Nordihydroguaiaretic acid microparticles are effective in the treatment of osteoarthritis.

Several disease-modifying osteoarthritis (OA) drugs have emerged, but none have been approved for clinical use due to their systemic side effects, short half-life, and rapid clearance from the joints. Nordihydroguaiaretic acid (NDGA), a reactive oxygen species (ROS) scavenger and autophagy inducer, could be a potential treatment for OA. In this report, we show for the first time that sustained delivery of NDGA through polymeric microparticles maintains therapeutic concentrations of drug in the joint and ameliorates post-traumatic OA (PTOA) in a mouse model. In vitro treatment of oxidatively stressed primary chondrocytes from OA patients using NDGA-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (NDGA-MP) inhibited 15-lipoxygenase, induced autophagy, prevented chondrosenescence, and sustained matrix production. In vivo intra-articular delivery of NDGA-MP was non-toxic and had prolonged retention time (up to 35 days) in murine knee joints. Intra-articular therapy using NDGA-MP effectively reduced cartilage damage and reduced pain in the surgery-induced PTOA mouse model. Our studies open new avenues to modulate the immune environment and treat post-traumatic OA using ROS quenchers and autophagy inducers.

Acute hepatic rupture causing hemoperitoneum in a dog with anaphylaxis.

A 2-year-old spayed female Siberian Husky was presented with a history of acute onset lethargy, collapse, haematochezia and vomiting. The patient was severely tachycardic and hypotensive. Point-of-care ultrasound revealed gallbladder wall thickening and peritoneal effusion consistent with haemorrhage on subsequent abdominocentesis. Despite attempted medical stabilization over the course of several hours, including blood products and multiple autotransfusions, the patient progressed to cardiopulmonary arrest. The dog was successfully resuscitated but was subsequently euthanized. Necropsy revealed a severe, acute hemoperitoneum secondary to rupture of the left lateral liver lobe. A tear in the hepatic capsule was identified along with a large hematoma. A single adult nematode, consistent with Dirofilaria immitis, was found in a pulmonary vessel in the right caudal lung lobe. The remaining necropsy findings were supportive of the clinical diagnosis of anaphylaxis. This report details a case, with necropsy findings, supporting a diagnosis of anaphylaxis and severe, refractory hemoperitoneum resulting from hepatic rupture. Acute hepatic rupture should be considered in cases of anaphylaxis-related hemoperitoneum.

Intra-articular injection of rapamycin microparticles prevent senescence and effectively treat osteoarthritis.

Trauma to the knee joint is associated with significant cartilage degeneration and erosion of subchondral bone, which eventually leads to osteoarthritis (OA), resulting in substantial morbidity and healthcare burden. With no disease-modifying drugs in clinics, the current standard of care focuses on symptomatic relief and viscosupplementation. Modulation of autophagy and targeting senescence pathways are emerging as potential treatment strategies. Rapamycin has shown promise in OA disease amelioration by autophagy upregulation, yet its clinical use is hindered by difficulties in achieving therapeutic concentrations, necessitating multiple weekly injections. Rapamycin-loaded in poly(lactic-co-glycolic acid) microparticles (RMPs) induced autophagy, prevented senescence, and sustained sulphated glycosaminoglycans production in primary human articular chondrocytes from OA patients. RMPs were potent, nontoxic, and exhibited high retention time (up to 35 days) in mice joints. Intra-articular delivery of RMPs effectively mitigated cartilage damage and inflammation in surgery-induced OA when administered as a prophylactic or therapeutic regimen. Together, the study demonstrates the feasibility of using RMPs as a potential clinically translatable therapy to prevent the progression of post-traumatic OA.