Nociceptive mechanisms driving pain in a post-traumatic osteoarthritis mouse model.

In osteoarthritis (OA), pain is the dominant clinical symptom, yet the therapeutic approaches remain inadequate. The knowledge of the nociceptive mechanisms in OA, which will allow to develop effective therapies for OA pain, is of utmost need. In this study, we investigated the nociceptive mechanisms involved in post-traumatic OA pain, using the destabilization of the medial meniscus (DMM) mouse model. Our results revealed the development of peripheral pain sensitization, reflected by augmented mechanical allodynia. Along with the development of pain behaviour, we observed an increase in the expression of calcitonin gene-related peptide (CGRP) in both the sensory nerve fibers of the periosteum and the dorsal root ganglia. Interestingly, we also observed that other nociceptive mechanisms commonly described in non-traumatic OA phenotypes, such as infiltration of the synovium by immune cells, neuropathic mechanisms and also central sensitization were not present. Overall, our results suggest that CGRP in the sensory nervous system is underlying the peripheral sensitization observed after traumatic knee injury in the DMM model, highlighting the CGRP as a putative therapeutic target to treat pain in post-traumatic OA. Moreover, our findings suggest that the nociceptive mechanisms involved in driving pain in post-traumatic OA are considerably different from those in non-traumatic OA.

Marsupialization for the treatment of nictitating membrane cyst in a dog: case report / Marsupialização para o tratamento de cisto em membrana nictitante de cão: relato de caso

This study aims to describe the first Brazilian report of a nictitating membrane cyst's surgical treatment in a dog. A 6-month-old female French Bulldog presented at HOSVET-UNIME with a reddish mass-like structure in the medial canthus of both eyes, with a history of recurrent third eyelid gland prolapse previously treated with two surgeries performed at another clinic. Physical examination revealed a third eyelid gland prolapse in the right eye and a cyst in the left eye's third eyelid. The animal was submitted to surgical correction of the right eye's third eyelid prolapse using pocket technique and of the left eye's third eyelid using marsupialization technique for the cyst's treatment. 180 days after th1e surgical procedure no recurrence was observed. The marsupialization technique for the treatment of a third eyelid's lacrimal cyst in a dog allowed the maintenance of its gland and prevented the formation of a new cystic cavity.(AU)

O objetivo do presente trabalho é descrever o primeiro relato no Brasil de tratamento cirúrgico de um cisto da membrana nictitante em um cão. Um Buldogue Francês, fêmea, seis meses, foi atendido no Hosvet-Unime, com queixa de aumento de volume avermelhado no canto medial de ambos os olhos, com histórico de recidiva de prolapso de glândula da terceira pálpebra, onde haviam sido realizadas duas cirurgias anteriormente em outro local. Ao exame físico, foi observado prolapso de glândula da terceira pálpebra no olho direito e a presença de um cisto na terceira pálpebra do olho esquerdo. O animal foi submetido ao procedimento cirúrgico de sepultamento de glândula da terceira pálpebra no olho direito e uma marsupialização na terceira pálpebra do olho esquerdo para o tratamento do cisto. Cento e oitenta dias após o procedimento cirúrgico, não foi observada recidiva. A técnica de marsupialização para tratamento de cisto lacrimal na terceira pálpebra em um cão possibilitou a manutenção da sua glândula e impediu a formação de nova cavidade cística.(AU)

Plant-Derived Compounds as a Tool for the Control of Gastrointestinal Nematodes: Modulation of Abamectin Pharmacological Action by Carvone.

