Central myelin-peripheral myelin junction in trigeminal, facial, and vestibulocochlear nerve: A histo-morphometric study.

BACKGROUND: The study aimed to locate the central myelin and peripheral myelin junction (CNS PNS Junction, CPJ) in trigeminal, facial and vestibulocochlear nerves. METHODS: The cisternal segments of the nerves were cut from the brainstem to the proximal margin of trigeminal ganglia (trigeminal nerve) and internal acoustic meatus (facial and vestibulocochlear nerve) from cadavers. Horizontal sections of H&E stained slides were analysed and histo morphometry was performed. The CPJ was confirmed by immunohistochemistry using monoclonal myelin basic protein antibody. RESULTS: The mean length of the trigeminal, facial and vestibulocochlear nerves were 13.6 ± 3.1 mm, 12.4 ± 1.9 mm and 11.5 ± 2.0 mm respectively; mean length of the centrally myelinated segment at the point of maximum convexity was 4.1 ± 1.5 mm, 3.7 ± 1.6 mm, 3.6 ± 1.4 mm respectively. Six different patterns were observed fortheCPJ.Utilizing the derived values, the CPJwas located at a distance of 18 - 48% and 17 - 61% of the total length of the nerve in all the cases in trigeminal and facial nerve respectively. In vestibulocochlear nerve, it was located at a distance of about 13 - 54% of the total length of the nerve. CONCLUSIONS: The location of the CPJ in the vestibulocochlear nerve was midway between the brainstem and internal acoustic meatus which is a novel observation.For all the nerves, the CPJ was located either at or before the half way along the length of the nerve in huge majority (97%); never crossing the 60% of the nerve length.

Glycol chitosan stabilized nanomedicine of lapatinib and doxorubicin for the management of metastatic breast tumor.

Advanced breast cancer is known to be highly evasive to conventional therapeutic regimes with a 5-year survival rate of less than 30% compared to over 90% for early stages. Although several new approaches are being explored to improve the survival outcome, there is still some room for equipping existing drugs such as lapatinib (LAPA) and doxorubicin (DOX) to fight the systemic disease. LAPA is associated with poorer clinical outcomes in HER2-negative patients. However its ability to also target EGFR has warranted its use in recent clinical trials. Nevertheless, the drug is poorly absorbed post oral administration and possess low aqueous solubility. DOX on the other hand is avoided in vulnerable patients in advanced stages due to its pronounced off-target toxicity. To overcome the pitfalls of the drugs, we have fabricated a nanomedicine co-loaded with LAPA & DOX and stabilized with glycol chitosan, a biocompatible polyelectrolyte. With a loading content of ~ 11.5% and ~ 15% respectively, LAPA and DOX in a single nanomedicine showed synergistic action against triple-negative breast cancer cells in comparison to physically mixed free drugs. The nanomedicine showed a time-dependent association with cancer cells thereon inducing apoptosis leading to ~ 80% cell death. The nanomedicine was found to be acutely safe in healthy Balb/c mice and could negate DOX-induced cardio toxicity. The combination nanomedicine significantly inhibited both the primary 4T1 breast tumor and its spread to the lung, liver, heart, and kidney compared to pristine drug controls. These preliminary data indicate bright prospects for the nanomedicine to be effective against metastatic breast cancer.

Nontoxic In Vivo Clearable Nanoparticle Clusters for Theranostic Applications.

Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T2 relaxivity of ∼223 mM-1 s-1and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.