Validation of four automatic devices for self-measurement of blood pressure according to the International Protocol of the European Society of Hypertension

Jalil Belghazi, Ramzi N El Feghali, Thérèse Moussalem, Maya Rejdych, Roland G AsmarThe CardioVascular Institute, Paris, FranceBackground: Four electronic devices for self-measurement of brachial blood pressure (BP): the Omron M1 Plus, the Omron M6 Comfort, the Spengler KP7500 D, and the Microlife BP A100 Plus, were evaluated in four separate studies according to the International Protocol of the European Society of Hypertension (ESH).Design: The International Validation Protocol is divided into 2 phases: the first phase is performed on 15 selected subjects (45 pairs of BP measurements); if the device passes this phase, 18 supplementary subjects are included (54 pairs of BP measurements) making a total number of 33 subjects (99 pairs of BP measurements) on which the final validation is performed.Methods: The same methodology recommended by the ESH protocol was applied for the 4 studies. In each study and for each subject, 4 BP measurements were performed simultaneously by 2 trained observers using mercury sphygmomanometers alternately with 3 measurements by the tested device. The difference between the BP value given by the device and that obtained by the two observers (mean of the two observers) was calculated for each measure. The 99 pairs of BP differences were classified into 3 categories (≤5, ≤10, ≤15 mmHg). The number of differences in each category was compared with the number required by the International Protocol. An individual analysis was then done to determine for each subject the number of comparisons ≤5 mmHg. At least 22 of the 33 subjects should have 2 of their 3 comparisons ≤5 mmHg.Results: All 4 tested devices passed the fi rst and the second phase of the validation process. The average differences between the device and mercury sphygmomanometer readings were –1.4 ± 5.5 and –0.4 ± 4.8 mmHg for SBP and DBP respectively for the Omron M1 Plus device, –2.1 ± 7.4 and 0.1 ± 4.9 mmHg for SBP and DBP respectively for the Omron M6 Comfort device, –1.4 ± 8.6 and –0.1 ± 3.5 mmHg for SBP and DBP respectively for the Spengler KP7500 D device, and 1.6 ± 4.2 mmHg and 0.54 ± 2.8 mmHg for SBP and DBP respectively for the Microlife BP A100 Plus device. For all devices, readings differing by less than 5, 10, and 15 mmHg for SBP and DBP values fulfill the recommendation criteria of the International Protocol as well as the individual analysis.Conclusions: Omron M1 Plus (HEM-4011C-E), Omron M6 Comfort (HEM 7000-E), Spengler KP7500 D, and Microlife BP A100 Plus devices fulfilled the validation recommendations of the International Protocol.Keywords: Omron M1 Plus (HEM-4011C-E), Omron M6 Comfort (HEM-7000-E), Spengler KP7500 D and Microlife BP A100 Plus, validation, International Protocol, self-blood pressure measuremen

Sultr4;1 mutant seeds of Arabidopsis have an enhanced sulphate content and modified proteome suggesting metabolic adaptations to altered sulphate compartmentalization

<p>Abstract</p> <p>Background</p> <p>Sulphur is an essential macronutrient needed for the synthesis of many cellular components. Sulphur containing amino acids and stress response-related compounds, such as glutathione, are derived from reduction of root-absorbed sulphate. Sulphate distribution in cell compartments necessitates specific transport systems. The low-affinity sulphate transporters SULTR4;1 and SULTR4;2 have been localized to the vacuolar membrane, where they may facilitate sulphate efflux from the vacuole.</p> <p>Results</p> <p>In the present study, we demonstrated that the <it>Sultr4;1 </it>gene is expressed in developing Arabidopsis seeds to a level over 10-fold higher than the <it>Sultr4;2 </it>gene. A characterization of dry mature seeds from a <it>Sultr4;1 </it>T-DNA mutant revealed a higher sulphate content, implying a function for this transporter in developing seeds. A fine dissection of the <it>Sultr4;1 </it>seed proteome identified 29 spots whose abundance varied compared to wild-type. Specific metabolic features characteristic of an adaptive response were revealed, such as an up-accumulation of various proteins involved in sugar metabolism and in detoxification processes.</p> <p>Conclusions</p> <p>This study revealed a role for SULTR4;1 in determining sulphate content of mature Arabidopsis seeds. Moreover, the adaptive response of <it>sultr4;1 </it>mutant seeds as revealed by proteomics suggests a function of SULTR4;1 in redox homeostasis, a mechanism that has to be tightly controlled during development of orthodox seeds.</p

Plasmodium falciparum proteome changes in response to doxycycline treatment

<p>Abstract</p> <p>Background</p> <p>The emergence of <it>Plasmodium falciparum </it>resistance to most anti-malarial compounds has highlighted the urgency to develop new drugs and to clarify the mechanisms of anti-malarial drugs currently used. Among them, doxycycline is used alone for malaria chemoprophylaxis or in combination with quinine or artemisinin derivatives for malaria treatment. The molecular mechanisms of doxycycline action in <it>P. falciparum </it>have not yet been clearly defined, particularly at the protein level.</p> <p>Methods</p> <p>A proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite <it>P. falciparum </it>following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and isobaric tagging reagents for relative and absolute quantification (iTRAQ).</p> <p>Results</p> <p>After doxycycline treatment, 32 and 40 <it>P. falciparum </it>proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm this hypothesis.</p> <p>Conclusions</p> <p>In this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.</p

Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria

International audienceBACKGROUND: Plasmodium falciparum infections could lead to severe malaria, principally in non-immune individuals as children and travellers from countries exempted of malaria. Severe malaria is often associated with the sequestration of P. falciparum-infected erythrocytes in deep micro-vascular beds via interactions between host endothelial receptors and parasite ligands expressed on the surface of the infected erythrocyte. Although, serological responses from individuals living in endemic areas against proteins expressed at surface of the infected erythrocyte have been largely studied, seldom data are available about the specific targets of antibody response from travellers. METHODS: In order to characterize antigens recognized by traveller sera, a comparison of IgG immune response against membrane protein extracts from uninfected and P. falciparum-infected red blood cells (iRBC), using immunoblots, was performed between non exposed individuals (n = 31) and briefly exposed individuals (BEI) (n = 38) to malaria transmission. RESULTS: Immune profile analysis indicated that eight protein bands from iRBC were significantly detected more frequently in the BEI group. Some of these antigenic proteins were identified by an original immuno-proteomic approach. CONCLUSION: Collectively, these data may be useful to characterize the singular serological immune response against a primary malaria infection in individuals briefly exposed to transmission

Altered Protein Networks and Cellular Pathways in Severe West Nile Disease in Mice

Background:The recent West Nile virus (WNV) outbreaks in developed countries, including Europe and the United States, have been associated with significantly higher neuropathology incidence and mortality rate than previously documented. The changing epidemiology, the constant risk of (re-)emergence of more virulent WNV strains, and the lack of effective human antiviral therapy or vaccines makes understanding the pathogenesis of severe disease a priority. Thus, to gain insight into the pathophysiological processes in severe WNV infection, a kinetic analysis of protein expression profiles in the brain of WNV-infected mice was conducted using samples prior to and after the onset of clinical sympt

Kinetic analysis of mouse brain proteome alterations following chikungunya virus infection before and after appearance of clinical symptoms

Recent outbreaks of Chikungunya virus (CHIKV) infection have been characterized by an increasing number of severe cases with atypical manifestations including neurological complications. In parallel, the risk map of CHIKV outbreaks has expanded because of improved vector competence. These features make CHIKV infection a major public health concern that requires a better understanding of the underlying physiopathological processes for the development of antiviral strategies to protect individuals from severe disease. To decipher the mechanisms of CHIKV in

Insights into the mechanisms governing P01 scorpion toxin effect against U87 glioblastoma cells oncogenesis

The emerging concept of small conductance Ca2+-activated potassium channels (SKCa) as pharmacological target for cancer treatment has significantly increased in recent years. In this study, we isolated the P01 toxin from Androctonus australis (Aa) scorpion venom and investigated its effect on biological properties of glioblastoma U87, breast MDA-MB231 and colon adenocarcinoma LS174 cancer cell lines. Our results showed that P01 was active only on U87 glioblastoma cells. It inhibited their proliferation, adhesion and migration with IC50 values in the micromolar range. We have also shown that P01 reduced the amplitude of the currents recorded in HEK293 cells expressing SK2 channels with an IC50 value of 3 pM, while it had no effect on those expressing SK3 channels. The investigation of the SKCa channels expression pattern showed that SK2 transcripts were expressed differently in the three cancer cell lines. Particularly, we highlighted the presence of SK2 isoforms in U87 cells, which could explain and rely on the specific activity of P01 on this cell line. These experimental data highlighted the usefulness of scorpion peptides to decipher the role of SKCa channels in the tumorigenesis process, and develop potential therapeutic molecules targeting glioblastoma with high selectivity

Physiological and proteomic approaches to address the active role of ozone in kiwifruit post-harvest ripening

Post-harvest ozone application has recently been shown to inhibit the onset of senescence symptoms on fleshy fruit and vegetables; however, the exact mechanism of action is yet unknown. To characterize the impact of ozone on the post-harvest performance of kiwifruit (Actinidia deliciosa cv. ‘Hayward’), fruits were cold stored (0 °C, 95% relative humidity) in a commercial ethylene-free room for 1, 3, or 5 months in the absence (control) or presence of ozone (0.3 μl l−1) and subsequently were allowed to ripen at a higher temperature (20 °C), herein defined as the shelf-life period, for up to 12 days. Ozone blocked ethylene production, delayed ripening, and stimulated antioxidant and anti-radical activities of fruits. Proteomic analysis using 1D-SDS-PAGE and mass spectrometry identified 102 kiwifruit proteins during ripening, which are mainly involved in energy, protein metabolism, defence, and cell structure. Ripening induced protein carbonylation in kiwifruit but this effect was depressed by ozone. A set of candidate kiwifruit proteins that are sensitive to carbonylation was also discovered. Overall, the present data indicate that ozone improved kiwifruit post-harvest behaviour, thus providing a first step towards understanding the active role of this molecule in fruit ripening

Metabolic Adaptation in Transplastomic Plants Massively Accumulating Recombinant Proteins

BACKGROUND: Recombinant chloroplasts are endowed with an astonishing capacity to accumulate foreign proteins. However, knowledge about the impact on resident proteins of such high levels of recombinant protein accumulation is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Here we used proteomics to characterize tobacco (Nicotiana tabacum) plastid transformants massively accumulating a p-hydroxyphenyl pyruvate dioxygenase (HPPD) or a green fluorescent protein (GFP). While under the conditions used no obvious modifications in plant phenotype could be observed, these proteins accumulated to even higher levels than ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco), the most abundant protein on the planet. This accumulation occurred at the expense of a limited number of leaf proteins including Rubisco. In particular, enzymes involved in CO(2) metabolism such as nuclear-encoded plastidial Calvin cycle enzymes and mitochondrial glycine decarboxylase were found to adjust their accumulation level to these novel physiological conditions. CONCLUSIONS/SIGNIFICANCE: The results document how protein synthetic capacity is limited in plant cells. They may provide new avenues to evaluate possible bottlenecks in recombinant protein technology and to maintain plant fitness in future studies aiming at producing recombinant proteins of interest through chloroplast transformation