeptide of type III procollagen, in suction blister fluid (SBF), in a study of 27 patients. All three parameters were significantly lower in the SBF of glucocorticoid-treated patients than in controls or patients undergoing treatment with isotretinoin, whereas the latter two groups did not differ significantly from each other. During glucocorticoid treatment, the concentrations of the procollagen propeptides were only about 20% of the corresponding control values, indicating that systemic therapy with prednisone at a dose of 0.48 mg/kg per day almost totally abolishes collagen synthesis in the skin. These results indicate that systemic glucocorticoid treatment suppresses the synthesis of both type I and type III collagen in the dermis, and suggest that many side-effects of these drugs, such as atrophy of the skin, are due to this inhibition. Systemic isotretinoin treatment did not stimulate skin collagen synthesis. Thus, its regenerative effect on connective tissue may be mediated by mechanisms other than direct stimulation of collagen synthesis.

Adult↗
PubMed1994

Interleukin 1 alpha (IL-1 alpha) in human skin in vivo: lack of correlation to markers of collagen metabolism.

Levels of interleukin 1 alpha (IL-1 alpha) were studied from blister fluids collected from 14 patients with various types of blistering diseases. In all the fluids, IL-1 alpha could be detected, the concentrations varying from 5 to 1730 pg/ml. For comparison IL-1 alpha was also assayed from suction blisters of 13 subjects; 8 atopic patients and 5 healthy controls. IL-1 alpha was also present in suction blisters in measurable quantities, suggesting that during suction IL-1 alpha is released into the blister cavity. Since IL-1 alpha has been shown to have marked effects on collagen metabolism, the marker of collagen synthesis (carboxyterminal propeptide of type I procollagen (PICP)) and gelatinase were assayed from the same samples. There was no apparent correlation between the levels of IL-1 alpha, PICP or gelatinase in blister fluids. The possible association of IL-1 alpha and collagen metabolism was further studied in experimental conditions. Topical glucocorticoid markedly decreased the level of PICP in suction blisters but did not have any significant effect on IL-1 alpha. UVB-radiation, on the other hand, caused increase in IL-1 alpha but did not have any profound effect on collagen metabolism. During the re-epithelialization of the blister floor the level of IL-1 alpha decreased markedly, and at the same time the expression of gelatinase was increased. The results indicate that IL-1 alpha is released in large quantities into blister fluid when using the suction blister model. However, no apparent correlation could be observed in healthy or diseased skin between the levels of IL-1 alpha, collagen synthesis marker or gelatinase.

Administration, Topical↗
PubMed1994

Collagen synthesis in human skin in vivo: modulation by aging, ultraviolet B irradiation and localization.

The effect of aging, sex, skin location and a short whole body ultraviolet B (UVB) phototherapy on type I and type III skin collagen synthesis were studied by measuring carboxy- and aminoterminal propeptides of type I and aminoterminal propeptide of type III procollagens (PICP, PINP and PIIINP, respectively) in suction blister fluid (SBF). The concentrations of PICP and PIIINP correlated negatively with age in the material of 30 men and 27 women (age range 23-86 years, mean age 51 years). As the subjects were divided into 3 age groups (23-34, 35-54 and 55-86 years) and the mean concentrations of the procollagens were compared between the groups, the youngest age groups in men and in the whole material had significantly higher concentrations than the two older age groups. These results confirm the previous results, which have shown by other methods that skin collagen synthesis decreases during aging. SBF was also obtained from 4 different body regions (back, arm, abdomen and leg) of 5 young male subjects and from 2 different body regions (abdomen and thigh) of 9 older subjects. Wide individual range in the concentrations of PICP, PINP and PIIINP was noticed but, in general, none of the body regions seemed to have more excessive collagen synthesis than the other ones. SBF was further collected from abdominal skin of 8 young male dermatological patients receiving UVB phototherapy. When the concentrations of PICP and PIIINP in SBF obtained before the treatment, after the treatment and from the covered control area were compared no statistical differences were noted, suggesting that short UVB treatment has no effect on skin collagen synthesis in vivo.

Abdomen↗
PubMed1993

Serum markers of collagen synthesis and degradation in skin diseases. Altered levels in diseases with systemic manifestation and during systemic glucocorticoid treatment.

