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Biomedical subjects

B Melnik

Publications and source records attributed to B Melnik.

At least 19 recordsLinked to original sources
PubMed1992

Are disturbances of omega-6-fatty acid metabolism involved in the pathogenesis of atopic dermatitis?

Recent evidence indicates that the primary defect in atopic dermatitis (AD) might concern the maturation and differentiation of T cells which infiltrate the skin or are unable to control T cell infiltration of the skin. Unfortunately, there is no information on thymus hormones, T cell differentiation factors or cytokines during early T cell maturation in atopic infants. One of these factors at fault might involve a deficiency of essential long-chain omega-6-fatty acids and E-type prostaglandins which are important for thymic T cell maturation and thymus hormone action. Deficiencies of 6-desaturated omega-6-fatty acids have been observed in plasma phospholipids, epidermal and red cell phospholipids of patients with AD, in umbilical cord plasma lecithin of newborn infants with increased cord blood IgE levels, in cord blood T-cells of 'atopy-at-risk' newborn infants, in atopic monocytes, in adipose tissue lipids of patients with AD, in breast milk lipids of mothers with a history of AD, and in breast milk lipids of mothers of infants with AD. Reduced release of arachidonic acid has been measured in atopic monocytes and platelets. Diminished formation of prostaglandin E2 (PGE2) has been observed in atopic monocytes under stimulated and unstimulated conditions and in inflamed and non-inflamed atopic epidermis. PGE2 is able to suppress interleukin 4-induced IgE synthesis of human non-atopic mononuclear cells in vitro. We have demonstrated a suppressive effect of PGE1 and PGE2 on in vitro IgE synthesis of mononuclear blood cells of patients with AD and respiratory allergies.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatitis, Atopic↗
PubMed1992

[The effect of UV-A and UV-B irradiation on the skin barrier. Skin physiologic, electron microscopy and lipid biochemistry studies].

In order to gain insight into the effects of UV-irradiation on the skin barrier, functional (skin reactivity), electron microscopic and lipid-biochemical studies were performed. In three different irritation models, both UV-A-irradiated and UV-B-irradiated areas proved to be more resistant to damage than normal skin, providing evidence for improvement of barrier function after UV irradiation. Electron microscopic evaluation showed that UV-B induced a significant increase in horny cell layers, whereas after UV-A no change was detected. However, both UV-B and UV-A exposure resulted in an increase in the amount of all stratum corneum lipids. This was also observed in all major ceramide subfractions, which are believed to be the essential lipid constituents for the epidermal barrier function. These findings may explain the known beneficial effects of phototherapy in dermatoses with impaired barrier function, i.e., atopic dermatitis.

Dose-Response Relationship, Radiation↗
PubMed1991

Are deficiencies of prostaglandin-E-mediated immunoregulation involved in increased IgE synthesis of atopic mononuclear cells in vitro?

We demonstrate that spontaneous in vitro immunoglobulin E synthesis of atopic peripheral blood mononuclear cells could be suppressed by the addition of 10(-6) M to 10(-5) M prostaglandin E1 (PGE1) or PGE2. Impaired suppressor T lymphocyte maturation and function in atopic individuals are explained by an insufficient transmission of prostaglandin E (PGE) signals during thymic lymphocyte differentiation as well as an impaired ability of the atopic immune system to activate suppressor T cells by PGE-mediated feed back mechanisms. Decreased levels of 6-desaturated PGE-precursor fatty acids in plasma, T lymphocytes, monocytes, adipose tissue and breast milk have been observed in atopic individuals. These insights might offer a novel approach to the prevention of atopic disease by substitution of the atopic pregnant and nursing woman and her newborn infant with long-chain omega-6-fatty acids.

Cells, Cultured↗
PubMed1991

[Immune regulatory importance of prostaglandins E in atopy].

