Plocamenols A-C, novel linear polyhalohydroxylated monoterpenes from Plocamium cartilagineum

Three new minor linear polyhalohydroxylated marine monoterpenes, plocamenols A-C (1-3), have been isolated from the red alga Plocamium cartilagineum. The structure and relative stereochemistry of these compounds were determined on the basis of spectroscopic evidence.     

Ba2LnSbO6 and Sr2LnSbO6 (Ln = Dy,Ho, Gd) double perovskites: lanthanides in the geometrically frustrating fcc lattice

Magnetic ground states in solids often arise as a result of a delicate balance between competing factors. One currently active area of research in magnetic materials involves compounds in which long-range magnetic ordering at low temperatures is frustrated by the geometry of the crystalline lattice, a situation known as geometrical magnetic frustration. The number of systems known to display the effects of such frustration is growing, but those that are sufficiently simple from theoretical, chemical, and physical perspectives to allow for detailed understanding remain very few. A search for model compounds in this family has led us to the double perovskites Ba2LnSbO6 and Sr2LnSbO6 (Ln = Dy, Ho, and Gd) reported here. Ba2DySbO6,Ba2HoSbO6,Sr2DySbO6, and Sr2HoSbO6 are structurally characterized by powder neutron diffraction at ambient temperature. The trivalent lanthanides and pentavalent antimony are found to be fully ordered in the double-perovskite arrangement of alternating octahedra sharing corner oxygens. In such a structure, the lanthanide sublattice displays a classical fcc arrangement, an edge-shared network of tetrahedra known to result in geometric magnetic frustration. No magnetic ordering is observed in any of these compounds down to temperatures of 2 K, and in the case of the Dy-based compounds in particular, frustration of the magnetic ordering is clearly present. Lanthanide-based double perovskites are proposed to be excellent model systems for the detailed study of geometric magnetic frustration.     

ABO System: molecular mimicry of Ascaris lumbricoides

A. lumbricoides has been associated to the ABO System by various authors. The objective was to detect ABO System epitopes in A. lumbricoides of groups O, A, B and AB patients. 28 adult parasites were obtained from children to be used as assay material. The patients ABO blood groups were determined. Extracts of A. lumbricoides [AE] were prepared by surgical remotion of the cuticle and refrigerated mechanical rupture. Agglutination Inhibition (AI) and Hemoagglutination Kinetics (HK) tests were used with the [AE]. Of the 28 [AE], eight belonged to O group patients, 15 to A group, three to B group and the remaining two to AB children. The AI Test showed A epitopes in two [AE] of group A patients and B epitopes in two [AE] of group B patients. The HK Test showed B antigenic determiners in two [AE] of group B patients and in two [AE] of group AB patients as well as A antigenic determiners in one [AE] of A group patient. Of the 28 [AE] studied in both tests B epitopes were detected in all [AE] from B and AB patients and A epitopes in three of the 15 [AE] of group A patients. The experiments carried out suggest that A. lumbricoides might absorb A and B antigens from the host, and/or modify the cuticular carbohydrates expression as a kind of antigenic mimicry.     

Technique of intramedullary osteosynthesis of the clavicle with elastic titanium nails

This prospective controlled clinical trial was performed to assess fracture healing and clinical outcome after intramedullary nailing of midclavicular fractures. Within 3.5 years elastic-stable intramedullary nailing was performed in 62 patients with 65 midclavicular fractures. Surgery was performed in supine position. The ventral cortex of the proximal clavicle was opened using a 2.5 mm drill. The nail was advanced laterally under fluoroscopic control. If closed reduction failed, an additional incision was made to enable direct manipulation of the fragments. There were no infections, no implant displacements or refractures. Postoperatively, the mean subjective pain was significantly lower, and the range of motion improved. We observed one nonunion. The mean Constant-score 6 months after hardware removal was 96.9 +/- 3.3 points. Intramedullary fixation of midclavicular fractures with an elastic titanium nail is a safe minimally invasive surgical technique, producing excellent functional and cosmetic results.     

Apotransferrin decreases migration and enhances differentiation of oligodendroglial progenitor cells in an in vitro system

We have previously shown that a single intracranial injection of apotransferrin (aTf) in neonatal rats produces an accelerated mylinogenesis and increases the expression of certain myelin proteins such as myelin basic protein (MBP). In the present work, we studied the effects of aTf upon oligodendrocyte progenitor cell (Opc) cultures. In the presence of aTf, cells developed a multipolar morphology and showed an increased expression of O(4), MBP, O(1) and myelin-associated glycoprotein compared to controls. Migration studies using the agarose drop assay showed that aTf strongly inhibited OPc migration. This effect was not observed when an antibody against the transferrin receptor was added. The expression of two cell adhesion molecules, neural cell adhesion molecule (NCAM), N-cadherin and of polysialylated NCAM (PSA-NCAM) was evaluated by immunocytochemistry and by Western blot. Although NCAM expression did not change, there was a significant increase in N-cadherin expression and a decrease in PSA-NCAM in the aTf-treated cells. Time lapse studies of the expression of PSA-NCAM as an indicator of migration and of MBP as a marker of differentiation showed that in the cultures treated with aTf there is first a decrease in the percentage of cells expressing the former molecule which is followed by an increase in the percentage of cells expressing MBP. These results suggest that aTf added in vitro to cultured OPcs inhibits first their migration and then enhances their differentiation.     

