Histamine in diabetes: is it time to reconsider?

The first studies of histamine and diabetes date back to the 1950s. Since that time the involvement of histamine in diabetes was related to its well known vasoactive properties and permeability leakage effects. In particular, the first evidence for a correlation between histamine and diabetes arose in 1989 when an increase in plasma and leucocyte histamine content was observed. Limited independent evidence followed in the subsequent two decades, focusing on both histamine glyceamic control and macro- and microvascular complications of diabetes. However, recent observations have sparked the question whether it is time to reconsider the functional contribution of histamine in diabetes. We reveal an interesting upsurge in the field which provides scope for new insights into the role of histamine in diabetes

Lamina-specific population encoding of cutaneous signals in the spinal dorsal horn using multi-electrode arrays

The dorsal spinal cord (DH) is a complex laminar structure integrating peripheral signals into the central nervous system. Spinal somatosensory processing is commonly measured electrophysiologically in vivo by recording the activity of individual Wide Dynamic Range neurons in the deep DH and extrapolating their behaviour to all cells in every lamina. This fails to account for the specialised processes that occur in each lamina and the considerable heterogeneity in cellular phenotype within and between laminae. Here we overcome this oversimplification by employing linear multi‐electrode arrays (MEAs) in the DH of anaesthetized rats to simultaneously measure activity across all laminae. The MEAs, comprised of 16‐channels, were inserted into the lumbar dorsal horn and peripheral neurones activated electrically via transcutaneous electrodes and ethologically with von Frey hairs (vFh) or an aluminium heating block. Ascending electrical stimuli showed fibre thresholds with distinct dorso‐ventral innervation profiles. Wind up was observed across the DH during the C‐fibre and post‐discharge latencies following 0.5Hz stimulation. Intrathecal application of morphine (5ng/50ul) significantly reduced Aδ and C‐fibre evoked activity in deep and superficial DH. Light vFhs (≤10g) predominantly activated intermediate and deep laminae whereas noxious vFh (26g) also activated the superficial laminae. Noxious heat (55°C) induced significantly greater activity in the superficial and deep laminae than the innocuous control (30°C). The application of these arrays produced the first description of the processing of innocuous and noxious stimuli throughout the intact DH

Votucalis, a Novel Centrally Sparing Histamine-Binding Protein, Attenuates Histaminergic Itch and Neuropathic Pain in Mice

Votucalis is a biologically active protein in tick (R. appendiculatus) saliva, which specifically binds histamine with high affinity and, therefore, has the potential to inhibit the host’s immunological responses at the feeding site. We hypothesized that scavenging of peripherally released endogenous histamine by Votucalis results in both anti-itch and anti-nociceptive effects. To test this hypothesis, adult male mice were subjected to histaminergic itch, as well as peripheral nerve injury that resulted in neuropathic pain. Thus, we selected models where peripherally released histamine was shown to be a key regulator. In these models, the animals received systemic (intraperitoneal, i.p.) or peripheral transdermal (subcutaneous, s.c. or intraplantar, i.pl.) administrations of Votucalis and itch behavior, as well as mechanical and thermal hypersensitivity, were evaluated. Selective histamine receptor antagonists were used to determine the involvement of histamine receptors in the effects produced by Votucalis. We also used the spontaneous object recognition test to confirm the centrally sparing properties of Votucalis. Our main finding shows that in histamine-dependent itch and neuropathic pain models peripheral (s.c. or i.pl.) administration of Votucalis displayed a longer duration of action for a lower dose range, when compared with Votucalis systemic (i.p.) effects. Stronger anti-itch effect was observed after co-administration of Votucalis (s.c.) and antagonists that inhibited peripheral histamine H1 and H2 receptors as well as central histamine H4 receptors indicating the importance of these histamine receptors in itch. In neuropathic mice, Votucalis produced a potent and complete anti-nociceptive effect on mechanical hypersensitivity, while thermal (heat) hypersensitivity was largely unaffected. Overall, our findings further emphasize the key role for histamine in the regulation of histaminergic itch and chronic neuropathic pain. Given the effectiveness of Votucalis after peripheral transdermal administration, with a lack of central effects, we provide here the first evidence that scavenging of peripherally released histamine by Votucalis may represent a novel therapeutically effective and safe long-term strategy for the management of these refractory health conditions

Approaches to the Rational Design of Molecularly Imprinted Polymers Developed for the Selective Extraction or Detection of Antibiotics in Environmental and Food Samples

The World Health Organisation (WHO) reported antimicrobial resistance (AMR) as a global threat comparable to terrorism and climate change. The use of antibiotics in veterinary or clinical practice exerts a selective pressure, which accelerates the emergence of antimicrobial resistance. Therefore, there is a clear need to detect antibiotic residues in complex matrices, such as water, food, and environmental samples, in a fast, selective, cost-effective, and quantitative manner. Once problematic areas are identified, can extraction of the antibiotics then be carried out to reduce AMR development. Molecularly imprinted polymer (MIPs) are synthetic recognition elements produced through the biomarker of interest being used as a template in order to manufacture tailor-made ligand selective polymeric recognition sites. They are emerging steadily as a viable alternative to antibiotics, especially given their low-cost, superior thermal and chemical stability that facilitates on-site detection, simplified manufacturing process, and avoiding the use of animals in the production process. In this paper, the authors critically review literature from primarily 2010–2020 on rational design approaches used to develop MIPs for sensing and extraction of antibiotics, providing an outlook on crucial issues that need to be tackled to bring MIPs for antibiotic sensing to the market