Titania nano-coated quartz wool for the photocatalytic mineralisation of emerging organic contaminants.

Many emerging contaminants pass through conventional wastewater treatment plants, contaminating surface and drinking water. The implementation of advanced oxidation processes in existing plants for emerging contaminant remediation is one of the challenges for the enhancement of water quality in the industrialised countries. This paper reports on the production of a TiO2 nano-layer on quartz wool in a relevant amount, its characterisation by X-ray diffraction and scanning electron microscopy, and its use as a photocatalyst under ultraviolet radiation for the simultaneous mineralisation of five emerging organic contaminants (benzophenone-3, benzophenone-4, carbamazepine, diclofenac, and triton X-100) dissolved in deionised water and tap water. This treatment was compared with direct ultraviolet photolysis and with photocatalytic degradation on commercial TiO2 micropearls. The disappearance of every pollutant was measured by high performance liquid chromatography and mineralisation was assessed by the determination of total organic carbon. After 4 hours of treatment with the TiO2 nano-coated quartz wool, the mineralisation exceeds 90% in deionised water and is about 70% in tap water. This catalyst was reused for seven cycles without significant efficiency loss.

New TFO conjugates containing a carminomycinone-derived chromophore.

Conjugates obtained by linking the anthracycline intercalating chromophore to triple helix forming oligonucleotides (TFOs) have been used in a physicochemical study of the stability of triple helices with DNA sequences of pharmacological relevance. The intercalating moiety is represented by carminomycinone derivatives obtained upon O-demethylation and hydrolysis of the glycosidic linkage of daunomycin followed by the introduction of an alkylating residue at two different positions. Results of experiments with a polypurinic region present in the multidrug resistance (MDR) gene indicate that the stability of the triple helix is significantly enhanced by replacement of C's with (5-Me)C's in the TFO sequences tested. The stability is not changed when a 3'-TpT is present in place of a 3'-CpG at the presumed intercalation site of the anthraquinone chromophore. The same carminomycinone derivatives were used for the preparation of conjugates able to form triple helices with the polypurine tract (PPT) present in the human integrated genome of HIV-1 infected cells. Three different TFOs (T(4)(Me)CT(4)(Me)CC, C2; T(4)(Me)CT(4)(Me)CC(Me)CC(Me)CCT, C6; and T(4)(Me)CT(4)G(6), G6) were designed and linked to the anthraquinone moiety. These conjugates showed a significantly enhanced ability to bind the PPT region of HIV with respect to the nonconjugated TFOs.

Evaluation of different types of end-capping modifications on the stability of oligonucleotides toward 3'- and 5'-exonucleases.

Synthetic oligonucleotides are increasingly used because of their potential activity as regulators of gene expression. One of their major drawbacks is instability toward nucleases, in particular exonucleases. In this article, we studied some terminal modifications that can enhance exonuclease resistance, such as end-capping with alkylic chains (1,3-propanediol and 1,6-hexanediol), and with a modified nucleotide (2',3'-secouridine). These compounds were compared with the parent (natural) oligodeoxynucleotide and with different analogs containing a progressive number of phosphorothioate linkages. The resistance toward SVPDE and CSPDE (a 3'- and a 5'-exonuclease) was assessed, in vitro, by two independent techniques, UV and HPLC. Our results showed that the stability of all the modified oligonucleotides was at least 12 times that of the parent compound.

Antisense inhibition of Bax mRNA increases survival of terminally differentiated HL60 cells.

Cell sensitivity to programmed cell death is primarily modulated by members of the Bcl-2 family, as the balance of homodimer or heterodimer formation between proapoptotic and antiapoptotic members defines apoptosis susceptibility in the great majority of cellular contexts. It is, therefore, important to clarify if the Bax protein is limiting for activation of the genetic program of programmed cell death or can be complemented by different Bcl-2 family members, such as Bak or Bad. To gain some insight into the role of Bax in the molecular mechanisms of apoptosis of myeloid cells, we inhibited this gene in all-trans-retinoic acid (ATRA)-treated HL60 cells using the methodology of antisense oligodeoxynucleotides (AS-ODN). Our results indicate that Bax inhibition has no effect on the proliferation and differentiation capacity of HL60 cells. Instead, the survival rate of terminally differentiated Bax-inactivated HL60 (Bax(-) HL60) cells is almost three times higher in respect to control cultures, indicating that in mature granulocytes Bax is not efficiently complemented by others members of the Bcl-2 family proteins.

Synthesis and binding properties of conjugates between oligodeoxynucleotides and daunorubicin derivatives.

Conjugation of an anthracycline to a triplex-forming oligonucleotide (TFO) allows delivery of this drug to a specific DNA site, preserving the intercalation geometry of this class of anticancer agents. Conjugate 11, in which the TFO is linked via a hexamethylene bridge to the O-4 on the D ring of the anthraquinone moiety, affords the most stable triple helix, through intercalation of the planar chromophore between DNA bases and binding of both the TFO and the amino sugar to the major and the minor groove respectively.

