Plasma levels of a low-dose constant-rate-infusion of ketamine and its effect on single and repeated nociceptive stimuli in conscious dogs

This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg(-1) bolus and at a dose rate of 10 microg kg(-1) min(-1)) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography. Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog.

Low-dosage clomiphene reduces premature ovulation rates and increases transfer rates in natural-cycle IVF

Natural-cycle IVF has been suggested as an alternative IVF treatment. However, efficacy is limited due to high premature ovulation rates, resulting in low transfer rates. This study investigates whether low dosages of clomiphene citrate reduce premature ovulation rate and increase transfer rate. Of 112 women included (aged 35.2 ± 4.5 years) 108 underwent one natural-cycle IVF cycle with human chorionic gonadotrophin (HCG) to induce ovulation and 103 underwent one natural-cycle IVF cycle with 25 mg/day clomiphene from about day 7 until HCG administration. Before retrieval, 1.2 monitoring consultations per cycle were required. Clomiphene reduced premature ovulation rate, from 27.8% without to 6.8% with clomiphene (P < 0.001) and increased transfer rate from 39.8% to 54.4% (P = 0.039). Clinical pregnancy rates without and with clomiphene were 27.9% versus 25.0% per transfer and 11.1% versus 13.6% per initiated cycle. Use of clomiphene resulted in mild hot flushes and headache in 5% of patients. Nausea and persisting ovarian cyst formation was not observed. In conclusion, clomiphene citrate led to very few side effects, required 1.2 monitoring consultations, significantly reduced premature ovulation rate and significantly increased transfer rate per initiated cycle, an effect which was not age dependent.

Effects of a low dose infusion of racemic and S-ketamine on the nociceptive withdrawal reflex in standing ponies

OBJECTIVE: To investigate the effect of plasma concentrations obtained by a low dose constant rate infusion (CRI) of racemic ketamine or S-ketamine on the nociceptive withdrawal reflex (NWR) in standing ponies. STUDY DESIGN: Prospective, blinded, cross-over study. ANIMALS: Six healthy 5-year-old Shetland ponies. METHODS: Ponies received either 0.6 mg kg(-1) racemic ketamine (group RS) or 0.3 mg kg(-1) S-ketamine (group S) intravenously (IV), followed by a CRI of 20 microg kg(-1)minute(-1) racemic ketamine (group RS) or 10 microg kg(-1)minute(-1) S-ketamine (group S) for 59 minutes. The NWR was evoked by transcutaneous electrical stimulation of a peripheral nerve before drug administration, 15 and 45 minutes after the start of the bolus injection and 15 minutes after the end of the CRI. Electromyographic responses were recorded and analysed. Arterial blood was collected before stimulation and plasma concentrations of ketamine and norketamine were measured enantioselectively using capillary electrophoresis. Ponies were video recorded and monitored to assess drug effects on behaviour, heart rate (HR), mean arterial blood pressure (MAP) and respiratory rate. RESULTS: The NWR was significantly depressed in group RS at plasma concentrations between 20 and 25 ng mL(-1) of each enantiomer. In group S, no significant NWR depression could be observed; plasma concentrations of S-ketamine (9-15 ng mL(-1)) were lower, compared to S-ketamine concentrations in group RS, although this difference was not statistically significant. Minor changes in behaviour, HR and MAP only occurred within the first 5-10 minutes after bolus drug administration in both groups. CONCLUSION: Antinociceptive activity in standing ponies, demonstrated as a depression of the NWR, could only be detected after treatment with racemic ketamine. S-ketamine may have lacked this effect as a result of lower plasma concentrations, a more rapid metabolism or a lower potency of S-ketamine in Equidae so further investigation is necessary.

Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging

PURPOSE: To compare dynamic contrast material-enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC(low); b = 0, 50, and 100 sec/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). The difference between ADC(low) and ADC(high) was used as a surrogate measure of tissue perfusion (ADC(low) - ADC(high) = ADC(perf)). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement-time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used. RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC(perf)) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC(perf) were correlated with changes in k (R(2) = 0.46, P < .001) and the initial slope (R(2) = 0.67, P < .001). CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.

