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Biomedical subjects

A Oikarinen

Publications and source records attributed to A Oikarinen.

At least 19 recordsLinked to original sources
PubMed2003

Modulation of collagen synthesis and mRNA by continuous and intermittent use of topical hydrocortisone in human skin.

BACKGROUND: Glucocorticoids have been shown to downregulate collagen synthesis in human skin in vivo, thereby contributing to skin atrophy. OBJECTIVES: To compare the effects of continuous and intermittent use of topical hydrocortisone on skin collagen synthesis and, furthermore, to elucidate the mechanism of collagen synthesis reduction induced by hydrocortisone. METHODS: Collagen propeptides reflecting the synthesis rate of type I and III collagens were studied from suction blister fluids in nine healthy subjects after 3 weeks of continuous (twice daily) or intermittent (on three consecutive days weekly) topical hydrocortisone treatment and 2 weeks after the termination of treatment. Type I collagen mRNA was studied in the same subjects from skin biopsies by using in situ hybridization (ISH) after 3 weeks of treatment. RESULTS: Three weeks of continuous treatment decreased the types I and III collagen propeptides in suction blister fluid by 89% and 82%, respectively, while intermittent treatment resulted in a corresponding decrease of 53% and 50%. ISH studies from skin biopsies showed type I collagen mRNA to be markedly reduced in fibroblasts after continuous and intermittent steroid treatment. After a 2-week drug-free interval, the synthesis rate was completely restored in both areas, and some subjects even showed upregulation of synthesis in previously steroid-treated skin. CONCLUSIONS: Continuous hydrocortisone for 3 weeks markedly decreases collagen propeptides and corresponding mRNA in human skin. Intermittent hydrocortisone has a less marked effect on the collagen synthesis rate.

Administration, Topical↗
PubMed2003

Immunohistological distribution of the tight junction components ZO-1 and occludin in regenerating human epidermis.

BACKGROUND: Molecular characterization of tight junction proteins during the past few years has provided novel methods for studying these specialized junctions. Tight junctions have recently been characterized in the granular cell layer of human epidermis, and the role of these junctions in the epidermal barrier is now being re-evaluated. OBJECTIVES: To investigate the expression of tight junction components during the re-epithelialization of suction blisters and the regeneration of the corneal layer after tape stripping. METHODS: Suction blisters were induced in eight healthy volunteers, and skin biopsies were taken 4 or 6 days afterwards. The restoration of epidermal barrier function was evaluated by measuring water evaporation (WE) from the wound area. Tape stripping was performed on three volunteers to remove the corneal layer. The tissues were immunolabelled using indirect immunofluorescence or the avidin-biotin method. RESULTS: Prior to the biopsies, WE from the blister wounds was markedly elevated in comparison with normal skin. In the epidermis surrounding the blister, occludin and ZO-1 were expressed in the granular cell layer only. In the hyperproliferative zone adjacent to the border of the blister, the expression of ZO-1 was redistributed into several spinous cell layers, while occludin expression was restricted to the upper epidermis. In the leading edge of migrating keratinocytes, both proteins were expressed exclusively in the most superficial layer of keratinocytes. Double labelling for ZO-1 and involucrin showed expression of both proteins in the same layers of hyperproliferative keratinocytes, while the expression patterns were clearly different in the migrating keratinocytes. CONCLUSIONS: Tight junctions of regenerating epidermis may provide a functional barrier prior to regeneration of the corneal layer.

Adult↗
PubMed2002

Smoking affects collagen synthesis and extracellular matrix turnover in human skin.

