Non-synonymous polymorphisms in the P2RX 4 are related to bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients

In the present study we investigated whether single nucleotide polymorphisms (SNPs) in the P2RX₄, which alter the P2X₄R function, are associated with the development of osteoporosis and whether an interaction between the P2X₄R and P2X₇R confer a synergistic effect of these two receptors on osteoporosis risk. Patients with fracture (690 females and 231 males, aged ≥50 years) were genotyped for three non-synonymous P2X₄R SNPs. Bone mineral density (BMD) was measured at the total hip, lumbar spine, and femoral neck. Subject carrying the variant allele of the Tyr315Cys polymorphism showed a 2.68-fold (95 % CI, 1.20–6.02) higher risk of osteoporosis compared with wild-type subject. Furthermore, significant lower lumbar spine BMD values were observed in subjects carrying the Cys315 allele as compared with wild-type (0.85 ± 0.17 and 0.93 ± 0.17 g/cm², respectively; p < 0.001). Assuming a recessive model, carriers of the variant allele of the Ser242Gly polymorphism showed increased BMD values at the lumbar spine compare to wild-type subject (1.11 ± 0.35 and 0.92 ± 0.17 g/cm², respectively; p = 0.0045). This is the first study demonstrating an association of non-synonymous polymorphisms in the P2RX₄ and the risk of osteoporosis, suggesting a role of the P2X₄R in the regulation of bone mass.

Electronic supplementary material

The online version of this article (doi:10.1007/s11302-012-9337-0) contains supplementary material, which is available to authorized users.     

Hemodynamic responses to 30-min cycling exercise at 70% VO2 max both in ambiant air and during chest-immersion

The aim of this study was to examine the influence of water immersion to the chest on cardio-vascular adaptation to exercise. Upright or sitting immersion causes an increase in central blood volume, but it remains controversial whether central blood volume remains elevated during dynamic exercise in water and facilitates cardiac adaptation, depending particularly on the intensity of exercise which can be matched for O2 consumption (metabolic range) or for mechanical intensity (work load). We have compared hemodynamic variables measured during two cycling exercises at the same mechanical intensity, performed both in ambiant air and during immersion up to the chest.     

SARS-CoV-2 in patients with cancer: possible role of mimicry of human molecules by viral proteins and the resulting anti-cancer immunity

A few reports suggest that molecular mimicry can have a role in determining the more severe and deadly forms of COVID-19, inducing endothelial damage, disseminated intravascular coagulation, and multiorgan failure. Heat shock proteins/molecular chaperones can be involved in these molecular mimicry phenomena. However, tumor cells can display on their surface heat shock proteins/molecular chaperones that are mimicked by SARS-CoV-2 molecules (including the Spike protein), similarly to what happens in other bacterial or viral infections. Since molecular mimicry between SARS-CoV-2 and tumoral proteins can elicit an immune reaction in which antibodies or cytotoxic cells produced against the virus cross-react with the tumor cells, we want to prompt clinical studies to evaluate the impact of SARS-CoV-2 infection on prognosis and follow up of various forms of tumors. These topics, including a brief historical overview, are discussed in this paper.     

Comparison of various techniques used to estimate spontaneous baroreflex sensitivity (the EuroBaVar study)

This study compared spontaneous baroreflex sensitivity (BRS) estimates obtained from an identical set of data by 11 European centers using different methods and procedures. Noninvasive blood pressure (BP) and ECG recordings were obtained in 21 subjects, including 2 subjects with established baroreflex failure. Twenty-one estimates of BRS were obtained by methods including the two main techniques of BRS estimates, i.e., the spectral analysis (11 procedures) and the sequence method (7 procedures) but also one trigonometric regressive spectral analysis method (TRS), one exogenous model with autoregressive input method (X-AR), and one Z method. With subjects in a supine position, BRS estimates obtained with calculations of alpha-coefficient or gain of the transfer function in both the low-frequency band or high-frequency band, TRS, and sequence methods gave strongly related results. Conversely, weighted gain, X-AR, and Z exhibited lower agreement with all the other techniques. In addition, the use of mean BP instead of systolic BP in the sequence method decreased the relationships with the other estimates. Some procedures were unable to provide results when BRS estimates were expected to be very low in data sets (in patients with established baroreflex failure). The failure to provide BRS values was due to setting of algorithmic parameters too strictly. The discrepancies between procedures show that the choice of parameters and data handling should be considered before BRS estimation. These data are available on the web site (http://www.cbi.polimi.it/glossary/eurobavar.html) to allow the comparison of new techniques with this set of results.