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Biomedical subjects

F J Evans

Publications and source records attributed to F J Evans.

At least 73 records · Page 4Linked to original sources
PubMed1983

New phorbol and deoxyphorbol esters: isolation and relative potencies in inducing platelet aggregation and erythema of skin.

Diester diterpenes based upon phorbol, 4-deoxyphorbol, 4 alpha-deoxyphorbol, 4-deoxy-5-hydroxyphorbol and 4,20-dideoxy-5-hydroxyphorbol were isolated from the fruit oil of Sapium indicum. Corresponding tri- and tetra-esters were produced by acetylation and mono-esters by selective hydrolysis. Twenty-six compounds were tested for production of erythema in vivo and induction of human and rabbit platelet aggregation in vitro. The flatter shape of the AB-ring trans compounds is necessary for interaction of phorbolesters at their receptor in that the cis analogues were inactive. The tertiary C-4 hydroxy group of phorbol was not necessary for activity although the 4-deoxy derivatives were less potent than the 4-hydroxy diterpenes. A primary hydroxy group at C-20 was essential for biological activity because the methyl and aldehyde derivatives of this position were inactive. The C-20 acetates were also inactive on platelets, but they did produce erythema, possibly because of the removal of the ester due to lipase activity in the skin. 5-hydroxy-analogues which undergo intramolecular hydrogen bonding had greatly reduced activities in both systems. Membrane stabilisers, phospholipase A2 and calmodulin inhibitors were antagonists for phorbol esters in platelet aggregation tests, whilst cyclo-oxygenase inhibitors and free radical scavengers had no inhibitory effects. Consequently, one electron withdrawal and free radical formation plays no part in the biological activity of these compounds.

Animals↗
PubMed1983

Tumor-promoting and nonpromoting proinflammatory esters act as human lymphocyte mitogens with different sensitivities to inhibition by cyclosporin A.

Ten closely related tumor-promoting and nonpromoting, proinflammatory phorbol derivatives were tested for stimulation of [3H]thymidine ( [3H]TdR) incorporation into human mononuclear cells. Co-mitogenic activity was assessed with maximally effective concentrations of phytohemagglutinin (PHA) or mixed-lymphocyte reactions (MLR) in the presence of phorbol esters. Tetradecanoyl phorbol acetate (TPA), two 4-deoxyphorbol esters, and two 12-deoxyphorbol monoesters stimulated [3H]TdR incorporation in a dose-related manner. Two established nonpromoting 12-deoxyphorbol diesters were also mitogenic, although less effective than TPA, and produced lower maximal responses. TPA, the 4-deoxyphorbol esters, the 12-deoxyphorbol monoesters, and the two nonpromoting diesters were able to increase MLR-induced incorporation to the same level. When conditions were used where PHA and phorbol esters were optimally mitogenic, inhibition resulted. With the exception of co-mitogenic activity of the nonpromoting diesters, the mitogenic, co-mitogenic, and PHA-inhibiting activities were correlatable. Phorbol, a 4 alpha-deoxyphorbol ester, and resiniferatoxin had no effects. Mitogenic activity of the phorbol esters was inhibited by dexamethasone, chloroquine, and p-bromophenacyl bromide. TPA, the 4-deoxyphorbol esters, and the 12-deoxyphorbol monoesters were resistant to inhibition of activity by cyclosporin A, whereas the noncorrelating diesters exhibited sensitivity to cyclosporin A inhibition comparable to that of PHA. MLR-induced [3H] TdR incorporation was susceptible to cyclosporin A, but the phorbol ester-enhanced responses were cyclosporin A-resistant.

Carcinogens↗
PubMed1982

Random number generation, psychopathology and therapeutic change.

In two studies, 145 psychiatric inpatients were each asked to say 100 numbers in random order, using the numbers 1 through 10. Compared with normative data, patients with personality disorders and neuroses were not impaired on the random number generation (RNG) task and patients with chronic alcoholism and primary affective disorder, depression, were significantly imparied, but not as much as those with schizophrenia and organic brain syndrome. The relationship between RNG performance and psychiatric diagnosis may reflect severity of disturbed cognitive functioning. The Randomization Index was sensitive to changes in symptoms during hospitalization. The RNG task provides a brief objective measure of those components of attention, cognitive capacity, and short-term memory that are affected by severity of psychopathology.

Attention↗
PubMed1982

Hypnotizability and outcome in brief psychotherapy.

The relationship between hypnotizability and clinical improvement following brief psychotherapy was investigated. Prior to treatment 32 patients were assessed for hypnotizability utilizing an objective standardized measure of hypnotizability. Measures of psychopathology were obtained at the conclusion of ten sessions and six months post-treatment. A positive relationship was found between outcome and hypnotizability. This was most pronounced at the conclusion of ten sessions. Use of hypnotic techniques as a therapeutic adjunct did not necessarily lead to greater therapeutic effects. Different approaches in using hypnotherapy are indicated depending on the hypnotizability of the patient.

Adjustment Disorders↗
PubMed1981

Vascular changes in rabbit skin induced by proinflammatory phorbol and 12-deoxyphorbol esters.

