A randomised clinical trial comparing the analgesic and anxiolytic efficacy and tolerability of Stilpane® and Tramacet® after third molar extraction

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The association between nm23 gene expression and survival in patients with sarcomas.

The relationship between the expression of nm23, a putative metastasis-suppressor gene and prognosis was determined for 88 patients with sarcomas. Immunohistochemistry using immunopurified anti-nm23 peptide antibodies was performed and the results of each case graded according to the degree of staining. Univariate and multivariate analyses were carried out to determine the prognostic significance of nm23 staining for sarcoma patients. Expression of nm23 was found to increase in line with metastatic potential in many cases but this did not reach significance for the study as a whole. However, the possibility of nm23 loss occurring in association with metastasis cannot be ruled out in some more aggressive sarcomas, as was demonstrated for six patients with low-scoring, unclassified and synovial sarcomas that had metastasized. The time to metastasis was longer for patients with grade 3 sarcomas (50-75% of tumour cells staining) than similar patients in other staining groups. These results suggest that expression of nm23 genes in sarcomas is variable and has no value as a prognostic indicator for these mesenchymal tumours

Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

BACKGROUND: We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. METHODS: Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. RESULTS: Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). CONCLUSIONS: In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion

A randomised clinical trail comparing the analgesic and anxiolytic efficacy and tolerability of Stilpane® and Tramacet® after third molar extraction

BACKGROUND : successful treatment of moderate to severe acute pain often necessitates several analgesics that target different sites of the nociceptive pathway. Fixed-dose combination analgesics facilitate a reduction in dose of individual components, increased compliance and strong-opioid sparing. The aim of this study was to compare the analgesic and anxiolytic efficacy and tolerability of two widely prescribed combination analgesics, Stilpane® (paracetamol/codeine/meprobamate) and Tramacet® (paracetamol/tramadol). METHODS : A prospective randomised parallel group phase IV clinical trial was conducted in 100 patients experiencing moderate to severe pain after third molar extraction at the Oral and Dental Hospital, University of Pretoria. Pain intensity and pain relief were assessed using Likert and visual analogue scales. Medication efficacy, time to perceptible pain relief and meaningful pain relief were also assessed. Primary variables included the Pain Intensity Difference (PID) between baseline and scheduled visits, and hourly pain relief (PAR). The Summed Pain Intensity Difference (SPID), Sum of hourly PAR, hourly PAR, hourly PIDs from baseline (SPRID) and Total Pain Relief (TOTPAR) were calculated according to standard methods. Beck Anxiety Questionnaire assessed anxiety. Tolerability was assessed chiefly by the reporting of adverse events. RESULTS : Stilpane® and Tramacet® were equally effective at relieving moderate to severe acute pain. No differences in anxiolytic efficacy were found between the two treatment arms and differences in tolerability failed to reach statistical significance. CONCLUSIONS : Despite their distinctive compositions and mechanisms of action, Stilpane® and Tramacet® are equally effective and well-tolerated combination analgesics in patients experiencing moderate to severe acute pain.Aspen Pharmacarehttp://www.tandfonline.com/ojfpam201

Can Clustal-style progressive pairwise alignment of multiple sequences be used in RNA secondary structure prediction?

<p>Abstract</p> <p>Background</p> <p>In ribonucleic acid (RNA) molecules whose function depends on their final, folded three-dimensional shape (such as those in ribosomes or spliceosome complexes), the secondary structure, defined by the set of internal basepair interactions, is more consistently conserved than the primary structure, defined by the sequence of nucleotides.</p> <p>Results</p> <p>The research presented here investigates the possibility of applying a progressive, pairwise approach to the alignment of multiple RNA sequences by simultaneously predicting an energy-optimized consensus secondary structure. We take an existing algorithm for finding the secondary structure common to two RNA sequences, Dynalign, and alter it to align profiles of multiple sequences. We then explore the relative successes of different approaches to designing the tree that will guide progressive alignments of sequence profiles to create a multiple alignment and prediction of conserved structure.</p> <p>Conclusion</p> <p>We have found that applying a progressive, pairwise approach to the alignment of multiple ribonucleic acid sequences produces highly reliable predictions of conserved basepairs, and we have shown how these predictions can be used as constraints to improve the results of a single-sequence structure prediction algorithm. However, we have also discovered that the amount of detail included in a consensus structure prediction is highly dependent on the order in which sequences are added to the alignment (the guide tree), and that if a consensus structure does not have sufficient detail, it is less likely to provide useful constraints for the single-sequence method.</p

