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Biomedical subjects

B Melnik

Publications and source records attributed to B Melnik.

27 records · Page 2Linked to original sources
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↗
PubMed1986

Stimulation of the scavenger receptor on monocytes-macrophages evokes release of arachidonic acid metabolites and reduced oxygen species.

Mouse peritoneal macrophages are endowed with a scavenger receptor recognizing modified low density lipoproteins (LDL). Metabolic sequelae of receptor occupancy distinct from lipoprotein processing were examined. Adherent peritoneal macrophages were kept in short term culture. Release into culture supernatants of the arachidonic acid derived eicosanoids prostaglandin E, 6-keto-prostaglandin F1a, thromboxane B2, and leukotriene C4 was assessed, and production of reduced oxygen species superoxide anion and hydrogen peroxide, generated in the oxidative burst, was monitored after challenge of macrophages with acetylated or malondialdehyde modified LDL. Modified LDL at concentrations ranging from 50 to 250 micrograms of protein/ml was noted to augment macrophage arachidonic acid metabolism within 6 hours of addition. Cyclo-oxygenase derivatives were synthesized predominantly, but leukotriene C4 generation was also observed. Further, scavenger receptor occupation triggered the release of superoxide anion and hydrogen peroxide which was more rapid in onset and plateaued after 60 minutes of incubation. Human monocyte-derived macrophages, after 4 days in culture, also generated reduced oxygen species and eicosanoids in response to modified LDL. Along with our previous finding of scavenger receptor mediated lysosomal enzyme liberation, the present study indicates novel functions of these binding sites. Our observations may shed new light on the possible role of monocyte-macrophages in atherogenesis.

Animals↗
PubMed1986

[Retinoids and lipid metabolism].

Since systemic administration of synthetic retinoids was introduced into dermatology and oncology, side-effects of synthetic vitamin-A derivatives on lipid and lipoprotein metabolism have become apparent. Retinoids of the first and second generation, 13-cis-retinoic acid and etretinate, are capable of inducing secondary hyperlipoproteinemias. For further evaluation of the atherogenic risk of retinoid-induced hyperlipoproteinemias, the most relevant effects of natural and synthetic retinoids on lipid metabolism as well as the interactions between lipid and retinoid metabolism are considered in this review.

Arteriosclerosis↗
PubMed1983

Isoproteins of human apolipoprotein A-II: isolation and characterization.

In human serum, polymorphism of apoA-II predominantly in HDL3 could be demonstrated. HDL3-apoA-II was composed of four isoproteins, each with a molecular weight of 8600 (reduced form) and identical immunological properties. The isoproteins are designated apoA-II-1 (pI 5.16), apoA-II-2 (pI 4.89) corresponding to the already known apoA-II monomer band, apoA-II-3 (pI 4.58), and apoA-II-4 (pI 4.31). The amino acid compositions of the A-II isoproteins were virtually identical with the published data for apoA-II. Treatment with acid phosphatase, alkaline phosphatase, or neuraminidase before electrophoresis did not alter the apoA-II pattern. The apoA-II isoprotein pattern was studied in ten male and ten female normolipidemic volunteers, in two patients with Tangier disease, and in three patients with abetalipoproteinemia. The isoelectric focusing patterns of apoA-II appeared virtually identical in all subjects. However, in Tangier disease, due to the low apo-A-II concentration, only apoA-II-1 and apoA-II-2 were detectable, and in abetalipoproteinemia a different relative distribution pattern of the individual isoforms was found as compared to normal HDL3. Our studies indicate that apoA-II, similar to apoA-I, exists in several isoforms. The relationship of these isoforms to each other is at present unclear. They may originate from relatively basic isoproteins that are modified in charge by post-translational processes such as proteolytic cleavage, sequential deamidation, or other mechanisms.

Abetalipoproteinemia↗
PubMed1982

The role of lecithin: cholesterol acyltransferase in high density lipoprotein3/high density lipoprotein2 interconversion.

Serum was incubated in vitro with and without inhibition of lecithin:cholesterol acyltransferase (LCAT, EC 2.3.1.43). High density lipoprotein2 (HDL2) and high density lipoprotein3 (HDL3) were separated by zonal ultracentrifugation and analysed for lipid and apoprotein contents. The incubation of fresh sera resulted in a time-dependent decrease in HDL3 and an increase in HDL2. At the end of 24 h incubation HDL3 disappeared completely and the HDL2 peak had reached its maximum. The newly formed HDL2 was relatively enriched in total protein (apoprotein A-I, C-apoproteins) and cholesteryl esters, and depleted in phosphatidylcholine. Its migration in polyacrylamide gel electrophoresis was identical with HDL2 contained in fresh serum or HDL2 isolated from serum by zonal ultracentrifugation. The generated HDL2 particles exhibited the same electron microscopical characteristics as reference HDL2 samples prior to incubation. Addition of Ellman's reagent to the incubation mixture or heat inactivation of the samples prior to incubation resulted in a complete inhibition of HDL3/HDL2 interconversion, whereas addition of 1 mol/l NaCl had no detectable influence. There was also a substantial increase in HDL2 when VLDL-deficient serum was incubated at 37 degrees C. Similarly, in fresh serum from a patient affected with familial lipoprotein lipase deficiency, HDL3 was completely converted to HDL2. Our experiments demonstrate that LCAT promotes HDL3/HDL2 interconversion in native serum irrespective of the presence or absence of triglyceride-rich lipoproteins and lipoprotein lipase.

Adult↗