Lichen planus and lichenoid dermatoses: Conventional and emerging therapeutic strategies.

Having reviewed the diverse clinical subtypes of lichenoid disease and the postulated molecular basis thereof in the first article in this 2-part continuing medical education series, we discuss herein the existing and emerging treatment strategies in the most common clinical forms of lichenoid inflammation and provide an overview of their pharmacodynamics and evidence base. The scope of this review is not to exhaustively discuss treatment modalities for all lichenoid variants discussed in the previous article of this series. Instead, the focus will be on frequently encountered subtypes of lichen planus and on linking mechanisms of disease with mechanisms of drug action. Future directions and potential avenues for translational research will also be discussed.

Lichen planus and lichenoid dermatoses: Clinical overview and molecular basis.

Deriving from the Greek word λειχήν for "tree moss" and the Latin word planus for "planar," lichen planus is a relatively uncommon and heterogeneous cutaneous disorder that typically develops in middle-aged adults. Despite the significant clinical burden associated with the disorder, little well-conducted molecular research has been undertaken, possibly because of heterogeneity impeding consistent and confident phenotyping. The multiple variants of lichenoid disease bear overlapping clinical and pathologic features despite manifesting as distinct clinical disorders. The first article in this 2-part continuing medical education series provides a comprehensive overview of the clinical and pathologic characteristics of cutaneous lichenoid dermatoses and links these manifestations to recent advances in our understanding of the underlying pathobiology of such diseases.

A Discussion on the Regulation of Blood Flow and Pressure.

This paper discusses two kinds of regulation essential to the circulatory system: namely the regulation of blood flow and that of (systemic) arterial blood pressure. It is pointed out that blood flow requirements sub-serve the nutritional needs of the tissues, adequately catered for by keeping blood flow sufficient for the individual oxygen needs. Individual tissue oxygen requirements vary between tissue types, while highly specific for a given individual tissue. Hence, blood flows are distributed between multiple tissues, each with a specific optimum relationship between the rate of oxygen delivery (DO2) and oxygen consumption (VO2). Previous work has illustrated that the individual tissue blood flows are adjusted proportionately, where there are variations in metabolic rate and where arterial oxygen content (CaO2) varies. While arterial blood pressure is essential for the provision of a sufficient pressure gradient to drive blood flow, it is applicable throughout the arterial system at any one time. Furthermore, It is regulated independently of the input resistance to individual tissues (local arterioles), since they are regulated locally, that being the means by which the highly specific adequate local requirement for DO2 is ensured. Since total blood flow is the summation of all the individually regulated tissue blood flows cardiac inflow (venous return) amounts to total tissue blood flow and as the heart puts out what it receives cardiac output is therefore determined at the tissues. Hence, regulation of arterial blood pressure is independent of the distributed independent regulation of individual tissues. It is proposed here that mechanical features of arterial blood pressure regulation will depend rather on the balance between blood volume and venous wall tension, determinants of venous pressure. The potential for this explanation is treated in some detail.

Analysis of Parkinson's disease brain-derived DNA for alpha-synuclein coding somatic mutations.

BACKGROUND: Although alpha-synuclein (SNCA) is crucial to the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), mutations in the gene appear to be rare. We have recently hypothesized that somatic mutations in early development could contribute to PD. METHODS: Expanding on our recent negative small study, we used high-resolution melting (HRM) analysis to screen SNCA coding exons for somatic point mutations in DNA from 539 PD and DLB cerebellar samples, with two additional regions (frontal cortex, substantia nigra) for 20 PD cases. We used artificial mosaics to determine sensitivity where possible. RESULTS: We did not detect any evidence of somatic coding mutations. Three cases were heterozygous for known silent polymorphisms. The protocol we used was sensitive enough to detect 5% to 10% mutant DNA. CONCLUSION: Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding SNCA point mutations.

A novel α-synuclein missense mutation in Parkinson disease.

Alpha-synuclein (SNCA) is central to the pathogenesis of Parkinson disease (PD), with 3 missense mutations reported to date. We report a novel mutation (p.H50Q) in a pathologically proven case.