Iridium(III)-Catalyzed C-H Cyclization of Sulfoximines with Diazo Meldrum's Acids for the Synthesis of Cyclic Sulfoximines.

Iridium(III)-catalyzed C-H cyclization of sulfoximines with diazo Meldrum's acid provided cyclic sulfoximines with a carbonyl group in good to excellent yields. These compounds were easily converted into unsubstituted and arylated sulfoximines. Moreover, the vinyl triflates obtained from the cyclic sulfoximines underwent palladium(II)-catalyzed cross-coupling reactions with a variety of aryl, arylalkynyl, and heteroatom (N and S) nucleophiles, affording a wide range of monosubstituted sulfoximines in high yields.

Antioxidative and anti-inflammatory activity of psiguadial B and its halogenated analogues as potential neuroprotective agents.

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: ß-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased H2O2-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl2 in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.

Systemic effect of endoscopic ultrasonography-guided pancreatic cyst ablation with ethanol and paclitaxel.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided pancreatic cyst ablation is a minimally invasive treatment modality. Local injection of ablative agents may rarely cause systemic effects in patients. AIMS: This study aimed to evaluate the systemic effect of ablative agents by analyzing the plasma drug concentration. METHODS: Ten patients with pancreatic cysts were enrolled. Cyst ablation was performed by 99 % ethanol lavage (2.5-70 mL) and paclitaxel (Genexol-polymeric micelle, 6.0-24.0) injection. Blood samples were collected at 0, 2, 4, 7 and 24 h. Plasma paclitaxel concentration was analyzed by a liquid chromatography-tandem mass spectrometry with the lowest limit of quantitation of 0.1 ng/mL. Procedure-related complications were closely monitored. RESULTS: Pancreatic cysts were located at the head in two, body in seven and tail in one patient. Eight cysts were septated. Median diameter and original volume were 39.5 mm (range 2.7-21.8) and 14.79 mL (3.42-343.30). Median cyst fluid CEA and amylase values were 17.10 ng/mL (0.5-14127.5) and 73.50 U/L (3.1-91,590). Peak plasma paclitaxel concentration values were observed between 2 and 7 h, ranging from 0.45 to 14.73 ng/mL. The highest concentration (17.10 ng/mL at 0 h) was observed in a patient who had intracystic bleeding. Mild abdominal pain occurred in five patients and vomiting in one patient during the first 48-h monitoring. CONCLUSION: Plasma paclitaxel concentration after EUS-guided pancreatic cyst ablation was nearly as low as the undetectable value and rarely caused systemic side-effect.

EUS-guided radiofrequency ablation of the porcine pancreas.

BACKGROUND: EUS-guided radiofrequency ablation (EUS-RFA) could be used as an adjunct and effective alternative mode of treatment for unresectable locally advanced and nonmetastatic pancreatic adenocarcinoma. However, its translation into clinical practice has been restricted because of limited data and high procedure-related risk. OBJECTIVE: To evaluate the feasibility, efficacy, and safety of EUS-RFA in the normal porcine pancreas. DESIGN: Prospective, endoscopic, experimental study in a porcine model. SETTING: Tertiary-care referral center animal laboratory. PATIENTS: Animal study. INTERVENTION: EUS-RFA of the pancreas was attempted on 10 adult mini pigs. An 18-gauge endoscopic RFA electrode was used to puncture the body and tail of the pancreas, with an output power of 50 W for 5 minutes. MAIN OUTCOME MEASUREMENTS: The feasibility, efficacy, and safety of EUS-RFA. RESULTS: A spherical necrotic lesion surrounded by fibrous tissue localized in the pancreatic parenchyma was observed on histopathologic examination. The mean diameter of the ablated tissue was 23.0 ± 6.9 mm. No major procedure-related complications were noted, and all pigs survived without any distress behavioral pattern for 7 days until autopsy. LIMITATIONS: Small sample size with short-term observation and the lack of evaluation of the head of the pancreas. CONCLUSION: EUS-RFA of the pancreatic body and tail was feasible, effective, and relatively safe in a porcine model. More animal studies to assess damage to adjacent organs are required before human trials can be conducted.

Factors affecting tumor ablation during high intensity focused ultrasound treatment.

BACKGROUND/AIMS: High intensity focused ultrasound (HIFU) utilizes a targeted extracorporeal focused ultrasound beam to ablate neoplastic pancreatic tissue. We used an in vitro model to examine the effects of bone, metallic stents, plastic stents, metal plates, and cyst-like lesions on HIFU treatment. METHODS: HIFU was delivered to the phantom models implanted with foreign bodies, and the location, shape, and size of the ablated zones were evaluated. RESULTS: Bone and metallic plates reflected the ultrasound beam, shifting the ablation zone from the focal zone to the prefocal area. In the phantoms containing metal stent, plastic stent, and cyst, most of the ablative energy was reflected to the prefocal area by the surface, with the remainder penetrating through the phantom. The area of the ablated margins was significantly larger in size and volume than the intended focal ablation zone. CONCLUSIONS: During HIFU therapy, artificial or anatomical barriers could affect the direction of the ultrasound beams, shifting the ablation zone from the focal area to a prefocal site with a larger than expected ablation zone. These factors should be considered prior to HIFU treatment for pancreatic tumors because they could limit ablation success, in addition to causing complications.

Forward-viewing endoscopic ultrasound-guided NOTES interventions: a study on peritoneoscopic potential.

AIM: To evaluate the feasibility of diagnostic and therapeutic transgastric (TG) peritoneoscopic interventions with a forward-viewing endoscopic ultrasound (FV-EUS). METHODS: This prospective endoscopic experimental study used an animal model. Combined TG peritoneoscopic interventions and EUS examination of the intra-abdominal organs were performed using an FV-EUS on 10 animal models (1 porcine and 9 canine). The procedures carried out include EUS evaluation and endoscopic biopsy of intraperitoneal organs, EUS-guided fine needle aspiration (EUS-FNA), EUS-guided radiofrequency ablation (EUS-RFA), and argon plasma coagulation (APC) for hemostatic control. The animals were kept alive for 7 d, and then necropsy was performed to evaluate results and complications. RESULTS: In all 10 animals, TG peritoneoscopy, followed by endoscopic biopsy for the liver, spleen, abdominal wall, and omentum, was performed successfully. APC helped control minor bleeding. Visualization of intra-abdominal solid organs with real-time EUS was accomplished with ease. Intraperitoneal EUS-FNA was successfully performed on the liver, spleen, and kidney. Similarly, a successful outcome was achieved with EUS-RFA of the hepatic parenchyma. No adverse events were recorded during the study. CONCLUSION: Peritoneoscopic natural orifice transluminal endoscopic surgery (NOTES) interventions through FV-EUS were feasible in providing evaluation and performing endoscopic procedures. It promises potential as a platform for future EUS-based NOTES.