Serum concentrations of the markers of collagen synthesis and degradation, collagen I propeptide (PICP), collagen III propeptide (PIIINP) and the cross-linked telopeptide of type I collagen (ICTP) were measured in young male dermatological patients and in control subjects. No significant differences were noted between patients suffering from atopic eczema (n = 24), other eczemas (n = 11), acne (n = 8), psoriasis (n = 7) or tinea (n = 9) and the control subjects (n = 24). In the total study population representing patients with common skin diseases and control subjects there was a significant correlation between the serum concentrations of PICP and PIIINP and between the concentrations of PICP and ICTP. This suggests that synthesis of type I and III collagens in vivo is coordinated and that the degradation and synthesis of type I collagen is balanced. These markers were also measured in older patients suffering from psoriasis, eczema and various connective tissue diseases. It was noted that the degree of skin involvement in these diseases was not related to the serum concentrations of the markers of collagen metabolism. The highest levels of PICP and PIIINP were observed in a patient with systemic mastocytosis (PICP 309 micrograms/l and PIIINP 8.0 micrograms/l). Increased levels of PIIINP were also found in patients with a high alcohol consumption. We have previously demonstrated that systemic glucocorticoids reduce collagen propeptide levels in serum. In the present study we also proved that systemic glucocorticoids have no effect on collagen degradation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Demonstration of 72-kDa and 92-kDa forms of type IV collagenase in human skin: variable expression in various blistering diseases, induction during re-epithelialization, and decrease by topical glucocorticoids.

Type IV collagenases have been shown to play an important role in tumor metastasis and wound healing. In the present study, we have demonstrated the presence of 72-kDa and 92-kDa forms of type IV collagenase in human skin by biochemical and in situ hybridization techniques. In situ hybridization allowed us to localize the 72-kDa form mostly to fibroblasts and the 92-kDa form to the epidermis and endothelial cells. The presence of type IV collagenase was confirmed by Western blotting. Enzyme activity was assayed in spontaneous blisters (18 subjects) and suction-induced blisters (29 subjects) by the zymography method, and by using type IV collagen as the substrate. Thus, it was possible to detect both the 92-kDa and 72-kDa forms in spontaneous and induced blisters. An especially high level of the 92-kDa enzyme was found in a bullous pemphigoid patient. Type IV collagenases were studied during re-epithelialization of the blister, using the suction-blister model. There was a marked induction of the 92-kDa type that was confirmed to be in the regenerating, migratory, epithelium by in situ hybridization studies. These results indicate that 92-kDa type IV collagenase may play an essential role in the normal physiology and integrity of the skin and may be an important regulator of re-epithelialization. It was also shown that potent topical glucocorticoid down-regulated the 92-kDa type collagenase, suggesting that glucocorticoids may have a beneficial role in some skin diseases by decreasing type IV collagenase activity and, thus, reducing tissue destruction.

Administration, Topical↗
PubMed1993

Effects of systemic isotretinoin on serum markers of collagen synthesis and degradation.

In the present investigation, collagen synthesis and degradation were studied by measuring the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) and a type I collagen-specific degradation peptide (ICTP) in the sera of 43 male patients, treated for acne with isotretinoin or with tetracycline. The values were compared with those observed in 24 acne patients without treatment and in healthy controls. The treatment with isotretinoin did not seem to affect these parameters in a cross-sectional setting, whereas tetracycline treatment was associated with slightly decreased levels of ICTP. Since there were marked variations in the PICP, PIIINP and ICTP levels between individual subjects, a follow-up study, including male and female patients, others than in the first part of the study, was conducted. Two other biochemical markers of bone metabolism, osteocalcin, reflecting osteoblastic activity, and tartrate-resistant acid phosphatase (TRAP), reflecting osteoclastic activity, were also analyzed. In females, all these parameters were lower than in males. In addition, the changes in females were more pronounced; in particular, PIIINP and TRAP were significantly increased in females during retinoid treatment (p < 0.05 and p < 0.01, respectively). Importantly, no increase was found in the synthesis of type I collagen during retinoid treatment, suggesting that the commonly used retinoid dosages do not stimulate the synthesis of type I collagen in vivo.

Acne Vulgaris↗
PubMed1992

A new method to measure type I and III collagen synthesis in human skin in vivo: demonstration of decreased collagen synthesis after topical glucocorticoid treatment.

