cyclic-gmp and Psoriasis

Topics: Animals; Arachidonic Acids; Cyclic AMP; Cyclic GMP; Disease Models, Animal; Epidermal Growth Factor; Phospholipids; Psoriasis; Skin; Swine

Topics: Arachidonic Acids; Cyclic AMP; Cyclic GMP; Humans; Leukotriene B4; Polyamines; Psoriasis; Skin; SRS-A

Anthralin was first synthesized in 1916. Earlier, a natural product, chrysarobin, originally derived from the South American araroba tree, had been used to treat psoriasis. Anthralin was first used in Germany, and later in the Ingram regimen in Britain, but it has never been popular with American dermatologists. This is probably due to the side effects of staining and irritation of the skin. Attempts to reduce these using low concentration, short contact therapy, and concomitant steroid therapy, have been only partially successful. It may be that better instruction of patients and physicians will lead to wider use of this effective topical agent for the treatment of psoriasis. The mode of action of anthralin is thought to be either through its effect on deoxyribonucleic acid (DNA), probably mitochondrial DNA, which reduces cell turnover, or through its effects on various enzyme systems, including those of polyamine synthesis and respiration. The aims of this review are to discuss historical aspects of anthralin and to update its chemistry, pharmacology, and clinical usage.

Topics: Anthracenes; Anthralin; Cell Division; Chemistry; Cyclic AMP; Cyclic GMP; DNA Replication; Drug Administration Schedule; England; Erythema; Glucosephosphate Dehydrogenase; History, 19th Century; History, 20th Century; Humans; Mitochondria; Oxidation-Reduction; Polyamines; Psoriasis; Skin Absorption; Skin Neoplasms; Structure-Activity Relationship

Topics: Adenylyl Cyclases; Arachidonic Acids; Calmodulin; Cell Division; Cyclic AMP; Cyclic GMP; Epidermis; Glycogen; Glycolysis; History, 20th Century; Homeostasis; Humans; Keratins; Lithium; Phosphorylation; Plasminogen Activators; Polyamines; Propranolol; Psoriasis; Receptors, Cell Surface; Skin

Topics: Antibody Formation; Autoantibodies; Chemotaxis, Leukocyte; Cyclic AMP; Cyclic GMP; Epidermis; HLA Antigens; Humans; Immunity, Cellular; Immunoglobulins; Lymphocyte Activation; Lymphocytes; Phagocytosis; Psoriasis; Rosette Formation; T-Lymphocytes, Regulatory

Topics: Arachidonic Acids; Cell Division; Culture Techniques; Cyclic AMP; Cyclic GMP; Epidermal Cells; Epidermis; Epinephrine; Homeostasis; Humans; Nucleotides, Cyclic; Polyamines; Prostaglandins; Prostaglandins E; Psoriasis; Receptors, Adrenergic, beta; Skin

Topics: Arachidonic Acids; Cell Differentiation; Cell Division; Cyclic AMP; Cyclic GMP; Epidermis; Humans; Polyamines; Prostaglandins; Psoriasis

Topics: Adenylyl Cyclases; Animals; Anti-Inflammatory Agents; Antiviral Agents; Asthma; Cardiovascular Diseases; Cricetinae; Cyclic AMP; Cyclic GMP; Disease; Enzyme Activation; Extracellular Space; Guanylate Cyclase; Humans; Hypoglycemic Agents; Isoenzymes; Kinetics; Mental Disorders; Mice; Neoplasms; Obesity; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Psoriasis; Rats

Topics: Adenylyl Cyclases; Cell Differentiation; Cyclic AMP; Cyclic GMP; DNA; Humans; Mitosis; Phosphoric Diester Hydrolases; Psoriasis

Psoriasis is a disease characterized by benign but unrestricted epithelial growth. The molecular pathophysiology of this unregulated growth has been discussed. A better understanding of the role of the cell surface, cyclic nucleotides, arachidonic acid-prostaglandin metabolism, and polyamines in psoriasis may clarify our understanding of this disease and produce clues pertinent to a general understanding of growth regulation.

