Ethylisopropylamiloride Diminishes Changes in Intracellular Na, Ca and pH in Ischemic Newborn Myocardium

Numerous studies suggest that in adult hearts myocardial ischemic injury is in part the result of proton stimulation of Na/H exchange which increases intracellular Na (Nai) and thus leads to increases in intracellular Ca concentration ( [Ca]i) due to changes in Na/Ca exchange flux. Corollary to the hypothesis, inhibition of Na/H exchange diminishes Na and Ca accumulation and improves heart function after ischemia. To test this hypothesis and its corollary in newborn hearts, NMR spectroscopy was used to measure intracellular pH (pHi), Nai, [Ca]i, and high energy phosphates in isolated, 4-7-day-old rabbit hearts, Langendorff-perfused with Krebs-Henseleit solution at pH 7.4+/-0.5 equilibrated with 95% O2/5% CO2 at 36+/-1 degrees C. Control hearts were perfused for 30 min before initiating 40 min of global ischemia followed by 40 min of reperfusion. In a second group of hearts ethylisopropylamiloride (EIPA-10 microM) was added to the perfusate 20 min before global ischemia to inhibit Na/H exchange. After 15 min ischemia, pHi in EIPA-treated hearts (6.41+/-0.04) was higher than that of the control hearts (6.20+/-0.08; P<0.05). EIPA also limited the increase in Nai and [Ca]i during ischemia and improved Nai and [Ca]i recovery during reperfusion (P<0.05). Nai (mEq/kg dry weight) rose from 18. 1+/-3.2 to 110.6+/-14.0 and recovered to 53.3+/-12.3 in the control group. The corresponding Nai values for EIPA-treated hearts were 16. 2+/-2.4, 39.6+/-9.6 and 12.6+/-3.5, respectively. In control hearts [Ca]i (nM/l) rose from 332+/-42 to 1157+/-89 and recovered to 842+/-55, whereas in EIPA-treated hearts the values were 255+/-32, 616+/-69 and 298+/-34, respectively. EIPA also preserved cellular ATP during ischemia and reperfusion and diminished inorganic phosphate during reperfusion (P<0.05). Finally, EIPA treatment improved recovery of left ventricular developed pressure (68.2+/-8.9 v 16.2+/-3.6% of control) and limited myocardial injury as indicated by decreased total creatine kinase release during reperfusion (348+/-132 v 2432+/-639 IU/g dry weight). Thus, as in adults, the results from newborn hearts are consistent with the hypothesis

The Abdominal Circulatory Pump

Blood in the splanchnic vasculature can be transferred to the extremities. We quantified such blood shifts in normal subjects by measuring trunk volume by optoelectronic plethysmography, simultaneously with changes in body volume by whole body plethysmography during contractions of the diaphragm and abdominal muscles. Trunk volume changes with blood shifts, but body volume does not so that the blood volume shifted between trunk and extremities (Vbs) is the difference between changes in trunk and body volume. This is so because both trunk and body volume change identically with breathing and gas expansion or compression. During tidal breathing Vbs was 50–75 ml with an ejection fraction of 4–6% and an output of 750–1500 ml/min. Step increases in abdominal pressure resulted in rapid emptying presumably from the liver with a time constant of 0.61±0.1SE sec. followed by slower flow from non-hepatic viscera. The filling time constant was 0.57±0.09SE sec. Splanchnic emptying shifted up to 650 ml blood. With emptying, the increased hepatic vein flow increases the blood pressure at its entry into the inferior vena cava (IVC) and abolishes the pressure gradient producing flow between the femoral vein and the IVC inducing blood pooling in the legs. The findings are important for exercise because the larger the Vbs the greater the perfusion of locomotor muscles. During asystolic cardiac arrest we calculate that appropriate timing of abdominal compression could produce an output of 6 L/min. so that the abdominal circulatory pump might act as an auxiliary heart

