Utility of mass spectrometry for the diagnosis of the unstable coronary plaque.

Mass spectrometry is a powerful technique that is used to identify unknown compounds, to quantify known materials, and to elucidate the structure and chemical properties of molecules. Recent advances in the accuracy and speed of the technology have allowed data acquisition for the global analysis of lipids from complex samples such as blood plasma or serum. Here, mass spectrometry as a tool is described, its limitations explained and its application to biomarker discovery in coronary artery disease is considered. In particular an application of mass spectrometry for the discovery of lipid biomarkers that may indicate plaque morphology that could lead to myocardial infarction is elucidated

Radiation in medicine: Origins, risks and aspirations.

The use of radiation in medicine is now pervasive and routine. From their crude beginnings 100 years ago, diagnostic radiology, nuclear medicine and radiation therapy have all evolved into advanced techniques, and are regarded as essential tools across all branches and specialties of medicine. The inherent properties of ionizing radiation provide many benefits, but can also cause potential harm. Its use within medical practice thus involves an informed judgment regarding the risk/benefit ratio. This judgment requires not only medical knowledge, but also an understanding of radiation itself. This work provides a global perspective on radiation risks, exposure and mitigation strategies

A global perspective of arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited heart disease characterized by ventricular arrhythmias and sudden cardiac death especially in the young. ARVC has been traditionally associated with the Mediterranean basin, as many seminal studies on the disease have originated from research groups of this region. Today, however, numerous ARVC registries from all over the world emphasize that the disease does not have a specific racial or geographical predilection. This work provides a review on the global perspective of ARVC

RF communication with implantable wireless device: effects of beating heart on performance of miniature antenna

The frequency response of an implantable antenna is key to the performance of a wireless implantable sensor. If the antenna detunes significantly, there are substantial power losses resulting in loss of accuracy. One reason for detuning is because of a change in the surrounding environment of an antenna. The pulsating anatomy of the human heart constitutes such a changing environment, so detuning is expected but this has not been quantified dynamically before. Four miniature implantable antennas are presented (two different geometries) along with which are placed within the heart of living swine the dynamic reflection coefficients. These antennas are designed to operate in the short range devices frequency band (863-870 MHz) and are compatible with a deeply implanted cardiovascular pressure sensor. The measurements recorded over 27 seconds capture the effects of the beating heart on the frequency tuning of the implantable antennas. When looked at in the time domain, these effects are clearly physiological and a combination of numerical study and posthumous autopsy proves this to be the case, while retrospective simulation confirms this hypothesis. The impact of pulsating anatomy on antenna design and the need for wideband implantable antennas is highlighted

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Membrane-transferring regions of gp41 as targets for HIV-1 fusion inhibition and viral neutralization

12 páginas, 4 figurasThe fusogenic function of HIV-1 gp41 transmembrane Env subunit relies on two different kinds of structural elements: i) a collapsible ectodomain structure (the hairpin or six-helix bundle) that opens and closes, and ii) two membrane- transferring regions (MTRs), the fusion peptide (FP) and the membrane-proximal external region (MPER), which ensure coupling of hairpin closure to apposition and fusion of cell and viral membranes. The isolation of naturally produced short peptides and neutralizing IgG-s, that interact with FP and MPER, respectively, and block viral infection, suggests that these conserved regions might represent useful targets for clinical intervention. Furthermore, MTR-derived peptides have been shown to be membrane-active. Here, it is discussed the potential use of these molecules and how the analysis of their membrane activity in vitro could contribute to the development of HIV fusion inhibitors and effective immunogensThe authors wish to thank financial support obtained from Spanish MICINN (BIO2008- 00772) (JLN) and University of the Basque Country (GIU 06/42 and DIPE08/12) (NH and JLN).Peer reviewe