BACKGROUND: Smoking is associated with premature facial wrinkling and aberrant wound healing, but the underlying mechanisms of skin injury are poorly understood. OBJECTIVES: To compare the in vivo collagen synthesis and degradation in the skin of smokers and non-smokers. METHODS: The study population consisted of 47 current smokers and 51 individuals who had never smoked from northern Finland. Suction blisters were induced in the sun-protected upper inner arm of the study subjects, after which suction blister fluid (SBF) was collected for analyses of the levels of aminoterminal procollagen propeptides of type I and III collagens (PINP and PIIINP, respectively), matrix metalloproteinase (MMP)-8 and tissue inhibitor of MMP (TIMP)-1. PINP, PIIINP and TIMP-1 were also determined from serum samples. The levels of active and pro MMP-1 were assessed from deep-frozen skin biopsies by Western blotting. RESULTS: The synthesis rates of type I and III collagens were lower by 18% and 22%, respectively, in the SBF of the smokers compared with the non-smokers. The levels of MMP-8 were higher by 100% in the SBF of the smokers. The levels of MMP-1 in the skin biopsies did not differ significantly between the groups. The levels of TIMP-1 in SBF were 14% lower in the smokers than in the non-smokers, whereas the serum concentrations of TIMP-1 did not differ between the groups. CONCLUSIONS: Smoking decreases the synthesis rates of type I and III collagens in skin in vivo and alters the balance of extracellular matrix turnover in skin.

Adult↗
PubMed2001

Type I collagen turnover and cross-linking are increased in irradiated skin of breast cancer patients.

BACKGROUND AND PURPOSE: The effects of radiation therapy on the turnover and structure of type I collagen were studied in irradiated and contralateral skin of 18 breast cancer patients without clinically evident fibrosis. MATERIALS AND METHODS: The rates of on-going type I collagen synthesis and degradation were assessed by the aminoterminal propeptide of type I procollagen (PINP) and by two different assays (ICTP and SP4) for the carboxyterminal telopeptide of type I collagen in the soluble tissue extracts, respectively. Also, TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex were measured in the tissue extracts. Insoluble skin matrices, containing the cross-linked type I collagen fibres, were heat-denatured and digested with trypsin. Then, the variants of the carboxyterminal telopeptide of type I collagen were separated by high performance liquid chromatography (HPLC). The major histidinohydroxylysinonorleucine (HHL)-cross-linked variant was quantified by the SP4 assay, and the minor pyridinoline analogue (PA)-cross-linked telopeptide was quantified by the ICTP assay. RESULTS: Both the synthesis and degradation of type I collagen were increased (r=0.906; P<0.001) on the irradiated side, whereas the concentration of the MMP-2/TIMP-2 complex was decreased. In the insoluble tissue digests, the HHL-cross-linked telopeptides of type I collagen, also, when expressed/tissue hydroxyproline, were increased in the irradiated skin. TIMP-1, TIMP-2 or PA-cross-linked telopeptides of type I collagen showed no differences between the two sides. CONCLUSIONS: Radiotherapy induces a long-term increase in the turnover of type I collagen and leads to the accumulation of cross-linked type I collagen in skin.

Adult↗
PubMed2001

Effects of glucose on collagen mRNA levels and collagen secretion in EAhy 926 endothelial cell line.

Diabetes mellitus (DM) is a complex metabolic disease associated with increased accumulation of extracellular matrix by endothelial cells and contributing to vascular complications of long-standing diabetes. On the other hand, DM is also associated with decreased accumulation of extracellular matrix in granulation tissue, which is suggested to be a consequence of impaired angiogenesis. The role of hyperglycemia in these situations is not fully understood. We examined the effects of high glucose concentrations on the gene expression and secretion of various collagens in cultured EAhy 926 endothelial cells. EAhy 926 endothelial cells expressed alpha 1(I) collagen mRNA at a low level and small amount of the corresponding peptide was secreted from the cells; mRNA was not affected but peptide secretion was increased by elevated glucose concentration. mRNAs for type III and VI collagens were not detected in the endothelial cells Furthermore, high glucose concentration in long term had no morphological effects on cultured endothelial cells but increased the expression of type IV collagen, which could rather be beneficial for angiogenesis in a healing wound. Our results suggest that high glucose concentration per se may contribute to increased accumulation of extracellular matrix in blood vessels but probably is not responsible for decreased angiogenesis and granulation tissue formation in diabetic patients.

Cell Line↗
PubMed2001

Effects of glucose on collagen mRNA levels and collagen secretion in EAhy 926 endothelial cell line.