Dielectric map of the Martian northern hemisphere and the nature of plain filling materials

[1] A number of observations suggest that an extended ocean once covered a significant part of the Martian northern hemisphere. By probing the physical properties of the subsurface to unprecedented depth, the MARSIS/Mars Express provides new geophysical evidences for the former existence of a Late Hesperian ocean. The Vastitas Borealis formation, located inside a putative shoreline of the ancient ocean, has a low dielectric constant compared with that of typical volcanic materials. We show that the measured value is only consistent with low-density sedimentary deposits, massive deposits of ground-ice, or a combination of the two. In contrast, radar observations indicate a distribution of shallow ground ice in equilibrium with the atmosphere in the south polar region. We conclude that the northern plains are filled with remnants of a late Hesperian ocean, fed by water and sediments from the outflow channels about 3 Gy ago.

Slab rollback orogeny in the Alps and evolution of the Swiss Molasse basin

The stratigraphies of foreland basins have been related to orogeny, where continent–continent collision causes the construction of topography and the downwarping of the foreland plate. These mechanisms have been inferred for the Molasse basin, stretching along the northern margin of the European Alps. Continuous flexural bending of the subducting European lithosphere as a consequence of topographic loads alone would imply that the Alpine topography would have increased at least between 30 Ma and ca. 5–10 Ma when the basin accumulated the erosional detritus. This, however, is neither consistent with observations nor with isostatic mass balancing models because paleoaltimetry estimates suggest that the topography has not increased since 20 Ma. Here we show that a rollback mechanism for the European plate is capable of explaining the construction of thick sedimentary successions in the Molasse foreland basin where the extra slab load has maintained the Alpine surface at low, but constant, elevations.

Review of lattice results concerning low-energy particle physics

We review lattice results related to pion, kaon, D- and B-meson physics with the aim of making them easily accessible to the particle-physics community. More specifically, we report on the determination of the lightquark masses, the form factor f+(0), arising in semileptonic K → π transition at zero momentum transfer, as well as the decay-constant ratio fK / fπ of decay constants and its consequences for the CKM matrix elements Vus and Vud. Furthermore, we describe the results obtained on the lattice for some of the low-energy constants of SU(2)L × SU(2)R and SU(3)L×SU(3)R Chiral Perturbation Theory and review the determination of the BK parameter of neutral kaon mixing. The inclusion of heavy-quark quantities significantly expands the FLAG scope with respect to the previous review. Therefore, we focus here on D- and B-meson decay constants, form factors, and mixing parameters, since these are most relevant for the determination of CKM matrix elements and the global CKM unitarity-triangle fit. In addition we review the status of lattice determinations of the strong coupling constant αs.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator.

OBJECTIVES Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. METHODS The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. RESULTS Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. CONCLUSIONS We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator

Gebiet: Chirurgie Biomedizintechnik Biophysik Transplantationsmedizin Kardiologie Abstract: OBJECTIVES: – Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. – – METHODS: – The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. – – RESULTS: – Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. – – CONCLUSIONS: – We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion. – – © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

The recoil transfer chamber - An interface to connect the physical preseparator TASCA with chemistry and counting setups

Performing experiments with transactinide elements demands highly sensitive detection methods due to the extremely low production rates (one-atom-at-a-time conditions). Preseparation with a physical recoil separator is a powerful method to significantly reduce the background in experiments with sufficiently long-lived isotopes (t1/2≥0.5 s). In the last years, the new gas-filled TransActinide Separator and Chemistry Apparatus (TASCA) was installed and successfully commissioned at GSI. Here, we report on the design and performance of a Recoil Transfer Chamber (RTC) for TASCA—an interface to connect various chemistry and counting setups with the separator. Nuclear reaction products recoiling out of the target are separated according to their magnetic rigidity within TASCA, and the wanted products are guided to the focal plane of TASCA. In the focal plane, they pass a thin Mylar window that separates the ∼1 mbar atmosphere in TASCA from the RTC kept at ∼1 bar. The ions are stopped in the RTC and transported by a continuous gas flow from the RTC to the ancillary setup. In this paper, we report on measurements of the transportation yields under various conditions and on the first chemistry experiments at TASCA—an electrochemistry experiment with osmium and an ion exchange experiment with the transactinide element rutherfordium.

