Phosphoregulation of K(+)-Cl(-) cotransporter 4 during changes in intracellular Cl(-) and cell volume

It has long been stated that the K(+)-Cl(-) cotransporters (KCCs) are activated during cell swelling through dephosphorylation of their cytoplasmic domains by a protein phosphatase (PP) but that other enzymes are involved by targeting this PP or the KCCs directly. To date, however, the role of signaling intermediates in KCC regulation has been deduced from indirect evidence rather than in vitro phosphorylation studies, and examined after simulation of ion transport through cell swelling or N-ethylmaleimide treatment. In this study, the oocyte expression system was used to examine the effects of changes in cell volume (C(VOL)) and intracellular [Cl(-)] ([Cl(-)](i)) on the activity and phosphorylation levels (P(LEV)) of KCC4, and determine whether these effects are mediated by PP1 or phorbol myristate acetate (PMA)-sensitive effectors. We found that (1) low [Cl(-)](i) or low C(VOL) leads to decreased activity but increased P(LEV), (2) high C(VOL) leads to increased activity but no decrease in P(LEV) and (3) calyculin A (Cal A) or PMA treatment leads to decreased activity but no increase in P(LEV). Thus, we have shown for the first time that one of the KCCs can be regulated through direct phosphorylation, that changes in [Cl(-)](i) or C(VOL) modify the activity of signaling enzymes at carrier sites, and that the effectors directly involved do not include a Cal A-sensitive PP in contrast to the widely held view. J. Cell. Physiol. 219: 787-796, 2009. (c) 2009 Wiley-Liss, Inc.

The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency

Total body water (TBW) is reduced in adult GH deficiency (GHD) largely due to a reduction of extracellular water. It is unknown whether total blood volume (TBV) contributes to the reduced extracellular water in GHD. GH and insulin-like growth factor I (IGF-I) have been demonstrated to stimulate erythropoiesis in vitro, in animal models, and in growing children. Whether GH has a regulatory effect on red cell mass (RCM) in adults is not known. We analyzed body composition by bioelectrical impedance and used standard radionuclide dilution methods to measure RCM and plasma volume (PV) along with measuring full blood count, ferritin, vitamin B12, red cell folate, IGF-I, IGF-binding protein-3, and erythropoietin in 13 adult patients with GHD as part of a 3-month, double blind, placebo-controlled trial of GH (0.036 U/kg.day). TBW and lean body mass significantly increased by 2.5 +/- 0.53 kg (mean +/- SEM; P < 0.004) and 3.4 +/- 0.73 kg (P < 0.004), respectively, and fat mass significantly decreased by 2.4 +/- 0.32 kg (P < 0.001) in the GH-treated group. The baseline RCM of all patients with GHD was lower than the predicted normal values (1635 +/- 108 vs. 1850 +/- 104 mL; P < 0.002). GH significantly increased RCM, PV, and TBV by 183 +/- 43 (P < 0.006), 350 +/- 117 (P < 0.03), and 515 +/- 109 (P < 0.004) mL, respectively. The red cell count increased by 0.36 +/- 0.116 x 10(12)/L (P < 0.03) with a decrease in ferritin levels by 39.1 +/- 4.84 micrograms/L (P < 0.001) after GH treatment. Serum IGF-I and IGF-binding protein-3 concentrations increased by 3.0 +/- 0.43 (P < 0.001) and 1.3 +/- 0.15 (P < 0.001) SD, respectively, but the erythropoietin concentration was unchanged after GH treatment. No significant changes in body composition or blood volume were recorded in the placebo group. Significant positive correlations could be established between changes in TBW and TBV, lean body mass and TBV (r = 0.78; P < 0.04 and r = 0.77; P < 0.04, respectively), and a significant negative correlation existed between changes in fat mass and changes in TBV in the GH-treated group (r = -0.95; P < 0.02). We conclude that 1) erythropoiesis is impaired in GHD; 2) GH stimulates erythropoiesis in adult GHD; and 3) GH increases PV and TBV, which may contribute to the increased exercise performance seen in these patients.

