Tissue-nonspecific alkaline phosphatase is an anti-inflammatory nucleotidase.

Tissue-nonspecific alkaline phosphatase (TNAP) is necessary for skeletal mineralization by its ability to hydrolyze the mineralization inhibitor inorganic pyrophosphate (PPi), which is mainly generated from extracellular ATP by ectonucleotide pyrophosphatase phosphodiesterase 1 (NPP1). Since children with TNAP deficiency develop bone metaphyseal auto-inflammations in addition to rickets, we hypothesized that TNAP also exerts anti-inflammatory effects relying on the hydrolysis of pro-inflammatory adenosine nucleotides into the anti-inflammatory adenosine. We explored this hypothesis in bone metaphyses of 7-day-old Alpl+/- mice (encoding TNAP), in mineralizing hypertrophic chondrocytes and osteoblasts, and non-mineralizing mesenchymal stem cells (MSCs) and neutrophils, which express TNAP and are present, or can be recruited in the metaphysis. Bone metaphyses of 7-day-old Alpl+/- mice had significantly increased levels of Il-1ß and Il-6 and decreased levels of the anti-inflammatory Il-10 cytokine as compared with Alpl+/+ mice. In bone metaphyses, murine hypertrophic chondrocytes and osteoblasts, Alpl mRNA levels were much higher than those of the adenosine nucleotidases Npp1, Cd39 and Cd73. In hypertrophic chondrocytes, inhibition of TNAP with 25 µM of MLS-0038949 decreased the hydrolysis of AMP and ATP. However, TNAP inhibition did not significantly modulate ATP- and adenosine-associated effects in these cells. We observed that part of TNAP proteins in hypertrophic chondrocytes was sent from the cell membrane to matrix vesicles, which may explain why TNAP participated in the hydrolysis of ATP but did not significantly modulate its autocrine pro-inflammatory effects. In MSCs, TNAP did not participate in ATP hydrolysis nor in secretion of inflammatory mediators. In contrast, in neutrophils, TNAP inhibition with MLS-0038949 significantly exacerbated ATP-associated activation and secretion of IL-1ß, and extended cell survival. Collectively, these results demonstrate that TNAP is a nucleotidase in both hypertrophic chondrocytes and neutrophils, and that this nucleotidase function is associated with autocrine effects on inflammation only in neutrophils.

[Reduction of the radiation exposure of patients caused by selected interventional and angiographic procedures]. / Reduzierung der Strahlenexposition von Patienten bei ausgewählten interventionellen und angiographischen Massnahmen.

PURPOSE: To reduce patient doses caused by selected interventional and angiographic procedures using the digital C-arm unit "Multiskop". MATERIALS AND METHODS: After a patient study done previously, physical measurements with test phantoms were carried out, and physical-technical parameters such as distance between focus and image intensifier, additional filtration, and radiation dose per image were optimised. Then, the dose-area product (DAP) and the fluoroscopic time were measured for 130 percutaneous transluminal angioplasties (PTA), 40 PTA with stent implantation, 61 embolisations, and 302 digital subtraction angiographies (DSA). In the case of 16 PTA, 9 embolisations, and 38 DSA the number of radiographs was determined, and the DAP was divided into two parts, fluoroscopy and radiography. The measuring values were compared with data of the patient study done previously. RESULTS: The median values of the DAP and the fluoroscopic time amounted to 25 Gy cm2 and 9.7 min for PTA, 97 Gy cm2 and 8.5 min for PTA with stent implantation, 88 Gy cm2 and 17.2 min for embolisation as well as 54 Gy cm2 and 2.8 min for DSA. For the relation between DAP caused by fluoroscopy and radiography, and the number of radiographs, median values of 0.76 and 63 for PTA, 0.81 and 123 for embolisation as well as 1.85 and 134 for DSA were determined. In comparison to the patient study done previously the median values of the DAP were reduced by 31% for PTA, 26% for PTA with stent implantation, 55% for embolisation, and 38% for DSA. CONCLUSIONS: The comparison between the patient studies done previously and recently indicates the great potential of dose reduction for interventional and angiographic procedures. Although the X-ray equipment is ten years old the patient dose can be reduced by organizational and physical-technical modifications to such an extent that preliminary national reference dose values will not be exceeded. For further significant dose reductions while maintaining adequate image quality it will be necessary to purchase a modern X-ray equipment with pulsed fluoroscopy and automatic filter selection.