Topics: Cell Membrane; Cyclic AMP; Cyclic GMP; HLA Antigens; Humans; Nucleotides, Cyclic; Polyamines; Prostaglandins; Prostaglandins E; Prostaglandins F; Psoriasis; Skin; Spermidine; Spermine

The second messengers cyclic AMP and cyclic GMP in several organs appear to coordinate those molecular events which are responsible for specialized organ function. As a result of balanced cell proliferation and specialization, epidermis functions by terminal specialization which provides a barrier between man and environment. Since the epidermal component of psoriasis is a classic example of deranged epidermal homeostasis, which has a low level of cyclic AMP and a high level of cyclic GMP, it seems reasonable that rebalancing these cyclic nucleotides might ultimately be a safe and effective therapy for psoriasis and other proliferative skin diseases.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenylyl Cyclases; Animals; Cyclic AMP; Cyclic GMP; Glycogen; Growth Inhibitors; Guanylate Cyclase; Homeostasis; Humans; Light; Mice; Mitosis; Protein Kinases; Psoriasis; Rats; Skin; Temperature

Topics: Animals; Cell Division; Cyclic AMP; Cyclic GMP; DNA; Fibroblasts; Humans; Hyperplasia; Lymphocytes; Phorbol Esters; Prostaglandins E; Psoriasis; Salivary Glands; Skin; Tretinoin; Ultraviolet Rays

This review deals with newer aspects of the pathogenesis of skin lesions in psoriasis vulgaris. Genetic determinants and mechanisms of provocation of psoriasis are discussed. The pathobiology of the psoriatic lesions is reviewed from a more functional point of view. The disturbances of epidermal cell proliferation and epidermal cell differentiation in the psoriatic lesions are discussed. Newer findings about chalones and the disturbances of the c-AMP/c-GMP-system are reviewed. The changes of capillaries and the inflammatory reaction in the psoriatic lesion, the morphology of the initial psoriatic lesion and newer immunological findings in patients with psoriasis are reviewed. A working hypothesis of the pathogenesis of the psoriatic lesion is given.

Topics: Capillaries; Cell Differentiation; Cell Division; Cyclic AMP; Cyclic GMP; Growth Inhibitors; Humans; Psoriasis; Skin

Topics: Cell Physiological Phenomena; Cyclic AMP; Cyclic GMP; Endothelium; Humans; Prostaglandins E; Psoriasis; Skin; Skin Diseases; Wound Healing

Numerous general metabolic systems are disturbed in association with psoriasis: the frequency of diabetes mellitus and of hyperuricaemia, lipid disturbances and a decrease in folates as a result of their excessive consumption by the skin. Cutaneous metabolism is also altered. Numerous compounds are formed in excess from glucose: amino acids, fatty acids and sterols, lactic acid--the formation of which persists in the corneal layer, ribose and ribulose--synthesised as a result of glucose-6-phosphate-dehydrogenase hyperactivity (role of the increased catabolism of dehydro-epi-androsterone) and uronic acids. The accumulation of glycogen is probably due to excessive synthesis and impaired breakdown. These abnormalities may exist to a lesser extent in healthy skin. In the corneal layer there are lipid vacuoles visible under the electron microscope. Lipogenesis is increased. The same may apply to lipolysis (blood NEFA are increased). Esterification of cholesterol is decreased. The utilisation of ATP by cell membranes is probably diminished (low ATP ase activity). The absence of formation of keratohyaline is due to persistence of the repression which normally prevents it in the mucus body. Renewal of collagen appears increased. The synthesis of DNA is increased in the lesions and neighbouring areas. It is possible that these various abnormalities are dependent upon modifications in the regulator systems of cyclic AMP and GMP, variations in which are however discussed.

Topics: Adenosine Triphosphatases; Blood Glucose; Collagen; Cyclic AMP; Cyclic GMP; DNA; Glycogen; Glycolysis; Humans; Keratins; Lipid Metabolism; Metabolic Diseases; Metals; Mitochondria; Oxygen Consumption; Pentosephosphates; Proteins; Psoriasis; Skin

The two cyclic nucleotides, cyclic AMP and cyclic GMP, appear to be central to the metabolic regulation of cell proliferation and differentiation in various cells. Moreover, in many systems glucocorticoids appear to act in concert with or parallel to cyclic AMP. The available evidence suggests that these three molecular species--cyclic AMP, cyclic GMP, and glucocorticoids--may be essential to the normal regulation of epidermal proliferation and differentiation. In 1970, we suggested that perturbed epidermal homeostasis, exemplified by psoriasis, might be associated with low cellular levels of cyclic AMP and, in 1972, with high levels of cyclic GMP as well. Subsequent measurements of these two cyclic nucleotides in our laboratory showed a probable reduction in the cyclic AMP/cyclic GMP ratio in lesional psoriatic tissue. This led to the hypothesis that the cardinal features of psoriatic epidermis--glycogen accumulation, excessive proliferation, and reduced cell specialization--are the results of this reduced ratio. A corollary of this hypothesis was that a psoriatic lesion could not begin or exist without this altered cyclic nucleotide ratio. Recently, four different agents--lithium, a beta adrenergic blocking agent, antimalarials, and iodide--have been found to exacerbate psoriasis and to reduce the formation of cyclic AMP in various tissues. Consequently we believe that cyclic nucleotides are of central importance in the pathogenesis of the epidermal component of psoriasis.

