Impairment of the Plasmodium falciparum Erythrocytic Cycle Induced by Angiotensin Peptides

Plasmodium falciparum causes the most serious complications of malaria and is a public health problem worldwide with over 2 million deaths each year. The erythrocyte invasion mechanisms by Plasmodium sp. have been well described, however the physiological aspects involving host components in this process are still poorly understood. Here, we provide evidence for the role of renin-angiotensin system (RAS) components in reducing erythrocyte invasion by P. falciparum. Angiotensin II (Ang II) reduced erythrocyte invasion in an enriched schizont culture of P. falciparum in a dose-dependent manner. Using mass spectroscopy, we showed that Ang II was metabolized by erythrocytes to Ang IV and Ang-(1–7). Parasite infection decreased Ang-(1–7) and completely abolished Ang IV formation. Similar to Ang II, Ang-(1–7) decreased the level of infection in an A779 (specific antagonist of Ang-(1–7) receptor, MAS)-sensitive manner. 10−7 M PD123319, an AT2 receptor antagonist, partially reversed the effects of Ang-(1–7) and Ang II. However, 10−6 M losartan, an antagonist of the AT1 receptor, had no effect. Gs protein is a crucial player in the Plasmodium falciparum blood cycle and angiotensin peptides can modulate protein kinase A (PKA) activity; 10−8 M Ang II or 10−8 M Ang-(1–7) inhibited this activity in erythrocytes by 60% and this effect was reversed by 10−7 M A779. 10−6 M dibutyryl-cAMP increased the level of infection and 10−7 M PKA inhibitor decreased the level of infection by 30%. These results indicate that the effect of Ang-(1–7) on P. falciparum blood stage involves a MAS-mediated PKA inhibition. Our results indicate a crucial role for Ang II conversion into Ang-(1–7) in controlling the erythrocytic cycle of the malaria parasite, adding new functions to peptides initially described to be involved in the regulation of vascular tonus

Impairment of the Plasmodium falciparum Erythrocytic Cycle Induced by Angiotensin Peptides

Plasmodium falciparum causes the most serious complications of malaria and is a public health problem worldwide with over 2 million deaths each year. The erythrocyte invasion mechanisms by Plasmodium sp. have been well described, however the physiological aspects involving host components in this process are still poorly understood. Here, we provide evidence for the role of renin-angiotensin system (RAS) components in reducing erythrocyte invasion by P. falciparum. Angiotensin II (Ang II) reduced erythrocyte invasion in an enriched schizont culture of P. falciparum in a dose-dependent manner. Using mass spectroscopy, we showed that Ang II was metabolized by erythrocytes to Ang IV and Ang-(1–7). Parasite infection decreased Ang-(1–7) and completely abolished Ang IV formation. Similar to Ang II, Ang-(1–7) decreased the level of infection in an A779 (specific antagonist of Ang-(1–7) receptor, MAS)-sensitive manner. 10−7 M PD123319, an AT2 receptor antagonist, partially reversed the effects of Ang-(1–7) and Ang II. However, 10−6 M losartan, an antagonist of the AT1 receptor, had no effect. Gs protein is a crucial player in the Plasmodium falciparum blood cycle and angiotensin peptides can modulate protein kinase A (PKA) activity; 10−8 M Ang II or 10−8 M Ang-(1–7) inhibited this activity in erythrocytes by 60% and this effect was reversed by 10−7 M A779. 10−6 M dibutyryl-cAMP increased the level of infection and 10−7 M PKA inhibitor decreased the level of infection by 30%. These results indicate that the effect of Ang-(1–7) on P. falciparum blood stage involves a MAS-mediated PKA inhibition. Our results indicate a crucial role for Ang II conversion into Ang-(1–7) in controlling the erythrocytic cycle of the malaria parasite, adding new functions to peptides initially described to be involved in the regulation of vascular tonus

Dynamic force calibration by impact excitation

Introduce a method of dynamic force calibration by impact excitation. An analysis of the 200kN standard dynamic force calibration equipment at NIM is presented. The heavy hammer and the force transducer under test are brought to collision, and the impact force is measured by laser-Doppler interferometer. Traceability of force is realized by the determination of mass and acceleration. Two experiments were introduced and a typical example of impact process was performed

Determination of laser tracker angle encoder errors

Errors in the angle encoders of a laser tracker may potentially produce large errors in long range coordinate measurements. To determine the azimuth angle encoder errors and verify their values stored in the tracker’s internal error map, several methodologies were evaluated, differing in complexity, measurement time and the need for specialised measuring equipment. These methodologies are: an artefact-based technique developed by NIST; a multi-target network technique developed by NPL; and the classical precision angular indexing table technique. It is shown that the three methodologies agree within their respective measurement uncertainties and that the NPL technique has the advantages of a short measurement time and no reliance on specialised measurement equipment or artefacts

Recent progress in high pressure metrology in Europe

Five European national metrology institutes in collaboration with a university, a research institute and five industrial companies are working on a joint research project within a framework of the European Metrology Research Programme aimed at development of 1.6 GPa primary and 1.5 GPa transfer pressure standards. Two primary pressure standards were realised as pressure-measuring multipliers, each consisting of a low pressure and a high pressure (HP) piston-cylinder assembly (PCA). A special design of the HP PCAs was developed in which a tungsten carbide cylinder is supported by two thermally shrunk steel sleeves and, additionally, by jacket pressure applied to the outside of the outer sleeve. Stress-strain finite element analysis (FEA) was performed to predict behaviour of the multipliers and a pressure generation system. With FEA, the pressure distortion coefficient was determined, taking into account irregularities of the piston-cylinder gap. Transfer pressure standards up to 1.5 GPa are developed on the basis of modern 1.5 GPa pressure transducers. This project shall solve a discrepancy between the growing needs of the industry demanding precise traceable calibrations of the high pressure transducers and the absence of adequate primary standards for pressures higher than 1 GPa in the European Union today