NF-κB inhibition impairs the radioresponse of hypoxic EMT-6 tumour cells through downregulation of inducible nitric oxide synthase

Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-κB (NF-κB). Both iNOS activation and radioresponse were impaired by the NF-κB inhibitors phenylarsine oxide and lactacystin. Contrasting to other studies, our data show that inhibition of NF-κB may impair the radioresponse of tumour cells through downregulation of iNOS. © 2003 Cancer Research UK.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network

Oesophageal adenocarcinoma, which arises from an acquired columnar lesion, Barrett's metaplasia, is rising in incidence more rapidly than any other cancer in the Western world. Elevated expression of c-MYC has been demonstrated in oesophageal adenocarcinoma; however, the expression of other members of the MYC/MAX/MAD network has not been addressed. The aims of this work were to characterise the expression of c-MYC, MAX and the MAD family in adenocarcinoma development and assess the effects of overexpression on cellular behaviour. mRNA expression in samples of Barrett's metaplasia and oesophageal adenocarcinoma were examined by qRT–PCR. Semi-quantitative immunohistochemistry and western blotting were used to examine cellular localisation and protein levels. Cellular proliferation and mRNA expression were determined in SEG1 cells overexpressing c-MYCER or MAD1 using a bromodeoxyuridine assay and qRT–PCR, respectively. Consistent with previous work expression of c-MYC was deregulated in oesophageal adenocarcinoma. Paradoxically, increased expression of putative c-MYC antagonists MAD1 and MXI1 was observed in tumour specimens. Overexpression of c-MYC and MAD proteins in SEG1 cells resulted in differential expression of MYC/MAX/MAD network members and reciprocal changes in proliferation. In conclusion, the expression patterns of c-MYC, MAX and the MAD family were shown to be deregulated in the oesophageal cancer model

Ascorbate content of clinical glioma tissues is related to tumour grade and to global levels of 5-hydroxymethyl cytosine.

peer reviewedGliomas are incurable brain cancers with poor prognosis, with epigenetic dysregulation being a distinctive feature. 5-hydroxymethylcytosine (5-hmC), an intermediate generated in the demethylation of 5-methylcytosine, is present at reduced levels in glioma tissue compared with normal brain, and that higher levels of 5-hmC are associated with improved patient survival. DNA demethylation is enzymatically driven by the ten-eleven translocation (TET) dioxygenases that require ascorbate as an essential cofactor. There is limited data on ascorbate in gliomas and the relationship between ascorbate and 5-hmC in gliomas has never been reported. Clinical glioma samples (11 low-grade, 26 high-grade) were analysed for ascorbate, global DNA methylation and hydroxymethylation, and methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Low-grade gliomas contained significantly higher levels of ascorbate than high-grade gliomas (p = 0.026). Levels of 5-hmC were significantly higher in low-grade than high-grade glioma (p = 0.0013). There was a strong association between higher ascorbate and higher 5-hmC (p = 0.004). Gliomas with unmethylated and methylated MGMT promoters had similar ascorbate levels (p = 0.96). One mechanism by which epigenetic modifications could occur is through ascorbate-mediated optimisation of TET activity in gliomas. These findings open the door to clinical intervention trials in patients with glioma to provide both mechanistic information and potential avenues for adjuvant ascorbate therapy