Diabetes mellitus (DM) is a complex metabolic disease associated with increased accumulation of extracellular matrix by endothelial cells and contributing to vascular complications of long-standing diabetes. On the other hand, DM is also associated with decreased accumulation of extracellular matrix in granulation tissue, which is suggested to be a consequence of impaired angiogenesis. The role of hyperglycemia in these situations is not fully understood. We examined the effects of high glucose concentrations on the gene expression and secretion of various collagens in cultured EAhy 926 endothelial cells. EAhy 926 endothelial cells expressed alpha1(I) collagen mRNA at a low level and small amount of the corresponding peptide was secreted from the cells; mRNA was not affected but peptide secretion was increased by elevated glucose concentration. mRNAs for type III and VI collagens were not detected in the endothelial cells. Furthermore, high glucose concentration in long term had no morphological effects on cultured endothelial cells but increased the expression of type IV collagen, which could rather be beneficial for angiogenesis in a healing wound. Our results suggest that high glucose concentration per se may contribute to increased accumulation of extracellular matrix in blood vessels but probably is not responsible for decreased angiogenesis and granulation tissue formation in diabetic patients.

Cell Line↗
PubMed2000

Occult neurofibroma and increased S100 protein in the skin of patients with neurofibromatosis type 1: new insight to the etiopathomechanism of neurofibromas.

BACKGROUND: Neurofibromas represent proliferation of the connective tissue cells of peripheral nerves and deposition of collagenous extracellular matrix. There is evidence that the appearance and growth of neurofibromas may be associated with prior or ongoing mechanical trauma in patients with neurofibromatosis type 1 (NF1). OBJECTIVE: To study the histologic characteristics of apparently healthy skin of patients with NF1. DESIGN: The histologic features of healthy-looking skin of patients with NF1 were analyzed. SETTING: University hospital. PATIENTS: Ten patients who fulfilled the criteria for NF1. INTERVENTIONS: Punch biopsy specimens of healthy-looking skin of the forearm from 9 volunteer patients and of the upper eyelid during cosmetic operation from 1 volunteer patient were obtained. MAIN OUTCOME MEASURES: The main outcomes were not predicted, and the hypothesis was formulated during data collection. RESULTS: Apparently unaffected skin of 5 patients with NF1 was studied by routine histologic testing with respect to expression of S100 protein. Unexpectedly, analysis of the samples revealed the presence of a small neurofibroma tumor in one of the samples. The tumor was located in deep dermis around a hair follicle. In addition, neurofibromatous tissue not large enough to be called a tumor was found on the same anatomical location in another patient. In further studies, 10 punch biopsy specimens of apparently healthy skin from patients with NF1 were similarly sectioned and analyzed. No tumors were found in these additional samples. In 4 patients, however, abundant S100 protein-positive cells were located within collagenous extracellular matrix surrounding hair follicles. CONCLUSIONS: The skin of patients with NF1 might be more widely affected than previously thought and occult neurofibromas are not rare.

Eyelid Neoplasms↗
PubMed2000

Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin.

Radiation-induced fibrosis is a common side-effect of cancer treatment. The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synthesis, skin thickness, gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for breast cancer with surgery and radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non-treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIMP-1 and TIMP-2) and MMP-9 and MMP-2/TIMP-2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for PIIINP. In irradiated skin, PINP, PIIINP, TIMP-1 and MMP-2/TIMP-2 complex levels in SBF and the number of PINP-positive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of TIMP-2 in irradiated and non-irradiated skin were similar. MMP-9 could not be detected in SBF with the assay used. The serum levels of MMP-9 were higher in the treated subjects than the reference values. The serum values of PINP, PIIINP, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were not significantly affected. These results indicate increased local collagen synthesis and accumulation of connective tissue in irradiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis.

Adult↗
PubMed2000

Re-epithelialization rate and protein expression in the suction-induced wound model: comparison between intact blisters, open wounds and calcipotriol-pretreated open wounds.

