Comparación de la eficacia analgésica de codeína más paracetamol vs tramadol en el tratamiento del dolor por cáncer / Comparison of the analgesic effectiveness of codeine plus paracetamol vs tramadol in the treatment of cáncer pain

Pain is the principal symptom in 70% of patients with severe cáncer. Analgesics therapy with a proper management controls pain in 80-90% of patients. Objective. Compare the analgesic efficacy and tolerability of codeine plus acetaminophen (CA) and tramadol clorhydrate (T) in the relief of cáncer pain. Method. A double blind, randomize controlled clinical trial was perform in patients with modérate to severe pain intensity. Randomly patients were assigned in a group for receiving codeine plus acetaminophen and in other group for receiving tramadol chlorhydrate for a three weeks period. Pain intensity was measure using a numeric scale from zero to ten in which modérate pain goes from 5-7, and severe pain goes from 8-10. Analgesic treatment was considered to be effective when pain disappear or become mild, 1-4 in the numeric scale. Results. One hundred fifteen patients participated, 59 receive CA and 56 T. In the group of patients that receive CA, 58% achieved pain relief with the initial dose of 150 mg/d and 8% responded to the double dose; 34% didn't experience pain relief. In the group patients treated with T pain relief occurred in 62% of patients with the initial dose of 200mg/d and 11% with the double dose; 27% didn't experienced pain relief. Differences between both groups were not significant in the analgesic efficacy. The tramadol group experienced in a significant way a higher incidence of adverse events of mild intensity: nausea (p: 0.05, RR: 0.62; IC95%: 0.38-1.01), dizziness (p: 0.04; RR: 0.58; IC95%: 0.33-1.01) and lost of appetite (p: 0.001; RR: 0.08; IC95%: 0.01-0.59). Conclusion. Efficacy of C and T during a treatment of 23 days was similar, no statistical differences were found. There were no differences in the analgesic effectiveness between CA and T in the management of cáncer pain. With the use of T a higher incidence of adverse events of mild intensity were reported (AU)

El dolor es el síntoma más importante en 70% de pacientes que padecen cáncer avanzado. La terapia con analgésicos utilizada en forma adecuada, controla el dolor en 80-90% de los pacientes. Objetivos. Comparar la eficacia analgésica y seguridad de la codeína más acetaminofén (CA) y Clorhidrato de Tramadol (T) en el alivio del dolor por cáncer. Método. Se realizó un ensayo clínico controlado doble ciego, en pacientes con dolor por cáncer de intensidad moderada o severa. En forma aleatoria se asignó un grupo de pacientes para ser tratados con la combinación de Codeína más paracetamol, mientras que el otro grupo recibió Clorhidrato de Tramadol por un periodo de tres semanas. La intensidad del dolor fue medida con una escala numérica de cero a diez, considerándose como dolor de intensidad moderada el marcado en la escala entre 5-7 y de intensidad severa de 8-10. El tratamiento analgésico se consideró eficaz cuando el dolor desapareció o disminuyó a una intensidad leve, comprendida entre 1-4. Resultados. Se incluyeron 115 pacientes: 59 recibieron CA y 56 recibieron T. En el grupo de pacientes que recibió CA 58% aliviaron con una dosis inicial de codeína de 150 mg/día y 8% con la dosis doblada; 34% no aliviaron. En el grupo de pacientes tratado con T el dolor alivió en 62% de los pacientes con la dosis inicial de 200mg/día y 11% con la dosis doblada, mientras que 27% no experimentó alivio. Las diferencias entre los dos grupos no fueron significativas en cuanto a su eficacia analgésica. El grupo que recibió Tramadol presentó en forma significativa, mayor incidencia de efectos colaterales de intensidad leve: náusea (p: 0.05, RR: 0.62; IC95%: 0.38-1.01), mareo (p: 0.04; RR: 0.58; IC95%: 0.33-1.01) y pérdida de apetito (p: 0.001; RR: 0.08; IC95%: 0.01-0.59). Conclusión. No existen diferencias en cuanto a la eficacia analgésica de CA y T en el tratamiento del dolor por cáncer. Con el uso de T se presentó una mayor incidencia de efectos colaterales de intensidad leve

Bacterial conjugation protein MobA mediates integration of complex DNA structures into plant cells.

