Mycophenolate mofetil and its mechanisms of action.

Mycophenolate mofetil (MMF, CellCept(R)) is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase (IMPDH). This is the rate-limiting enzyme in de novo synthesis of guanosine nucleotides. T- and B-lymphocytes are more dependent on this pathway than other cell types are.

Immunosuppressive drugs: the first 50 years and a glance forward.

During the past 50 years, many immunosuppressive drugs have been described. Often their mechanisms of action were established long after their discovery. Eventually these mechanisms were found to fall into five groups: (i) regulators of gene expression; (ii) alkylating agents; (iii) inhibitors of de novo purine synthesis; (iv) inhibitors of de novo pyrimidine synthesis; and (v) inhibitors of kinases and phosphatases.

Evolutionary relationships among 12 species belonging to three genera of the family Microhylidae in Papua New Guinea revealed by allozyme analysis.

To elucidate the potential of electrophoretic analysis for understanding relationships among microhylid frogs in Papua New Guinea, an allozyme analysis was conducted. A total of 119 individuals from nine species of Cophixalus, two species of Sphenophryne and one species of Barygenys, all of which belong to the family Microhylidae, were studied. Fourteen enzymes extracted from skeletal muscles and livers were analyzed by starch-gel electrophoresis.

Squalene and squalane emulsions as adjuvants.

Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen.

Rooperol tetraacetate decreases cytokine mRNA levels and binding capacity of transcription factors in U937 cells.

We have previously described inhibition of the synthesis of three acute-phase inflammatory cytokines in human and rat macrophages by acetate esters of rooperol, a dicatechol of plant origin. Analysing the mechanism of anticytokine activity of rooperol, we compared levels of TNFalpha, IL-1beta and IL-6 mRNAs in the human promonocytic U937 cell line pretreated with phorbol myristate acetate (PMA) and incubated with rooperol tetraacetate (RTA) alone or in combination with LPS (500 ng/ml). It was found that 10 microM RTA decreased the levels of cytokine mRNAs both in the presence and absence of LPS, suggesting pretranslational inhibition of cytokine synthesis.

Tensions in sharing client confidences while respecting autonomy: implications for interprofessional practice.

This article aims to explore the ethical issues arising from the sharing of information in the context of interprofessional collaboration. The increased emphasis on interprofessional working has highlighted the need for greater collaboration and sharing of client information. Through the medium of a case study, we identify a number of tensions that arise from collaborative relationships, which are not conducive to supporting interprofessional working in an ethically sound manner.

The mode of action of immunological adjuvants.

Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions.

Antioxidants inhibit the in vitro production of inflammatory cytokines in Crohn's disease and ulcerative colitis.

Background: Modulation of cytokine secretion may be of interest in the treatment of Crohn's disease or ulcerative colitis.

Methods: The effect of three antioxidants - butylated hydroxyanisol, tetrahydropapaveroline and nordihydroguaiaretic acid - on the production of tumour necrosis factor (TNF), interleukin (IL) 1, IL-6 and IL-8 (measured by enzyme-linked immunosorbent assay) by peripheral mononuclear cells and biopsies of inflamed colonic mucosa from inflammatory bowel disease patients were studied.

Results: We observed a decrease in IL-1 and IL-6 production by peripheral mononuclear cells from inflammatory bowel disease patients (approximately 50% of control).

Shared learning for primary health care teams: a success story.

This paper sets out an educational model for shared learning for professionals working in primary health care teams (PHCTs). It presents an outline of an experiential educational programme using a simulated learning exercise based on a genogram. Multidisciplinary programmes are inherently problematic and tend to be ad hoc in their choice of educational theory.

Rooperol, an inhibitor of cytokine synthesis, decreases the respiratory burst in human and rat leukocytes and macrophages.

Luminol-enhanced chemiluminescence was measured in fresh whole human blood, or human neutrophils isolated from heparinized blood, human alveolar macrophages and rat alveolar macrophages stimulated with bacterial endotoxin (LPS). Tetraacetate esters of rooperol, a dicatechol showing anticytokine activity, added to cells simultaneously with LPS inhibited the respiratory burst. The effective concentrations of rooperol were in the range of 1-10 muM depending on cell type and corresponded well with inhibition of nitric oxide production by rat alveolar macrophages.

Immunological adjuvants and their modes of action.

New adjuvant formulations contain a vehicle, which carries antigens to antigen-presenting cells. Examples of vehicles are liposomes, immune-stimulating complexes and microfluidized squalene-in-water emulsions. Adjuvant formulations may contain immunomodulators, which augment cytokine production, such as a synthetic muramyl dipeptide analog or monophosphoryl lipid A.

Inhibitory effect of di-catechol rooperol on VCAM-1 and iNOS expression in cytokine-stimulated endothelium.

