Cyclic AMP increases the release of parathyroid hormone-related protein from a lung-cancer cell line

Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of malignant hypercalcemia by stimulating bone resorption and/or renal tubular reabsorption of calcium. In cultured cancer cells, its production can be influenced by various factors or ions, but the regulation of its production is still poorly understood. We investigated the effects of stimulators of cAMP synthesis on PTHrP release by a human lung squamous-carcinoma cell line (BEN). In supervised cells grown on microcarrier beads, PTHrP production was significantly increased after incubation with calcitonin for only 20 min. The release of immunoreactive and bioactive PTHrP was increased by incubating the cells with forskolin, 3-isobutyl-I-methylxanthine or dibutyryl cAMP even in the presence of the protein-synthesis inhibitor cycloheximide for 6 hr. The calcitonin-mediated stimulation was not accompanied by. concomitant changes in PTHrP mRNA. The microfilament-disrupter cytocha-lasin D was shown to enhance the basal and calcitonin-induced production of PTHrP. These results indicate that stimulators of cAMP synthesis enhanced PTHrP release by BEN cells.     

Linear β-amino alcohol catalyst anchored on functionalized magnetite nanoparticles for enantioselective addition of dialkylzinc to aromatic aldehydes

A linear β-amino alcohol ligand, previously found to be a very efficient catalyst for enantioselective addition of dialkylzinc to aromatic aldehydes, has been anchored on differently functionalized superparamagnetic core–shell magnetite–silica nanoparticles (1a and 1b). Its catalytic activity in the addition of dialkylzinc to aldehydes has been evaluated, leading to promising results, especially in the case of 1b for which the recovery by simple magnetic decantation and reuse was successfully verified.

The catalytic activity of a linear β-amino alcohol ligand anchored on functionalized magnetite/silica core–shell nanoparticles has been evaluated in the addition of dialkylzinc to aldehydes leading to promising results.     

Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints

OBJECTIVE—To analyse the functional activity of the plasminogen activators urokinase (uPA) and tissue type plasminogen activator (tPA) in human synovial membrane, and to compare the pattern of expression between normal, osteoarthritic, and rheumatoid synovium. The molecular mechanisms underlying differences in PA activities between normal and pathological synovial tissues have been further examined.
METHODS—Synovial membranes from seven normal (N) subjects, 14 osteoarthritis (OA), and 10 rheumatoid arthritis (RA) patients were analysed for plasminogen activator activity by conventional zymography and in situ zymography on tissue sections. The tissue distribution of uPA, tPA, uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) was studied by immunohistochemistry. uPA, tPA, uPAR, and PAI-1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively.
RESULTS—All normal and most OA synovial tissues expressed predominantly tPA catalysed proteolytic activity mainly associated to the synovial vasculature. In some OA, tPA activity was expressed together with variable amounts of uPA mediated activity. By contrast, most RA synovial tissues exhibited considerably increased uPA activity over the proliferative lining areas, while tPA activity was reduced when compared with N and OA synovial tissues. This increase in uPA activity was associated with increased levels of uPA antigen and its corresponding mRNA, which were localised over the synovial proliferative lining areas. In addition, in RA tissues, expression of the specific uPA receptor (uPAR) and of the plasminogen activator inhibitor-type 1 (PAI-1) were also increased.
CONCLUSION—Taken together, these results show an alteration of the PA/plasmin system in RA synovial tissues, resulting in increased uPA catalytic activity that may play a part in tissue destruction in RA.

     

Collective effective dose received by the population of Egypt from building materials

Natural radioactivity due to the presence of 226Ra, 232Th and 40K in selected building materials (cement, sand, bricks, gypsum and ceramic) used in Egypt was measured using a gamma-ray spectrometer with an HPGe detector. The average activity concentrations observed in different building materials ranged from 10.0 +/- 1.3 to 109 +/- 6, <2 to 55.8 +/- 2.2 and 5.5 +/- 1.7 to 684 +/- 34 Bq kg(-1) for 226Ra, 232Th and 40K, respectively. Based on these, together with previously reported results, the effective doses received by the residents of different types of house within all Egyptian governorates were assessed using the WinMat computer program. The results were below 1 mSv a(-1) in all cases. The collective effective dose indoors was assessed as 15,000 man Sv and the excess effective dose due to building materials was 0.07 mSv a(-1).     

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis

In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a meta-analysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16-2.84), CD34 (HR: 1.99; 95% CI: 1.53-2.58) or CD31 (HR: 1.80; 95% CI: 1.10-2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.     

Direct transoral approach to C2 for percutaneous vertebroplasty

Percutaneous vertebroplasty was performed via a transoral route in a 70-year-old woman with a C2 metastasis of thyroid origin involving anterior vertebral elements. Complete pain relief was obtained after an uncomplicated minimally invasive procedure. This preliminary experience demonstrates that a transoral approach under fluoroscopic control can provide safe access to the upper cervical spine at C2 level.     

