UGT1A1 genotype influences clinical outcome in patients with intermediate-risk acute myeloid leukemia treated with cytarabine-based chemotherapy.

The treatment of acute myeloid leukemia (AML) is adjusted according to cytogenetic risk factors and molecular markers. Cytarabine remains the main drug to treat AML, and several studies have explored the prognostic relevance of the genotype of cytarabine metabolizing enzymes in AML. Glucuronidation has been identified to be relevant in the cytarabine clearance, but there are still few data concerning the clinical impact of genetic polymorphisms known to condition the activity of UDP-glucuronosyl transferases in AML patients. Here we report the association between the UGT1A1 rs8175347 genotype and the clinical outcome of 455 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients with the UGT1A1*28 homozygous variant (associated to a lower UGT1A1 activity) had a lower overall survival (OS) (25.8% vs. 45.5%; p: 0.004). Multivariate analysis confirmed this association (p: 0.008; HR: 1.79; 95% CI: 1.16-2.76). Subgroup analysis showed the negative effect of the UGT1A1*28 homozygous genotype on OS in women (14.8% vs. 52.7%; p: 0.001) but not in men. This lower OS was associated with longer neutropenia after consolidation chemotherapy and with higher mortality without previous relapse, suggesting an association between a low glucuronidation activity and mortal toxic events.

Bioavailability and dosing strategies of mineral in anaerobic mono-digestion of maize straw.

The influence of the bonding form distribution of Fe, Ni, Co and Mn and their potential bioavailability during the anaerobic degradation of maize straw was investigated. Two reactors were operated over 117 days at 37°C and different dosage strategies of mineral were studied in reactor (R2). Control reactor (R1) was metal-limited over time. mineral supplementation (1 g L-1) once a week reported the highest methane yield (257 mL g-1 VS) with 30% of increment. Ni and Co predominated in their oxidizable bonding forms and Fe mainly existed as residual and oxidizable fractions. The potential bioavailability (Mn ˃˃ Co ≈ Ni ˃ Fe) of R2 was higher comparing to R1. Metal deprivation in R1 led to depletion of both sequential extraction fractions and total metal concentrations until the end of the process. This study confirmed that the dosage strategy of mineral has a stimulatory effect on methane production from crop maize waste.

Energy balance, greenhouse gas emissions, and profitability of thermobarical pretreatment of cattle waste in anaerobic digestion.

In this study modeled full scale application of thermobarical hydrolysis of less degradable feedstock for biomethanation was assessed in terms of energy balance, greenhouse gas emissions, and economy. Data were provided whether the substitution of maize silage as feedstock for biogas production by pretreated cattle wastes is beneficial in full-scale application or not. A model device for thermobarical treatment has been suggested for and theoretically integrated in a biogas plant. The assessment considered the replacement of maize silage as feedstock with liquid and/or solid cattle waste (feces, litter, and feed residues from animal husbandry of high-performance dairy cattle, dry cows, and heifers). The integration of thermobarical pretreatment is beneficial for raw material with high contents of organic dry matter and ligno-cellulose: Solid cattle waste revealed very short payback times, e.g. 9 months for energy, 3 months for greenhouse gases, and 3 years 3 months for economic amortization, whereas, in contrast, liquid cattle waste did not perform positive replacement effects in this analysis.

Effects of thermobarical pretreatment of cattle waste as feedstock for anaerobic digestion.

Lab-scale experiments were conducted to assess the impact of thermobarical treatment of cattle waste on anaerobic digestion. Treatment was at temperatures of 140-220°C in 20K steps for a 5-min duration. Methane yields could be increased by up to 58% at a treatment temperature of 180°C. At 220°C the abundance of inhibitors and other non-digestible substances led to lower methane yields than those obtained from untreated material. In an extended analysis it could be demonstrated that there is a functional correlation between the methane yields after 30 days and the formation rate and methane yield in the acceleration phase. It could be proved in a regression of these correlation values that the optimum treatment temperature is 164°C and that the minimum treatment temperature should be above 115°C.