Induced expression of vascular cell adhesion molecule-1 (VCAM-1) and of nitric oxide synthase (iNOS) is believed to play a role in the pathogenesis of atherosclerosis, asthma, as well as other inflammatory disorders. In the current study we examined the effect of the di-catechol rooperol [(E)-1,5-bis (3',4'-dihydroxyphenyl) pent-4-en-1-yne] on the process of microvascular endothelial cell (MME) activation by TNF-alpha and IFN-gamma. We show that rooperol decreases VCAM-1 and iNOS mRNA levels in cytokine-activated MME with subsequent inhibition of VCAM-1 membrane expression as measured by adhesion of P815 cells to MME monolayers, and NO production, as reflected in the nitrite concentration in culture medium.

Cytokine production in human and rat macrophages and dicatechol rooperol and esters.

The ability of dicatechol rooperol and esters to inhibit the production of cytokines in endotoxin-stimulated human alveolar macrophages, human blood monocyte/macrophages, histiocytic cell line U937, and rat alveolar macrophages was examined in vitro. Rooperol derivatives inhibited the production of tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. Of the esters tested on human cells, rooperol diacetate and tetraacetate were more potent inhibitors of cytokine production (IC50 in the range of 10-20 microM) than rooperol disulphate (IC50 in the range of 25-75 microM).

Effect of in vitro passage of healthy human gingival fibroblasts on cellular morphology and cytokine expression.

Cytokines have been implicated in the regulation of antibody and inflammatory responses, but their role in periodontal diseases has not been elucidated. In the present study, cytokine production by human gingival fibroblasts (HGF) following in vitro passage was assessed in order to determine the basal levels of cytokine message and protein and to determine if the cellular morphology and the profile of cytokines produced differed with passage. The HGF cell line F-CL was established by explantation from non-inflamed gingival tissue, and cells from passages 1-10 were studied.

Transforming growth factor beta1 induces angiogenesis in vivo with a threshold pattern.

The true role of transforming growth factor beta1 (TGFbeta) on angiogenesis is in question. Several in vitro studies have shown inhibition of proliferation and migration of endothelial cells (EC). However, some investigators have observed that TGFbeta stimulates the formation of EC tubes in vitro.

Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF).

Mycophenolate mofetil (MMF) is a novel immunosuppressive drug that shows promise in preventing the rejection of organ allografts and in the treatment of ongoing rejection. Orally administered MMF is hydrolyzed by esterases in the intestine and blood to release mycophenolic acid (MPA), a potent, selective, noncompetitive inhibitor of the type 2 isoform of inosine monophosphate dehydroxygenase (IMPDH) expressed in activated human T and B lymphocytes. By inhibiting IMPDH, MPA depletes the pool of dGTP required for DNA synthesis.

Inhibition of experimental autoimmune uveoretinitis by mycophenolate mofetil, an inhibitor of purine metabolism.

Mycophenolate mofetil (MM), an inhibitor of purine metabolism, was found to effectively inhibit the development of experimental autoimmune uveoretinitis (EAU) induced by S-antigen (SAg) in Lewis rats. MM completely inhibited EAU development in the majority of rats when administered daily, on days 0-13, at a dose of 30 mg kg-1 day-1. The drug was less effective, however, when given on days 7-20: minimal disease inhibition was achieved with the drug at 30 mg kg-1 day-1, although at 60 mg kg-1 day-1 the drug inhibited EAU development in most treated rats during the period of its administration.

Effect of eight weeks of treatment with salmeterol on bronchoalveolar lavage inflammatory indices in asthmatics.

Using BAL, we studied the effects of 8 wk of treatment with salmeterol on airway inflammation in nine asthmatic subjects in a double-blind crossover placebo-controlled protocol. The study patients were all receiving regular inhaled corticosteroid therapy (400 to 1,000 micrograms beclomethasone dipropionate per day) and inhaled albuterol for symptomatic relief, i.e.

Dementia in acute units: the issues.

To coincide with World Alzheimer's Day, Nursing Standard this week launches a major new series which looks in detail at one of the most pressing nursing problems of the age--coping with the behaviours of people with dementia who are admitted to acute care units. The series, which consists of seven articles, presented at monthly intervals, takes a very practical look at how nurses in such units can cope with patients who display behaviours such as wandering, aggression, sexual disinhibition and agitation--behaviours which nurses have difficulty understanding and managing.(ABSTRACT TRUNCATED AT 250 WORDS)

Intususception in infancy and childhood: an analysis of 69 cases.

A retrospective study of 69 cases of intususception treated at the University of Port Harcourt Teaching Hospital, Port Harcourt in the past seven years from October, 1985 to September, 1992 is presented. The diagnosis was made clinically and confirmed at operation. Fifty (72.