ABSTRACT
INTRODUCTION: Metronidazole, a nitroimidazole antibiotic, is a well-known antibacterial and antiprotozoal agent that is generally well tolerated without many serious side effects. Most adverse reactions affect the gastrointestinal or genitourinary system, but the central nervous system may also be afflicted. In addition to headache and dizziness, cerebellar dysfunction can occur with metronidazole use. CASE REPORT: We discuss the clinical presentation and imaging findings of metronidazole-induced encephalopathy in a 12-year-old male. The patient had a history of Crohn's disease and chronic Clostridium difficile infection for which he had received metronidazole for approximately 75 days prior to arrival to a local emergency department (ED). He presented with five days of progressive vertigo, nausea, vomiting, and ataxia. Subsequent magnetic resonance imaging showed symmetric hyperintense dentate nuclei lesions, characteristic of metronidazole-induced encephalopathy. The patient's symptoms improved rapidly after cessation of metronidazole, and his symptoms had completely resolved by discharge on hospital day two. CONCLUSION: Metronidazole-induced encephalopathy is a rare cause of vertigo and ataxia that can lead to permanent sequela if not identified and treated promptly. Thus, it is important for physicians to keep this diagnosis in mind when evaluating patients on metronidazole who present to the ED with new neurologic complaints.
ABSTRACT
Capsaicin, the active component of chili peppers, is an alkaloid that causes tissue irritation and burning especially upon contact with mucous membranes. While favored in certain cuisines around the world, it has also been weaponized in the form of pepper sprays and bear repellents. When significant capsaicin exposures occur, patients may present to the emergency department; thus, providers should be prepared to manage these cases effectively. In this case report we discuss an unusual exposure of capsaicin to the vaginal mucosa with successful treatment.
ABSTRACT
Hypervariable loops of HIV-1 Env protein gp120 are speculated to play roles in the conformational transition of Env to the receptor binding-induced metastable state. Structural analysis of full-length Env-based immunogens, containing the entire V2 loop, displayed tighter association between gp120 subunits, resulting in a smaller trimeric diameter than constructs lacking V2. A prominent basal quaternary location of V2 and V3' that challenges previous reports would facilitate gp41-independent gp120-gp120 interactions and suggests a quaternary mechanism of epitope occlusion facilitated by hypervariable loops. Deletion of V2 resulted in dramatic exposure of basal, membrane-proximal gp41 epitopes, consistent with its predicted basal location. The structural features of HIV-1 Env characterized here provide grounds for a paradigm shift in loop exposure and epitope occlusion, while providing substantive rationale for epitope display required for elicitation of broadly neutralizing antibodies, as well as substantiating previous pertinent literature disregarded in recent reports.
Subject(s)
Epitopes/chemistry , Peptide Fragments/chemistry , Protein Multimerization , env Gene Products, Human Immunodeficiency Virus/chemistry , CD4 Antigens/chemistry , CD4 Antigens/metabolism , Epitopes/genetics , HIV Envelope Protein gp120/chemistry , HIV Envelope Protein gp120/genetics , HIV Envelope Protein gp120/metabolism , HIV Envelope Protein gp41/chemistry , HIV Envelope Protein gp41/genetics , HIV Envelope Protein gp41/metabolism , Humans , Models, Molecular , Peptide Fragments/genetics , Protein Binding , Protein Conformation , Protein Interaction Domains and Motifs , Sequence Deletion , env Gene Products, Human Immunodeficiency Virus/genetics , env Gene Products, Human Immunodeficiency Virus/metabolismABSTRACT
OBJECTIVE: To study the dose-dependent manner of HIV-1 Tat-induced effects on viral replication, internalization and spread, and to directly observe these effects on soluble Env immunogens and virus-like particles. DESIGN: In order to determine the manner through which Tat affects viral replication, we incubated cells, virions and soluble Env spikes with Tat at different concentrations, and directly visualized the effects of such incubation. METHODS: Cell-based infectivity assays were carried out to assay Tat dose-dependency of viral infectivity. Transmission electron microscopy of virus-like particles and soluble gp140 immunogens incubated with Tat at various concentrations was performed to directly observe Tat-induced effects. RESULTS: Treating virus with exogenous Tat increased infectivity in a dose-dependent manner. In the presence of anti-Tat antibodies, virus replication and spread were repressed, postulating Tat contributions to disease progression. When CXCR4 coreceptors were blocked, Tat treatment overcame the inhibition relative to absence of Tat treatment. Similarly, syncytium formation between chronically infected and uninfected target cells was also increased by exogenous Tat treatment. Inhibiting the CD4 receptor for virus entry abolished syncytium formation and Tat treatment was unable to overcome CD4 dependency. We show that Tat reduces virus infectivity at higher Tat concentrations through Env interactions resulting in viral aggregation. CONCLUSION: Treating virions or chronically infected cells with exogenous Tat could enhance virus infectivity and spread through coreceptor tropism switch or through another undetermined mechanism. The aggregation potential of Tat suggests a mechanism of negative-feedback regulation of viral replication, providing another regulative function to control viral replication.