Topics: Animals; Antimalarials; Cell Differentiation; Cell Division; Cyclic AMP; Cyclic GMP; Drug Synergism; Glucocorticoids; Humans; Iodine; Lithium; Mice; Nucleotides, Cyclic; Psoriasis; Skin

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Adenylyl Cyclases; Arteriosclerosis; Calcium; Catecholamines; Cyclic AMP; Cyclic GMP; Endocrine System Diseases; Enzyme Activation; Humans; Hypertension; Psoriasis; Receptors, Cell Surface; Vascular Resistance

Topics: Adenylyl Cyclases; Animals; Cell Differentiation; Cell Division; Cyclic AMP; Cyclic GMP; Glycogen; Guanylate Cyclase; Histocytochemistry; Humans; Microscopy, Electron; Phentolamine; Phosphoric Diester Hydrolases; Propranolol; Protein Kinases; Psoriasis; Skin

Topics: Affective Symptoms; Animals; Asthma; Caffeine; Calcitonin; Calcium; Catecholamines; Circadian Rhythm; Cyclic AMP; Cyclic GMP; Dermatitis, Atopic; Diabetes Insipidus; Glucagon; Growth Hormone; Humans; Hypercalcemia; Hyperparathyroidism; Hypocalcemia; Hypoparathyroidism; Insulin; Organ Specificity; Parathyroid Hormone; Psoriasis; Vasopressins

A positive association between intake of calcium channel blockers and psoriasis has been observed recently. Intake of blockers of voltage-gated calcium ion channels is associated with outbreaks of psoriasis after a latent period in patients with and without a previous family history of psoriasis. This suggests that interfering with calcium influx may trigger psoriasis. Calcium influx also occurs via cyclic guanosine monophosphate-gated channels; human keratinocytes contain functional and non-functional (splice variants) versions of these channels. We show here that keratinocytes and skin from psoriatic individuals express higher levels of mRNA encoding a non-functional cyclic guanosine monophosphate-gated calcium channel and that high expression of the splice variant by transfection of cells in culture leads to loss of protein expression for the functional cyclic guanosine monophosphate-gated Ca2+ channels.

Topics: Adult; Aged; Biopsy, Needle; Calcium Channels; Calcium Signaling; Case-Control Studies; Cells, Cultured; Cyclic GMP; Female; Genetic Markers; Humans; Immunohistochemistry; Ion Channel Gating; Keratinocytes; Male; Middle Aged; Probability; Psoriasis; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; RNA, Messenger; Sampling Studies; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric

Topics: Animals; Cell Division; Cyclic GMP; Humans; Interferon-gamma; Keratinocytes; Langerhans Cells; Neurosecretory Systems; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Protein Kinase C; Psoriasis

Topics: Adolescent; Adult; Cyclic AMP; Cyclic GMP; Female; Humans; Male; Middle Aged; Psoriasis; Skin

Topics: Connective Tissue Diseases; Cyclic AMP; Cyclic GMP; Humans; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Plant Extracts; Plants, Medicinal; Psoriasis; Sialic Acids

cAMP and cGMP production was determined in normal and psoriatic (involved or uninvolved) epidermis. After homogenization, epidermal strips were incubated with saturating concentrations of ATP or GTP, respectively, for cAMP and cGMP production. Cyclic nucleotides were measured by radioimmunoassay before and after 5, 10, 20 min of incubation. The kinetics of cAMP and cGMP production were linear during the 20 min of incubation. Comparison of normal skin, uninvolved and involved psoriatic skin, prior to and after 20 min of incubation showed the following results: cAMP levels were significantly higher in normal skin than in psoriatic skin at zero time (p less than 0.01) and after incubation (p less than 0.05). cGMP levels were not significantly different in the three tissues at zero time. After incubation, psoriatic involved epidermis exhibited a higher production of cGMP than normal skin (p less than 0.05). Thus, the ratio cAMP/cGMP was higher in normal skin than in psoriatic skin at the basic level (p less than 0.05) and after incubation (p less than 0.01). These results indicate an imbalance in cyclic nucleotides metabolism in psoriatic skin without a significant difference between uninvolved and involved epidermis.