We have investigated re-epithelialization following induction of suction blisters in humans in intact blisters, open wounds, i.e. blister roofs removed immediately after blister induction, and calcipotriol-pretreated open wounds. Intact blisters simulate blister healing in bullous disease, while open wounds simulate re-epithelialization during wound healing. Re-epithelialization was clearly faster in open wounds than in intact blisters, and was not affected by calcipotriol pretreatment. Bullous pemphigoid antigen 2 (BP180), bullous pemphigoid antigen 1 (BP230), plectin/hemidesmosomal 1 protein (HD1), laminin 5, laminin alpha5, laminin beta1, type VII collagen, tenascin-C, beta4, alphavbeta5, alpha5 and alpha9 integrins were studied in intact blisters and open wounds by immunohistochemistry. Hemidesmosomal plaque proteins BP230 and plectin/HD1, which connect the keratin cytoskeleton to the hemidesmosome, appeared earlier at the leading edge in intact blisters than in open wounds. Band-like immunostaining in the basement membrane for laminin 5, alpha5 and beta1 chains was continuous in blister bases, but partially discontinuous in open wound bases. The other antigens studied showed similar expression in intact blisters and open wounds. BP180, BP230, plectin/HD1, beta4 integrin, laminin 5 and tenascin-C expression were further studied in calcipotriol-pretreated open wounds. Calcipotriol did not affect the expression of these antigens. The immunohistochemical results suggest that the keratin cytoskeleton is linked to the basal plasma membrane of migrating basal cells via BP230 and plectin/HD1 earlier in the more slowly re-epithelializing blisters than in open wounds. An intact laminin sheath may inhibit keratinocyte migration in intact blisters.

Adult↗
PubMed2000

Microcirculatory response of skin to benzoic acid and methyl nicotinate in patients with diabetes.

AIMS: In view of the relationship between microvascular pathology and organ complications in diabetes mellitus, the aim of the present study was to examine the microvascular response of upper arm skin to non-immunological contact irritants in 17 insulin-dependent diabetic patients and 11 non-diabetic controls. METHODS: Non-immunological contact urticaria, an inflammatory reaction mediated in a unique way, not previously studied in diabetic patients, was examined. The test agents were benzoic acid and methyl nicotinate. The intensity of the reactions was measured using laser-Doppler flowmetry and colorimetry. The patients were divided into two groups, depending on whether they had had diabetes for less or more than 10 years. RESULTS: There were no differences in the maximal blood flow responses between the groups, but the diabetic patients showed increased blood flow responses to the lowest irritant concentrations compared to the controls. The reactions in the two groups of diabetic patients were similar. CONCLUSIONS: The present study suggests that the microvascular reactivity of diabetic skin to non-immunological contact irritants is increased.

Adult↗
PubMed2000

Systemic estrogens have no conclusive beneficial effect on human skin connective tissue.

SUBJECT: Aging of the skin is affected by intrinsic and extrinsic factors. Especially important extrinsic factor is ultraviolet radiation, which causes premature aging of the skin. Intrinsic aging is influenced by genetic factors, and changes in hormones. In menopause, changes in hormonal balance have been suggested to enhance aging of the skin. DISCUSSION: Accordingly, several studies have been accomplished, in which hormone replacement therapy (HRT) has been used in order to prevent skin aging at or after the menopause. In this overview the results of previous studies, and a study done recently, are critically reviewed. CONCLUSION: One year systemic replacement therapy has no beneficial effect on the skin thickness, collagen synthesis, or elastin. Topical estrogens might have some beneficial effects. However, since the number of patients treated with topical estrogens is relatively small, further studies are needed.

Aged↗
PubMed2000

Melanoma and other skin cancers in circumpolar areas.

