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Biomedical subjects

Else Tonnesen

Publications and source records attributed to Else Tonnesen.

3 recordsLinked to original sources

Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery.

BACKGROUND: The recommended dose for intravenous (IV) paracetamol injection in adults is 1g, however pharmacokinetic and pharmacodynamic findings suggest that a better analgesia could be obtained with a 2 g starting dose. METHODS: A single-centre, randomised, double-blind, placebo-controlled, 3-parallel group study was performed to demonstrate the analgesic efficacy and safety of IV paracetamol 2 g. Following third molar surgery, patients reporting moderate to severe pain received a single 15-min infusion of either IV paracetamol 2 g, IV paracetamol 1g or placebo. Efficacy and safety were evaluated over 8 h. Laboratory tests were performed before and 48 h after drug administration. RESULTS: Two hundred and ninety seven patients (132 = IV paracetamol 2g; 132 = IV paracetamol 1g; 33 = placebo) were randomised and completed the study. The summed pain relief over 6h (TOTPAR6) was significantly superior with IV paracetamol 2 g as compared to IV paracetamol 1g and placebo (p < 0.0001). Pain relief scores of IV paracetamol 2g were significantly superior to IV paracetamol 1g and to placebo from T30' to T8h (p < 0.0001). Median duration of analgesia was significantly longer following IV paracetamol 2 g compared to IV paracetamol 1g and placebo (p < 0.0001). Adverse events occurred with the same frequency in the 3 treatment groups. No clinically significant changes from baseline were observed for vital signs or laboratory tests. CONCLUSION: The analgesic efficacy of a 2 g starting dose of IV paracetamol was superior over the recommended dose of 1g in terms of magnitude and duration of analgesic effect for postoperative pain following third molar surgery, with no significant difference between groups regarding safety.

Acetaminophen↗

Human gliomas contain morphine.

BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous morphine via high pressure liquid chromatography (HPLC). The HPLC peak corresponding to an authentic morphine standard had its morphine level determined via radioimmune assay. The identity of this material was established by Q-TOF-MS analysis. RESULTS: Each glioma exhibited an endogenous morphine presence. Tumor extractions demonstrated a molecular mass of 286.14 da, identical to authentic morphine. Subsequent fragmentation analysis of this molecule revealed fragment masses of 129.01 da, 183.09 da and 201.07 da, corresponding to authentic morphine fragments. This material was not found in any of the solutions used in the study nor was it present as a residual material in blank HPLC runs. CONCLUSIONS: Morphine is present in human gliomas, suggesting that it may exert an action that effects tumour physiology/pathology.

Brain Neoplasms↗

Endogenous morphinergic signaling and tumor growth.

The mu3 opiate receptor subtype has been characterized by various binding assays as opiate alkaloid selective (e.g. morphine) and opioid peptide (e.g. methionine enkephalin) insensitive. This opiate receptor subtype has been found on human, including cancer cell lines, and invertebrate tissues, demonstrating that it has been conserved during evolution. Furthermore, in numerous reports, this receptor is coupled to constitutive nitric oxide release. In this regard, for example, morphine immune down regulating activities parallels those actions formerly attributed to nitric oxide. We have now identified the mu3 receptor at the molecular level and sequence analysis of the isolated cDNA suggests that it is a novel, alternatively spliced variant of the mu opiate receptor gene (MOR). Furthermore, using Northern blot, reverse transcription coupled to polymerase chain reaction (RT-PCR) and sequence analysis, we have demonstrated the expression of this new mu variant in human vascular tissue, mononuclear cells, polymorphonuclear cells, and human neuroblastoma cells. The presence of this mu splice variant, adds to the growing body of evidence supporting the hypothesis that morphine is an endogenous signaling molecule in neural, immune and vascular systems. In addition to their use in the treatment of pain, opioid peptides appear to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of opiate alkaloids, e.g., morphine, on tumor growth, with emphasis on immuno-regulatory and antiproliferative mechanisms.

Alternative Splicing↗