Topics: Adenosine Triphosphate; Culture Techniques; Cyclic AMP; Cyclic GMP; Guanosine Triphosphate; Humans; Psoriasis; Radioimmunoassay; Skin

Cyclic GMP levels in epidermis of normal subjects and of psoriatic patients were measured with a highly sensitive radioimmunoassay method. Technical improvements for the assay are 2-fold: (1) skin samples were frozen in vivo before biopsy and local injection of any anesthetic was avoided to overcome ischemia effect which could lower cyclic GMP artificially; (2) epidermis was microdissected to avoid contamination of dermis and keratin layers. The results show that on a per mg tissue dry weight basis the cyclic GMP levels are about 200 fmol in the involved lesional epidermis and 70 fmol in the uninvolved or normal epidermis. Similarly increases in the cyclic GMP levels in the lesional epidermis are observed when the data are expressed either on a DNA or protein basis. The cyclic GMP level in normal epidermis from nonpsoriatic subjects is the same as that in the uninvolved epidermis of psoriasis patients.

Topics: Cyclic GMP; Epidermis; Humans; Psoriasis

Eighteen patients with active psoriasis were investigated for antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by monocytes and neutrophil leukocytes. Patients with extensive psoriatic lesions showed increased ADCC whereas patients with minimal psoriasis had normal monocyte and neutrophil function. After clinical remission the ADCC became normal. No stimulatory factors in psoriatic serum could be demonstrated. The increased monocyte and neutrophil cytotoxicity in severe psoriasis is not explained by altered cyclic nucleotide levels as cAMP and cGMP levels were normal in psoriatic monocytes and neutrophils showing both increased and normal ADCC. Our results indicate that increased ADCC is secondary to the psoriatic activity.

Topics: Adolescent; Adult; Aged; Antibody-Dependent Cell Cytotoxicity; Cyclic AMP; Cyclic GMP; Female; Humans; Leukocyte Count; Male; Middle Aged; Monocytes; Neutrophils; Psoriasis

Lymphocytes from psoriatic patients were found to contain reduced levels of adenosine 3':5'-cyclic phosphate, guanosine 5'-cyclic phosphoric acid, and prostaglandin E, as compared with lymphocytes from normal subjects. The difference in prostaglandin F levels between psoriatic and control subjects was not statistically significant. These results could point to an immunologic defect in the immune system in psoriasis.

Topics: Adult; Cyclic AMP; Cyclic GMP; Female; Humans; Immunity, Cellular; Lymphocytes; Male; Prostaglandins E; Psoriasis

Psoriasis, like diabetes, is a multifactorial genetic disease with complex interactions of deranged metabolism. Factors that affect epidermal differentiation and proliferation include cyclic nucleotide interactions, polyamine metabolism, cell surface--cytoskeleton interactions, and arachidonic acid--prostaglandin cascade. Evidence indicates that pharmacologic manipulation of the so-called critical metabolic systems not only may help us to understand the pathophysiology of psoriasis but also may yield improved treatments for the disease.

Topics: Arachidonic Acids; Cell Membrane; Cyclic AMP; Cyclic GMP; HLA Antigens; Humans; Polyamines; Prostaglandins E; Prostaglandins F; Psoriasis; Skin

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Aloe; Anthraquinones; Bacteria; Cassia; Chelating Agents; Cyclic AMP; Cyclic GMP; Humans; Medicine, Traditional; Nucleic Acids; Phytotherapy; Plant Extracts; Plants, Medicinal; Psoriasis; Urinary Calculi

Absolute values of both cAMP and cGMP leves were measured in the involved and uninvolved skin of psoriatic patients, and also the effect of topical therapy on these levels in the involved skin was studied. The mean cGMP level in the untreated psoriatic plaque was increased by 300% compared to the non-involved skin (which did not differ from normal skin), but no significant difference in cAMP levels was found. Epidermal stripping of uninvolved skin, which stimulates cell proliferation, did not change the cGMP level. Treatment of the psoriasis with dithranol caused the cGMP levels to return to normal, but a potent topical glucocorticoid, in contrast, produced no such decrease. This may imply that the two drugs act at different levels in suppressing cell replication, and dithranol may be a useful tool for the further investigation of cyclic nucleotide metabolism.

