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Dermatology and Therapy Aug 2023Chronic spontaneous urticaria (CSU) is a condition in which wheals, angioedema, and pruritus occur spontaneously and recurrently for at least 6 weeks. The etiology of... (Review)
Review
Chronic spontaneous urticaria (CSU) is a condition in which wheals, angioedema, and pruritus occur spontaneously and recurrently for at least 6 weeks. The etiology of this disease is partially dependent on production of autoantibodies that activate and recruit inflammatory cells. Although the wheals can resolve within 24 h, symptoms have a significant detrimental impact on the quality of life of these patients. Standard therapy for CSU includes second-generation antihistamines and omalizumab. However, many patients tend to be refractory to these therapies. Available treatments such as cyclosporine, dapsone, dupilumab, and tumor necrosis factor alpha (TNFa) inhibitors have been used with success in some cases. Furthermore, various biologics and other novel drugs have emerged as potential treatments for this condition, and many more are currently under investigation in randomized clinical trials.
PubMed: 37386330
DOI: 10.1007/s13555-023-00972-6 -
Chinese Medical Journal Jul 2023
Topics: Humans; Dapsone; Drug Hypersensitivity; Hypersensitivity; Syndrome
PubMed: 37057725
DOI: 10.1097/CM9.0000000000002492 -
Cureus Dec 2023Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated... (Review)
Review
Hansen disease, known as Leprosy, is an infectious disease caused by . The disease was once thought to be highly contiguous, and patients with leprosy were treated poorly and had to face discrimination due to the gruesome disease's complications. , the bacterium causative of leprosy, can generally be found in the nine-banded armadillo. The bacterium is transmitted via aerosol droplets and broken skin-to-skin contact. Once M enters the body, it will target peripheral nerves and the lining mucosa of the skin and eyes, thus causing inflammation and tenderness of the affected area. Over time, this will lead to peripheral neuropathy and weakness of the affected body parts. Treatment of leprosy involves multi-drug combinations such as dapsone, rifampin, and clofazimine. Even though leprosy is curable, early detection and treatment are crucial to preventing irreversible damage and disabilities. Prevention measures include early detection, treatment regimen adherence, close contact prophylaxis, contact tracing, and community awareness. This review aims to provide the latest diagnostic and therapeutic recommendations for leprosy. It outlines the epidemiology, microbiology, clinical treatment, and immunological methods used to detect leprosy.
PubMed: 38179342
DOI: 10.7759/cureus.49954 -
European Journal of Medicinal Chemistry Dec 2023Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely,...
Perforin is a pore-forming protein whose normal function enables cytotoxic T and natural killer (NK) cells to kill virus-infected and transformed cells. Conversely, unwanted perforin activity can also result in auto-immune attack, graft rejection and aberrant responses to pathogens. Perforin is critical for the function of the granule exocytosis cell death pathway and is therefore a target for drug development. In this study, by screening a fragment library using NMR and surface plasmon resonance, we identified 4,4-diaminodiphenyl sulfone (dapsone) as a perforin ligand. We also found that dapsone has modest (mM) inhibitory activity of perforin lytic activity in a red blood cell lysis assay in vitro. Sequential modification of this lead fragment, guided by structural knowledge of the ligand binding site and binding pose, and supported by SPR and ligand-detected F NMR, enabled the design of nanomolar inhibitors of the cytolytic activity of intact NK cells against various tumour cell targets. Interestingly, the ligands we developed were largely inert with respect to direct perforin-mediated red blood cell lysis but were very potent in the context of perforin's action on delivering granzymes in the immune synapse, the context in which it functions physiologically. Our work indicates that a fragment-based, structure-guided drug discovery strategy can be used to identify novel ligands that bind perforin. Moreover, these molecules have superior physicochemical properties and solubility compared to previous generations of perforin ligands.
Topics: Perforin; Ligands; Killer Cells, Natural; Cell Death; Dapsone
PubMed: 37716187
DOI: 10.1016/j.ejmech.2023.115786 -
The Korean Journal of Pain Jul 2023There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through... (Review)
Review
There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through numerous mechanisms such as direct tissue damage and inflammation, the induction of excessive immunologic activity, and the development of peripheral or central sensitization. Treating infections might relieve pain by attenuating these processes, but a growing body of literature suggests that some antimicrobial therapies confer analgesic effects, including for nociceptive and neuropathic pain symptoms, and affective components of pain. The analgesic mechanisms of antimicrobials are indirect, but might be conceptualized into two broad categories: 1) the reduction of the infectious burden and associated pro-inflammatory processes; and 2) the inhibition of signaling processes (e.g., enzymatic and cytokine activity) necessary for nociception and maladaptive neuroplastic changes via off-target effects (unintended binding sites). For the former, there is evidence that symptoms of chronic low back pain (when associated with Modic type 1 changes), irritable bowel syndrome, inflammatory bowel disease, chronic pelvic pain, and functional dyspepsia might be improved after antibiotic treatment, though significant questions remain regarding specific regimens and dose, and which subpopulations are most likely to benefit. For the latter, there is evidence that several antimicrobial classes and medications exert analgesic effects independent of their reduction of infectious burden, and these include cephalosporins, ribavirin, chloroquine derivatives, rapalogues, minocycline, dapsone, and piscidin-1. This article aims to comprehensively review the existing literature for antimicrobial agents that have demonstrated analgesic efficacy in preclinical or clinical studies.
PubMed: 37394272
DOI: 10.3344/kjp.23129