Collagen is synthesized as procollagen and large extra domains known as propeptides are cleaved off enzymatically. In the present study we have measured the carboxyterminal propeptide of type I collagen (PICP) and the aminoterminal propeptide of type III collagen (PIIINP) in blister fluids of human skin. High concentrations of PICP were found in the spontaneous blisters of patients with bullous pemphigoid, erysipelas, or erythema multiforme. Detectable amounts were also found in suction blisters induced on healthy skin. Because the concentrations in suction blisters were several times higher than in corresponding serum, most of PICP and PIIINP was derived from the underlying dermis. This method was used for assessing type I and type III collagen synthesis after topical glucocorticoid treatment. Clobetasol-17-propionate (CP) decreased the concentrations of PICP by 75% after 1 d of treatment, the maximum inhibition (92%) being found after 2 d treatment. PIIINP was also affected. Hydrocortisone and hydrocortisone-17-butyrate also decreased the concentrations of PICP and PIIINP, but less markedly than CP. Partial recovery was seen 3 d after stopping the treatment. Thus measurement of collagen type specific propeptides in suction blisters can be used as an estimate of collagen synthesis in vivo, avoiding both local anesthesia and skin biopsing. With radioimmunoassays for PICP and PIIINP a large number of samples can also be processed simultaneously.

Administration, Topical↗
PubMed1992

Systemic glucocorticoid treatment decreases serum concentrations of carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen.

The effect of systemic glucocorticoid treatment on collagen synthesis in patients with various dermatoses was studied by measuring the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) in serum. Changes in the propeptide concentrations were compared with those of osteocalcin, which reflects osteoblastic activity, and tartrate resistant acid phosphatase (TRAP), which reflects osteoclastic activity. The treatment caused significant decreases in levels of PICP, PIIINP and osteocalcin of 38, 34 and 49%, respectively (P less than 0.001). For TRAP, both increases and decreases were seen. The effects on PICP and PIIINP were evident 2-4 days after the onset of steroid therapy. The decrease in PICP was dose-related (r = 0.470, P less than 0.005) but even relatively small doses (0.1 mg of prednisone/kg/1 day) caused a significant reduction in PICP. After cessation of treatment, the levels of PICP returned to the pretreatment level in 1 week. The present study demonstrates that systemic glucocorticoid therapy in humans suppresses the synthesis of type I and III collagens and also non-collagenous bone matrix proteins.

Acid Phosphatase↗
PubMed1992

Comparison of muscle-derived serum carbonic anhydrase III and myoglobin in dermatological patients: effects of isotretinoin treatment.

The serum levels of muscle-specific serum carbonic anhydrase III (S-CAIII) and myoglobin (S-Myo) were analyzed in various male dermatological patients of the same age. The mean levels of S-CAIII and S-Myo were essentially similar in patients with acne, psoriasis vulgaris, atopic eczema and tinea, suggesting that common dermatological diseases do not affect the serum levels of the muscle markers. Increased levels of S-CAIII, which is specific for skeletal muscle cells, were found in the acne patients who had been treated with isotretinoin. However, when S-CAIII and S-Myo were studied in 24 patients (16 males, 8 females) before and during isotretinoin treatment, no constant increases in these markers could be observed. When individual patients were followed for several months, transient increases or decreases could be observed. The changes in S-CAIII, or S-Myo, did not correlate with the dose of isotretinoin, nor with the duration of the treatment. The results suggest that systemic isotretinoin does not specifically affect skeletal or myocardial muscles. The increases in these markers observed in the course of dermatological diseases and isotretinoin treatment are obviously due to other factors, such as exercise.

Adolescent↗
PubMed1991

In-vivo effects of solar-simulated ultraviolet irradiation on antioxidant enzymes and lipid peroxidation in human epidermis.

The effects of solar-simulated UV-irradiation on the activity of antioxidant enzymes and the amount of diene conjugation were studied in human epidermis in vivo. A single dose of UV-irradiation was found to result in a transient reduction in superoxide dismutase activity and this was followed by increased amounts of conjugated diene double bonds, an index for oxidative stress. This suggests that in-vivo exposure of human epidermis to solar-simulated UV-irradiation causes changes in the enzymic antioxidant defence system which, in turn, are accompanied by increased level of oxidative stress.

Adolescent↗
PubMed1991

New aspects of the mechanism of corticosteroid-induced dermal atrophy.

Glucocorticoids are effective for the treatment of various inflammatory skin diseases, but their long-term use may lead to serious side-effects such as osteoporosis and skin atrophy. The incidence of skin atrophy following application of potent corticosteroids is especially high among children and the elderly. During recent years the effects of glucocorticoids on connective tissue have been elucidated, and it is evident that skin atrophy is mostly due to a decrease in collagen synthesis. Since collagen is the most abundant protein in the skin, the inhibition of its synthesis leads to atrophy. This review discusses the molecular mechanisms of glucocorticosteroid-induced skin atrophy and therapeutic possibilities.

Aged↗