Infant feeding patterns in the Finnish type I diabetes prediction and prevention nutrition study cohort.

OBJECTIVE: To investigate infant feeding patterns during the first 2 y and their relation to sociodemographic factors. DESIGN: A population-based cohort study. SETTING: Oulu and Tampere University Hospital district areas 1996-1999, Finland. SUBJECTS AND METHODS: All newborn infants (n=675) with increased genetic risk for type I diabetes were invited to the study in 1996-1997. Of these, 429 (64%) completed the dietary follow-up form by the time they reached 2 y of age. RESULTS: The median duration of exclusive breastfeeding (BF) was 1.8 months (range 0-6 months) and that of total BF 7.0 months (0.3-25 months). Among the infants 20% were exclusively breastfed at least 4 months (recommendation 4-6 months). Infants were introduced to infant formula at the median age of 1.8 months (range 0-25 months) and other supplementary foods at the median age of 3.5 months (1-6 months). Infant's ponderal index at birth was inversely associated with the duration of total BF. The age of introduction of supplementary foods correlated positively with the duration of total BF. Longer parental education and increased maternal age were associated with a longer duration of BF and older age at introduction of supplementary foods. Infant formula and other supplementary foods were added earlier to the diet of the boys than that of the girls. CONCLUSION: Duration of breastfeeding in Finland is shorter than recommended. Compliance with the current recommendations on the timing of introduction of first supplementary food and dairy products is relatively poor. The diet during infancy seems to be conspicuously influenced by the duration of parental education, maternal age and the sex of the infant.

Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group.

OBJECTIVE: To evaluate whether the increased risk of type 1 diabetes conferred by an early introduction of cow's milk supplements can be mediated by accelerated growth in formula-fed infants. RESEARCH DESIGN AND METHODS: All children < or = 14 years of age who were diagnosed with type 1 diabetes from September 1986 to April 1989 were invited to participate in the study. Birth date- and sex-matched control children were randomly selected from the Finnish Population Registry. At least three weight measurements from the first year of life were obtained for 435 full-term diabetic subjects and 386 control subjects from well-baby clinics and school health care units. RESULTS: Increase in body weight was greater in the diabetic girls than in the control girls, and the difference increased from 111 g (95% CI 0-218, P = 0.04) at 1 month of age to 286 g (95% CI 123-450, P = 0.0006) at 7 months. For boys, the difference in weight between the diabetic subjects and the control subjects remained stable during infancy (difference 95 g, 95% CI-2-205, P = 0.09). Increased weight was associated on average with a 1.5-fold risk of type 1 diabetes. Early introduction of formula feeding (< 3 vs. > or = 3 months) was also associated with an increased risk of type 1 diabetes after adjustment for the individual weight gain curve (adjusted odds ratio 1.53, 95% CI 1.1-2.2). No evidence for interaction was observed. CONCLUSIONS: These observations indicate that an early exposure to cow's milk formula-feeding and rapid growth in infancy are independent risk factors of childhood type 1 diabetes.

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.

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.

Tacrolimus ointment does not affect collagen synthesis: results of a single-center randomized trial.

We conducted a randomized, double-blind, placebo-controlled trial to assess the atrophogenicity of tacrolimus ointment. In a combined group of atopic dermatitis patients (n = 14) and healthy volunteers (n = 12), 0.3% tacrolimus, 0.1% tacrolimus, betamethasone-valerate, and a vehicle control were applied in a randomized order to nonsymptomatic, 4 cm x 4 cm regions of abdominal skin. After 7 d of treatment under occlusion, the carboxy- and amino-terminal propeptides of procollagen I (PICP, PINP) and the amino-terminal propeptide of procollagen III (PIIINP) were measured from suction blister fluid with specific radioimmunoassays. In addition, ultrasound measurements of skin thickness were taken. Betamethasone-treated areas showed median PICP, PINP, and PIIINP concentrations of 17.0%, 17.6%, and 39.5% of the vehicle control at the end of the treatment period, respectively, whereas the 0.1% and 0.3% tacrolimus-treated areas showed median concentrations of approximately 100% of the vehicle control (p < 0.001). Betamethasone was also the only treatment to reduce skin thickness; the median decrease in skin thickness was 7.4% relative to 0.1% tacrolimus, 7.1% relative to 0.3% tacrolimus, and 8.8% relative to the vehicle control (p < 0.01). Results for atopic dermatitis patients and healthy volunteers were similar. These findings suggest that tacrolimus does not cause skin atrophy.

