Browsing by Author "Calvo, Margarita"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination: A report of three cases and review of the literature
    (2022) Abbott, Molly G.; Allawi, Zahra; Hofer, Monika; Ansorge, Olaf; Brady, Stefen; Fadic Ruiz, Ricardo; Torres Riveros, Gustavo Andres; Knight, Ravi; Calvo, Margarita; Bennett, David L. H.; Themistocleous, Andreas C.
    Small fiber neuropathy usually presents with gradual and progressive chronic length-dependent pain. Acute small fiber neuropathy is rarely reported. Three patients with acute onset neuropathic pain after Oxford-AstraZeneca ChAdOx1-S vaccination are described. Two patients were identified at the Oxford University NHS Foundation Trust, Oxford, UK and one patient in Red de Salud UC Christus, Santiago, Chile. All patients underwent a clinical assessment that included a detailed neurological examination, laboratory investigations, nerve conduction studies, thermal threshold testing, and skin biopsy for intra-epidermal nerve fiber density. Patients seen in Oxford underwent MRI of the brain and spinal cord. Cerebrospinal analysis was not performed. Neuropathic symptoms (burning pain, dysaesthesias) developed in the hands and feet within 2 weeks of vaccination. On clinical examination, there was pinprick and thermal hyposensitivity in the area of neuropathic pain. Laboratory investigation, nerve conduction tests, sympathetic skin responses, and MRI showed no relevant abnormalities. Thermal thresholds were abnormal and intra-epidermal nerve fiber density in the lower leg was reduced. In two cases symptoms persist after several months. Three cases of definite acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination are described. At follow up, neuropathic pain was present in two of the patients.
  • No Thumbnail Available
    Item
    Betaine-urea deep eutectic solvent improves imipenem antibiotic activity
    (2022) Olivares, Belen; Martinez, Fabian A.; Ezquer, Marcelo; Morales, Bernardo J.; Fuentes, Ignacia; Calvo, Margarita; Campodonico, Paola R.
    Beta-lactam antibiotics are highly unstable in aqueous media, which may lead to subclinical concentrations, antimicrobial resistance and therapeutic failure. In previous work we demonstrated that a natural deep eutectic solvent consisting of betaine and urea (BU) is capable of improving the stability of some beta-lactams, including imipenem (IMP), the most unstable antibiotic of the family. Here, IMP-BU was studied by selective protonic Nuclear Overhauser Effect Spectroscopy Magnetic Resonance (H-1 NOESY NMR) to gain insight into the mechanism by which BU protects IMP. The kinetics of IMP release and its antibacterial activity were evaluated in diffusional, time-kill and antibiofilm assays. It was found that BU is a protective matrix which allows a fast release of IMP, resulting in superior antibacterial activity when compared to IMP in aqueous solution, both against bacteria growing in planktonic form and in biofilms. Furthermore, it was shown that BU is nontoxic when evaluated in fibroblast primary cell cultures and in organotypic skin cultures, and is not immunogenic when tested in vitro in macrophage cultures, suggesting that BU has potential application as a biomaterial or excipient. (C) 2022 Published by Elsevier B.V.
  • No Thumbnail Available
    Item
    Lidocaine use in localized thin fiber neuropathy associated with lichen simplex chronicus
    (2023) Sandoval, Mauricio; Curi, Maximiliano; Solis-Avaca, Marco; Espinoza, Fernanda; Almeida, Paula; Calvo, Margarita
    Lichen simplex chronicus (LSC) is a common condition whose pathophysiology is partially known. The sensory innervation of the skin consists of a dermal plexus made up of myelinated and unmyelinated fibers. The epidermis only contains unmyelinated fibers, which indicate temperature, pain, and/or itching. Until now, the presence of small-fiber neuropathy in LSC had not been studied and its role in this disease was not known. Therefore, there was no documented therapy to treat this disease with the knowledge of its presence in it. A cohort of 33 patients with LSC who underwent study for the presence of fine fiber neuropathy and alteration in its function is presented.According to the results, a concept test of a novel therapy with lidocaine patches was carried out, proving to be effective.
  • No Thumbnail Available
    Item
    Maximizing treatment efficacy through patient stratification in neuropathic pain trials
    (2023) Baron, Ralf; Dickenson, Anthony H.; Calvo, Margarita; Dib-Hajj, Sulayman D.; Bennett, David L.
    Despite substantial research advances, treatment of neuropathic pain remains inadequate and responses to treatment are highly variable. In this Perspective, the authors argue that rational stratification of patients with neuropathic pain will aid identification of subgroups of patients who will benefit most from a given treatment.
  • No Thumbnail Available
    Item
    Studying Independent Kcna6 Knock-out Mice Reveals Toxicity of Exogenous LacZ to Central Nociceptor Terminals and Differential Effects of Kv1.6 on Acute and Neuropathic Pain Sensation
    (2021) Peck, Liam J.; Patel, Ryan; Diaz, Paula; Wintle, Yolanda M.; Dickenson, Anthony H.; Todd, Andrew J.; Calvo, Margarita; Bennett, David L. H.
    The potassium channel Kv1.6 has recently been implicated as a major modulatory channel subunit expressed in primary nociceptors. Furthermore, its expression at juxtaparanodes of myelinated primary afferents is induced following traumatic nerve injury as part of an endogenous mechanism to reduce hyperexcitability and pain-related hypersensitivity. In this study, we compared two mouse models of constitutive Kv1.6 knock-out (KO) achieved by different methods: traditional gene trap via homologous recombination and CRISPR-mediated excision. Both Kv1.6 KO mouse lines exhibited an unexpected reduction in sensitivity to noxious heat stimuli, to differing extents: the Kv1.6 mice produced via gene trap had a far more significant hyposensitivity. These mice (Kcna6lacZ) expressed the bacterial reporter enzyme LacZ in place of Kv1.6 as a result of the gene trap mechanism, and we found that their central primary afferent pre -synaptic terminals developed a striking neurodegenerative phenotype involving accumulation of lipid species, development of "meganeur-ites," and impaired transmission to dorsal horn wide dynamic range neurons. The anatomic defects were absent in CRISPR-mediated Kv1.6 KO mice (Kcna6-/-) but were present in a third mouse model expressing exogenous LacZ in nociceptors under the control of a Nav1.8-promoted Cre recombinase. LacZ reporter enzymes are thus intrinsically neurotoxic to sensory neurons and may induce patho-logic defects in transgenic mice, which has confounding implications for the interpretation of gene KOs using lacZ. Nonetheless, in Kcna6-/-mice not affected by LacZ, we demonstrated a significant role for Kv1.6 regulating acute noxious thermal sensitivity, and both mechanical and thermal pain-related hypersensitivity after nerve injury.