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.     

Retroperitoneal leiomyosarcoma mimicking acute appendicitis: laparoscopic management.

BACKGROUND: Retroperitoneal leiomyosarcomas (RLMS) are a challenging clinical entity. The vast majority of patients are operated on when tumors are advanced. We report herein a case of RLMS, mimicking acute appendiceal disease and treated successfully via laparoscopy. METHODS: A 37-year-old woman, para 1, was admitted to our department for right lower quadrant abdominal pain, fever, and leukocytosis. She had no changes in gastrointestinal and urologic function. A physical examination revealed the presence of abdominal guarding, rebound, and a tender mass in the right lower quadrant. The abdominal ultrasound showed an inhomogeneous ovoid mass (6 cm in diameter) located below the cecum, with no definite margins, and consistent with an appendiceal abscess. The patient was referred for laparoscopy. The procedure was performed with the aid of 3 ports: a 12-mm trocar in the umbilicus (open technique), a 10-mm trocar in the left iliac fossa, and a 5-mm one in the supra-pubic space. On inspection of the abdominal cavity, a retroperitoneal 6-cm mass was immediately found below the cecum and the appendix. Neither intraperitoneal seeding nor suspected lymph nodes were present. After dissection of the parietal peritoneum, the mass appeared to be encapsulated and well demarcated from all surrounding structures. It was eventually dissected and removed via a plastic bag. A standard appendectomy was also performed. The postoperative course was uneventful, and the patient was discharged on the 3rd day. The histology analysis of the resected specimen showed a totally excised G2 leiomyosarcoma. The appendix had no signs of inflammation. Postoperatively, the patient underwent a total-body CT-scan, which had no signs of residual or distant disease. No adjuvant therapy was necessary. At an 18-month follow-up, the patient was doing well and was disease free. CONCLUSION: Surgery represents the main therapeutic option for resectable RLMS. Laparoscopy is a useful diagnostic tool that allows safe resection of incidentally discovered, small and well encapsulated RLMS.     

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.     

Autoamputation of the foot caused by untreated gas gangrene: a case report

Gas-producing diabetic foot infections are limb-threatening emergencies commonly encountered by foot and ankle surgeons. Appropriate treatment includes aggressive surgical debridement, parenteral antibiotics, and postoperative wound care. The authors present a unique case of a patient who refused treatment for a deep-space gas-producing infection, resulting in autoamputation of the foot. The authors also discuss the confusion surrounding the definition of gas gangrene.     

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.