Mitochondrial compromise in 3‐year old patas monkeys exposed in utero to human‐equivalent antiretroviral therapies

Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother‐to‐child transmission of human immunodeficiency virus 1 (HIV‐1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15‐year old human) after exposure of the dams to human‐equivalent in utero ARV exposure protocols. Pregnant patas dams (3–5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation. Infants kept for 1 and 3 years also received drug for the first 6 weeks of life. In offpsring at birth, 1 and 3 years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (P < 0.05), but not in those exposed to AZT/3TC/ABC at any age. Compared to unexposed controls, mitochondrial reserve capacity oxygen consumption rate (OCR by Seahorse) in cultured bone marrow mesenchymal fibroblasts from 3‐year‐old patas offspring was ～50% reduced in AZT/3TC/ABC‐exposed patas (P < 0.01), but not in AZT/3TC/NVP‐exposed patas. Overall the data show that 3‐year‐old patas sustain persistent mitochondrial dysfunction as a result of perinatal ARV drug exposure. Environ. Mol. Mutagen. 57:526–534, 2016. © 2016 Wiley Periodicals, Inc.     

Erratum: Correction of Nomenclature of Mutations

[This corrects the article on p. 1111 in vol. 26, PMID: 21860566.].     

A Large Retroperitoneal Encapsulation of Bile from a Spontaneous Perforation of the Common Bile Duct

We report a patient with spontaneous rupture of the common bile duct. This is an extremely rare condition which produces free leakage of bile into the peritoneal cavity. There has been no previous report concerning the formation of a large retroperitoneal encapsulation of bile. The preoperative diagnosis in our patient was very difficult and endoscopic retrograde pancreatocholangiography and cystography by ultrasound guidance were helpful.     

Successful defibrotide treatment of a patient with veno-occlusive disease after living-donor liver transplantation: A case report

Rationale:Veno-occlusive disease (VOD) is characterized by painful hepatomegaly, ascites, weight gain, and jaundice with nonthrombotic, fibrous obliteration of the centrilobular hepatic veins. VOD after liver transplantation is a rare complication, with an incidence of approximately 2%; however, it can be life-threatening in severe cases. The precise etiology and mechanism of VOD after liver transplantation remains unclear. Acute cellular rejection, antibody-mediated rejection, and treatment with tacrolimus or azathioprine may be associated with the development of VOD after liver transplantation. Additionally, the optimal treatment of VOD after liver transplantation has not yet been established and focuses on supportive care. Defibrotide is an anti-ischemic and antithrombotic drug with no systemic anticoagulant effects. Moreover, only a few reports have investigated the use of defibrotide for VOD after liver transplantation, which has shown promising results.Patient concerns:A 39-year-old woman with primary biliary cholangitis underwent living-donor liver transplantation at our center. She experienced right upper quadrant pain with increased ascites, pleural effusion, and weight gain on postoperative day 14.Diagnoses:Imaging and pathological tests showed no evidence of rejection or vessel complications. VOD was diagnosed clinically based on the findings of weight gain, ascites, jaundice, and pathological biopsy.Interventions:Defibrotid, 25 mg/kg/day, was administered intravenously for 21 days.Outcomes:She showed complete clinical resolution of the VOD.Lessons:Herein, we report a case of successful defibrotide treatment of VOD after living-donor liver transplantation.