Potential added value of combined DPYD/DPD genotyping and phenotyping to prevent severe toxicity in patients with a DPYD variant and decreased dihydropyrimidine dehydrogenase enzyme activity

Decreased dihydropyrimidine dehydrogenase enzyme activity is associated with severe fluoropyrimidine-associated toxicity. Four clinically relevant variants in the DPYD gene are associated with decreased dihydropyrimidine dehydrogenase activity. However, only ∼25% of DPYD variant carriers show a decreased dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells. Objective To investigate if dihydropyrimidine dehydrogenase phenotyping has added value when combined with DPYD genotyping in predicting fluoropyrimidine-related toxicity. Methods Retrospective cohort study in which treatment and toxicity data were collected of 228 patients genotyped for four DPYD variants and phenotyped using an ex vivo peripheral blood mononuclear cell assay. Results Severe toxicity occurred in 25% of patients with a variant and normal dihydropyrimidine dehydrogenase activity, in 21% of patients without a variant and with decreased dihydropyrimidine dehydrogenase activity, and in 29% of patients without a variant and with normal dihydropyrimidine dehydrogenase activity (controls). The majority of patients with a variant or a decreased dihydropyrimidine dehydrogenase activity received an initial dose reduction (68% and 53% vs 19% in controls) and had a lower mean dose intensity (75% and 81% vs 91% in controls). Fifty percent of patients with a variant and decreased enzyme activity experienced severe toxicity, despite the lowest initial dose and whole treatment dose intensity. They also experienced more grade 4/5 toxicities. Conclusions Our results indicate that a combined genotype–phenotype approach could be useful to identify patients at increased risk for fluoropyrimidine-associated toxicity (e.g. patients with a variant and decreased dihydropyrimidine dehydrogenase activity). Because the group sizes are too small to demonstrate statistically significant differences, this warrants further research in a prospective study in a larger cohort.

Antibacterial, antifungal and antioxidant activities of whole plant chemical constituents of Rumex abyssinicus

Background Antibiotic resistance has contributed to the burden of infectious diseases both in the hospital and community setting, and represents a great threat to public health. Previous studies have revealed the role of reactive oxygen species as intermediate mediators of tissue damage, following antibiotherapies, indicating the need of associating antioxidants to these treatments. Therefore, the present work was designed to study the antibacterial, antifungal and antioxidant activities of extracts and compounds from Rumex abyssinicus Jacq. (Polygonaceae), as well as to investigate the antibacterial mechanisms of action of the most effective agents. Methods The plant extracts were prepared by maceration in organic solvents followed by column chromatography of the EtOAc fraction and purification of different fractions which led to the isolation and characterization of pure compounds. The antimicrobial activities of the extracts/compounds and their combinations with ciprofloxacin and fluconazole were evaluated using the broth microdilution method by determining the minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC). The effects of the extracts on the bacterial cell membrane and microbial respiratory chain dehydrogenase enzyme activity were determined by spectrophotometric methods. Antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and gallic acid equivalent antioxidant capacity (GAEAC) assays. Results Chrysophanol (1), physcion (2), Ergosta-6,22-diene-3,5,8-triol (3), emodin (4), 6-hydroxyemodin (citreorosein) (5), chrysophanein (6) and physcionin (7) were isolated from EtOAc fraction of R. abyssinicus and displayed different degrees of antimicrobial activities (MIC = 8–256 μg/mL). The MeOH extract and compounds 2 and 4 exhibited synergistic effects with ciprofloxacin and fluconazole. Compounds 1, 2 and the combined mixture of 6 + 7 displayed the highest antioxidant activity (GAEAC = 83.38–106.03 μg/mL). Conclusion R. abyssinicus is a potential source of antibacterial, antifungal and antioxidant agents. The antibacterial mechanisms of action of the MeOH extract and compound 2 are due to disruption of the cytoplasmic membrane and inhibition of the microbial respiratory chain dehydrogenase enzyme activity. To the best of our knowledge, this is the first report of test samples and ciprofloxacin / fluconazole association against MDR strains. The observed activity of the isolated compounds against bacteria and fungi including MDR strains deserves further exploration.

Pengaruh Penambahan Asam Sitrat Terhadap Proses Non-Enzimatik Browning Jus Buah Pir Yali (Pyrus bretschneideri Rehd.)

