Expression of inhibitors of apoptosis family protein in 7,12-dimethylbenz[a]anthracene-induced hamster buccal-pouch squamous-cell carcinogenesis is associated with mutant p53 accumulation and epigenetic changes

Fifty outbred Syrian golden hamsters were equally divided into three experimental groups and two control groups. The pouches of the experimental groups were painted bilaterally with a 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) solution thrice a week for 3, 7 and 14 weeks. One of the control groups was applied with mineral oil while another control group remained untreated throughout the experiment. Neither survivin nor cIAP2 could be detected in any of the control tissues, whereas survivin and cIAP2 were found to be significantly increased in 3-, 7- and 14-week DMBA-treated pouches compared with the control pouches. Expression of XIAP, cIAP1 and NAIP were noted for both the control and 3-, 7- and 14-week DMBA-treated pouches, but levels were found to be significantly elevated in the experimental groups compared with the control pouches. p53 was not detected in any control tissues, but was significantly increased in 3-, 7- and 14-week DMBA-treated pouches. Direct sequencing revealed a point mutation (C-->G) of p53 for pouch tissues treated with DMBA for 3 and 7 weeks, and there was a wide variation in the p53 sequence of the 14-week DMBA-treated pouch tissues, as compared with the control tissues. The control tissues had a survivin- and cIAP2-methylated allele, whereas the DMBA-treated tissues showed no evidence of survivin- and cIAP2-methylation. Neither the control nor DMBA-treated pouches showed evidence of XIAP-, cIAP1- or NAIP-methylation. Our results suggest that the expression of inhibitors of apoptosis family in DMBA-induced hamster buccal-pouch squamous-cell carcinogenesis may be modulated by both genetic (mutant p53) and epigenetic mechanisms.     

Accumulation of technetium-99m glucarate: in vitro cell cultures and in vivo tumour models

99mTc-glucarate is an investigational radiopharmaceutical which has been shown to accumulate in acute cerebral and myocardial injuries and in some tumours. In the present work, a survey of possible factors affecting the cellular accumulation of 99mTc-glucarate was carried out in cell lines and strains in vitro and in murine tumours in vivo. Accumulation was enhanced under hypoxic conditions in 12 of the 16 human and murine cell lines and strains studied, and inhibited in the presence of nitroimidazoles. At temperatures lower than 37 degrees C, accumulation was reduced, but a hypoxic/aerobic differential was maintained. Aerobic accumulation of 99mTc-glucarate was enhanced by cyanide. In transplanted tumours in mice, 99mTc-glucarate showed high tumour/muscle and tumour/blood ratios at early times after injection. Pharmacological enhancement of the extent of hypoxia by the administration of hydralazine or nitro-L-arginine resulted in significantly increased accumulation of 99mTc-glucarate in the tumour. The in vitro and in vivo properties of 99mTc-glucarate suggest that it may be useful for tumour imaging in the clinic, although the exact mechanism(s) by which it localizes in tumours remains unknown.     

Dural cavernous angioma mimicking a meningioma and causing facial pain.

An 18-year-old girl who had severe headaches in the left temporal and facial regions was found to have a small enhanced dural-based parietal convexity mass. On magnetic resonance imaging (MRI), this mass was homogeneously enhanced with "dural tail sign," and was similar to a meningioma. This mass was completely removed surgically, and pathology proved it to be a cavernous angioma without previous hemorrhages. The patient's facial pain was dramatically relieved after surgery. A small dural mass causing severe facial pain is an unusual situation. The lack of hemosiderin in the extra-axial cavernous angioma often leads to the preoperative diagnosis of meningioma.     

Diastolic Dysfunction in Individuals With Human Immunodeficiency Virus Infection: Literature Review,Rationale and Design of the Characterizing Heart Function on Antiretroviral Therapy (CHART) Study

Antiretroviral therapy (ART) has been associated with a shift in the epidemiology of human immunodeficiency virus (HIV)–associated cardiomyopathy from a phenotype of primarily left ventricular (LV) systolic dysfunction to LV diastolic dysfunction (DD). Patients with HIV receiving ART have higher rates of DD compared with age-matched control subjects and develop DD at a younger age. However, little is known about the natural history and pathogenesis of DD in virally suppressed HIV-infected patients. Current evidence suggests that immune processes modulate the risk for cardiac involvement in HIV-infected persons. Ongoing inflammation appears to have myocardial effects, and accelerated myocardial fibrosis appears to be a key mediator of HIV-induced DD. The Characterizing Heart Function on Antiretroviral Therapy (CHART) study aims to systematically investigate determinants, mechanisms, and consequences of DD in HIV-infected patients. We will compare ART-treated virally suppressed HIV-infected individuals with and without DD and HIV? individuals with DD regarding (1) systemic inflammation, myocardial stress, and subclinical myocardial necrosis as indicated by circulating biomarkers; (2) immune system activation as indicated by cell surface receptors; (3) myocardial fibrosis according to cardiac magnetic resonance examination; (4) markers of fibrosis and remodeling, oxidative stress, and hypercoagulability; (5) left atrial function according to echocardiographic examination; (6) myocardial stress and subclinical necrosis as indicated by circulating biomarkers; (7) proteomic and metabolic profiles; and (8) phenotype signatures derived from clinical, biomarker, and imaging data.     

Hemodynamic and arrhythmogenic effects of cocaine in hypertensive individuals

J Clin Hypertens (Greenwich). 2011;13:744–749. ©2011 Wiley Periodicals, Inc. Despite the increased risk of myocardial infarction, aortic dissection, and arrhythmias in patients with hypertension who use cocaine, the hemodynamic and arrhythmogenic effects of cocaine use have not been well characterized in this population. The authors hypothesized that patients with hypertension demonstrate extreme, transient changes in arterial pressures as well as new arrhythmic activity during cocaine use. Ambulatory blood pressures, heart rates, and electrocardiograms (AECGs) were recorded for 48 hours in 10 patients with a history of hypertension who smoke cocaine. Active cocaine use was identified through patient diaries and manual activation of the blood pressure cuff. Of the 10 patients studied (6 men, 7 African Americans, age 49±8 years), 8 were taking antihypertensive medications. The mean blood pressure prior to cocaine use was 126/77 mm Hg and average increase in systolic, diastolic, and mean arterial pressure after use was 74 mm Hg, 30 mm Hg, and 45 mm Hg, respectively (P<.0001 for all). There was no significant change in heart rate. AECGs demonstrated arrhythmic activity during cocaine use, including 6 patients with increased atrial and ventricular ectopy, 2 patients with episodes of nonsustained atrial tachycardia, and 1 patient with 3 episodes of nonsustained monomorphic ventricular tachycardia. Cocaine use resulted in extreme elevations in arterial pressures in patients with hypertension taking medication. Cocaine use was also associated with an increase in arrhythmic activity. These findings may underlie the heightened risk of myocardial infarction, aortic dissection, and potentially lethal arrhythmias in patients with hypertension who use cocaine.     

Antibiotic desensitization therapy in secondary syphilis and Listeria infection: case reports and review of desensitization therapy

Two adult cases, one of secondary syphilis and one of Listeria monocytogenes bacteremia, in which antibiotic desensitization therapy was utilized to assist treatment of active infection in the face of severe penicillin allergy. Clinical considerations are discussed that led to the decision to employ a formal desensitization procedure. Antibiotic desensitization protocols can facilitate optimal and safe antibiotic therapy in the appropriate clinical setting.