Insuline-like effects of vanadate on glucokinase activity and fructose 2,6-bisphosphate levels in the liver of diabetic rats

Streptozotocin diabetic rats showed more than a 4-fold increase in blood glucose levels, whereas hepatic glycogen, fructose 2,6-bisphosphate concentration, and 6-phosphofructo-2-kinase activity were decreased. The 'total' 6-phosphofructo-2-kinase and the 'active' (nonphosphorylated) form of the enzyme were decreased to a different extent, resulting in a fall of the 'active'/'total' activity ratio. Vanadate administration for a 2-week period restored the altered values in the diabetic rats without modifying significantly in the control animals any of the parameters studied. Glucokinase activity was essentially lacking in the diabetic animals, and vanadate treatment restored the activity to about 65% of its control value, a good correlation between the recovery of the enzyme and the blood glucose level being observed. These results show an insulin-like effect of vanadate in the whole animal and suggest that insulin and vanadate possess similar actions on hepatic intracellular events

Development of a Teaching Program on The State of the Salt Ingestion Which Prevents Heatstroke and High Blood Pressure

In vitro enzymatic profiles for tofacitinib and PIK-294. (DOC 35 kb

Investigation of guided wave propagation in pipes fully- and partially-embedded in concrete

The application of long-range guided-wave testing to pipes embedded in concrete results in unpredictable test-ranges. The influence of the circumferential extent of the embedding-concrete around a steel pipe on the guided wave propagation is investigated. An analytical model is used to study the axisymmetric fully embedded pipe case, while explicit finite-element and semi-analytical finite-element simulations are utilised to investigate a partially embedded pipe. Model predictions and simulations are compared with full-scale guided-wave tests. The transmission-loss of the T(0,1)-mode in an 8 in. steel pipe fully embedded over an axial length of 0.4 m is found to be in the range of 32–36 dB while it reduces by a factor of 5 when only 50% of the circumference is embedded. The transmission-loss in a fully embedded pipe is mainly due to attenuation in the embedded section while in a partially embedded pipe it depend strongly on the extent of mode-conversion at entry to the embedded-section; low loss modes with energy concentrated in the region of the circumference not-covered with concrete have been identified. The results show that in a fully embedded pipe, inspection beyond a short distance will not be possible, whereas when the concrete is debonded over a fraction of the pipe circumference, inspection of substantially longer lengths may be possible

Transient receptor potential cation channel, subfamily V, member 4 and airway sensory afferent activation: Role of adenosine triphosphate

BackgroundSensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored.ObjectiveWe hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung.MethodsWe used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues.ResultsHere we show TRPV4-induced activation of guinea pig airway–specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough.ConclusionThis study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP–mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough

Vanadate increases L-type pyruvate kinase mRNAs level in adult rat hepatocytes in primary culture

In primary culture of adult rat hepatocytes, vanadate in the presence of glucose stimulates the expression of the liver (L-type) pyruvate kinase gene. Glucose by itself was inactive, and vanadate, like insulin, was also inefficient in the absence of glucose. Similar results were obtained on glucokinase gene expression. An analogue of cAMP, 8-(4-chlorophenylthio)-cAMP, inhibited the production of L-type pyruvate kinase and glucokinase mRNAs in the presence of glucose plus vanadate

Vanadate increases L-type pyruvate kinase mRNAs level in adult rat hepatocytes in primary culture

In primary culture of adult rat hepatocytes, vanadate in the presence of glucose stimulates the expression of the liver (L-type) pyruvate kinase gene. Glucose by itself was inactive, and vanadate, like insulin, was also inefficient in the absence of glucose. Similar results were obtained on glucokinase gene expression. An analogue of cAMP, 8-(4-chlorophenylthio)-cAMP, inhibited the production of L-type pyruvate kinase and glucokinase mRNAs in the presence of glucose plus vanadate

PI3K, p38 and JAK/STAT signalling in bronchial tissue from patients with asthma following allergen challenge.

Abstract Background Inhaled allergen challenges are often used to evaluate novel asthma treatments in early phase clinical trials. Current novel therapeutic targets in asthma include phosphoinositide 3-kinases (PI3K) delta and gamma, p38 mitogen-activated protein kinase (p38) and Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling pathways. The activation of these pathways following allergen exposure in atopic asthma patients it is not known. Methods We collected bronchial biopsies from 11 atopic asthma patients at baseline and after allergen challenge to investigate biomarkers of PI3K, p38 MAPK and JAK/STAT activation by immunohistochemistry. Cell counts and levels of eosinophil cationic protein and interleukin-5 were also assessed in sputum and bronchoalvelar lavage. Results Biopsies collected post-allergen had an increased percentage of epithelial cells expressing phospho-p38 (17.5 vs 25.6%, p = 0.04), and increased numbers of sub-epithelial cells expressing phospho-STAT5 (122.2 vs 540.6 cells/mm2, p = 0.01) and the PI3K marker phospho-ribosomal protein S6 (180.7 vs 777.3 cells/mm2, p = 0.005). Type 2 inflammation was increased in the airways post allergen, with elevated levels of eosinophils, interleukin-5 and eosinophil cationic protein. Conclusions Future clinical trials of novel kinase inhibitors could use the allergen challenge model in proof of concept studies, while employing these biomarkers to investigate pharmacological inhibition in the lungs