Effects of Slc26a6 deletion and CFTR inhibition on HCO3- secretion by mouse pancreatic duct

Pancreatic duct epithelium secretes HCO3--rich fluid, which is dependent on cystic fibrosis transmembrane conductance regulator (CFTR). HCO3- transport across the apical membrane is thought to be mediated by both SLC26A6 Cl--HCO3- exchange and CFTR HCO3- conductance. In this study we examined the relative contribution and interaction of SLC26A6 and CFTR in apical HCO3- transport. Interlobular pancreatic ducts were isolated from slc26a6 null mice. Intracellular pH (pHi) was measured by BCECF microfluorometry. Duct cells were stimulated with forskolin and alkalinized by acetate pre-pulse in the presence ofHCO3--CO2. Apical HCO3- secretion was estimated from the recovery rate of pHi from alkaline load. When the lumen was perfused with high-Cl- solution, the rate of apical HCO3- secretion was increased by luminal application of CFTRinh-172 in ducts from wild-type mice but it was decreased in ducts from slc26a6 -/- mice. This suggests that slc26a6 and CFTR compensate/compete with each other for apical HCO3- secretion with high Cl- in the lumen. With high HCO3- in the lumen, luminal CFTRinh-172 reduced the rate of apical HCO3- secretion in both wild-type and slc26a6 -/- ducts. This suggests that HCO3- conductance of CFTR mediates a significant portion of apical HCO3- secretion with high HCO3- in the lumen

Apical Cl-/HCO3- exchanger stoichiometry in the modeling of HCO3- transport by pancreatic duct epithelium

Pancreatic duct cells secrete a HCO3--rich (～140 mM) fluid. Using a computer model of the pancreatic duct, Sohma, et al. have demonstrated that the activity of a Cl-/ HCO3- exchanger with a 1 : 1 stoichiometry at the apical membrane would have to be suppressed in order to achieve such a HCO3--rich secretion. Recently the apical exchanger in pancreatic ducts has been identified as SLC26A6 and this probably mediates most of Cl--dependent HCO3- secretion across the apical membrane. SLC26A6 is reported to mediate electrogenic Cl-/2HCO3- exchange when expressed in Xenopus oocytes. To assess the implications of this 1 : 2 stoichiometry for HCO3- secretion, we have reconstructed the Sohma model using MATLAB/Simulink. To do this we have formulated an expression for the turnover rate of Cl-/2HCO3- exchange using network thermodynamics and we have estimated the constants from published experimental data. Preliminary data suggest that the 1 : 2 stoichiometry of SLC26A6 would favor HCO3- secretion at higher concentrations

Rotational level structure of sodium isotopes inside the "island of inversion"

The neutron-rich nuclei 33,34,35Na were studied via in-beam γ-ray spectroscopy following nucleon removal reactions from a 36Mg secondary beam at ~220 MeV/u. Excited states of 34,35Na are reported for the first time. A third transition was observed for 33Na in addition to the known 7/2+ 1 → 5/2+ 1 → 3/2+ g.s. cascade and is suggested to be the 9/2+ 1 → 7/2+ 1 transition. Similarly, a 7/2+ 1 → 5/2+ 1 → 3/2+ g.s. cascade is proposed for the decay pattern observed for 35Na. The transition energy ratios are close to expectation values for K = 3/2 rotational bands in the strong coupling limit. Comparisons to large-scale shell model calculations in the sd-p f model space support the spin-parity assignments. © The Author(s) 2014.published_or_final_versio

Glucose transport in interlobular ducts isolated from rat pancreas

Pancreatic duct cells express Na+-dependent glucose transporter, SGLT1 and Na+-independent glucose transporters, GLUT1, GLUT2, and GLUT8. We examined transepithelial glucose transport by pancreatic duct. Interlobular ducts were isolated from rat pancreas. During overnight culture both ends of the duct segments sealed spontaneously. The lumen of the sealed duct was micropunctured and the luminal fluid was replaced by HEPES-buffered solution containing 10.0 mM or 44.4 mM glucose. The bath was perfused with HEPES-buffered solution at 37℃ containing 10.0 or 44.4 mM glucose. Transepithelial differences in osmolality were balanced with mannitol. Glucose transport across ductal epithelium was measured by monitoring changes in luminal volume. When the lumen was filled with 44.4 mM glucose, with either 10.0 or 44.4 mM glucose in the bath, the luminal volume decreased to 65～70% of the initial volume in 15 min. Luminally-injected phlorizin, an inhibitor of SGLT1, abolished the decrease in luminal volume. With 10.0 mM glucose in the lumen and 44.4 mM glucose in the bath, the luminal volume did not change significantly. Luminal application of phlorizin under identical condition led to an increase in luminal volume. The data suggest that both active and passive transport mechanisms of glucose are present in pancreatic ductal epithelium

