Improvement in right ventricular function during reversibility testing in pulmonary arterial hypertension: a case report

A right heart catheterization with reversibility testing is recommended for the diagnosis and treatment of pulmonary arterial hypertension. In this 24 years-old woman, the inhalation of 5 μg iloprost transiently decreased mean pulmonary artery pressure from 62 to 36 mmHg and pulmonary vascular resistance from 11.0 to 4.9 Wood units, meeting the criteria of a "positive response". The echocardiographic examination showed normalization of right heart chamber dimensions and of the right ventricular performance (Tei) index. Pulsed tissue Doppler imaging of the right ventricle showed a decrease in the isovolumic relaxation time from 102 to 73 ms, and an increase of the E/A ratio from 0.72 to 1.38, together with marked improvements in mid-apical free wall systolic strain and strain rate. A positive response to reversibility testing of pulmonary arterial hypertension may be associated with quasi normalization of right ventricular function, in spite of still elevated pulmonary artery pressure

Simulations of energetic beam deposition: from picoseconds to seconds

We present a new method for simulating crystal growth by energetic beam deposition. The method combines a Kinetic Monte-Carlo simulation for the thermal surface diffusion with a small scale molecular dynamics simulation of every single deposition event. We have implemented the method using the effective medium theory as a model potential for the atomic interactions, and present simulations for Ag/Ag(111) and Pt/Pt(111) for incoming energies up to 35 eV. The method is capable of following the growth of several monolayers at realistic growth rates of 1 monolayer per second, correctly accounting for both energy-induced atomic mobility and thermal surface diffusion. We find that the energy influences island and step densities and can induce layer-by-layer growth. We find an optimal energy for layer-by-layer growth (25 eV for Ag), which correlates with where the net impact-induced downward interlayer transport is at a maximum. A high step density is needed for energy induced layer-by-layer growth, hence the effect dies away at increased temperatures, where thermal surface diffusion reduces the step density. As part of the development of the method, we present molecular dynamics simulations of single atom-surface collisions on flat parts of the surface and near straight steps, we identify microscopic mechanisms by which the energy influences the growth, and we discuss the nature of the energy-induced atomic mobility

A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = −0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model

CXCR7 Protein Expression in Human Adult Brain and Differentiated Neurons

Background: CXCR7 and CXCR4 are receptors for the chemokine CXCL12, which is involved in essential functions of the immune and nervous systems. Although CXCR7 transcripts are widely expressed throughout the central nervous system, little is known about its protein distribution and function in the adult brain. To evaluate its potential involvement in CXCL12/CXCR4 signaling in differentiated neurons, we studied CXCR7 protein expression in human brain and cultured neurons. Methodology/Principal Findings: Immunohistochemistry and RT-PCR analyses of cortex and hippocampus from control and HIV-positive subjects provided the first evidence of CXCR7 protein expression in human adult neurons, under normal and pathological conditions. Furthermore, confocal microscopy and binding assays in cultured neurons show that CXCR7 protein is mainly located into cytoplasm, while little to no protein expression is found on neuronal plasma membrane. Interestingly, specific CXCR7 ligands that inhibit CXCL12 binding to CXCR7 do not alter CXCR4-activated survival signaling (pERK/pAkt) in rat cortical neurons. Neuronal CXCR7 co-localizes to some extent with the endoplasmic reticulum marker ERp29, but not with early/late endosome markers. Additionally, large areas of overlap are detected in the intracellular pattern of CXCR7 and CXCR4 expression. Conclusions/Significance: Overall, these results implicate CXCR4 as the main CXCL12 signaling receptor on the surface o

Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy

RATIONALE: Adjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment. OBJECTIVES: The present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine. METHODS: Male Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified. RESULTS: MTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers. CONCLUSIONS: These results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors

Can environmental or occupational hazards alter the sex ratio at birth? A systematic review

More than 100 studies have examined whether environmental or occupational exposures of parents affect the sex ratio of their offspring at birth. For this review, we searched Medline and Web of Science using the terms ‘sex ratio at birth’ and ‘sex ratio and exposure’ for all dates, and reviewed bibliographies of relevant studies to find additional articles. This review focuses on exposures that have been the subject of at least four studies including polychlorinated biphenyls (PCBs), dioxins, pesticides, lead and other metals, radiation, boron, and g-forces. For paternal exposures, only dioxins and PCBs were consistently associated with sex ratios higher or lower than the expected 1.06. Dioxins were associated with a decreased proportion of male births, whereas PCBs were associated with an increased proportion of male births. There was limited evidence for a decrease in the proportion of male births after paternal exposure to DBCP, lead, methylmercury, non-ionizing radiation, ionizing radiation treatment for childhood cancer, boron, or g-forces. Few studies have found higher or lower sex ratios associated with maternal exposures. Studies in humans and animals have found a reduction in the number of male births associated with lower male fertility, but the mechanism by which environmental hazards might change the sex ratio has not yet been established