ABSTRACT
Temporal and concentration dependences of the effect of the new synthetic gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (ABMP) and reference glucocorticoids (dexamethasone and hydrocortisone) and progesterone on the proliferative activity of rat skin fibroblasts were examined using the MTT assay. The results demonstrated that ABMP along with glucocorticoids produced an antiproliferative action against fibroblasts, with the maximum (38%) suppression of the metabolic activity of cells observed after 5-day incubation at a drug concentration of 10(-5) M.
Subject(s)
Cell Proliferation/drug effects , Fibroblasts/metabolism , Glucocorticoids/pharmacology , Progestins/pharmacology , Skin/metabolism , Animals , Dose-Response Relationship, Drug , Fibroblasts/cytology , Rats , Skin/cytologyABSTRACT
The effects of a new synthetic gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-on (ABMP) and reference drug progesterone on rat skin fibroblasts were evaluated by variations in lysosomal enzyme activity (cathepsin D and beta-glucosidase). Our results suggest that ABMP exhibits lysosomotropic properties, which depended on its concentration and time of treatment. The direct effect of progesterone on lysosomal enzyme activity in skin fibroblasts was compared to the influence of systemic treatment with gestagens on skin lysosomes. The data indicate that local application of gestagen preparations holds much promise for the therapy of skin diseases accompanied by increased proliferation (e.g. psoriasis).
Subject(s)
17-alpha-Hydroxyprogesterone/analogs & derivatives , Cathepsin D/metabolism , Progesterone/pharmacology , Progestins/pharmacology , Skin/drug effects , beta-Glucosidase/metabolism , 17-alpha-Hydroxyprogesterone/pharmacology , 17-alpha-Hydroxyprogesterone/therapeutic use , Animals , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/enzymology , Humans , Lysosomes/enzymology , Progesterone/therapeutic use , Progestins/therapeutic use , Rats , Skin/cytology , Skin/enzymology , Skin Diseases/drug therapy , Skin Diseases/pathologyABSTRACT
The in vitro study of the action of the complex of natural cytokines (CNC), or preparation Superlymph, on different microbial test strains (Staphylococcus aureus, Escherichia coli, yeast-like fungi of the genus Candida) was carried out. CNC suppressed the growth of S. aureus test culture, depending on the concentration of the preparation. The inhibiting effect was observed in the presence of Ca and Mg bivalent cations in the medium. Under the chosen conditions of the experiment CNC did not inhibit the growth of E. coli test cultures, as well as test cultures of yeast-like fungi of the genus Candida. In addition to its antibacterial effect, Superlymph also produced some effect on the release of cathepsin G, the lysosomal enzyme of human leukocyte granules.
Subject(s)
Anti-Bacterial Agents/pharmacology , Cytokines/pharmacology , Staphylococcus aureus/drug effects , Calcium , Cations , Culture Media , Dose-Response Relationship, Drug , Magnesium , Staphylococcus aureus/growth & developmentSubject(s)
Dermatitis, Allergic Contact/metabolism , Glutathione/metabolism , Lipid Peroxidation/drug effects , Progesterone/pharmacology , Skin/drug effects , Administration, Cutaneous , Animals , Dermis/drug effects , Dermis/metabolism , Epidermis/drug effects , Epidermis/metabolism , Female , Injections, Subcutaneous , Ointments , Oxidation-Reduction , Progesterone/administration & dosage , Rats , Skin/metabolismSubject(s)
Dermatitis, Allergic Contact/metabolism , Glucocorticoids/pharmacology , Glutathione/metabolism , Progestins/pharmacology , Skin/drug effects , Animals , Dermatitis, Allergic Contact/enzymology , Dermis/drug effects , Dermis/metabolism , Epidermis/drug effects , Epidermis/metabolism , Female , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Hydrocortisone/pharmacology , Oxidation-Reduction , Progesterone/pharmacology , Rats , Skin/enzymology , Skin/metabolismSubject(s)
Hormones/pharmacology , Phospholipases A/metabolism , Skin/drug effects , Skin/enzymology , Animals , Cell Membrane/drug effects , Cell Membrane/enzymology , Dermis/drug effects , Dermis/enzymology , Dermis/ultrastructure , Epidermis/drug effects , Epidermis/enzymology , Epidermis/ultrastructure , Estradiol/pharmacology , Female , Hydrocortisone/pharmacology , Intracellular Membranes/drug effects , Intracellular Membranes/enzymology , Lysosomes/drug effects , Lysosomes/enzymology , Male , Phospholipases A2 , Progesterone/pharmacology , Rats , Skin/ultrastructure , Testosterone/pharmacologySubject(s)
