Oxidative metabolic responses of rabbit pulmonary alveolar macrophages

During phagocytosis of opsonized lipopolysaccharide-coated paraffin oil droplets, rabbit alveolar macrophages reduced nitroblue tetrazolium, which effect was in part inhibitable with the use of superoxide dismutase. Exposure of cytochalasin-B-treated rabbit alveolar macrophages to opsonized zymosan led to the generation of superoxide, as quantitated by ferricytochrome C reduction. It was found that nitroblue tetrazolium in the presence of ferricytochrome C could in turn serve as scavenger of superoxide during stimulation of cytochalasin-B-treated rabbit alveolar macrophages. Following challenge with either opsonized zymosan or the membrane perturbant digitonin, rabbit alveolar macrophages released hydrogen peroxide into the extracellular medium. Employment of the surface membrane stimulant phorbol myristrate acetate led to activation of the hexose monophosphate shunt, which activity could be further enhanced in the presence of superoxide dismutase or attenuated in the presence of catalase. These studies demonstrate that rabbit alveolar macrophages release superoxide and hydrogen peroxide during surface membrane perturbation. In turn, hydrogen peroxide generation can stimulate the hexose monophosphate shunt.     

A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function

The role of the cardiac myocyte as a mediator of paracrine signaling in the heart has remained unclear. To address this issue, we generated mice with cardiac myocyte-specific deletion of the vascular endothelial growth factor gene, thereby producing a cardiomyocyte-specific knockout of a secreted factor. The hearts of these mice had fewer coronary microvessels, thinned ventricular walls, depressed basal contractile function, induction of hypoxia-responsive genes involved in energy metabolism, and an abnormal response to beta-adrenergic stimulation. These findings establish the critical importance of cardiac myocyte-derived vascular endothelial growth factor in cardiac morphogenesis and determination of heart function. Further, they establish an adult murine model of hypovascular nonnecrotic cardiac contractile dysfunction.     

Irradiation induces release of von Willebrand protein from endothelial cells in culture

Human umbilical vein endothelial cells in tissue culture were irradiated with doses between 0 and 40 Gy, and the released von Willebrand (vW) protein and that which remained associated with the cells was quantitated. Doses of 20 Gy and higher produced a statistically significant increase in amount of vW protein secreted. This release was present whether the cells were labeled continuously throughout the experiment or just prelabeled before irradiation. An increase in fibronectin secretion was not observed. The release response to radiation was slow, reaching significance close to 24 hours after irradiation. The release of vW protein was not due to cell lysis, because the secreted vW protein contained very little of the large 260- kilodalton vW precursor subunit present in cell lysates and the cells appeared intact by immunofluorescence staining.     

Cost analysis and outcome of endoscopic submucosal dissection for colorectal lesions in an outpatient setting

Background and study aims

Endoscopic submucosal dissection (ESD), a minimally invasive treatment for early gastrointestinal (GI) cancer, is considered challenging and risky in the colorectum. As such, most patients undergoing ESD are hospitalized due to the perceived increased risk of adverse events. The aim of this study was to compare the costs, safety and efficacy of colorectal-ESD in an outpatient vs inpatient setting in a tertiary level center.

A 2D Echo color-Doppler study of the extracranial carotid arteries in borderline arterial isolated systolic hypertension

BACKGROUND: The aim of this study was to evaluate the prevalence of atherosclerotic carotid lesions in isolated systolic borderline arterial hypertension by 2D echo color-Doppler and effect of night-time pressure fall by ambulatory blood pressure monitoring. METHODS: Outpatients from January 1992 to December 1998 were examined. One hundred and twenty normotensive control subjects and 99 isolated systolic borderline untreated hypertensives were studied, based on blood pressure fall were divided into dippers, with nocturnal systolic and/or diastolic blood pressure fall of >10%, and non dippers. Subjects with ischemic heart disease, valvulopathies, heart failure, renal insufficiency, cerebrovasculopathies, hypercholesterolemia (total cholesterol >200 mg/dl) and diabetes. Normotensives and hypertensives were homogenous for cardiovascular risk factors. A thickness of =/> 0.95 mm, calculated as a mean of 5 measurements of the common carotid artery, 2-3 cm from the carotid bifurcation, was considered a sign of myointimal thickening, and the plaque as a focal thickening of =/> 2 mm, based on echogenic characteristics and site. RESULTS: Compared to normotensives, isolated systolic borderline hypertensives, showed carotid arteries with an intima-media thickening (p=0.002) with one or more plaques (p=0.0001) much more frequently, while normal carotid arteries (p=0.0001) were less frequent. In normotensives, like in hypertensives, the prevalence of vasal lesions was not significantly different in dippers compared with non dippers. Plaques were most often localized at level of the common carotid and lesions were hard. CONCLUSIONS: The conclusions is drawn that isolated systolic hypertension is the sign of major vascular atherosclerotic lesions. The night-time pressure fall does not affect the importance of the lesions.     

5-Aza-2''-deoxycytidine induces terminal differentiation of leukemic blasts from patients with acute myeloid leukemias

In this study, the effects of 5-aza-2'-deoxycytidine on differentiation of human leukemic cells in primary suspension culture are reported for the first time. Morphological and functional differentiation was induced in cells from two acute monoblastic leukemias and two of three acute myeloid leukemias following repeated exposures to 1 mumol/L 5-aza- 2'-deoxycytidine. The observation that nontoxic concentrations of the drug are able to induce the in vitro differentiation of both monoblastic and myeloblastic leukemic cells into mature elements may encourage the exploitation of the differentiating properties of 5-aza- 2'-deoxycytidine in chemotherapy protocols for acute non-lymphoblastic leukemias.     

Congestive heart failure in the elderly

Several aspects of congestive heart failure are discussed in the light of international literature and of recent findings of our group. The annual incidence of heart failure in elderly subjects, aged >or=75y, is 13 to 50/1000, while it is 1.6/1000 in people aged 45-54 y. The prevalence of heart failure is about 3% in subjects aged 45-64% in subjects aged more than 65 y and 10% in subjects aged more than 75 y. These data are confirmed by our population based study in elderly subjects. The etiology of congestive heart failure is similar in elderly and middle-aged patients. However, several anatomo-functional, hormonal and autonomic nervous system changes, typical of congestive heart failure, occur during physiologic ageing processes also. These findings may explain the dramatic evolution of congestive heart failure in elderly patients. Moreover, some features of the elderly - e.g. comorbidity, atypical clinical presentations, loss of autonomy, increased iatrogen risk should be considered. No specific drugs exist for the pharmacologic treatment of heart failure in the elderly, so that the geriatric specificity in the treatment of heart failure can be recognized in the art of drug choice and dosage, to obtain the best results with the least side effects. The multiple etiology of congestive heart failure, the comorbidity, the loss of autonomy and the deterioration of cognitive functions suggest the need for multidimensional approach and continuative intervention in elderly patients with heart disease, and in particular with congestive heart failure. Further studies on disease- and age-related changes are necessary to develop new and more potent strategies to secure 'successful ageing'.