Plant growth promotion by inoculation with selected bacterial strains versus mineral soil supplements.

In the process of remediation of mine sites, the establishment of a vegetation cover is one of the most important tasks. This study tests two different approaches to manipulate soil properties in order to facilitate plant growth. Mine waste from Ingurtosu, Sardinia, Italy rich in silt, clay, and heavy metals like Cd, Cu, and Zn was used in a series of greenhouse experiments. Bacteria with putative beneficial properties for plant growth were isolated from this substrate, propagated and consortia of ten strains were used to inoculate the substrate. Alternatively, sand and volcanic clay were added. On these treated and untreated soils, seeds of Helianthus annuus, of the native Euphorbia pithyusa, and of the grasses Agrostis capillaris, Deschampsia flexuosa and Festuca rubra were germinated, and the growth of the seedlings was monitored. The added bacteria established well under all experimental conditions and reduced the extractability of most metals. In association with H. annuus, E. pithyusa and D. flexuosa bacteria improved microbial activity and functional diversity of the original soil. Their effect on plant growth, however, was ambiguous and usually negative. The addition of sand and volcanic clay, on the other hand, had a positive effect on all plant species except E. pithyusa. Especially the grasses experienced a significant benefit. The effects of a double treatment with both bacteria and sand and volcanic clay were rather negative. It is concluded that the addition of mechanical support has great potential to boost revegetation of mining sites though it is comparatively expensive. The possibilities offered by the inoculation of bacteria, on the other hand, appear rather limited.

Polyamines secreted by cancer cells possibly account for the impairment of the human erythrocyte sodium pump activity.

Using an original microcalorimetric method, we previously showed that in erythrocytes from cancer patients, the sodium pump activity was decreased and returned to normal in patient in remission. In addition we suggested that a plasma-borne factor probably secreted by cancer cells accounted for this impairment of the sodium transporter. In the present study we sought to identify this factor as well as its mechanism of action. First we determined the effect of culture media from undifferentiated and differentiated colon cancer cell lines (Caco-2 and HT29-D4) on the sodium pump activity of normal human erythrocytes. The inhibitory powers of culture media from undifferentiated cells were higher than those of differentiated cells (38.6 +/- 3.5% vs 6.9 +/- 4.6%, p<0.05 for Caco-2 and 45.8 +/- 6.2% vs 9.0 +/- 5.0%, <0.05 for HT29-D4). The use of alpha difluoro-methylomithine (2 mM) to inhibit ornithine decarboxylase, the rate-limiting enzyme for polyamine biosynthesis, dramatically reduced the sodium pump inhibition induced by the two undifferentiated cell lines (75% for Caco-2 and 89% for HT29-D4). Polyamines secreted by undifferentiated cells and then taken up by human erythrocytes thus appeared as inhibitors of sodium pump of these red blood cells. Putrescine, spermidine, and spermine (the main polyamines) exerted a similar inhibitory effect (33 +/- 2%). Tested in vitro on Na,KATPase, these polyamines (3 mM) were inhibitors (putrescine = 23 +/- 2%; spermidine= 48 +/- 3%; spermine= 55 +/- 2%) when assay condition for the ATPase reaction was suboptimal (Na+ = 10 mM; K+ = 1 mM). The inhibitory effect appeared to be related to their charge and their aliphatic chain length. The effect of spermidine and spermine on the ionic substrates and ATP-Mg showed that molecules decreased the affinity (Km) of the Na,K-ATPase for Na+ (11.24 +/- 0.49 mM for control vs 23.51 +/- 1.53 mM for spermine and 18.86 +/- 0.98 mM for spermidine), indicating that polyamines exerted their inhibitory effect in a competitive manner.

Sodium pump and Na+/H+ antiport restoration in erythrocytes from cancer patients in remission.