The concept proposed for the pathogenesis and prevention of atopy [Hautarzt (1989) 40:685-692] is refined by further insights into the immunoregulatory role of E-prostaglandins. It is demonstrated that in vitro IgE synthesis of peripheral blood mononuclear cell cultures of patients with atopic dermatitis is suppressed by the addition of PGE1 or PGE2. The enhanced IgE production in atopy is explained by insufficient PGE-mediated down-regulation of interleukin-4-induced IgE synthesis.

Dermatitis, Atopic↗
PubMed1991

Effects of ultraviolet A and B on the skin barrier: a functional, electron microscopic and lipid biochemical study.

To investigate the effects of ultraviolet A (UVA) and B (UVB) on the skin barrier, functional, electron microscopic and lipid biochemical studies were performed on normal and UV-irradiated skin of volunteers. Skin reactivity against primary irritants was evaluated using the alkali resistance test, the dimethylsulfoxide test and the sodium lauryl sulfate test. In all 3 irritation models, UVA- and UVB-irradiated areas were more resistant to damage than normal skin, indicating improvement of the barrier function after UV irradiation. In a second series of experiments, biopsies were taken and processed for electron microscopic evaluation of the stratum corneum. UVB significantly increased the horny cell layers; UVA did not alter the thickness of the stratum corneum. Finally, stratum corneum lipids were extracted in vivo and quantified after high-performance thin-layer chromatography. UVB and, to some extent, UVA exposure increased the amount of all stratum corneum lipids. This was also observed in all major ceramide subfractions.

Adolescent↗
PubMed1989

Autosomal dominant lamellar ichthyosis exhibits an abnormal scale lipid pattern.

Autosomal dominant lamellar ichthyosis (ADLI) is a recently recognized genetic skin disorder. Clinically and histologically, it cannot be distinguished with certainty from the more frequent autosomal recessive lamellar ichthyosis (ARLI), which in itself may still be heterogeneous. By ultrastructural examination of ADLI a prominent transforming zone between the stratum granulosum and stratum corneum and lipid inclusions in the stratum corneum have been observed. Using sequential high-performance thin-layer chromatography, we studied the plantar scale lipid pattern of two patients, mother and daughter, affected with ADLI. We found a distinctive alteration in the relative composition of the scale lipid pattern characterized by excessive amounts of free fatty acids, triglycerides, elevated n-alkanes, reduced free sterols and decreased total ceramides. This scale lipid profile clearly differs from that of the erythrodermic and non-erythematous variants of ARLI and confirms that this disorder is a distinct entity of the heterogeneous group of lamellar ichthyoses.

Alkanes↗
PubMed1989

[A new concept of the etiopathogenesis and prevention of atopic dermatitis].

The hypothesis proposed for the pathogenesis of atopy links the well-known alterations in cell-mediated and humoral immunity, the disturbances of mediator metabolism and the increased disposition of atopic epidermis for inflammation to a common underlying deficiency in the production of prostaglandin E1. The PGE1 deficiency is explained as the result of reduced delta-6-desaturase activity in atopic patients. The development of depressed cell-mediated immunity is regarded as a PGE1-dependent T-cell-maturation defect of the newborn's immune system post partum. Our hypothesis offers a novel approach to the prevention of atopy by administration of gamma-linolenic acid to newborns with increased risk of atopy and to nursing atopic mothers. Furthermore, it provides an explanation for the beneficial therapeutic effects of dietary supplementation of gamma-linolenic acid in patients with atopic dermatitis.

Alprostadil↗
PubMed1988

[New lipid biochemical aspects in the pathogenesis of a follicular keratinization disorder in acne vulgaris].

