Effect of low-dose exogenous secretin and somatostatin on pentagastrin-stimulated gastric acid secretion in man

The inhibitory effect of intravenous infusion of secretin (0.05 CU kg-1h-1) and somatostatin (60 pmol kg-1h-1), given alone or in combination, on pentagastrin-stimulated (100 ng kg-1 h-1) acid secretion was studied in 10 healthy subjects. Secretin inhibited acid secretion by 54% (p less than 0.05), and somatostatin inhibited by 70% (p less than 0.05). The combined infusion of secretin and somatostatin decreased acid output by 64% (p less than 0.05). The differences between the three groups were not significant (p greater than 0.05). Median plasma concentrations of secretin and somatostatin were of the same magnitude as seen after duodenal acidification. The present study did not demonstrate any interaction between secretin and somatostatin in the inhibition of gastric acid secretion.     

Targeted inactivation of αi2 or αi3 disrupts activation of the cardiac muscarinic K+ channel, IK+Ach, in intact cells

Cardiac muscarinic receptors activate an inwardly rectifying K⁺ channel, I_K^+Ach, via pertussis toxin (PT)-sensitive heterotrimeric G proteins (in heart G_i2, G_i3, or G_o). We have used embryonic stem cell (ES cell)-derived cardiocytes with targeted inactivations of specific PT-sensitive α subunits to determine which G proteins are required for receptor-mediated regulation of I_K^+Ach in intact cells. The muscarinic agonist carbachol increased I_K^+Ach activity in ES cell-derived cardiocytes from wild-type cells, in cells lacking α_o, and in cells lacking the PT-insensitive G protein α_q. In cells with targeted inactivation of α_i2 or α_i3, channel activation by both carbachol and adenosine was blocked. Carbachol-induced channel activation was restored in the α_i2- and α_i3-null cells by reexpressing the previously targeted gene and guanosine 5′-[γ-thio] triphosphate was able to fully activate I_K^+Ach in excised membranes patches from these mutants. In contrast, negative chronotropic responses to both carbachol and adenosine were preserved in cells lacking α_i2 or α_i3. Our results show that expression of two specific PT-sensitive α subunits (α_i2 and α_i3 but not α_o) is required for normal agonist-dependent activation of I_K^+Ach and suggest that both α_i2- and α_i3-containing heterotrimeric G proteins may be involved in the signaling process. Also the generation of negative chronotropic responses to muscarinic or adenosine receptor agonists do not require activation of I_K^+Ach or the expression of α_i2 or α_i3.     

Early Diagnosis of Colonic Anastomotic Leak With Peritoneal Endoscopy

Background and Objectives:

At present, we do not have a reliable method for the early diagnosis of colorectal anastomotic leakage (AL). We tested peritoneal flexible endoscopy through a port placed in the abdominal wall in the early postoperative course, as a new diagnostic method for detection of this complication and evaluated the suggested method for safety, feasibility, and accuracy.

Methods:

Ten swine were randomized into 2 groups: group A, colorectal anastomosis without leakage; and group B, colorectal anastomosis with leakage. A button gastrostomy feeding tube was inserted percutaneously into the peritoneal cavity. Colorectal anastomosis (with or without defect) was created 48 hours after the first operation. The swine were examined by peritoneal flexible endoscopy 8 and 24 hours after the colonic operation, by a consultant surgeon who was blinded to both the presence and the allocated location of the of the anastomotic defect.

Results:

None of the animals showed signs of illness 48 hours after the intraperitoneal gastrostomy tube placement. More than half of the anastomosis circumference was identified in 60 and 10% of the animals at endoscopy 8 and 24 hours, respectively, after the anastomosis was created. Excessive adhesion formation was observed in all animals, irrespective of AL. The sensitivity and specificity of endoscopy in detecting peritonitis 24 hours after AL were both 60%.

Conclusions:

Peritoneal endoscopy is a safe and simple procedure. Visualization of the peritoneal cavity in the early postoperative course was limited due to adhesion formation. Further studies are needed to clarify the accuracy of the procedure and to address additional methodological concerns.     

Bronchoscintigraphic visualization of the acute effect of tobacco exposure and terbutaline on mucociliary clearance in smokers

The aim of this study was to examine the acute effect of tobacco smoke exposure and inhaled terbutaline on mucociliary clearance in 9 healthy smokers. It was based on a recently described method for scintigraphic visualization of the bronchi (bronchoscintigraphy). After an initial bronchoscintigram had been made by having the subjects inhale aerosolized 99mTc-albumin, they inhaled either terbutaline or placebo from a metered-dose inhaler. Subsequently, data acquisition for production of bronchoscintigrams was repeated at 10 min intervals for 120 min, and the mucociliary clearance was estimated from the movement of radioactivity in the series of bronchoscintigrams thus obtained. On two study days the subjects remained tobacco abstinent, while on two occasions they chain-smoked during the examination. Acute tobacco exposure resulted in an increased clearance rate in the lobar bronchi in 8 of the 9 smokers (p less than 0.03), while in the main bronchi and the trachea the effect was inconsistent. In all subjects terbutaline systematically increased the clearance rate in all visible bronchial structures compared to placebo (p less than 0.04). The combination of smoking and terbutaline caused a faster clearance rate in the lobar bronchi in most subjects than tobacco smoke or terbutaline alone. It is concluded that both acute tobacco exposure and terbutaline increase mucociliary clearance in healthy smokers.     

Physiological role of taurine – from organism to organelle

Taurine is often referred to as a semi‐essential amino acid as newborn mammals have a limited ability to synthesize taurine and have to rely on dietary supply. Taurine is not thought to be incorporated into proteins as no aminoacyl tRNA synthetase has yet been identified and is not oxidized in mammalian cells. However, taurine contributes significantly to the cellular pool of organic osmolytes and has accordingly been acknowledged for its role in cell volume restoration following osmotic perturbation. This review describes taurine homeostasis in cells and organelles with emphasis on taurine biophysics/membrane dynamics, regulation of transport proteins involved in active taurine uptake and passive taurine release as well as physiological processes, for example, development, lung function, mitochondrial function, antioxidative defence and apoptosis which seem to be affected by a shift in the expression of the taurine transporters and/or the cellular taurine content.     

Cripto‐1 Expression in Glioblastoma Multiforme

Human glioblastoma multiforme (GBM) is an aggressive cancer with a very poor prognosis. Cripto‐1 (CR‐1) has a key regulatory role in embryogenesis, while in adult tissue re‐expression of CR‐1 has been correlated to malignant progression in solid cancers of non‐neuronal origin. As CR‐1 expression has yet to be described in cerebral cancer and CR‐1 is regulated by signaling pathways dysregulated in GBM, we aimed to investigate CR‐1 in the context of expression in GBM. The study was performed using enzyme‐linked immunosorbent assay (ELISA), Western blotting, polymerase chain reaction (PCR) and immunohistochemistry to analyze the blood and tissue from 28 GBM and 4 low‐grade glioma patients. Within the patient cohort, we found high CR‐1 protein levels in blood plasma to significantly correlate with a shorter overall survival. We identified CR‐1 in different areas of GBM tissue, including perivascular tumor cells, and in endothelial cells. Collectively, our data suggest that CR‐1 could be a prognostic biomarker for GBM with the potential of being a therapeutic target.