Antiphospholipid antibodies can specifically target placental mitochondria and induce ROS production.

Women with antiphospholipid antibodies (aPL) have increased risks of pregnancy complications, including a ten-fold increased risk of preeclampsia, which is potentially triggered by the release of placental toxins. Previously, aPL were shown to enter the outer layer of the placenta, the syncytiotrophoblast, associate with mitochondria, and alter mitochondrial function. We hypothesised that aPL may also increase mitochondrial reactive oxygen species (ROS) production, leading to cellular dysfunction and release of toxins. First trimester placental explants were incubated with monoclonal aPL, ID2 and IIC5 (25, 50, and 100 µg/mL), for 3 h at 37 °C and ROS production followed using CellROX Deep Red. In addition, the candidate treatment compounds chloroquine, melatonin, and Mito-Q were tested at therapeutic concentrations for their ability to prevent ROS production. Mitochondria isolated from term placentae were incubated with fluorescently-labelled ID2, IIC5, or control IgG antibodies (2.5, 5, 10, or 20 µg/mL) for 30 min, and mitochondria with bound antibodies were quantified using flow cytometry. In addition, respirometry coupled with fluorimetry was used to interrogate explant mitochondrial respiration and ROS production following incubation with 25, 50, or 100 µg/mL ID2, IIC5, or control IgG for 3 h at 37 °C. ID2 increased explant ROS production in a manner that was completely prevented by the endocytosis inhibitor chloroquine, and partially prevented by the antioxidants melatonin and Mito-Q. Both ID2 and IIC5 displayed a greater ability to bind isolated mitochondria than control antibodies, and increased ROS production attributable to the mitochondrial enzyme glycerol 3-phosphate dehydrogenase (mGPDH). Our evidence supports the hypothesis that aPL interact with syncytiotrophoblast mitochondria, likely via the binding of cardiolipin and ß2 glycoprotein I in mitochondrial membranes, and induce ROS production which contributes to overall oxidative stress and placental dysfunction.

A Rare Case of Spontaneous Intussusception in an Elderly Patient.

Intussusception is an uncommon pathology in the adult population. Most intussusception cases result from an underlying pathological lead point, oftentimes a malignant neoplasm. We report a case of intussusception in an adult male patient who presented with abdominal pain and currant jelly diarrhea. The patient underwent laparoscopic right hemicolectomy and the biopsy of the affected colon did not show any pathological lead point. Intussusception remains an important differential diagnosis in patients presenting with abdominal pain and bloody diarrhea.

Incidental follicular cholecystitis with periductal fibrosis on liver biopsy: Rare findings.

INTRODUCTION AND IMPORTANCE: Follicular cholecystitis (FC) is a rare entity found, it is found in 0.1-1 % of patients with chronic cholecystitis. 1,2 This pathologic finding has been associated with extrahepatic biliary obstruction distal to the gallbladder, such as primary sclerosing cholangitis, choledocholithiasis, and distal biliary strictures. CASE PRESENTATION: Our patient is a 32-year-old female with a past medical history significant for obesity presented with symptoms of postprandial nausea and spasmodic abdominal pain. An abdominal ultrasound was performed with findings adenomyosis and possible gallbladder polyps or adherent stones. The patient was referred to surgery and a routine laparoscopic cholecystectomy with liver biopsy was performed. On pathology, the gallbladder was found to have chronic, active follicular cholecystitis with cholelithiasis. Percutaneous needle liver biopsy revealed the following: focal, mild periductal fibrosis, mild portal fibrosis with minimal mixed micro- and macrovesicular steatosis, and no significant steatohepatitis. CLINICAL DISCUSSION: To the best of our knowledge, this is the first documented case of follicular cholecystitis with associated hepatic findings on pathology. Follicular cholecystitis is strongly associated with extrahepatic biliary obstruction distal to the gallbladder, but it has not been previously associated with liver fibrosis. We hope to bring awareness to this rare but significant pathology. CONCLUSION: Our case is unusual due to the findings of hepatic periductal fibrosis with follicular cholecystitis. Follicular cholecystitis is strongly associated with extrahepatic biliary obstruction distal to the gallbladder but it has not been documented it to be associated with any hepatic findings or pathology.