The immunogenicity to the first anti-TNF therapy determines the outcome of switching to a second anti-TNF therapy in spondyloarthritis patients

Introduction

Anti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA to the first anti-TNF drug SpA patients.

Methods

Forty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration.

Results

All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14 ± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p = 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002).

Conclusions

In SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.     

Functional imaging in radiation therapy planning for head and neck cancer

Functional imaging and its application to radiotherapy (RT) is a rapidly expanding field with new modalities and techniques constantly developing and evolving. As technologies improve, it will be important to pay attention to their implementation. This review describes the main achievements in the field of head and neck cancer (HNC) with particular remarks on the unsolved problems.     

Patterns of care of radiotherapy in México

Aim

This survey is performed to learn about the structure of radiotherapy in México.

Background

Radiation oncology practice is increasing because of the higher incidence of cancer. There is no published data about radiotherapy in México.

Materials and methods

A questionnaire was sent to the 83 registered centers in the database of the Mexican regulatory agency. One out of the 32 states has no radiotherapy. 27 centers from 14 states provided their answers.

Results

829 patients are treated annually with any radiotherapy modality in each center. Two centers have one cobalt machine, 7 have a cobalt and a linac and 10 have more than one linac. Five centers use 2D planning systems, 22 use 3D; 9, conventional simulators; 22, CT based simulation, and 1 center has no simulation. Most of the centers verify beams with films, electronic portal image devices and cone beam CTs are also used. Intensity modulated and image guided radiotherapy are performed in 5 states. Breast, prostate, cervix, lung, rectum and head and neck cancer are the six most common locations. There are 45 public and 38 private centers, 2 dedicated to children. Two gamma knife units, 5 Novalis systems, 1 tomotherapy and 2 cyberknife machines are working. All centers have at least one radiation oncologist, one physicist and one radiotherapist.

Conclusions

Definitive conclusions cannot be drawn from this limited feedback due to a low participation of centers. This survey about radiotherapy in Mexico shows the heterogeneity of equipment as well as medical and technical staff in the whole country.     

Long-Term Biomonitoring of Soil Contamination Using Poplar Trees: Accumulation of Trace Elements in Leaves and Fruits

Phytostabilization aims to immobilize soil contaminants using higher plants. The accumulation of trace elements in Populus alba leaves was monitored for 12 years after a mine spill. Concentrations of As and Pb significantly decreased, while concentrations of Cd and Zn did not significantly over time. Soil concentrations extracted by CaCl₂ were measured by ICP-OES and results of As and Pb were below the detection limit. Long-term biomonitoring of soil contamination using poplar leaves was proven to be better suited for the study of trace elements. Plants suitable for phytostabilization must also be able to survive and reproduce in contaminated soils. Concentrations of trace elements were also measured in P. alba fruiting catkins to determine the effect on its reproduction potential. Cadmium and Zn were found to accumulate in fruiting catkins, with the transfer coefficient for Cd significantly greater than Zn. It is possible for trace elements to translocate to seed, which presents a concern for seed germination, establishment and colonization. We conclude that white poplar is a suitable tree for long-term monitoring of soil contaminated with Cd and Zn, and for phytostabilization in riparian habitats, although some caution should be taken with the possible effects on the food web.

Supplemental materials are available for this article. Go to the publisher's online edition of International Journal of Phytoremediation to view the supplemental file.     

Synthesis and Antiviral Activity of 5′-O-Sulfamoyluridine Derivatives

Abstract

A series of 5′-O-[[[[(alkyl)oxy]carbonyl] amino] sulfonyl] uridines have been synthesized by reaction of cyclohexanol, palmityl alcohol, 1,2-di-O-benzoylpropanetriol and 2,3,4,6-tetra-O-benzoyl-L-glucopyranose with chlorosulfonyl isocyanate and 2,3′-O-isopropylidene-uridine. Another series of 5′-O-(N-ethyl and N-isopropylsulfamoyl) uridines have been prepared by reaction of 2′,3′-O-isopropylidene and 2′,3′-di-O-acetyluridine with N-ethylsulfamoyl and N-isopropylsulfamoyl chlorides. All compounds were tested against HSV-2, VV, SV and ASFV viruses. 2′,3′-Di-O-acetyl-5′-O-(N-ethyl and N-isopropylsulfamoyl) uridine showed significant activities against HSV-2. 5′-O-[[[[(2,3,4,6-Tetra-O-benzoyl-β-L-glucopyranosyl)oxy]carbonyl]amino] sulfonyl]-2′,3′-O-isopropylideneuridine was very active against ASFV.     

Effects of Intracellular Calcium Chelation and Pifithrin-α on Deoxynucleotide Metabolism in Human Lymphocytes

Previously, we have found that activation of deoxycytidine kinase elicited by various DNA-damaging chemical agents could be prevented by BAPTA-AM, a cell-permeable calcium chelator or by pifithrin-α, a pharmacological inhibitor of p53. Here, we show that stimulation of deoxycytidine kinase by UV-light also is calcium-dependent and pifithrin-α-sensitive in tonsillar lymphocytes, while thymidine kinase 1 activity is stabilised in the presence of BAPTA-AM. Importantly, both UV-irradiation and calcium chelation decreased the incorporation of labelled deoxycytidine and thymidine into DNA. Pifithrin-alpha dramatically reduced the labelling of both the nucleotide and DNA fractions, possibly due to inhibition of transmembrane nucleoside transport.     

Diamino-Antraquinone: A New Intercalating Agent. Synthesis and Linking to Oligodeoxynucleotide

Abstract

Phosphoramidite derivative of 1,4-diamino antraquinone was synthesized, characterized, and incorporated into oligonucleotides. Intercalative interaction between the dye and the nucleic acid was confirmed by CD spectroscopy.     

Novel Series of [ddN]-[TSAO-T] Heterodimers as Potential Bi-Functional Inhibitors of HIV-1 RT. Studies in the Linker and ddN Region

Abstract

Novel series of [ddN]-(CH₂)_n-[TSAO-T] heterodimers have been prepared and tested for their anti-HIV-1 and HIV-2 activity. The most active compound of this series was the [d4T]-(CH₂)₃-[TSAO-T] heterodimer (EC₅₀ = 0.018 ± 0.03 μM).     

Asymptomatic Hyperuricemia: Impact of Ultrasonography

Thirty-five patients (23 males) with asymptomatic hyperuricemia for at least two years underwent two-dimensioal ultrasonography of knees and ankles. Urate deposits (tophi) in tendons, synovium, and other soft tissues were detected in 12 patients (34%). Increased vascularity (inflammation) was evident in 8 of these patients (23%). Tophi were more frequently found in knees than in ankles and were especially prevalent in the distal patellar tendon. The presence of tophi was unrelated to the known duration of hyperuricemia (mean, 5 years). Ultrasonography allows detection of tophi and inflammation in a third and in a fourth, respectively, of asymptomatic hyperuricemic patients.     

A New Synthesis of 2′,3′-Didehydro-3′-deoxy-3-Alkylthymidine

Abstract

The preparation of 3-alkyl D4T derivatives has been carried out starting from the corresponding 5′-O-t-butyldimethylsilyl-3′-O-methanesulfonylthymidine 2 by way of deprotection-elimination and succesive alkylation reactions.