Estradiol/pharmacology , Hydrocortisone/pharmacology , Lysosomes/metabolism , Membrane Lipids/metabolism , Phospholipids/metabolism , Skin/metabolism , Animals , Chromatography, Thin Layer , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/ultrastructure , In Vitro Techniques , Intracellular Membranes/drug effects , Intracellular Membranes/metabolism , Lysosomes/drug effects , Rats , Skin/drug effects , Skin/ultrastructureSubject(s)
Acid Phosphatase/metabolism , Cardiotonic Agents/pharmacology , Digoxin/pharmacology , Myocardium/enzymology , beta-Galactosidase/metabolism , beta-Glucosidase/metabolism , Acid Phosphatase/antagonists & inhibitors , Animals , Cardiotonic Agents/administration & dosage , Digoxin/administration & dosage , Dose-Response Relationship, Drug , Enzyme Activation , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/pharmacology , Male , Rats , Time Factors , beta-Galactosidase/antagonists & inhibitors , beta-Glucosidase/antagonists & inhibitorsSubject(s)
Lipid Peroxidation/drug effects , Progesterone/pharmacology , Skin/drug effects , Animals , Cathepsin D/metabolism , Female , Free Radicals , Hydrolysis , Lysosomes/drug effects , Lysosomes/enzymology , Lysosomes/metabolism , Male , Oxidation-Reduction , Phospholipases A/metabolism , Rats , Skin/enzymology , Skin/metabolism , beta-Glucosidase/metabolismABSTRACT
The effect of ultrasound (US) and the antibiotic amphotericin (A-B) on the structure of Candida albicans membranes. The most expression of destructive processes and appearance of free radicals in mycetic cells was observed in combination of US and A-B by chemiluminescence and ultrastructural analyses. The mechanisms of action of US and A-B on mycetic cells were discussed in the article. The expedience of the combination of US and A-B in candidiasis as a factor, increasing fungicidal effect on the candidiasis agent of Candida albicans.
Subject(s)
Amphotericin B/pharmacology , Candida albicans/drug effects , Ultrasonics , Analysis of Variance , Candida albicans/metabolism , Candida albicans/ultrastructure , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Luminescent Measurements , Microscopy, ElectronABSTRACT
The study was undertaken to examine the lipid composition of and the activity of phospholipase A2 in the skin of patients with psoriasis. There were increases in the levels of phosphatidylcholine, phosphatidylethanolamine and the activity of phospholipase A2 in psoriatic papule as compared to the normal skin. A possible role of glucocorticoids and the revealed abnormalities in the pathogenesis of psoriasis is discussed.
Subject(s)
Lipids/analysis , Psoriasis/metabolism , Skin/chemistry , Chromatography, Thin Layer , Humans , Phospholipases A/analysis , Phospholipases A2ABSTRACT
The activity of one of the lysosomal membrane marker enzymes--acid phosphatase from the Candida yeast fungi on their exposure to ultrasound (US), polyenic antibiotics (amphotericin B and nystatin) dye antiseptics (ethacridine lactate, methylene blue), and their combinations was assayed. The impact of US and the drugs, in particular their combination, was found to be followed by activation of the fungal lysosomal apparatus function and increases in their catabolic processes. The highest rise in lysosomal catabolic activity was found when the polyenic antibiotics were used in combination with US, which reflects the higher damaging effect of this combination against Candida lysosomal membranes than the dyes and of these antibiotics and US alone. The studies provide strong evidence for the preference of the combined use of US and the polyenic antibiotics in candidiasis as a factor enhancing their fungicidal effect against Candida yeast fungi.
Subject(s)
Acid Phosphatase/drug effects , Anti-Bacterial Agents/pharmacology , Candida/enzymology , Coloring Agents/pharmacology , Ultrasonics , Acid Phosphatase/analysis , Antifungal Agents/pharmacology , Candida/chemistry , Candida/drug effects , Intracellular Membranes/enzymology , Lysosomes/enzymology , Polyenes/pharmacology , SpectrophotometryABSTRACT
The effects of estradiol on intensity of lipid peroxidation in rats' derma and epiderma have been studied. More high level of lipid peroxidation, correlating with activity of water-solved antioxidants of these tissues in comparison with epidermis has been detected in derma. The level of lipid peroxidation decreased in proportion to hormone concentration when adding estradiol to tissue homogenates in vitro.
