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Biomedical subjects

F J Evans

Publications and source records attributed to F J Evans.

At least 55 records · Page 3Linked to original sources

Hypnosis and chronic pain. Two contrasting case studies.

Some of the theoretical and technical problems associated with the use of hypnosis for chronic pain are discussed in the context of two similar case studies, one of which had an unsuccessful outcome. Different hypnotic strategies are discussed which depend on a careful, direct evaluation of the role of secondary gain and depression in maintaining the pain in the two patients. Specific hypnotic interventions are described, based on dissociation, imagery and the non-specific components of the hypnotic relationship. Self-hypnotic procedures are described stressing the development of mastery and self-control over pain. Differences in the kinds of hypnotic intervention that are appropriate when secondary gain or depression are central to the pain problem, compared to the more direct techniques available when they are not, are discussed.

Abdominal Pain↗

The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation.

Olivetol, cannabigerol (CBG), cannabidiol (CBD), cannabinol (CBN) and tetrahydrocannabinol (delta 1-THC) were assessed for their ability to inhibit agonist-induced platelet aggregation and [14C]5-HT release. With the exception of olivetol, (40% maximal effectiveness), none of the compounds inhibited tetradecanoylphorbolacetate (TPA)-induced aggregation of human or rabbit platelets. All of these cannabinoids partially inhibited primary aggregation and totally inhibited secondary aggregation of human platelets when adrenaline was used as the agonist. Inhibition was dose-dependent over the range 10(-3)-10(-5) M. Both rabbit and human platelet aggregation induced by adenosine diphosphate was inhibited in a dose-dependent manner and the order of potency was CBG greater than CBD greater than olivetol greater than THC greater than CBN, the IC50 of CBG being 2.7 x 10(-4) M. PAF-induced aggregation of rabbit platelets was also inhibited by these compounds in a dose-dependent manner over the concentration range 10(-3) to 10(-4) M, however [14C]5-HT release was only partially prevented by the cannabinoids in a manner which did not correlate with inhibition of aggregation.

Animals↗

Phorbol esters of different biological activities may preferentially act as mitogens of human suppressor T-cells and are equi-effective mitogens of IL-2 dependent cells.

The actions of tetradecanoylphorbolacetate (TPA) and 12-deoxyphorbolphenylacetate-20-acetate (DPPAA) together with a phytohaemagglutinin (PHA) have been examined on the proliferative responses of human mononuclear cells (MNC) depleted of specific cell subsets by the use of monoclonal antibodies. PHA-induced proliferation was found to be reduced when monocytes/macrophages and T-helper cells were depleted from MNC, but enhanced compared with MNC responses when T-suppressor cells were depleted. In contrast, TPA- and DPPAA-induced proliferation was unchanged or slightly enhanced following macrophage/monocyte depletion, and whereas TPA-induced proliferation was largely independent of subtype constitution, the non-tumour promoting DPPAA appeared to selectively enhance proliferation of the T8+ suppressor subset. Indomethacin increased the proliferative MNC responses of phorbol esters whilst having little effect upon the PHA response, an effect antagonized by addition of PGE2. The addition of interleukin-2 (IL-2) increased the proliferative response, as well as resistance to inhibition induced by cyclosporin A and dexamethasone and partially abolished the selective actions of DPPAA and PHA. In IL-2 dependent cultures PHA induced stimulation was more sensitive to inhibition by cyclosporin than were the phorbol esters. The results suggest that, although induction of lymphocyte proliferation by phorbol esters is not a correlate for tumour promotion itself, non-promoting phorbol esters may have a more restricted ability to induce proliferation than TPA.

Antibodies, Monoclonal↗

Analgesic and antiinflammatory activity of constituents of Cannabis sativa L.