Neonatal outcome after exposure to selective serotonin reuptake inhibitors late in pregnancy]

OBJECTIVES: To analyse neonatal effects after in utero selective serotonin reuptake inhibitors exposure and the pertinence of recommendations delivered by our team. MATERIALS AND METHODS: We report a series of 27 pregnancies exposed late in pregnancy including the period of delivery, to the Selective Serotonin Reuptake Inhibitors (SSRI) and having been the subject of a call to the Regional Center of Pharmacovigilance of Tours (CRPV). RESULTS: Twenty-seven children were born without malformation. Twelve children were hospitalized because of prematurity (two), exposure to other drugs imposing particular surveillance (eight) or in view of abnormal neonatal effects (two). Five newborns (18.5%) of which three had also been exposed to other drugs (benzodiazepine, neuroleptic, H1-antagonist) had presented one or more neonatal adverse effects compatible with the role of the SSRI (irritability, agitation, shivering, hypotonia) but with uncertainty about a clear discrimination between withdrawal syndrome and serotonin impregnation. All the symptoms disappeared spontaneously. One of the five children had a described in treated adults but two neonatal observations were published. No child had hemorrhagic symptoms as described in treated adults despite the fact that two neonatal observations were reported. CONCLUSION: This study confirms the relative benignity of SSRI exposure during late pregnancy. Our recommendations for monitoring the newborns during their stay in maternity wards were well respected. The risk of hemorrhagic symptoms or hyponatremia, not well known by pediatricians, deserves to be recalled to medical teams who take in charge newborns exposed to SSRI.     

Elevated levels of angiogenic cytokines in the plasma of cancer patients

Although in the normal healthy organism angiogenesis is a tightly regulated process, under a variety of circumstances it may contribute to disease states. These include the growth of solid tumors, the hematogenous spread of tumor cells and the growth of metastasis. Our aim was to measure the levels of 5 angiogenic cytokines in the plasma of patients with a variety of cancers, to establish a plasmatic angiogenic profile. We prospectively obtained blood samples in citrated tubes from 40 healthy individuals and 75 patients with a variety of solid tumors. Patients who had received any form of treatment in the preceeding 6 months were excluded from the study. Plasma levels of the following 5 cytokines were determined by ELISA: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor, transforming growth factor-beta and tumor necrosis factor-alpha. In some cases, additional samples were taken 4 and 15 days after surgical removal of the tumor. Our findings demonstrate, that firstly, compared to the tumor group VEGF was almost always undetectable or present at very low levels in healthy individuals; secondly, a threshold value for HGF was found to exist between the 2 groups (healthy vs. tumor); and thirdly, there was a clear relationship between plasma levels of VEGF and HGF and extension of disease (i.e., without or with metastases). The timing of blood sampling in the post-operative period was found to be critical, particularly with regard to VEGF and HGF. The existence of a systemic angiogenic profile in the plasma of cancer patients may be useful as a diagnostic and prognostic tool and may help in the future to monitor the responses of individual patients to anti-tumor and, particularly, anti-angiogenic therapy.     

The effects of interferon-α on the proliferation of CML progenitor cells in vitro are not related to the precise position of the M-BCR breakpoint

We investigated the effects of brief (2 h) and continuous exposure to recombinant interferon-alpha (2a) (rIFN-alpha) on the proliferation of primitive (blast colony-forming cells, Bl-CFC) and committed myeloid progenitor cells (BFU-E and GM-CFC) derived from blood and bone marrow of patients with chronic myeloid leukaemia (CML) and normal subjects. In all three clonogenic assays, rIFN-alpha suppressed colony formation in a dose-dependent manner. No differences were detected in the proliferation of CML or normal Bl-CFC and GM-CFC exposed to rIFN-alpha. Erythroid colony formation by normal, but not by CML BFU-E, was inhibited by relatively low concentrations (100 U/ml) of rIFN-alpha. However, in patients whose blood or marrow contained a mixture of Philadelphia chromosome (Ph)-positive and Ph-negative BFU-E, cytogenetic analysis of individual erythroid colonies showed no differential inhibition by rIFN-alpha. We found no difference in the sensitivity to rIFN-alpha of GM-CFC from patients whose leukaemic cells expressed BCR/ABL mRNA with the b2a2 junction and that of GM-CFC from patients with the b3a2 mRNA. We conclude that (1) rIFN-alpha does not have a significant leukaemia-specific effect on the progenitor cells detected in these assays, and (2) the sensitivity of CML GM-CFC to rIFN-alpha is independent of the type of BCR/ABL message present in the cells. The clinical efficacy of rIFN-alpha could be due to selective toxicity to cells not assayed in this study, to effects on accessory cells or to alterations induced in progenitor cell/stromal cell interactions.     

In vitro susceptibility testing of amorolfine in pathogenic fungi isolated from dermatomycosis patients in China

The antifungal susceptibility of isolates from Chinese dermatomycosis patients to amorolfine was investigated following National Committee for Clinical Laboratory Standards (NCCLS) protocols. In total, 383 isolates were tested, including 132 strains from tinea pedis, 148 strains from tinea corporis/cruris, and 103 strains from onychomycosis. The minimum inhibitory concentration (MIC) of amorolfine against dermatophytes ranged from 0.01 to 0.08 microg ml(-1). The MIC(50) and MIC(90) of amorolfine for Trichophyton rubrum were both equal to 0.04 micro ml(-1); for T. mentagrophytes these MICs were 0.04 microg ml(-1) and 0.08 microg ml(-1) respectively; and for Epidermophyton floccosum they were 0.02 microg ml(-1) and 0.04 microg ml(-1) respectively. The MIC range of amorolfine against Candida parapsilosis was 0.5-16 microg ml(-1). MIC(50) and MIC(90) for C. parapsilosis were 0.5 and 2 microg ml(-1). MIC ranges of amorolfine against Scopulariopsis spp. and Acremonium spp. were 0.5-4 and 2-8 microg ml(-1), respectively. Candida albicans, Fusarium solani and Aspergillus flavus required relatively higher concentrations of amorolfine to inhibit their growth (MIC 0.125-64 microg ml(-1), MIC(50) and MIC(90) were 4 and 64 microg ml(-1)). The results demonstrated that amorolfine is the only topical agent that has such a potent antifungal activity and a broad spectrum against a wide range of pathogenic fungi.