Yaron, Jordan R.

Abstract Accurate endoscopic marking of suspicious lesions and polyps is essential for the effective surgical management of gastrointestinal (GI) diseases, including colorectal cancer and inflammatory bowel disease. Currently, lesion localization relies on submucosal injection of a carbon-based tattoo ink; however, this ink exhibits extensive tissue diffusion and extravasation, leading to poor spatial fidelity, compromised precision, and risk for fibrotic responses. Given the need for contrast relative to endoscopic white light and biocompatibility, we report here the design and evaluation of melanin-inspired nanoparticle tattoo (MINT) inks, formulated from synthetic melanin nanoparticles and biopolymer-encapsulated synthetic melanin. MINT inks are designed to be durable, high-contrast, easily injectable, and colloidally stable for at least 2 months and to elicit minimal macrophage-mediated inflammatory responses in vitro. In live porcine colon studies, submucosal injection of MINT inks resulted in highly localized tattoos with minimal lateral spread over 9 weeks of follow-up, which is a significant advantage over the extensive diffusion observed with clinical carbon ink. MINT tattoo markings were distinctly visible from both mucosal and serosal surfaces of the intestine and enabled reproducible multipoint and quadrant-based marking, which enhanced spatial orientation. Collectively, these findings demonstrate that MINT inks are biocompatible and capable of providing precise, long-lasting, high-contrast marking of lesions in the colon. By overcoming the limitations of conventional carbon-particle-based tattoos, MINT inks represent a promising next-generation contrast agent for improving endoscopic localization and surgical outcomes in GI diseases.

Saturated fat breaks down less during sudden illnesses, resulting in lower monomer concentrations, and reducing disease severity.

Objective: Ringer’s lactate may improve early systemic inflammation during critical illnesses like severe acute pancreatitis, which are associated with hypocalcemia. Ringer’s lactate is buffered and contains lactate and calcium. We, thus analyzed extracellular calcium or lactate’s effects on the mechanisms, intermediary markers, and organ failure in models mimicking human disease with nonesterified fatty acid (NEFA) elevation. Methods: Meta-analyses and experimental studies were performed. Experimentally, extracellular calcium and lactate were compared in their interaction with linoleic acid (LA; a NEFA increased in human severe pancreatitis), and its subsequent effects on mitochondrial depolarization and cytosolic calcium signaling resulting in cell injury. In vivo, the effect of LA was studied on organ failure, along with the effect of calcium or lactate (pH 7.4) on severe acute pancreatitis-associated organ failure. A meta-analysis of human randomized control trials comparing Ringer’s lactate to normal saline was done, focusing on necrosis and organ failure. Results: Calcium reacted ionically with LA and reduced lipotoxic necrosis. In vivo, LA induced organ failure and hypocalcemia. During severe pancreatitis, calcium supplementation in saline pH 7.4, unlike lactate, prevented hypocalcemia, increased NEFA saponification, reduced circulating NEFA and C-reactive protein, reduced pancreatic necrosis adjacent to fat necrosis, and normalized shock (carotid pulse distension) and blood urea nitrogen elevation on day 1. This, however, did not prevent the later increase in serum NEFA which caused delayed organ failure. Meta-analysis showed Ringer’s lactate reduced necrosis, but not organ failure, compared with normal saline. Conclusion: Hypocalcemia occurs due to excess NEFA binding calcium during a critical illness. Ringer’s lactate’s early benefits in systemic inflammation are by the calcium it provides reacting ionically with NEFA. This, however, does not prevent later organ failure from sustained NEFA generation. Future studies comparing calcium supplemented saline resuscitation to Ringer’s lactate may provide insights to this pathophysiology.