Follicular hyperkeratinization of the epithelium of the acroinfundibulum of sebaceous follicles is one of the primary events in the pathogenesis of acne vulgaris. Oral treatment with 13-cis-retinoic acid can reduce these hyperkeratoses. In order to determine whether follicular hyperkeratinization is related to disturbances of epidermal follicular lipids, we analyzed the lipids of initial comedones from 10 patients with nodulocystic acne before and after a 6th weeks oral therapy with 13-cis-retinoic acid (0.7 mg/kg body weight). The treatment with retinoid resulted in a significant increase of epidermal lipids (free sterols: +34%; ceramides: +19%, whereas the lipids of sebaceous origin decreased (glycerides: -36%). The mass ratio of free sterols to cholesterol sulfate increased by 86% compared to pre-treatment levels. These findings support the hypothesis that local follicular deficiencies of epidermal lipids due to increased sebum secretion might induce abnormal follicular keratinization.

Acne Vulgaris↗
PubMed1988

Influence of oral isotretinoin treatment on the composition of comedonal lipids. Implications for comedogenesis in acne vulgaris.

One of the primary events in the pathogenesis of acne vulgaris is abnormal follicular keratinization. Since oral isotretinoin therapy reduces follicular hyperkeratinization in acne, our study has been designed to determine whether epidermal lipid composition of the epithelium of sebaceous follicles is affected by isotretinoin treatment. Noninflamed early comedones obtained from ten patients with nodulocystic acne before and after the 6th week of isotretinoin therapy (mean daily dose 0.7 mg/kg b. wt.) were used as probes of the hyperkeratinizing follicular epithelium. Comedonal lipids were analyzed by high-performance thin-layer chromatography. Oral isotretinoin caused a decrease of the comedonal glyceride fraction by 36% (P less than 0.01), whereas free sterols and total ceramides increased by 34% (P less than 0.10) and 19%, respectively. The changes of comedonal lipids were associated with a significant elevation of the free sterols/cholesterol sulfate ratio of 86% from pretreatment levels (P less than 0.05). The isotretinoin-induced changes of the comedonal lipid composition in direction to a pattern of epidermal lipids of normal desquamating stratum corneum are discussed as a possible comedolytic mechanism of oral isotretinoin treatment.

Acne Vulgaris↗
PubMed1988

[Disorders of retinal function in long-term therapy with retinoid etretinate].

Four patients receiving etretinate as long-term therapy were examined. The accumulated dosage was 135 g for Patient 1, about 80 g for Patients 2 and 3, and 31 g etretinate and 4.8 g etretine (Ro 10-1670; main metabolite of etretinate) for Patient 4. Clinical examinations, visual fields (Haitz, Amsler, Goldmann), and EOGs (two patients) were normal. Patient 1 (135 g) showed a decreased level of rod sensitivity at dark adaptation (Goldmann-Weekers), whereas the cone responses were regular in all cases. Furthermore, Patient 1 showed reduced scotopic ERG amplitudes. Aside from this, photopic and scotopic ERGs were normal as far as a- and b-wave amplitudes and peak latencies were concerned. The flicker fusion frequencies were found to be regular. The peak latencies of the R2-component of the early receptor potentials seemed rather short. In all four patients alterations of color sense were analyzed in the Farnsworth Munsell 100 Hue test. The color sense defect seems to originate in the blue-yellow spectrum and--at higher dosages--extends to the red-green spectrum. Examinations with the anomaloscope revealed deuteranomalous settings. Ophthalmological checks for patients receiving long-term aromatic retinoid therapy are recommended, especially with regard to dark adaptation and color sense.

Adult↗
PubMed1987

Retrospective radiographic study of skeletal changes after long-term etretinate therapy.

Radiographic skeletal examinations were performed in eight adult patients who had received the aromatic retinoid etretinate for various disorders of keratinization over periods ranging from 1 to 7 years. Age- and sex-matched controls were also examined. In all patients, alterations of ossification were found to a varying degree, including calcification of the anterior spinal ligament, vertebral hyperostoses at the anterosuperior and anteroinferior margins of the vertebral bodies, unilateral bridging of vertebral bodies, hyperostoses of the calcanei at the insertion of the plantar ligament and bone accretion at the anterolateral lips of the acetabula. All the bone changes were asymptomatic. Serum calcium, inorganic phosphate, alkaline phosphatase, calcitonin and parathormone were within normal physiological ranges. In general, the bone changes observed after long-term etretinate treatment closely resembled the effects of isotretinoin on the skeleton.

