Oxidative metabolism of lung macrophages exposed to sodium arsenite

Arsenic pollution has become increasingly severe. It occurs as the result of geological processes and different human activities. Arsenic toxicity at the respiratory level occurs mainly by inhalation of products of coal combustion. The aim of this study was to evaluate sodium arsenite (As³⁺) toxicity in murine alveolar macrophages (AMs) in vitro and its association with the alterations in cell metabolism.

No changes in viability, apoptosis or cell area were detected in AMs treated with As³⁺ concentrations up to 2 μM for 24–96 h. A marked decrease in these end-points was observed for As³⁺ concentrations ranging from 2.5 μM to 10 μM.

Regarding the dynamics of the endo-exocytic process triggered by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell incorporation, no variations were detected for As³⁺ concentrations lower than 2 μM while higher concentrations markedly modified this response.

MTT specific activity, as a measure of cell metabolic activity, was not modified irrespective of the As³⁺ concentration assayed. However, nitroblue tetrazolium (NBT) specific activity, as a measure of superoxide anion generation, is responsive but only to low As³⁺ doses.

Although this study focuses on lung macrophages, the effects of As³⁺ described herein may also apply to the response of macrophages residing in other organs.

Arsenite modifies the metabolic and the oxidative status of AMs in vitro. When macrophages are in an As³⁺ rich medium, they exhibit a reduction in respiratory burst levels and lose their intrinsic capacity to respond to toxicants.     

Upregulation of epidermal growth factor receptor induced by alpha-interferon in human epidermoid cancer cells

Unregulated or increased expression of epidermal growth factor receptor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant alpha-interferon (IFN-alpha). After 48 h of treatment, IFN-alpha induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [125I]EGF total binding assessed after 48 h of treatment with IFN-alpha shows a dose-dependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-alpha treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-alpha only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [35S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-alpha consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies.     

Morphometric evidence of the trophic effect of L-carnitine on human skeletal muscle

We investigated the effect of long-term i.v. administration of L-carnitine on human muscle fibers using morphometric parameters. We administered 2g/day L-carnitine to patients undergoing hemodialysis for at least 12 months. At the end of this period a marked increase in serum and muscle carnitine levels was observed in all patients, together with hypertrophy and predominance of type 1 fibers. L-carnitine was withheld for 4 months, during which time serum and muscle levels gradually decreased and no changes were observed in muscle fibers. Subsequent addition of L-carnitine to dialysis fluid for another 4 months stabilized lower levels. At the end of this period reduction of diameter of type 1 fibers was observed. Type 2 fibers remained unchanged. Moreover, type 1 fibers remained predominant in all cases. Hence, we suggest that carnitine has a specific trophic effect on type 1 fibers which are characterized by an oxidative metabolism.     

Synthesis and anti-microbial activity of benzo-condensed heterocyclic derivatives

The synthesis of 2,4-dione derivatives of 1,5-benzodithiepine, 1,5-benzodiazepine and 1,5-benzothiazepine and the anti-microbial activity in vitro of these derivatives and of analogous of 1,5-benzodioxepine, 1,5-benzoxathiepine and 1,5-benzoxazepine, previously prepared, are reported. Some of these compounds showed a good activity against some Gram positive microorganisms and blastomycetes.     

The role of donor and recipient factors in initial renal graft non-function

ATN is a deleterious problem in the outcome of kidney transplantation. This complication is usually related to multiple factors including donor parameters, surgical technique, ischemic time, and recipient variables. In order to develop prophylactic measures, out of 430 kidney transplants performed in our Department, a series of 90 consecutive cadaveric renal allografts has been considered in this study. The overall incidence of IGNF was 23/90 (25.5%). Kidneys from MOD revealed a lower rate of IGNF (7/35 = 20%) when compared with organs from SOD (16/55 = 29%, P = NS). No difference was noted when kidneys were removed together with heart and/or liver and/or pancreas. Out of the donor factors, only CID was significant (17 +/- 9 hours in IGNF v 11 +/- 10 hours in patients with IGF, P = less than .05). Analysis of data concerning the fate of paired kidneys revealed two cases of IGNF in both kidneys from the same donor v 14 cases of IGNF in only one of the two paired grafts (P = NS). We conclude that: 1. Donor factors are clearly associated with a minority of IGNF. 2. The introduction of multiorgan procurement programs does not complicate early function. 3. Recipient factors (immunological events and intraoperative fluid management) provides important additive effects on initial graft nonfunction.     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.     

In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Stapled Hemorrhoidopexy: A Prospective Study From Pathology to Clinical Outcome

Stapled hemorrhoidopexy is widely accepted to treat hemorrhoids, but serious complications have been reported. In this prospective audit, we correlated clinical outcome with pathological findings. From January 2003 to April 2007, 94 patients underwent hemorrhoidopexy. Macroscopic appearance of the specimen (shape, size, and depth) was recorded. Microscopically, the presence of columnar, transitional, and squamous epithelium, the involvement of circular/longitudinal smooth muscle, and features of mucosal prolapse were assessed. Clinical outcome was evaluated by a validated questionnaire. Postoperative pain, secretion, and bleeding durations were 12.7 +/− 10.6, 5.6 +/− 9.6, and 6.3 +/− 8.4 days. Patient’s return to work averaged 16.7 +/− 10.7 days. Fissure, skin tags, and anal strictures were observed in 23.4%. Seven patients experienced pain for a significantly longer period of time. All specimens contained columnar mucosa, but 29.8% contained columnar and transitional epithelium and 12.8% contained columnar, anal transitional, and stratified squamous epithelium. Smooth muscle was observed in 62.7%. Pain was significantly increased if transitional epithelium was present in the specimen. No correlation or differences were observed if smooth muscle was present, although postoperative bleeding was more frequent. Hemorrhoidopexy is safe and effective. The specimen should always be sent for pathology examination. Only columnar epithelium should be present and, although the presence of smooth muscle does not influence the outcome in terms of functional results, its presence may play a role in postoperative bleeding. Presented as poster at the Digestive Disease Week, May 2007, Washington, USA