We previously showed that in erythrocytes from cancer patients, the sodium pump is decreased and the optimal intracellular pH for Na+/H+ antiport activity is shifted toward an acidic value. We now have studied these sodium transporters in erythrocytes from patients in remission. Moreover, we intended to explain why the transporters were impaired in erythrocytes, which have no apparent bearing on cancer tissues. The sodium pump was studied through a microcalorimetric method, and the Na+/H+ antiport by a titrimetric method. In patients in remission the sodium pump activity returned to normal: 15.10 +/- 6.00 vs. 14.12 +/- 5.28 mW/l cells for remission and control, respectively. The optimal intracellular pH for Na+/H+ antiport activity was identical in remission and control: 6.09 +/- 0.23 vs. 6.10 +/- 0.10. Restoration of sodium pump activity and optimal intracellular pH for Na+/H+ antiport activity in erythrocytes were thus linked to remission. Moreover, we showed that the impairments of the sodium transporters were due to the presence of plasma-borne factors, the existence of which explained why the sodium transporters were impaired in erythrocytes.

[Chondrosarcoma in nasal fossae and Maffucci's syndrome]. / Chondrosarcome des fosses nasales et syndrome de Maffucci-Kast.

INTRODUCTION: Maffucci's syndrome is a congenital non-hereditary disease very similar to Ollier's disease and associates multiple cutaneous hemangiomas, dyschondroplasia and often enchondromas. EXEGESIS: We report a unique case involving synchronous localization of chondrosarcoma in nasal fossae and anterior chest wall, disclosing Maffucci's syndrome. CONCLUSION: Atypical chondrosarcoma localization must lead to further investigation of potential multiple enchondromatosis.

[Clinical pilot study on repeated use of heparin, vancomycin, colimycine locked flush solution for central intravenous implanted catheter in oncology]. / Etude clinique pilote de l'utilisation repétée dune solution héparine, vancomycine, colimycine en verrouillage systématique des chambres implantables avec cathéter centeral en cancérologie.

With an anti-infectious and an antithrombotic prophylaxis aims, a locked flush solution including heparin and vancomycin, was used systematically for implantable venous access system for each patient, from january to april 1995. Since the 6th of april 1995, in order to widen the antibiotic spectrum on Gram negative bacteriae, we added colimycin at the flush solution. In 1995, 342 hospitalised patients held this type of venous access and received chemotherapy and/or radiochemotherapy for cancer. Two thousand six hundred thirty three manipulations were done, 575 with the first flush solution, 2058 with the second. During the year, 15 implantable access system (4.4%) were considered as infected, only 3 (0.9%) were removed, in the first period. THe infectious rate seemed to be stable, but the bacterial assessment to be modified between the two periods. The Gram negative bacterial infections seemed to decrease with colimycin addition (33% versus 50%). These results must be confirmed by a long term and/or randomized study.

A Bayesian dosing method for carboplatin given by continuous infusion for 120 h.

Carboplatin (CBDCA), an analogue of cisplatin, exhibits reduced toxicity but wide interpatient variability of its pharmacokinetic parameters. Individualization of the CBDCA dose is therefore necessary. Although various formulas have been developed for this purpose, major side effects have been reported on CBDCA administration by short-term infusion (0.5 or 1 h). We therefore propose a new schedule of CBDCA administration. Instead of a dosing method based on the estimation of renal function when a classic administration schedule is used, we propose a pharmacokinetic dosing method (Bayesian method), whereby CBDCA is given by continuous infusion for 120 h. First, CBDCA was given to 21 patients to determine the population pharmacokinetic parameters of carboplatin. Then, on the basis of total platinum plasma concentration measurements and Bayesian estimation of pharmacokinetic parameters, it was possible to individualize the CBDCA dose within the first 24 h of the infusion. This new protocol for CBDCA administration was evaluated in 36 new patients (60 courses). Three theoretical end points at the end of the infusion were considered. For a given theoretical end point, 20 courses were taken into account. The theoretical end points (i.e., 1, 1.5, and 1.8 mg/l) were compared with the concentrations measured at the end of the infusion, which were 0.99 +/- 0.10, 1.41 +/- 0.13, and 1.72 +/- 0.20 mg/l, respectively. This Bayesian dosing method can easily be used in clinical practice, and the determination of predictive performances has shown that the method is precise and unbiased. With no more toxicity or practical difficulties than those produced by other methods, and with acceptable tolerance, it was possible to reach a median dose that was 20% higher than the usual dose (484 +/- 190 mg/m2 as compared with 400 mg/m2). In conclusion, this new schedule of CBDCA administration appears to be interesting in terms of tolerance. However, new studies are required to confirm that this new scheme leads to equal or better efficacy than the classic protocol.