Factors affecting the predictive validity of the Braden Scale.

This descriptive correlational study explored the predictive validity of the Braden Scale and factors affecting it A Braden score was determined within 4 hours of admission for 50 adult medical/surgical inpatients. Independent skin assessments were made three times a week and at discharge. Fourteen patients (28%) developed pressure ulcers. A Braden score cutoff of 18 or less resulted in a 71% sensitivity, 83% specificity, 63% predictive value of a positive test, and 88% predictive value of a negative test. Three of the four patients incorrectly predicted to be not at risk scored "inadequate" on the nutrition subscale. Two of the four also were underweight. Of the six patients incorrectly predicted at risk for a pressure ulcer, three had been placed on air mattresses and were receiving levothyroxine (Synthroid). This study provides further evidence of the Braden Scale's predictive validity. The results suggest that patients who are underweight or getting inadequate nutrition be considered at increased risk for pressure ulcers.

3'-5' L-capped-antisense oligodeoxynucleotides targeted at the SV40 T-antigen gene: pharmacological and biological properties.

This paper reports on some pharmacological and biological properties of 22-mer antisense oligodeoxynucleotides which contain an L-deoxyribonucleoside at each terminus. Compared with natural compounds, of which they retain the DNA hybridizing ability and the cell uptake mechanism, the L-22-mers exhibited an increased resistance to phosphodiesterase degradation, an apparent higher intracellular concentration and a longer intracellular half life. Antiviral activity was not prominent.

L-DNAs as potential antimessenger oligonucleotides: a reassessment.

Unnatural L-2'-deoxyribonucleosides L-T, L-dC, L-dA and L-dG were prepared from L-arabinose and assembled, by solution or solid phase synthesis, to give L-oligonucleotides (L-DNAs), which contain all four natural bases. The affinity of these modified oligomers for complementary D-ribo- and D-deoxyribo-oligomers was studied with NMR, UV and CD spectroscopies and mobility shift assay on native PAGE. All experimental results indicate that L-DNAs do not, in general, recognize single-stranded, natural DNA and RNA. Hence, contrary to previous suggestions, it is not possible to envisage their use as wide scope antimessenger agents in the selective control of gene expression.

Interactions between morpholinyl anthracyclines and DNA. The crystal structure of a morpholino doxorubicin bound to d(CGTACG).

Anthracycline antibiotics daunomycin and adriamycin are among the most widely used in cancer chemotherapy and DNA is believed to be the primary target of their biological action. The crystal structure of a morpholino derivative of adriamycin bound to the DNA hexamer d(CGTACG) has been determined at 1.5 A resolution. The complex crystallizes in space group P1 with unit cell dimensions a = 18.01 A, b = 18.83 A, c = 27.65 A, alpha = 92.6 degrees, beta = 100.5 degrees, gamma = 94.9 degrees and there are two drug molecules bound per duplex. Morpholino derivatives differ greatly from their parent compounds in their biological and pharmacological properties. Structural comparison of this complex with the series of previously reported anthracycline-DNA complexes offers an opportunity for studying relationships between structure and function. The anthracycline chromophore intercalates at the CpG step and DNA distortions from a B-type conformation are similar to those observed in the other DNA-anthracycline complexes. Interactions between drug and DNA show no differences at the intercalation site, while in the minor groove they are significantly affected by the presence of the bulky morpholinyl moiety on the anthracycline amino sugar. The binding site involves four base-pairs and the absence of a positive charge on the amino sugar appears to influence the hydration pattern on both grooves. The two halves of the duplex are symmetrically related by a non-crystallographic 2-fold axis but they are not equivalent. In one half, one magnesium cluster bridges both drug and DNA, further stabilizing the complex.

Interactions of nucleic acids with distamycins. Binding of Dst-3 to d(CGTTTAAACG)2 and d(CGTACGTACG)2.

The binding between Distamycin 3 and the palindromic duplexes d(CGTTTAAACG)2 and d(CGTACGTACG)2 was investigated by two independent techniques: UV-Vis absorption in the Job's plot approach and Induced Circular Dichroism. Both decamers bind two molecules of peptide per duplex, with close overall affinities. This result indicates that a row of six A:T base pairs can accommodate two molecules of drug and that the minimal binding site of Distamycin 3 can consist of just two A:T base pairs.

One pot solution synthesis of cyclic oligodeoxyribonucleotides.

Several cyclic oligodeoxynucleotides with different base composition and size have been prepared from 5',3'-unprotected linear precursors, using a bifunctional phosphorylating reagent. The final deprotected oligomers have been characterized by 1H- and 31P-NMR. The present procedure is particularly useful for millimolar scale syntheses.