Subject(s)
Antibodies, Neutralizing/pharmacology , Epithelium/physiology , HIV Antibodies/pharmacology , HIV Infections/therapy , HIV-1/physiology , Immunotherapy/methods , Animals , Cells, Cultured , Epithelium/virology , HIV Infections/immunology , Humans , Immunoglobulin A/pharmacology , Immunoglobulin G/pharmacology , Primates , Transcytosis , Virion/drug effects , VirulenceABSTRACT
Broadly neutralizing antibodies (bNAbs) offer promising opportunities for preventing HIV-1 infection in humans. Immunoprophylaxis with potent bNAbs efficiently protects non-human primates from mucosal transmission even after repeated challenges. However, the precise mechanisms of bNAb-mediated viral inhibition in mucosal tissues are currently unknown. Here, we show that immunoglobulin (Ig)G and IgA bNAbs do not interfere with the endocytic transport of HIV-1 across epithelial cells, a process referred to as transcytosis. Instead, both viruses and antibodies are translocated to the basal pole of epithelial cells, possibly in the form of an immune complex. Importantly, as opposed to free virions, viral particles bound by bNAbs are no longer infectious after transepithelial transit. Post-transcytosis neutralization activity of bNAbs displays comparable inhibitory concentrations as those measured in classical neutralization assays. Thus, bNAbs do not block the transport of incoming HIV-1 viruses across the mucosal epithelium but rather neutralize the transcytosed virions, highlighting their efficient prophylactic and protective activity in vivo.
Subject(s)
AIDS Vaccines/immunology , Antibodies, Neutralizing/immunology , Epithelial Cells/immunology , HIV Antibodies/immunology , HIV Infections/immunology , HIV-1/physiology , Virion/metabolism , Animals , Cells, Cultured , Cross Reactions , Epithelial Cells/virology , HIV Antigens/immunology , HIV-1/pathogenicity , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Primates , Transcytosis , VirulenceABSTRACT
Periodic hypokaliemic paralysis is an usual cause of severe hypokaliemia. Thyrotoxicosis periodic paralysis (TPP) is less common. Incidence is high in Asian people and rarely reported in caucasian people. We describe the case of a young caucasian male, with a TPP. Clinical symptoms of hypokaliemia are strong, when thyrotoxicosis symptoms appear only on blood tests. The clinical course is good with beta-blockers and antithyroid treatment. These treatments induce a total clinical and biological cure. In all the cases of hypokaliemic paralysis, even without symptom, an hyperthyroïdia must be searched for.
Subject(s)
Hypokalemic Periodic Paralysis/etiology , Thyrotoxicosis/complications , Adrenergic beta-Antagonists/therapeutic use , Adult , Antithyroid Agents/therapeutic use , Humans , Male , Thyrotoxicosis/blood , Thyrotoxicosis/drug therapyABSTRACT
The authors report a case of a cerebral embolism, with a rapidly resolving course, during late fibrinolysis using tissue plasminogen activator in a patient with a posterolateral myocardial infarction. A review of the literature is used as basis for considering the effects of fibrinolytic treatment on left intraventricular thrombi during the acute phase of myocardial infarction. The risk of systemic embolism during such treatment is stressed.
