摘要:

AbstractMethylprednisolone aceponate is a new potent topical corticosteroid. Chemically it is a corticoid diester that rapidly penetrates the skin. It is rapidly metabolised and then conjugated so that although potent, it does not appear to cause serious local or systemic side effects. Clinical trials indicate that once daily applications are sufficient to control most eczematous disorders and that it is suitable and effective in atopic dermatitis.

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb01057.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractAn overview of the salient developments in definition, classification, etiology and pathogenesis, and treatment of the eczemas in recent years is given. On the basis of the pathogenesis of allergic contact eczema and atopic dermatitis, possible future therapeutic approaches are discussed. The indispensability of the use of topical corticosteroids in eczema treatment at the present time, and the demand for preparations with high potency and absent or low systemic and local side effects is stressed.

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb01064.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe most prominent and most discussed local side effect of topical corticosteroids is the thinning of the skin. Therefore, the atrophogenic potential is an important indication of the quality of a new corticosteroid. Several studies have been conducted to investigate this parameter. In rats, the effect of breaking strength of the skin, the most appropriate model for evaluating atrophogenicity in animals, showed that MPA and prednicarbate (PC) reduced the breaking strengh only slightly compared to clobetasol propionate (CBP). These results indicate that MPA could be classified as a corticosteroid with low local atrophogenic potential. This was confirmed in humans by a placebo controlled double‐blind study comparing intra/interindividuals MPA (cream, ointment and fatty ointment) and bethamethasone‐17‐valerate (BMV), CBP and PC (cream only) under occlusive dressing over 6 weeks. Three different parameters were assessed (dermal atrophy (clinical picture), surfometric measurement of the dermatoglyphic pattern, visual evaluation of telangiectasia). In all three formulations, MPA is of lower atrophogenic potential than CBP. While there is no statistical difference between BMV and MPA, the atrophogenic potential of MPA is low. In order to reflect more the clinical use of topical corticosteroids, MPA preparations (cream 0.1% and fatty ointment) has been evaluated in comparison to BMV in an 8‐week non‐occluded application test. MPA was applied once a day (5 days a week) and BMV twice in 20 healthy subjects according to a double‐blind randomized design. Assessment of atrophogenic potential was performed weekly using clinical scores (atrophy and telangiectasia) as main criteria and skin thickness measurements (ultrasound imaging) as a second criterion. BMV cream gives higher numbers of telangiectasia than MPA preparations and vehicles. From the skin thickness measurements, MPA treatments once a day has a lower thinning potential than BMV twice a day. These findings were confirmed by clinical trials. In 1145 patients suffering from various types of eczema who used MPA in cream and ointment, mild atrophy of the skin was observed in only one patient. Moreover, clinical signs of atrophy were present in only two out of a group of 673 patients (590 adult and 83 children) treated with MPA fatty ointment. In a group of 66 patients who used this same MPA fatty ointment during 3–4 months, no signs of skin atrophy were observed. Considering animal and human studies, MPA can be classified as a corticoid with low atrophoge

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb01058.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractBackgroundThe role of psychological factors is conflicting in alopecia areata (AA). Acute as well as chronic stress have been observed in patients with AA.DesignA descriptive study of psychological and social factors which may play a role in the pathogenesis and prognosis of childhood AA. Seventeen patients with AA were dermatologically examined and psychosocially studied. Behavioral and emotional problems and possible psychopathology in the child's actual functioning were scored with the Child Behavior Checklist (CBCL) and a life events scale. Fifteen patients with visible atopic dermatitis (AD) formed a reference group.ResultsAlthough, on average, children with AA do not have higher behavior problem scores than children in the normative group, more children had scores in the clinical range. However, AA and AD children did not differ in this respect. More AA and AD children than children in the normative group had low social competence scores. Thus, although some AA children differ from children from the normative group, this difference is not specific compared with other children with affected skin, i.e., the AD group. The mean total score and the mean number of life events did not differ significantly from the corresponding data on the international control population.ConclusionA tendency was observed that psychosocial factors play a role in maintaining or inducing AA and AD.

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb00064.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractAim6α‐Methylprednisolone aceponate (MPA) is a new steroid double ester for topical use, the potent action and lack of untoward side‐effects of which became evident in two different studies.BackgroundRecent studies have proved the concept that MPA is both potent and extremely well tolerated when used for a relatively short time.MethodsTwo multicentre studies on patients with steroid responsive dermatoses using either MPA fatty ointment (n= 66) or MPA in a vehicle individually adapted to the patients' skin condition (n= 256) were conducted over a maximum of 4 and 6 months, respectively. Plasma Cortisol levels were determined in study I (n= 45) to reveal potential systemic effects.ResultsComplete healing and marked improvement were achieved in 86 % of 322 patients. There were no systemic side effects and no significant alteration in plasma Cortisol levels during and after treatment. Minor temporary local side effects were observed in 7%.ConclusionMPA (Advantan) is a potent antiinflammatory topical steroid virtually devoid of systemic adverse effects and with a low incidence of local side‐e