Topics: Anthracenes; Anthralin; Clobetasol; Cyclic AMP; Cyclic GMP; Epidermis; Humans; Psoriasis; Skin

The changes in cAMP, cGMP, adenylate cyclase, cyclic phosphodiesterase, and prostaglandins in psoriatic epidermal cells were compiled and critically discussed. The results of the pertinent studies permit the assumption that therapeutic approaches in psoriasis via the system of cyclic nucleotides and prostaglandins might be promising.

Topics: Adenylyl Cyclases; Cyclic AMP; Cyclic GMP; Glucosephosphates; Humans; Pentosephosphates; Phosphoric Diester Hydrolases; Photochemistry; Prostaglandins; Psoriasis; Skin; Skin Pigmentation

Topics: Animals; Cell Division; Cyclic AMP; Cyclic GMP; Enzyme Activation; Humans; Protein Kinases; Psoriasis; Skin; Skin Physiological Phenomena

Immunohistochemical localizations of 3',5'-cyclic AMP (cAMP) and 3',5'-cyclic GMP (cGMP) were performed in the involved and non-involved epidermis of psoriasis and in the normal controls. The following results were obtained: 1. In the normal epidermis, cAMP was located in the cytoplasm throughout the epidermis but it was more pronounced in its upper portions, especially in the granular layers. Occasionally it was also observed in the nuclear membrane. However, cGMP was located mainly in the cytoplasm of the lower layers of epidermis, though the fluorescence was less pronounced as compared with that of cAmP. 2. In the noninvolved psoriatic epidermis, the localization pattern of cAMP was basically similar to that in the normal control, but its fluorescence seemed more pronounced. The fluorescence of cGMP was essentially the same as that in the normal control. 3. In the involved psoriatic epidermis, the distribution pattern of cAMP was essentially the same as that in the normal control, but its fluorescence seemed more pronounced. Marked increase in the fluorescence of cGMP was observed in the involved psoriatic epidermis, though it was much more pronounced in its lower portions.

Topics: Cell Differentiation; Cell Division; Cyclic AMP; Cyclic GMP; Epidermal Cells; Epidermis; Humans; Immunologic Techniques; Psoriasis

Neutrophil chemotaxis was assessed in 69 psoriatic patients and 37 healthy human subjects. It was found to be significantly enhanced in 52 untreated patients. In 20 patients treated with an orally-administered phosphodiesterase inhibitor, Diphylline, neutrophil chemotaxis was normal. The enhanced chemotactic response of neutrophils from untreated patients with minimal skin lesions was at least equal to the response of those from patients with extensive skin lesions. Preincubation of normal human leukocytes with plasma derived from patients with widespread lesions markedly reduced their chemotactic activity. Plasma derived from patients with extensive skin lesions exhibited marked chemoattracting properties in comparison with plasma from healthy subjects. It is postulated that the basic intrinsic abnormality of neutrophil function in psoriasis could be caused by a decreased cyclic AMP/cyclic GMP ratio, similar to the decreased cyclic AMP/cyclic GMP ratio found in the lesional epidermis of this disease. Plasma factors which influence chemotaxis in psoriasis are related to the extent of the eruption and their effect is contrary to the effect of the basic intrinsic abnormality of psoriatic neutrophils.

Topics: Administration, Oral; Adolescent; Adult; Aged; Chemotaxis, Leukocyte; Child; Cyclic AMP; Cyclic GMP; Epidermis; Ethylenediamines; Female; Humans; Hydroxyurea; Male; Methotrexate; Middle Aged; Neutrophils; Phosphodiesterase Inhibitors; Psoriasis; Skin; Theophylline

Topics: Cyclic AMP; Cyclic GMP; Epidermis; Humans; Protein Binding; Psoriasis; Radioimmunoassay

Topics: Cyclic AMP; Cyclic GMP; Humans; Psoriasis; Skin

The psoriatic epidermis is more active metabolically and its rate of proliferation is faster, showing incomplete differentiation as a result of the imbalance between the low level of cyclic AMP and the high level of cyclic GMP. The low cyclic AMP levels are due to hyperactivity of the phosphodiesterase which hydrolyzes cyclic AMP. Xanthine derivatives are found to be potent phosphodiesterase inhibitors. 15 psoriatic patients were treated with tablets of xanthine derivatives (dyphylline, aminophylline). The obtained results are discussed.

