Diminished macrophage apoptosis and reactive oxygen species generation after phorbol ester stimulation in Crohn's disease.

BACKGROUND: Crohn's Disease (CD) is a chronic relapsing disorder characterized by granulomatous inflammation of the gastrointestinal tract. Although its pathogenesis is complex, we have recently shown that CD patients have a systemic defect in macrophage function, which results in the defective clearance of bacteria from inflammatory sites. METHODOLOGY/PRINCIPAL FINDINGS: Here we have identified a number of additional macrophage defects in CD following diacylglycerol (DAG) homolog phorbol-12-myristate-13-acetate (PMA) activation. We provide evidence for decreased DNA fragmentation, reduced mitochondrial membrane depolarization, impaired reactive oxygen species production, diminished cytochrome c release and increased IL-6 production compared to healthy subjects after PMA exposure. The observed macrophage defects in CD were stimulus-specific, as normal responses were observed following p53 activation and endoplasmic reticulum stress. CONCLUSION: These findings add to a growing body of evidence highlighting disordered macrophage function in CD and, given their pivotal role in orchestrating inflammatory responses, defective apoptosis could potentially contribute to the pathogenesis of CD

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

Cigarette smoke is a major risk factor for a number of diseases including lung cancer and respiratory infections. Paradoxically, it also contains nicotine, an anti-inflammatory alkaloid. There is increasing evidence that smokers have a lower incidence of some inflammatory diseases, including ulcerative colitis, and the protective effect involves the activation of a cholinergic anti-inflammatory pathway that requires the α7 nicotinic acetylcholine receptor (α7nAChR) on immune cells. Obesity is characterized by chronic low-grade inflammation, which contributes to insulin resistance. Nicotine significantly improves glucose homeostasis and insulin sensitivity in genetically obese and diet-induced obese mice, which is associated with suppressed adipose tissue inflammation. Inflammation that results in disruption of the epithelial barrier is a hallmark of inflammatory bowel disease, and nicotine is protective in ulcerative colitis. This article summarizes current evidence for the anti-inflammatory effects of nicotine in obesity and ulcerative colitis. Selective agonists for the α7nAChR could represent a promising pharmacological strategy for the treatment of inflammation in obesity and ulcerative colitis. Nevertheless, we should keep in mind that the anti-inflammatory effects of nicotine could be mediated via the expression of several nAChRs on a particular target cell

Guidelines for prescribing azathioprine in dermatology

Azathioprine has been available as an immunosuppressive agent for over 40 years, and current routine usage in dermatology is not restricted to licensed indications. Advances in understanding the metabolic fate of azathioprine have led to significant changes in prescribing practice and toxicity monitoring by U.K. dermatologists. The current state of knowledge concerning the use of azathioprine in dermatology is summarized, with identification of strength of evidence. Clinical indications and contraindications for azathioprine usage in dermatology are identified. Evidence-based recommendations are made for routine safety monitoring of patients treated with azathioprine, including pretreatment assessment of red blood cell thiopurine methyltransferase activity

Pressure Measurement Systems

Measurements of the steady pressure in a fluid flow may be required to determine other thermodynamic properties, to determine forces on a body due to the pressure distribution over it, or in order to determine the dynamic head and flow velocity (for further details on the latter see Sect. 5.1. Pressure is a scalar representation of molecular activity, a measure of the nondirectional molecular motions. Thus it must, by definition, be measured by a device at rest relative to the flow. Whilst the common practice in the fluid mechanics community is to denote the pressure as static (as opposed to the coordinate-dependent total pressure, Sect. 3.1), this terminology introduces a fundamental redundancy. In practice, pressure is commonly measured both at walls and in the freestream using the types of measurement device shown in Fig. 4.1 connected to a transducer of suitable sensitivity and range. The orifice of a small wall tapping represents a simple way to obtain the pressure impressed on the wall by the external flow. So-called static pressure tubes approximate the local fluid pressure in the freestream if the disturbance presented to the flow can either be accounted for or is not large to begin with. However this can only ever be strictly true for steady laminar flow due to the normal velocity component introduced when a flow becomes turbulent. Measurement of freestream pressure is one of the hardest challenges in fluid mechanics. Fig. 4.1 This chapter addresses measurement of pressure using wall tappings (Sect. 4.1) and static pressure tubes (Sect. 4.2), and especially errors due to the intrusive flow presence of real, finite-sized devices and calibrations to correct for these. Bryer and Pankhurst [4.1] and Chue [4.2] provided seminal monographs on the general topic of pressure probes in 1971 and 1975, respectively, which give detailed descriptions of measurement devices, coverage of the background to the various corrections and a survey of older data. The topic is covered here more concisely, with a view to practical use by the engineer, and with reference to modern literature. The reader is referred to Bryer and Pankhurst [4.1] and Chue [4.2] for further details on most sections. In more recent years a further method for obtaining pressure on the surface of a wind tunnel model has been developed, based on pressure sensitive paints (PSP). The introduction of PSP provides a method to measure the pressure on the surface of a model directly without the transducers and tubing associated with conventional means. A paint, the luminescence of which is dependent on air pressure, is applied to the surface of a wind tunnel model and the pressure distribution is obtained from the images produced by proper illumination. In Sect. 4.4 the basics of PSP are discussed and further subsections address in detail different paints, paint application procedures, imaging systems and image processing. In discussing the achievable accuracy of PSP techniques, both the spatial and temporal resolution is examined. The thermal sensitivity of the paint dye is introduced and this is closely linked to temperature-sensitive paints (TSP), as discussed in Chap. 7, Sect. 7.4