A Clinical Trial Evaluating the Usefulness of Tailored Antimicrobial Prophylaxis Using Rectal-culture Screening Media Prior to Transrectal Prostate Biopsy: A Multicenter, Randomized Controlled Trial

The aim of this report is to introduce an on-going, multicenter, randomized controlled trial to evaluate whether tailored antimicrobial prophylaxis guided by rectal culture screening prevents acute bacterial prostatitis following transrectal prostate biopsy (TRPB). Patients will be randomized into an intervention or non-intervention group; tazobactam-piperacillin or levofloxacin will be prophylactically administered according to the results of rectal culture prior to TRPB in the intervention group whereas levofloxacin will be routinely given in the non-intervention group. The primary endpoint is the occurrence rate of acute bacterial prostatitis after TRPB. Recruitment begins in April, 2021 and the target total sample size is 5,100 participants

CFTR Functions as a Bicarbonate Channel in Pancreatic Duct Cells

Pancreatic duct epithelium secretes a HCO3−-rich fluid by a mechanism dependent on cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane. However, the exact role of CFTR remains unclear. One possibility is that the HCO3− permeability of CFTR provides a pathway for apical HCO3− efflux during maximal secretion. We have therefore attempted to measure electrodiffusive fluxes of HCO3− induced by changes in membrane potential across the apical membrane of interlobular ducts isolated from the guinea pig pancreas. This was done by recording the changes in intracellular pH (pHi) that occurred in luminally perfused ducts when membrane potential was altered by manipulation of bath K+ concentration. Apical HCO3− fluxes activated by cyclic AMP were independent of Cl− and luminal Na+, and substantially inhibited by the CFTR blocker, CFTRinh-172. Furthermore, comparable HCO3− fluxes observed in ducts isolated from wild-type mice were absent in ducts from cystic fibrosis (ΔF) mice. To estimate the HCO3− permeability of the apical membrane under physiological conditions, guinea pig ducts were luminally perfused with a solution containing 125 mM HCO3− and 24 mM Cl− in the presence of 5% CO2. From the changes in pHi, membrane potential, and buffering capacity, the flux and electrochemical gradient of HCO3− across the apical membrane were determined and used to calculate the HCO3− permeability. Our estimate of ∼0.1 µm sec−1 for the apical HCO3− permeability of guinea pig duct cells under these conditions is close to the value required to account for observed rates of HCO3− secretion. This suggests that CFTR functions as a HCO3− channel in pancreatic duct cells, and that it provides a significant pathway for HCO3− transport across the apical membrane

Results of the search for inspiraling compact star binaries from TAMA300's observation in 2000-2004

We analyze the data of TAMA300 detector to search for gravitational waves from inspiraling compact star binaries with masses of the component stars in the range 1-3Msolar. In this analysis, 2705 hours of data, taken during the years 2000-2004, are used for the event search. We combine the results of different observation runs, and obtained a single upper limit on the rate of the coalescence of compact binaries in our Galaxy of 20 per year at a 90% confidence level. In this upper limit, the effect of various systematic errors such like the uncertainty of the background estimation and the calibration of the detector's sensitivity are included.Comment: 8 pages, 4 Postscript figures, uses revtex4.sty The author list was correcte

Observation results by the TAMA300 detector on gravitational wave bursts from stellar-core collapses

We present data-analysis schemes and results of observations with the TAMA300 gravitational-wave detector, targeting burst signals from stellar-core collapse events. In analyses for burst gravitational waves, the detection and fake-reduction schemes are different from well-investigated ones for a chirp-wave analysis, because precise waveform templates are not available. We used an excess-power filter for the extraction of gravitational-wave candidates, and developed two methods for the reduction of fake events caused by non-stationary noises of the detector. These analysis schemes were applied to real data from the TAMA300 interferometric gravitational wave detector. As a result, fake events were reduced by a factor of about 1000 in the best cases. The resultant event candidates were interpreted from an astronomical viewpoint. We set an upper limit of 2.2x10^3 events/sec on the burst gravitational-wave event rate in our Galaxy with a confidence level of 90%. This work sets a milestone and prospects on the search for burst gravitational waves, by establishing an analysis scheme for the observation data from an interferometric gravitational wave detector