Spinal release of tumour necrosis factor activates c-Jun N-terminal kinase and mediates inflammation-induced hypersensitivity.

BackgroundMounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo.MethodsTNF levels in lumbar cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay, spinal TNF gene expression by real-time polymerase chain reaction and TNF protein expression, JNK and c-Jun phosphorylation by western blotting. The role of spinal TNF and JNK in inflammation-induced mechanical and thermal hypersensitivity was assessed by injecting the TNF inhibitor etanercept and the JNK inhibitors SP600125 and JIP-1 intrathecally (i.t.). TNF-mediated regulation of JNK activity was examined by assessing the effect of i.t. etanercept on inflammation-induced spinal JNK activity.ResultsTNF levels were increased in CSF and spinal cord following carrageenan-induced inflammation. While JNK phosphorylation followed the same temporal pattern as TNF, c-jun was only activated at later time points. Intrathecal injection of TNF and JNK inhibitors attenuated carrageenan-induced mechanical and thermal hypersensitivity. TNF stimulation induced JNK phosphorylation in cultured spinal astrocytes and blocking the spinal actions of TNF in vivo by i.t. injection of etanercept reduced inflammation-induced spinal JNK activity.ConclusionsHere we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation

Modification of montmorillonite and its effect on the thermal stability of PP/APP

149-156The effect of montmorillonite (Mt) and the treated montmorillonite (MtT) with sulfuric acid on the efficiency of nanoparticles of ammonium polyphosphate (APP) has been studied. Five samples containing different percentage of montmorillonite are prepared and other five samples containing treated montmorillonite also prepared. The chemical analysis (XRF), the spectroscopic measurements (XRD and IR) and the morphology (SEM) studied have been performed to identify the sulfuric acid treatment for the montmorillonite on the chemical composition and on the structure of the montmorillonite layers. The results have been revealed that the acid treatment changes the layered structure of montmorillonite and no effects on the chemical composition. The thermogravimetric analysis (TGA) is used to evaluate the ammonium polyphosphate (APP)/ montmorillonite (Mt) or APP/ montmorillonite treatment (MtT) as flame retardants for Polypropylene (PP). The results show that both treated and untreated montmorillonite when mixed with APP accelerate the first step of the thermal degradation. Also, it is indicated that the time of degradation increased by adding treated or untreated montmorillonite to APP in the following sequence PP<PP/APP<PP/(APP/Mt)<PP/(APP/MtT). Overall, the results indicated that the modification of added montmorillonite to App improves the flammability of the PP

Antioxidant rich flavonoids from Oreocnide integrifolia enhance glucose uptake and insulin secretion and protects pancreatic β-cells from streptozotocin insult

<p>Abstract</p> <p>Background</p> <p>Insulin deficiency is the prime basis of all diabetic manifestations and agents that can bring about insulin secretion would be of pivotal significance for cure of diabetes. To test this hypothesis, we carried out bioactivity guided fractionation of <it>Oreocnide integrifolia </it>(Urticaceae); a folklore plant consumed for ameliorating diabetic symptoms using experimental models.</p> <p>Methods</p> <p>We carried out bioassay guided fractionation using RINmF and C2C12 cell line for glucose stimulated insulin secretion (GSIS) and glucose uptake potential of fractions. Further, the bioactive fraction was challenged for its GSIS in cultured mouse islets with basal (4.5 mM) and stimulated (16.7 mM) levels of glucose concentrations. The Flavonoid rich fraction (FRF) was exposed to 2 mM streptozotocin stress and the anti-ROS/RNS potential was evaluated. Additionally, the bioactive fraction was assessed for its antidiabetic and anti-apoptotic property <it>in-vivo </it>using multidose streptozotocin induced diabetes in BALB/c mice.</p> <p>Results</p> <p>The results suggested FRF to be the most active fraction as assessed by GSIS in RINm5F cells and its ability for glucose uptake in C2C12 cells. FRF displayed significant potential in terms of increasing intracellular calcium and cAMP levels even in presence of a phosphodiesterase inhibitor, IBMX in cultured pancreatic islets. FRF depicted a dose-dependent reversal of all the cytotoxic manifestations except peroxynitrite and NO formation when subjected <it>in-vitro </it>along with STZ. Further scrutinization of FRF for its <it>in-vivo </it>antidiabetic property demonstrated improved glycemic indices and decreased pancreatic β-cell apoptosis.</p> <p>Conclusions</p> <p>Overall, the flavonoid mixture has shown to have significant insulin secretogogue, insulinomimetic and cytoprotective effects and can be evaluated for clinical trials as a therapeutant in the management of diabetic manifestations.</p

Improving the hydraulic efficiency of Ibrahemia canal

Ibrahemia canal is one of the longest irrigation canals in Egypt. It starts at 400 m upstream of Asuit barrages and ends in Giza Irrigation General Directorate of 316.300 km length. The canal cross section is bounded in many reaches along canal length by railway line in right bank and Cairo-Aswan agriculture road in left bank. The canal passes through many cities and residential areas, its cross section is affected negatively due to interpenetrate with road section and railway lines. Wastes and deposits increase the contraction of canal cross section. The reach from km 122 to km 132 which located within El Menya City is one of the most critical reaches owing to its length, complicity of maintenance and its effect on canal water hydraulic gradient. The objective of the study is to introduce the most convenient maintenance program to improve the hydraulic efficiency of the studied reach and reduce the loss in water levels along it, also to insure that the reach is capable of passing the required discharge to downstream reaches. The canal cross sections were surveyed along the study reach, the flow velocities were measured and flow discharge was calculated. The study reach was simulated using one dimension mathematical model (SOBEK 1D) to predict the change of hydraulic parameters of the study reach after the execution of the suggested training programs. Finally four maintenance scenarios were suggested and evaluated hydraulically to improve the hydraulic efficiency of the selected reach of Ibrahemia canal