Adult↗
PubMed1987

Characterization of apoprotein metabolism and atherogenic lipoproteins during oral isotretinoin treatment.

Apoprotein, lipoprotein and lipid parameters of 36 normolipidemic subjects (23 males, mean age 22.7 +/- 7.6 years; 13 females, mean age 26.2 +/- 9.8 years) receiving oral isotretinoin (mean daily dose 0.73 +/- 0.26 mg/kg body weight) for nodulocystic acne (n = 18), severe acne papulopustulosa (n = 15), gram-negative folliculitis (n = 2) and papulopustular rosacea (n = 1) were monitored before and during isotretinoin therapy at biweekly intervals over a period of 14.6 +/- 5.6 weeks. Pretreatment values of mean plasma triglycerides increased significantly (p less than 0.001) from 81.8 +/- 31.9 mg/dl to 112.4 +/- 38.7 mg/dl (47.4%) during isotretinoin treatment. With respect to the mean percent increase of plasma triglycerides from pretreatment levels, patients were classified as nonresponders (less than 10% triglyceride increase), responders (greater than 10% less than 50% triglyceride increase) and hyperresponders (greater than 50% triglyceride increase), revealing a distribution of 25.0, 36.1 and 38.9%, respectively. Isotretinoin treatment had no influence on the isoelectric focusing pattern of apoprotein E isoforms and C apoproteins. In particular, apoprotein C-II, the cofactor of lipoprotein lipase, was not affected. No correlation between apoprotein E phenotypes (2/3, 3/3, 3/4) and the mean plasma triglyceride increase could be demonstrated. Apoprotein B-48, a marker of chylomicrons and atherogenic chylomicron remnants, could not be detected by SDS-PAGE. On the other hand in 21.0% of patients with preexisting mean lipoprotein Lp(a) levels of 18.1 +/- 12.9 mg/dl a moderate increase of atherogenic Lp(a) to mean levels of 37.0 +/- 22.0 mg/dl was observed. Pretreatment values of very-low-density lipoprotein (VLDL) apoprotein (apo) B (7.5 +/- 2.0 mg/dl), low-density lipoprotein apo B (67.3 +/- 17.5 mg/dl) and total plasma apo B (76.6 +/- 19.0 mg/dl) increased significantly to levels of 10.3 +/- 2.4 mg/dl (p less than 0.001), 75.7 +/- 15.8 mg/dl (p less than 0.10) and 85.9 +/- 17.7 mg/dl (p less than 0.05), respectively. As lipoprotein lipase and hepatic lipase activities have been shown to be unaffected by isotretinoin treatment, our data support the hypothesis that isotretinoin induces hepatic oversecretion of VLDL, a condition resembling type IV hyperlipidemia in diabetics, familial hypertriglyceridemia of familial combined hyperlipidemia.

Acne Vulgaris↗
PubMed1987

[Unwanted bone changes in systemic treatment with synthetic retinoids].

An update is presented of bone changes taking place in association with oral treatment with the two most relevant synthetic retinoids, 13-cis-retinoic acid (isotretinoin; Roaccutan, Accutane) and etretinate (aromatic retinoid; Tigason, Tegison). All of the important clinical studies are reviewed, including our own results concerning etretinate-associated bone changes. While there are no more doubts about the potential bone toxicity of 13-cis-retinoic acid, the possibility of etretinate-induced bone changes probably occurring within a longer latency period cannot be conclusively assessed at present. The available clinical data concerning the potential skeletal toxicity of 13-cis-retinoic acid and etretinate should be carefully taken into consideration when determining the risk/benefit ratio, especially for long-term oral retinoid treatment.

Administration, Oral↗