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

PHYSIOLOGY AND PATHOPHYSIOLOGY OF BICARBONATE SECRETION BY PANCREATIC DUCT EPITHELIUM

2012-02HCO3–-rich fluid in the pancreatic juice (2~3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar cells with a small amount of Cl–-rich fluid. Ductal HCO3– secretion is not only regulated by gastrointestinal hormones and cholinergic nerves but is also influenced by luminal factors: intraductal pressure, Ca2+ concentration, pathological activation of protease and bile reflux. The maximum HCO3– concentration of the juice under secretin stimulation reaches 140–150 mM. Thus pancreatic duct cells secrete HCO3– against a ~7-fold concentration gradient. HCO3– secretion critically depends on the activity of CFTR, a cAMP-dependent anion channel localized in the apical membrane of various epithelia. In the proximal part of pancreatic ducts close to acinar cells HCO3– secretion across the apical membrane is largely mediated by SLC26A6 Cl–-HCO3– exchanger. In distal ducts where the luminal HCO3– concentration is already high, most of the HCO3– secretion is mediated by HCO3– conductance of CFTR. CFTR is the causative gene for cystic fibrosis. Loss of function due to severe mutations in both alleles causes typical cystic fibrosis characterized by dehydrated, thick, and viscous luminal fluid/mucus in the respiratory and gastrointestinal tract, pancreatic duct, and vas deferens. A compound heterozygote of mutations/polymorphisms (causing a mild dysfunction of CFTR) involves a risk of developing CFTR-related diseases such as chronic pancreatitis. In cystic fibrosis and certain cases of chronic pancreatitis, the pancreatic duct epithelium secretes a small amount of fluid with neutral~acidic pH, which causes an obstruction of the duct lumen by a protein plug or viscous mucus.departmental bulletin pape

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

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

名古屋大学生協におけるハラルメニュー提供の現状と給食における多様性対応への一考察

It has been reported that at food service facilities such as hospitals and business establishments nationwide, there is a demand for diversity due to the increase in the proportion of foreigners eligible for food service, and that it is being implemented. At present, there are few reports on the operation method of halal menus in food service facilities, especially the correspondence method in the cooking process, and it is thought that there is not enough information to be used as a reference for considering the introduction. We investigated in detail the current situation and correspondence of university cafeterias that implement halal menus, and aimed to serve as materials for the introduction of halal correspondences in the future. At Nagoya University, the co-op, student representatives, and university executives discussed the foodstuffs to be removed from the halal menus. By manufacturing the halal menus using the cook freeze method of one day a week, the efficiency of the production process was realized. By having the halal menus, which are cook-freeze products, as standby menus and as alternative menus, and by developing menus that also were considered the needs of general users, the system that could be profitable was realized.departmental bulletin pape

Clinical and genetic features of cystic fibrosis in Japan

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.journal articl

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