Modeling of Heat Transfer in Microchannel Gas Flow

Due to the existence of a velocity slip and temperature jump on the solid walls, the heat transfer in microchannels significantly differs from the one in the macroscale. In our research, we have focused on the pressure driven gas flows in a simple finite microchannel geometry, with an entrance and an outlet, for low Reynolds (Re<200) and low Knudsen (Kn<0.01) numbers. For such a regime, the slip induced phenomena are strongly connected with the viscous effects. As a result, heat transfer is also significantly altered. For the optimization of flow conditions, we have investigated various temperature gradient configurations, additionally changing Reynolds and Knudsen numbers. The entrance effects, slip flow, and temperature jump lead to complex relations between flow behavior and heat transfer. We have shown that slip effects are generally insignificant for flow behavior. However, two configuration setups (hot wall cold gas and cold wall hot gas) are affected by slip in distinguishably different ways. For the first one, which concerns turbomachinery, the mass flow rate can increase by about 1% in relation to the no-slip case, depending on the wall-gas temperature difference. Heat transfer is more significantly altered. The Nusselt number between slip and no-slip cases at the outlet of the microchannel is increased by about 10%.

The effect of standard and low-modulus cement augmentation on the stiffness, strength, and endplate pressure distribution in vertebroplasty

Vertebroplasty restores stiffness and strength of fractured vertebral bodies, but alters their stress transfer. This unwanted effect may be reduced by using more compliant cements. However, systematic experimental comparison of structural properties between standard and low-modulus augmentation needs to be done. This study investigated how standard and low-modulus cement augmentation affects apparent stiffness, strength, and endplate pressure distribution of vertebral body sections.

Effects of low abdominal blood flow and dobutamine on blood flow distribution and on the hepatic arterial buffer response in anaesthetized pigs

Low cardiac output impairs the hepatic arterial buffer response (HABR). Whether this is due to low abdominal blood flow per se is not known. Dobutamine is commonly used to increase cardiac output, and it may further modify hepatosplanchnic and renal vasoregulation. We assessed the effects of isolated abdominal aortic blood flow changes and dobutamine on hepatosplanchnic and renal blood flow. Twenty-five anesthetized pigs with an abdominal aorto-aortic shunt were randomized to 2 control groups [zero (n = 6) and minimal (n = 6) shunt flow], and 2 groups with 50% reduction of abdominal blood flow and either subsequent increased abdominal blood flow by shunt reduction (n = 6) or dobutamine infusion at 5 and 10 microg kg(-1) min(-1) with constant shunt flow (n = 7). Regional (ultrasound) and local (laser Doppler) intra-abdominal blood flows were measured. The HABR was assessed during acute portal vein occlusion. Sustained low abdominal blood flow, by means of shunt activation, decreased liver, gut, and kidney blood flow similarly and reduced local microcirculatory blood flow in the jejunum. Shunt flow reduction partially restored regional blood flows but not jejunal microcirculatory blood flow. Low-but not high-dose dobutamine increased gut and celiac trunk flow whereas hepatic artery and renal blood flows remained unchanged. Neither intervention altered local blood flows. The HABR was not abolished during sustained low abdominal blood flow despite substantially reduced hepatic arterial blood flow and was not modified by dobutamine. Low-but not high-dose dobutamine redistributes blood flow toward the gut and celiac trunk. The jejunal microcirculatory flow, once impaired, is difficult to restore.

Study of Staphylococcus aureus pathogenic genes by transfer and expression in the less virulent organism Streptococcus gordonii

Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordonii was more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deleting clfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity of clfA-positive streptococci when both clfA and coa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.