Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos

Oxidative damage is a proposed mechanism of asbestos-induced carcinogenesis, but the detection of oxidative DNA lesions in target cells of asbestos-induced mesothelioma has not been examined. In studies here, DNA was isolated from both rat pleural mesothelial (RPM) cells and a human mesothelial cell line (MET5A) after exposure in vitro to crocidolite asbestos at various concentrations. DNA was then examined for formation of 8-hydroxydeoxyguanosine (8-OHdG) at 24, 48 and 72 h using HPLC with electrochemical detection. In addition, steady- state mRNA levels of manganese-containing superoxide dismutase (MnSOD) were assessed as an indication of oxidative stress. Whereas RPM cells showed dose-dependent and significant increases in 8-OHdG formation in response to crocidolite asbestos or iron-chelated crocidolite fibers (but not after exposure to glass beads), MET5A cells showed decreases in 8-OHdG. Both cell types exhibited elevations in message levels of MnSOD. In comparison with human MET5A cells, RPM cells exhibited increased cytotoxicity and apoptosis in response to asbestos, as documented by cell viability assays and flow cytometry analysis using propidium iodide. Results in RPM cells indicate that asbestos causes oxidative damage that may result in potentially mutagenic lesions in DNA and/or apoptosis, despite compensatory increases in expression of an antioxidant enzyme.      

Blue toe syndrome: treatment with percutaneous atherectomy

"Blue toe syndrome" refers to digital ischemia of the foot in the presence of palpable or Doppler audible pedal pulses. This clinical syndrome is caused by microembolization to small vessels from a proximal source. The use of percutaneous transluminal atherectomy is described in the treatment of embologenic superficial femoral artery lesions in seven patients. All seven had prompt healing of the ischemic toes, and none required surgical revascularization or amputation. One patient developed a recurrent stenosis at the atherectomy site and had a second episode of digital ischemia, which was treated by means of atherectomy with a larger device. Histologic study of atherectomy specimens suggests that emboli arise from adherent fibrinoplatelet aggregates or thrombus and less often from cholesterol-rich atheromatous plaque. Although either percutaneous transluminal angioplasty or atherectomy can be used to treat the underlying stenosis, percutaneous atherectomy offers the advantage of nonsurgical removal of embologenic material and provides material for histologic study. Percutaneous atherectomy is an effective method of treating embologenic superficial femoral stenoses in patients with ipsilateral blue toe syndrome.     

Polyanalgesic Consensus Conference—2012: Consensus on Diagnosis,Detection, and Treatment of Catheter‐Tip Granulomas (Inflammatory Masses)

Introduction: Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications. Methods: The Polyanalgesic Consensus Conference is a meeting of a group of well‐published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas. Results: The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas. Conclusion: The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space‐occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain.     

Polyanalgesic Consensus Conference—2012: Recommendations to Reduce Morbidity and Mortality in Intrathecal Drug Delivery in the Treatment of Chronic Pain

Introduction: Targeted intrathecal drug infusion to treat moderate to severe chronic pain has become a standard part of treatment algorithms when more conservative options fail. This therapy is well established in the literature, has shown efficacy, and is an important tool for the treatment of both cancer and noncancer pain; however, it has become clear in recent years that intrathecal drug delivery is associated with risks for serious morbidity and mortality. Methods: The Polyanalgesic Consensus Conference is a meeting of experienced implanting physicians who strive to improve care in those receiving implantable devices. Employing data generated through an extensive literature search combined with clinical experience, this work group formulated recommendations regarding awareness, education, and mitigation of the morbidity and mortality associated with intrathecal therapy to establish best practices for targeted intrathecal drug delivery systems. Results: Best practices for improved patient care and outcomes with targeted intrathecal infusion are recommended to minimize the risk of morbidity and mortality. Areas of focus include respiratory depression, infection, granuloma, device‐related complications, endocrinopathies, and human error. Specific guidance is given with each of these issues and the general use of the therapy. Conclusions: Targeted intrathecal drug delivery systems are associated with risks for morbidity and mortality that can be devastating. The panel has given guidance to treating physicians and healthcare providers to reduce the incidence of these problems and to improve outcomes when problems occur.     

Distribution of enteric glia and GDNF during gut inflammation

Background  

The enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. The aim of the study was to determine the distribution of EGCs and GDNF during gut inflammation and to elucidate a possible diminished enteric glia network in IBD.