Estudio de la diversidad microbiana asociadas a suelos cacaoteros con presencia de cadmio (Cd) y evaluación de su potencial biorremediador del metal a la planta; esta

Backgrund: Lobaplatin, D-19466, l,2-diamminomethyl-cyclobutane-platinum-(II)-lactate, is a new watersoluble platin complex which showed a better therapeutic index than cisplatin or carboplatin in murine and human tumor models. Preclinical toxicology studies showed myelosuppression with predominant thrombocytopenia as the dose-limiting toxicity in rodents. Materials and Methods: The phase I study group of the AIO performed the phase I study with Lobaplatin administered as an intravenous bolus injection repeated every 4 weeks without hydration. Results: The maximum tolerated dose was 60 mg/m2, thrombocytopenia was the dose-limiting toxicity. The nadir occurred after 2 weeks with recovery within a week. Mild anemia and leukopenia were found with a nadir after 3 weeks. Nausea and vomiting occurred in half of the patients, however, they were well controlled by antiemetics. No alopecia, renal, CNS or ototoxicity were observed. Overall, Lobaplatin is well tolerated. The intravenous bolus injection without the need for hydration makes this therapy suitable for outpatient therapy. One partial remission was observed in a patient with an adenocarcinoma of the lung. Conclusion: The recommended dose for phase II studies is 50 mg/m2 every 3-4 weeks in good-risk patients with a normal kidney function.

Background: Lobaplatin (D-19466) is a platinum compound with greater anticancer activity in NSCLC, stomach, breast and ovarian cancer in the human tumor xeno-graft model. Preclinical studies suggested a low or absence of cross resistance to CDDP and CBDCA. Methods: During a clinical phase I trial a pharmacokinetic study was performed. The amount of platinum in plasma, plasma ultrafiltrate and urine samples was measured with atomic absorption spectometry (AAS) during a 48 hour sampling period. In total, 15 patients were studied receiving 17 treatment cycles. Pharmacokinetic parameters were determined by use of a software package TopFIT version 1.1. Toxicity data (reduction of platelets and leucocytes at the nadir) were correlated to either pharmacokinetic parameters as well as to kidney function parameters (ECC). In-vitro binding of D-19466 to plasma proteins was studied. Results: The c(t)-curves of total platinum were best described by a three compartment model. The mean residence time ranged from 5.1 to 37.8 hours in patients treated with 20 respectively 60 mg/m2. The volume of distribution was ranging from 0.64 up to 3.95 L/kg, the total plasma clearance was independent from dose with a mean of 172 ml/min. The area under the curve was increasing by dose from 2490 up to 10,000 μg h/L. The urinary excretion of total platinum during 48 hours was 27.8% of the total dose. The c(t)-curves of free platinum were best described by a two-compartment model. The mean residence time, volume of distribution as well as the total plasma clearance were independent from dose with mean values of MRT – 2.6 hours, Vdss = 0.44 L/kg and Clp = 202 ml/min. The area under the curve was increasing by dose from 2215 to 5200 μg h/L. The part of the free (unbound) platinum was calculated by comparison of the AUCs of c(t)-curves of free and total platinum and was 64% with a wide range (27-95%). In-vitro studies showed an increasing binding to proteins during time. Only a poor correlation was found between the estimated creatinine clearance and the drop of platelets and leucocytes at the nadir whereas a good correlation was found between the AUC of free as well as total platinum and reduction of platelets and leucocytes. Conclusion: In-vitro studies with D-19466 showed a slow binding to plasma proteins. This corresponds with the result that only 64% of the total platinum administered is free (= unbound) platinum. The terminal half-life of the ultrafilterable (free) platinum remains short in comparison to total platinum which includes the plasma bound platinum. There was no good correlation found between estimated creatine clearance and the drop of platelets and leucocytes at the nadir. There is no need to adjust the D-19466 dose to kidney function as far as patients are treated with normal values of creatinine.

The blackening of tissues or mucus of benthic animals from sulphidic environments is a remarkable phenomenon whose ecological interpretation is disputed. In the Baltic clam Macoma balthica the mantle edge turned black after sulphide exposure owing to numerous precipitates in the extracellular matrix underneath the epidermal cells. In the apical parts of these cells, similar precipitates were found, albeit in lower abundance. Elemental analyses showed that copper (214.7 pg g-' ww [wet weight]) and sulphur (1328.6 pg g.' ww) were the main components, with iron (311.2 pg g-' ww) and zinc (112.7 pg g-' \W) in lower concentration. Apparently, these precipitates become phagocytosed by amoebocytes and concentrated in haemocytic granules. This is interpreted as a pathway of removal from the mantle edge. On the basis of calculated diffusion rates (DHS-= 1.9 X cm2 S-'). there is a sulphide influx of 61 nmol h-' into the body of M. balthica. Even under conservative assumptions, this would lead to the binding of all the copper present in about 30 min. It is concluded that the process of sulphide precipitation can represent a temporarily effective pathway attenuating sulphide toxification.