Unusual Case of Metformin-Associated Lactic Acidosis in Patient with Type 2 Diabetes Mellitus.

BACKGROUND Metformin is recommended as the first-line therapy for type 2 diabetes mellitus, according to the American Diabetes Association. It is considered a safe medication with minimal adverse effects, with the most common being gastrointestinal. Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication. MALA usually occurs in patients with kidney dysfunction. However, it can still occur with preserved kidney function with the ingestion of a large dose of metformin. CASE REPORT A 66-year-old man with a significant medical history of type 2 diabetes mellitus presented after an intentional ingestion of a high dose of metformin (3000 mg/day). He was admitted to our hospital with symptoms of fatigue, nausea, vomiting, abdominal pain, and watery diarrhea lasting for 3 days. His initial laboratory findings were remarkable, with a serum creatinine level of 819 µmol/L. Arterial blood gas revealed severe lactic acidosis, with a pH of 6.94, HCO3⁻- of 3 mEq/L, anion gap of 48 mmol/L, and lactate level of 15 mmol/L. Emergent continuous renal replacement therapy was done. Two days later, his condition improved considerably, and the lactic acidosis was resolved entirely. He was discharged on day 11 of hospitalization. CONCLUSIONS MALA is rare but life-threatening complication of treatment with metformin. MALA should be considered when there is evidence of metformin ingestion and renal insufficiency in patients with lactic acidosis. The curative treatment of MALA is based on hemodialysis, but the main remedy is prevention, which requires patient compliance with taking metformin as prescribed.

Enhanced Catalytic Activities of TiO2 Nanotube Arrays Co-Sensitized with Pt/CdS/ZnS via Electrodeposition and Successive Ionic Layer Adsorption and Reaction (SILAR) Method Approach.

In this work, we have synthesized a nanocomposite ZnS/CdS/Pt/TiO2 nanotube arrays (denoted ZCP-NTAs). Firstly, TiO2 nanotube array (NTAs) material was fabricated by the anodic method of a titanium plate in an electrolyte solution containing 0.35 M NaHSO4 and 0.24 M NaF and incubated in the air at 500 ºC for 2 hours. After that, pulsed electrodeposition technology was used to decorate platinum nanoparticles (denoted as Pt NPs) onto the surface of TiO2 nanotubes to form P-NTAs photoelectrodes. Then, the SILAR method is used to deposition CdS quantum dots (symbolized as CdS QDs) on the surface of P-NTAs to form CP-NTAs material. Finally, by the SILAR method, a ZnS passive layer that protects against optical corrosion and inhibits recombination of e-/h+ pairs was coated onto the CP-NTAs to form ZCP-NTAs material. As-prepared ZCP-NTAs photocatalytic material has good absorbability of light in the visible region with light absorption wavelength up to 608 nm, photon conversion efficiency up to 5.32% under light intensity AM1.5G, and decomposition efficiency of 10 mg L-1 methyl orange (MO) in 120 minutes reached 91.50%. This material promises to bring high application ability in the photocatalytic field applied for environmental treatment and other applications.

Discovery of Conformationally Restricted Human Glutaminyl Cyclase Inhibitors as Potent Anti-Alzheimer's Agents by Structure-Based Design.

Alzheimer's disease (AD) is an incurable, progressive neurodegenerative disease whose pathogenesis cannot be defined by one single element but consists of various factors; thus, there is a call for alternative approaches to tackle the multifaceted aspects of AD. Among the potential alternative targets, we aim to focus on glutaminyl cyclase (QC), which reduces the toxic pyroform of ß-amyloid in the brains of AD patients. On the basis of a putative active conformation of the prototype inhibitor 1, a series of N-substituted thiourea, urea, and α-substituted amide derivatives were developed. The structure-activity relationship analyses indicated that conformationally restrained inhibitors demonstrated much improved QC inhibition in vitro compared to nonrestricted analogues, and several selected compounds demonstrated desirable therapeutic activity in an AD mouse model. The conformational analysis of a representative inhibitor indicated that the inhibitor appeared to maintain the Z-E conformation at the active site, as it is critical for its potent activity.