Simultaneous removing of Pb2+ ions and alizarin red S dye after their complexation by ultrasonic waves coupled adsorption process: Spectrophotometry detection and optimization study.

Funthenalized chitosan (CS) was composited with mesoprous SBA-15 and characterized via. different techniques such as FT-IR and FE-SEM. Subsequently, this new material was applied for simulations ultrasound-assisted adsorption of Pb2+ ion and alizarin red S (ARS) dye after their complexation. Efficient conventional variables in adsorption process such as initial ARS and Pb2+ concentration, adsorbent mass and sonication time were studied by small central composite design (CCD) and optimized with desirability function approach. Lack of fit testes and model summary statistics for linear, 2FI, quadratic and cubic models were investigated and according to the insignificant lack of fit and maximizing the R-squared (R2), adjusted R-squared and the predicted R-squared quadratic model was selected for other step analysis for removal of ARS dye, while, for Pb2+ ions 2FI model was selected as best model. Quadratic model ANOVA for ARS dye removal shows the F-value parameter (683.91), very low p-value model (<0.0001) and p-value lack of fit (0.0568) that implied this model was highly significant. Also, 2FI model ANOVA for Pb2+ ions removal shows the F-value parameter (282.51), very low p-value model (<0.0001) and p-value lack of fit (2.05). According to desirability function approach maximum removal percentage of ARS (87.61%) and Pb2+ ions (83.54%) was shown at optimum of condition that were set as at: 25 and 25mgL-1, 0.028g and 11.8min for initial ARS and Pb2+ ions concentration, adsorbent mass and sonication time, respectively. Finally, it was found that the equilibrium and kinetic of adsorption process follow the Langmuir isotherm and pseudo-second-order kinetic model, respectively. From the Langmuir isotherm, maximum monolayer capacity (qmax) was obtained 50.25 and 57.14mgg-1 for ARS and Pb2+ ions removal, respectively.

Induction of apoptosis using 2',2' difluorodeoxycytidine (gemcitabine) in combination with antimetabolites or anthracyclines on malignant lymphatic and myeloid cells. Antagonism or synergism depends on incubation schedule and origin of neoplastic cells.

Induction of apoptosis in vitro using gemcitabine (dFdC) in combination with cladribine (2-CdA) and other cytotoxic drugs on malignant mononuclear cells (MNCs) of patients with acute myeloid leukemia (AML, n=20) and chronic lymphocytic leukemia (CLL, n =20) in myeloid (HL60, HEL) and lymphatic cell lines (HUT78, JURKAT) was investigated using different incubation conditions (simultaneous and consecutive). Furthermore, the influence of dFdC on the level of intracellular metabolites of 2-CdA was studied using high-performance liquid chromatography (HPLC). Apoptosis was evaluated using flow cytometry with 7-aminoactinomycin D. In MNCs of patients with CLL, dFdC + 2-CdA showed an antagonistic effect when applied simultaneously. This antagonism was reduced by consecutive application. The combination of dFdC with doxorubicin was synergistic, independent of incubation schedule. In blasts from newly diagnosed patients with de novo AML, all drug combinations (dFdC+2-CdA, doxorubicin, or cytosine arabinoside) were antagonistic by simultaneous incubation. Reduced antagonism or even synergism was shown (P<0.001) by consecutive incubation. The simultaneous combination of dFdC with 2-CdA in all tested cell lines resulted in a competitive inhibition on the rate of apoptosis. By changing the incubation period to a consecutive schedule, the antagonism was diminished or synergism of apoptosis was measured (P< 0.001). Using similar incubation conditions, these experiments were supported by HPLC measurement of intracellular metabolites of 2-CdA influenced by dFdC application. In conclusion, we demonstrated that the efficacy of dFdC in vitro in combination with other cytotoxic drugs depends on the incubation condition and on the origin of neoplastic cells (lymphatic vs myeloid). The data suggest that simultaneous combination therapy with purine and pyrimidine analogues may not improve the clinical efficacy of one or the other drug administered alone.

Induction of apoptosis by 2-chloro-2'deoxyadenosine (2-CdA) alone and in combination with other cytotoxic drugs: synergistic effects on normal and neoplastic lymphocytes by addition of doxorubicin and mitoxantrone.

2-CdA is active as a single agent in the treatment of low-grade lymphomas. We analyzed the induction of apoptosis by 2-CdA alone (n=5) and in combination with other drugs in peripheral lymphocytes from 25 patients with leukemic low-grade lymphomas and from 25 healthy volunteers. 2-CdA was tested in 4 escalating concentrations (0.05 microg/ml to 0.4 microg/ml). Linear regressions showed a dose dependent apoptosis rate of 0.29 x microg 2-CdA/ml + 0.11 (r2=0.88, p=0.006) in normal cells and 0.41 x microg 2-CdA/ml + 0.15 (r2=0.88, p=0.005) in leukemic cells. Intracellular metabolization of 2-CdA into 2-CdA-5'mono-, -di- and the active metabolite -triphosphate was analyzed by HPLC and paralleled the dose dependent increase of apoptosis. The combination of 2-CdA with doxorubicin or mitoxantrone had a synergistic effect on the induction of apoptosis (p<0.001) in both normal and neoplastic lymphocytes, whereas 2-CdA plus etoposide or cytosine arabinoside were only additive. Due to the flat slope of the dose response of 2-CdA concentration on apoptosis we assume that higher in vivo dosages of 2-CdA in the treatment of low-grade lymphomas may not result in a higher clinical efficacy. The synergistic lymphocytotoxic effect of 2-CdA combined with doxorubicin or mitoxantrone may be relevant for new treatment approaches.