The purpose of this study was to find out how effective citric acid is against the nonenzymaticprocess of browning Yali Pear fruit juice (Pyrus bretschneideri Rehd. Theresearch was conducted in a complete randomized design consisting of 5 replications. Thenon-enzymatic browning inhibition process was tested with citric acid treatment as the mainfactor with five concentrations ie 0% w/v, 2,5% w/v, 5% w/v, 7,5% w/v and 10% w/v.Qualitative parameters were dehydrogenase enzyme activity and reducing sugar level.Quantitative parameters were browning index and total soluble carbohydrate content.Levene test, analysis of variance, and Tukey test were performed at 5% significant level. Theresults showed that decrease in dehydrogenase enzyme activity occurs along with increasingthe concentration of citric acid. The level of reducing sugar has increased along with theincrease of citric acid concentration. The 7,5% w/v citric acid concentration effectivelyinhibited non-enzymatic browning of Yali Pear juice with a 21% reduction in the browningindex. Total soluble carbohydrate content increased 7% at 7.5% w/v citric acidconcentration. From the results of the study it was concluded that citric acid at 7,5% w / vconcentration was the inhibitor of non-enzymatic browning and dehydrogenase enzymeactivity, but stimulator of total soluble carbohydrate and reducing sugar level.

EFFECT OF SALACIA OBLONGA ROOT EXTRACT AGAINST CLINICAL ISOLATES STAPHYLOCOCCUS AUREUS

Objective: Salacia oblonga Wall. is an important medicinal plant belonging to the family Celastraceae. The study reports the effect of S. oblonga root extracts against clinical isolate Staphylococcus aureus Methods: Antibacterial activity was evaluated by agar diffusion method and assay for minimum inhibitory concentration (MIC) of extract. Further, the effect of S. oblonga extract determined by DNA fragmentation and respiratory dehydrogenase enzyme activity assays. Results: S. oblonga ethyl acetate root extract was evaluated for antibacterial activity towards clinical isolate S. aureus. Bacterial growth was determined in treated and control cells. Extract displayed good growth inhibition and MIC of the extract was 80 μg/ml. DNA fragmentation assay was carried out, this result has shown that treated bacterial cell has DNA damage compared to the control cell. Further, respiratory dehydrogenase enzyme activity was determined. In the treated cells, enzyme activity was low compared to the control cells. Conclusion: Salacia oblonga root extract inhibiting the growth of S. aureus by different modes of action.

ANALISIS BROWNING BUAH PISANG KEPOK (Musa paradisiaca L.) SETELAH PERLAKUAN ASAM ASKORBAT DAN LIDAH BUAYA (Aloe barbadensis L.)

Fruit is a necessity for most Indonesian people. Kepok banana is a climacteric fruit that can experience browning quickly. Therefore, this study was conducted to find a safe and effective material to prevent the browning process of kepok bananas. This study aims to determine the differences in the browning index, and the activity of the enzyme dehydrogenase in kepok banana cells. This study was conducted using a 2x3 factorial design. Factor A is ascorbic acid with 2 concentration levels namely 0% (b / v) and 5% (b / v). Factor B is Aloe (Aloebarbadensis L.) leaf extract with 3 levels, namely 0%, 5%, and 10%. The quantitative parameters are browning index and total dissolved carbohydrate content. The qualitative parameter is dehydrogenase enzyme activity. Levene test and variance analysis were carried out with 5% real level. The results obtained were kepok bananas with treatments coloured brighter than control. Ascorbic acid and Aloe (Aloe barbadensis L.) affect the browning index and dissolved total carbohydrate content of the sample. A decrease in dehydrogenase enzyme activity happened in the ascorbic acid treatment. Conclusions obtained from the study are ascorbic acid with a concentration of 5% can reduce the browning index of kepok banana by 31%, ascorbic acid with a concentration of 5% can maintain total dissolved carbohydrate content kepok banana as much as 53%, and Aloe extract 10% retain total dissolved carbohydrate content sample is 20%.

Risk of soil contamination by heavy metals through gas-dust emissions

The risk of chronic and emergency contamination of soils by heavy metals through gas-dust emissions by the method protected by the patent of the Russian Federation No. 2617533 on an invention including contamination diagnostics by means of the dehydrogenase enzyme activity analysis is estimated. This method of diagnostics allows to reduce time, to increase the accuracy and quality of examination on territories with an unsuccessful geoecological situation.