Cell entry of a host targeting protein of oomycetes requires gp96

This work is supported by the [European Community’s] Seventh Framework Programme [FP7/2007–2013] under grant agreement no. [238550] (L.L., J.D.-U., C.J.S., P.v.W.); BBSRC [BBE007120/1, BB/J018333/1 and BB/G012075/1] (F.T., I.d.B., C.J.S., S.W., P.v.W.); Newton Global Partnership Award [BB/N005058/1] (F.T., P.v.W.), the University of Aberdeen (A.D.T., T.R., C.J.S., P.v.W.) and Deutsche Forschungsgemeinschaft [CRC1093] (P.B., T.S.). We would like to acknowledge the Ministry of Higher Education Malaysia for funding INA. We would like to thank Brian Haas for his bioinformatics support. We would like to acknowledge Neil Gow and Johannes van den Boom for critical reading of the manuscript. We would like to acknowledge Svetlana Rezinciuc for technical help with pH-studies.Peer reviewedPublisher PD

Treatment planning system and beam data validation for the ZAP‐X: A novel self‐shielded stereotactic radiosurgery system

PURPOSE: To evaluate the treatment planning system (TPS) performance of the ZAP-X stereotactic radiosurgery (SRS) system through nondosimetric, dosimetric, and end-to-end (E2E) tests. METHODS: A comprehensive set of TPS commissioning and validation tests was developed using published guidelines. Nondosimetric validation tests included information transfer, computed tomography-magnetic resonance (CT-MR) image registration, structure/contouring, geometry, dose tools, and CT density. Dosimetric validation included comparisons between TPS and water tank/Solid Water measurements for various geometries and beam arrangements and end-to-end (E2E) tests. Patient-specific quality assurance was performed with an ion chamber in the Lucy phantom and with Gafchromic EBT3 film in the CyberKnife head phantom. RadCalc was used for independent verification of monitor units. Additional E2E tests were performed using the RPC Gamma Knife thermoluminescent dosimeter (TLD) phantom, MD Anderson SRS head phantom, and PseudoPatient gel phantom for independent absolute dose verification. RESULTS: CT-MR image registrations with known translational and rotational offsets were within tolerance (\u3c0.5 × maximum voxel dimension). Slice thickness and distance accuracy were within 0.1 mm, and volume accuracy was within 0 to 0.11 cm . Treatment planning system volume measurement uncertainty was within 0.1 to 0.4 cm . Ion chamber point-dose measurements for a single beam in a water phantom agreed to TPS-calculated values within ±4% for collimator diameters 10 to 25 mm, and ±6% for 7.5 mm, for all measured depths (7, 50, 100, 150, and 200 mm). In homogeneous Solid Water, point-dose measurements agreed to within ±4% for cones sizes 7.5 to 25 mm. With 1-cm high/low density inserts, measurements were within ±4.2% for cone sizes 10 to 25 mm. Film-based E2E using 4/5-mm cones resulted in a gamma passing rate (%GP) of 99.8% (2%/1.5 mm). Point-dose measurements in a Lucy phantom with an ion chamber using 36 beams distributed along three noncoplanar arcs agreed to within ±4% for cone sizes 10 to 25 mm. The RPC Gamma Knife TLD phantom yielded passing results with a measured-to-expected TLD dose ratio of 1.02. The MD Anderson SRS head phantom yielded passing results, with 4% TLD agreement and %GP of 95%/93% (5%/3 mm) for coronal/sagittal film planes. The RTsafe gel phantom gave %GP of \u3e95% (5%/2 mm) for all four targets. For our first 58 patients, film-based patient-specific quality assurance has resulted in an average %GP of 98.7% (range, 94-100%) at 2%/2 mm. CONCLUSIONS: Core ZAP-X features were found to be functional. On the basis of our results, point-dose and planar measurements were in agreement with TPS calculations using multiple phantoms and setup geometries, validating the ZAP-X TPS beam model for clinical use