Activation of rat masticatory muscle afferent fibres by acidic pH

Abstract

Previous research findings have suggested an important role for acid sensing ion channels (ASICs) in muscle pain mechanisms. This study was conducted to determine if masticatory muscle afferent fibres express ASICs, if there are sex differences in this expression, and to compare the effects of low pH and hypertonic saline on afferent fibres that innervate the masticatory muscle in vivo. Immunohistochemistry methods were applied to examine the expression of ASICs in trigeminal ganglion neurons, while in vivo electrophysiology techniques were employed to examine changes in masticatory muscle afferent fibre excitability. Both ASIC₁ and ASIC₃ were expressed by predominantly larger masticatory muscle ganglion neurons, but the frequency of ASIC₃ expression (56%) was significantly greater than ASIC₁ (35%). No sex-related differences in expression were identified. Injection of pH 5.8, but not pH 6.8, phosphate buffered saline evoked afferent discharges that were significantly greater than those evoked by pH 7.4 buffer (control). Since ASIC₃ channels are not activated until the pH is around 6, these results indicate that activation of both channels contributes to excitation of masticatory muscle afferent fibres. The results further show that many masticatory muscle afferent fibres, which respond to low pH, are low threshold mechanoreceptors. These findings may explain why injection of low pH solutions into the masticatory muscles of healthy humans is not associated with significant muscle pain.     

Water‐miscible ionic liquids as novel effectors for the firefly luciferase reaction

Ionic liquids (IL) are used as a new class of solvents for various reactions. Especially using IL in biocatalysis in an aqueous milieu has attracted considerable attention because enzymes show remarkable differences in their catalytic features in IL‐containing reaction media. Firefly luciferase is widely used in many analytical techniques, because light production of firefly luciferase is one of the most sensitive analytical measures in the ultrasensitive detection of adenosine‐5′‐triphosphate, e.g. for measuring microbial contamination and monitoring gene expression, as well as for monitoring tumor growth and metastasis in whole animals. Firefly luciferase is an unstable enzyme and its inactivation can lead to low sensitivity in the above‐mentioned assays. The present study addresses the comparative influence of six different water‐immiscible IL, the 3‐methylimidazolium derivatives [BMIM]Cl, [HMIM]Cl, [BMIM]Br, [EMIM]Br, [HMIM]Br, and [BMIM]BF₄, on the kinetic properties, structural stability, and function of firefly luciferase from Photinus pyralis using circular dichroism, fluorescence spectroscopy, and a bioluminescence assay. The incubation of luciferase with various IL showed that, with the exception of [BMIM]BF₄, the activity and stability of luciferase was considerably increased in the presence of IL, compared to luciferase in aqueous medium. Moreover, K_m for the substrate adenosine‐5′‐triphosphate in the presence of IL (except for [BMIM]BF₄) decreased while K_m for luciferin remained constant.     

Coordination chemistry of two new tetraaza Ni(II) and Cu(II) macrocyclic and two new Co(II) and Zn(II) macroacyclic Schiff base complexes containing piperazine moiety: X-ray crystal structures of Ni(II) and Zn(II) complexes

A new potentially tetradentate (N₄) Schiff base ligand (L), 1,9,12,20-tetraazatetracyclo[18.2.2.02,7.014,19]tetracosa-2(7),3,5,8,12,14(19),15,17-octaene containing a piperazine moiety is described. Macrocyclic Schiff base complexes, [NiL](ClO₄)₂ (1) and [CuL](ClO₄)₂ (2) have been obtained from equimolar amounts of ligand (L) with nickel(II) and copper(II) metal ions. While the equilibrium reaction in the presence of cobalt(II) and zinc(II) metal ions with ligand L in a 1:1 molar ratio yielded the open-chain Schiff base complexes, [CoL′](ClO₄)₂ (3) and [ZnL′](ClO₄)₂ (4) containing two terminal primary amino groups. The ligand L′ is 1,4-bis(2-(2-aminoethyliminomethyl)phenyl)piperazine. The crystal structures of (1) and (4) have been also determined by X-ray diffraction. It was shown that the Ni(II) is coordinated to the ligand L by two nitrogen atoms of piperazine group and two nitrogen atoms of the imine groups, in a slightly distorted square-planar geometry. Also single crystal X-ray analysis of (4) confirmed a distorted octahedral arrangement in the vicinity of Zn atom with N₆ donor set. The spectroscopic characterization of all complexes is consistent with their crystal structures.     

A Multifactorial Role for P. falciparum Malaria in Endemic Burkitt's Lymphoma Pathogenesis

Endemic Burkitt''s lymphoma (eBL) arises from the germinal center (GC). It is a common tumor of young children in tropical Africa and its occurrence is closely linked geographically with the incidence of P. falciparum malaria. This association was noted more than 50 years ago. Since then we have learned that eBL contains the oncogenic herpes virus Epstein-Barr virus (EBV) and a defining translocation that activates the c-myc oncogene. However the link to malaria has never been explained. Here we provide evidence for a mechanism arising in the GC to explain this association. Accumulated evidence suggests that eBL arises in the GC when deregulated expression of AID (Activation-induced cytidine deaminase) causes a c-myc translocation in a cell latently infected with Epstein-Barr virus (EBV). Here we show that P. falciparum targets GC B cells via multiple pathways to increase the risk of eBL. 1. It causes deregulated expression of AID, thereby increasing the risk of a c-myc translocation. 2. It increases the number of B cells transiting the GC. 3. It dramatically increases the frequency of these cells that are infected with EBV and therefore protected from c-myc induced apoptosis. We propose that these activities combine synergistically to dramatically increase the incidence of eBL in individuals infected with malaria.     

Exosomal noncoding RNAs: key players in glioblastoma drug resistance

Molecular and Cellular Biochemistry - Glioma, as one of the most severe human malignancies, is defined as the Central Nervous System’s (CNS) tumors. Glioblastoma (GBM) in this regard, is the...     

Inflammatory,antioxidant and glycemic status to different mode of high-intensity training in type 2 diabetes mellitus

Molecular Biology Reports - Exercise has traditionally been used and prescribed as an effective and suitable way to treat type 2 diabetics Mellitus (T2DM). In this regard, we compared inflammatory,...     

Rapamycin alleviates memory deficit against pentylenetetrazole-induced neural toxicity in Wistar male rats

Molecular Biology Reports - Numerous studies have reported that epilepsy causes memory deficits. The present study was aimed at studying the effect of rapamycin against the memory deficiency of the...