A Physiological Controller for Turbodynamic Ventricular Assist Devices Based on a Measurement of the Left Ventricular Volume

The current article presents a novel physiological control algorithm for ventricular assist devices (VADs), which is inspired by the preload recruitable stroke work. This controller adapts the hydraulic power output of the VAD to the end-diastolic volume of the left ventricle. We tested this controller on a hybrid mock circulation where the left ventricular volume (LVV) is known, i.e., the problem of measuring the LVV is not addressed in the current article. Experiments were conducted to compare the response of the controller with the physiological and with the pathological circulation, with and without VAD support. A sensitivity analysis was performed to analyze the influence of the controller parameters and the influence of the quality of the LVV signal on the performance of the control algorithm. The results show that the controller induces a response similar to the physiological circulation and effectively prevents over- and underpumping, i.e., ventricular suction and backflow from the aorta to the left ventricle, respectively. The same results are obtained in the case of a disturbed LVV signal. The results presented in the current article motivate the development of a robust, long-term stable sensor to measure the LVV.

La compétence en matière contractuelle selon le règlement 44/2001 "Bruxelles I" et la Convention de Lugano révisée à la Suite de l'arrêt CJCE Color Drack

Ce volume recueille les actes du colloque qui sest tenu le 16 mars 2007 à lInstitut suisse de droit comparé (Lausanne) à loccasion de la 19e Journée de droit international privé. Le processus de révision de la Convention de Lugano, instrument dimportance centrale dans le contentieux international impliquant la Suisse, aura duré plus de dix ans. La signature de la Convention révisée est intervenue, pour le compte de la Suisse, le 30 octobre 2007. Le texte a subi un remodelage à laune du droit européen, tout en consacrant sans bouleversement majeur les acquis de la jurisprudence. Limportance de cet événement a incité une dizaine dexperts suisses et étrangers, spécialistes chevronnés et jeunes chercheurs à faire le point sur les quelques innovations du texte ainsi quà rappeler les solutions originelles qui ont résisté au temps.

Protein deficiency and the growing rat lung. I. Nutritional findings and related lung volumes

We investigated the consequences of early malnutrition on milk production by dams and on body weight and structural lung growth of young rats using two models of protein restriction. Dams of the early restriction group were fed an 8% casein diet starting at parturition. Those of the delayed restriction group received a 12% casein diet from lactation d 8-14 and thereafter the 8% diet. After weaning, early restriction and delayed restriction group rats were maintained on low protein until d 49, then refed the control diet (18% casein) up to d 126. Milk was analyzed on d 12. Animals were killed at d 21, 49, and 126 for lung fixation in situ. In this report, we show that protein restriction lowered milk yield to 38% of normal. Milk lipid per gram of dry weight tended to be increased, whereas lactose and protein were significantly decreased. Pups from protein-restricted dams grew less and had lower lung volumes, effects being more serious at d 49. However, specific lung volumes (in milliliters per 100 g body weight) were constantly increased. This means that lung was either less affected than body mass or overdistended due to less connective tissue. After refeeding, both groups showed a remarkable catch-up in growth with restoration of the normal allometric relationship between lung volume and body weight. Thus, even after an early onset of protein restriction to total body, the lung is still capable to substantially recover from growth retardation.

Solute transport in crystalline rocks at Äspö — I: Geological basis and model calibration

