How should we define a nociceptor in the gut-brain axis?

In the past few years, there has been extraordinary interest in how the gut communicates with the brain. This is because substantial and gathering data has emerged to suggest that sensory nerve pathways between the gut and brain may contribute much more widely in heath and disease, than was originally presumed. In the skin, the different types of sensory nerve endings have been thoroughly characterized, including the morphology of different nerve endings and the sensory modalities they encode. This knowledge is lacking for most types of visceral afferents, particularly spinal afferents that innervate abdominal organs, like the gut. In fact, only recently have the nerve endings of spinal afferents in any visceral organ been identified. What is clear is that spinal afferents play the major role in pain perception from the gut to the brain. Perhaps surprisingly, the majority of spinal afferent nerve endings in the gut express the ion channel TRPV1, which is often considered to be a marker of nociceptive neurons. And, a majority of gut-projecting spinal afferent neurons expressing TRPV1 are activated at low thresholds, in the normal physiological range, well below the normal threshold for detection of painful sensations. This introduces a major conundrum regarding visceral nociception. How should we define a nociceptor in the gut? We discuss the notion that nociception from the gut wall maybe a process encrypted into multiple different morphological types of spinal afferent nerve ending, rather than a single class of sensory ending, like free-endings, suggested to underlie nociception in skin

Fixed drug eruption induced by atenolol

Fixed drug eruption (FDE) is characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. We report here a case of multiple FDE induced by atenolol in a 48-year-old woman confirmed by positive patch test in previously affected sites. Beta-blockers-induced FDE are very rare. Only two cases had been reported in the literature. To the best of our knowledge, this is the first case reported of atenolol-induced FDE confirmed by a positive patch test

T-Helper Cell Cytokine Expression Profiling in Rheumatoid Arthritis Patients by Flow Cytometric Bead Array Analysis

Background: Rheumatoid arthritis (RA) is the most common chronic autoimmune disease affecting multiple joints. A chronic imbalance in cytokine production by T-helper (Th) cells is likely a key factor in RA development. Our objective was to profile the serum cytokine expression from three key Th cell types (Th1, Th2, and Th17) in RA patients in order to correlate the resulting cytokine expression profiles with RA activity. Material and Methods: From a population of RA patients (n = 71) and healthy controls (n = 18), the serum concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) were analyzed by flow cytometric bead array (CBA). Results: The serum concentrations of all seven cytokines were significantly higher in RA patients than in healthy controls. Interestingly, the serum concentration profiles varied with the 28-joint Disease Activity Score (DAS28), a measure of RA activity derived from joint indices (tender joints and swollen joints count) and the erythrocyte sedimentation rate. In the high RA activity group (DAS28 > 5.1), all seven cytokines were significantly elevated. In the moderate RA activity group (DAS28 between 3.2 and 5.1), only IL-2, IL-6, IL-10, and IL-17A were significantly increased. In the low RA activity group (DAS28 ≤ 3.2), only IL-2, IL-4, and TNF-α were significantly elevated. Conclusions: The Th cell-derived cytokine expression profile significantly changes across varying levels of RA activity. Th1/Th17 cell-derived TNF-α and Th2 cell-derived IL-4 appear to play more important roles in the early stages of RA, while all seven cytokines derived from Th1, Th2, and Th17 cells (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) are overtly involved in the advanced stages of RA

Conoscopic interferometry for optimal acoustic pulse detection in ultrafast acoustics

Conoscopic interferometry is a promising detection technique for ultrafast acoustics. By focusing a probe beam through a birefringent crystal before passing it through a polarizer, conoscopic interferences sculpt the spatial profile of the beam. The use of these patterns for acoustic wave detection revealed a higher detection sensitivity over existing techniques, such as reflectometry and beam distortion detection. However, the physical origin of the increased sensitivity is unknown. In this work, we present a model, describing the sensitivity behaviour of conoscopic interferometry with respect to the quarter-wave plate orientation and the diaphragm aperture, which is validated experimentally. Using the model, we optimize the detection sensitivity of conoscopic interferometry. We obtain a maximal sensitivity of detection when placing the diaphragm edge on the dark fringes of the conoscopic interference patterns. In the configurations studied in this work, conoscopic interferometry can be 8x more sensitive to acoustic waves than beam distortion detection

Stepwise Synthesis of Tetra-imidazolium Macrocycles and Their N-Heterocyclic Carbene Metal Complexes

A modular stepwise synthetic method has been developed for the preperation of tetra-imidazolium macrocycles. Initially a series of three bis(imidazolylmethyl)benzene precursors were alkylated with 1,2-dibromoethane to produce the corresponding bis-bromoethylimidazolium bromide salts. In the second step the bis-bromoethylimidazolium bromide salts were reacted with selected bis(imidazolylmethyl)benzene molecules to produce a series of two symmetrical and three asymmetrical tetra-imidazolium macrocycles. These tetra-imidazolium salts act receptors for anions and 1H-NMR titration studies were used to determine the association constants between two of the macrocycles and the halide anions chloride, bromide and iodide. The tetra-imidazolium salts are precursors for N-heterocyclic carbene (NHC) ligands and the corresponding silver(I), gold(I), and palladium(II) NHC complexes have been prepared. Varied structures were obtained, which depend on the chosen macrocyclic ligand and metal ion and in the case of the coinage metals Ag(I) and Au(I), mono, di, and hexanuclear complexes were formed

Modification of neurogenic colonic motor behaviours by chemogenetic ablation of calretinin neurons

How the enteric nervous system determines the pacing and propagation direction of neurogenic contractions along the colon remains largely unknown. We used a chemogenetic strategy to ablate enteric neurons expressing calretinin (CAL). Mice expressing human diphtheria toxin receptor (DTR) in CAL neurons were generated by crossin