Acetaminophen Interactions with Phospholipid Vesicles Induced Changes in Morphology and Lipid Dynamics.

Acetaminophen (APAP) or paracetamol, despite its wide and common use for pain and fever symptoms, shows a variety of side effects, toxic effects, and overdose effects. The most common form of toxic effects of APAP is in the liver where phosphatidylcholine is the major component of the cell membrane with additional associated functionalities. Although this is the case, the effects of APAP on pure phospholipid membranes have been largely ignored. Here, we used 1,2-di-(octadecenoyl)-sn-glycero-3-phosphocholine (DOPC), a commonly found phospholipid in mammalian cell membranes, to synthesize large unilamellar vesicles to investigate how the incorporation of APAP changes the pure lipid vesicle structure, morphology, and fluidity at different concentrations. We used a combination of dynamic light scattering, small-angle neutron and X-ray scattering (SANS, SAXS), and cryo-TEM for structural characterization, and neutron spin-echo (NSE) spectroscopy to investigate the dynamics. We showed that the incorporation of APAP in the lipid bilayer significantly impacts the spherical phospholipid self-assembly in terms of its morphology and influences the lipid content in the bilayer, causing a decrease in bending rigidity. We observe a decrease in the number of lipids per vesicle by almost 28% (0.06 wt % APAP) and 19% (0.12 wt % APAP) compared to the pure DOPC (0 wt % APAP). Our results showed that the incorporation of APAP reduces the membrane rigidity by almost 50% and changes the spherical unilamellar vesicles into much more irregularly shaped vesicles. Although the bilayer structure did not show much change when observed by SAXS, NSE and cryo-TEM results showed the lipid dynamics change with the addition of APAP in the bilayer, which causes the overall decreased membrane rigidity. A strong effect on the lipid tail motion showed that the space explored by the lipid tails increases by a factor of 1.45 (for 0.06 wt % APAP) and 1.75 (for 0.12 wt % APAP) compared to DOPC without the drug.

A Systematic Review of Sellar and Parasellar Brown Tumors: An Analysis of Clinical, Diagnostic, and Management Profiles.

OBJECTIVE: To systematically review and analyze clinical, diagnostic, and management trends in sellar and parasellar brown tumors reported in existing literature. METHODS: In this systematic review, PubMed, Ovid MEDLINE, Scopus, and Google Scholar databases were searched for reported cases of sellar/parasellar brown tumors. Relevant titles and abstracts were screened in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Articles meeting inclusion criteria were subjected to data extraction, summarization, and analysis. A rare case of parasellar brown tumor was also presented. RESULTS: Eight reports (including the current report) were eligible for inclusion. Mean patient age was 42.75 years. Reported symptoms included visual disturbances (n = 6), headache (n = 5), fatigue (n = 3), nausea/vomiting (n = 2), chest pain (n = 1), neck pain (n = 1), and dysphagia (n = 1). In cases where computed tomography findings were provided (n = 6), lesions were noted to be expansile and lytic. Lesions were hyperintense on T2-weighted magnetic resonance imaging (66.7%) and demonstrated contrast enhancement (83.3%). Histology unanimously showed multinucleated giant cells in a fibrovascular connective tissue stroma. Dramatic symptom resolution was noted in all patients who underwent resection of the sellar/parasellar brown tumor (n = 4; 50%). CONCLUSIONS: Sellar/parasellar brown tumors are a rare, tertiary manifestation of hyperparathyroidism and can be elusive to diagnose. Diagnosis requires a high index of clinical suspicion in addition to comprehensive biochemical testing, imaging, and histopathologic analysis. Surgical extirpation is favored in cases where the lesion is causing compressive symptoms, or if it is unresponsive to management of hyperparathyroidism.