Agrobacterium tumefaciens transfers T-DNA to plant cells, where it integrates into the genome, a property that is ensured by bacterial proteins VirD2 and VirE2. Under natural conditions, the protein MobA mobilizes its encoding plasmid, RSF1010, between different bacteria. A detailed analysis of MobA-mediated DNA mobilization by Agrobacterium to plants was performed. We compared the ability of MobA to transfer DNA and integrate it into the plant genome to that of pilot protein VirD2. MobA was found to be about 100-fold less efficient than VirD2 in conducting the DNA from the pTi plasmid to the plant cell nucleus. However, interestingly, DNAs transferred by the two proteins were integrated into the plant cell genome with similar efficiencies. In contrast, most of the integrated DNA copies transferred from a MobA-containing strain were truncated at the 5' end. Isolation and analysis of the most conserved 5' ends revealed patterns which resulted from the illegitimate integration of one transferred DNA within another. These complex integration patterns indicate a specific deficiency in MobA. The data conform to a model according to which efficiency of T-DNA integration is determined by plant enzymes and integrity is determined by bacterial proteins.

The omega sequence of VirD2 is important but not essential for efficient transfer of T-DNA by Agrobacterium tumefaciens.

The VirD2 protein of Agrobacterium tumefaciens contains defined sequences necessary for processing and transferring the T-DNA during transformation of plant cells. We performed a mutational analysis of the conserved omega sequence of VirD2, whose role has proven to be difficult to elucidate so far. In this report, we show that a deletion of these 5 amino acids or their replacement by 5 glycines reduced T-DNA transfer considerably, compared with wild type, demonstrating that the omega sequence is important for the efficient transfer of T-DNAs. However, the efficiency and pattern of integration of the T-DNAs were not affected by any modifications of the omega sequence. The importance of the C terminus of VirD2 for T-DNA transfer is discussed.

The binding motifs for Ac transposase are absolutely required for excision of Ds1 in maize.

A reverse genetic system for studying excision of the transposable element Ds1 in maize plants has been established previously. In this system, the Ds1 element, as part of the genome of maize streak virus (MSV), is introduced into maize plants via agroinfection. In the presence of the Ac element, excision of Ds1 from the MSV genome results in the appearance of viral symptoms on the maize plants. Here, we used this system to study DNA sequences required in cis for excision of Ds1. The Ds1 element contains the Ac transposase binding motif AAACGG in only one of its subterminal regions (defined here as the 5' subterminal region). We showed that mutation of these motifs abolished completely the excision capacity of Ds1. This is the first direct demonstration that the transposase binding motifs are essential for excision. Mutagenesis with oligonucleotide insertions in the other (3') subterminal region resulted in elements with either a reduced or an increased excision efficiency, indicating that this subterminal region also has an important function.

The Agrobacterium tumefaciens virulence D2 protein is responsible for precise integration of T-DNA into the plant genome.

The VirD2 protein of Agrobacterium tumefaciens was shown to pilot T-DNA during its transfer to the plant cell nucleus. We analyze here its participation in the integration of T-DNA by using a virD2 mutant. This mutation reduces the efficiency of T-DNA transfer, but the efficiency of integration of T-DNA per se is unaffected. Southern and sequence analyses of integration events obtained with the mutated VirD2 protein revealed an aberrant pattern of integration. These results indicate that the wild-type VirD2 protein participates in ligation of the 5'-end of the T-strand to plant DNA and that this ligation step is not rate limiting for T-DNA integration.