Two extracts of Cannabis sativa herb, one being cannabinoid-free (ethanol) and the other containing the cannabinoids (petroleum), were shown to inhibit PBQ-induced writhing in mouse when given orally and also to antagonize tetradecanoylphorbol acetate (TPA)-induced erythema of mouse skin when applied topically. With the exception of cannabinol (CBN) and delta 1-tetrahydrocannabinol (delta 1-THC), the cannabinoids and olivetol (their biosynthetic precursor) demonstrated activity in the PBQ test exhibiting their maximal effect at doses of about 100 micrograms/kg. delta 1-THC only became maximally effective in doses of 10 mg/kg. This higher dose corresponded to that which induced catalepsy and is indicative of a central action. CNB demonstrated little activity and even at doses in excess of 10 mg/kg could only produce a 40% inhibition of PBQ-induced writhing. Cannabinoid (CBD) was the most effective of the cannabinoids at doses of 100 micrograms/kg. Doses of cannabinoids that were effective in the analgesic test orally were used topically to antagonize TPA-induced erythema of skin. The fact that delta 1-THC and CBN were the least effective in this test suggests a structural relationship between analgesic activity and antiinflammatory activity among the cannabinoids related to their peripheral actions and separate from the central effects of delta 1-THC.

Analgesics↗

Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L.

Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced catalepsy in the mornings and the evenings, but cannabidiol (CBD) exhibited this effect only in the evenings. A combination of CBN and CBD inhibited THC-induced catalepsy equal to that of CBN alone in the mornings, but this inhibition was greater than that produced by CBN alone in the evenings.

Animals↗

The stimulation of phosphorylation of intracellular proteins in GH3 rat pituitary tumour cells by phorbol esters of distinct biological activity.

Using a pituitary tumour cell line (GH3), we have studied the phosphorylation of intracellular proteins induced by phorbol esters of diverse biological activity. All the active phorbol esters, including the weakly tumour-promoting but non-platelet aggregatory compound DOPPA, stimulated the phosphorylation of a cytosolic 80 kDa protein. A protein of this molecular mass has been suggested to be a marker of PKC activity. In contrast, only TPA and the non-tumour promoting but highly active phorbol ester SAP A stimulated the phosphorylation of a 130 kDa membrane protein. The results suggest that these phorbol esters activate PKC, but induce the differential phosphorylation of a variety of intracellular proteins.

Animals↗

Activation of phospholipase A2 by cannabinoids. Lack of correlation with CNS effects.

Cannabinoids delta 1-tetrahydrocannabinol, cannabinol, cannabidiol and cannabigerol have been shown to affect directly the activity of phospholipase A2 in a cell-free assay. The compounds produced a biphasic activation of the enzyme, with EC50 values in the range 6.0-20.0 X 10(-6) M and IC50 values in the range 50.0-150.0 X 10(-6) M. These results correlated well with the relative potencies reported for the stimulation of prostaglandin release from human synovial cells in vitro, confirming that activation of phospholipase A2 is the predominant action of cannabinoids on arachidonate metabolism in tissue culture. However, since delta 1-tetrahydrocannabinol is unique among these compounds in possessing cataleptic activity, it is unlikely that phospholipase A2 is the major receptor mediating the psychotropic effects of cannabis.

Animals↗

Toxic phorbol esters from Chinese tallow stimulate protein kinase C.

Phorbol esters were isolated from the seeds of Chinese tallow (Sapium sebiferum L. Roxb.). These compounds were based on the tigliane nuclei, 4-deoxyphorbol, 12-deoxyphorbol and 4,20-dideoxy-5-hydroxyphorbol. The pro-inflammatory activity (ID50) of the pure compounds was between 0.042 and 2.6 nmoles per ear. Protein kinase C activation assays were carried out on samples of enzyme purified from mammalian brain and the activities (Ka) were in the range 76-176 nM. The 4,20-dideoxy-5-hydroxy analogue was inactive in both tests. Chinese tallow, which is used as a substitute for linseed oil, may represent an industrial toxic hazard in terms of both pro-inflammatory and tumour-promoting effects.

Animals↗

Sapintoxin A. A fluorescent phorbol ester that is a potent activator of protein kinase C but is not a tumour promoter.