Effect of Carbamate Insecticide, Lannate, on the Gonads of Mice

The effect of the carbamate insecticide, lannate, on the gonads of mice was studied. Treating mice with lannate at a dose level of 10mg/kg body weight daily for 3-6 weeks had induced degenerative effects in the gonads, as follows, first in testis, a significant reduction in the diameter of the seminiferous tubules and germinal epithelial height. Histological examination of the testis showed that the seminiferous tubules were elongated and contained reduced spermatogenic cells. The number, of mature sperms was markedly reduced and after 3 weeks the sperm bundles were completely absent. On the other hand, the effect on the ovarian structure showed that, decrease in the number of secondary ovarian follicles and corpora lutea was recorded, while, the number of atretic follicles showed a significant increase. It is speculated that it may be resulted from the inhibition of RNA synthesis due to the effect of lannate

Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca2+-induced Ca2+ release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart–lung trans-plantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca2+ release synchronicity was reduced at 8 weeks moderate unloading only. Ca2+ sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule mor-phology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37 % reduction in cell volume at 4 weeks compared to 56 % reduction after severe mechanical unloading) and did not cause depres-sion and delay of the Ca2+ transient, increased Ca2+ spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiologi-cal states of increased and reduced cell size, without pathological changes are possible

Impact of Combined Clenbuterol and Metoprolol Therapy on Reverse Remodelling during Mechanical Unloading

Clenbuterol (Cl), a β2 agonist, is associated with enhanced myocardial recovery during left ventricular assist device (LVAD) support, and exerts beneficial remodelling effects during mechanical unloading (MU) in rodent heart failure (HF). However, the specific effects of combined Cl+β1 blockade during MU are unknown.We studied the chronic effects (4 weeks) of β2-adrenoceptor (AR) stimulation via Cl (2 mg/kg/day) alone, and in combination with β1-AR blockade using metoprolol ((Met), 250 mg/kg/day), on whole heart/cell structure, function and excitation-contraction (EC) coupling in failing (induced by left coronary artery (LCA) ligation), and unloaded (induced by heterotopic abdominal heart transplantation (HATx)) failing rat hearts. Combined Cl+Met therapy displayed favourable effects in HF: Met enhanced Cl's improvement in ejection fraction (EF) whilst preventing Cl-induced hypertrophy and tachycardia. During MU combined therapy was less beneficial than either mono-therapy. Met, not Cl, prevented MU-induced myocardial atrophy, with increased atrophy occurring during combined therapy. MU-induced recovery of Ca2+ transient amplitude, speed of Ca2+ release and sarcoplasmic reticulum Ca2+ content was enhanced equally by Cl or Met mono-therapy, but these benefits, together with Cl's enhancement of sarcomeric contraction speed, and MU-induced recovery of Ca2+ spark frequency, disappeared during combined therapy.Combined Cl+Met therapy shows superior functional effects to mono-therapy in rodent HF, but appears inferior to either mono-therapy in enhancing MU-induced recovery of EC coupling. These results suggest that combined β2-AR simulation +β1-AR blockade therapy is likely to be a safe and beneficial therapeutic HF strategy, but is not as effective as mono-therapy in enhancing myocardial recovery during LVAD support

A simple device for multiplex ELISA made from melt-extruded plastic microcapillary film

We present a simple device for multiplex quantitative enzyme-linked immunosorbant assays (ELISA) made from a novel melt-extruded microcapillary film (MCF) containing a parallel array of 200µm capillaries along its length. To make ELISA devices different protein antigens or antibodies were immobilised inside individual microcapillaries within long reels of MCF extruded from fluorinated ethylene propylene (FEP). Short pieces of coated film were cut and interfaced with a pipette, allowing sequential uptake of samples and detection solutions into all capillaries from a reagent well. As well as being simple to produce, these FEP MCF devices have excellent light transmittance allowing direct optical interrogation of the capillaries for simple signal quantification. Proof of concept experiments demonstrate both quantitative and multiplex assays in FEP MCF devices using a standard direct ELISA procedure and read using a flatbed scanner. This new multiplex immunoassay platform should find applications ranging from lab detection to point-of-care and field diagnostics