The combination of synthetic anthelmintics and bioactive phytochemicals may be a pharmacological tool for improving nematode control in livestock. Carvone (R-CNE) has shown in vitro activity against gastrointestinal nematodes; however, the anthelmintic effect of bioactive phytochemicals either alone or combined with synthetic drugs has been little explored in vivo. Here, the pharmacological interaction of abamectin (ABM) and R-CNE was assessed in vitro and in vivo. The efficacy of this combination was evaluated in lambs naturally infected with resistant gastrointestinal nematodes. Additionally, the ligand and molecular docking of both molecules to P-glycoprotein (P-gp) was studied in silico. The presence of R-CNE produced a significant (p < 0.05) increase of Rho123 and ABM accumulation in the intestinal explants. After 60 min of incubation, Rho123 incubated with R-CNE had a 67 ± 21% higher concentration (p < 0.01) than when it was incubated alone. In the case of ABM, a significant increase in the intestinal concentrations was observed at 15 and 30 min after incubation with R-CNE. In the in vivo assay, no undesirable effects were observed after the oral administration of R-CNE. The coadministration of the natural compound prolonged ABM absorption in lambs. ABM T ½ absorption was 1.57-fold longer (p < 0.05) in the coadministered group. Concentrations of R-CNE between 420 and 2,593 ng/mL were detected in the bloodstream between 1 and 48 h posttreatment. The in vivo efficacy of ABM against gastrointestinal nematodes increased from 94.9 to 99.8% in the presence of R-CNE, with the lower confidence interval limit being >90%. In vitro/in vivo pharmacoparasitological studies are relevant for the knowledge of the interactions and the efficacy of bioactive natural products combined with synthetic anthelmintics. While ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and the molecular docking study showed a good interaction between ABM and P-gp, R-CNE does not appear to modulate this efflux protein. Therefore, the pharmacokinetic-pharmacodynamic effect of R-CNE on ABM should be attributed to its effect on membrane permeability. The development of pharmacology-based information is critical for the design of successful strategies for the parasite control.

The blood-tendon barrier: identification and characterisation of a novel tissue barrier in tendon blood vessels.

In the last decade, nanobiotechnology research has emerged as a revolutionising new approach to the 21st century pharmaceutical challenges, offering valuable gains in a vast set of biomedical applications. In the field of bone tissue engineering, a broad range of nanotechnology-based delivery systems have been researched and the most recent developments in high-throughput technology and in silico approaches are creating very high expectations. This review presents a comprehensive overview of the emergent nanotechnology-based materials, processing techniques and research strategies for the delivery of pharmaceutics to bone including the materials general characteristics and the available drug delivery systems to distribute agents systemically or locally. Complementary to what was stated above, it also reviews the latest high-throughput processing techniques and the existent in silico tools (mathematical and computational models) used to help on the design of delivery systems.

NPY signalling pathway in bone homeostasis: Y1 receptor as a potential drug target.

Neuropeptide (NPY) is a neurotransmitter widely distributed in central and peripheral nervous system that has been implicated in several physiological processes through activation of five different Y receptors: Y1, Y2, Y4, Y5, and y6. NPY system has been extensively studied for the last decades due to its implications in a wide variety of physiological processes. For this purpose a diversity of sophisticated animal models and receptors agonists and antagonists has been developed to better understand its actions throughout body homeostasis. Consequently, NPY and its receptors have recently emerged as a potential regulator of bone homeostasis. This is supported by the demonstration of an increase of bone mass in mice lacking Y1 or Y2 receptor genes. Recent findings revealed Y1 receptor as a potential drug target candidate for prevention and treatment of bone loss. Indeed, it has been demonstrated that osteoblasts express Y1 receptor while no other Y receptor was detected in these cells, implicating Y1 receptor signalling in the local control of bone turnover. In this review, we have summarized the findings obtained from studies on NPY system in skeletogenesis focusing on Y1 receptor.

Novel pulsed switched power supply for a fast field cycling NMR spectrometer.

In this paper, we outline the operating principles of a pulsed switched power supply for a fast field-cycling nuclear magnetic resonance spectrometer. The power supply uses a variant of a four-quadrant chopper with a duty cycle that defines the average output current. With this topology only two semiconductors are necessary to drive hundreds of amperes with an output power of several kilowatts. The output current ripple has a well-defined shape that can be reduced to acceptable values by a careful design of the semiconductors' controlling circuits and drivers. A power supply prototype was tested with a home build air-core magnet operating with fields between 0 and 0.21 T. The system is computer controlled using pulse generator and data acquisition PC cards, and specific user-friendly home-developed software. A comparative proton relaxometry study in two well-known liquid crystal compounds 5CB and MBBA was performed to check the reproducibility of the T1 measurements.