Tumor cytosol carcinoembryonic antigen as prognostic parameter in non-small cell lung cancer

AIMS AND BACKGROUND: Carcinoembryonic antigen (CEA) belongs to a family of cell surface glycoproteins. Its level in serum has a significant value for the follow-up and treatment of patients with malignancies. The aim of this study was to correlate the concentration of tumor cytosol CEA (cCEA) with tumor size, patient age and sex, clinical stage, lymph node metastases, and overall survival rate in primary non-small cell lung carcinoma (NSCLC). METHODS AND STUDY DESIGN: The cCEA levels were determined in 76 NSCLC patients by luminescence assay (LIA) and radioimmunoassay (RIA). RESULTS: A strong correlation between LIA and RIA assay results was found (r = 0.992). No correlation was observed between serum CEA and cCEA levels. Tumors smaller than 3 cm had significantly higher cCEA levels than larger tumors, but when a logistic modeling process was applied this difference was not significant (P = 0.038). Histologically well-differentiated tumors also showed a significantly higher expression of cCEA (P <0.05). In addition, patients without lymph node involvement had higher cCEA levels than patients with tumor-positive lymph nodes (P < 0.05). Univariate statistical analysis revealed that the risk of lymph node metastases was 1.8-fold higher in patients with low cCEA levels than in patients with higher levels, taking the median value as cutoff (P = 0.04, Kruskal-Wallis test). CONCLUSIONS: According to the results of our study, patients with overexpression of cCEA may have a better prognosis than those with low cCEA expression. cCEA might therefore be considered a good prognostic parameter as well as a prognostic factor independent of the traditional parameters for lymph node metastases.     

Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide

Ewing sarcoma is the second most common bone tumor in childhood. Despite aggressive chemotherapy and radiotherapy strategies, the prognosis of patients with metastatic disease remains poor. We have recently reported that Ewing tumor cell proliferation was strongly inhibited by IFN-beta and to a lesser degree by IFN-alpha. Moreover, under IFN-beta treatment, some cell lines undergo apoptosis. Since the possibility of using IFNs for Ewing tumor treatments may be of interest, we have evaluated the efficacy of Hu-IFNs in a nude mice model of Ewing tumor xenografts. The results reported here show that human type I IFNs, Hu-IFN-alpha and Hu-IFN-beta impaired tumor xenograft take and displayed an anti-growth effect toward established xenografts. Furthermore, we have also shown that combined therapy with Hu-IFNs and ifosfamide (IFO), an alkylating agent widely used in high-dose chemotherapy of Ewing tumors, results in a strong antitumor effect. Pathological analysis showed that Hu-IFN-alpha/IFO and Hu-IFN-beta/IFO were characterized by a dramatic decrease in the mitotic index and marked necrosis, as well as extensive fibrosis associated with numerous calcifications. To our knowledge, this is the first demonstration of a potential antitumor effect of human type I IFNs and IFO on Ewing tumors, providing a rational foundation for a promising therapeutic approach to Ewing sarcoma.     

Comparative analysis of aggregate shapes by digitized microscopic images. Application to hypertension

The main objective of the present work was to study modifications in RBC aggregate morphology by analyzing digitized microscopic images and compare them between healthy subjects and patients suffering from essential hypertension. Blood samples were obtained from normal subjects (n=30) and patients suffering from essential hypertension (n=20). RBC aggregate morphology was quantified using direct microscopic observation and numerical analysis of images. ASP (Aggregation Shape Parameter) defined as the ratio of the area of the projected image to its square perimeter was calculated. Other rheological parameters have been determined in order to establish the hemorheological profile of the studied hypertension states. ASP appears significantly higher (p<0.001) in patients suffering essential hypertension (0.69+/-0.11) than in normal control subjects (0.25+/-0.12). RBC aggregation is known to be responsible for the high increase in apparent blood viscosity at low shear rates. By compare ASP values with whole blood viscosity at low rate (2.30 s(-1)) a high correlation was formed between both parameters (Spearman coefficient was 0.8835 and p<0.001). The applied method is simple, direct and quantitative and provides a useful tool for measuring deviations of RBC aggregate morphology.     

Inhibitory smads and tgf-Beta signaling in glomerular cells

Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-beta, receptor tyrosine kinase (RTK), JAK/STAT, and NF-kappaB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGF-beta signaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is upregulated in podocytes in all examined glomerular diseases (focal segmental glomerulosclerosis [FSGS], minimal-change disease [MCD], membranous nephropathy [MNP], lupus nephritis [LN], and diabetic nephropathy [DN]) with a statistically significant upregulation in "classical" podocyte-diseases such as FSGS and MCD. TGF-beta induces Smad7 synthesis in cultured podocytes and Smad6 synthesis in cultured mesangial cells. Although Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-beta signaling in podocytes, it inhibited only Smad3 but not Smad2 signaling in mesangial cells. In contrast, Smad6 had no effect on TGF-beta/Smad signaling in podocytes and enhanced Smad3 signaling in mesangial cells. These data suggest that Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-beta/Smad signaling in addition to its pro-apoptotic activity, whereas Smad6 has no role in TGF-beta response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-beta/Smad signaling. These data indicate an important role for Smad6 and Smad7 in glomerular cells in vivo that could be important for the cell homeostasis in physiologic and pathologic conditions.