Bharati Vidya Peeth College of Engineering

Chronic treatment with levodopa often leads to levodopa-induced dyskinesia (LID), around 40% of individuals are affected. Stigmasterol exhibits antioxidant, anti-inflammatory, and glutamate-antagonist properties, acting through AKT-1, VEGFR, and IL-6 to prevent neuronal death. This study investigates the STI potential to mitigate LID. Male Sprague Dawley rats were assigned to five groups (SHAM, 6-OHDA, LID, STI 10, STI 20), with n = 10. PD was induced by stereotaxic infusion of 6-OHDA (3 µg/µL × 2.5 µL) into the right medial forebrain bundle. After a 21-day recovery period, development of PD was confirmed through behavioral assessment, including APO-induced rotation, footprint analyses, and a stepping test assessment conducted over 7 days. Subsequently, the rats were treated with levodopa + carbidopa and stigmasterol (10/20 mg/Kg) orally for 28 days. Abnormal involuntary movements (AIMs) were assessed at intervals of 1, 14, 21, and 28th days to evaluate the effect of stigmasterol on LID. On day 28, rats were euthanized, and brain samples were analyzed for biochemical, and histopathological changes in the striatum and substantia nigra using nissl staining. STI treatment (10/20 mg/Kg) significantly decreased AIMS, MDA level, TNF-α, IL-1β, NF- kB, and NLRP3 and significantly increased GSH, SOD, catalase and dopamine levels. The histopathology assessment restored neurons in the striatum and substantia nigra of the brain. The result concludes that co-administration of stigmasterol (10/20 mg/Kg) with L-DOPA + carbidopa restores DA level, showing anti-inflammatory, anti-oxidant properties, and neuroprotective activity. Stigmasterol can therefore be administered as an adjuvant treatment to delay LID.

Gastric neuroendocrine tumors (NETs), although rare, are highly vascular subepithelial lesions that can pose significant bleeding risks during endoscopic submucosal dissection (ESD). Traditionally, bleeding is managed intraoperatively with mechanical or thermal hemostasis, but pre-emptive strategies remain underexplored. Here, we report the use of EUS-guided pre-emptive epinephrine injection to minimize the bleeding risk during gastric NET ESD.

To minimize the risk of bleeding during ESD of large gastric NETs, a pre-emptive EUS-guided epinephrine injection was administered at the base of the lesion near the feeder vessel.

A 38-year-old female was diagnosed with a large gastric subepithelial lesion during evaluation for upper gastrointestinal bleeding. EUS revealed a large hypoechoic tumor confined to the submucosa with a prominent feeding vessel. Given the predominantly submucosal location, ESD was planned. However, significant bleeding was anticipated due to the large feeder vessel. Therefore, a pre-emptive EUS-guided adrenaline injection (5 mL of 1:10,000 diluted epinephrine) was administered at the base of the lesion after confirming absence of blood return on fine-needle aspiration. Instantaneous pallor of the lesion was observed. ESD was subsequently completed successfully without any bleeding.

This case highlights a novel, effective, and safe use of EUS-guided pre-emptive epinephrine injection to minimize bleeding during ESD of vascular gastric NETs. This approach could enhance procedural safety and warrants further prospective evaluation.

This work aimed to formulate surface-modified berberine hydrochloride (BER)-loaded liposomes containing in-situ nasal gel for bran targeting. The liposomes were prepared by ethanol-injection method and optimized following a 3² full-factorial design. Size, morphology, zeta potential, ex-vivo permeation, and in-vitro release were estimated. The surface of optimized liposome was modified with ascorbic acid. The size of surface-modified liposomes was bigger (191.4 nm) than the unmodified liposomes (171 nm). Surface-modified liposomes were embedded in in-situ gel using poloxamer and Carbopol 934P. Liposomal in-situ gel showed higher permeation (71.94%) in contrast to the plain gel (46.64%). In-vivo pharmacokinetic examination of payload from liposomal in-situ gel displayed higher concentration in brain (C_max of 93.50 ng/mL). The liposomal in-situ nasal gel had a higher drug targeting efficiency (138.43%) and a higher drug targeting potential (27.77%) confirming improved brain targeting. In male Wistar rats, the pharmacodynamic parameters (path length and escape latency) were evaluated with trimethyl tin-induced neurodegeneration. Animals treated with BER-loaded in-situ gel significantly decreased escape latency and path length in comparison to the control group. Histopathological assessment showed that the formulated gel was safe for intranasal administration. The developed formulation has the potential to effectively enhance the efficacy of BER in Alzheimer's disease management.