Attenuation of azoxymethane-induced colonic mucosal ornithine decarboxylase and tyrosine kinase activity by calcium in rats

Two in vivo and one in vitro studies were performed to evaluate the chemoprotective role of calcium during the early period of azoxymethane (AOM) induction. In the first set of experiments, groups of male Fischer 344 rats were s.c. injected with either AOM (20 mg/kg) or water (controls) and sacrificed immediately (0 time), and 1, 3, 5, and 7 days postinjection. In the second set of experiments, animals were injected with the same dose of AOM and subsequently pair-fed with rat chow containing either calcium carbonate or diet devoid of added calcium. The amount of calcium consumed was calculated to be 250 mg/kg b.w. In both experiments, colonic mucosa was assayed for ornithine decarboxylase (ODC). In addition, tyrosine kinase (Tyr-k) activity as well as tyrosine specific phosphorylation of membrane proteins were determined. Results revealed that maximal stimulation by AOM of ODC and Tyr-k activity occurred 5 days postinjection. This stimulation was significantly suppressed by calcium. AOM also produced an increase in the rate of tyrosine specific phosphorylation of two distinct colonic mucosal membrane proteins with Mr of 57,000 and 59,000. Again, dietary calcium suppressed the stimulation. In the third set of experiments, organ culture was utilized. Methylazoxymethanol, the active metabolite of AOM, was used instead of AOM in this part of the study. Four hour exposure of mucosal explants to methylazoxymethanol (1 microgram/ml) resulted in a significant (20-30%) increase in ODC and Tyr-k activity when compared to controls. Addition of either CaCl2 (2 mumol/ml) or difluoromethylornithine (2 nmol/ml) the irreversible inhibitor of ODC, significantly suppressed the methylazoxymethanol-induced activity of both ODC and Tyr-k. We conclude that calcium may have a chemoprotective role and tyrosine kinases may have a regulatory role in the early stages of AOM induction of colon cancer.     

Recurrent ventricular fibrillation during a febrile illness as the first manifestation of Brugada syndrome--a case report

A case of a 33-year-old male who was admitted to the hospital due to recurrent ventricular fibrillation during a febrile illness is presented. Initially, the patient was diagnosed with acute myocardial infarction and received thrombolytic treatment. Echocardiography and coronary angiography were normal. Right precordial ECG leads recorded one and two intercostal spaces higher than normal as well as ECG obtained following ajmaline administration revealed a typical Brugada pattern.     

X-ray-visible microcapsules containing mesenchymal stem cells improve hind limb perfusion in a rabbit model of peripheral arterial disease

The therapeutic goal in peripheral arterial disease (PAD) patients is to restore blood flow to ischemic tissue. Stem cell transplantation offers a new avenue to enhance arteriogenesis and angiogenesis. Two major problems with cell therapies are poor cell survival and the lack of visualization of cell delivery and distribution. To address these therapeutic barriers, allogeneic bone marrow-derived mesenchymal stem cells (MSCs) were encapsulated in alginate impregnated with a radiopaque contrast agent (MSC-Xcaps). In vitro MSC-Xcap viability by a fluorometric assay was high (96.9% ± 2.7% at 30 days postencapsulation) and as few as 10 Xcaps were visible on clinical x-ray fluoroscopic systems. Using an endovascular PAD model, rabbits (n = 21) were randomized to receive MSC-Xcaps (n = 6), empty Xcaps (n = 5), unencapsulated MSCs (n = 5), or sham intramuscular injections (n = 5) in the ischemic thigh 24 hours postocclusion. Immediately after MSC transplantation and 14 days later, digital radiographs acquired on a clinical angiographic system demonstrated persistent visualization of the Xcap injection sites with retained contrast-to-noise. Using a modified TIMI frame count, quantitative angiography demonstrated a 65% improvement in hind limb perfusion or arteriogenesis in MSC-Xcap-treated animals versus empty Xcaps. Post-mortem immunohistopathology of vessel density by anti-CD31 staining demonstrated an 87% enhancement in angiogenesis in Xcap-MSC-treated animals versus empty Xcaps. MSC-Xcaps represent the first x-ray-visible cellular therapeutic with enhanced efficacy for PAD treatment.