Effects of a self-management program on antiemetic-induced constipation during chemotherapy among breast cancer patients: a randomized controlled clinical trial.

Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, -3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy

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

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

Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in patients with early gastric cancer: increase of cell proliferation in paramalignant lesions

Gastric cancer is typically an end result of Helicobacter pylori -associated chronic gastritis. The pathogenesis is thought to involve effects on gastric mucosal epithelial cell turnover. In this study, we aimed to compare apoptosis and proliferation in the noncancer-containing mucosa of H. pylori -positive patients with early gastric cancer with these phenomena in H. pylori -positive controls.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41590/1/535_2004_Article_1549.pd

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

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

Aquaporin 1 water channel is overexpressed in the plasma membranes of pancreatic ducts in patients with autoimmune pancreatitis

Chronic pancreatitis with all kinds of etiologies is characterized by pancreatic exocrine dysfunction especially impaired fluid secretion from pancreatic ducts. However, the molecular mechanism of this impaired fluid secretion in chronic pancreatitis is largely unknown. Aquaporin water channels are intrinsic membrane proteins expressed most of the cell types which have high osmotic water permeability. Among them aquaporin 1 (AQP1) is a predominant water channel expressed in the plasma membranes of human pancreatic ducts. Exocrine function test revealed that fluid secretion was severely impaired in AIP. immunohistochemical analysis revealed that AQP1 is localized mainly in the apical and lateral membranes of small pancreatic ducts in control subjects. AQP1 expression was significantly increased in plasma membranes of pancreatic ducts in AIP. Upregulation of AQP1 expression seen in pancreatic ducts of patient with AIP may be caused by the reduced fluid secretion from the pancreas as compensation. Further study would be required to elucidate the precise molecular mechanism for the role of AQP1 in pancreatic fluid secretion from the pancreas in diseases characterized by the impaired ductal fluid secretion such as cystic fibrosis

Spectral evolution of dark asteroid surfaces induced by space weathering over a decade

The surface of airless bodies like asteroids in the Solar System are known to be affected by space weathering. Experiments simulating space weathering are essential for studying the effects of this process on meteorite samples, but the problem is that the time spent to reproduce space weathering in these experiments is billions of times shorter than the actual phenomenon. In December 2010, the T-type asteroid 596 Scheila underwent a collision with a few-tens-of-meters impactor. A decade later, there is an opportunity to study how the surface layer of this asteroid is being altered by space weathering after the impact. To do so, we performed visible spectrophotometric and near-infrared spectroscopic observations of 596 Scheila. The acquired spectrum is consistent with those observed shortly after the 2010 impact event within the observational uncertainty range. This indicates that the surface color of dark asteroids is not noticeably changed by space weathering over a 10-year period. This study is the first to investigate color changes due to space weathering on an actual asteroid surface in the Solar System. Considering that fresh layers are regularly created on asteroid surfaces by collisions, we suggest a genetic link between D/T-type and dark (low albedo) X-complex asteroids and very red objects such as 269 Justitia, 732 Tjilaki (and 203 Pompeja). New observations show that 203 Pompeja has a X-type-like surface, with some local surface areas exhibiting a very red spectrum.Comment: 16 pages, 9 figures, 2 tables, Accepted for publication in ApJ Letter

Clinical and MRI Characteristics of Uterine Cervical Adenocarcinoma: Its Variants and Mimics

Adenocarcinoma currently accounts for 10–25% of all uterine cervical carcinomas and has a variety of histopathological subtypes. Among them, mucinous carcinoma gastric type is not associated with high-risk human papillomavirus (HPV) infection and a poor prognosis, while villoglandular carcinoma has an association with high-risk HPV infection and a good prognosis. They show relatively characteristic imaging findings which can be suggested by magnetic resonance imaging (MRI), though the former is sometimes difficult to be distinguished from lobular endocervical glandular hyperplasia. Various kinds of other tumors including squamous cell carcinoma should be also differentiated on MRI, while it is currently difficult to distinguish them on MRI, and HPV screening and pathological confirmation are usually necessary for definite diagnosis and further patient management