Microcystin-LR induces angiodysplasia and vascular dysfunction through promoting cell apoptosis by the mitochondrial signaling pathway.

The harmful algal blooms are becoming increasingly problematic in the regions that drinking water production depends on surface waters. With a global occurrence, microcystins are toxic peptides produced by multiple cyanobacterial genera in the harmful algal blooms. In this study, we examined the effects of microcystin-LR (MC-LR), a representative toxin of the microcystin family, on vascular development in zebrafish and the apoptosis of human umbilical vein endothelial cells (HUVECs). In zebrafish larvae, MC-LR induced angiodysplasia, damaged vascular structures and reduced lumen size at 0.1 µM and 1 µM, leading to the decrease of the blood flow area in the blood vessels and brain hemorrhage, which showed that MC-LR could dose-dependently inhibit vascular development and cause vascular dysfunction. In MC-LR treated HUVECs, the proportion of early apoptosis and late apoptosis cells increased in a concentration-dependent manner. Different concentrations of MC-LR could also activate caspase 3/9 in HUVECs, increase the level of mitochondrial ROS and reduce mitochondrial membrane potential. Additionally, MC-LR could promote the expression of p53 and inhibit the expression of PCNA. The findings showed that MC-LR could promote apoptosis of HUVECs through the mitochondrial signaling pathway. Combined with these results, MC-LR may promote vascular endothelial cell apoptosis through mitochondrial signaling pathway, leading to angiodysplasia and vascular dysfunction.

Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran.

BACKGROUND AND AIM: Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. METHODS: Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). RESULTS: Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). CONCLUSIONS: In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.

[Coronary thrombosis and ectasia of coronary arteries after long-term use of anabolic steroids]. / Koronarthrombosen und -ektasien nach langjähriger Einnahme von anabolen Steroiden.

Chronic abuse of anabolic steroids is widespread. Hypertrophy of skeletal and heart muscle is a well-known effect of chronic anabolic steroid abuse. Structural alterations of blood vessels are new side effects. We report a case of a 32-year-old bodybuilder after long-term use of anabolic steroids who died of cardiac arrest. Coronary angiography and autopsy findings showed especially a hypertrophic heart, structural changes of coronary arteries, intracoronary thrombosis and myocardial infarction, ventricular thrombosis and systemic embolism

[Successful emergency operation for massive hemorrhage due to jejunal angiodysplasia after intensive chemotherapy in a patient with refractory anemia with excess of blasts].

A 59-year-old man was referred to our hospital because of pancytopenia. Peripheral blood examination showed a WBC of 1,500/microliters with 2% blasts, Hb 8.1 g/dl and a platelet count of 4.1 x 10(4)/microliters. A bone marrow aspiration revealed hyperplasia with proliferation of blasts (15.7%) and myelodysplasia. Chromosome analysis revealed multiple aberrations, including -5, -7, +8. The patient was given a diagnosis of refractory anemia with excess of blasts (RAEB) and treated with combination chemotherapy. Agranulocytosis and high fever remained after chemotherapy, and abdominal pain and diarrhea developed. An abdominal X-ray film and computed tomography scan demonstrated dilated small bowel, thickness of the bowel wall, and ascites. A diagnosis of neutropenic enterocolitis was given. During the WBC recovery period from nadir, massive hematochezia developed in the patient. Angiography detected the leakage of contrast medium from a peripheral region of the first jejunal artery into the jejunal lumen. A partial resection of the jejunum was thus performed, and a histological examination revealed the presence of irregularly dilated blood vessels in the submucosal layer. These findings were consistent with the features of angiodysplasia, and indicate that angiodysplasia should be considered one cause of intestinal hemorrhage in elderly patients during intensive chemotherapy.