During the recent decades, the thickness of the ozone layer over the northern hemisphere has declined by 10 to 40 percent during the winter and spring months. Since ozone is the major barrier protecting the earth from dangerous short wave UV-radiation (UVB), the depletion in the ozone layer consequently increases the amount of UV-radiation reaching the earth's surface. As a rule a 10 percent reduction in the ozone layer causes ca. 20% increase in UV-radiation and a 40% increase in skin cancers. Thus relatively minor changes in ozone layer thickness may a have marked impact on the health of humans. Skin cancer is the most common cancer in humans, i.e. in Finland about 4000 new basal cell carcinomas, 700 other skin cancers, mostly spinous cell carcinomas and 500 melanomas occur yearly. Up to recent years the incidence of skin cancers has steadily increased in northern countries. As an explanation, changes in sunbathing habits have been suggested to play a central role. Due to the high mortality rate in melanoma, and marked morbidity in other skin cancers, it is important to try to prevent skin cancers and inform the public about the risks of excessive sun exposure, and of the ways in which the skin can be protected. Proper clothing and use of sunscreens have been shown to reduce the incidence of both melanomas and other skin cancers. Furthermore, it is important to identify those at high risk for acquiring skin cancers, like individuals with type 1 skin character (fair skin which burns easily), or numerous dysplastic nevi, or a family history of skin cancers.

Antarctic Regions↗
PubMed1999

Increased prevalence of vitiligo, but no evidence of premature ageing, in the skin of patients with bp 3243 mutation in mitochondrial DNA in the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS).

The MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) belongs to the category of mitochondrial disorders. The most common molecular aetiology of the syndrome is a mutation at base pair (bp) 3243 in the mitochondrial genome (mtDNA). The phenotype is varied and, apart from central nervous system involvement, the patients with this mutation may present with neurosensory hearing loss, diabetes mellitus and cardiomyopathy. These phenotypes suggest that organs dependent on aerobic metabolism suffer most. We investigated the possible clinical and physiological manifestations of impaired energy metabolism in the skin of 28 patients with the bp 3243 mutation in mtDNA. Non-invasive sonography and laser Doppler flowmetry were used to measure skin thickness and the blood flow of the skin. Skin collagen synthesis was assayed from suction blister fluid. Evaporimetry was used to assess the re-epithelialization rate of suction blister wounds. Histochemistry and immunohistochemistry were used to evaluate the melanocytes and pigment in the skin. Vitiligo was found in three of the 28 patients (11%), which was markedly more than in the general population. Histological findings showed an absence of pigment, but an apparently normal distribution of melanocytes in the dermoepidermal junction. Seborrhoeic eczema and atopy were also somewhat more frequent. No features of premature ageing, such as a marked decrease in skin thickness, blood flow, collagen synthesis or re-epithelialization rate, were demonstrated.

Adult↗
PubMed1999

Delayed restoration of epidermal barrier function after suction blister injury in patients with diabetes mellitus.

AIMS: Diabetes mellitus is a risk factor for compromised wound healing. The present study examines the restoration of the epidermal barrier function using the suction blister wound model. METHODS: The healing process was evaluated over time by measuring water evaporation (WE) and blood flow (BF) in the wound area. Seventeen Type 1 diabetic males and 11 non-diabetic control males were studied. RESULTS: At the onset, the WE of diabetic patients was 116 +/- 11 g x m(-2) x h(-1) and that of controls 95 +/- 13 g x m(-2) x h(-1) (P < 0.001). On the second day, the WE of diabetic patients was 90 +/- 21 g x m(-2) x h(-1) and that of controls 60 +/- 24 g x m(-2) x h(-1) (P < 0.02). The most profound difference was encountered during the fourth day, when the WE of diabetic patients was 40 +/- 17 g x m(-2) x h(-1) and that of controls 14 +/- 8 g x m(-2) x h(-1) (P < 0.001). The value recorded on the fourth day was 37% of the onset value in diabetic patients and 16% in controls (P < 0.001). Eight days after wounding the values were close to that of normal skin in both diabetic and control subjects. At the onset, the BF was 93 +/- 20 (arbitrary units) in diabetic men and 112 +/- 18 in controls (P = 0.02). On the second, fourth and eighth day there was no significant differences. CONCLUSIONS: The results suggest that restoration of the epidermal barrier function is delayed in the patients with diabetes. There were also a trend toward an initially weaker inflammatory response.

Adult↗