Spinal release of tumour necrosis factor activates c‐ J

BACKGROUND: Mounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo. METHODS: TNF levels in lumbar cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay, spinal TNF gene expression by real-time polymerase chain reaction and TNF protein expression, JNK and c-Jun phosphorylation by western blotting. The role of spinal TNF and JNK in inflammation-induced mechanical and thermal hypersensitivity was assessed by injecting the TNF inhibitor etanercept and the JNK inhibitors SP600125 and JIP-1 intrathecally (i.t.). TNF-mediated regulation of JNK activity was examined by assessing the effect of i.t. etanercept on inflammation-induced spinal JNK activity. RESULTS: TNF levels were increased in CSF and spinal cord following carrageenan-induced inflammation. While JNK phosphorylation followed the same temporal pattern as TNF, c-jun was only activated at later time points. Intrathecal injection of TNF and JNK inhibitors attenuated carrageenan-induced mechanical and thermal hypersensitivity. TNF stimulation induced JNK phosphorylation in cultured spinal astrocytes and blocking the spinal actions of TNF in vivo by i.t. injection of etanercept reduced inflammation-induced spinal JNK activity. CONCLUSIONS: Here we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation

Effect of Rigid Aquatic Bank Weeds on Flow Velocities and Bed Morphology

The prediction of changes in velocity distribution and channel bed morphology is significant in open channel management and design. This paper implements experimental work to realize and quantify the effect of rigid aquatic bank weeds on vertical velocity profiles and channel bed morphology. In the experimental work, weeds were given a staggered distribution using three distances of 25, 50, and 75 mm, unilaterally and bilaterally, with Froude numbers ranging from 0.11 to 0.30, achieving 168 scenarios. Results for the tested weed cases showed that the average velocity was directly proportional to the weed density and approached the Froude number. By comparing the smooth and weeded velocities, it was found that the velocity inside the infested reach was close to the downstream velocity and exceeded the upstream velocity by about 10% and 41%, respectively. Scour depths along the centerline of the vegetated reach for the bilateral weeds were higher by 11% to 33% than those for the unilateral weeds. The maximum observed depth of the scour holes along the smooth bank was about 30% to 60% of the maximum scour depth at the middle line. Finally, to quantify the results, multiple regression analysis was performed to develop empirical equations to assist in the water management process

Combination of Surgical Technique and Bioresorbable Mesh Reinforcement of the Crural Repair Leads to Low Early Hernia Recurrence Rates with Laparoscopic Paraesophageal Hernia Repair

© 2019, The Society for Surgery of the Alimentary Tract. Introduction: Laparoscopic paraesophageal hernia (PEH) is associated with a low morbidity and mortality but an objective hernia recurrence rate in excess of 50% at 5 years. Biologic mesh has not been shown to reduce hernia recurrence rates. Recently, a new bioresorbable mesh made with poly-4-hydroxybutyrate with a Sepra-Technology coating on one side (Phasix-ST mesh) has become available. The aim of this study was to evaluate the feasibility, safety, and short-term efficacy of Phasix-ST mesh for reinforcement of the primary crural closure in patients undergoing elective, laparoscopic PEH repair. Methods: A prospective database was initiated and maintained for all patients undergoing PEH repair with the use of Phasix-ST mesh. We retrospectively reviewed the records of consecutive patients who had an elective, first-time laparoscopic PEH repair with Phasix-ST mesh and who completed their 1-year objective follow-up study. Patients having a reoperation, non-laparoscopic repair, or who failed to comply with the objective follow-up were excluded. Results: To achieve the desired 50 patients with 1-year objective follow-up, we reviewed the records of 90 consecutive PEH patients. In the final cohort of 50 patients, there were 32 females (64%) and 18 males. The median age of the patients at surgery was 67 years (range 44–84). The operation was PEH repair with fundoplication alone in 29 patients (58%) and PEH repair with Collis gastroplasty and fundoplication in 21 patients (42%). Phasix-ST mesh was used for crural reinforcement in all patients, and there were no intraoperative issues with the mesh or any difficulty placing or fixating the mesh at the hiatus. A diaphragm relaxing incision was performed in 2 patients (4%). The mean length of hospital stay was 2.8 days, and there was no major morbidity or mortality. On the 1-year objective follow-up study (median 12 months) a recurrent hernia was found in 4 patients (8%). No patient that had a Collis gastroplasty or a relaxing incision had a recurrent hernia. No patient had a reoperation. No patient had a mesh infection or mesh erosion. Conclusions: Phasix-ST mesh reinforcement of the crural closure during laparoscopic primary, elective PEH repair was associated with no adverse mesh-related events such as infection or erosion. Phasix-ST crural reinforcement in combination with tension-reduction techniques when necessary resulted in a very low (8%) objective hernia recurrence rate at a median follow-up of 1 year. These results demonstrate the safety of Phasix-ST mesh for use at the hiatus for crural reinforcement. This safety, along with the encouraging short-term efficacy for reducing hernia recurrence, should encourage further studies using the combination of resorbable biosynthetic mesh crural reinforcement and tension-reducing techniques during repair of paraesophageal hernias