Isavuconazole: A Promising Salvage Therapy for Invasive Mucormycosis.

A patient with invasive mucormycosis whose disease progresses despite optimal treatment including surgical debridement, intravenous (IV) amphotericin B, and control of the predisposing factors can be clinically challenging. We report a case of a 67-year-old Caucasian man with invasive mucormycosis that did not respond to first-line treatment. He was subsequently started on isavuconazole in addition to amphotericin B.

Immune Reconstitution Inflammatory Syndrome Associated Thrombocytopenia in a Patient with Human Immunodeficiency Virus Infection: A Rare Hematological Manifestation.

Human immunodeficiency virus (HIV) associated thrombocytopenia was commonly encountered in the era prior to the advent of antiretroviral therapy (ART). With the widespread use of ART, its incidence has significantly declined. Immune reconstitution inflammatory syndrome (IRIS) is an immune dysregulation phenomenon that reveals itself clinically as paradoxical deterioration after the commencement of ART in HIV infected patients.

Infective Endocarditis Presenting as Bilateral Orbital Cellulitis: An Unusual Case.

Orbital cellulitis is a severe and sight-threatening infection of orbital tissues posterior to the orbital septum. The most common causes of orbital cellulitis are rhinosinusitis, orbital trauma, and surgery. Infective endocarditis (IE) is a systemic infection that begins on cardiac valves and spreads by means of the bloodstream to peripheral organs.

Potent adjuvantic activity of a CCR1-agonistic bis-quinoline.

A bis-quinoline compound, (7-chloro-N-(4-(7-chloroquinolin-4-ylamino)butyl)quinolin-4-amine; RE-660) was found to have C-C chemokine receptor type 1 (CCR1)-agonistic properties. RE-660 displayed strong adjuvantic activity in mice when co-administered with bovine α-lactalbumin used as a model subunit protein antigen. RE-660 evoked a balanced Th1 (IgG2)/Th2 (IgG1) antibody profile, and the quality of antibodies elicited by the bis-quinoline was found to be superior to that evoked by glucopyranosyl lipid A by surface plasmon resonance experiments.

Toward self-adjuvanting subunit vaccines: model peptide and protein antigens incorporating covalently bound toll-like receptor-7 agonistic imidazoquinolines.

Toll-like receptor (TLR)-7 agonists show prominent Th1-biased immunostimulatory activities. A TLR7-active N(1)-(4-aminomethyl)benzyl substituted imidazoquinoline 1 served as a convenient precursor for the syntheses of isothiocyanate and maleimide derivatives for covalent attachment to free amine and thiol groups of peptides and proteins. 1 was also amenable to direct reductive amination with maltoheptaose without significant loss of activity.

Structure-activity relationships in nucleotide oligomerization domain 1 (Nod1) agonistic γ-glutamyldiaminopimelic acid derivatives.

N-acyl-γ-glutamyldiaminopimelic acid is a prototype ligand for Nod1. We report a detailed SAR of C(12)-γ-D-Glu-DAP. Analogues with glutaric or γ-aminobutyric acid replacing the glutamic acid show greatly attenuated Nod1-agonistic activity.

Syntheses of fluorescent imidazoquinoline conjugates as probes of Toll-like receptor 7.

Toll-like receptor (TLR)-7 agonists show prominent immunostimulatory activities. The synthesis of a TLR7-active N(1)-(4-aminomethyl)benzyl substituted imidazoquinoline 5d served as a convenient precursor for the covalent attachment of fluorophores without significant loss of activity. Fluorescence microscopy experiments show that the fluorescent analogues are internalized and distributed in the endosomal compartment.

Structure-activity relationships in toll-like receptor-2 agonistic diacylthioglycerol lipopeptides.

The N-termini of bacterial lipoproteins are acylated with a (S)-(2,3-bisacyloxypropyl)cysteinyl residue. Lipopeptides derived from lipoproteins activate innate immune responses by engaging Toll-like receptor 2 (TLR2) and are highly immunostimulatory and yet without apparent toxicity in animal models. The lipopeptides may therefore be useful as potential immunotherapeutic agents.