The effects of proinflammatory phorbol and 12-deoxyphorbol esters were determined on blood flow changes and plasma exudation in rabbit skin. Blood flow changes were measured by means of 133Xe washout over that in control-treated sites, while plasma exudation was measured by 131I-labeled human serum albumin leakage from skin blood vessels. 12-Deoxyphorbol-13-phenylacetate, 12-deoxyphorbol-13-angelate, and their C-20 acetates induced vasoconstriction in rabbit skin in doses of 100 ng/site. Tetradecanoyl phorbol acetate indiced vasoconstriction to a far lower degree, while the parent alcohol phorbol and 9,13,14-orthophenylacetyl-resiniferonol had no significant effects on rabbit microvasculature. The ability of tigliane esters to contract rabbit blood vessels was confirmed in vitro in that each of these esters induced a prolonged contraction of superfused rabbit aorta in doses of 1-5 microgram. Plasma exudation in rabbit skin was not significantly increased by the phorbol and 12-deoxyphorbol esters, but in a second determination using 100 ng of PGE1 together with 100 ng of ester, plasma exudations of up to 40 microliter per site were recorded.

Animals↗
PubMed1981

Inhibition of erythema induced by pro-inflammatory esters of 12-deoxyphorbol.

The pro-inflammatory tigliane esters 12-deoxyphorbolphenylacetate (12-DOPPA) and 12-deoxyphorbolphenylacetate-20-acetate (12-DOPPAA) at a dose of 0.1 microgram induced erythema in the mouse ear. Observations of ear redness were made both two and four hours after application. Indomethacin was only partly successful as an antagonist since 10% inhibition of 12-DOPPA and no inhibition of 12-DOPPAA induced erythema was produced four hours after application. The free radical scavengers, phenol, thioanisole and sodium benzoate all produced less than 30% inhibition of 12-DOPPA induced erythema and less than 15% inhibition of 12-DOPPAA, whereas aminopyrine produced 70% and 25% inhibition of 12-DOPPA and 12-DOPPAA respectively. The fact that free radical scavengers (with the exception of aminopyrine) and indomethacin, failed to markedly change the mouse ear reaction to 12-deoxyphorbol esters, indicated that this erythema is not entirely mediated via cyclooxygenase products. Mepyramine and cyproheptadine also failed to inhibit the erythema, whereas hydrocortisone produced a 55% inhibition of the 12-DOPPA and a 20% inhibition of the 12-DOPPAA reaction. The membrane stabilising agents trifluoperazine, promethazine, imipramine and desmethylimipramine were the most successful compounds used in inhibiting both 12-DOPPA and 12-DOPPAA induced erythema. In addition propranolol, which inhibits stimulus activation of phospholipase A2, produced 70% and 55% inhibition of the reaction of mice ears to 12-DOPPA and 12-DOPPAA.

Animals↗
PubMed1980

Constituents of Egyptian Euphorbiaceae. IX. Irritant and cytotoxic ingenane esters from Euphorbia paralias L.

The irritant and cytotoxic constituents of the latex of Euphorbia paralias L. were separated from the hydrocarbon fraction by means of solvent partition. 3 new ingenane esters were identified from the toxic ether fraction. The major compound was 3-angelyl-20-deoxyingenol and the 2 minor compounds were 3-hexanoyl-20-deoxyingenol and 3-angelyl-ingenol. These compounds were of a similar potency to podophyllin in the inhibition of 3H-thymidine uptake by TLX/5 mouse lymphoma cells. In addition the compounds produced a persistent erythema of the mouse ear in sub-microgram doses.

Animals↗
PubMed1980

Skin irritant effects of esters of phorbol and related polyols.

The skin irritant potencies of several naturally occurring and semi-synthetic polyfunctional esters based on the tigliane hydrocarbon skeleton were studied using a mouse ear irritancy assay. The compounds used were esters of 12-deoxyphorbol, 12-deoxy-16-hydroxyphorbol, and phorbol. Observations were also made on the time interval between application of these compounds in acetone solution to the mouse ear, and the attainment of maximum response. Structure/activity relationships are discussed and compared with previous observations on the skin irritant potencies of esters based on the closely related daphnane hydrocarbon skeleton. The possible nature of the site of action in the target membrane is also discussed.

Alcohols↗
PubMed1980

Skin irritants of the sun spurge (Euphorbia helioscopia L.).

Euphorbia helioscopia is a common herbaceous week found in the British Isles and parts of Europe. It has been responsible for poisoning of livestock resulting in severe inflammation particularly of mucous membranes and the eyes. Four esters of 12-deoxyphorbol were isolated from the fresh aerial parts of the plant and their irritant doses 50% (I.D.50) ascertained using female L.A.C.A. mice, 12-Deoxyphorbol-13-phenylacetate-20-acetate was found to be the major component of the toxic fraction and occurred in yields of 0.0012% w/w. This compound was also the most irritant substance isolated and exhibited an I.D.50 of 0.038microgram, and is accordingly considered to be responsible for the major part of the toxicity of E. helioscopia. A high molecular weight aliphatic ester, 12-deoxyphorbol-13-dodecdienoate-20-acetate, was also obtained in low yields. This compound exhibited an I.D.50 of 0.12microgram. The final two esters obtained from the toxic fraction of the plant were the low molecular weight homologues, 12-deoxyphorbol-13-[2-methyl-cis-2-butenoate]-20-acetate and 12-deoxyphorbol-13-[2-methyl-cis-2-butenoate]. These compounds exhibited I.D.50 of 3.09 and 0.72 microgram, respectively and were the least irritant of the series of compounds isolated.

Animals↗