Impairment of sodium pump and Na+/H+ antiport in erythrocytes isolated from cancer patients.

We sought to determine whether the impairment of sodium pump activity and Na+/H+ exchange reported in tumorigenic cells was specific to these cells or more general. Sodium pump activity and Na+/H+ exchange were measured in erythrocytes from 49 cancer patients and 51 healthy subjects. Cancer patients with a newly detected cancer or in relapse and without associated pathologies known to modify these sodium transporters were included in this study. Two sodium pump statuses reflecting its physiological modulation were evidenced for healthy subjects (10.3 +/- 0.2 and 19.4 +/- 0.8 mW/liter of cells). In cancer patients, only one basal status lower than those of controls was observed (8.3 +/- 0.5 mW/liter of cells; P < 0.001). Cooperativity of the Na+/H+ antiporter is the same in cancer patients and controls (2.58 +/- 0.27 versus 2.60 +/- 0.15). The intracellular pH (pHi) dependence curve of the antiporter was shifted toward more acidic values, and optimal pH1 was lower in cancer patients than in controls (5.80 +/- 0.03 versus 6.08 +/- 0.02; P < 0.0001). The mean maximal rate and the Km of H+ for the Na+/H+ antiporter were higher: 8.4 +/- 1.2 versus 4.6 +/- 0.4 mmol H+/liter of cells/h (P < 0.01) and 514 +/- 12 versus 322 +/- 16 nM (P < 0.05), respectively. Alterations of these Na+ transporters, therefore, were not restricted to cancerous cells. Among the alterations, the acidic shift in the pHi dependence of Na+/H+ exchange appears associated with cancer because this behavior has never been reported in other pathologies.

[Individual dose adjustment of high-dose methotrexate in clinical practice]. / Adaptation individuelle de posologie du méthotrexate à haute dose (MTX-HD) en pratique clinique courante.

Since its discovery in 1948 the clinical applications of methotrexate have widened; and in order to overcome resistances to methotrexate, the concept of high-dose methotrexate has been proposed. The use of rescue by folinic acid, as well as rapid dosage of MTX coupled with pharmacokinetic studies, have permitted us to administer an optimum dose of drug, with maximum therapeutic effects, but with reduced toxicity. Individual adaptation of posology, calculated using the test dose or according to population pharmacokinetic with a Bayesian method of parameter estimation (which allows us to adjust the dose of high-dose methotrexate during its infusion) permits control of inter and intra-individual variations of this drug. After analysis of the different methods proposed, we now present the results of 778 courses of treatment by high-dose methotrexate (while separating 238 courses for osteosarcoma as these formed a homogeneous group of patients). Theoretical maximum concentration and length of infusion were decided by physicians, followed by individual adaptation of posology by pharmacologists at the sixth hour of infusion of methotrexate. This treatment unites maximum security for the patient with no serious side effects (no grade 4 toxicity according to WHO classification), while receiving an optimum dose of methotrexate. In courses of MTX for osteosarcoma, the dose of MTX can be further intensified without risk, by administering on average 65% more than the usual dose in adults (8 g/m2) and 10% more than the usual dose in children (12 g/m2).