Water-conducting faults and fractures were studied in the granite-hosted A¨ spo¨ Hard Rock Laboratory (SE Sweden). On a scale of decametres and larger, steeply dipping faults dominate and contain a variety of different fault rocks (mylonites, cataclasites, fault gouges). On a smaller scale, somewhat less regular fracture patterns were found. Conceptual models of the fault and fracture geometries and of the properties of rock types adjacent to fractures were derived and used as input for the modelling of in situ dipole tracer tests that were conducted in the framework of the Tracer Retention Understanding Experiment (TRUE-1) on a scale of metres. After the identification of all relevant transport and retardation processes, blind predictions of the breakthroughs of conservative to moderately sorbing tracers were calculated and then compared with the experimental data. This paper provides the geological basis and model calibration, while the predictive and inverse modelling work is the topic of the companion paper [J. Contam. Hydrol. 61 (2003) 175]. The TRUE-1 experimental volume is highly fractured and contains the same types of fault rocks and alterations as on the decametric scale. The experimental flow field was modelled on the basis of a 2D-streamtube formalism with an underlying homogeneous and isotropic transmissivity field. Tracer transport was modelled using the dual porosity medium approach, which is linked to the flow model by the flow porosity. Given the substantial pumping rates in the extraction borehole, the transport domain has a maximum width of a few centimetres only. It is concluded that both the uncertainty with regard to the length of individual fractures and the detailed geometry of the network along the flowpath between injection and extraction boreholes are not critical because flow is largely one-dimensional, whether through a single fracture or a network. Process identification and model calibration were based on a single uranine breakthrough (test PDT3), which clearly showed that matrix diffusion had to be included in the model even over the short experimental time scales, evidenced by a characteristic shape of the trailing edge of the breakthrough curve. Using the geological information and therefore considering limited matrix diffusion into a thin fault gouge horizon resulted in a good fit to the experiment. On the other hand, fresh granite was found not to interact noticeably with the tracers over the time scales of the experiments. While fracture-filling gouge materials are very efficient in retarding tracers over short periods of time (hours–days), their volume is very small and, with time progressing, retardation will be dominated by altered wall rock and, finally, by fresh granite. In such rocks, both porosity (and therefore the effective diffusion coefficient) and sorption Kds are more than one order of magnitude smaller compared to fault gouge, thus indicating that long-term retardation is expected to occur but to be less pronounced.

Increase in hippocampal water diffusion and volume during experimental pneumococcal meningitis is aggravated by bacteremia

BACKGROUND The hippocampus undergoes apoptosis in experimental pneumococcal meningitis leading to neurofunctional deficits in learning and memory function. The aim of the present study was 1) to investigate hippocampal apparent diffusion coefficient (ADC) and volume with MRI during the course of experimental pneumococcal meningitis, 2) to explore the influence of accompanying bacteremia on hippocampal water distribution and volume, 3) and to correlate these findings to the extent of apoptosis in the hippocampus. METHODS Experimental meningitis in rats was induced by intracisternal injection of live pneumococci. The study comprised of four experimental groups. I. Uninfected controls (n = 8); II. Meningitis (n = 11); III. Meningitis with early onset bacteremia by additional i.v. injection of live pneumococci (n = 10); IV. Meningitis with attenuated bacteremia by treatment with serotype-specific anti-pneumococcal antibodies (n = 14). T2 and diffusion weighted MR images were used to analyze changes in hippocampus volume and water diffusion (ADC). The results were correlated to ADC of the cortex, to ventricular volume, and to the extent of hippocampal apoptosis. RESULTS Both ADC and the volume of hippocampus were significantly increased in meningitis rats compared to uninfected controls (Kruskal-Wallis test, p = 0.0001, Dunns Post Test, p < 0.05), and were significantly increased in meningitis rats with an early onset bacteremia as compared to meningitis rats with attenuated bacteremia (p < 0.05). Hippocampal ADC and the volume and size of brain ventricles were positively correlated (Spearman Rank, p < 0.05), whereas no association was found between ADC or volume and the extent of apoptosis (p > 0.05). CONCLUSIONS In experimental meningitis increase in volume and water diffusion of the hippocampus are significantly associated with accompanying bacteremia.

SADMFR Guidelines for the Use of Cone-Beam Computed Tomography/Digital Volume Tomography

In 2011, the first consensus conference on guidelines for the use of cone-beam computed tomography (CBCT) was convened by the Swiss Society of Dentomaxillofacial Radiology (SGDMFR). This conference covered topics of oral and maxillofacial surgery, temporomandibular joint dysfunctions and disorders, and orthodontics. In 2014, a second consensus conference was convened on guidelines for the use of CBCT in endodontics, periodontology, reconstructive dentistry and pediatric dentistry. The guidelines are intended for all dentists in order to facilitate the decision as to when the use of CBCT is justified. As a rule, the use of CBCT is considered restrictive, since radiation protection reasons do not allow its routine use. CBCT should therefore be reserved for complex cases where its application can be expected to provide further information that is relevant to the choice of therapy. In periodontology, sufficient information is usually available from clinical examination and periapical radiographs; in endodontics alternative methods can often be used instead of CBCT; and for implant patients undergoing reconstructive dentistry, CT is of interest for the workflow from implant planning to the superstructure. For pediatric dentistry no application of CBCT is seen for caries diagnosis.