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb01059.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractAimThe aim of this study is to correlate the β‐endorphin levels at the early and more chronic stages of the disease in an attempt to find or confirm an etiological factor of vitiligo.BackgroundThe exact pathogenesis of vitiligo is still unclear. The most important theories are the self destruction, the autoimmune and the neural theories.MethodsPatients with vitiligo (n= 28) were divided into two groups according to the duration of their disease. A group of 15 members of medical staff was the control group. β‐endorphin levels were determined with a radioimmunoassay (125I‐β‐endorphin IncstarCo).ResultsThe mean β‐endorphin levels (11.88 ± 2.25 pmol/l) in patients at the early years of the disease (Group A) were statistically elevated compared to those of patients with ‘chronic’ vitiligo (9.27 ± 2.73 pmol/l) and to those of controls (8.53 ± 2.53) pmol/l).ConclusionWe suggest that high β‐endorphin levels play a role in the pathogenesis of vitiligo as well as in the p

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb00065.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIn order to display its pharmacological and therapeutic effects, a local corticosteroid has to be bioavailable at its target site in the skin. The intensity and duration of its activity depend on the time course of its concentration in the target tissue, the number of receptors within this, tissue and on the intrinsic pharmacological activity of the molecule respectively of its active metabolite(s). It is commonly accepted that the desired and the adverse corticosteroid effects are mediated by receptor mechanisms. Since all nucleated cells contain corticosteroid receptors with the same specifity yet in different numbers, a dissociation between wanted anti‐inflammatory and unwanted local and systemic effects is not achievable at the receptor level. A certain dissociation seems to be possible pharmacokinetically: structural modification of the corticosteroid molecule, especially introduction of suitable side chains, can lead to high concentrations of the active principal at the site of the desired effect and to low levels at the site of undesired effects. In the following, the most important pharmacokinetic properties of methylprednisolonaceponate (MPA), the active ingredient of Advantan® are presented: MPA is a di‐ester of the non‐halogenated methylprednisolone with a propionate group at C‐atom 17 and an acetate group at C‐atom 21. The introduction of both ester groups increase markedly the lipophilicity of the molecule and thus penetration into the skin. In addition the acetate side chain at C21 prevents a so‐called acyl‐migration of the propionic acid from C17 to C21 and thus stabilizes the molecule. After penetration out of the formulation into the living skin, MPA is hydrolized by the esterases in the epidermis and dermis at position 21, leading to the formation of methylprednisolone‐17‐propionate (MP‐17‐Prop). MP‐17‐Prop binds more strongly to the corticosteroid receptor than the parent substance MPA and represents the active principle in the skin. This so‐called ‘bioactivation’ proceeds distinctly faster in damaged and inflamed skin compared to healthy skin. After percutaneous absorption MP‐17‐Prop is inactivated by conjugation with glucuronic acid

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb01060.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractBackgroundAttempts to elucidate the pathophysiology of chronic urticaria and its relation with stress have implicated many factors among which the increased activity of the opioid system seems to be particularly interesting.Material and MethodsWe determined the β‐endorphin serum levels in 14 patients with chronic urticaria and 15 healthy members of the medical staff of comparable age.ResultsThe mean β‐endorphin levels of our patients (15.95 ± 2.75 pmol/l) were statistically elevated (P<0.001) compared to those of controls (8.53 ± 2.53 pmol/l).ConclusionsIt is suggested that the opioid system of patients with chronic urticaria is strongly activated in the chronic stage of the

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb00066.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractAimTo investiate the presence of antinuclear and anticytoskeletal autoantibodies in patients with systemic autoimmune and connective tissue diseases.Setting646 sera of 322 patients with systemic sclerosis, systemic lupus eryhtematosus, mixed connective tissue disease, rheumatoid arthritis with or without secondary Sjögren's syndrome, and localized scleroderma, and 127 healthy controls were tested.Methods‘Routine’ indirect immunofluorescence technique on HEp‐2 cells.ResultsAntinuclear antibodies were found in 45–91.1% of the sera. Anti‐intermediate filament antibodies were detected in 24 patients. Eight of the 24 cases had another (second) organ‐specific autoimmune disease, mainly chronic active hepatitis or autoimmune thy

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb00067.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractObjective: Preclinical characterization of methylprednisolone aceponate.Results: The local antiinflammatory potency of methylprednisolone aceponate was equal to the very strong glucocorticoid clobetasol 17‐propionate but higher than the potency of hydrocortisone 17‐butyrate after topical application in 2 animal models of inflammation. Methylprednisolone aceponate is activated enzymatically in the skin. This activation proceeds faster in inflamed tissue. In contrast to clobetasol 17‐propionate, methylprednisolone aceponate was devoid of systemic effects after topical application for 3 days. Finally, whereas clobetasol 17‐propionate induced marked skin atrophy, methylprednisolone aceponate induced only slight atrophogenic changes after long‐term application (up to 43 days) on rat skin, comparable to the effects of hydrocortisone 17‐butyrate.Conclusions: Methylprednisolone aceponate combines high local antiinflammatory potency with very low systemic side effects and only minor local atrophogenic activity. The reason for the dissociation between local antiinflammatory and atrophogenic effects is not known so far. It may be speculated that one of the reasons for the very strong local antiinflammatory activity may reside in the faster enzymatic activation in inflamed tissue. Methylprednisolone aceponate represents a new corticosteroid with which it is possible to improve the dissociation between desired antiinflammatory activity and undesired side effects of topical gluc

ISSN:0926-9959    

DOI:10.1111/j.1468-3083.1994.tb01061.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY