Styryl-based and tricyclic compounds as potential anti-prion agents.

Prion diseases currently have no effective therapy. These illnesses affect both animal and human populations, and are characterized by the conformational change of a normal self protein PrP(C) (C for cellular) to a pathological and infectious conformer, PrP(Sc) (Sc for scrapie). We used a well characterized tissue culture model of prion infection, where mouse neuroblastoma cells (N2a) were infected with 22L PrP(Sc), to screen compounds for anti-prion activity.

Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy believed to be caused by the bovine spongiform encephalopathy agent, an abnormal isoform of the prion protein (PrP(sc)). At present there is no specific or effective treatment available for any form of CJD. Pentosan polysulphate (PPS), a large polyglycoside molecule with weak heparin-like activity, has been shown to prolong the incubation period of the intracerebral infection when administered to the cerebral ventricles in a rodent scrapie model.

Pentosan polysulfate as a prophylactic and therapeutic agent against prion disease.

Pentosan polysulfate (PPS) acts by imitating the physiological roles of the heparans. It binds to heparan binding sites on proteins and alters the physiological actions of these proteins. PPS acts as a prophylactic agent against infection with prions both in vivo and in vitro.

The key must fit: macrophages transport prion infection to the central nervous system and may determine the sites of infection within it.

It is suggested that the agent for transmissible spongiform encephalopathies is transferred from an original peripheral site of infection into the brain by recruited and selected circulating macrophages/monocytes. It is because of this selection that strains of disease appear to be different when infecting separate species, but retain characteristics when infecting a single species.

A matter for debate: the risk of bovine spongiform encephalopathy to humans posed by blood transfusion in the UK.

If human infection with bovine spongiform encephalopathy (BSE) were to occur, donated peripheral blood from humans that might have become infected from eating adequate quantities of food containing BSE should, until evidence is available to the contrary, be assumed to contain the human form of the disease. The chance of disease transfer to a blood recipient in 1995, which might in turn cause clinical disease with an incubation period of 20 years, is calculated. Transfusion is calculated to be a potential cause of a maximum of only 0.

Alkaloidal glycosidase inhibitors (AGIs) as the cause of sporadic scrapie, and the potential treatment of both transmissible spongiform encephalopathies (TSEs) and human immunodeficiency virus (HIV) infection.

AGIs are produced by plants and microorgansims in the environment. They are absorbed from the gut, distributed throughout the body and are concentrated inside cells. AGIs alter the glycan chains of cellular glycoproteins (CGP) during their formation so that the same CGP produced by different clones of cells (and hence with different glycan chains) becomes structurally the same.

Septic arthritis and unpasteurised milk.

Green-top, or unpasteurised, milk is an increasing source of illness. A case of a previously unreported cause of septic arthritis of the hip joint, secondary to the ingestion of raw milk is reported.