Familial high serum PICP: high even in skin interstitial fluid, suppressible by topical corticosteroid treatment.

Circulating C-terminal propeptide of type I procollagen (PICP), mostly originating from bone, is mainly cleared by mannose receptors (MRs) in liver endothelial cells (LECs). We hypothesized that skin macrophage MRs could also play a role in local (in situ) clearance of PICP originating from skin type I procollagen synthesis. We tested this hypothesis in a male subject with a genetic systemic clearance defect, apparently due to an abnormality in MR function in LECs (or in PICP structure). Since skin macrophages may express the same MRs as LECs do, the genetic defect could affect them as well; hence, if elevated PICP concentrations even in skin interstitial fluid (IF) were found in our subject, it would suggest a role for local MR-mediated PICP clearance in skin. Since glucocorticoids (GCs) upregulate MRs in vitro, we measured the effect of topical GC on suction blister fluid (SBF)-PICP of the test person as compared with normal subjects. SBF-PICP was elevated in the case, which was consistent with the hypothesis. Furthermore, the GC-induced decrease was accentuated. The results suggest that skin macrophage MRs can have a role in skin PICP clearance in situ.

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.

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)

Angiosarcoma. A rare secondary malignancy after breast cancer treatment.

Life-saving mastectomy and radiation therapy are established in the treatment of early stage breast cancer. Angiosarcoma, i.e. malignant angioendothelioma, is a rare tumor which can develop after several years of such treatment. The number of post-operative and post-irradiation angiosarcomas has increased in recent years. We report four cases of angiosarcoma which occurred after treatment of breast cancer and review the literature. In two of these cases the angiosarcoma developed on the irradiated breast skin after partial mastectomy and radiation therapy, in the other two cases the angiosarcoma appeared on a chronically edematous arm after radical mastectomy and radiation therapy.

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.

Changes in food habits in families with a newly diagnosed child with type 1 diabetes mellitus.

Dietary recommendations for children with type 1 diabetes mellitus (DM) are in line with the recommendations for the general population and applicable to the whole family. We review what is known about the food habits of non-diabetic family members and present original data on dietary changes in families with a child with DM. Some studies suggest that family members eat mostly the same food as the affected child. In a Finnish study of siblings of children with DM, favourable changes were observed after diagnosis in the type of milk and fat used. In a study of young children with DM, family members increased their consumption of skim milk, low-fat cheese and low-fat cold meat cuts. The consumption frequencies of fruit and vegetables increased. In conclusion, family members of a child with DM are willing to change their food habits towards the recommended diet. Dietary advice should be directed to the whole family from the very beginning.

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.

Suction blister techniques for measurement of human skin collagen synthesis.

BACKGROUND/AIMS: Types I and III collagen are the main fibrillar collagens in the skin. Marked changes occur in the biosynthesis of these proteins during treatment with various drugs, upon ageing and in several diseases. Since conventional methods of assessing these changes have several disadvantages, a new method for estimating collagen synthesis in human skin in vivo has recently been developed. In this method suction blisters are induced on intact, and treated or diseased skin and types I and III procollagen propeptides are measured radioimmunologically in suction blister fluid (SBF). CONCLUSIONS: The concentrations of type I and III procollagen propeptides in SBF reflect the corresponding local ongoing skin collagen synthesis. This method offers a new sensitive tool for experimental and clinical dermatology for monitoring skin collagen synthesis. With this method it has been possible, for example, for the first time directly to show in vivo that glucocorticoids rapidly and dramatically decrease human skin collagen synthesis.

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.

[Tetracyclines as anti-inflammatory treatment in skin diseases]. / Tetracykliner som antiinflammatorisk behandling vid hudsjukdomar.

Tetracyclines are broad-spectrum bacteriostatic antimicrobials drugs, traditionally used in dermatology for the treatment of acne. Owing to their beneficial antiinflammatory properties, and the low risk and modest side effects associated with them, tetracyclines are also useful in treating several other skin diseases-either alone, or in combination regimens to reduce the intensity of the immunosuppressive effect.

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.