Novel agents targeting bioactive sphingolipids for the treatment of cancer.

Sphingolipids are a class of lipids that have important functions in a variety of cellular processes such as, differentiation, proliferation, senescence, apoptosis and chemotherapeutic resistance. The most widely studied bioactive shingolipids include ceramides, dihydroceramide (dhCer), ceramide-1-phosphate (C1P), glucosyl-ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P). Although the length of fatty acid chain affects the physiological role, ceramides and sphingosine are known to induce apoptosis whereas C1P, S1P and GluCer induce proliferation of cells, which causes the development of chemoresistance. Previous studies have implicated the significance of bioactive shingolipids in oncogenesis, cancer progression and drug- and radiation-resistance. Therefore, targeting the elements of sphingolipid metabolism appears important for the development of novel therapeutics or to increase the effectiveness of the current treatment strategies. Some approaches involve the development of synthetic ceramide analogs, small molecule inhibitors of enzymes such as sphingosine kinase, acid ceramidase or ceramide synthase that catalyze ceramide catabolism or its conversion to various molecular species and S1P receptor antagonists. These approaches mainly aim to up-regulate the levels of apoptotic shingolipids while the proliferative ones are down-regulated, or to directly deliver cytotoxic sphingolipids like short-chain ceramide analogs to tumor cells. It is suggested that a combination therapy with conventional cytotoxic approaches while preventing the conversion of ceramide to S1P and consequently increasing the ceramide levels would be more beneficial. This review compiles the current knowledge about sphingolipids, and mainly focuses on novel agents modulating sphingolipid pathways that represent recent therapeutic strategies for the treatment of cancer.

Ozonation of synthetic versus natural textile tannins: recalcitrance and toxicity towards Phaeodactylum tricornutum.

A sound in-plant pollution control strategy can only be defined by paying due attention to bio-recalcitrance and toxicity. In this context the levels of toxicity and inert COD introduced to textile dyebath discharges by two alternative auxiliary chemicals, namely natural tannin (NT) and synthetic tannin (ST), were investigated. The effect of 40 minutes ozonation at 1,000 mg h(-1) at pH 3.5 on the segregated effluent streams containing the above-mentioned tannin formulations was evaluated in terms of changes in toxicity and recalcitrance. The effect of ozonation on the COD distribution of raw and ozonated NT and ST samples according to their molecular weight cut-offs was also assessed. Both untreated tannin formulations exerted high acute toxicity towards marine microalgae Phaeodactylum tricornutum. Moderate decrease in the toxicity levels of both tannins was observed upon ozonation. The raw NT formulation with a COD content more than twice that of its alternative raw ST had an initially inert soluble COD content of only 25 mg/L, while the initially inert COD was 135 mg/L for ST. As the initially inert soluble COD content of NT was considerably lower, this textile auxiliary did not need chemical pretreatment to improve its biodegradability. On the other hand, the initially inert soluble COD content of ST was reduced by 70% by ozone pretreatment. In terms of residual COD contents achievable after passing through a biological treatment system, raw NT and pretreated ST formulations yielded 100 and 95 mg/L COD, respectively. The highest proportion of COD (46% for NT and 88% for ST) was found in the <1 kDa range. The same fraction increased to 93% for NT after ozonation, while for ST no significant change was observed in the COD distribution of the molecular weight cut-offs after ozonation.

Treatability of cefazolin antibiotic formulation effluent with O3 and O3/H2O2 processes.

The effect of applying ozonation and perozonation to antibiotic cefazolin-Na formulation effluents were investigated in this study. Twenty minutes of ozonation at a rate of 1,500 mg/L-h was observed to remove COD by 38%, whereas a COD removal efficiency of 40% was achieved via H2O2 enhanced ozonation (same conditions + 31.25 mM H2O2). Both of the pretreatment alternatives were monitored to elevate the BOD5/COD ratio from 0.01 to 0.08. The initially inert COD was reduced by 38% using ozonation and by 60% employing H2O2 enhanced ozonation. In terms of the lowest achievable effluent COD levels after bio-treatment, ozonation was observed to yield a residual COD of 205 mgL(-1), while a residual COD of 135 mgL(-1) was involved for perozonation. According to the results of acute toxicity on Phaedactylum tricornutum, ozonated and perozonated samples exhibited more toxicity than the untreated effluent after 4 days. The activated sludge inhibition test demonstrated that both of the pretreatment alternatives efficiently eliminated the inhibition of investigated formulation effluent.

Effect of chemical treatment on the acute toxicity of two commercial textile dye carriers.

In the present experimental study, the effect of chemical treatment (coagulation-flocculation) on the acute toxicity exerted by two commercial dye carriers (called Carrier A and B herein) often used in the textile industry was investigated. Two different test organisms were selected to elucidate the situations in activated sludge treatment systems (activated sludge microorganisms) as well as in receiving water bodies (ultimate marine discharge). According to the results of a comprehensive analysis covering COD removal efficiencies, sludge settling characteristics and operating costs involved in coagulation-flocculation, the optimum treatment conditions were defined as follows; application of 750 mg/L ferrous sulphate at a pH of 9.0 for Carrier A; and application of 550 mg/L ferrous sulphate at a pH of 9.0 for Carrier B. The acute toxicities of both dye carriers towards marine microalgea Phaeodactylum tricornutum could be reduced significantly after being subjected to coagulation-flocculation. Fair toxicity removals (towards heterotrophic mixed bacterial culture accommodated in activated sludge treatment) were obtained with coagulation-flocculation for both of the carriers under investigation.