Topics: Adolescent; Adult; Aged; Aminophylline; Child; Cyclic AMP; Cyclic GMP; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Psoriasis; Skin; Theophylline

Topics: Cyclic AMP; Cyclic GMP; DNA; HLA Antigens; Humans; Psoriasis

Although psoriasis is a genetically transferred disease, little is known of the factors causing spontaneous eruption of a proliferative lesion in apparently normal epidermis. Cell kinetic studies indicate an increased epidermal turnover in clinically normal and involved skin, but the pharmacological events regulating epidermopoiesis remain elusive. Possible candidates for the defect in psoriasis are the cyclic nucleotides with their associated enzyme systems. The cyclic AMP: cyclic GMP ratio appears to be reduced in lesional skin. Further phosphodiesterase inhibitors are reported to improve psoriasis. Since prostaglandins stimulate epidermal cyclic AMP in vitro they have been investigated, but with conflicting results. However, the prostaglandins' precursor, arachidonic acid, appears to be elevated in the psoriatic lesion. Epidermal levels of cyclic AMP are also elevated by histamine via H2 receptors and the possibility that histamine exerts a regulatory role needs to be investigated. In conclusion, the pharmacology of psoriasis is complex. Not only do we need to know which pharmacological agents are present in abnormal amounts but more importantly we need to know more about their interactions with one another and with their specific epidermal 'receptors'.

Topics: Animals; Cyclic AMP; Cyclic GMP; Humans; Prostaglandins; Psoriasis; Skin

Leukocytes derived from the peripheral blood of psoriatic patients demonstrated an enhanced chemotactic response compared with leukocytes from healthy subjects. No significant difference was detected between the chemotactic response of leukocytes from patients with minimal or no skin involvement and those from patients with extensive lesions. Psoriatic leukocytes also had a significantly higher capacity to engulf 125I labeled Shigella flexneri than control leukocytes. It is postulated that a decrease in the cyclic AMP/cyclic GMP ratio in psoriatic leukocytes, similar to the imbalance of these 2 cyclic nucleotides found in the lesional epidermis of psoriasis, might be the cause of their enhanced chemotactic and phagocytic activities.

Topics: Cyclic AMP; Cyclic GMP; Female; Humans; Iodine Radioisotopes; Leukocytes; Male; Phagocytosis; Psoriasis; Shigella flexneri; Skin

Daily treatment of guinea-pig ear skin with topical 0.5% retinoic acid in acetone produced erythematous scaly dermatitis. Histologic sections revealed bandlike thickening of the epidermis on days 2 to 4, psoriasiform acanthosis, papillomatosis and increased mitotic activity on days 5 to 6. Also seen were dilatation of the upper dermal blood vessels and a fibroblastic, histiocytic reaction in the dermis. Prostaglandin E, cyclic AMP, and cyclic GMP levels were increased in the treated skin and thymidine incorporation was enhanced. Cyclic AMP and GMP levels peaked on day 5 simultaneous with maximal epidermal hyperplasia, increased mitotic activity and dermal reaction. Tritiated thymidine uptake peaked on days 4 and 5, and prostaglandin E levels continued to increase up to day 6. Cyclic AMP phosphodiesterase activity of treated skin on day 5 did not appear to be significantly different from control.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Administration, Topical; Animals; Cell Division; Cyclic AMP; Cyclic GMP; Disease Models, Animal; Erythema; Guinea Pigs; Male; Models, Biological; Prostaglandins E; Psoriasis; Skin; Skin Physiological Phenomena; Thymidine; Tretinoin; Vitamin A

Topics: Animals; Bucladesine; Cell Differentiation; Cell Division; Cells, Cultured; Cyclic AMP; Cyclic GMP; DNA; Glycogen; Humans; Mice; Papaverine; Psoriasis; Skin; Theophylline; Xanthines

The inhibitory effects of various agents on the enzyme glucose-6-phosphate dehydrogenase have been studied in vitro. Stress is laid on the calculation of kinetic parameters such as true K-I values. The most active inhibitor was methotrexate, closely followed by cGMP. The increase in inhibitory activity after incubation of methotrexate with liver slices is discussed.

Topics: Animals; Betamethasone; Cattle; Cyclic GMP; Drug Evaluation, Preclinical; Folic Acid; Glucosephosphate Dehydrogenase; Guinea Pigs; Kinetics; Methotrexate; Psoriasis

Topics: Cell Division; Cyclic AMP; Cyclic GMP; DNA; Glycogen; Humans; Organ Size; Proteins; Psoriasis