In this communication we report on the activity of the naturally occurring, highly fluorescent phorbol ester Sapintoxin A (12-o-[2-methylaminobenzoate]-4-deoxyphorbol 13-acetate). This compound potently activates the enzyme protein kinase C (PKC) (Ka 76 nM) but is neither a complete nor second-stage tumour promoter in traditional Berenblum tests. Sapintoxin A has properties in common with promoters such as 12-o-tetradecanoylphorbol 13-acetate (TPA) in that it will induce erythema in vivo, induce lymphocyte mitogenesis in vitro and cause aggregation of human and rabbit platelets. Accordingly, Sapintoxin A is a suitable negative control compound for biochemical studies concerning the involvement of PKC in tumour promotion and cell proliferation.

Animals↗

The potentiation of phorbol ester-induced aggregation of human platelets by the prostaglandin endoperoxide analogue, U46619.

It was not possible to desensitize human blood platelets to 12-deoxyphorbol-phenylacetate (DOPP) stimulation in a manner analogous with that to platelet aggregating factor (PAF), prostaglandin-endoperoxide analogue (U46619) or adenosine diphosphate (ADP). Platelets previously desensitized to U46619, when challenged with DOPP and ADP, showed an increased aggregation and release of 5-HT. Sub-threshold aggregating doses of U46619 also caused a potentiation of the platelet response and release reaction to DOPP. The concentration of U46619 used to pretreat platelets affected the extent of potentiation of platelet stimulation induced by DOPP. The degree of potentiation was also affected by the time interval between addition of U46619 and DOPP. U46619 did not potentiate the aggregating effects of PAF, or ionophore A23187. The stimulus potentiation of DOPP by U46619 was abolished by prostacyclin (PGI2) and an antibody to U46619, but was unaffected by indomethacin and CP/CPK.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Evaluation of a computerized version of the Diagnostic Interview Schedule.

An interactive, computerized version of the Diagnostic Interview Schedule (DIS) was completed by 135 randomly selected psychiatric inpatients and evaluated by the patients and their psychiatrists. The results showed that the majority of the patients interacted well with the computer and that the treating psychiatrists found the computer reports generally accurate and helpful. Analysis of the agreement between the computer and the psychiatrists' diagnoses yielded mixed results depending on the method of analysis chosen. The thoroughness, consistency, and broad perspective of the computer interview combined with the insight, creativity, and experience of the well-trained clinician may ultimately provide a method of diagnosis that is superior to either used alone.

Adolescent↗

Cannflavin A and B, prenylated flavones from Cannabis sativa L.

Two novel prenylated flavones, termed Cannflavin A and B, were isolated from the cannabinoid free ethanolic extract of Cannabis sativa L. Both compounds inhibited prostaglandin E2 production by human rheumatoid synovial cells in culture.

Arthritis, Rheumatoid↗

Isolation from Cannabis sativa L. of cannflavin--a novel inhibitor of prostaglandin production.

The isolation from Cannabis sativa L. of an inhibitor of prostaglandin (PG) E2 production by cultured rheumatoid synovial cells is described. This agent, for which the name Cannflavin has been coined, is distinct from cannabinoids on the basis of isolation procedure, preliminary structural analysis and biological properties. The activity of Cannflavin has been compared with several established anti-inflammatory drugs and the major cannabinoids.

Anti-Inflammatory Agents↗

Structural correlations of phorbol-ester-induced stimulation of PGE2 production by human rheumatoid synovial cells.

Eight phorbol esters were studied for their ability to stimulate prostaglandin production in human rheumatoid synovial cells over the dose range 0.1 ng to 1.0 micrograms. These derivatives were based upon phorbol, 4-deoxyphorbol, and 12-deoxyphorbol nuclei. This activity was structurally dependent and, although it did not correlate with the actions of the same compounds to induce erythema in vivo, it did correlate with their ability to stimulate human lymphocyte mitogenesis. Stimulation of PGE2 production by a phorbol and a 12-deoxyphorbol analog was inhibited in this system by both indomethacin and dexamethasone.

Arthritis, Rheumatoid↗

Pseudomalignant osseous tumor of the temporalis muscle.

A case is presented of a 10-year-old girl who had a benign osseous tumor of the temporalis muscle. The tumor appeared to be a variant of the so-called pseudomalignant osseous tumor of the soft tissues and could readily be distinguished from both osteogenic sarcoma and myositis ossificans.

Child↗