Subject(s)
Epidermis/drug effects , Estradiol/pharmacology , Lipid Peroxidation/drug effects , Sex Characteristics , Skin/drug effects , Animals , Epidermis/metabolism , Female , Ferrous Compounds/pharmacology , Luminescent Measurements , Male , Oxidation-Reduction , Rats , Skin/metabolismABSTRACT
The effect of dexamethasone on content of phospholipids in rats' and rabbits' skin has been studied. It has been shown that the present of phospholipids in total content of lipids was more in skin of rats than skin of rabbits. Phosphocholine and phosphatidylethanolamine predominated among phospholipids in human skin as well. Dexamethasone changed both the total content of phospholipids and its fractions. The role of observed alterations to the regulation of cell process has been discussed.
Subject(s)
Dexamethasone/pharmacology , Phospholipases A/metabolism , Phospholipids/metabolism , Skin/drug effects , Animals , Male , Phosphatidylcholines/metabolism , Phosphatidylethanolamines/metabolism , Rabbits , Rats , Skin/metabolism , Species SpecificityABSTRACT
The mechanisms of glucocorticoids' effect on the functional activity of lysosomes in rats dermis and epidermis have been studied. The activity of enzymes in both parts of skin in females was more than in ones in males. Intraperitoneal injection of hydrocortisone doesn't change the functional activity of lysosomes in skin in doses less than 1 mg per 100 g of weight apart from the sex of rats. The hormone in dose 1 mg/100 g of weight causes statistically reliable releasing of lysosomal glycosidases from the epidermis and dermis of both of the sex of rats, and cathepsin D in females as well. In experiments in vitro the concentration of hormone 10(-8) M causes the fall of possibility of enzymatic fission of substrates in dermis, but the concentration 10(-3) M causes the increasing of the one on the contrary. Enzymatic alterations in the results of action of glucocorticoids in dermis and in epidermis as in males so in females of rats and the causes of their distinguishes have been discussed.
Subject(s)
Epidermis/drug effects , Hydrocortisone/pharmacology , Lysosomes/drug effects , Skin/drug effects , Adrenal Glands/physiology , Adrenalectomy , Animals , Cathepsin D/metabolism , Dose-Response Relationship, Drug , Epidermis/enzymology , Female , Lysosomes/enzymology , Male , Rats , Sex Characteristics , Skin/enzymologyABSTRACT
The study was concerned with evaluation of the parameters of specific binding of 17-beta-estradiol to myometrial plasma membrane in tumor growth versus lipid profile of the membrane and A2 and C phospholipase activity. Tumor growth was shown to involve an increase in the association constant of plasma membrane, changes in the lipid profile and activity of the enzymes. The role of these factors in myometrial carcinogenesis is discussed.
Subject(s)
Cell Membrane/metabolism , Estradiol/metabolism , Membrane Lipids/metabolism , Myometrium/metabolism , Uterine Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Myometrium/cytology , Myometrium/pathology , Phospholipases A/metabolism , Phospholipids/metabolism , Receptors, Estradiol/metabolism , Type C Phospholipases/metabolism , Uterine Neoplasms/enzymology , Uterine Neoplasms/pathologyABSTRACT
It was found out that thymus accumulated 3H-testosterone from blood at the same degree as liver, prostate and skeletal muscle. However, hormone was quickly eliminated from the thymus and prostate accumulated it. Thymocytes bound about 5% of testosterone accumulated by the organ. The dependence of binding of 3H-testosterone by thymocytes in vitro and the absence of competition between labelled and unlabelled forms of hormone were revealed. The results obtained make it possible to conclude that thymocytes lack the systems of specific binding of androgen.
Subject(s)
Testosterone/metabolism , Thymus Gland/metabolism , Animals , Dose-Response Relationship, Drug , Male , Orchiectomy , Rats , Testosterone/pharmacology , Thymus Gland/cytology , Thymus Gland/drug effects , Time Factors , Tissue Distribution , TritiumABSTRACT
The data on lysosomotropic effect of steroid hormones are reviewed. The effect of steroid hormones correlated with the type of tissues and dose of hormones. A possible role of lysosomes in realization of hormonal signal in the cell biological response is discussed.
Subject(s)
Lysosomes/metabolism , Steroids/pharmacokinetics , Animals , Biological Transport , Humans , Receptors, Steroid/drug effects , Receptors, Steroid/metabolism , Steroids/therapeutic useABSTRACT
Lipid composition of cell plasma membranes and hepatocyte lysosome phospholipase activity were studied. The data obtained have shown the phospholipid involvement in the realization of steroid hormone effect on the effector cells. The role of lysosomes in the same process is discussed.