A Visual Analog Scale for Self-Reported Quality of Life: A Comparison of VAS and QoL-AD in Older Adults.

Purpose: People with dementia (PWD) are one of the fastest-growing clinical populations for speech-language pathologists. Self-reported quality of life (QoL) assessments are critical patient-reported outcome measures that align with person-centered care principles. However, proxy-reporting is most often used due to assumptions that PWD cannot provide reliable self-report.

RPR203494 a pyrimidine analogue of the p38 inhibitor RPR200765A with an improved in vitro potency.

Following the discovery of RPR200765, a series of pyrimidine analogues have been prepared as backups. Amongst them, RPR203494 was identified with a better in vitro profile than RPR200765A.

The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy.

RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM).

Tumour necrosis factor-alpha has few morphological effects within the dorsal columns of the spinal cord, in contrast to its effects in the peripheral nervous system.

There is circumstantial evidence implicating the pro-inflammatory cytokine tumour necrosis factor (TNF) in the pathogenesis of multiple sclerosis (MS), but there is no direct evidence that TNF can produce demyelination in the central nervous system (CNS). We demonstrate here that single injections of TNF into the dorsal columns of adult rats produced a mild inflammatory response indistinguishable from that seen in control cords, but did not induce demyelination. A similar response was seen when TNF-alpha was injected into dorsal columns where central axons had been remyelinated by Schwann cells.

Matrix metalloproteinase expression during experimental autoimmune neuritis.

Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome. We have shown recently that BB-1101, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, prevents development of EAN when given from the day of immunization and, more important clinically, reduces disease severity when given from symptom onset. This suggests the involvement of MMP activity in the pathogenesis of EAN.

Nitric oxide donors reversibly block axonal conduction: demyelinated axons are especially susceptible.

Diseases such as multiple sclerosis and Guillain-Barré syndrome are characterized not only by widespread loss of myelin from nerve fibres, but also by widespread inflammation in the central and peripheral nervous systems, respectively. While the demyelination alone is sufficient to block conduction and thereby cause symptoms, there is increasing evidence that the inflammation may also contribute significantly to the conduction block, although the mechanisms are not understood. Nitric oxide is an important inflammatory mediator which is elevated within the central nervous system in multiple sclerosis and which can be experimentally applied to tissues using nitric oxide donors.

A combined inhibitor of matrix metalloproteinase activity and tumour necrosis factor-alpha processing attenuates experimental autoimmune neuritis.

Matrix metalloproteinases (MMPs) and the cytokine tumour necrosis factor (TNF)-alpha are implicated in the pathology of inflammatory demyelinating diseases of the CNS, and may also be involved in peripheral demyelinating diseases such as acute inflammatory demyelinating polyradiculoneuropathy. We have tested an inhibitor of MMP activity and TNF-alpha processing, BB-1101, in experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome. Treatment with BB-1101 from the time of immunization prevented the development of EAN, and when given from the onset of symptoms, it significantly reduced disease severity.

Human immunoglobulin ameliorates rat experimental autoimmune neuritis.

Human immunoglobulin is an effective treatment for Guillain-Barré syndrome, although the mechanism of action is not understood. We have investigated the effect of human immunoglobulin in an animal model of Guillain-Barré syndrome, namely experimental autoimmune neuritis (EAN), induced in Lewis rats by immunization with bovine spinal root myelin. Human immunoglobulin administered intraperitoneally at the time of onset of disease accelerated the rate of recovery from EAN.

Vascular changes and demyelination induced by the intraneural injection of tumour necrosis factor.

Several observations suggest that tumour necrosis factor (TNF) plays a role in demyelination, although direct evidence for this is lacking. We have examined ultrastructurally rat sciatic nerves injected with TNF-alpha or TNF-beta: the effects of the two cytokines were found to be qualitatively similar. One day after injection nerves were oedematous and contained many inflammatory cells.